Dosimetric evaluation of three adaptive strategies for prostate cancer treatment including pelvic lymph nodes irradiation.

PubMed

Cantin, Audrey; Gingras, Luc; Lachance, Bernard; Foster, William; Goudreault, Julie; Archambault, Louis

2015-12-01

The movements of the prostate relative to the pelvic lymph nodes during intensity-modulated radiation therapy treatment can limit margin reduction and affect the protection of the organs at risk (OAR). In this study, the authors performed an analysis of three adaptive treatment strategies that combine information from both bony and gold marker registrations. The robustness of those treatments against the interfraction prostate movements was evaluated. A retrospective study was conducted on five prostate cancer patients with 7-13 daily cone-beam CTs (CBCTs). The clinical target volumes (CTVs) consisting of pelvic lymph nodes, prostate, and seminal vesicles as well as the OARs were delineated on each CBCT and the initial CT. Three adaptive strategies were analyzed. Two of these methods relied on a two-step patient positioning at each fraction. First step: a bony registration was used to deliver the nodal CTV prescription. Second step: a gold marker registration was then used either to (1) complete the dose delivered to the prostate (complement); (2) or give almost the entire prescription to the prostate with a weak dose gradient between the targets to compensate for possible motions (gradient). The third method (COR) used a pool of precalculated plans based on images acquired at previous treatment fractions. At each new fraction, a plan is selected from that pool based on the daily position of prostate center-of-mass. The dosimetric comparison was conducted and results are presented with and without the systematic shift in the prostate position on the CT planning. The adaptive strategies were compared to the current clinical standard where all fractions are treated with the initial nonadaptive plan. The minimum daily prostate D95% is improved by 2%, 9%, and 6% for the complement, the gradient, and the COR approaches, respectively, compared to the nonadaptive method. The average nodal CTV D95% remains constant across the strategies, except for the gradient approach where a reduction of 7% is observed. However, a correction of the systematic shift reduced the problem, and the adaptive strategies remain robust against the prostate movement across the fraction. The bladder V55Gy is reduced by 35% on average for the adaptive strategies. Because they offer increased CTV coverage and OAR sparing, adaptive methods may be suitable candidates for simple and efficient adaptive treatment strategies for prostate cancer. Margin reduction and systematic error correction in the prostate position improve the protection of the OAR and the dose coverage. A cumulative dose to simulate a complete treatment would show real effects and allow a better comparison between each method.

Tendencies for higher co-expression of EGFR and HER2 and downregulation of HER3 in prostate cancer lymph node metastases compared with corresponding primary tumors.

PubMed

Carlsson, J; Shen, L; Xiang, J; Xu, J; Wei, Q

2013-01-01

The epidermal growth factor receptor (EGFR) family members are potential targets for therapy using extra-cellular domain receptor binding agents, such as the antibodies trastuzumab and cetuximab, or antibodies labeled with therapeutically useful radionuclides or toxins. This is especially the case when the tumor cells are resistant to chemotherapy and tyrosine kinase inhibitors. Studies concerning the expression of these receptors in prostate cancer vary in the literature, possibly due to differences in patient inclusion, sample preparations and scoring criteria. In our study, EGFR, HER2 and HER3 expression was analyzed in prostate cancer samples from primary tumors and corresponding lymph node metastases from 12 patients. The expression of HER2 and EGFR was scored from immunohistochemical preparations and the HercepTest criteria (0, 1+, 2+ or 3+), while HER3 expression was scored as no, weak or strong staining. There were 5 EGFR-positive (2+ or 3+) primary tumors and 6 EGFR-positive lymph node metastases, and there was EGFR upregulation in one metastasis. Only 4 of the 12 patients had marked HER2 expression (2+ or 3+) in their primary tumors and there was one downregulation and 5 cases of upregulation in the metastases. Thus, a total of 8 out of 12 analyzed metastases were HER2-positive. Of the 12 primary tumors, 9 expressed HER3 while only 2 of the lymph node metastases expressed recognizable HER3 staining, so 7 metastases appeared to have downregulated HER3 expression. In one of the primary tumors there was positive co-expression of EGFR and HER2, while this co-expression was observed in 4 of the metastases. Thus, there were tendencies for upregulation of HER2, increased co-expression of EGFR and HER2 and downregulation of HER3 in the prostate cancer lymph node metastases in comparison to the primary tumors. The results are encouraging for studies involving more patients. Possible strategies for EGFR- and HER2-targeted therapy are briefly discussed in the present study, especially with regard to the expression and co-expression of EGFR and HER2 in metastases.

Dosimetric evaluation of three adaptive strategies for prostate cancer treatment including pelvic lymph nodes irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cantin, Audrey; Gingras, Luc; Archambault, Louis, E-mail: louis.archambault@phy.ulaval.ca

Purpose: The movements of the prostate relative to the pelvic lymph nodes during intensity-modulated radiation therapy treatment can limit margin reduction and affect the protection of the organs at risk (OAR). In this study, the authors performed an analysis of three adaptive treatment strategies that combine information from both bony and gold marker registrations. The robustness of those treatments against the interfraction prostate movements was evaluated. Methods: A retrospective study was conducted on five prostate cancer patients with 7–13 daily cone-beam CTs (CBCTs). The clinical target volumes (CTVs) consisting of pelvic lymph nodes, prostate, and seminal vesicles as well asmore » the OARs were delineated on each CBCT and the initial CT. Three adaptive strategies were analyzed. Two of these methods relied on a two-step patient positioning at each fraction. First step: a bony registration was used to deliver the nodal CTV prescription. Second step: a gold marker registration was then used either to (1) complete the dose delivered to the prostate (complement); (2) or give almost the entire prescription to the prostate with a weak dose gradient between the targets to compensate for possible motions (gradient). The third method (COR) used a pool of precalculated plans based on images acquired at previous treatment fractions. At each new fraction, a plan is selected from that pool based on the daily position of prostate center-of-mass. The dosimetric comparison was conducted and results are presented with and without the systematic shift in the prostate position on the CT planning. The adaptive strategies were compared to the current clinical standard where all fractions are treated with the initial nonadaptive plan. Results: The minimum daily prostate D{sub 95%} is improved by 2%, 9%, and 6% for the complement, the gradient, and the COR approaches, respectively, compared to the nonadaptive method. The average nodal CTV D{sub 95%} remains constant across the strategies, except for the gradient approach where a reduction of 7% is observed. However, a correction of the systematic shift reduced the problem, and the adaptive strategies remain robust against the prostate movement across the fraction. The bladder V{sub 55Gy} is reduced by 35% on average for the adaptive strategies. Conclusions: Because they offer increased CTV coverage and OAR sparing, adaptive methods may be suitable candidates for simple and efficient adaptive treatment strategies for prostate cancer. Margin reduction and systematic error correction in the prostate position improve the protection of the OAR and the dose coverage. A cumulative dose to simulate a complete treatment would show real effects and allow a better comparison between each method.« less

Nodal Clearance Rate and Long-Term Efficacy of Individualized Sentinel Node–Based Pelvic Intensity Modulated Radiation Therapy for High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Müller, Arndt-Christian, E-mail: arndt-christian.mueller@med.uni-tuebingen.de; Eckert, Franziska; Paulsen, Frank

2016-02-01

Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement − n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN–pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapymore » sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series.« less

[Changes in prostatic circulation in response to laser therapy and magnetic therapy in patients with benign prostatic hyperplasia].

PubMed

2005-01-01

The results of preoperative preparation were analysed in 59 patients with prostatic benign hyperplasia (PBH) subjected to TUR. Treatment outcomes were assessed by transrectal ultrasound (color Doppler mapping) in two groups of patients. Group 1 received combined therapy including transrectal laser radiation of the prostate, group 2--transrectal magnetotherapy. The analysis showed that laser radiation reduced insignificantly the size of the prostate and adenomatous node, improved microcirculation and circulation in the prostate. This resulted in relief of inflammation and reduction of the number of postoperative inflammatory complications. Transrectal magnetotherapy has a positive effect on vascularization and hemodynamics of the prostate, local immunity, contamination of the tissues with pathogenic flora.

Comparison of the Walz Nomogram and Presence of Secondary Circulating Prostate Cells for Predicting Early Biochemical Failure after Radical Prostatectomy for Prostate Cancer in Chilean Men.

PubMed

Murray, Nigel P; Reyes, Eduardo; Orellana, Nelson; Fuentealba, Cynthia; Jacob, Omar

2015-01-01

To determine the utility of secondary circulating prostate cells for predicting early biochemical failure after radical prostatectomy for prostate cancer and compare the results with the Walz nomagram. A single centre, prospective study of men with prostate cancer treated with radical prostatectomy between 2004 and 2014 was conducted, with registration of clinical-pathological details, total serum PSA pre-surgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes, seminal vesicles and pathological stage. Secondary circulating prostate cells were obtained using differential gel centrifugation and assessed using standard immunocytochemistry with anti-PSA. Biochemical failure was defined as a PSA >0.2ng/ml, predictive values werecalculated using the Walz nomagram and CPC detection. A total of 326 men participated, with a median follow up of 5 years; 64 had biochemical failure within two years. Extracapsular extension, positive surgical margins, pathological stage, Gleason score ≥ 8, infiltration of seminal vesicles and lymph nodes were all associated with higher risk of biochemical failure. The discriminative value for the nomogram and circulating prostate cells was high (AUC >0.80), predictive values were higher for circulating prostate cell detection, with a negative predictive value of 99%, sensitivity of 96% and specificity of 75%. The nomagram had good predictive power to identify men with a high risk of biochemical failure within two years. The presence of circulating prostate cells had the same predictive power, with a higher sensitivity and negative predictive value. The presence of secondary circulating prostate cells identifies a group of men with a high risk of early biochemical failure. Those negative for secondary CPCs have a very low risk of early biochemical failure.

No Detrimental Effect of a Positive Family History on Long-Term Outcomes Following Radical Prostatectomy.

PubMed

Brath, Johannes M S; Grill, Sonja; Ankerst, Donna P; Thompson, Ian M; Gschwend, Juergen E; Herkommer, Kathleen

2016-02-01

Overall 1 in 5 patients with prostate cancer has a positive family history. In this report we evaluated the association between family history and long-term outcomes following radical prostatectomy. Patients treated with radical prostatectomy were identified from a German registry, and separated into positive first-degree family history vs negative family history (strictly negative, requiring at least 1 male first-degree relative older than 60 years and no prostate cancer in the family). Kaplan-Meier curves and Cox proportional hazards models were used for association analyses with biochemical recurrence-free and prostate cancer specific survival. Median followup for 7,690 men included in the study was 8.4 years. Of the 754 younger patients less than 55 years old 50.9% (384) had a family history compared to 40.4% of the older patients (2,803; p <0.001). The 10-year biochemical recurrence-free (62.5%) and prostate cancer specific survival (96.1%) rates did not differ between patients with vs without a family history, nor between the younger vs older patient groups (all p >0.05). Prostate specific antigen, pathological stage, node stage and Gleason score were the only significant predictors for biochemical recurrence-free survival, while pathological stage, node stage (all p <0.005) and Gleason score (Gleason 7 vs 6 or less-HR 1.711, 95% CI 1.056-2.774, p = 0.03; Gleason 8 or greater vs 6 or less-HR 4.516, 95% CI 2.776-7.347, p <0.0001) were the only predictors for prostate cancer specific survival. A family history of prostate cancer has no bearing on long-term outcomes after radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Aggressive rat prostate tumors reprogram the benign parts of the prostate and regional lymph nodes prior to metastasis

PubMed Central

Thysell, Elin; Halin Bergström, Sofia; Bergh, Anders

2017-01-01

In order to grow and spread tumors need to interact with adjacent tissues. We therefore hypothesized that small but aggressive prostate cancers influence the rest of the prostate and regional lymph nodes differently than tumors that are more indolent. Poorly metastatic (Dunning AT1) or highly metastatic (Dunning MLL) rat prostate tumor cells were injected into the ventral prostate lobe of immunocompetent rats. After 10 days—when the tumors occupied about 30% of the prostate lobe and lymph node metastases were undetectable—the global gene expression in tumors, benign parts of the prostate, and regional iliac lymph nodes were examined to define tumor-induced changes related to preparation for future metastasis. The tumors induced profound effects on the gene expression profiles in the benign parts of the prostate and these were strikingly different in the two tumor models. Gene ontology enrichment analysis suggested that tumors with high metastatic capacity were more successful than less metastatic tumors in inducing tumor-promoting changes and suppressing anti-tumor immune responses in the entire prostate. Some of these differences such as altered angiogenesis, nerve density, accumulation of T-cells and macrophages were verified by immunohistochemistry. Gene expression alterations in the regional lymph nodes suggested decreased quantity and activation of immune cells in MLL-lymph nodes that were also verified by immunostaining. In summary, even when small highly metastatic prostate tumors can affect the entire tumor-bearing organ and pre-metastatic lymph nodes differently than less metastatic tumors. When the kinetics of these extratumoral influences (by us named TINT = tumor instructed normal tissue) are more precisely defined they could potentially be used as markers of disease aggressiveness and become therapeutic targets. PMID:28472073

Irradiation of the prostate and pelvic lymph nodes with an adaptive algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, A. B.; Chen, J.; Nguyen, T. B.

2012-02-15

Purpose: The simultaneous treatment of pelvic lymph nodes and the prostate in radiotherapy for prostate cancer is complicated by the independent motion of these two target volumes. In this work, the authors study a method to adapt intensity modulated radiation therapy (IMRT) treatment plans so as to compensate for this motion by adaptively morphing the multileaf collimator apertures and adjusting the segment weights. Methods: The study used CT images, tumor volumes, and normal tissue contours from patients treated in our institution. An IMRT treatment plan was then created using direct aperture optimization to deliver 45 Gy to the pelvic lymphmore » nodes and 50 Gy to the prostate and seminal vesicles. The prostate target volume was then shifted in either the anterior-posterior direction or in the superior-inferior direction. The treatment plan was adapted by adjusting the aperture shapes with or without re-optimizing the segment weighting. The dose to the target volumes was then determined for the adapted plan. Results: Without compensation for prostate motion, 1 cm shifts of the prostate resulted in an average decrease of 14% in D-95%. If the isocenter is simply shifted to match the prostate motion, the prostate receives the correct dose but the pelvic lymph nodes are underdosed by 14% {+-} 6%. The use of adaptive morphing (with or without segment weight optimization) reduces the average change in D-95% to less than 5% for both the pelvic lymph nodes and the prostate. Conclusions: Adaptive morphing with and without segment weight optimization can be used to compensate for the independent motion of the prostate and lymph nodes when combined with daily imaging or other methods to track the prostate motion. This method allows the delivery of the correct dose to both the prostate and lymph nodes with only small changes to the dose delivered to the target volumes.« less

Non-invasive imaging of prostate cancer progression in nude mice using iRFP gene reporter

NASA Astrophysics Data System (ADS)

Zhu, Banghe; Wu, Grace; Robinson, Holly; Wilganowski, Nathaniel; Sevick-Muraca, Eva M.

2013-03-01

Prostate cancer (PCa) is the second most common cancer in US men. Metastasis is the final step of tumor progression and remains the primary cause of PCa death. Hence preclinical, orthotopic models of PCa metastasis are necessary to develop new therapeutics against metastatic disease. Yet unlike irrelevant subcutaneous tumor models, the deployment of orthotopic models of cancer metastasis in drug research and development is limited by the inability to longitudinally monitor cancer progression/regression in response to administration of experimental pharmaceuticals. Recently, a nearinfrared fluorescent protein (iRFP) was created for deeper imaging [1]. Imaging prostate tumor growth and lymph node metastasis in nude mice therefore becomes possible using this new fluorescent gene reporter. In this study, we first developed an intensified CCD (ICCD)-based iRFP fluorescence imaging device. Then human PCa PC3 cell lines expressing iRFP gene reporter were orthotopically implanted in male Nu/Nu mice at 8-10 weeks old. After 6-10 weeks, in vivo, in situ and ex vivo fluorescence imaging was performed. In vivo iRFP fluorescence imaging showed that the detected fluorescence concentrated at the prostate and became stronger over time, indicating the growth of implanted PCa. Fluorescence was non-invasively detected at locations of prostate-draining lymph nodes as early as 5 weeks post implantation, indicating the metastasis to lymph nodes. In situ and ex vivo fluorescence imaging demonstrated that the detected signals from PCa and lymph nodes were correlated with cancer positive status of tissues as assessed through standard pathology.

Characterization of an ICII82, 780-Induced, Estrogen Receptor (ER)-beta Mediated Apoptotic Pathway in Prostate Cancer Cells and Establishment of (ER)-beta-Regulated Electrophile-Processing Phase II Enzyme Downregulation as a Promotional Factor in Human Prostatic Carcinogenesis

DTIC Science & Technology

2001-05-01

absent in higher-grade cancers. ERP3 expression reappeared in metastatic prostatic carcinomas . The results were also compared to ERMo and androgen...metastatic prostatic carcinomas in bone and lymph nodes. The results were compared to ERax and androgen receptor expressions in those samples. Taken... carcinomas of the peripheral zone were in contrast strongly positive for the 13 receptor whereas its expression in grade 415 cancers was negligible to

Beyond the Briganti nomogram: Individualisation of lymphadenectomy using selective sentinel node biopsy during radical prostatectomy for prostate cancer.

PubMed

Monserrat-Monfort, J J; Martinez-Sarmiento, M; Vera-Donoso, C D; Vera-Pinto, V; Sopena-Novales, P; Bello-Arqués, P; Boronat-Tormo, F

To validate the technique of selective sentinel node biopsy for diagnosing and staging intermediate to high-risk prostate cancer by comparing the technique with conventional extended lymphadenectomy (eLFD) in a prospective, longitudinal comparative study. We applied the technique to 45 patients. After an intraprostatic injection of 99m Tc-nanocolloid and preoperative single-photon emission computed tomography (SPECT/CT), we extracted the sentinel lymph nodes, guided by a portable Sentinella® gamma camera and a laparoscopic gamma-ray detection probe. The eLFD was completed to establish the negative predictive value of the technique. SPECT/CT showed radiotracer deposits outside the eLFD territory in 73% of the patients and the laparoscopic gamma probe in 60%. The mean number of active foci per patient was 4.3 in the SPECT/CT and 3.2 in the laparoscopic gamma probe. The mean number of extracted sentinel lymph nodes was 4.3 (0-14), with 26% outside the eLFD territory. The lymph nodes were metastatic in 10 patients (22%), 6/40 (15%) when the prostatectomy was the primary treatment. In all cases with metastatic lymph nodes, there was at least one positive sentinel node. Metastatic sentinel lymph nodes were found outside the eLFD territory in 3/10 patients (30%). The sensitivity was 100%, the specificity was 94.73%, the positive predictive value was 81.81%, and the negative predictive value was 100%. Selective sentinel node biopsy is superior to eLFD for diagnosing lymph node involvement and can avoid eLFD when metastatic sentinel lymph nodes are not found (85%), with the consequent functional advantages. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

68Ga-Labeled Anti-Prostate-Specific Membrane Antigen Peptide as Marker for Androgen Deprivation Therapy Response in Prostate Cancer.

PubMed

Schlenkhoff, Carl Diedrich; Gaertner, Florian; Essler, Markus; Hauser, Stefan; Ahmadzadehfar, Hojjat

2016-05-01

Prostate cancer was diagnosed in a 71-year-old man with an elevated prostate-specific antigen. The CT of the abdomen showed multiple para-aortal lymph nodes, and thus, a Ga anti-prostate-specific membrane antigen (PSMA-11) PET/CT was initiated, which showed, aside from the prostate cancer and multiple iliacal and para-aortal lymph node metastases, an increased tracer uptake in a lymph node left cervical. According to this advanced disease, a palliative therapy with GnRH agonist was initiated. A second PSMA-11 PET/CT was performed 4 months later, which showed a very good response; thus, additional radiation of the pelvis and the draining lymphatic system was performed.

Robotic-assisted pelvic lymph node dissection for prostate cancer: frequency of nodal metastases and oncological outcomes.

PubMed

Ledezma, Rodrigo A; Negron, Edris; Razmaria, Aria A; Dangle, Pankaj; Eggener, Scott E; Shalhav, Arieh L; Zagaja, Gregory P

2015-11-01

Limited data are available regarding the oncologic efficacy of pelvic lymph node dissection (PLND) performed during robotic-assisted laparoscopic prostatectomy (RALP) for prostate cancer. We aimed to determine the frequency of pelvic lymph node metastasis and oncological outcomes following RALP with PLND in patients who did not receive adjuvant androgen deprivation therapy (ADT). We retrospectively reviewed the records of 1740 consecutive patients who underwent RALP and extended PLND. The primary endpoint was biochemical recurrence (BCR). The estimated BCR probability was obtained using the Kaplan-Meier method. Cox proportional hazard regression models were used to assess for predictors of BCR. One hundred and eight patients (6 %) with positive LNs were identified. The median number of LNs removed was 17 (IQR 11-24), and median follow-up was 26 months (IQR 14-43). Ninety-one (84 %) patients did not receive adjuvant ADT of whom 60 % had BCR with a median time to recurrence of 8 months. The 1- and 3-year BCR-free probability was 42 and 28 %, respectively. Patients with ≤2 LN+ had significantly better biochemical-free estimated probability compared to those with >2 LN+ (p = 0.002). The total number of LN+ (HR = 1.1; 95 % CI 1.01-1.2, p = 0.04) and Gleason 8-10 (HR = 1.96; 95 % CI 1.1-3.4, p = 0.02) were predictors of BCR on multivariate analysis. Among men with positive lymph nodes at time of robotic prostatectomy, those with two or fewer positive nodes and Gleason <8 exhibited favorable biochemical-free survival without adjuvant therapy.

Correlation between prolonged use of aspirin and prognostic risk in prostate cancer.

PubMed

Dell'Atti, Lucio

2014-01-01

In recent years the role of inflammation in cancer etiology has gained attention and several studies have suggested that acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs may have chemopreventive activity and reduce the risk of prostate cancer. We investigated whether there is a correlation between prolonged use of aspirin and prognostic risk in prostate cancer. From January 2002 to December 2007 we performed 385 radical prostatectomies for localized prostate cancer. Patients were divided into 2 groups: group A (GA) comprised 174 patients who took aspirin 100 mg once daily for 2 years or more; group B (GB) consisted of 211 patients who did not take NSAIDs, or only occasionally. To evaluate the correlation between aspirin use and prognostic risk in prostate cancer we examined the following factors: biochemical recurrence, percentage of positive surgical margins, pathological stage, pathological Gleason score, percentage of positive lymph nodes, and preoperative PSA level. There was no statistical difference in preoperative PSA levels (6.5 and 6.9 ng/mL; P = 0.045) between the 2 groups. The incidence of positive surgical margins was 18.9% in GA and 28.9% in GB (P <0.002). The percentage of positive lymph nodes in patients with positive surgical margins in GB (47.5%) was statistically higher than that in GA (27.2%). With an average follow-up period of 4.6 years, 22.7% of patients in GA and 32.7% in GB developed biochemical recurrence. In the stratified analysis we observed significant differences in the association between prediagnostic aspirin use and prognostic risk for patients with Gleason score 7 and T2 stage of disease. The daily use of aspirin was significantly associated with a lower risk of disease progression, with a hazard ratio of 0.92 (95% CI 0.85-0.99). These results provide further evidence that aspirin may have chemopreventive activity against prostate cancer and highlight the need for additional research. Additional studies with more detailed exposure measurement are warranted to evaluate questions about dose, the best age to begin treatment, and the duration of therapy.

Expression of the gastrin-releasing peptide receptor, the prostate stem cell antigen and the prostate-specific membrane antigen in lymph node and bone metastases of prostate cancer.

PubMed

Ananias, Hildo J K; van den Heuvel, Marius C; Helfrich, Wijnand; de Jong, Igle J

2009-07-01

Cell membrane antigens like the gastrin-releasing peptide receptor (GRPR), the prostate stem cell antigen (PSCA), and the prostate-specific membrane antigen (PSMA), expressed in prostate cancer, are attractive targets for new therapeutic and diagnostic applications. Therefore, we investigated in this study whether these antigens are expressed in metastasized prostate cancer. Formalin-fixed, paraffin-embedded specimens of 15 patients with uni- or bilateral lymph node metastases of prostate cancer (totaling 21 cases) and 17 patient-cases of bone metastases were processed for immunohistochemistry with anti-GRPR, anti-PSCA, and anti-PSMA antibodies. A pathologist blinded to clinical and pathological data scored the immunoreactivity for these antibodies on a four-point scale (0 = no staining; 1+ = weak staining; 2+ = moderate staining; 3+ = strong staining) and documented the distribution pattern. GRPR staining in lymph node metastases was seen in 85.7% of cases (18 of 21 cases), PSCA in 95.2% (20/21), and PSMA in 100% (21/21). GRPR in bone metastases was seen in 52.9% of cases (9/17), PSCA in 94.1% (16/17), and PSMA in 100% (17/17). We have shown for the first time that GRPR is expressed in the vast majority of lymph node metastases and in 52.9% of bone metastases of prostate cancer. PSCA and PSMA are both highly expressed in lymph node and bone metastases. Although PSCA and PSMA are mostly expressed in prostate cancer metastases, GRPR offers an interesting alternative target as it can be targeted relatively easy with peptide-based (radio)pharmaceuticals. (c) 2009 Wiley-Liss, Inc.

Simplified intraoperative sentinel-node detection performed by the urologist accurately determines lymph-node stage in prostate cancer.

PubMed

Kjölhede, Henrik; Bratt, Ola; Gudjonsson, Sigurdur; Sundqvist, Pernilla; Liedberg, Fredrik

2015-04-01

The reference standard for lymph-node staging in prostate cancer is currently an extended pelvic lymph-node dissection (ePLND), which detects most, but not all, regional lymph-node metastases. As an alternative to ePLND, sentinel-node dissection with preoperative isotope injection and imaging has been reported. The objective was to determine whether intraoperative sentinel-node detection with a simplified protocol can accurately determine lymph-node stage in prostate cancer patients. Patients with biopsy-verified high-risk prostate cancer with tumour stage T2-3 were included in the study. All patients underwent both ePLND and sentinel-node detection. (99m)Tc-marked nanocolloid was injected peritumourally by the operating urologist after induction of anaesthesia just before surgery. Sentinel nodes were detected both in vivo and ex vivo intraoperatively using a gamma probe. Sentinel nodes and metastases and their locations were recorded. Sensitivity and specificity were calculated. At least one sentinel node was detected in 72 (87%) of the 83 patients. In 13 (18%) of these 72 patients sentinel nodes were detected outside the ePLND template. In six of these 13 patients, the Sentinel nodes from outside the template contained metastases, which proved to be the only metastases in two. For 12 patients the only metastatic deposit found was a micrometastasis (≤2 mm) in a sentinel node. In the 72 patients with detectable sentinel nodes, pathological analysis of the sentinel node correctly categorized 71 and ePLND 70 patients. This protocol yielded results comparable to the commonly used technique of sentinel-node detection, but with more cases of non-detection.

Early diagnostic role of PSA combined miR-155 detection in prostate cancer.

PubMed

Guo, T; Wang, X-X; Fu, H; Tang, Y-C; Meng, B-Q; Chen, C-H

2018-03-01

As a kind of malignant tumor in the male genitourinary system, prostate cancer exhibits significantly increased occurrence. Prostate-specific antigen (PSA) expression can be seen in the prostate cancer, prostatitis, and other diseases, therefore, lack of diagnostic specificity. The miR-155 expression is abnormally increased in the tumors. Therefore, this study aims to explore the clinical significance of PSA combined miR-155 detection in the early diagnosis of prostate cancer. A total of 86 patients diagnosed with prostate cancer were enrolled in this study. PSA and miR-155 gene expression in tumor tissue were detected by using Real-time PCR. The serum levels of PSA were measured by using enzyme-linked immunosorbent assay (ELISA). The correlation of PSA and miR-155 expression with age, body mass index (BMI), tumor volume, tumor-node-metastasis (TNM) stage, lymph node metastasis (LNM), and other clinicopathological features were analyzed, respectively. Serum PSA expression and PSA gene in tumor tissue were significantly higher compared to that in adjacent tissues (p<0.05). PSA gene and protein increased significantly with the clinical stage of TNM and decreased following the increase of grade (p<0.05). The miR-155 level was significantly elevated in the tumor tissue compared with para-carcinoma tissue (p<0.05). PSA and miR-155 expressions were positively correlated with TNM stage, tumor volume, and LNM, and negatively correlated with grade (p<0.05). PSA and miR-155 were closely related to the clinicopathological features of prostate cancer. Combined detection is helpful for the early diagnosis of prostate cancer.

Comparison of semi-extended and standard lymph node dissection in radical prostatectomy: A single-institute experience.

PubMed

Hoshi, Senji; Hayashi, Natuho; Kurota, Yuuta; Hoshi, Kiyotsugu; Muto, Akinori; Sugano, Osamu; Numahata, Kenji; Bilim, Vladimir; Sasagawa, Isoji; Ohta, Shoichiro

2015-09-01

Standard lymphadenectomy for prostate cancer is limited to the obturator lymph nodes (LNs), although the internal and external iliac LNs represent the primary landing zone for prostatic lymphatic drainage. We performed anatomically semi-extended pelvic lymph node dissection (PLND) to assess the incidence of LN metastasis in cases of clinically localized prostate cancer. A total of 730 consecutive patients underwent radical prostatectomy with either semi-extended PLND, comprising 6 selective fields, namely the external iliac, internal iliac and obturator LNs bilaterally, or standard LND (obturator LNs alone). A total of 131 patients undergoing semi-extended PLND were compared with 599 patients undergoing standard LND. The patients were stratified into high-risk [prostate-specific antigen (PSA)>20 ng/ml, Gleason score (GS)≥8], intermediate-risk (PSA 10-20 ng/ml, GS=4+3) and low-risk (PSA<10 ng/ml, GS≤3+4) subgroups. Following semi-extended LND, positive LNs were detected in 12/61 (20%) of the high-risk, 1/30 (3%) of the intermediate-risk and 0/40 (0%) of the low-risk cases. Following standard LND, positive LNs were detected in 13/182 (7%) of the high-risk, 1/164 (0.6%) of the intermediate-risk and 0/253 (0%) of the low-risk cases. In high-risk patients, the detection rate of LN metastasis was significantly higher following extended LND compared with standard LND (P<0.01). In 9 of 13 patients (69%), metastases were identified in the internal and external iliac regions, despite negative obturator LNs. There were no significant differences regarding intraoperative and postoperative complications or blood loss in the two groups. There was no lymphocele formation in patients undergoing either standard or semi-extended LND. Extended pelvic LND (PLND) is associated with a high rate of LN metastasis detection outside the fields of standard LND in cases with clinically localized prostate cancer. Therefore, LND including the internal and external iliac LNs should be performed in all patients with high-risk prostate cancer; however, in the low-risk group, PLND may be omitted.

Adaptive intensity modulated radiotherapy for advanced prostate cancer

NASA Astrophysics Data System (ADS)

Ludlum, Erica Marie

The purpose of this research is to develop and evaluate improvements in intensity modulated radiotherapy (IMRT) for concurrent treatment of prostate and pelvic lymph nodes. The first objective is to decrease delivery time while maintaining treatment quality, and evaluate the effectiveness and efficiency of novel one-step optimization compared to conventional two-step optimization. Both planning methods are examined at multiple levels of complexity by comparing the number of beam apertures, or segments, the amount of radiation delivered as measured by monitor units (MUs), and delivery time. One-step optimization is demonstrated to simplify IMRT planning and reduce segments (from 160 to 40), MUs (from 911 to 746), and delivery time (from 22 to 7 min) with comparable plan quality. The second objective is to examine the capability of three commercial dose calculation engines employing different levels of accuracy and efficiency to handle high--Z materials, such as metallic hip prostheses, included in the treatment field. Pencil beam, convolution superposition, and Monte Carlo dose calculation engines are compared by examining the dose differences for patient plans with unilateral and bilateral hip prostheses, and for phantom plans with a metal insert for comparison with film measurements. Convolution superposition and Monte Carlo methods calculate doses that are 1.3% and 34.5% less than the pencil beam method, respectively. Film results demonstrate that Monte Carlo most closely represents actual radiation delivery, but none of the three engines accurately predict the dose distribution when high-Z heterogeneities exist in the treatment fields. The final objective is to improve the accuracy of IMRT delivery by accounting for independent organ motion during concurrent treatment of the prostate and pelvic lymph nodes. A leaf-shifting algorithm is developed to track daily prostate position without requiring online dose calculation. Compared to conventional methods of adjusting patient position, adjusting the multileaf collimator (MLC) leaves associated with the prostate in each segment significantly improves lymph node dose coverage (maintains 45 Gy compared to 42.7, 38.3, and 34.0 Gy for iso-shifts of 0.5, 1 and 1.5 cm). Altering the MLC portal shape is demonstrated as a new and effective solution to independent prostate movement during concurrent treatment.

Prognostic factors in prostate cancer patients treated by radical external beam radiotherapy.

PubMed

Garibaldi, Elisabetta; Gabriele, Domenico; Maggio, Angelo; Delmastro, Elena; Garibaldi, Monica; Russo, Filippo; Bresciani, Sara; Stasi, Michele; Gabriele, Pietro

2017-09-01

The aim of this paper was to analyze, retrospectively, in prostate cancer patients treated in our Centre with external beam radiotherapy, the prognostic factors and their impact on the outcome in terms of cancer-specific survival (CSS), biochemical disease-free survival (BDFS) and clinical disease-free survival (CDFS). From October 1999 and March 2012, 1080 patients were treated with radiotherapy at our Institution: 87% of them were classified as ≤cT2, 83% had a Gleason Score (GS) ≤7, their mean of iPSA was 18 ng/mL, and the rate of clinical positive nodes was 1%. The mean follow-up was 81 months. The statistically significant prognostic factors for all groups of patients at both, univariate and multivariate analysis, were the GS and the iPSA. In intermediate- and high- or very-high-risk patients at multivariate analysis other prognostic factors for CSS were positive nodes on computed tomography (CT) scan and rectal preparation during the treatment; for BDFS, the prognostic factors were patient risk classification, positive lymph nodes on CT scan and rectal/bladder preparation; for CDFS, the prognostic factors were the number of positive core on biopsy (P=0.003), positive lymph nodes on CT scan, and radiotherapy (RT) dose. In high/very-high risk patient group at multivariate analysis other prognostic factors for CSS were clinical/radiological stage and RT dose, for BDFS they were adjuvant hormone therapy, clinical/radiological stage, and RT dose >77.7 Gy, and for CDFS they were clinical/radiological stage and RT dose >77.7 Gy. The results of this study confirm the prognostic factors described in the recent literature, with the addition of rectal/bladder preparation, generally known for its effect on toxicity but not yet on outcome.

The STAMPEDE trial: paradigm-changing data through innovative trial design.

PubMed

Carthon, Bradley C; Antonarakis, Emmanuel S

2016-09-01

Despite the numerous regulatory approvals for prostate cancer, metastatic prostate cancer remains a huge burden for men worldwide. In an exciting development, James et al . recently published data from the Systemic Therapy in Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: a multi-stage multi-arm randomised control trial (STAMPEDE). This is an innovative multi-arm multi-stage (MAMS) trial that has utilized one control arm and several comparator arms in order to provide evidence for the inclusion of therapies beyond standard androgen deprivation alone. The patient population included: (I) men with high-risk, non-metastatic, node-negative disease; (II) men with distant-metastatic or node-positive disease; and (III) men with previously-treated prostate cancer by prostatectomy or definitive radiotherapy presenting with relapse. Men were to continue androgen deprivation for at least 2 years. The current data published by this group supports earlier results and provides additional evidence that docetaxel utilized in an up-front fashion provides a survival benefit in men with hormone-sensitive metastatic prostate cancer. Moreover, the initial results from STAMPEDE show how therapies without a demonstrated survival benefit can be efficiently excluded from further study once the likelihood of a benefit is ruled out by a predetermined analysis. In this piece, we will review the STAMPEDE data, contrast it with existing results, and provide our perspectives on how this will affect future trial conduct in the field of prostate cancer.

RTOG GU Radiation Oncology Specialists Reach Consensus on Pelvic Lymph Node Volumes for High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawton, Colleen A.F.; Michalski, Jeff; El-Naqa, Issam

2009-06-01

Purpose: Radiation therapy to the pelvic lymph nodes in high-risk prostate cancer is required on several Radiation Therapy Oncology Group (RTOG) clinical trials. Based on a prior lymph node contouring project, we have shown significant disagreement in the definition of pelvic lymph node volumes among genitourinary radiation oncology specialists involved in developing and executing current RTOG trials. Materials and Methods: A consensus meeting was held on October 3, 2007, to reach agreement on pelvic lymph node volumes. Data were presented to address the lymph node drainage of the prostate. Extensive discussion ensued to develop clinical target volume (CTV) pelvic lymphmore » node consensus. Results: Consensus was obtained resulting in computed tomography image-based pelvic lymph node CTVs. Based on this consensus, the pelvic lymph node volumes to be irradiated include: distal common iliac, presacral lymph nodes (S{sub 1}-S{sub 3}), external iliac lymph nodes, internal iliac lymph nodes, and obturator lymph nodes. Lymph node CTVs include the vessels (artery and vein) and a 7-mm radial margin being careful to 'carve out' bowel, bladder, bone, and muscle. Volumes begin at the L5/S1 interspace and end at the superior aspect of the pubic bone. Consensus on dose-volume histogram constraints for OARs was also attained. Conclusions: Consensus on pelvic lymph node CTVs for radiation therapy to address high-risk prostate cancer was attained and is available as web-based computed tomography images as well as a descriptive format through the RTOG. This will allow for uniformity in evaluating the benefit and risk of such treatment.« less

A rare presentation of metastasis of prostate adenocarcinoma to the stomach and rectum.

PubMed

Soe, Aye Min; Bordia, Sonal; Xiao, Philip Q; Lopez-Morra, Hernan; Tejada, Juan; Atluri, Sreedevi; Krishnaiah, Mahesh

2014-12-01

Prostate cancer is the second most common cause of cancer death in men in the United States. The most common sites of metastasis include the bone, lymph nodes, lung, liver, pleura, and adrenal glands, whereas metastatic prostate cancer involving the gastrointestinal tract has been rarely reported. A 64-year-old African-American man with a history of prostate cancer presented with anemia. He reported the passing of dark colored stools but denied hematemesis or hematochezia. Colonoscopy revealed circumferential nodularity, and histology demonstrated metastatic carcinoma of the prostate. Esophagogastroduodenoscopy showed hypertrophic folds in the gastric fundus, and microscopic examination revealed tumor cells positive for prostate-specific antigen. Bone scanning and computed tomography of the abdomen and pelvis did not show metastasis. It is crucial to distinguish primary gastrointestinal cancer from metastatic lesions, especially in patients with a history of cancer at another site, for appropriate management.

A Rare Presentation of Metastasis of Prostate Adenocarcinoma to the Stomach and Rectum

PubMed Central

Bordia, Sonal; Xiao, Philip Q; Lopez-Morra, Hernan; Tejada, Juan; Atluri, Sreedevi; Krishnaiah, Mahesh

2014-01-01

Prostate cancer is the second most common cause of cancer death in men in the United States. The most common sites of metastasis include the bone, lymph nodes, lung, liver, pleura, and adrenal glands, whereas metastatic prostate cancer involving the gastrointestinal tract has been rarely reported. A 64-year-old African-American man with a history of prostate cancer presented with anemia. He reported the passing of dark colored stools but denied hematemesis or hematochezia. Colonoscopy revealed circumferential nodularity, and histology demonstrated metastatic carcinoma of the prostate. Esophagogastroduodenoscopy showed hypertrophic folds in the gastric fundus, and microscopic examination revealed tumor cells positive for prostate-specific antigen. Bone scanning and computed tomography of the abdomen and pelvis did not show metastasis. It is crucial to distinguish primary gastrointestinal cancer from metastatic lesions, especially in patients with a history of cancer at another site, for appropriate management. PMID:25580360

Intraoperative Fluorescence Imaging for Detection of Sentinel Lymph Nodes and Lymphatic Vessels during Open Prostatectomy using Indocyanine Green.

PubMed

Yuen, Keiji; Miura, Tetsuya; Sakai, Iori; Kiyosue, Akiko; Yamashita, Masuo

2015-08-01

We investigated the feasibility and validity of intraoperative fluorescence imaging using indocyanine green for the detection of sentinel lymph nodes and lymphatic vessels during open prostatectomy. Indocyanine green was injected into the prostate under transrectal ultrasound guidance just before surgery. Intraoperative fluorescence imaging was performed using a near-infrared camera system in 66 consecutive patients with clinically localized prostate cancer after a 10-patient pilot test to optimize indocyanine green dosing, observation timing and injection method. Lymphatic vessels were visualized and followed to identify the sentinel lymph nodes. Confirmatory pelvic lymph node dissection including all fluorescent nodes and open radical prostatectomy were performed in all patients. Lymphatic vessels were successfully visualized in 65 patients (98%) and sentinel lymph nodes in 64 patients (97%). Sentinel lymph nodes were located in the obturator fossa, internal and external iliac regions, and rarely in the common iliac and presacral regions. A median of 4 sentinel lymph nodes per patient was detected. Three lymphatic pathways, the paravesical, internal and lateral routes, were identified. Pathological examination revealed metastases to 9 sentinel lymph nodes in 6 patients (9%). All pathologically positive lymph nodes were detected as sentinel lymph nodes using this imaging. No adverse reactions due to the use of indocyanine green were observed. Intraoperative fluorescence imaging using indocyanine green during open prostatectomy enables the detection of lymphatic vessels and sentinel lymph nodes with high sensitivity. This novel method is technically feasible, safe and easy to apply with minimal additional operative time. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

SHBG Is an Important Factor in Stemness Induction of Cells by DHT In Vitro and Associated with Poor Clinical Features of Prostate Carcinomas

PubMed Central

Ma, Yuanyuan; Liang, Dongming; Liu, Jian; Wen, Jian-Guo; Servoll, Einar; Waaler, Gudmund; Sæter, Thorstein; Axcrona, Karol; Vlatkovic, Ljiljana; Axcrona, Ulrika; Paus, Elisabeth; Yang, Yue; Zhang, Zhiqian; Kvalheim, Gunnar; Nesland, Jahn M.; Suo, Zhenhe

2013-01-01

Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG) was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression. PMID:23936228

A Comprehensive Review of Contemporary Role of Local Treatment of the Primary Tumor and/or the Metastases in Metastatic Prostate Cancer

PubMed Central

Aoun, Fouad; Peltier, Alexandre; van Velthoven, Roland

2014-01-01

To provide an overview of the currently available literature regarding local control of primary tumor and oligometastases in metastatic prostate cancer and salvage lymph node dissection of clinical lymph node relapse after curative treatment of prostate cancer. Evidence Acquisition. A systematic literature search was conducted in 2014 to identify abstracts, original articles, review articles, research articles, and editorials relevant to the local control in metastatic prostate cancer. Evidence Synthesis. Local control of primary tumor in metastatic prostate cancer remains experimental with low level of evidence. The concept is supported by a growing body of genetic and molecular research as well as analogy with other cancers. There is only one retrospective observational population based study showing prolonged survival. To eradicate oligometastases, several options exist with excellent local control rates. Stereotactic body radiotherapy is safe, well tolerated, and efficacious treatment for lymph node and bone lesions. Both biochemical and clinical progression are slowed down with a median time to initiate ADT of 2 years. Salvage lymph node dissection is feasible in patients with clinical lymph node relapse after local curable treatment. Conclusion. Despite encouraging oncologic midterm results, a complete cure remains elusive in metastatic prostate cancer patients. Further advances in imaging are crucial in order to rapidly evolve beyond the proof of concept. PMID:25485280

Magnetic Resonance Lymphography Findings in Patients With Biochemical Recurrence After Prostatectomy and the Relation With the Stephenson Nomogram

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meijer, Hanneke J.M., E-mail: H.Meijer@rther.umcn.nl; Debats, Oscar A.; Roach, Mack

2012-12-01

Purpose: To estimate the occurrence of positive lymph nodes on magnetic resonance lymphography (MRL) in patients with a prostate-specific antigen (PSA) recurrence after prostatectomy and to investigate the relation between score on the Stephenson nomogram and lymph node involvement on MRL. Methods and Materials: Sixty-five candidates for salvage radiation therapy were referred for an MRL to determine their lymph node status. Clinical and histopathologic features were recorded. For 49 patients, data were complete to calculate the Stephenson nomogram score. Receiver operating characteristic (ROC) analysis was performed to determine how well this nomogram related to the MRL result. Analysis was donemore » for the whole group and separately for patients with a PSA <1.0 ng/mL to determine the situation in candidates for early salvage radiation therapy, and for patients without pathologic lymph nodes at initial lymph node dissection. Results: MRL detected positive lymph nodes in 47 patients. ROC analysis for the Stephenson nomogram yielded an area under the curve (AUC) of 0.78 (95% confidence interval, 0.61-0.93). Of 29 patients with a PSA <1.0 ng/mL, 18 had a positive MRL. Of 37 patients without lymph node involvement at initial lymph node dissection, 25 had a positive MRL. ROC analysis for the Stephenson nomogram showed AUCs of 0.84 and 0.74, respectively, for these latter groups. Conclusion: MRL detected positive lymph nodes in 72% of candidates for salvage radiation therapy, in 62% of candidates for early salvage radiation therapy, and in 68% of initially node-negative patients. The Stephenson nomogram showed a good correlation with the MRL result and may thus be useful for identifying patients with a PSA recurrence who are at high risk for lymph node involvement.« less

Robot-assisted Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer.

PubMed

Montorsi, Francesco; Gandaglia, Giorgio; Fossati, Nicola; Suardi, Nazareno; Pultrone, Cristian; De Groote, Ruben; Dovey, Zach; Umari, Paolo; Gallina, Andrea; Briganti, Alberto; Mottrie, Alexandre

2017-09-01

Salvage lymph node dissection has been described as a feasible treatment for the management of prostate cancer patients with nodal recurrence after primary treatment. To report perioperative, pathologic, and oncologic outcomes of robot-assisted salvage nodal dissection (RASND) in patients with nodal recurrence after radical prostatectomy (RP). We retrospectively evaluated 16 patients affected by nodal recurrence following RP documented by positive positron emission tomography/computed tomography scan. Surgery was performed using DaVinci Si and Xi systems. A pelvic nodal dissection that included lymphatic stations overlying the external, internal, and common iliac vessels, the obturator fossa, and the presacral nodes was performed. In 13 (81.3%) patients a retroperitoneal lymph node dissection that included all nodal tissue located between the aortic bifurcation and the renal vessels was performed. Perioperative outcomes consisted of operative time, blood loss, length of hospital stay, and complications occurred within 30 d after surgery. Biochemical response (BR) was defined as a prostate-specific antigen level <0.2 ng/ml at 40 d after RASND. Median operative time, blood loss, and length of hospital stay were 210min, 250ml, and 3.5 d. The median number of nodes removed was 16.5. Positive lymph nodes were detected in 11 (68.8%) patients. Overall, four (25.0%) and five (31.2%) patients experienced intraoperative and postoperative complications, respectively. Overall, one (6.3%) and four (25.0%) patients had Clavien I and II complications within 30 d after RASND, respectively. Overall, five (33.3%) patients experienced BR after surgery. Our study is limited by the small cohort of patients evaluated and by the follow-up duration. RASND represents a feasible procedure in patients with nodal recurrence after RP and provides acceptable short-term oncologic outcomes, where one out of three patients experience BR immediately after surgery. Long-term data are needed to confirm the effectiveness of this approach. We report our initial experience with robot-assisted salvage nodal dissection for the management of patients with lymph node recurrence after radical prostatectomy. This technique represents a feasible and effective approach, where no high-grade complications were recorded and one out of three patients experienced biochemical response at 40 d after surgery. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

[11C]choline-PET-guided helical tomotherapy and estramustine in a patient with pelvic-recurrent prostate cancer: local control and toxicity profile after 24 months.

PubMed

Alongi, Filippo; Schipani, Stefano; Samanes Gajate, Ana Maria; Rosso, Alberto; Cozzarini, Cesare; Fiorino, Claudio; Alongi, Pierpaolo; Picchio, Maria; Gianolli, Luigi; Messa, Cristina; Di Muzio, Nadia

2010-01-01

[11C]choline positron emission tomograhy can be useful to detect metastatic disease and to localize isolated lymph node relapse after primary treatment in case of prostate-specific antigen failure. In case of lymph node failure in prostate cancer patients, surgery or radiotherapy can be proposed with a curative intent. Some reports have suggested that radiotherapy could have a role in local control of oligometastatic lymph node disease. This is the first reported case of [11C]choline positron emission tomography-guided helical tomotherapy concomitant with estramustine for the treatment of pelvic-recurrent prostate cancer. At 24 months after the end of helical tomotherapy, prostate-specific antigen was undetectable and no late toxicities were recorded. A disease-free survival of 24 months, in the absence of any type of systemic therapy, is uncommon in metastatic prostate cancer. The therapeutic approach of the case report is discussed and a literature review on the issue is presented.

Comparison of 18F-FACBC and 11C-choline PET/CT in patients with radically treated prostate cancer and biochemical relapse: preliminary results.

PubMed

Nanni, Cristina; Schiavina, Riccardo; Boschi, Stefano; Ambrosini, Valentina; Pettinato, Cinzia; Brunocilla, Eugenio; Martorana, Giuseppe; Fanti, Stefano

2013-07-01

We assessed the rate of detection rate of recurrent prostate cancer by PET/CT using anti-3-(18)F-FACBC, a new synthetic amino acid, in comparison to that using (11)C-choline as part of an ongoing prospective single-centre study. Included in the study were 15 patients with biochemical relapse after initial radical treatment of prostate cancer. All the patients underwent anti-3-(18)F-FACBC PET/CT and (11)C-choline PET/CT within a 7-day period. The detection rates using the two compounds were determined and the target-to-background ratios (TBR) of each lesion are reported. No adverse reactions to anti-3-(18)F-FACBC PET/CT were noted. On a patient basis, (11)C-choline PET/CT was positive in 3 patients and negative in 12 (detection rate 20%), and anti-3-(18)F-FACBC PET/CT was positive in 6 patients and negative in 9 (detection rate 40%). On a lesion basis, (11)C-choline detected 6 lesions (4 bone, 1 lymph node, 1 local relapse), and anti-3-(18)F-FACBC detected 11 lesions (5 bone, 5 lymph node, 1 local relapse). All (11)C-choline-positive lesions were also identified by anti-3-(18)F-FACBC PET/CT. The TBR of anti-3-(18)F-FACBC was greater than that of (11)C-choline in 8/11 lesions, as were image quality and contrast. Our preliminary results indicate that anti-3-(18)F-FACBC may be superior to (11)C-choline for the identification of disease recurrence in the setting of biochemical failure. Further studies are required to assess efficacy of anti-3-(18)F-FACBC in a larger series of prostate cancer patients.

Fluorescence-enhanced robotic radical prostatectomy using real-time lymphangiography and tissue marking with percutaneous injection of unconjugated indocyanine green: the initial clinical experience in 50 patients.

PubMed

Manny, Ted B; Patel, Manish; Hemal, Ashok K

2014-06-01

Pilot studies have demonstrated the utility of indocyanine green (ICG) sentinel lymphadenectomy for prostate cancer. Prior work has used ICG with radiocontrast agents injected at a separate procedure and relied on assistant-controlled fluorescence systems, making the technique costly and cumbersome. To describe the initial optimization and feasibility of fluorescence-enhanced robotic radical prostatectomy (FERRP) using real-time injection of ICG for tissue marking and identification of sentinel lymphatic drainage visualized by a fully integrated surgeon-controlled system. Patients with clinically localized prostate cancer at a tertiary referral center were offered FERRP. Ten patients participated in a pilot arm in which ICG dosing and injection technique were optimized. Fifty consecutive patients then underwent FERRP. After development of the space of Retzius, 0.4 ml of a 2.5 mg/ml ICG solution were injected into each lobe of the prostate using a robotically guided percutaneous needle. After ICG was allowed to travel through the pelvic lymphatics, lymphadenectomy was performed from the endopelvic fascia to the aortic bifurcation. Parameters describing the time course of tissue fluorescence and pelvic lymphangiography were systematically recorded. Lymphatic packets containing fluorescent nodes were considered sentinel. Percutaneous, robotic-guided ICG injection proved superior to cystoscope or transrectal delivery. Tissue marking was achieved in all patients, positively identifying the prostate with uniform fluorescence relative to the obturator nerve, seminal vesicles, vas deferens, and neurovascular pedicles at a mean time of 10 min postinjection. Sentinel nodes were identified in 76% of patients at a mean time of 30 min postinjection and had 100% sensitivity, 75.4% specificity, 14.6% positive predictive value, and 100% negative predictive value for the detection of nodal metastasis. FERRP is safe, feasible, and allows for reliable prostate tissue marking and identification of sentinel lymphatic drainage in the majority of patients. ICG sentinel nodes are highly sensitive but relatively nonspecific for the detection of nodal metastasis. Copyright © 2013. Published by Elsevier B.V.

Role of c-Src Activation on Prostate Cancer Lymph Node Metastases

DTIC Science & Technology

2008-10-01

dentistry Yonsei University College of Dentistry , Seoul, Korea D.D.S. 1995-1999 Dentistry Korea University Graduate School, Seoul, Korea M.S. 1999-2001...School of Dentistry , Ann Arbor, MI Postdoctoral training 2008- Present Cancer Biology A. Positions and Honors. Positions and Employment...Michigan School of Dentistry , Ann Arbor, MI Other Experience and Professional Memberships 2007- Associate Member, American Association for

The evaluation of multi-structure, multi-atlas pelvic anatomy features in a prostate MR lymphography CAD system

NASA Astrophysics Data System (ADS)

Meijs, M.; Debats, O.; Huisman, H.

2015-03-01

In prostate cancer, the detection of metastatic lymph nodes indicates progression from localized disease to metastasized cancer. The detection of positive lymph nodes is, however, a complex and time consuming task for experienced radiologists. Assistance of a two-stage Computer-Aided Detection (CAD) system in MR Lymphography (MRL) is not yet feasible due to the large number of false positives in the first stage of the system. By introducing a multi-structure, multi-atlas segmentation, using an affine transformation followed by a B-spline transformation for registration, the organ location is given by a mean density probability map. The atlas segmentation is semi-automatically drawn with ITK-SNAP, using Active Contour Segmentation. Each anatomic structure is identified by a label number. Registration is performed using Elastix, using Mutual Information and an Adaptive Stochastic Gradient optimization. The dataset consists of the MRL scans of ten patients, with lymph nodes manually annotated in consensus by two expert readers. The feature map of the CAD system consists of the Multi-Atlas and various other features (e.g. Normalized Intensity and multi-scale Blobness). The voxel-based Gentleboost classifier is evaluated using ROC analysis with cross validation. We show in a set of 10 studies that adding multi-structure, multi-atlas anatomical structure likelihood features improves the quality of the lymph node voxel likelihood map. Multiple structure anatomy maps may thus make MRL CAD more feasible.

Multiadaptive Plan (MAP) IMRT to Accommodate Independent Movement of the Prostate and Pelvic Lymph Nodes

DTIC Science & Technology

2013-06-01

08-1-0358 TITLE: Multiadaptive Plan (MAP) IMRT to Accommodate Independent Movement of the Prostate and Pelvic Lymph Nodes PRINCIPAL...AND SUBTITLE Multi-Adaptive Plan (MAP) IMRT to Accommodate Independent 5a. CONTRACT NUMBER W81XWH-08-1-0358 Movement of the Prostate and...multi-adaptive plan (MAP) IMRT to accommodate independent movement of the two targeted tumor volumes. In this project, we evaluated two adaptive

Diagnostic Accuracy of 64Copper Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging of Intermediate- to High-risk Prostate Cancer: Our Preliminary Experience.

PubMed

Cantiello, Francesco; Gangemi, Vincenzo; Cascini, Giuseppe Lucio; Calabria, Ferdinando; Moschini, Marco; Ferro, Matteo; Musi, Gennaro; Butticè, Salvatore; Salonia, Andrea; Briganti, Alberto; Damiano, Rocco

2017-08-01

To assess the diagnostic accuracy of 64 Copper prostate-specific membrane antigen ( 64 Cu-PSMA) positron emission tomography/computed tomography (PET/CT) in the primary lymph node (LN) staging of a selected cohort of intermediate- to high-risk prostate cancer (PCa) patients. An observational prospective study was performed in 23 patients with intermediate- to high-risk PCa, who underwent 64 Cu-PSMA PET/CT for local and lymph nodal staging before laparoscopic radical prostatectomy with an extended pelvic LN dissection. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for LN status of 64 Cu-PSMA PET/CT were calculated using the final pathological findings as reference. Furthermore, we evaluated the correlation of intraprostatic tumor extent and grading with 64 Cu-PSMA intraprostatic distribution. Pathological analysis of LN involvement in 413 LNs harvested from our study cohort identified a total of 22 LN metastases in 8 (5%) of the 23 (35%) PCa patients. Imaging-based LN staging in a per-patient analysis showed that 64 Cu-PSMA PET/CT was positive in 7 of 8 LN-positive patients (22%) with a sensitivity of 87.5%, specificity of 100%, PPV of 100%, and NPV of 93.7%, considering the maximum standardized uptake value (SUV max ) at 4 hours as our reference. Receiver operating characteristic curve was characterized by an area under the curve of 0.938. A significant positive association was observed between SUV max at 4 hours with Gleason score, index, and cumulative tumor volume. In our intermediate- to high-risk PCa patients study cohort, we showed the high diagnostic accuracy of 64 Cu-PSMA PET/CT for primary LN staging before radical prostatectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pommier, Pascal, E-mail: Pascal.pommier@lyon.unicancer.fr; Chabaud, Sylvie; Lagrange, Jean-Leon

Purpose: To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. Patients and Methods: Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: “low risk” (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus “high risk” (T3 or Gleason score >6 ormore » prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. Results: With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. Conclusion: Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.« less

PI-RADS version 2: Preoperative role in the detection of normal-sized pelvic lymph node metastasis in prostate cancer.

PubMed

Park, Sung Yoon; Shin, Su-Jin; Jung, Dae Chul; Cho, Nam Hoon; Choi, Young Deuk; Rha, Koon Ho; Hong, Sung Joon; Oh, Young Taik

2017-06-01

To analyze whether Prostate Imaging Reporting and Data System (PI-RADSv2) scores are associated with a risk of normal-sized pelvic lymph node metastasis (PLNM) in prostate cancer (PCa). A consecutive series of 221 patients who underwent magnetic resonance imaging and radical prostatectomy with pelvic lymph node dissection (PLND) for PCa were retrospectively analyzed under the approval of institutional review board in our institution. No patients had enlarged (≥0.8cm in short-axis diameter) lymph nodes. Clinical parameters [prostate-specific antigen (PSA), greatest percentage of biopsy core, and percentage of positive cores], and PI-RADSv2 score from two independent readers were analyzed with multivariate logistic regression and receiver operating-characteristic curve for PLNM. Diagnostic performance of PI-RADSv2 and Briganti nomogram was compared. Weighted kappa was investigated regarding PI-RADSv2 scoring. Normal-sized PLNM was found in 9.5% (21/221) of patients. In multivariate analysis, PI-RADSv2 (reader 1, p=0.009; reader 2, p=0.026) and PSA (reader 1, p=0.008; reader 2, p=0.037) were predictive of normal-sized PLNM. Threshold of PI-RADSv2 was a score of 5, where PI-RADSv2 was associated with high sensitivity (reader 1, 95.2% [20/21]; reader 2, 90.5% [19/21]) and negative predictive value (reader 1, 99.2% [124/125]; reader 2, 98.6% [136/138]). However, diagnostic performance of PI-RADSv2 (AUC=0.786-0.788) was significantly lower than that of Briganti nomogram (AUC=0.890) for normal-sized PLNM (p<0.05). The inter-reader agreement was excellent for PI-RADSv2 of 5 or not (weighted kappa=0.804). PI-RADSv2 scores may be associated with the risk of normal-sized PLNM in PCa. Copyright © 2017. Published by Elsevier B.V.

Comparison of 68Ga-PSMA PET/CT and multiparametric MRI for staging of high-risk prostate cancer68Ga-PSMA PET and MRI in prostate cancer.

PubMed

Tulsyan, Shruti; Das, Chandan J; Tripathi, Madhavi; Seth, Amlesh; Kumar, Rajeev; Bal, Chandrasekhar

2017-12-01

We carried out this study to compare Glu-NH-CO-NH-Lys-(Ahx) [Ga(HBED-CC)] [Ga prostate-specific membrane antigen-11 (PSMA-11)] PET with multiparametric MRI (mpMRI) for the staging of high-risk prostate cancer. This was a prospective study in which 36 patients with high-risk prostate cancer were included. The criteria for inclusion were biopsy-proven prostate cancer with a serum prostate specific antigen of at least 20 and/or Gleason's score of at least 8. Each patient then underwent both gallium-68 (Ga)-PSMA PET/computed tomography (CT) and mpMRI including diffusion-weighted whole-body imaging with background body signal suppression within an interval of 1 week and both modalities were compared for staging of primary disease, lymph node, and distant metastasis. The median age of the 36 patients included was 65 years (range: 44-80 years) and the median prostate specific antigen was 94.3 ng/ml (range: 20-19005  ng/ml). Concordance for localization of primary on Ga-PSMA PET/CT and MRI was observed in 19/36 (52.7%) patients. Concurrence for T staging on Ga-PSMA and MRI was observed in 58.3% of patients. Ga-PSMA PET/CT detected higher numbers of patients with regional (29) and nonregional (15) lymph nodes in comparison with MRI (20 and 5, respectively). Concurrence for regional and nonregional lymph node staging was observed in 72.2% of patients. Additional sites of metastatic disease reported on Ga-PSMA PET/CT were to the skeleton in one patient, the lung in two patients, and the liver in one patient. This study suggests that Ga-PSMA PET/CT is useful for lymph node and metastases staging in high-risk prostate cancers, whereas its utility for staging of disease in the prostate is limited.

Evaluating the predictive accuracy and the clinical benefit of a nomogram aimed to predict survival in node-positive prostate cancer patients: External validation on a multi-institutional database.

PubMed

Bianchi, Lorenzo; Schiavina, Riccardo; Borghesi, Marco; Bianchi, Federico Mineo; Briganti, Alberto; Carini, Marco; Terrone, Carlo; Mottrie, Alex; Gacci, Mauro; Gontero, Paolo; Imbimbo, Ciro; Marchioro, Giansilvio; Milanese, Giulio; Mirone, Vincenzo; Montorsi, Francesco; Morgia, Giuseppe; Novara, Giacomo; Porreca, Angelo; Volpe, Alessandro; Brunocilla, Eugenio

2018-04-06

To assess the predictive accuracy and the clinical value of a recent nomogram predicting cancer-specific mortality-free survival after surgery in pN1 prostate cancer patients through an external validation. We evaluated 518 prostate cancer patients treated with radical prostatectomy and pelvic lymph node dissection with evidence of nodal metastases at final pathology, at 10 tertiary centers. External validation was carried out using regression coefficients of the previously published nomogram. The performance characteristics of the model were assessed by quantifying predictive accuracy, according to the area under the curve in the receiver operating characteristic curve and model calibration. Furthermore, we systematically analyzed the specificity, sensitivity, positive predictive value and negative predictive value for each nomogram-derived probability cut-off. Finally, we implemented decision curve analysis, in order to quantify the nomogram's clinical value in routine practice. External validation showed inferior predictive accuracy as referred to in the internal validation (65.8% vs 83.3%, respectively). The discrimination (area under the curve) of the multivariable model was 66.7% (95% CI 60.1-73.0%) by testing with receiver operating characteristic curve analysis. The calibration plot showed an overestimation throughout the range of predicted cancer-specific mortality-free survival rates probabilities. However, in decision curve analysis, the nomogram's use showed a net benefit when compared with the scenarios of treating all patients or none. In an external setting, the nomogram showed inferior predictive accuracy and suboptimal calibration characteristics as compared to that reported in the original population. However, decision curve analysis showed a clinical net benefit, suggesting a clinical implication to correctly manage pN1 prostate cancer patients after surgery. © 2018 The Japanese Urological Association.

Application of Cu-64 NODAGA-PSMA PET in Prostate Cancer.

PubMed

Sevcenco, Sabina; Klingler, Hans Christoph; Eredics, Klaus; Friedl, Alexander; Schneeweiss, Jenifer; Knoll, Peter; Kunit, Thomas; Lusuardi, Lukas; Mirzaei, Siroos

2018-06-01

The high diagnostic potential of 64 Cu-PSMA PET-CT imaging was clinically investigated in prostate cancer patients with recurrent disease and in the primary staging of selected patients with advanced local disease. The aim of our study is to assess the uptake behavior in the clinical setting of 64Copper Prostate-Specific Membrane Antigen ( 64 Cu PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) in prostate cancer. A retrospective study was performed in 23 patients with intermediate, high risk and progressive disease at primary staging of prostate cancer. All patients underwent 64 Cu-PSMA PET. Overall, 250 MBq (4 MBq per kg bodyweight, range 230-290 MBq) of 64 Cu-NODAGA PSMA was intravenously applied. PET images were performed 30 min (pelvis and abdomen) and 1-2 h post-injection (skull base to mid-thigh). Maximum standardized uptake values (SUVmax) were measured in the organs with high physiological uptake such as liver and kidney, and, additionally, background activity was measured in the gluteal area and in suspected tumor lesions using a HERMES workstation. PSMA uptake was detected in prostate bed in nine patients, in six patients in distant metastases (bone, lung and liver) and in nine patients in lymph nodes. Of 23 patients, 5 (20.8%) did not show any focal pathological uptake in the whole body. The number of sites (prostate bed, lymph nodes, distant metastases) with positive PSMA uptake was significantly associated with PSA values before imaging (P = 0.0032). The 64 Cu PSMA uptake increased significantly from 30 min to 1-3 h post-injection (Wilcoxon signed rank test, P = 0.002). 64 Cu NODAGA-PSMA PET is a promising imaging tool in the detection of residual disease in patients with recurrent or primary progressive prostate cancer. Furthermore, the increased tracer uptake over time indicates in vivo stability of the diagnostic radiopharmaceutical.

A novel mouse model of human prostate cancer to study intraprostatic tumor growth and the development of lymph node metastases.

PubMed

Linxweiler, Johannes; Körbel, Christina; Müller, Andreas; Hammer, Markus; Veith, Christian; Bohle, Rainer M; Stöckle, Michael; Junker, Kerstin; Menger, Michael D; Saar, Matthias

2018-06-01

In this study, we aimed to establish a versatile in vivo model of prostate cancer, which adequately mimics intraprostatic tumor growth, and the natural routes of metastatic spread. In addition, we analyzed the capability of high-resolution ultrasonography (hrUS), in vivo micro-CT (μCT), and 9.4T MRI to monitor tumor growth and the development of lymph node metastases. A total of 5 × 10 5 VCaP cells or 5 × 10 5 cells of LuCaP136- or LuCaP147 spheroids were injected into the prostate of male CB17-SCID mice (n = 8 for each cell type). During 12 weeks of follow-up, orthotopic tumor growth, and metastatic spread were monitored by repetitive serum-PSA measurements and imaging studies including hrUS, μCT, and 9.4T MRI. At autopsy, primary tumors and metastases were harvested and examined by histology and immunohistochemistry (CK5, CK8, AMACR, AR, Ki67, ERG, and PSA). From imaging results and PSA-measurements, tumor volume doubling time, tumor-specific growth rate, and PSA-density were calculated. All 24 mice developed orthotopic tumors. The tumor growth could be reliably monitored by a combination of hrUS, μCT, MRI, and serum-PSA measurements. In most animals, lymph node metastases could be detected after 12 weeks, which could also be well visualized by hrUS, and MRI. Immunohistochemistry showed positive signals for CK8, AMACR, and AR in all xenograft types. CK5 was negative in VCaP- and focally positive in LuCaP136- and LuCaP147-xenografts. ERG was positive in VCaP- and negative in LuCaP136- and LuCaP147-xenografts. Tumor volume doubling times and tumor-specific growth rates were 21.2 days and 3.9 %/day for VCaP-, 27.6 days and 3.1 %/day for LuCaP136- and 16.2 days and 4.5 %/day for LuCaP147-xenografts, respectively. PSA-densities were 433.9 ng/mL per milliliter tumor for VCaP-, 6.5 ng/mL per milliliter tumor for LuCaP136-, and 11.2 ng/mL per milliliter tumor for LuCaP147-xenografts. By using different monolayer and 3D spheroid cell cultures in an orthotopic xenograft model, we established an innovative, versatile in vivo model of prostate cancer, which enables the study of both intraprostatic tumor growth as well as metastatic spread to regional lymph nodes. HrUS and MRI are feasible tools to monitor tumor growth and the development of lymph node metastases while these cannot be visualized by μCT. © 2018 Wiley Periodicals, Inc.

All-Cause Mortality for Life Insurance Applicants with a History of Prostate Cancer.

PubMed

Freitas, Stephen A; MacKenzie, Ross; Wylde, David N; Roudebush, Bradley T; Bergstrom, Richard L; Holowaty, J Carl; Beckman, Margaret; Rigatti, Steven J; Gill, Stacy

2017-01-01

- To determine the all-cause mortality of life insurance applicants diagnosed with prostate cancer currently or at some time in the past. - Prostate cancer is common and a frequent cause of cancer death. Both the frequency of prostate cancer in men and its propensity for causing premature mortality require insurance company medical directors and underwriters to have a good understanding of prostate cancer-related mortality trends, patterns, and outcomes in the insured population. - Life insurance applicants with reported prostate cancer were extracted from data covering United States residents between November 2007 and November 2014. Information about these applicants was matched to the Social Security Death Master (SSDMF) file for deaths occurring from 2007 to 2011 and to another commercially available death source file (Other Death Source, ODS) for deaths occurring from 2007 to 2014 to determine vital status. Actual to Expected (A/E) mortality ratios were calculated using the Society of Actuaries 2015 Valuation Basic Table (2015VBT), select and ultimate table (age last birthday) and the 2013 US population as expected mortality ratios. All expected bases were not smoker distinct. - The study covered applicants between the ages of 45 and 75 and had approximately 405,000 person-years of exposure. Older aged applicants had a lower mortality ratio than those who were younger. Applicants 45 to 54 had the highest mortality ratios in the first year after diagnosis which steadily decreased in years 6 to 10 with an increase in the mortality ratio for those over 10 years from diagnosis. Relative mortality rate was close to unity for those with localized cancer across all age groups. The mortality ratio was 2 to 4 times greater for those with cancer in 1 positive node, and much greater with 3 positive nodes. For each time-from-diagnosis category, the relative mortality ratios compared to age were highest in the 45-54 age group. The A/E mortality ratios based on the 2015VBT were consistently 3 to 4 times that of the mortality ratios based on the 2013 US population. - The mortality patterns of insurance applicants with prostate cancer were similar to that observed in individuals with prostate cancer in the general population. Applicant age, time to diagnosis and cancer severity were the most significant variables to predict mortality.

[18F]fluoroethylcholine-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes.

PubMed

Würschmidt, Florian; Petersen, Cordula; Wahl, Andreas; Dahle, Jörg; Kretschmer, Matthias

2011-05-01

At present there is no consensus on irradiation treatment volumes for intermediate to high-risk primary cancers or recurrent disease. Conventional imaging modalities, such as CT, MRI and transrectal ultrasound, are considered suboptimal for treatment decisions. Choline-PET/CT might be considered as the imaging modality in radiooncology to select and delineate clinical target volumes extending the prostate gland or prostate fossa. In conjunction with intensity modulated radiotherapy (IMRT) and imaged guided radiotherapy (IGRT), it might offer the opportunity of dose escalation to selected sites while avoiding unnecessary irradiation of healthy tissues. Twenty-six patients with primary (n = 7) or recurrent (n = 19) prostate cancer received Choline-PET/CT planned 3D conformal or intensity modulated radiotherapy. The median age of the patients was 65 yrs (range 45 to 78 yrs). PET/CT-scans with F18-fluoroethylcholine (FEC) were performed on a combined PET/CT-scanner equipped for radiation therapy planning. The majority of patients had intermediate to high risk prostate cancer. All patients received 3D conformal or intensity modulated and imaged guided radiotherapy with megavoltage cone beam CT. The median dose to primary tumours was 75.6 Gy and to FEC-positive recurrent lymph nodal sites 66,6 Gy. The median follow-up time was 28.8 months. The mean SUV(max) in primary cancer was 5,97 in the prostate gland and 3,2 in pelvic lymph nodes. Patients with recurrent cancer had a mean SUV(max) of 4,38. Two patients had negative PET/CT scans. At 28 months the overall survival rate is 94%. Biochemical relapse free survival is 83% for primary cancer and 49% for recurrent tumours. Distant disease free survival is 100% and 75% for primary and recurrent cancer, respectively. Acute normal tissue toxicity was mild in 85% and moderate (grade 2) in 15%. No or mild late side effects were observed in the majority of patients (84%). One patient had a severe bladder shrinkage (grade 4) after a previous treatment with TUR of the prostate and seed implantation. FEC-PET/CT planning could be helpful in dose escalation to lymph nodal sites of prostate cancer.

Novel technology of molecular radio-guidance for lymph node dissection in recurrent prostate cancer by PSMA-ligands.

PubMed

Rauscher, Isabel; Horn, Thomas; Eiber, Matthias; Gschwend, Jürgen E; Maurer, Tobias

2018-04-01

Recently, prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) has been introduced as a promising new and individual treatment concept in patients with localised recurrent prostate cancer (PC). In the following, we want to review our experience with PSMA-RGS in patients with localised biochemical recurrent PC. A non-systematic review of the literature was carried out with focus on technical and logistical aspects of PSMA-RGS. Furthermore, published data on intraoperative detection of metastatic lesions compared to preoperative PSMA-PET and postoperative histopathology, postoperative complications as well as oncological follow-up data are summarized. Finally, relevant aspects on prerequisites for PSMA-RGS, patient selection, and the potential benefit of additional salvage radiotherapy or potential future applications of robotic PSMA-RGS with drop-in γ-probes are discussed. First results show that PSMA-RGS is very sensitive and specific in tracking suspicious lesions intraoperatively. Prerequisite for patient selection and localisation of tumour recurrence is a positive Ga-HBED-CC PSMA positron-emission tomography (PET) scan with preferably only singular soft tissue or lymph node recurrence after primary treatment. Furthermore, PSMA-RGS has the potential to positively influence oncological outcome. PSMA-RGS seems to be of high value in patients with localised PC recurrence for exact localisation and resection of oftentimes small metastatic lesions using intraoperative and ex vivo γ-probe measurements. However, patient identification on the basis of Ga-HBED-CC-PSMA PET imaging as well as clinical parameters is crucial to obtain satisfactory results.

Physician level reporting of surgical and pathology performance indicators: a regional study to assess feasibility and impact on quality.

PubMed

McFadyen, Craig; Lankshear, Sara; Divaris, Dimitrios; Berry, Mark; Hunter, Amber; Srigley, John; Irish, Jonathan

2015-02-01

There is increased awareness that, to minimize variation in clinician practice and improve quality, performance reporting should be implemented at the provider level. This optimizes physician engagement and creates a sense of professional responsibility for quality and performance measurement at the individual and organizational levels. Individual provider level reporting was implemented within a provincial health region involving 56 clinicians (general surgeons, surgical oncologists, urologists and pathologists). The 2 surgical pathology indicators chosen were colorectal cancer (CRC) lymph node retrieval rate and pT2 prostate cancer margin positivity rate. Surgical resections for all prostate and colorectal cancer performed between Jan. 1, 2011, and Mar. 30, 2012, were included. We used a pre- and postsurvey design to obtain physician perceptions and focus groups with program leadership to determine organizational impact. Survey results showed that respondents felt the data provided in the reports were valid (67%), consistent with expectations (70%), maintained confidentiality (80%) and were not used in a punitive manner (77%). During the study period the pT2 prostate margin positivity rate decreased from 57.1% to 27.5%. For the CRC lymph node retrieval rate indicator, high baseline performance was maintained. We developed a robust process for providing physicians with confidential, individualized surgical and pathology quality indicator reports. Our results reinforce the importance of individual physician feedback as a strategy for improving and sustaining quality in surgical and diagnostic oncology.

Sentinel Lymph Node Dissection to Select Clinically Node-negative Prostate Cancer Patients for Pelvic Radiation Therapy: Effect on Biochemical Recurrence and Systemic Progression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grivas, Nikolaos, E-mail: n.grivas@nki.nl; Wit, Esther; Pos, Floris

Purpose: To assess the efficacy of robotic-assisted laparoscopic sentinel lymph node (SLN) dissection (SLND) to select those patients with prostate cancer (PCa) who would benefit from additional pelvic external beam radiation therapy and long-term androgen deprivation therapy (ADT). Methods and Materials: Radioisotope-guided SLND was performed in 224 clinically node-negative patients scheduled to undergo external beam radiation therapy. Patients with histologically positive SLNs (pN1) were also offered radiation therapy to the pelvic lymph nodes, combined with 3 years of ADT. Biochemical recurrence (BCR), overall survival, and metastasis-free (including pelvic and nonregional lymph nodes) survival (MFS) rates were retrospectively calculated. The Briganti andmore » Kattan nomogram predictions were compared with the observed pN status and BCR. Results: The median prostate-specific antigen (PSA) value was 15.4 ng/mL (interquartile range [IQR] 8-29). A total number of 834 SLNs (median 3 per patient; IQR 2-5) were removed. Nodal metastases were diagnosed in 42% of the patients, with 150 SLNs affected (median 1; IQR 1-2). The 5-year BCR-free and MFS rates for pN0 patients were 67.9% and 87.8%, respectively. The corresponding values for pN1 patients were 43% and 66.6%. The PSA level and number of removed SLNs were independent predictors of BCR and MFS, and pN status was an additional independent predictor of BCR. The 5-year overall survival rate was 97.6% and correlated only with pN status. The predictive accuracy of the Briganti nomogram was 0.665. Patients in the higher quartiles of Kattan nomogram prediction of BCR had better than expected outcomes. The complication rate from SLND was 8.9%. Conclusions: For radioisotope-guided SLND, the high staging accuracy is accompanied by low morbidity. The better than expected outcomes observed in the lower quartiles of BCR prediction suggest a role for SLN biopsy as a potential selection tool for the addition of pelvic radiation therapy and ADT intensification in pN1 patients.« less

False Positive Uptake in Bilateral Gynecomastia on 68Ga-PSMA PET/CT Scan.

PubMed

Sasikumar, Arun; Joy, Ajith; Nair, Bindu P; Pillai, M R A; Madhavan, Jayaprakash

2017-09-01

A 66-year-old man on hormonal therapy with prostate cancer was referred for Ga-PSMA PET/CT scan for biochemical recurrence. Ga-PSMA PET/CT scan detected moderate heterogeneous tracer concentration in bilateral breast parenchyma, in addition to the abnormal tracer concentration in enlarged prostate gland, right external iliac lymph node, and sclerotic lesion in L4 vertebra. On clinical examination, he was found to have bilateral gynecomastia. Abnormal concentration of Ga-PSMA in breast cancer is now well known, and in this context, it is important to know that tracer localization can occur in gynecomastia as well, as evidenced in this case.

(18)F-FACBC (anti1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid) versus (11)C-choline PET/CT in prostate cancer relapse: results of a prospective trial.

PubMed

Nanni, Cristina; Zanoni, Lucia; Pultrone, Cristian; Schiavina, Riccardo; Brunocilla, Eugenio; Lodi, Filippo; Malizia, Claudio; Ferrari, Matteo; Rigatti, Patrizio; Fonti, Cristina; Martorana, Giuseppe; Fanti, Stefano

2016-08-01

To compare the accuracy of (18)F-FACBC and (11)C-choline PET/CT in patients radically treated for prostate cancer presenting with biochemical relapse. This prospective study enrolled 100 consecutive patients radically treated for prostate cancer and presenting with rising PSA. Of these 100 patients, 89 were included in the analysis. All had biochemical relapse after radical prostatectomy (at least 3 months previously), had (11)C-choline and (18)F-FACBC PET/CT performed within 1 week and were off hormonal therapy at the time of the scans. The two tracers were compared directly in terms of overall positivity/negativity on both a per-patient basis and a per-site basis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for both the tracers; follow-up at 1 year (including correlative imaging, PSA trend and pathology when available) was considered as the standard of reference. In 51 patients the results were negative and in 25 patients positive with both the tracers, in eight patients the results were positive with (18)F-FACBC but negative with (11)C-choline, and in five patients the results were positive with (11)C-choline but negative with (18)F-FACBC. Overall in 49 patients the results were false-negative (FN), in two true-negative, in 24 true-positive (TP) and in none false-positive (FP) with both tracers. In terms of discordances between the tracers: (1) in one patient, the result was FN with (11)C-choline but FP with (18)F-FACBC (lymph node), (2) in seven, FN with (11)C-choline but TP with (18)F-FACBC (lymph node in five, bone in one, local relapse in one), (3) in one, FP with (11)C-choline (lymph node) but TP with (18)F-FACBC (local relapse), (4) in two, FP with (11)C-choline (lymph nodes in one, local relapse in one) but FN with (18)F-FACBC, and (5) in three, TP with (11)C-choline (lymph nodes in two, bone in one) but FN with (18)F-FACBC. With (11)C-choline and (18)F-FACBC, sensitivities were 32 % and 37 %, specificities 40 % and 67 %, accuracies 32 % and 38 %, PPVs 90 % and 97 %, and NPVs 3 % and 4 %, respectively. Categorizing patients by PSA level (<1 ng/ml 28 patients, 1 - <2 ng/ml 28 patients, 2 - <3 ng/ml 11 patients, ≥3 ng/ml 22 patients), the number (percent) of patients with TP findings were generally higher with (18)F-FACBC than with (11)C-choline: six patients (21 %) and four patients (14 %), eight patients (29 %) and eight patients (29 %), five patients (45 %) and four patients (36 %), and 13 patients (59 %) and 11 patients (50 %), respectively. (18)F-FACBC can be considered an alternative tracer superior to (11)C-choline in the setting of patients with biochemical relapse after radical prostatectomy.

The use of artificial intelligence technology to predict lymph node spread in men with clinically localized prostate carcinoma.

PubMed

Crawford, E D; Batuello, J T; Snow, P; Gamito, E J; McLeod, D G; Partin, A W; Stone, N; Montie, J; Stock, R; Lynch, J; Brandt, J

2000-05-01

The current study assesses artificial intelligence methods to identify prostate carcinoma patients at low risk for lymph node spread. If patients can be assigned accurately to a low risk group, unnecessary lymph node dissections can be avoided, thereby reducing morbidity and costs. A rule-derivation technology for simple decision-tree analysis was trained and validated using patient data from a large database (4,133 patients) to derive low risk cutoff values for Gleason sum and prostate specific antigen (PSA) level. An empiric analysis was used to derive a low risk cutoff value for clinical TNM stage. These cutoff values then were applied to 2 additional, smaller databases (227 and 330 patients, respectively) from separate institutions. The decision-tree protocol derived cutoff values of < or = 6 for Gleason sum and < or = 10.6 ng/mL for PSA. The empiric analysis yielded a clinical TNM stage low risk cutoff value of < or = T2a. When these cutoff values were applied to the larger database, 44% of patients were classified as being at low risk for lymph node metastases (0.8% false-negative rate). When the same cutoff values were applied to the smaller databases, between 11 and 43% of patients were classified as low risk with a false-negative rate of between 0.0 and 0.7%. The results of the current study indicate that a population of prostate carcinoma patients at low risk for lymph node metastases can be identified accurately using a simple decision algorithm that considers preoperative PSA, Gleason sum, and clinical TNM stage. The risk of lymph node metastases in these patients is < or = 1%; therefore, pelvic lymph node dissection may be avoided safely. The implications of these findings in surgical and nonsurgical treatment are significant.

Clinical performance of 68Ga-PSMA-11 PET/MRI for the detection of recurrent prostate cancer following radical prostatectomy.

PubMed

Kranzbühler, Benedikt; Nagel, Hannes; Becker, Anton S; Müller, Julian; Huellner, Martin; Stolzmann, Paul; Muehlematter, Urs; Guckenberger, Matthias; Kaufmann, Philipp A; Eberli, Daniel; Burger, Irene A

2018-01-01

Sensitive visualization of recurrent prostate cancer foci is a challenge in patients with early biochemical recurrence (EBR). The recently established 68 Ga-PSMA-11 PET/CT has significantly improved the detection rate with published values of up to 55% for patients with a serum PSA concentration between 0.2-0.5 ng/mL. The increased soft tissue contrast in the pelvis using simultaneous 68 Ga-PSMA-11 PET/MRI might further improve the detection rate in patients with EBR and low PSA values over PET/CT. We retrospectively analyzed a cohort of 56 consecutive patients who underwent a 68 Ga-PSMA-11 PET/MRI for biochemical recurrence in our institution between April and December 2016 with three readers. Median PSA level was 0.99 ng/mL (interquartile range: 3.1 ng/mL). Detection of PSMA-positive lesions within the prostate fossa, local and distant lymph nodes, bones, or visceral organs was recorded. Agreement among observers was evaluated with Fleiss's kappa (k). Overall, in 44 of 56 patients (78.6%) PSMA-positive lesions were detected. In four of nine patients (44.4%) with a PSA < 0.2 ng/mL, suspicious lesions were detected (two pelvic and one paraaortic lymph nodes, and two bone metastases). In eight of 11 patients (72.7%) with a PSA between 0.2 and < 0.5 ng/mL, suspicious lesions were detected (two local recurrences, six lymph nodes, and one bone metastasis). Five out of 20 patients with a PSA < 0.5 ng/mL had extrapelvic disease. In 12 of 15 patients (80.0%) with a PSA between 0.5 and < 2.0 ng/mL, suspicious lesions were detected (four local recurrences, nine lymph nodes, and four bone metastases). In 20 of 21 patients (95.2%) with a PSA >2.0 ng/mL, suspicious lesions were detected. The overall interreader agreement for cancer detection was excellent (κ = 0.796, CI 0.645-0.947). Our data show that 68 Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer even at very low PSA levels <0.5 ng/mL. Furthermore, even at those low levels extrapelvic disease can be localized in 25% of the cases and local recurrence alone is seen only in 10%.

Robot-assisted radical cystectomy and pelvic lymph node dissection: initial experience at Roswell Park Cancer Institute.

PubMed

Guru, Khurshid A; Kim, Hyung L; Piacente, Pamela M; Mohler, James L

2007-03-01

One series of robot-assisted radical cystectomy with pelvic lymph node dissection has been reported. We report our operative technique and initial experience. Twenty consecutive patients underwent robot-assisted radical cystectomy, pelvic lymph node dissection, and open urinary diversion for operable bladder cancer from October 2005 to June 2006. Data were collected prospectively on patient demographics, intraoperative parameters, pathologic staging, and postoperative outcomes. The mean patient age was 70 years (range 56 to 90). The mean body mass index was 26 kg/m2 (range 17.3 to 36). Fourteen patients had undergone previous abdominal surgery. The mean operative time was 197 minutes for robot-assisted radical cystectomy, 44 minutes for pelvic lymph node dissection, and 133 minutes for urinary diversion. The mean blood loss was 555 mL. One case was converted to an open procedure because of the patient's inability to tolerate the Trendelenburg position. The mean hospital stay was 10 days. Two patients had major complications. One patient had positive vaginal margins and 9 of 26 nodes were positive. Four patients had incidental prostate cancer. The mean time to the return to nonstrenuous activity was 4 weeks and to strenuous activity was 10 weeks. Robot-assisted radical cystectomy and pelvic lymph node dissection can be performed safely in patients who are considered candidates for open cystectomy. Long-term oncologic control data and functional outcomes are needed to assess the true benefits of robot-assisted radical cystectomy.

VPAC1 targeted 64Cu-TP3805 PET imaging of prostate cancer: preliminary evaluation in man

PubMed Central

Tripathi, Sushil; Trabulsi, Edouard J; Gomella, Leonard; Kim, Sung; McCue, Peter; Intenzo, Charles; Birbe, Ruth; Gandhe, Ashish; Kumar, Pardeep; Thakur, Mathew

2015-01-01

Objectives To evaluate 64Cu-TP3805 as a novel biomolecule, to PET image prostate cancer (PC), at the onset of which VPAC1, the superfamily of G-protein coupled receptors, is expressed in high density on PC cells, but not on normal cells. Methods 25 patients undergoing radical prostatectomy were PET/CT imaged preoperatively with 64Cu-TP3805. Standardized uptake values (SUVmax) were determined, malignant lesions (SUV > 1.0) counted, and compared with histologic findings. Whole mount pathology slides from 6 VPAC1 PET imaged patients, 3 BPH patients, one malignant and one benign lymph node underwent digital autoradiography (DAR) after 64Cu-TP3805 incubation and compared to H&E stained slides. Results In 25 patient PET imaging, 212 prostate gland lesions had SUVmax > 1.0 vs.127 lesions identified by histology of biopsy tissues. The status of the additional 85 PET identified prostate lesions remains to be determined. In 68 histological slides from 6 PET imaged patients, DAR identified 105/107 PC foci, 19/19 HGPIN, and ejaculatory ducts and verumontanum involved with cancer. Additionally, DAR found 9 PC lesions not previously identified histologically. The positive and negative lymph nodes were correctly identified and in 3/3 BPH patients and 5/5 cysts, DAR was negative. Conclusion This feasibility study demonstrated that 64Cu-TP3805 delineates PC in vivo and ex vivo, provided normal images for benign masses, and is worthy of further studies. PMID:26519886

Oligorecurrent prostate cancer limited to lymph nodes: getting our ducks in a row

PubMed

Fodor, Andrei; Lancia, Andrea; Ceci, Francesco; Picchio, Maria; Hoyer, Morten; Jereczek-Fossa, Barbara Alicja; Ost, Piet; Castellucci, Paolo; Incerti, Elena; Di Muzio, Nadia; Ingrosso, Gianluca

2018-05-11

Oligorecurrent prostate cancer with exclusive nodal involvement represents a common state of disease, amenable to local therapy. New radio-labeled tracers have enriched the possibility of cancer detection and treatment. In this review, we aim to illustrate the main nuclear medicine diagnostic options and the role of radiotherapy in this setting of patients. We performed a PubMed search referring to the PRISMA guidelines to analyze the performance of PSMA- and choline-PET in detecting oligorecurrence limited to lymph nodes, and to review the main studies supporting either ablative stereotactic body radiotherapy or regional lymph node irradiation in this clinical setting. PSMA-PET has shown higher efficacy in the diagnosis of nodal lesions if compared with choline-PET. More specifically, for PSA ≤ 2 ng/ml, the median detection rate of choline-PET ranges from 19.5 to 44.5%, whereas PSMA ranges from 51.5 to 74%. SBRT achieves high local control rates positively affecting progression-free survival (PFS), with androgen deprivation therapy (ADT)-free survival ranging from 25 to 44 months and with low toxicity rates (0-15%). Prophylactic nodal irradiation shows 3-year PFS rates ranging from 62 to 75%, but with a potential higher risk of toxicity. However, the chosen treatment option needs to be tailored on the single patient. Newer PET/CT radio-labeled tracers have increased disease detection in oligorecurrent prostate cancer patients. Growing evidence of their impact on metastasis-directed therapy encourages the use of the most advanced radiotherapy techniques in the clinical management of such patients.

Intensity-modulated radiotherapy improves lymph node coverage and dose to critical structures compared with three-dimensional conformal radiation therapy in clinically localized prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang-Chesebro, Alice; Xia Ping; Coleman, Joy

2006-11-01

Purpose: The aim of this study was to quantify gains in lymph node coverage and critical structure dose reduction for whole-pelvis (WP) and extended-field (EF) radiotherapy in prostate cancer using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3DCRT) for the first treatment phase of 45 Gy in the concurrent treatment of lymph nodes and prostate. Methods and Materials: From January to August 2005, 35 patients with localized prostate cancer were treated with pelvic IMRT; 7 had nodes defined up to L5-S1 (Group 1), and 28 had nodes defined above L5-S1 (Group 2). Each patient had 2 plans retrospectively generated:more » 1 WP 3DCRT plan using bony landmarks, and 1 EF 3DCRT plan to cover the vascular defined volumes. Dose-volume histograms for the lymph nodes, rectum, bladder, small bowel, and penile bulb were compared by group. Results: For Group 1, WP 3DCRT missed 25% of pelvic nodes with the prescribed dose 45 Gy and missed 18% with the 95% prescribed dose 42.75 Gy, whereas WP IMRT achieved V{sub 45Gy} = 98% and V{sub 42.75Gy} = 100%. Compared with WP 3DCRT, IMRT reduced bladder V{sub 45Gy} by 78%, rectum V{sub 45Gy} by 48%, and small bowel V{sub 45Gy} by 232 cm{sup 3}. EF 3DCRT achieved 95% coverage of nodes for all patients at high cost to critical structures. For Group 2, IMRT decreased bladder V{sub 45Gy} by 90%, rectum V{sub 45Gy} by 54% and small bowel V{sub 45Gy} by 455 cm{sup 3} compared with EF 3DCRT. Conclusion: In this study WP 3DCRT missed a significant percentage of pelvic nodes. Although EF 3DCRT achieved 95% pelvic nodal coverage, it increased critical structure doses. IMRT improved pelvic nodal coverage while decreasing dose to bladder, rectum, small bowel, and penile bulb. For patients with extended node involvement, IMRT especially decreases small bowel dose.« less

Impact of conventional fractionated RT to pelvic lymph nodes and dose-escalated hypofractionated RT to prostate gland using IMRT treatment delivery in high-risk prostate cancer

NASA Astrophysics Data System (ADS)

Pervez, Nadeem

Prostate cancer is the most common cancer among Canadian men. The standard treatment in high-risk category is radical radiation, with androgen suppression treatment (AST). Significant disease progression is reported despite this approach. Radiation dose escalation has been shown to improve disease-free survival; however, it results in higher toxicities. Hypofractionated radiation schedules (larger dose each fraction in shorter overall treatment time) are expected to deliver higher biological doses. A hypofractionated scheme was used in this study to escalate radiation doses with AST. Treatment was well tolerated acutely. Early results of self-administered quality of life reported by patients shows a decrease in QOL which is comparable to other treatment schedules. Significant positional variation of the prostate was observed during treatment. Therefore, we suggest daily target verification to avoid a target miss. Initial late effects are reasonable and early treatment outcomes are promising. Longer follow-up is required for full outcomes assessments.

Activin type IB receptor signaling in prostate cancer cells promotes lymph node metastasis in a xenograft model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nomura, Masatoshi, E-mail: nomura@med.kyushu-u.ac.jp; Tanaka, Kimitaka; Wang, Lixiang

Highlights: Black-Right-Pointing-Pointer ActRIB signaling induces Snail and S100A4 expressions in prostate cancer cells. Black-Right-Pointing-Pointer The prostate cancer cell lines expressing an active form of ActRIB were established. Black-Right-Pointing-Pointer ActRIB signaling promotes EMT and lymph node metastasis in xenograft model. -- Abstract: Activin, a member of the transforming growth factor-{beta} family, has been known to be a growth and differentiating factor. Despite its pluripotent effects, the roles of activin signaling in prostate cancer pathogenesis are still unclear. In this study, we established several cell lines that express a constitutive active form of activin type IB receptor (ActRIBCA) in human prostate cancermore » cells, ALVA41 (ALVA-ActRIBCA). There was no apparent change in the proliferation of ALVA-ActRIBCA cells in vitro; however, their migratory ability was significantly enhanced. In a xenograft model, histological analysis revealed that the expression of Snail, a cell-adhesion-suppressing transcription factor, was dramatically increased in ALVA-ActRIBCA tumors, indicating epithelial mesenchymal transition (EMT). Finally, mice bearing ALVA-ActRIBCA cells developed multiple lymph node metastases. In this study, we demonstrated that ActRIBCA signaling can promote cell migration in prostate cancer cells via a network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancers.« less

Indocyanine Green Guided Pelvic Lymph Node Dissection: An Efficient Technique to Classify the Lymph Node Status of Patients with Prostate Cancer Who Underwent Radical Prostatectomy.

PubMed

Ramírez-Backhaus, Miguel; Mira Moreno, Alejandra; Gómez Ferrer, Alvaro; Calatrava Fons, Ana; Casanova, Juan; Solsona Narbón, Eduardo; Ortiz Rodríguez, Isabel María; Rubio Briones, José

2016-11-01

We evaluated the effectiveness of indocyanine green guided pelvic lymph node dissection for the optimal staging of prostate cancer and analyzed whether the technique could replace extended pelvic lymph node dissection. A solution of 25 mg indocyanine green in 5 ml sterile water was transperineally injected. Pelvic lymph node dissection was started with the indocyanine green stained nodes followed by extended pelvic lymph node dissection. Primary outcome measures were sensitivity, specificity, predictive value and likelihood ratio of a negative test of indocyanine green guided pelvic lymph node dissection. A total of 84 patients with a median age of 63.55 years and a median prostate specific antigen of 8.48 ng/ml were included in the study. Of these patients 60.7% had intermediate risk disease and 25% had high or very high risk disease. A median of 7 indocyanine green stained nodes per patient was detected (range 2 to 18) with a median of 22 nodes excised during extended pelvic lymph node dissection. Lymph node metastasis was identified in 25 patients, 23 of whom had disease properly classified by indocyanine green guided pelvic lymph node dissection. The most frequent location of indocyanine green stained nodes was the proximal internal iliac artery followed by the fossa of Marcille. The negative predictive value was 96.7% and the likelihood ratio of a negative test was 8%. Overall 1,856 nodes were removed and 603 were stained indocyanine green. Pathological examination revealed 82 metastatic nodes, of which 60% were indocyanine green stained. The negative predictive value was 97.4% but the likelihood ratio of a negative test was 58.5%. Indocyanine green guided pelvic lymph node dissection correctly staged 97% of cases. However, according to our data it cannot replace extended pelvic lymph node dissection. Nevertheless, its high negative predictive value could allow us to avoid extended pelvic lymph node dissection if we had an accurate intraoperative lymph fluorescent analysis. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Patterns of failure after radical prostatectomy in prostate cancer - implications for radiation therapy planning after 68Ga-PSMA-PET imaging.

PubMed

Schiller, Kilian; Sauter, K; Dewes, S; Eiber, M; Maurer, T; Gschwend, J; Combs, S E; Habl, G

2017-09-01

Salvage radiotherapy (SRT) after radical prostatectomy (RPE) and lymphadenectomy (LAE) is the appropriate radiotherapy option for patients with persistent/ recurrent prostate cancer (PC). 68 Ga-PSMA-PET imaging has been shown to accurately detect PC lesions in a primary setting as well as for local recurrence or for lymph node (LN) metastases. In this study we evaluated the patterns of recurrence after RPE in patients with PC, putting a highlight on the differentiation between sites that would have been covered by a standard radiation therapy (RT) field in consensus after the RTOG consensus and others that would have not. Thirty-one out of 83 patients (37%) with high-risk PC were the subject of our study. Information from 68 Ga-PSMA-PET imaging was used to individualize treatment plans to include suspicious lesions as well as possibly boost sites with tracer uptake in LN or the prostate bed. For evaluation, 68 Ga-PSMA-PET-positive LN were contoured in a patient dataset with a standard lymph drainage (RTOG consensus on CTV definition of pelvic lymph nodes) radiation field depicting color-coded nodes that would have been infield or outfield of that standard lymph drainage field and thereby visualizing typical patterns of failure of a "blind" radiation therapy after RPE and LAE. Compared to negative conventional imaging (CT/MRI), lesions suspicious for PC were detected in 27/31 cases (87.1%) by 68 Ga-PSMA-PET imaging, which resulted in changes to the radiation concept. There were 16/31 patients (51.6%) that received a simultaneous integrated boost (SIB) to a subarea of the prostate bed (in only three cases this dose escalation would have been planned without the additional knowledge of 68 Ga-PSMA-PET imaging) and 18/31 (58.1%) to uncommon (namely presacral, paravesical, pararectal, preacetabular and obturatoric) LN sites. Furthermore, 14 patients (45.2%) had a changed TNM staging result by means of 68 Ga-PSMA-PET imaging. Compared to conventional CT or MRI staging, 68 Ga-PSMA-PET imaging detects more PC lesions and, thus, significantly influences radiation planning in recurrent prostate cancer patients enabling individually tailored treatment.

IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy.

PubMed

Li, Dujuan; Kan, Yunzhen; Fu, Fangfang; Wang, Shuhuan; Shi, Ligang; Liu, Jie; Kong, Lingfei

2015-01-01

Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment.

Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis.

PubMed

Evangelista, Laura; Guttilla, Andrea; Zattoni, Fabio; Muzzio, Pier Carlo; Zattoni, Filiberto

2013-06-01

Determination of tumour involvement of regional lymph nodes in patients with prostate cancer (PCa) is of key importance for the proper planning of treatment. To provide a critical overview of published reports and to perform a meta-analysis about the diagnostic performance of 18F-choline and 11C-choline positron emission tomography (PET) or PET/computed tomography (CT) in the lymph node staging of PCa. A Medline, Web of Knowledge, and Google Scholar search was carried out to select English-language articles published before January 2012 that discussed the diagnostic performance of choline PET to individualise lymph node disease at initial staging in PCa patients. Articles were included only if absolute numbers of true-positive, true-negative, false-positive, and false-negative test results were available or derivable from the text and focused on lymph node metastases. Reviews, clinical reports, and editorial articles were excluded. All complete studies were reviewed; thus qualitative and quantitative analyses were performed. From the year 2000 to January 2012, we found 18 complete articles that critically evaluated the role of choline PET and PCa at initial staging. The meta-analysis was carried out and consisted of 10 selected studies with a total of 441 patients. The meta-analysis provided the following results: pooled sensitivity 49.2% (95% confidence interval [CI], 39.9-58.4) and pooled specificity 95% (95% CI, 92-97.1). The area under the curve was 0.9446 (p<0.05). The heterogeneity ranged between 22.7% and 78.4%. The diagnostic odds ratio was 18.999 (95% CI, 7.109-50.773). Choline PET and PET/CT provide low sensitivity in the detection of lymph node metastases prior to surgery in PCa patients. A high specificity has been reported from the overall studies. Studies carried out on a larger scale with a homogeneous patient population together with the evaluation of cost effectiveness are warranted. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Biomarker Identification for Prostate Cancer and Lymph Node Metastasis from Microarray Data and Protein Interaction Network Using Gene Prioritization Method

PubMed Central

Arias, Carlos Roberto; Yeh, Hsiang-Yuan; Soo, Von-Wun

2012-01-01

Finding a genetic disease-related gene is not a trivial task. Therefore, computational methods are needed to present clues to the biomedical community to explore genes that are more likely to be related to a specific disease as biomarker. We present biomarker identification problem using gene prioritization method called gene prioritization from microarray data based on shortest paths, extended with structural and biological properties and edge flux using voting scheme (GP-MIDAS-VXEF). The method is based on finding relevant interactions on protein interaction networks, then scoring the genes using shortest paths and topological analysis, integrating the results using a voting scheme and a biological boosting. We applied two experiments, one is prostate primary and normal samples and the other is prostate primary tumor with and without lymph nodes metastasis. We used 137 truly prostate cancer genes as benchmark. In the first experiment, GP-MIDAS-VXEF outperforms all the other state-of-the-art methods in the benchmark by retrieving the truest related genes from the candidate set in the top 50 scores found. We applied the same technique to infer the significant biomarkers in prostate cancer with lymph nodes metastasis which is not established well. PMID:22654636

[A case of locally advanced prostate cancer with low serum testosterone associated with intake of an androgenic medicine].

PubMed

Sakura, Mizuaki; Tsukamoto, Tetsurou; Yonese, Junji; Nakaishi, Masayuki; Maezawa, Takuya; Takimoto, Keita; Fukui, Iwao

2003-05-01

A 74-year-old man was referred to our clinic for the work-up of digitally hard and irregularly surfaced prostate and elevated serum prostate-specific antigen (PSA). His serum PSA was elevated to 41 ng/ml, but testosterone and LH level were decreased to 23.5 ng/dl and 0.5 mIU/ml, respectively. He had a history of taking an androgenic medicine containing methyl-testosterone 2 to 3 times a week for 2 year and 6 months. Transrectal sextant prostatic biopsy revealed moderately differentiated adenocarcinoma (Gleason score: 3 + 4) in 6 of 6 specimens and CT scan of the abdomen showed an enlarged obturator lymph-node (15 mm), resulting in the diagnosis of stage D1 (T3aN1M0) prostate cancer. Since serum testosterone level seemed to recover around the normal level after discontinuation of the exogenous androgen, we treated him with combination androgen blockade with LHRH agonist and bicaltamide, although his testosterone level was very low. Indeed, serum PSA decreased to 0.09 ng/ml and the right obturator node was markedly reduced by the hormone treatment. After the neoadjuvant therapy of 6 months duration, radical prostatectomy and limited pelvic lymph node dissection was carried out. Histologically, viable cancer cells were not found in any of resected lymph nodes, but they remained in bilateral lobes of the prostate (pT2bN0). The histological effect of the neoadjuvant hormone therapy according to General rule for Clinical and Pathological Studies on Prostate Cancer (3rd ed.) was grade 2. The patient has been well with undetectable PSA and no evidence of clinical failure for more than 12 months, though serum testosterone level recovered to near normal (288 ng/dl) 8 months after the cessation of the hormone treatment following the operation. Combination androgen blockade or non-steroidal anti-androgen agent appears to be effective for the treatment of prostatic cancer patients who takes exogenous androgenic medicine, even with a suppressed low serum testosterone level.

Assessment of Lymph Nodes and Prostate Status Using Early Dynamic Curves with (18)F-Choline PET/CT in Prostate Cancer.

PubMed

Mathieu, Cédric; Ferrer, Ludovic; Carlier, Thomas; Colombié, Mathilde; Rusu, Daniela; Kraeber-Bodéré, Françoise; Campion, Loic; Rousseau, Caroline

2015-01-01

Dynamic image acquisition with (18)F-Choline [fluorocholine (FCH)] PET/CT in prostate cancer is mostly used to overcome the bladder repletion, which could obstruct the loco-regional analysis. The aim of our study was to analyze early dynamic FCH acquisitions to define pelvic lymph node or prostate pathological status. Retrospective analysis was performed on 39 patients for initial staging (n = 18), or after initial treatment (n = 21). Patients underwent 10-min dynamic acquisitions centered on the pelvis, after injection of 3-4 MBq/kg of FCH. Whole-body images were acquired about 1 h after injection using a PET/CT GE Discovery LS (GE-LS) or Siemens Biograph mCT (mCT). Maximum and mean SUV according to time were measured on nodal and prostatic lesions. SUVmean was corrected for partial volume effect (PVEC) with suitable recovery coefficients. The status of each lesion was based on histological results or patient follow-up (>6 months). A Mann-Whitney test and ANOVA were used to compare mean and receiver operating characteristic (ROC) curve analysis. The median PSA was 8.46 ng/mL and the median Gleason score was 3 + 4. Ninety-two lesions (43 lymph nodes and 49 prostate lesions) were analyzed, including 63 malignant lesions. In early dynamic acquisitions, the maximum and mean SUV were significantly higher, respectively, on mCT and GE-LS, in malignant versus benign lesions (p < 0.001, p < 0.001). Mean SUV without PVEC, allowed better discrimination of benign from malignant lesions, in comparison with maximum and mean SUV (with PVEC), for both early and late acquisitions. For patients acquired on mCT, area under the ROC curve showed a trend to better sensitivity and specificity for early acquisitions, compared with late acquisitions (SUVmax AUC 0.92 versus 0.85, respectively). Assessment of lymph nodes and prostate pathological status with early dynamic imaging using PET/CT FCH allowed prostate cancer detection in situations where proof of malignancy is difficult to obtain.

Body mass index was associated with upstaging and upgrading in patients with low-risk prostate cancer who met the inclusion criteria for active surveillance.

PubMed

de Cobelli, Ottavio; Terracciano, Daniela; Tagliabue, Elena; Raimondi, Sara; Galasso, Giacomo; Cioffi, Antonio; Cordima, Giovanni; Musi, Gennaro; Damiano, Rocco; Cantiello, Francesco; Detti, Serena; Victor Matei, Deliu; Bottero, Danilo; Renne, Giuseppe; Ferro, Matteo

2015-05-01

Obesity is associated with an increased risk of high-grade prostate cancer (PCa). The effect of body mass index (BMI) as a predictor of progression in men with low-risk PCa has been only poorly assessed. In this study, we evaluated the association of BMI with progression in patients with low-risk PCa who met the inclusion criteria for the active surveillance (AS) protocol. We assessed 311 patients who underwent radical prostatectomy and were eligible for AS according to the following criteria: clinical stage T2a or less, prostate-specific antigen level < 10 ng/ml, 2 or fewer cores involved with cancer, Gleason score ≤ 6 grade, and prostate-specific antigen density < 0.2 ng/ml/cc. Reclassification was defined as upstaged (pathological stage > pT2) and upgraded (Gleason score ≥ 7; primary Gleason pattern 4) disease. Seminal vesicle invasion, positive lymph nodes, and tumor volume ≥ 0.5 ml were also recorded. We found that high BMI was significantly associated with upgrading, upstaging, and seminal vesicle invasion, whereas it was not associated with positive lymph nodes or large tumor volume. At multivariate analysis, 1 unit increase of BMI significantly increased the risk of upgrading, upstaging, seminal vesicle invasion, and any outcome by 21%, 23%, 27%, and 20%, respectively. The differences between areas under the receiver operating characteristics curves comparing models with and without BMI were statistically significant for upgrading (P = 0.0002), upstaging (P = 0.0007), and any outcome (P = 0.0001). BMI should be a selection criterion for inclusion of patients with low-risk PCa in AS programs. Our results support the idea that obesity is associated with worse prognosis and suggest that a close AS program is an appropriate treatment option for obese subjects. Copyright © 2015 Elsevier Inc. All rights reserved.

Does Choline PET/CT Change the Management of Prostate Cancer Patients With Biochemical Failure?

PubMed

Goldstein, Jeffrey; Even-Sapir, Einat; Ben-Haim, Simona; Saad, Akram; Spieler, Benjamin; Davidson, Tima; Berger, Raanan; Weiss, Ilana; Appel, Sarit; Lawrence, Yaacov R; Symon, Zvi

2017-06-01

The FDA approved C-11 choline PET/computed tomography (CT) for imaging patients with recurrent prostate cancer in 2012. Subsequently, the 2014 NCCN guidelines have introduced labeled choline PET/CT in the imaging algorithm of patients with suspected recurrent disease. However, there is only scarce data on the impact of labeled choline PET/CT findings on disease management. We hypothesized that labeled-choline PET/CT studies showing local or regional recurrence or distant metastases will have a direct role in selection of appropriate patient management and improve radiation planning in patients with disease that can be controlled using this mode of therapy. This retrospective study was approved by the Tel Aviv Sourasky and Sheba Medical Center's Helsinki ethical review committees. Patient characteristics including age, PSA, stage, prior treatments, and pre-PET choline treatment recommendations based on NCCN guidelines were recorded. Patients with biochemical failure and without evidence of recurrence on physical examination or standard imaging were offered the option of additional imaging with labeled choline PET/CT. Treatment recommendations post-PET/CT were compared with pre-PET/CT ones. Pathologic confirmation was obtained before prostate retreatment. A nonparametric χ test was used to compare the initial and final treatment recommendations following choline PET/CT. Between June 2010 and January 2014, 34 labeled-choline PET/CT studies were performed on 33 patients with biochemical failure following radical prostatectomy (RP) (n=6), radiation therapy (RT) (n=6), brachytherapy (n=2), RP+salvage prostate fossa RT (n=14), and RP+salvage prostate fossa/lymph node RT (n=6). Median PSA level before imaging was 2 ng/mL (range, 0.16 to 79). Labeled choline PET/CT showed prostate, prostate fossa, or pelvic lymph node increased uptake in 17 studies, remote metastatic disease in 9 studies, and failed to identify the cause for biochemical failure in 7 scans.PET/CT altered treatment approach in 18 of 33 (55%) patients (P=0.05). Sixteen of 27 patients (59%) treated previously with radiation were retreated with RT and delayed or eliminated androgen deprivation therapy: 1 received salvage brachytherapy, 10 received salvage pelvic lymph node or prostate fossa irradiation, 2 brachytherapy failures received salvage prostate and lymph nodes IMRT, and 3 with solitary bone metastasis were treated with radiosurgery. Eleven of 16 patients retreated responded to salvage therapy with a significant PSA response (<0.2 ng/mL), 2 patients had partial biochemical responses, and 3 patients failed. The median duration of response was 500±447 days. Two of 6 patients with no prior RT were referred for salvage prostatic fossa RT: 1 received dose escalation for disease identified in the prostate fossa and another had inclusion of "hot" pelvic lymph nodes in the treatment volume. These early results suggest that labeled choline PET/CT imaging performed according to current NCCN guidelines may change management and improve care in prostate cancer patients with biochemical failure by identifying patients for referral for salvage radiation therapy, improving radiation planning, and delaying or avoiding use of androgen deprivation therapy.

Potential advantage of studying the lymphatic drainage by sentinel node technique and SPECT-CT image fusion for pelvic irradiation of prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krengli, Marco; Ballare, Andrea; Cannillo, Barbara

2006-11-15

Purpose: This study aims to investigate the in vivo drainage of lymphatic spread by using the sentinel node (SN) technique and single-photon emission computed tomography (SPECT)-computed tomography (CT) image fusion, and to analyze the impact of such information on conformal pelvic irradiation. Methods and Materials: Twenty-three prostate cancer patients, candidates for radical prostatectomy already included in a trial studying the SN technique, were enrolled. CT and SPECT images were obtained after intraprostate injection of 115 MBq of {sup 99m}Tc-nanocolloid, allowing identification of SN and other pelvic lymph nodes. Target and nontarget structures, including lymph nodes identified by SPECT, were drawnmore » on SPECT-CT fusion images. A three-dimensional conformal treatment plan was performed for each patient. Results: Single-photon emission computed tomography lymph nodal uptake was detected in 20 of 23 cases (87%). The SN was inside the pelvic clinical target volume (CTV{sub 2}) in 16 of 20 cases (80%) and received no less than the prescribed dose in 17 of 20 cases (85%). The most frequent locations of SN outside the CTV{sub 2} were the common iliac and presacral lymph nodes. Sixteen of the 32 other lymph nodes (50%) identified by SPECT were found outside the CTV{sub 2}. Overall, the SN and other intrapelvic lymph nodes identified by SPECT were not included in the CTV{sub 2} in 5 of 20 (25%) patients. Conclusions: The study of lymphatic drainage can contribute to a better knowledge of the in vivo potential pattern of lymph node metastasis in prostate cancer and can lead to a modification of treatment volume with consequent optimization of pelvic irradiation.« less

Interleukin-30: A novel microenvironmental hallmark of prostate cancer progression.

PubMed

Di Carlo, Emma

2014-01-01

Metastatic prostate cancer is a leading cause of cancer-related death in men worldwide. We have recently discovered that IL-30 shapes the microenvironment of prostate cancer and tumor-draining lymph nodes to favor tumor progression. IL-30 supports tumor growth in vitro, and IL-30 expression in prostate cancer patients is associated with high tumor grade and metastatic stage of disease. Thus, IL-30 may constitute a valuable target for modern therapeutic approaches to hamper prostate cancer progression.

Multiadaptive Plan (MAP) IMRT to Accommodate Independent Movement of the Prostate and Pelvic Lymph Nodes

DTIC Science & Technology

2010-12-01

the second Innovative Minds in Prostate Cancer Today (IMPaCT) conference, sponsored by prostate cancer research program of USAMRMC (Appendix B...presentation in the second Innovative Minds in Prostate Cancer Today (IMPaCT) conference, sponsored by prostate cancer research program of USAMRMC...NUMBER W81XWH-08-1-0358 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Ping Xia 5d. PROJECT NUMBER Xiap@ccf.org 5e. TASK NUMBER 5f. WORK

[PET/CT and biochemical recurrence of prostate adenocarcinoma: Added value of 68Ga-PSMA-11 when 18F-fluorocholine is non-contributive].

PubMed

Gauthé, M; Belissant, O; Girard, A; Zhang Yin, J; Ohnona, J; Cottereau, A-S; Nataf, V; Balogova, S; Pontvert, D; Lebret, T; Guillonneau, B; Cussenot, O; Talbot, J-N

Since April 201, we have introduced PET/CT using a ligand of prostate-specific membrane antigen labeled with gallium-68 (PSMA-11). We aimed to evaluate its positivity rate and impact in patients presenting biochemical recurrence of prostate cancer whose 18 F-fluorocholine (FCH) PET/CT was non-contributive. Patients were prospectively included between April and December 2016. PET/CT was performed 60min after injection of 2MBq/kg of body mass of 68 Ga-PSMA-11. Three anatomical areas were considered: prostatic lodge, pelvic lymph nodes and distant locations. The impact of PSMA-11 PET/CT was assessed by comparing changes in therapeutic strategy decided during multidisciplinary meeting. Thirty-three patients were included. The mean PSA serum level measured on the month of the PSMA-11 PET/CT was 2,8ng/mL. Twenty-five (76%) PSMA-11 PET/CT were positive, 7 (21%) negative and 1 (3%) equivocal. Of 11 patients whose FCH PET/CT showed equivocal foci, PSMA-11 PET/CT confirmed those foci in 5 cases. Follow-up was available for 18 patients (55%). PSMA-11 PET/CT results led to a change in management in 12 patients (67%). 68 Ga-PSMA-11 PET/CT is useful in detecting recurrence of prostate cancer, by identifying residual disease which was not detected on other imaging modalities and by changing management of 2 patients out of 3. 5. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Heterogeneous PSMA expression on circulating tumor cells - a potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer

PubMed Central

Gorges, Tobias M.; Riethdorf, Sabine; von Ahsen, Oliver; Nastały, Paulina; Röck, Katharina; Boede, Marcel; Peine, Sven; Kuske, Andra; Schmid, Elke; Kneip, Christoph; König, Frank; Rudolph, Marion; Pantel, Klaus

2016-01-01

The prostate specific membrane antigen (PSMA) is the only clinically validated marker for therapeutic decisions in prostate cancer (PC). Characterization of circulating tumor cells (CTCs) obtained from the peripheral blood of PC patients might provide an alternative to tissue biopsies called “liquid biopsy”. The aim of this study was to develop a reliable assay for the determination of PSMA on CTCs. PSMA expression was analyzed on tissue samples (cohort one, n = 75) and CTCs from metastatic PC patients (cohort two, n = 29). Specific signals for the expression of PSMA could be seen for different prostate cancer cell line cells (PC3, LaPC4, 22Rv1, and LNCaP) by Western blot, immunohistochemistry (IHC), immunocytochemistry (ICC), and FACS. PSMA expression was found to be significantly increased in patients with higher Gleason grade (p = 0.0011) and metastases in lymph nodes (p = 0.0000085) or bone (p = 0.0020) (cohort one). In cohort two, CTCs were detectable in 20 out of 29 samples (69 %, range from 1 - 1000 cells). Twelve out of 20 CTC-positive patients showed PSMA-positive CTCs (67 %, score 1+ to 3+). We found intra-patient heterogeneity regarding the PSMA status between CTCs and the corresponding primary tumors. The results of our study could help to address the question whether treatment decisions based on CTC PSMA profiling will lead to a measurable benefit in clinical outcome for prostate cancer patients in the near future. PMID:27145459

Three-phase 18F-fluorocholine PET/CT in the evaluation of prostate cancer recurrence.

PubMed

Steiner, Ch; Vees, H; Zaidi, H; Wissmeyer, M; Berrebi, O; Kossovsky, M P; Khan, H G; Miralbell, R; Ratib, O; Buchegger, F

2009-01-01

Contribution of 3-phase 18F-fluorocholine PET/CT in suspected prostate cancer recurrence at early rise of PSA. Retrospective analysis was performed in 47 patients after initial treatment with radiotherapy (n=30) or surgery (n=17). Following CT, 10 minutes list-mode PET acquisition was done over the prostate bed after injection of 300 MBq of 18F-fluorocholine. Three timeframes of 3 minutes each were reconstructed for analysis. All patients underwent subsequent whole body PET/CT. Delayed pelvic PET/CT was obtained in 36 patients. PET/CT was interpreted visually by two observers and SUVmax determined for suspicious lesions. Biopsies were obtained from 13 patients. Biopsies confirmed the presence of cancer in 11 of 13 patients with positive PET for a total of 15 local recurrences in which average SUVmax increased during 14 minutes post injection and marginally decreased in delayed scanning. Conversely inguinal lymph nodes with mild to moderate metabolic activity on PET showed a clearly different pattern with decreasing SUVmax on dynamic images. Three-phase PET/CT contributed to the diagnostic assessment of 10 of 47 patients with biological evidence of recurrence of cancer. It notably allowed the discrimination of confounding blood pool or urinary activity from suspicious hyperactivities. PET/CT was positive in all patients with PSA>or=2 ng/ml (n=34) and in 4/13 patients presenting PSA values<2 ng/ml. 18F-fluorocholine 3-phase PET/CT showed a progressively increasing SUVmax in biopsy confirmed cancer lesions up to 14 minutes post injection while decreasing in inguinal lymph nodes interpreted as benign. Furthermore, it was very useful in differentiating local recurrences from confounding blood pool and urinary activity.

Prognostic significance of epithelial/stromal caveolin-1 expression in prostatic hyperplasia, high grade prostatic intraepithelial hyperplasia and prostatic carcinoma and its correlation with microvessel density.

PubMed

Mohammed, Dareen A; Helal, Duaa S

2017-03-01

Caveolin-1 may play a role in cancer development and progression. The aim was to record the expression and localization of caveolin-1 in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostatic carcinoma (PCa). Microvessel density was evaluated with CD34 immunostain. Correlations with known prognostic factors of PCa were recorded. Immunohistochemical expression of caveolin-1 and the MVD was evaluated in 65 cases; BPH (25), HGPIN (20) and PCa (20). Stromal caveolin-1expression was significantly higher in BPH than HGPIN and PCca. There was significant inverse relation between stromal caveolin-1 expression and extension to lymph node and seminal vesicle in carcinoma cases. Epithelial caveolin-1 was significantly higher in carcinomas than in BPH and HGPIN. Epithelial expression in carcinoma was significantly associated with preoperative PSA, Gleason score and lymph node extension. MVD was significantly higher in PCa than in BPH and HGPIN. There were significant relations between MVD and preoperative PSA, Gleason score, lymph node and seminal vesicle extension. Stromal caveolin-1 was associated with low MVD while epithelial caveolin-1 with high MVD. Caveolin-1 plays an important role in prostatic carcinogenesis and metastasis. Stromal expression of caveolin-1 in PCa is lowered in relation to BPH and HGPIN. In PCa; stromal caveolin-1 was associated with good prognostic parameters. Epithelial caveolin-1 is significantly increased in PCa than BPH and HGPIN. It is associated with clinically aggressive disease. Caveolin-1 may play a role in angiogenesis. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Comparison of 68Ga-PSMA-11 PET-CT with mpMRI for preoperative lymph node staging in patients with intermediate to high-risk prostate cancer.

PubMed

Zhang, Qing; Zang, Shiming; Zhang, Chengwei; Fu, Yao; Lv, Xiaoyu; Zhang, Qinglei; Deng, Yongming; Zhang, Chuan; Luo, Rui; Zhao, Xiaozhi; Wang, Wei; Wang, Feng; Guo, Hongqian

2017-11-07

To evaluate the diagnostic value of 68 Ga-PSMA-11 PET-CT with multiparametric magnetic resonance imaging (mpMRI) for lymph node (LN) staging in patients with intermediate- to high-risk prostate cancer (PCa) undergoing radical prostatectomy (RP) with pelvic lymph node dissection (PLND). We retrospectively identified 42 consecutive patients with intermediate- to high-risk PCa according to D'Amico and without concomitant cancer. Preoperative 68 Ga-PSMA-11 PET-CT, pelvic mpMRI and subsequent robot assisted laparoscopic RP with PLND were performed in all patients. Among 42 patients assessed, the preoperative PSA value, Gleason score, pT stage and intraprostatic PCa volume of patients with LN metastases were all significantly higher than those without metastases (P = 0.029, 0.028, 0.004, respectively). The average maximum standardized uptake value (SUV) of 68 Ga-PSMA-11 PET-CT positive PCa of patients with or without LN metastases were 13.10 (range 6.12-51.75) and 7.22 (range 5.4-11.2), respectively (P < 0.001). 68 Ga-PSMA-11 PET-CT and pelvic mpMRI had the ability of succeed on preoperative definite accurate diagnosis and accurate localization of primary PCa in all 42 patients. Fifteen patients (35.71%) had a pN1 stage. 51 positive LN were found. Both 68 Ga-PSMA-11 PET-CT and pelvic mpMRI displayed brillient patient-based and region-based sensitivity, specificity, negative predictive value and positive predictive value. There was no statistical difference for the detection of LNMs according to the diameter of the LNMs between 68 Ga-PSMA-11 PET-CT and mpMRI in this study. Both 68 Ga-PSMA-11 PET-CT and mpMRI performed great value for LN staging in patients with intermediate- to high-risk PCa undergoing RP with PLND. However, despite excellent performance of 68 Ga-PSMA-11 PET-CT, it cannot replace mpMRI that remains excellent for lymph node staging.

Whole-Pelvic Nodal Radiation Therapy in the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step Forward

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaidar-Person, Orit; Roach, Mack; Créhange, Gilles, E-mail: gcrehange@cgfl.fr

2013-07-15

Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted conventional radiation therapy to the prostate only. In high-risk prostate cancer patients, there is accumulating evidence that either dose escalation to the prostate or hypofractionation may improve outcome. Nevertheless, selected patients who have amore » high risk of lymph node involvement may benefit from whole-pelvic radiation therapy (WPRT). Although combining WPRT with hypofractionated prostate radiation therapy is feasible, it remains investigational. By combining modern advances in radiation oncology (high-dose-rate prostate brachytherapy, intensity modulated radiation therapy with an improved image guidance for soft-tissue sparing), it is hypothesized that WPRT could take advantage of recent results from hypofractionation trials. Moreover, the results from hypofractionation trials raise questions as to whether hypofractionation to pelvic lymph nodes with a high risk of occult involvement might improve the outcomes in WPRT. Although investigational, this review discusses the challenging idea of WPRT in the context of hypofractionation for patients with high-risk prostate cancer.« less

Distribution of Prostate Sentinel Nodes: A SPECT-Derived Anatomic Atlas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganswindt, Ute, E-mail: ute.ganswindt@med.uni-muenchen.d; Schilling, David; Mueller, Arndt-Christian

2011-04-01

Purpose: The randomized Radiation Therapy Oncology Group 94-13 trial revealed that coverage of the pelvic lymph nodes in high-risk prostate cancer confers an advantage (progression-free survival and biochemical failure) in patients with {>=}15% risk of lymph node involvement. To facilitate an improved definition of the adjuvant target volume, precise knowledge regarding the location of the relevant lymph nodes is necessary. Therefore, we generated a three-dimensional sentinel lymph node atlas. Methods and Materials: In 61 patients with high-risk prostate cancer, a three-dimensional visualization of sentinel lymph nodes was performed using a single photon emission computed tomography system after transrectal intraprostatic injectionmore » of 150 to 362 (median 295) mega becquerel (MBq) {sup 99m}Technetium-nanocolloid (1.5-3h after injection) followed by an anatomic functional image fusion. Results: In all, 324 sentinel nodes in 59 of 61 patients (96.7%) were detected, with 0 to 13 nodes per patient (median 5, mean 5.3). The anatomic distribution of the sentinel nodes was as follows: external iliac 34.3%, internal iliac 17.9%, common iliac 12.7%, sacral 8.6%, perirectal 6.2%, left paraaortic 5.3%, right paraaortic 5.3%, seminal vesicle lymphatic plexus 3.1%, deep inguinal 1.5%, superior rectal 1.2%, internal pudendal 1.2%, perivesical 0.9%, inferior rectal 0.9%, retroaortic 0.3%, superficial inguinal 0.3%, and periprostatic 0.3%. Conclusions: The distribution of sentinel nodes as detected by single photon emission computed tomography imaging correlates well with the distribution determined by intraoperative gamma probe detection. A lower detection rate of sentinels in close proximity to the bladder and seminal vesicles is probably caused by the radionuclide accumulation in the bladder. In regard to intensity-modulated radiotherapy techniques, the presented anatomic atlas may allow optimized target volume definitions.« less

Synchronous Detection of Male Breast Cancer and Prostatic Cancer in a Patient With Suspected Prostatic Carcinoma on 68Ga-PSMA PET/CT Imaging.

PubMed

Kumar, Rajender; Mittal, Bhagwant Rai; Bhattacharya, Anish; Singh, Harmandeep; Singh, Shrawan Kumar

2018-06-01

The male breast cancer is very less common as compared with the female breast cancer. We report a case of 64-year-old man who presented with the history of lower urinary tract symptoms. The digital rectal examination revealed hard and nodular prostate, and serum prostate-specific antigen level was 23.4 ng/mL. Ga-labeled prostate-specific membrane antigen PET/CT revealed prostate-specific membrane antigen-expressing lesions in the prostate, axillary tail of the right breast, and axillary lymph nodes. Histology from prostate revealed prostate carcinoma, whereas fine-needle aspiration from the breast revealed invasive ductal carcinoma of the breast.

Diagnostic Performance of 11C-choline PET/CT and FDG PET/CT in Prostate Cancer.

PubMed

Kitajima, Kazuhiro; Yamamoto, Shingo; Odawara, Soichi; Kobayashi, Kaoru; Fujiwara, Masayuki; Kamikonya, Norihiko; Fukushima, Kazuhito; Nakanishi, Yukako; Hashimoto, Takahiko; Yamada, Yusuke; Suzuki, Toru; Kanematsu, Akihiro; Nojima, Michio; Yamakado, Koichiro

2018-06-01

We compared 11C-choline and FDG PET/CT scan findings for the staging and restaging of prostate cancer. Twenty Japanese prostate cancer patients underwent 11C-choline and FDG PET/CT before (n=5) or after (n=15) treatment. Using a five-point scale, we compared these scanning modalities regarding patient- and lesion-based diagnostic performance for local recurrence, untreated primary tumor, and lymph node and bony metastases. Of the 20 patients, documented local lesions, and node and bony metastases were present in 11 (55.0%), 9 (45.0%), and 13 (65.0%), respectively. The patient-based sensitivity/specificity/accuracy/area under the receiver-operating-characteristic curve (AUC) values for 11C-choline-PET/CT for diagnosing local lesions were 90.9% /100%/ 95.0% / 1.0, whereas those for FDG-PET/CT were 45.5% /100%/ 75.0% / 0.773. Those for 11C-choline-PET/CT for node metastasis were 88.9% /100%/ 95.0% / 0.944, and those for FDG-PET/CT were 44.4%/100%/75.0%/0.722. Those for 11C-choline-PET/CT for bone metastasis were 84.6%/100%/90.0%/0.951, and those for FDG-PET/CT were 76.9% /100%/ 85.0% / 0.962. The AUCs for local lesion and node metastasis differed significantly (p=0.0039, p=0.011, respectively). The lesion-based detection rates of 11C-choline compared to FDG PET/CT for local lesion, and node and bone metastases were 91.7% vs. 41.7%, 92.0% vs. 32.0%, and 94.8% vs. 83.0% (p=0.041, p=0.0030, p<0.0001), respectively. 11C-choline-PET/CT is more useful for the staging and restaging of prostate cancer than FDG-PET/CT in Japanese men.

Standardized comparison of robot-assisted limited and extended pelvic lymphadenectomy for prostate cancer.

PubMed

Yuh, Bertram E; Ruel, Nora H; Mejia, Rosa; Novara, Giacomo; Wilson, Timothy G

2013-07-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Extended pelvic lymphadenectomy is the present standard of care according to European Association of Urology guidelines. Extended dissection improves staging, removes more metastatic lymph nodes, and potentially has therapeutic benefits. Previous reports have examined the morbidity of extended dissection compared with a more limited dissection in the open and laparoscopic setting. While some have suggested an increased complication rate with extended node dissection, others have not. This represents the first study focused on comparing the complications associated with the extent of node dissection using the modified Clavien system and Martin criteria in the literature on robot-assisted surgery. In a single surgeon series, we found no statistically significant differences in complications. With careful anatomic dissection, robot-assisted extended lymph node dissection can be performed safely and effectively, although operating time and length of hospital of stay are slightly increased. To compare the perioperative course of patients undergoing robot-assisted limited lymph node dissection (LLND) or extended lymph node dissection (ELND) for prostate cancer. To examine the differential lymph node counts and rates of detection of lymph node metastases. Between 2008 and 2012, 406 consecutive patients with D'Amico intermediate- or high-risk prostate cancer underwent either bilateral LLND (n = 204) or ELND (n = 202) and robot-assisted laparoscopic radical prostatectomy by a single surgeon. The region of dissection was the obturator fossa for LLND, while ELND included, in addition, the common iliac, external iliac and internal iliac lymph nodes. All complications within 90 days of surgery were recorded according to a modified Clavien system. Clinical variables were summarized and compared. Logistic regression was used to identify predictors of complications. There were no differences in demographics when comparing patients who underwent ELND with those who underwent LLND. The median operating time was 3.0 h for the ELND cohort and 2.8 h in the LLND cohort (P < 0.001). Intraoperative blood loss was 200 mL in both cohorts. Hospital stay was longer for a small percentage of patients in the ELND cohort, with 75% of ELND patients and 85% of LLND patients staying 1 day (P = 0.004). No significant difference was found in the overall or major complication rates between LLND (21.6% overall; 6.9% major) and ELND (22.8% overall; 4.5% major). No difference was seen in the symptomatic lymphocele rate between LLND and ELND, 2.9 vs 2.5%, respectively. Overall, the lymph-node-positive rate was 12% compared with 4% for the ELND and LLND groups, respectively (P = 0.002). A higher Charlson comorbidity index score was associated with the development of major complications. ELND at the time of robot-assisted radical prostatectomy can be performed safely with minimal additional morbidity. Long-term oncological and functional outcomes require further study. © 2013 BJU International.

First postoperative PSA is associated with outcomes in patients with node positive prostate cancer: Results from the SEARCH database.

PubMed

McDonald, Michelle L; Howard, Lauren E; Aronson, William J; Terris, Martha K; Cooperberg, Matthew R; Amling, Christopher L; Freedland, Stephen J; Kane, Christopher J

2018-05-01

To analyze factors associated with metastases, prostate cancer-specific mortality, and all-cause mortality in pN1 patients. We analyzed 3,642 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Pathologic Gleason grade, number of lymph nodes (LN) removed, and first postoperative prostate-specific antigen (PSA) (<0.2 ng/ml or ≥0.2 ng/ml) were among covariates assessed. Cox regression was used to analyze the association between characteristics and survival outcomes. Kaplan-Meier was used to estimate survival in pN1 patients stratified by first postoperative PSA. Of 3,642 patients, 124 (3.4%) had pN1. There were 71 (60%) patients with 1 positive LN, 32 (27%) with 2 positive LNs, and 15 (13%) with ≥3. Among men with pN1, first postoperative PSA was<0.2ng/ml in 46 patients (51%) and ≥0.2ng/ml in 44 patients (49%). Univariable Cox regression determined pathological Gleason grade (P = 0.021), seminal vesicle invasion (P = 0.010), and first postoperative PSA ≥0.2 ng/ml (P = 0.005) were associated with metastases. First postoperative PSA ≥0.2ng/ml was associated with metastasis on multivariable analysis (P = 0.046). Log-rank analysis revealed a more favorable metastases-free survival in patients with a first postoperative PSA<0.2ng/ml (P = 0.001). Estimated 5-year metastases-free survival rate was 99% for patients with a first postoperative PSA<0.2ng/ml and 87% for ≥0.2ng/ml. pN1 patients with a first postoperative PSA ≥0.2ng/ml were more likely to develop metastases. First postoperative PSA may be useful in identifying pN1 patients who harbor distant disease and aid in secondary treatment decisions. Copyright © 2018 Elsevier Inc. All rights reserved.

Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer.

PubMed

Park, Sonya Youngju; Zacharias, Claudia; Harrison, Caitlyn; Fan, Richard E; Kunder, Christian; Hatami, Negin; Giesel, Frederik; Ghanouni, Pejman; Daniel, Bruce; Loening, Andreas M; Sonn, Geoffrey A; Iagaru, Andrei

2018-05-16

Purpose To report the results of dual-time-point gallium 68 ( 68 Ga) prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi ± 0.7 (151.7 MBq ± 25.9) of 68 Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUV max ]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at 68 Ga-PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation of 68 Ga-PSMA-11 increased at later acquisition times, with higher mean SUV max (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that 68 Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence, 68 Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection. © RSNA, 2018 Online supplemental material is available for this article.

18F-DCFPyL PET/CT in the Detection of Prostate Cancer at 60 and 120 Minutes: Detection Rate, Image Quality, Activity Kinetics, and Biodistribution.

PubMed

Wondergem, Maurits; van der Zant, Friso M; Knol, Remco J J; Lazarenko, Sergiy V; Pruim, Jan; de Jong, Igle J

2017-11-01

There is increasing interest in PET/CT with prostate-specific membrane antigen (PSMA) tracers for imaging of prostate cancer because of the higher detection rates of prostate cancer lesions than with PET/CT with choline. For 68 Ga-PSMA-11 tracers, late imaging at 180 min after injection instead of imaging at 45-60 min after injection improves the detection of prostate cancer lesions. For 18 F-DCFPyL, improved detection rates have recently been reported in a small pilot study. In this study, we report the effects of PET/CT imaging at 120 min after injection of 18 F-DCFPyL in comparison to images acquired at 60 min after injection in a larger clinical cohort of 66 consecutive patients with histopathologically proven prostate cancer. Methods: Images were acquired 60 and 120 min after injection of 18 F-DCFPyL. We report the positive lesions specified for anatomic locations (prostate, seminal vesicles, local lymph nodes, distant lymph nodes, bone, and others) at both time points by visual analysis, the image quality at both time points, and a semiquantitative analysis of the tracer activity in both prostate cancer lesions as well as normal tissues at both time points. Results: Our data showed a significantly increasing uptake of 18 F-DCFPyL between 60 and 120 min after injection in 203 lesions characteristic for prostate cancer (median, 10.78 vs. 12.86, P < 0.001, Wilcoxon signed-rank test). By visual analysis, 38.5% of all patients showed more lesions using images at 120 min after injection than using images at 60 min after injection, and in 9.2% a change in TNM staging was found. All lesions seen on images 60 min after injection were also visible on images 120 min after injection. A significantly better mean signal-to-noise ratio of 11.93 was found for images acquired 120 min after injection ( P < 0.001, paired t test; signal-to-noise ratio at 60 min after injection, 11.15). Conclusion: 18 F-DCFPyL PET/CT images at 120 min after injection yield a higher detection rate of prostate cancer characteristic lesions than images at 60 min after injection. Further studies are needed to elucidate the best imaging time point for 18 F-DCFPyL. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Increased Expression of ALDH1A1 in Prostate Cancer is Correlated With Tumor Aggressiveness: A Tissue Microarray Study of Iranian Patients.

PubMed

Kalantari, Elham; Saadi, Faezeh H; Asgari, Mojgan; Shariftabrizi, Ahmad; Roudi, Raheleh; Madjd, Zahra

2017-09-01

Subpopulations of prostate cancer (PCa) cells expressing putative stem cell markers possess the ability to promote tumor growth, maintenance, and progression. This study aimed to evaluate the expression patterns and clinical significance of putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH1A1) in prostate tumor tissues. ALDH1A1 expression was examined in a well-defined series of prostate tissues, including 105 (68%) samples of PCa, 21 (13%) samples of high-grade prostatic intraepithelial neoplasia, and 31 (19%) samples of benign prostate hyperplasia, which were embedded in tissue microarray blocks. The correlation of ALDH1A1 expression with clinicopathologic parameters was also assessed. There was a significant difference between the expression level of ALDH1A1 in PCa compared with the high-grade prostatic intraepithelial neoplasia and benign prostate hyperplasia samples (P<0.001). PCa cells expressing ALDH1A1 were more often seen in samples with advanced Gleason score (P=0.05) and high serum prostate specific antigen level (P=0.02). In addition, a positive correlation was found between ALDH1A1 expression and primary tumor stage and regional lymph node involvement (P=0.04 and 0.03, respectively). The significant association between ALDH1A1 expressions with Gleason score indicates the potential role of this protein in PCa tumorigenesis and aggressive behavior; therefore, this cancer stem cell marker can be used as a promising candidate for targeted therapy of PCa, especially those with high Gleason score.

The Outcome for Patients With Pathologic Node-Positive Prostate Cancer Treated With Intensity Modulated Radiation Therapy and Androgen Deprivation Therapy: A Case-Matched Analysis of pN1 and pN0 Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Hemelryk, Annelies; De Meerleer, Gert; Ost, Piet

Purpose: Improved outcome is reported after surgery or external beam radiation therapy (EBRT) plus androgen deprivation therapy (ADT) for patients with lymph node (LN) positive (N1) prostate cancer (PC). Surgical series have shown that pathologic (p)N1 PC does not behave the same in all patients. The aim of this study was to perform a matched-case analysis to compare the outcome of pN1 and pN0 PC after high-dose EBRT plus ADT. Methods and Materials: Radiation therapy up to 80 Gy was delivered to the prostate with a minimal dose of 45 Gy to the pelvis for pN1 patients. After matching, Kaplan-Meier statistics weremore » used to compare the 5-year biochemical and clinical relapse-free survival (bRFS and cRFS), prostate cancer–specific survival (PCSS), and overall survival (OS). Acute and late rectal and urinary toxicity was evaluated. Results: Sixty-nine pN1 PC patients were matched 1:1 with pN0 PC patients. The median follow-up time was 60 months. The 5-year bRFS and cRFS for pN1 versus pN0 PC patients were 65% ± 7% versus 79% ± 5% (P=.08) and 70% ± 6% versus 83% ± 5% (P=.04) respectively. No significant difference was found in bRFS or cRFS rates between low volume pN1 (≤2 positive LNs) and pN0 patients. The 5-year PCSS and OS were comparable between pN1 and pN0 PC patients: PCSS: 92% ± 4% versus 93% ± 3% (P=.66); OS: 82% ± 5% versus 80% ± 5% (P=.58). Severe toxicity was rare for both groups, although pN1 patients experienced significantly more acute grade 2 rectal toxicity. Conclusion: Primary EBRT plus 2 to 3 years of ADT is a legitimate treatment option for pN1 PC patients, especially those with ≤2 positive LNs, and this with bRFS and cRFS rates comparable to those in pN0 PC patients. For pN1 PC patients with >2 positive LNs, bRFS and cRFS are worse than in pN0 patients, but even in this subgroup, long-term disease control is obtained.« less

Impact of time-of-flight PET on quantification accuracy and lesion detection in simultaneous 18F-choline PET/MRI for prostate cancer.

PubMed

Mühlematter, Urs J; Nagel, Hannes W; Becker, Anton; Mueller, Julian; Vokinger, Kerstin N; de Galiza Barbosa, Felipe; Ter Voert, Edwin E G T; Veit-Haibach, Patrick; Burger, Irene A

2018-05-31

Accurate attenuation correction (AC) is an inherent problem of positron emission tomography magnetic resonance imaging (PET/MRI) systems. Simulation studies showed that time-of-flight (TOF) detectors can reduce PET quantification errors in MRI-based AC. However, its impact on lesion detection in a clinical setting with 18 F-choline has not yet been evaluated. Therefore, we compared TOF and non-TOF 18 F-choline PET for absolute and relative difference in standard uptake values (SUV) and investigated the detection rate of metastases in prostate cancer patients. Non-TOF SUV was significantly lower compared to TOF in all osseous structures, except the skull, in primary lesions of the prostate, and in pelvic nodal and osseous metastasis. Concerning lymph node metastases, both experienced readers detected 16/19 (84%) on TOF PET, whereas on non-TOF PET readers 1 and 2 detected 11 (58%), and 14 (73%), respectively. With TOF PET readers 1 and 2 detected 14/15 (93%) and 11/15 (73%) bone metastases, respectively, whereas detection rate with non-TOF PET was 73% (11/15) for reader 1 and 53% (8/15) for reader 2. The interreader agreement was good for osseous metastasis detection on TOF (kappa 0.636, 95% confidence interval [CI] 0.453-0.810) and moderate on non-TOF (kappa = 0.600, CI 0.438-0.780). TOF reconstruction for 18 F-choline PET/MRI shows higher SUV measurements compared to non-TOF reconstructions in physiological osseous structures as well as pelvic malignancies. Our results suggest that addition of TOF information has a positive impact on lesion detection rate for lymph node and bone metastasis in prostate cancer patients.

Trajectory optimization for dynamic couch rotation during volumetric modulated arc radiotherapy

NASA Astrophysics Data System (ADS)

Smyth, Gregory; Bamber, Jeffrey C.; Evans, Philip M.; Bedford, James L.

2013-11-01

Non-coplanar radiation beams are often used in three-dimensional conformal and intensity modulated radiotherapy to reduce dose to organs at risk (OAR) by geometric avoidance. In volumetric modulated arc radiotherapy (VMAT) non-coplanar geometries are generally achieved by applying patient couch rotations to single or multiple full or partial arcs. This paper presents a trajectory optimization method for a non-coplanar technique, dynamic couch rotation during VMAT (DCR-VMAT), which combines ray tracing with a graph search algorithm. Four clinical test cases (partial breast, brain, prostate only, and prostate and pelvic nodes) were used to evaluate the potential OAR sparing for trajectory-optimized DCR-VMAT plans, compared with standard coplanar VMAT. In each case, ray tracing was performed and a cost map reflecting the number of OAR voxels intersected for each potential source position was generated. The least-cost path through the cost map, corresponding to an optimal DCR-VMAT trajectory, was determined using Dijkstra’s algorithm. Results show that trajectory optimization can reduce dose to specified OARs for plans otherwise comparable to conventional coplanar VMAT techniques. For the partial breast case, the mean heart dose was reduced by 53%. In the brain case, the maximum lens doses were reduced by 61% (left) and 77% (right) and the globes by 37% (left) and 40% (right). Bowel mean dose was reduced by 15% in the prostate only case. For the prostate and pelvic nodes case, the bowel V50 Gy and V60 Gy were reduced by 9% and 45% respectively. Future work will involve further development of the algorithm and assessment of its performance over a larger number of cases in site-specific cohorts.

MUC1, MUC2, MUC4, MUC5AC and MUC6 expression in the progression of prostate cancer.

PubMed

Cozzi, Paul J; Wang, Jian; Delprado, Warick; Perkins, Alan C; Allen, Barry J; Russell, Pamela J; Li, Yong

2005-01-01

Molecular changes are vital for the development of prognostic markers and therapeutic modalities of prostate cancer (CaP). There is growing interest in mucins as treatment targets in human malignancies, including CaP. The role of their expression in the progression of CaP is however unclear. We examined the expressions MUC1, MUC2, MUC4, MUC5AC and MUC6 in CaP tissues using tissue microarrays (TMAs) to look for tumor-associated antigens (TAAs) for targeted therapy. In this study, 120 paraffin-embedded specimens were selected from patients who underwent radical retro-pubic prostatectomy (RRP) or trans-urethral-resection of the prostate (TURP) for primary, untreated CaP and 10 matched lymph node metastases. A series of MUC monoclonal antibodies (mAbs) was used on TMAs by standard immunohistochemistry. Our results indicate that the over-expression of MUC1 was detected in 58% of primary CaP tissues and 90% of lymph node metastases but not in normal prostate or benign tissues, while the expression of MUC2, MUC4, MUC5AC and MUC6 was found to be negative in both normal and cancer tissues. Of the MUC1 positive tumors 86% were Gleason grade 7 or higher. Over-expression of MUC1 was found in late stage CaP while MUC2, 4, 5AC and 6 were negative in CaP. MUC1 is a TAA that is highly related to tumor progression in CaP patients. This antigen is ideal for targeted therapy to control micrometastases and hormone refractory disease but additional studies are necessary to assess its usefulness in patient biopsies and CaP bone metastases before clinical trial.

68Ga-PSMA-11 PET/CT Mapping of Prostate Cancer Biochemical Recurrence After Radical Prostatectomy in 270 Patients with a PSA Level of Less Than 1.0 ng/mL: Impact on Salvage Radiotherapy Planning.

PubMed

Calais, Jeremie; Czernin, Johannes; Cao, Minsong; Kishan, Amar U; Hegde, John V; Shaverdian, Narek; Sandler, Kiri; Chu, Fang-I; King, Chris R; Steinberg, Michael L; Rauscher, Isabel; Schmidt-Hegemann, Nina-Sophie; Poeppel, Thorsten; Hetkamp, Philipp; Ceci, Francesco; Herrmann, Ken; Fendler, Wolfgang P; Eiber, Matthias; Nickols, Nicholas G

2018-02-01

Target volume delineations for prostate cancer (PCa) salvage radiotherapy (SRT) after radical prostatectomy are usually drawn in the absence of visibly recurrent disease. 68 Ga-labeled prostate-specific membrane antigen (PSMA-11) PET/CT detects recurrent PCa with sensitivity superior to standard-of-care imaging at serum prostate-specific antigen (PSA) values low enough to affect target volume delineations for routine SRT. Our objective was to map the recurrence pattern of PCa early biochemical recurrence (BCR) after radical prostatectomy with 68 Ga-PSMA-11 PET/CT in patients with serum PSA levels of less than 1 ng/mL, determine how often consensus clinical target volumes (CTVs) based on the Radiation Therapy Oncology Group (RTOG) guidelines cover 68 Ga-PSMA-11 PET/CT-defined disease, and assess the potential impact of 68 Ga-PSMA-11 PET/CT on SRT. Methods: This was a post hoc analysis of an intention-to-treat population of 270 patients who underwent 68 Ga-PSMA-11 PET/CT at 4 institutions for BCR after prostatectomy without prior radiotherapy at a PSA level of less than 1 ng/mL. RTOG consensus CTVs that included both the prostate bed and the pelvic lymph nodes were contoured on the CT dataset of the PET/CT image by a radiation oncologist masked to the PET component. 68 Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68 Ga-PSMA-11-positive lesions not covered by planning volumes based on the consensus CTVs were considered to have a potential major impact on treatment planning. Results: The median PSA level at the time of 68 Ga-PSMA-11 PET/CT was 0.48 ng/mL (range, 0.03-1 ng/mL). One hundred thirty-two of 270 patients (49%) had a positive 68 Ga-PSMA-11 PET/CT result. Fifty-two of 270 (19%) had at least one PSMA-11-positive lesion not covered by the consensus CTVs. Thirty-three of 270 (12%) had extrapelvic PSMA-11-positive lesions, and 19 of 270 (7%) had PSMA-11-positive lesions within the pelvis but not covered by the consensus CTVs. The 2 most common 68 Ga-PSMA-11-positive lesion locations outside the consensus CTVs were bone (23/52, 44%) and perirectal lymph nodes (16/52, 31%). Conclusion: Post hoc analysis of 68 Ga-PSMA-11 PET/CT implied a major impact on SRT planning in 52 of 270 patients (19%) with PCa early BCR (PSA < 1.0 ng/mL). This finding justifies a randomized imaging trial of SRT with or without 68 Ga-PSMA-11 PET/CT investigating its potential benefit on clinical outcome. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Prostate Cancer Cell–Stromal Cell Cross-Talk via FGFR1 Mediates Antitumor Activity of Dovitinib in Bone Metastases

PubMed Central

Wan, Xinhai; Corn, Paul G.; Yang, Jun; Palanisamy, Nallasivam; Starbuck, Michael W.; Efstathiou, Eleni; Li-Ning Tapia, Elsa M.; Zurita, Amado J.; Aparicio, Ana; Ravoori, Murali K.; Vazquez, Elba S.; Robinson, Dan R.; Wu, Yi-Mi; Cao, Xuhong; Iyer, Matthew K.; McKeehan, Wallace; Kundra, Vikas; Wang, Fen; Troncoso, Patricia; Chinnaiyan, Arul M.; Logothetis, Christopher J.; Navone, Nora M.

2015-01-01

Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell–bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors. PMID:25186177

Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases.

PubMed

Wan, Xinhai; Corn, Paul G; Yang, Jun; Palanisamy, Nallasivam; Starbuck, Michael W; Efstathiou, Eleni; Li Ning Tapia, Elsa M; Tapia, Elsa M Li-Ning; Zurita, Amado J; Aparicio, Ana; Ravoori, Murali K; Vazquez, Elba S; Robinson, Dan R; Wu, Yi-Mi; Cao, Xuhong; Iyer, Matthew K; McKeehan, Wallace; Kundra, Vikas; Wang, Fen; Troncoso, Patricia; Chinnaiyan, Arul M; Logothetis, Christopher J; Navone, Nora M

2014-09-03

Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell-bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in serum prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors. Copyright © 2014, American Association for the Advancement of Science.

Prostate-specific Membrane Antigen PET: Clinical Utility in Prostate Cancer, Normal Patterns, Pearls, and Pitfalls.

PubMed

Hofman, Michael S; Hicks, Rodney J; Maurer, Tobias; Eiber, Matthias

2018-01-01

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in prostate cancer. Radiolabeled small molecules that bind with high affinity to its active extracellular center have emerged as a potential new diagnostic standard of reference for prostate cancer, resulting in images with extraordinary tumor-to-background contrast. Currently, gallium 68 ( 68 Ga)-PSMA-11 (or HBED-PSMA) is the most widely used radiotracer for PSMA positron emission tomography (PET)/computed tomography (CT) or PSMA PET/magnetic resonance (MR) imaging. Evolving evidence demonstrates superior sensitivity and specificity of PSMA PET compared to conventional imaging, with frequent identification of subcentimeter prostate cancer lesions. PSMA PET is effective for imaging disease in the prostate, lymph nodes, soft tissue, and bone in a "one-stop-shop" examination. There is emerging evidence for its clinical value in staging of high-risk primary prostate cancer and localization of disease in biochemical recurrence. The high sensitivity provided by PSMA PET, with frequent identification of small-volume disease, is redefining patterns of disease spread compared with those seen at conventional imaging. In metastatic castration-resistant prostate cancer, PSMA PET is frequently used for theranostic selection (eg, lutetium 177-PSMA radionuclide therapy), but its potential use for therapy monitoring is still under debate. However, evidence on its proper use to improve patient-related outcomes, particularly in the setting of early biochemical recurrence and targeted treatment of oligometastatic disease, is still missing. Despite the term prostate specific, PSMA functions as a folate hydrolase and is expressed in a range of normal tissues and in other benign and malignant processes. Knowledge of its physiologic distribution and other causes of uptake is essential to minimize false-positive imaging findings. © RSNA, 2018.

Lymph node yield during radical prostatectomy does not impact rate of biochemical recurrence in patients with seminal vesicle invasion and node-negative disease.

PubMed

Badani, Ketan K; Reddy, Balaji N; Moskowitz, Eric J; Paulucci, David J; Beksac, Alp Tuna; Martini, Alberto; Whalen, Michael J; Skarecky, Douglas W; Huynh, Linda My; Ahlering, Thomas E

2018-06-01

Seminal vesicle invasion (SVI) is a risk factor for poor oncologic outcome in patients with prostate cancer. Modifications to the pelvic lymph node dissection (PLND) during radical prostatectomy (RP) have been reported to have a therapeutic benefit. The present study is the first to determine if lymph node yield (LNY) is associated with a lower risk of biochemical recurrence (BCR) for men with SVI. A total of 220 patients from 2 high-volume institutions who underwent RP without adjuvant treatment between 1990 and 2015 and had prostate cancer with SVI (i.e., pT3b) were identified, and 21 patients did not undergo lymph node dissection. BCR was defined as a postoperative PSA>0.2ng/mL, or use of salvage androgen deprivation therapy (ADT) or radiation. Multivariable Cox proportional hazards models were used to determine whether LNY was predictive of BCR, controlling for PSA, pathologic Gleason Score, pathologic lymph node status, NCCN risk category, etc. The Kaplan-Meier method was used to determine 3-year freedom from BCR. Median number of lymph nodes sampled were 7 (IQR: 3-12; range: 0-35) and 90.5% underwent PLND. The estimated 3-year BCR rate was 43.9%. Results from multivariable analysis demonstrated that LNY was not significantly associated with risk of BCR overall (HR = 1.00, 95% CI: 0.98-1.03; P = 0.848) for pN0 (HR = 0.99, 95% CI: 0.97-1.03; P = 0.916) or pN1 patients (HR = 0.96, 95% CI: 0.88-1.06; P = 0.468). Overall, PSA (HR = 1.02, P<0.001) and biopsy Gleason sum ≥ 8 (HR = 1.81, P = 0.001) were associated with an increased risk of BCR, and increasing LNY increased the likelihood of detecting>2 positive lymph nodes (OR = 1.27, 95% CI: 1.06-1.65, P = 0.023). Seminal vesicle invasion is associated with an increased risk of BCR at 3 years, primarily due to pathologic Gleason score and PSA. Although greater lymph node yield is diagnostic and facilitates more accurate pathologic staging, our data do not show a therapeutic benefit in reducing BCR. Copyright © 2018 Elsevier Inc. All rights reserved.

Relationship between intraprostatic tracer deposits and sentinel lymph node mapping in prostate cancer patients.

PubMed

Buckle, Tessa; Brouwer, Oscar R; Valdés Olmos, Renato A; van der Poel, Henk G; van Leeuwen, Fijs W B

2012-07-01

Intraprostatic injection of the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid enables both preoperative sentinel node (SN) identification and intraoperative visualization of the SN. Relating the fluorescence deposits in embedded prostate tissue specimens to the preoperatively detected SNs also provides the opportunity to study the influence of their placement on lymphatic drainage pattern. Nineteen patients with prostate carcinoma scheduled for robot-assisted laparoscopic prostatectomy and lymph node (LN) dissection were included. ICG-(99m)Tc-nanocolloid was injected intraprostatically, guided by ultrasound. SN biopsy was performed using a combination of radioguidance and fluorescence guidance. Tracer distribution was visualized in paraffin-embedded prostate samples using ex vivo fluorescence imaging. This distribution was correlated to the number and location of the SNs identified on preoperative lymphoscintigraphy and SPECT/CT. ICG-(99m)Tc-nanocolloid helped guide surgical excision of the SNs. Ex vivo fluorescence imaging revealed a large variation in the locations of intraprostatic tracer deposits among patients. Tracer deposits in the peripheral zone correlated with a higher number of visualized LNs than deposits in the central zone (on average, 4.7 vs. 2.4 LNs per patient). Furthermore, tracer deposits in the mid gland correlated with a higher number of visualized LNs than deposits near the base or apex of the prostate (on average, 6 vs. 3.5 LNs per patient). The hybrid nature of the tracer not only enables surgical guidance but also provides an opportunity to study the correlation between the location of tracer deposits within the prostate and the number and location of preoperatively visualized SNs. These data suggest that the location at which a tracer deposit is placed influences the lymphatic drainage pattern.

The combination of 13N-ammonia and 18F-FDG whole-body PET/CT on the same day for diagnosis of advanced prostate cancer

PubMed Central

Yi, Chang; Yu, Donglan; Shi, Xinchong; Luo, Ganhua; He, Qiao; Zhang, Xuezhen

2016-01-01

Purpose The aim of the study was to evaluate the efficacy of 13N-ammonia and 18F-fluorodeoxyglucose (18F-FDG) PET performed on the same day in the detection of advanced prostate cancer (PC) and its metastases. Patients and methods Twenty-six patients with high-risk PC [Gleason score 8–10 or prostate-specific antigen (PSA)>20 ng/ml or clinical tumor extension≥T2c] were recruited into the study. 13N-Ammonia and 18F-FDG PET/CT were performed on the same day (18F-FDG followed ammonia, with an interval of a minimum of 2 h). Lesions were interpreted as positive, negative, or equivocal. Patient-based and field-based performance characteristics for both imaging techniques were reported. Results There was significant correlation between 13N-ammonia and 18F-FDG PET/CT in the detection of primary PC (κ=0.425, P=0.001) and no significant difference in sensitivity (60.2 vs. 54.5%) and specificity (100 vs. 83.3%). The maximum standard uptake values and corresponding target-to-background ratio values of the concordantly positive lesions in prostate glands in the two studies did not differ significantly (P=0.124 and 0.075, respectively). The sensitivity and specificity of PET imaging using 13N-ammonia for lymph node metastases were 77.5 and 96.3%, respectively, whereas the values were 75 and 44.4% using 18F-FDG. The two modalities were highly correlated with respect to the detection of lymph nodes and bone metastases. Conclusion The concordance between the two imaging modalities suggests a clinical impact of 13N-ammonia PET/CT in advanced PC patients as well as of 18F-FDG. 13N-Ammonia is a useful PET tracer and a complement to 18F-FDG for detecting primary focus and distant metastases in PC. The combination of these two tracers on the same day can accurately detect advanced PC. PMID:26588068

Isolated Hepatic Metastasis from Prostate Carcinoma.

PubMed

Wang, Stephani C; McCarthy, Lezah P; Mehdi, Syed

2017-01-01

Worldwide, prostate cancer is considered the second most common cancer in men. Most common sites for metastatic disease are lymph nodes and bones. However, isolated liver metastasis from prostate cancer is rare. We present a 75 year-old male with prostate adenocarcinoma diagnosed 7 years ago. With rising PSA, he underwent imaging and found to have isolated hepatic metastasis. After left hepatic lobectomy, his PSA dramatically decreased to < 0.01. Physicians should be aware of isolated hepatic metastasis in patients with prostate cancer. Metastasectomy should be considered in such case, and combined medical and surgical approach may prolong the overall survival.

PET Using a GRPR Antagonist 68Ga-RM26 in Healthy Volunteers and Prostate Cancer Patients.

PubMed

Zhang, Jingjing; Niu, Gang; Fan, Xinrong; Lang, Lixin; Hou, Guozhu; Chen, Libo; Wu, Huanwen; Zhu, Zhaohui; Li, Fang; Chen, Xiaoyuan

2018-06-01

This study was designed to analyze the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR) antagonist PET tracer, 68 Ga-RM26; to assess its clinical diagnostic value in prostate cancer patients; and to perform a direct comparison between GRPR antagonist 68 Ga-RM26 and agonist 68 Ga-BBN. Methods: Five healthy volunteers were enrolled to validate the safety of 68 Ga-RM26 and calculate dosimetry. A total of 28 patients with prostate cancer (17 newly diagnosed and 11 posttherapy) were recruited and provided written informed consent. All the cancer patients underwent PET/CT at 15-30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of 68 Ga-RM26. Among them, 22 patients (11 newly diagnosed and 11 posttherapy) underwent 68 Ga-BBN PET/CT for comparison within 1 wk. 99m Tc-MDP (methylene diphosphonate) bone scans were obtained within 2 wk for comparison. GRPR immunohistochemical staining of tumor samples was performed. Results: The administration of 68 Ga-M26 was well tolerated by all subjects, with no adverse symptoms being noticed or reported during the procedure and at 2-wk follow-up. The total effective dose equivalent and effective dose were 0.0912 ± 0.0140 and 0.0657 ± 0.0124 mSv/MBq, respectively. In the 17 patients with newly diagnosed prostate cancer, 68 Ga-RM26 PET/CT showed positive prostate-confined findings in 15 tumors with an SUV max of 6.49 ± 2.37. In the 11 patients who underwent prostatectomy or brachytherapy with or without androgen deprivation therapy, 68 Ga-RM26 PET/CT detected 8 metastatic lymph nodes in 3 patients with an SUV max of 4.28 ± 1.25 and 21 bone lesions in 8 patients with an SUV max of 3.90 ± 3.07. Compared with 68 Ga-RM26 PET/CT, GRPR agonist 68 Ga-BBN PET/CT detected fewer primary lesions and lymph node metastases as well as demonstrated lower tracer accumulation. There was a significant positive correlation between SUV derived from 68 Ga-RM26 PET and the expression level of GRPR ( P < 0.001). Conclusion: This study indicates the safety and significant efficiency of GRPR antagonist 68 Ga-RM26. 68 Ga-RM26 PET/CT would have remarkable value in detecting both primary prostate cancer and metastasis. 68 Ga-RM26 is also expected to be better than GRPR agonist as an imaging marker to evaluate GRPR expression in prostate cancer. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Linking γ-aminobutyric acid A receptor to epidermal growth factor receptor pathways activation in human prostate cancer.

PubMed

Wu, Weijuan; Yang, Qing; Fung, Kar-Ming; Humphreys, Mitchell R; Brame, Lacy S; Cao, Amy; Fang, Yu-Ting; Shih, Pin-Tsen; Kropp, Bradley P; Lin, Hsueh-Kung

2014-03-05

Neuroendocrine (NE) differentiation has been attributed to the progression of castration-resistant prostate cancer (CRPC). Growth factor pathways including the epidermal growth factor receptor (EGFR) signaling have been implicated in the development of NE features and progression to a castration-resistant phenotype. However, upstream molecules that regulate the growth factor pathway remain largely unknown. Using androgen-insensitive bone metastasis PC-3 cells and androgen-sensitive lymph node metastasis LNCaP cells derived from human prostate cancer (PCa) patients, we demonstrated that γ-aminobutyric acid A receptor (GABA(A)R) ligand (GABA) and agonist (isoguvacine) stimulate cell proliferation, enhance EGF family members expression, and activate EGFR and a downstream signaling molecule, Src, in both PC-3 and LNCaP cells. Inclusion of a GABA(A)R antagonist, picrotoxin, or an EGFR tyrosine kinase inhibitor, Gefitinib (ZD1839 or Iressa), blocked isoguvacine and GABA-stimulated cell growth, trans-phospohorylation of EGFR, and tyrosyl phosphorylation of Src in both PCa cell lines. Spatial distributions of GABAAR α₁ and phosphorylated Src (Tyr416) were studied in human prostate tissues by immunohistochemistry. In contrast to extremely low or absence of GABA(A)R α₁-positive immunoreactivity in normal prostate epithelium, elevated GABA(A)R α₁ immunoreactivity was detected in prostate carcinomatous glands. Similarly, immunoreactivity of phospho-Src (Tyr416) was specifically localized and limited to the nucleoli of all invasive prostate carcinoma cells, but negative in normal tissues. Strong GABAAR α₁ immunoreactivity was spatially adjacent to the neoplastic glands where strong phospho-Src (Tyr416)-positive immunoreactivity was demonstrated, but not in adjacent to normal glands. These results suggest that the GABA signaling is linked to the EGFR pathway and may work through autocrine or paracine mechanism to promote CRPC progression. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Differential expression of VEGF ligands and receptors in prostate cancer.

PubMed

Woollard, David J; Opeskin, Kenneth; Coso, Sanja; Wu, Di; Baldwin, Megan E; Williams, Elizabeth D

2013-05-01

Prostate cancer disseminates to regional lymph nodes, however the molecular mechanisms responsible for lymph node metastasis are poorly understood. The vascular endothelial growth factor (VEGF) ligand and receptor family have been implicated in the growth and spread of prostate cancer via activation of the blood vasculature and lymphatic systems. The purpose of this study was to comprehensively examine the expression pattern of VEGF ligands and receptors in the glandular epithelium, stroma, lymphatic vasculature and blood vessels in prostate cancer. The localization of VEGF-A, VEGF-C, VEGF-D, VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 was examined in cancerous and adjacent benign prostate tissue from 52 subjects representing various grades of prostate cancer. Except for VEGFR-2, extensive staining was observed for all ligands and receptors in the prostate specimens. In epithelial cells, VEGF-A and VEGFR-1 expression was higher in tumor tissue compared to benign tissue. VEGF-D and VEGFR-3 expression was significantly higher in benign tissue compared to tumor in the stroma and the endothelium of lymphatic and blood vessels. In addition, the frequency of lymphatic vessels, but not blood vessels, was lower in tumor tissue compared with benign tissue. These results suggest that activation of VEGFR-1 by VEGF-A within the carcinoma, and activation of lymphatic endothelial cell VEGFR-3 by VEGF-D within the adjacent benign stroma may be important signaling mechanisms involved in the progression and subsequent metastatic spread of prostate cancer. Thus inhibition of these pathways may contribute to therapeutic strategies for the management of prostate cancer. Copyright © 2012 Wiley Periodicals, Inc.

[Concomitant oncopathological changes in the prostate of urinary bladder cancer patients undergoing radical cystoprostateectomy].

PubMed

Komyakov, B K; Sergeev, A V; Fadeev, V A; Ismailov, K I; Ulyanov, A Yu; Shmelev, A Yu; Onoshko, M V

2017-09-01

To determine the incidence of spreading bladder transitional cell carcinoma and primary adenocarcinoma to the prostate in patients with bladder cancer undergoing radical cystectomy. From 1995 to 2016, 283 men underwent radical cystectomy with removal of the bladder, perivesical tissue, prostate, seminal vesicles and pelvic lymph nodes. Prostate sparing cystectomy was performed in 45 (13.7%) patients. The whole prostate and the apex of the prostate were preserved in 21 (6.4%) and 24 (7.3%) patients, respectively. The spread of transitional cell cancer of the bladder to the prostate occurred in 50 (15.2%) patients. Twelve (3.6%) patients were found to have primary prostate adenocarcinoma. Clinically significant prostate cancer was diagnosed in 4 (33.3%) patients. We believe that the high oncological risk of prostate sparing cystectomy, despite some functional advantages, dictates the need for complete removal of the prostate in the surgical treatment of bladder cancer.

Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using (11)C-choline PET/CT.

PubMed

García, J R; Cozar, M; Soler, M; Bassa, P; Riera, E; Ferrer, J

2016-01-01

To assess the prognostic value of the therapeutic response by (11)C-choline PET/CT in prostate cancer patients with biochemical recurrence in which (11)C-choline PET/CT indicated radio-guided radiotherapy. The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. (11)C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and (11)C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. (11)C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by (11)C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and (11)C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). (11)C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by (11)C-choline PET/CT has prognostic significance. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Staging of pelvic lymph nodes in patients with prostate cancer: Usefulness of multiple b value SE-EPI diffusion-weighted imaging on a 3.0 T MR system.

PubMed

Vallini, Valentina; Ortori, Simona; Boraschi, Piero; Manassero, Francesca; Gabelloni, Michela; Faggioni, Lorenzo; Selli, Cesare; Bartolozzi, Carlo

2016-01-01

To evaluate the usefulness of diffusion-weighted imaging (DWI) with a multiple b value SE-EPI sequence on a 3.0 T MR scanner for staging of pelvic lymph nodes in patients with prostate cancer candidate to radical prostatectomy and extended pelvic lymph node dissection (PLND). Institutional review board approval was obtained and written informed consent was taken from all enrolled subjects. A series of 26 patients with pathologically proven prostate cancer (high or intermediate risk according to D'Amico risk groups) scheduled for radical prostatectomy and PLND underwent 3 T MRI before surgery. DWI was performed using an axial respiratory-triggered spin-echo echo-planar sequence with multiple b values (500, 800, 1000, 1500 s/mm(2)) in all diffusion directions. ADC values were calculated by means of dedicated software fitting the curve obtained from the corresponding ADC for each b value. Fitted ADC measurements were performed at the level of proximal and distal external iliac, internal iliac, and obturator nodal stations bilaterally. Lymph node appearance was also assessed in terms of short axis, long-to-short axis ratio, node contour and intranodal heterogeneity of signal intensity. A total of 173 lymph nodes and 104 nodal stations were evaluated on DWI and pathologically analysed. Mean fitted ADC values were 0.79 ± 0.14 × 10(-3) mm(2)/s for metastatic lymph nodes and 1.13 ± 0.29 × 10(-3) mm(2)/s in non-metastatic ones (P < 0.0001). The cut-off for fitted ADC obtained by ROC curve analysis was 0.91 × 10(-3) mm(2)/s. A two-point-level score was assigned for each qualitative parameter, and the mean grading score was 6.09 ± 0.61 for metastastic lymph nodes and 5.42 ± 0.79 for non-metastatic ones, respectively (P = 0.001). Using a score threshold of 4 for morphological, structural, and dimensional MRI analysis and a cut--off value of 0.91 × 10(-3) mm(2)/s for fitted ADC measurements of pelvic lymph nodes, per--station sensitivity, specificity, PPV, NPV and diagnostic accuracy were 100%, 7.9%, 15.6%, 100% and 21.3%, and 84.6%, 89.5%, 57.9%, 97.1% and 88.8%, respectively. 3.0T DWI with a multiple b value SE-EPI sequence may help distinguish benign from malignant pelvic lymph nodes in patients with prostate cancer.

Synchronous prostate and rectal adenocarcinomas irradiation utilising volumetric modulated arc therapy.

PubMed

Ng, Sweet Ping; Tran, Thu; Moloney, Philip; Sale, Charlotte; Mathlum, Maitham; Ong, Grace; Lynch, Rod

2015-12-01

Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high-dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was delivered to the prostate only, using VMAT. Treatment-related toxicities and follow-up prostate-specific antigen and carcinoembryonic antigen were collected for data analysis. At 12 months, the patient achieved complete response for both rectal and prostate cancers without significant treatment-related toxicities.

A first-in-man study of 68Ga-nanocolloid PET-CT sentinel lymph node imaging in prostate cancer demonstrates aberrant lymphatic drainage pathways.

PubMed

Doughton, Jacki A; Hofman, Michael S; Eu, Peter; Hicks, Rodney J; Williams, Scott G

2018-05-04

Purpose: To assess feasibility, safety and utility of a novel 68 Ga-nanocolloid radio-tracer with PET-CT lymphoscintigraphy for identification of sentinel lymph nodes (SLN). Methods: Pilot study of patients from a tertiary cancer hospital who required insertion of gold fiducials for prostate cancer radiation therapy. Participation did not affect cancer management. Ultrasound-guided transperineal intra-prostatic injection of PET tracer (iron oxide nanocolloid labelled with gallium-68) after placement of fiducials. PET-CT lymphoscintigraphy imaging at approximately 45 and 100 minutes after in-jection of tracer. The study was monitored using Bayesian trial design with the as-sumption that at least one sentinel lymph node (SLN) could be identified in at least two-thirds of cases with >80% confidence. Results: SLN identification was successful in all 5 participants, allowing completion of the pilot study as per protocol. No adverse effects were observed. Unexpected po-tential pathways for transit of malignant cells as well as expected regional drainage pathways were discovered. Rapid tracer drainage to pelvic bone, perivesical, mesorec-tal, inguinal and Virchow's nodes was identified. Conclusion: SLN identification using 68 Ga-nanocolloid PET-CT can be successfully performed. Non-traditional pathways of disease spread were identified including drainage to pelvic bone as well as perivesical, mesorectal, inguinal and Virchow's nodes. Prevalence of both aberrant and non-lymphatic pathways of spread should be further investigated with this technique. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Could 68-Ga PSMA PET/CT become a new tool in the decision-making strategy of prostate cancer patients with biochemical recurrence of PSA after radical prostatectomy? A preliminary, monocentric series.

PubMed

De Bari, Berardino; Mazzola, Rosario; Aiello, Dario; Fersino, Sergio; Gregucci, Fabiana; Alongi, Pierpaolo; Nicodemo, Maurizio; Cavalleri, Stefano; Salgarello, Matteo; Alongi, Filippo

2018-04-23

To evaluate the impact of gallium68 PSMA-11 (HBED-CC)-PET/CT on decision-making strategy of patients with relapsing prostate cancer (PC) presenting a second biochemical relapse after radical prostatectomy (RP) and salvage RT or salvage androgen deprivation therapy (ADT). 40 patients were retrospectively analyzed. All of them had received prostatectomy. Thirteen out of 40 were addressed to gallium68 PSMA-11 (HBED-CC)-PET/CT for a biochemical relapse after RP, 14/40 after a salvage RT and 13/40 after salvage or adjuvant ADT. The PSA level ranged between 0.1 and 1.62 ng/ml (median value: 0.51 ng/ml). We studied the impact on the decision-making process of a multidisciplinary tumor board of additional data obtained from gallium68 PSMA-11 (HBED-CC)-PET/CT. Thirty-one out of 40 evaluated patients showed positive findings at gallium68 PSMA-11 (HBED-CC)-PET/CT (77.5%). Of them, five were positive in the prostatic bed, nine in the pelvic nodes, twelve in nodes outside the pelvis and eight at bone level. Nine patients presented two different sites of relapse (22.5%). Gallium68 PSMA-11 (HBED-CC)-PET/CT data changed the therapeutic approach in 28 patients (70%). Gallium68 PSMA-11 (HBED-CC)-PET/CT can be a useful tool in the restaging of post-RP, RT or ADT patients presenting biochemical relapse of PC and it could change the decision-making process in up of 70% of these patients. Prospective, larger series are needed to establish the correct role of this very promising tool in the staging and therapeutic approach of PC patients.

68Ga-PSMA PET/CT in patients with recurrent prostate cancer after radical treatment: prospective results in 314 patients.

PubMed

Caroli, Paola; Sandler, Israel; Matteucci, Federica; De Giorgi, Ugo; Uccelli, Licia; Celli, Monica; Foca, Flavia; Barone, Domenico; Romeo, Antonino; Sarnelli, Anna; Paganelli, Giovanni

2018-06-19

We studied the usefulness of 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT for detecting relapse in a prospective series of patients with biochemical recurrence (BCR) of prostate cancer (PCa) after radical treatment. Patients with BCR of PCa after radical surgery and/or radiotherapy with or without androgen-deprivation therapy were included in the study. 68 Ga-PSMA PET/CT scans performed from the top of the head to the mid-thigh 60 min after intravenous injection of 150 ± 50 MBq of 68 Ga-PSMA were interpreted by two nuclear medicine physicians. The results were correlated with prostate-specific antigen (PSA) levels at the time of the scan (PSApet), PSA doubling time, Gleason score, tumour stage, postsurgery tumour residue, time from primary therapy to BCR, and patient age. When available, 68 Ga-PSMA PET/CT scans were compared with negative 18 F-choline PET/CT scans routinely performed up to 1 month previously. From November 2015 to October 2017, 314 PCa patients with BCR were evaluated. Their median age was 70 years (range 44-92 years) and their median PSApet was 0.83 ng/ml (range 0.003-80.0 ng/ml). 68 Ga-PSMA PET/CT was positive (one or more suspected PCa lesions detected) in 197 patients (62.7%). Lesions limited to the pelvis, i.e. the prostate/prostate bed and/or pelvic lymph nodes (LNs), were detected in 117 patients (59.4%). At least one distant lesion (LNs, bone, other organs, separately or combined with local lesions) was detected in 80 patients (40.6%). PSApet was higher in PET-positive than in PET-negative patients (P < 0.0001). Of 88 patients negative on choline PET/CT scans, 59 (67%) were positive on 68 Ga-PSMA PET/CT. We confirmed the value of 68 Ga-PSMA PET/CT in restaging PCa patients with BCR, highlighting its superior performance and safety compared with choline PET/CT. Higher PSApet was associated with a higher relapse detection rate.

Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging.

PubMed

Demirci, Emre; Sahin, Onur Erdem; Ocak, Meltem; Akovali, Burak; Nematyazar, Jamal; Kabasakal, Levent

2016-11-01

Ga-PSMA-11 is a novel PET tracer suggested to be used for imaging of advanced prostate cancer. In this study, we aimed to present a detailed biodistribution of Ga-PSMA-11, including physiological and benign variants of prostate-specific membrane antigen (PSMA) imaging. We carried out a retrospective analysis of 40 patients who underwent PSMA PET/computed tomography (CT) imaging and who had no evidence of residual or metastatic disease on the scans. In addition, 16 patients who underwent PSMA PET/CT imaging with any indication other than prostate cancer were included in the study to evaluate physiological uptake in the normal prostate gland. The median, minimum-maximum, and mean standardized uptake value (SUV) values were calculated for visceral organs, bone marrow and lymph nodes, and mucosal areas. Any physiological variants or benign lesions with Ga-PSMA-11 were also noted. Ga-PSMA-11 uptake was noted in the kidneys, parotid and submandibular glands, duodenum, small intestines, spleen, liver, and lacrimal glands, and mucosal uptake in the nasopharynx, vocal cords, pancreas, stomach, mediastinal blood pool, thyroid gland, adrenal gland, rectum, vertebral bone marrow, and testes. Celiac ganglia showed slight Ga-PSMA-11 uptake in 24 of 40 patients without the presence of any other pathologic lymph nodes in abdominal and pelvic areas. Variable uptake of Ga-PSMA-11 was observed in calcified choroid plexus, a thyroid nodule, an adrenal nodule, axillary lymph nodes and celiac ganglia, occasional osteophytes, and gallbladder. The patient group with PSMA PET/CT for indications other than prostate cancer (n=16) showed a slight radiotracer uptake in normal prostate gland (SUVmax: 5.5±1.6, range: 3.5-8.3). This study shows normal distribution pattern, range of SUVs, and physiological variants of Ga-PSMA-11. In addition, several potential pitfalls were documented to prevent misinterpretations of the scan.

Association between surgeon and hospital characteristics and lymph node counts from radical prostatectomy and pelvic lymph node dissection.

PubMed

Wang, Elyn H; Yu, James B; Gross, Cary P; Abouassaly, Robert; Cherullo, Edward E; Smaldone, Marc C; Shah, Nilay D; Kiechle, Jonathon; Trinh, Quoc-Dien; Sun, Maxine; Kim, Simon P

2015-04-01

To assess whether surgical approach and hospital characteristics independently determine the number of lymph nodes (LNs) removed from prostate cancer patients undergoing radical prostatectomy (RP) and pelvic LN dissection (PLND). Using the National Cancer Database, we identified all surgically treated patients diagnosed with pretreatment intermediate- or high-risk prostate cancer from 2010 to 2011. The primary outcome was the number of LNs retrieved at the time of RP. Generalized estimating equations were used to assess for differences in the adjusted number of LNs retrieved after accounting for patient and hospital characteristics and surgical approach. Overall, 35,876 patients were diagnosed with intermediate-risk (61.2%) and high-risk (38.8%) prostate cancer and underwent RP and PLND.On multivariate analysis, open RP and high-volume and academic hospitals were independently associated with greater LN counts compared with robotic-assisted RP and medium or low and community hospitals, respectively (all P <.001). After adjusting for patient and hospital variables, higher adjusted LN counts were observed for open RP compared with robotic-assisted RP (7.1 vs 6.1; P <.001). Adjusted counts were also higher for high-volume hospitals compared with medium- or low-volume hospitals (7.8 vs 5.9; P <.001), and academic compared with community hospitals (7.3 vs 5.6; P <.001). Among patients with aggressive prostate cancer treated with RP and PLND, retrieval of LN counts varied by surgical approach and hospital characteristics. Copyright © 2015 Elsevier Inc. All rights reserved.

Favorable outcome of intraoperative radiotherapy to the primary site in patients with metastatic prostate cancer.

PubMed

Kanda, Toshihiro; Fukuda, Syohei; Fukui, Naotaka; Ohkubo, Yu; Kazumoto, Tomoko; Saito, Yoshihiro; Ishikawa, Ayataka; Kurosumi, Masafumi; Kageyama, Yukio; Fujii, Yasuhisa; Kihara, Kazunori

2016-08-01

The aim of this study was to determine whether local radiotherapy to the prostate by intraoperative radiotherapy (IORT) increases the overall and cancer-specific survival rates of patients with metastatic prostate cancer. Between 1993 and 2000, 102 patients with prostate cancer were treated with a combination of (a) IORT of the prostate (25 or 30 Gy per fraction); (b) external beam radiotherapy of the prostate (30 Gy in 10 fractions), starting approximately 1 week post-operatively; and (c) endocrine treatment. Of these, 16 patients had stage D1 disease (D1 IORT group), 32 had stage D2 disease without visceral metastasis (D2 IORT group), and 38 had stage D2 disease without visceral metastasis and did not receive local therapy (D2 control group). Overall and cancer-specific survival rates were compared. The 5- and 10-year cancer-specific survival rates were 75.9 and 52.7 %, respectively, in the (D1 + D2) IORT group and 45.8 and 33.5 %, respectively, in the D2 control group, with cancer-specific survival being significantly longer in the D2 IORT than in the D2 control group (P = 0.030). Univariate and multivariate reduced-rank regression analyses showed that extent of skeletal disease Grade 4 and non-regional lymph node metastasis were significantly prognostic of poorer cancer-specific survival (P < 0.001 each). Local radiotherapy to the prostate by IORT in patients with metastatic prostate cancer may contribute to better survival, especially in patients without extent of skeletal disease Grade 4 or non-regional lymph node metastasis.

Diagnostic sensitivity of Tc-99m HYNIC PSMA SPECT/CT in prostate carcinoma: A comparative analysis with Ga-68 PSMA PET/CT.

PubMed

Lawal, Ismaheel O; Ankrah, Alfred O; Mokgoro, Neo P; Vorster, Mariza; Maes, Alex; Sathekge, Mike M

2017-08-01

Emerging data from published studies are demonstrating the superiority of Ga-68 PSMA PET/CT imaging in prostate cancer. However, the low yield of the Ge-68/Ga-68 from which Gallium-68 is obtained and fewer installed PET/CT systems compared to the SPECT imaging systems may limit its availability. We, therefore, evaluated in a head-to-head comparison, the diagnostic sensitivity of Ga-68 PSMA PET/CT and Tc-99m PSMA SPECT/CT in patients with prostate cancer. A total of 14 patients with histologically confirmed prostate cancer were prospectively recruited to undergo Ga-68 PSMA PET/CT and Tc-99m HYNIC PSMA SPECT/CT. The mean age of patients was 67.21 ± 8.15 years and the median PSA level was 45.18 ng/mL (range = 1.51-687 ng/mL). SUVmax of all lesions and the size of lymph nodes with PSMA avidity on Ga-68 PSMA PET/CT were determined. Proportions of these lesions detected on Tc-99m HYNIC PSMA SPECT/CT read independent of PET/CT findings were determined. A total of 46 lesions were seen on Ga-68 PSMA PET/CT localized to the prostate (n = 10), lymph nodes (n = 24), and bones (n = 12). Of these, Tc-99m HYNIC PSMA SPECT/CT detected 36 lesions: Prostate = 10/10 (100%), lymph nodes = 15/24 (62.5%), and bones = 11/12 (91.7%) with an overall sensitivity of 78.3%. Lesions detected on Tc-99m HYNIC PSMA SPECT/CT were bigger in size (P < 0.001) and had higher SUVmax (P < 0.001) as measured on Ga-68 PSMA PET/CT compared to those lesions that were not detected. All lymph nodes greater than 10 mm in size were detected while only 28% of nodes less than 10 mm were detected by Tc-99m HYNIC PSMA SPECT/CT. In a univariate analysis, Lymph node size (P = 0.033) and the SUVmax of all lesions (P = 0.007) were significant predictors of lesion detection on Tc-99m HYNIC PSMA SPECT/CT. Tc-99m HYNIC PSMA may be a useful in imaging of prostate cancer although with a lower sensitivity for lesion detection compared to Ga-68 PSMA PET/CT. Its use is recommended when Ga-68 PSMA is not readily available, in planning radio-guided surgery or the patient is being considered for radio-ligand therapy with Lu-177 PSMA. It performs poorly in detecting small-sized lesions hence its use is not recommended in patients with small volume disease. © 2017 Wiley Periodicals, Inc.

Phase I-II Study of Intraoperative Radiation Therapy (IORT) After Radical Prostatectomy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saracino, Biancamaria; Gallucci, Michele; De Carli, Piero

2008-07-15

Purpose: Recent studies have suggested an {alpha}/{beta} ratio in prostate cancer of 1.5-3 Gy, which is lower than that assumed for late-responsive normal tissues. Therefore the administration of a single, intraoperative dose of irradiation should represent a convenient irradiation modality in prostate cancer. Materials and Methods: Between February 2002 and June 2004, 34 patients with localized prostate cancer with only one risk factor (Gleason score {>=}7, Clinical Stage [cT] {>=}2c, or prostate-specific antigen [PSA] of 11-20 ng/mL) and without clinical evidence of lymph node metastases were treated with radical prostatectomy (RP) and intraoperative radiotherapy on the tumor bed. A dose-findingmore » procedure based on the Fibonacci method was employed. Dose levels of 16, 18, and 20 Gy were selected, which are biologically equivalent to total doses of about 60-80 Gy administered with conventional fractionation, using an {alpha}/{beta} ratio value of 3. Results: At a median follow-up of 41 months, 24 (71%) patients were alive with an undetectable PSA value. No patients died from disease, whereas 2 patients died from other malignancies. Locoregional failures were detected in 3 (9%) patients, 2 in the prostate bed and 1 in the common iliac node chain outside the radiation field. A PSA rise without local or distant disease was observed in 7 (21%) cases. The overall 3-year biochemical progression-free survival rate was 77.3%. Conclusions: Our dose-finding study demonstrated the feasibility of intraoperative radiotherapy in prostate cancer also at the highest administered dose.« less

Toxicity and efficacy of salvage carbon 11-choline positron emission tomography/computed tomography-guided radiation therapy in patients with lymph node recurrence of prostate cancer.

PubMed

Fodor, Andrei; Berardi, Genoveffa; Fiorino, Claudio; Picchio, Maria; Busnardo, Elena; Kirienko, Margarita; Incerti, Elena; Dell'Oca, Italo; Cozzarini, Cesare; Mangili, Paola; Pasetti, Marcella; Calandrino, Riccardo; Gianolli, Luigi; Di Muzio, Nadia G

2017-03-01

To report the 3-year toxicity and outcomes of carbon 11 (11C)-choline-positron emission tomography (PET)/computed tomography (CT)-guided radiotherapy (RT), delivered via helical tomotherapy (HTT; Tomotherapy ® Hi-Art II ® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node (LN) relapses in patients with prostate cancer. From January 2005 to March 2013, 81 patients with biochemical recurrence after surgery, with or without adjuvant/salvage RT or radical RT, and with evidence of LN 11C-choline-PET/CT pathological uptake, underwent HTT (median [range] prostate-specific antigen level 2.59 [0.61-187] ng/mL). Of the 81 patients, 72 were treated at the pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C-choline-PET/CT. Nine patients were treated without simultaneous integrated boost (50-65.5 Gy, 25-30 fr). With a median (range) follow-up of 36 (9-116) months, 91.4% of the patients had a PSA reduction 3 months after HTT. The 3-year overall, local relapse-free and clinical relapse-free survival rates were 80.0, 89.8 and 61.8%, respectively. The 3-year actuarial incidences of ≥grade 2 rectal and ≥grade 2 genitourinary toxicity were 6.6% (±2.9%) and 26.3% (±5.5%), respectively. A PSA nadir of ≥0.26 ng/mL (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7-7.7; P = 0.001), extrapelvic 11C-choline-PET/CT-positive LN location (HR 2.4, 95% CI 0.9-6.4; P = 0.07), RT previous to HTT (HR 2.7; 95% CI 1.07-6.9, P = 0.04) and number of positive LNs (HR 1.13, 95% CI 1.04-1.22; P = 0.003) were the main predictors of clinical relapse after HTT. 11C-choline-PET/CT-guided HTT is safe and effective in the treatment of LN relapses of prostate cancer in previously treated patients. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Feasibility of minimally invasive radical prostatectomy in prostate cancer patients with high prostate-specific antigen: feasibility and 1-year outcomes.

PubMed

Do, Minh; Ragavan, Narasimhan; Dietel, Anja; Liatsikos, Evangelos; Anderson, Chris; McNeill, Alan; Stolzenburg, Jens-Uwe

2012-10-01

Urologists are cautious to offer minimally invasive radical prostatectomy in prostate cancer patients with high prostate-specific antigen (and therefore anticipated to have locally advanced or metastatic disease) because of concerns regarding lack of complete cure after minimally invasive radical prostatectomy and of worsening of continence if adjuvant radiotherapy is used. A retrospective review of our institutional database was carried out to identify patients with PSA ≥20 ng/mL who underwent minimally invasive radical prostatectomy between January 2002 and October 2010. Intraoperative, pathological, functional and short-term oncological outcomes were assessed. Overall, 233 patients met study criteria and were included in the analysis. The median prostate-specific antigen and prostate size were 28.5 ng/mL and 47 mL, respectively. Intraoperative complications were the following: rectal injury (0.86%) and blood transfusion (1.7%). Early postoperative complications included prolonged (>6 days) catheterization (9.4%), hematoma (4.7%), deep venous thrombosis (0.86%) and lymphocele (5.1%). Late postoperative complications included cerebrovascular accident (0.4%) and anastomotic stricture (0.8%). Pathology revealed poorly differentiated cancer in 48.9%, pT3/pT4 disease in 55.8%, positive margins in 28.3% and lymph node disease in 20.2% of the cases. Adverse pathological findings were more frequent in patients with prostate-specific antigen >40 ng/mL and (or) in those with locally advanced disease (pT3/pT4). In 62.2% of the cases, adjuvant radiotherapy was used. At 1-year follow up, 80% of patients did not show evidence of biochemical recurrence and 98.8% of them had good recovery of continence. Minimally invasive radical prostatectomy might represent a reasonable option in prostate cancer patients with high prostate-specific antigen as a part of a multimodality treatment approach. © 2012 The Japanese Urological Association.

Strong expression of the neuronal transcription factor FOXP2 is linked to an increased risk of early PSA recurrence in ERG fusion-negative cancers.

PubMed

Stumm, Laura; Burkhardt, Lia; Steurer, Stefan; Simon, Ronald; Adam, Meike; Becker, Andreas; Sauter, Guido; Minner, Sarah; Schlomm, Thorsten; Sirma, Hüseyin; Michl, Uwe

2013-07-01

Transcription factors of the forkhead box P (FOXP1-4) family have been implicated in various human cancer types before. The relevance and role of neuronal transcription factor FOXP2 in prostate cancer is unknown. A tissue microarray containing samples from more than 11 000 prostate cancers from radical prostatectomy specimens with clinical follow-up data was analysed for FOXP2 expression by immunohistochemistry. FOXP2 data were also compared with pre-existing ERG fusion (by fluorescence in situ hybridisation and immunohistochemistry) and cell proliferation (Ki67 labelling index) data. There was a moderate to strong FOXP2 protein expression in basal and secretory cells of normal prostatic glands. As compared with normal cells, FOXP2 expression was lost or reduced in 25% of cancers. Strong FOXP2 expression was linked to advanced tumour stage, high Gleason score, presence of lymph node metastases and early tumour recurrence (p<0.0001; each) in ERG fusion-negative, but not in ERG fusion-positive cancers. High FOXP2 expression was linked to high Ki67 labelling index (p<0.0001) in all cancers irrespective of ERG fusion status. These data demonstrate that similar high FOXP2 protein levels as in normal prostate epithelium exert a 'paradoxical' oncogenic role in 'non fusion-type' prostate cancer. It may be speculated that interaction of FOXP2 with members of pathways that are specifically activated in 'non fusion-type' cancers may be responsible for this phenomenon.

Clinical evaluation of multi-atlas based segmentation of lymph node regions in head and neck and prostate cancer patients.

PubMed

Sjöberg, Carl; Lundmark, Martin; Granberg, Christoffer; Johansson, Silvia; Ahnesjö, Anders; Montelius, Anders

2013-10-03

Semi-automated segmentation using deformable registration of selected atlas cases consisting of expert segmented patient images has been proposed to facilitate the delineation of lymph node regions for three-dimensional conformal and intensity-modulated radiotherapy planning of head and neck and prostate tumours. Our aim is to investigate if fusion of multiple atlases will lead to clinical workload reductions and more accurate segmentation proposals compared to the use of a single atlas segmentation, due to a more complete representation of the anatomical variations. Atlases for lymph node regions were constructed using 11 head and neck patients and 15 prostate patients based on published recommendations for segmentations. A commercial registration software (Velocity AI) was used to create individual segmentations through deformable registration. Ten head and neck patients, and ten prostate patients, all different from the atlas patients, were randomly chosen for the study from retrospective data. Each patient was first delineated three times, (a) manually by a radiation oncologist, (b) automatically using a single atlas segmentation proposal from a chosen atlas and (c) automatically by fusing the atlas proposals from all cases in the database using the probabilistic weighting fusion algorithm. In a subsequent step a radiation oncologist corrected the segmentation proposals achieved from step (b) and (c) without using the result from method (a) as reference. The time spent for editing the segmentations was recorded separately for each method and for each individual structure. Finally, the Dice Similarity Coefficient and the volume of the structures were used to evaluate the similarity between the structures delineated with the different methods. For the single atlas method, the time reduction compared to manual segmentation was 29% and 23% for head and neck and pelvis lymph nodes, respectively, while editing the fused atlas proposal resulted in time reductions of 49% and 34%. The average volume of the fused atlas proposals was only 74% of the manual segmentation for the head and neck cases and 82% for the prostate cases due to a blurring effect from the fusion process. After editing of the proposals the resulting volume differences were no longer statistically significant, although a slight influence by the proposals could be noticed since the average edited volume was still slightly smaller than the manual segmentation, 9% and 5%, respectively. Segmentation based on fusion of multiple atlases reduces the time needed for delineation of lymph node regions compared to the use of a single atlas segmentation. Even though the time saving is large, the quality of the segmentation is maintained compared to manual segmentation.

PET imaging in adaptive radiotherapy of prostate tumors.

PubMed

Beuthien-Baumann, Bettina; Koerber, Stefan A

2018-06-04

The integration of data from positron-emission-tomography, combined with computed tomography as PET/CT or combined with magnet resonance imaging as PET/MRI, into radiation treatment planning of prostate cancer is gaining higher impact with the development of more sensitive and specific radioligands. The classic PET-tracer for prostate cancer imaging are [11C]choline and [11C]acetate, which are currently outperformed by ligands binding to the prostate-specific- membrane-antigen (PSMA). [68Ga]PSMA-11, which is the most frequently applied tracer, has shown to detect lymph node metastases, local recurrences, distant metastases and intraprostatic foci with high sensitivity, even at relatively low PSA levels. The results from PET-imaging may influence radiotherapeutic (RT) management at different stages of the disease i.e. during primary staging or biochemical recurrence, when the detection of distant metastases may alter the curative treatment concept into a palliative approach. On the other hand, the clinical target volume could be adapted by visualizing lymph node metastases at locations, which might not have been suspicious on morphologic imaging alone. The treatment plan might contain a boost to the dominant intraprostatic lesion, which could be delineated by a combination of PET-tracer uptake and multiparametric MRI. Therefore, PSMA-PET imaging is well suited for being integrated into prostate radiation planning. However, further prospective trials evaluating the impact on oncological outcome are indicated.

Comparative analysis of the effect of prostatic invasion patterns on cancer-specific mortality after radical cystectomy in pT4a urothelial carcinoma of the bladder.

PubMed

Vallo, Stefan; Gilfrich, Christian; Burger, Maximilian; Volkmer, Björn; Boehm, Katharina; Rink, Michael; Chun, Felix K; Roghmann, Florian; Novotny, Vladimir; Mani, Jens; Brisuda, Antonin; Mayr, Roman; Stredele, Regina; Noldus, Joachim; Schnabel, Marco; May, Matthias; Fritsche, Hans-Martin; Pycha, Armin; Martini, Thomas; Wirth, Manfred; Roigas, Jan; Bastian, Patrick J; Nuhn, Philipp; Dahlem, Roland; Haferkamp, Axel; Fisch, Margit; Aziz, Atiqullah

2016-10-01

To evaluate the prognostic relevance of different prostatic invasion patterns in pT4a urothelial carcinoma of the bladder (UCB) after radical cystectomy. Our study comprised a total of 358 men with pT4a UCB. Patients were divided in 2 groups-group A with stromal infiltration of the prostate via the prostatic urethra with additional muscle-invasive UCB (n = 121, 33.8%) and group B with continuous infiltration of the prostate through the entire bladder wall (n = 237, 66.2%). The effect of age, tumor grade, carcinoma in situ, lymphovascular invasion, soft tissue surgical margin, lymph node metastases, administration of adjuvant chemotherapy, and prostatic invasion patterns on cancer-specific mortality (CSM) was evaluated using competing-risk regression analysis. Decision curve analysis was used to evaluate the net benefit of including the variable invasion pattern within our model. The estimated 5-year CSM-rates for group A and B were 50.1% and 66.0%, respectively. In multivariable competing-risk analysis, lymph node metastases (hazard ratio [HR] = 1.73, P<0.001), lymphovascular invasion (HR = 1.62, P = 0.0023), soft tissue surgical margin (HR = 1.49, P = 0.026), absence of adjuvant chemotherapy (HR = 2.11, P<0.001), and tumor infiltration of the prostate by continuous infiltration of the entire bladder wall (HR = 1.37, P = 0.044) were significantly associated with a higher risk for CSM. Decision curve analysis showed a net benefit of our model including the variable invasion pattern. Continuous infiltration of the prostate through the entire bladder wall showed an adverse effect on CSM. Besides including these patients into clinical trials for an adjuvant therapy, we recommend including prostatic invasion patterns in predictive models in pT4a UCB in men. Copyright © 2016 Elsevier Inc. All rights reserved.

SU-G-BRA-17: Tracking Multiple Targets with Independent Motion in Real-Time Using a Multi-Leaf Collimator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ge, Y; Keall, P; Poulsen, P

Purpose: Multiple targets with large intrafraction independent motion are often involved in advanced prostate, lung, abdominal, and head and neck cancer radiotherapy. Current standard of care treats these with the originally planned fields, jeopardizing the treatment outcomes. A real-time multi-leaf collimator (MLC) tracking method has been developed to address this problem for the first time. This study evaluates the geometric uncertainty of the multi-target tracking method. Methods: Four treatment scenarios are simulated based on a prostate IMAT plan to treat a moving prostate target and static pelvic node target: 1) real-time multi-target MLC tracking; 2) real-time prostate-only MLC tracking; 3)more » correcting for prostate interfraction motion at setup only; and 4) no motion correction. The geometric uncertainty of the treatment is assessed by the sum of the erroneously underexposed target area and overexposed healthy tissue areas for each individual target. Two patient-measured prostate trajectories of average 2 and 5 mm motion magnitude are used for simulations. Results: Real-time multi-target tracking accumulates the least uncertainty overall. As expected, it covers the static nodes similarly well as no motion correction treatment and covers the moving prostate similarly well as the real-time prostate-only tracking. Multi-target tracking reduces >90% of uncertainty for the static nodal target compared to the real-time prostate-only tracking or interfraction motion correction. For prostate target, depending on the motion trajectory which affects the uncertainty due to leaf-fitting, multi-target tracking may or may not perform better than correcting for interfraction prostate motion by shifting patient at setup, but it reduces ∼50% of uncertainty compared to no motion correction. Conclusion: The developed real-time multi-target MLC tracking can adapt for the independently moving targets better than other available treatment adaptations. This will enable PTV margin reduction to minimize health tissue toxicity while remain tumor coverage when treating advanced disease with independently moving targets involved. The authors acknowledge funding support from the Australian NHMRC Australia Fellowship and NHMRC Project Grant No. APP1042375.« less

Effect of MLC leaf width on treatment adaptation and accuracy for concurrent irradiation of prostate and pelvic lymph nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shang Qingyang; Qi Peng; Ferjani, Samah

2013-06-15

Purpose: The aim of the study was to evaluate the impact of multileaf collimator (MLC) leaf width on treatment adaptation and delivery accuracy for concurrent treatment of the prostate and pelvic lymph nodes with intensity modulated radiation therapy (IMRT). Methods: Seventy-five kilovoltage cone beam CTs (KV-CBCT) from six patients were included for this retrospective study. For each patient, three different IMRT plans were created based on a planning CT using three different MLC leaf widths of 2.5, 5, and 10 mm, respectively. For each CBCT, the prostate displacement was determined by a dual image registration. Adaptive plans were created bymore » shifting selected MLC leaf pairs to compensate for daily prostate movements. To evaluate the impact of MLC leaf width on the adaptive plan for each daily CBCT, three MLC shifted plans were created using three different leaf widths of MLCs (a total of 225 adaptive treatment plans). Selective dosimetric endpoints for the tumor volumes and organs at risk (OARs) were evaluated for these adaptive plans. Using the planning CT from a selected patient, MLC shifted plans for three hypothetical longitudinal shifts of 2, 4, and 8 mm were delivered on the three linear accelerators to test the deliverability of the shifted plans and to compare the dose accuracy of the shifted plans with the original IMRT plans. Results: Adaptive plans from 2.5 and 5 mm MLCs had inadequate dose coverage to the prostate (D99 < 97%, or D{sub mean} < 99% of the planned dose) in 6%-8% of the fractions, while adaptive plans from 10 mm MLC led to inadequate dose coverage to the prostate in 25.3% of the fractions. The average V{sub 56Gy} of the prostate over the six patients was improved by 6.4% (1.6%-32.7%) and 5.8% (1.5%-35.7%) with adaptive plans from 2.5 and 5 mm MLCs, respectively, when compared with adaptive plans from 10 mm MLC. Pelvic lymph nodes were well covered for all MLC adaptive plans, as small differences were observed for D99, D{sub mean}, and V{sub 50.4Gy}. Similar OAR sparing could be achieved for the bladder and rectum with all three MLCs for treatment adaptation. The MLC shifted plans can be accurately delivered on all three linear accelerators with accuracy similar to their original IMRT plans, where gamma (3%/3 mm) passing rates were 99.6%, 93.0%, and 92.1% for 2.5, 5, and 10 mm MLCs, respectively. The percentages of pixels with dose differences between the measurement and calculation being less than 3% of the maximum dose were 85.9%, 82.5%, and 70.5% for the original IMRT plans from the three MLCs, respectively. Conclusions: Dosimetric advantages associated with smaller MLC leaves were observed in terms of the coverage to the prostate, when the treatment was adapted to account for daily prostate movement for concurrent irradiation of the prostate and pelvic lymph nodes. The benefit of switching the MLC from 10 to 5 mm was significant (p Much-Less-Than 0.01); however, switching the MLC from 5 to 2.5 mm would not gain significant (p= 0.15) improvement. IMRT plans with smaller MLC leaf widths achieved more accurate dose delivery.« less

F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients.

PubMed

Giesel, Frederik L; Hadaschik, B; Cardinale, J; Radtke, J; Vinsensia, M; Lehnert, W; Kesch, C; Tolstov, Y; Singer, S; Grabe, N; Duensing, S; Schäfer, M; Neels, O C; Mier, W; Haberkorn, U; Kopka, K; Kratochwil, C

2017-04-01

The prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer 68 Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, 68 Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of 18 F-labelled analogs. 18 F-PSMA-1007 was selected among several 18 F-PSMA-ligand candidate compounds because it demonstrated high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. Here, we describe the properties of 18 F-PSMA-1007 in human volunteers and patients. Radiation dosimetry of 18 F-PSMA-1007 was determined in three healthy volunteers who underwent whole-body PET-scans and concomitant blood and urine sampling. Following this, ten patients with high-risk prostate cancer underwent 18 F-PSMA-1007 PET/CT (1 h and 3 h p.i.) and normal organ biodistribution and tumor uptakes were examined. Eight patients underwent prostatectomy with extended pelvic lymphadenectomy. Uptake in intra-prostatic lesions and lymph node metastases were correlated with final histopathology, including PSMA immunostaining. With an effective dose of approximately 4.4-5.5 mSv per 200-250 MBq examination, 18 F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other 18 F-labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, 18 F-PSMA-1007 has reduced urinary clearance enabling excellent assessment of the prostate. Similar to 18 F-DCFPyL and with slightly slower clearance kinetics than PSMA-11, favorable tumor-to-background ratios are observed 2-3 h after injection. In eight patients, diagnostic findings were successfully validated by histopathology. 18 F-PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter. 18 F-PSMA-1007 performs at least comparably to 68 Ga-PSMA-11, but its longer half-life combined with its superior energy characteristics and non-urinary excretion overcomes some practical limitations of 68 Ga-labelled PSMA-targeted tracers.

Preclinical Evaluation of 18F-PSMA-1007, a New Prostate-Specific Membrane Antigen Ligand for Prostate Cancer Imaging.

PubMed

Cardinale, Jens; Schäfer, Martin; Benešová, Martina; Bauder-Wüst, Ulrike; Leotta, Karin; Eder, Matthias; Neels, Oliver C; Haberkorn, Uwe; Giesel, Frederik L; Kopka, Klaus

2017-03-01

In recent years, several radiotracers targeting the prostate-specific membrane antigen (PSMA) have been introduced. Some of them have had a high clinical impact on the treatment of patients with prostate cancer. However, the number of 18 F-labeled tracers addressing PSMA is still limited. Therefore, we aimed to develop a radiofluorinated molecule resembling the structure of therapeutic PSMA-617. Methods: The nonradioactive reference compound PSMA-1007 and the precursor were produced by solid-phase chemistry. The radioligand 18 F-PSMA-1007 was produced by a 2-step procedure with the prosthetic group 6- 18 F-fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester. The binding affinity of the ligand for PSMA and its internalization properties were evaluated in vitro with PSMA-positive LNCaP (lymph node carcinoma of the prostate) cells. Further, organ distribution studies were performed with mice bearing LNCaP and PC-3 (prostate cancer cell line; PSMA-negative) tumors. Finally, small-animal PET imaging of an LNCaP tumor-bearing mouse was performed. Results: The identified ligand had a binding affinity of 6.7 ± 1.7 nM for PSMA and an exceptionally high internalization ratio (67% ± 13%) in vitro. In organ distribution studies, high and specific tumor uptake (8.0 ± 2.4 percentage injected dose per gram) in LNCaP tumor-bearing mice was observed. In the small-animal PET experiments, LNCaP tumors were clearly visualized. Conclusion: The radiofluorinated PSMA ligand showed promising characteristics in its preclinical evaluation, and the feasibility of prostate cancer imaging was demonstrated by small-animal PET studies. Therefore, we recommend clinical transfer of the radioligand 18 F-PSMA-1007 for use as a diagnostic PET tracer in prestaging and monitoring of prostate cancer. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

11C-Choline-Pet Guided Stereotactic Body Radiation Therapy for Lymph Node Metastases in Oligometastatic Prostate Cancer.

PubMed

Franzese, Ciro; Lopci, Egesta; Di Brina, Lucia; D'Agostino, Giuseppe Roberto; Navarria, Pierina; Mancosu, Pietro; Tomatis, Stefano; Chiti, Arturo; Scorsetti, Marta

2017-10-21

aim is outcome of 11C-Choline-PET guided SBRT on lymph node metastases. patients with 1 - 4 lymph node metastases detected by 11C-choline-PET were treated with SBRT. Toxicity, treated metastases control and Progression Free Survival were computed. twenty-six patients, 38 lymph node metastases were irradiated. No grade ≥ 2 toxicity. Median PSA-nadir after RT was 1.02 ng/mL. Post-treatment 11C-Choline-PET showed metabolic complete response in 17 metastases (44,7%), partial response in 9 metastases (38%). SBRT is effective and safe for lymph node metastases. PET is important in identification of gross tumor and evaluation of the response.

Salvage radiotherapy after postprostatectomy biochemical failure: does pretreatment radioimmunoscintigraphy help select patients with locally confined disease?

PubMed

Liauw, Stanley L; Weichselbaum, Ralph R; Zagaja, Gregory P; Jani, Ashesh B

2008-08-01

Radioimmunoscintigraphy (RIS) has the potential to demonstrate early recurrences after prostatectomy and might be useful in selecting patients for salvage radiotherapy (RT). A total of 82 patients with adenocarcinoma of the prostate were treated with salvage RT between 1988 and 2005, for an elevated prostate-specific antigen (PSA) level after prostatectomy. Of the 82 patients, 32% had Gleason score 6 or less disease, 54% Gleason score 7 disease, 70% had Stage pT3 disease, 55% had positive margins, and 5% had pathologic lymph node involvement. The median pre-RT PSA level was 0.63 ng/mL. Of the 82 patients, 47 (57%) had a pre-RT RIS (ProstaScint) scan, which was used for both patient selection and target delineation. The RT regimen was a median dose of 66 Gy to the prostate bed. Also, 64% received androgen deprivation therapy. Biochemical failure was defined as a PSA level >0.1 ng/mL and increasing. Patients with a pre-RT RIS scan had a lower preoperative PSA level (p = 0.0240) and shorter follow-up (p = 0.0221) than those without RIS. With a median follow-up of 44 months, the biochemical control rate was 56% at 3 years and 48% at 5 years. Margin status was the only factor associated with biochemical control on univariate (p = 0.0055) and multivariate (p = 0.0044) analysis. Patients who had prostate bed-only uptake on RIS (n = 38) did not have improved outcomes, with biochemical control rates of 51% at 3 years and 40% at 5 years. Patients treated with salvage RT had modest responses. Patients who were selected for treatment with RIS did not have better biochemical outcomes. Our results indicated that patients with positive margins were most likely to benefit from salvage RT.

Contemporary Population-Based Comparison of Localized Ductal Adenocarcinoma and High-Risk Acinar Adenocarcinoma of the Prostate.

PubMed

Packiam, Vignesh T; Patel, Sanjay G; Pariser, Joseph J; Richards, Kyle A; Weiner, Adam B; Paner, Gladell P; VanderWeele, David J; Zagaja, Gregory P; Eggener, Scott E

2015-10-01

To compare pathological characteristics, treatment patterns, and survival in patients with ductal adenocarcinoma (DC) compared to those with acinar adenocarcinoma (AC). Using the National Cancer Database, we identified patients diagnosed with clinically localized (cN0, cM0) pure DC (n = 1328) and AC (n = 751,635) between 1998 and 2011. High-risk AC was defined as Gleason 8-10. Demographic, treatment, pathological, and survival characteristics of patients were compared. Compared to patients with Gleason 8-10 AC, those with DC presented with lower mean prostate-specific antigen (10.3 vs 16.2 ng/mL, P <.001), had similar rates (11.7% vs 11.5%, P = .8) of clinical extra-capsular extension (stage ≥ cT3), and were more likely to undergo prostatectomy (54% vs 36%, P <.001). Compared to patients with Gleason 8-10 AC undergoing prostatectomy, those with DC had more favorable pathology: stage ≥ T3 (39% vs 52%, P <.001), fewer positive lymph nodes (4% vs 11%, P <.001), and fewer positive margins (25% vs 33%, P <.001). On Kaplan-Meier analysis, patients with DC had similar 5-year survival (75.0%, 95% confidence interval [CI] [71.7-78.9]) compared to those with Gleason 8-10 AC (77.1%, 95% CI [76.6%-77.6%], P = .2). On Cox multivariable analysis, patients with Gleason 8-10 AC had a similar risk of death compared to those with DC (hazards ratio = 0.92, 95% CI [0.69-1.23], P = 6). In this large contemporary population-based series, patients with DC of the prostate presented with lower prostate-specific antigen, had more favorable pathological features, and similar overall survival compared to men with Gleason 8-10 AC. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of 68Ga-PSMA-11 and 18F-Fluciclovine PET/CT in a Case Series of 10 Patients with Prostate Cancer Recurrence.

PubMed

Calais, Jeremie; Fendler, Wolfgang P; Herrmann, Ken; Eiber, Matthias; Ceci, Francesco

2018-05-01

This was a head-to-head comparison between 68 Ga-labeled prostate-specific membrane antigen (PSMA)-11 and 18 F-fluciclovine PET/CT in a series of 10 patients with prostate cancer (PCa) recurrence. Methods: In total, 288 patients with PCa recurrence were enrolled in a prospective study of 68 Ga-PSMA-11 PET/CT imaging for recurrent disease localization (ClinicalTrials.gov identifier NCT02940262). We retrospectively identified 10 patients who underwent clinically indicated 18 F-fluciclovine PET/CT prior to enrollment. Results: The median time between the 2 scans was 2.2 mo (range, 0.2-4.2 mo). The median prostate-specific antigen (PSA) value was 1.0 ng/mL (mean, 4.7 ng/mL; range, 0.13-18.1 ng/mL) and 1.1 ng/mL (mean, 6.2 ng/mL; range, 0.24-31.3 ng/mL) at the time of 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT, respectively. Five of 10 patients (50%) were negative with 18 F-fluciclovine but positive with 68 Ga-PSMA-11 PET/CT. Two of 10 patients (20%) were positive with both 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT, but 68 Ga-PSMA-11 PET/CT showed additional lymph nodes metastasis. Three of 10 patients (30%) were negative with both 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT. Conclusion: This case series suggests improved detection rates for 68 Ga-PSMA-11 PET/CT when compared with 18 F-fluciclovine PET/CT in patients with recurrent PCa. Prospective trials designed to directly compare the two should be initiated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis.

PubMed

Dell'Atti, Lucio

2015-03-31

We retrospectively reviewed data of patients with incidental prostate cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. 11 out of 64 patients (17.2%) who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as significant PCa, while 8 cases (72.7%) were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79). During the follow-up, biochemical recurrence occurred in 1 patient (9%). Concerning the cancer specific survival there was no statistical significance (P = 0.326) between the clinically significant and clinical insignificant cancer group. In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

Pretreatment tables predicting pathologic stage of locally advanced prostate cancer.

PubMed

Joniau, Steven; Spahn, Martin; Briganti, Alberto; Gandaglia, Giorgio; Tombal, Bertrand; Tosco, Lorenzo; Marchioro, Giansilvio; Hsu, Chao-Yu; Walz, Jochen; Kneitz, Burkhard; Bader, Pia; Frohneberg, Detlef; Tizzani, Alessandro; Graefen, Markus; van Cangh, Paul; Karnes, R Jeffrey; Montorsi, Francesco; van Poppel, Hein; Gontero, Paolo

2015-02-01

Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. Retropubic RP and pelvic lymphadenectomy. Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Long-term outcomes of open radical retropubic prostatectomy for clinically localized prostate cancer in the prostate-specific antigen era.

PubMed

Dorin, Ryan P; Daneshmand, Siamak; Lassoff, Mark A; Cai, Jie; Skinner, Donald G; Lieskovsky, Gary

2012-03-01

To determine long-term oncological outcomes and complication rates for patients with clinically organ confined prostate adenocarcinoma (PCa) treated with open radical retropubic prostatectomy and pelvic lymph node dissection (RRP/PLND) in the prostate-specific antigen (PSA) era. Outcomes data were obtained from a prospectively maintained prostate cancer database. Patients with cT1/cT2 PCa undergoing RRP/PLND without neoadjuvant therapy between July 1988 and June 2008 were included. Kaplan-Meier and Cox proportional regression models were used to evaluate factors influencing biochemical recurrence, clinical recurrence, and overall survival (OS). A total of 2487 patients met inclusion criteria, and median follow-up was 7.2 years (range 1-21 years). Of the patients, 49.7% were low risk, 33.2% intermediate risk, and 16.1% high risk by D'Amico criteria, and 6% were LN+. The 10-year biochemical recurrence-free survival (BCRFS) for low-, intermediate-, and high-risk patients was 92%, 83%, and 76%, respectively (P < .001), and 10 year OS was 91%, 83%, and 74%, respectively (P < .001). BCRFS at 10 years was 76% and 88% for patients with positive and negative margins, respectively (P < .001). Of the 2487 patients, 11% developed BCR, and 3.7% experienced CR, with 9 local recurrences. The overall complication rate was 2.3%, and the cancer specific mortality rate was 2%. D'Amico risk group, margin status, and LN status are significantly correlated with outcomes in patients undergoing RRP/PLND for clinically localized PCa. Local recurrence and death from prostate cancer are rare in patients undergoing open RRP/PLND for clinically organ confined disease in the PSA era. Copyright © 2012 Elsevier Inc. All rights reserved.

18F-Fluorocholine PET/CT Complementing the Role of Dynamic Contrast-Enhanced MRI for Providing Comprehensive Diagnostic Workup in Prostate Cancer Patients With Suspected Relapse Following Radical Prostatectomy.

PubMed

Vadi, Shelvin Kumar; Singh, Baljinder; Basher, Rajender K; Watts, Ankit; Sood, Ashwani K; Lal, Anupam; Kakkar, Nandita; Singh, S K

2017-08-01

The aim of this study was to compare the diagnostic performance of F-fluorocholine (FCH) PET/CT and dynamic contrast-enhanced MRI (DCE-MRI) of pelvis in restaging prostate cancer (PC) patients with biochemical recurrence (BCR) following radical prostatectomy (RP). Twenty PC patients who had undergone RP and had BCR were recruited in this study. All the patients underwent whole-body FCH PET/CT and DCE-MRI of the pelvis. An overall pattern of recurrent disease was analyzed, and diagnostic accuracy for the detection of pelvic disease recurrence by the 2 modalities was evaluated by taking histopathologic analysis as the criterion standard. The whole-body FCH PET/CT images were also analyzed separately for the presence of any extra lesion(s). The initial mean Gleason score was 6.3 ± 1.53 (range, 4-9). The mean prostate-specific antigen levels at the time of relapse were 1.9 ± 2.87 ng/mL (range, 0.24-13.2 ng/mL). MRI findings were positive for primary tumor recurrence in the prostate bed in 6 patients (6/20 [30.0%]), pelvic lymph node metastases in 4 patients (4/20 [20.0%]), and for pelvic skeletal metastases in 2 patients (2/20 [10.0%]), respectively. On the other hand, FCH PET/CT results were positive in the corresponding sites in 7 (7/20 [35.0%]), 9 (9/20 [45.0%]), and 2 patients (2/20 [10.0%]), respectively. F-fluorocholine PET/CT and MRI showed comparable results in terms of sensitivity, specificity, and positive and negative predictive values for PC characterization. The whole-body FCH PET/CT was found to be useful in identifying unknown distant metastases in a significant proportion of patients. The correlative whole-body FCH PET/CT and pelvic DCE-MRI offer a complementary and comprehensive diagnostic workup for better management of PC patients with BCR following RP.

Is there still a role for computed tomography and bone scintigraphy in prostate cancer staging? An analysis from the EUREKA-1 database.

PubMed

Gabriele, D; Collura, D; Oderda, M; Stura, I; Fiorito, C; Porpiglia, F; Terrone, C; Zacchero, M; Guiot, C; Gabriele, P

2016-04-01

According to the current guidelines, computed tomography (CT) and bone scintigraphy (BS) are optional in intermediate-risk and recommended in high-risk prostate cancer (PCa). We wonder whether it is time for these examinations to be dismissed, evaluating their staging accuracy in a large cohort of radical prostatectomy (RP) patients. To evaluate the ability of CT to predict lymph node involvement (LNI), we included 1091 patients treated with RP and pelvic lymph node dissection, previously staged with abdomino-pelvic CT. As for bone metastases, we included 1145 PCa patients deemed fit for surgery, previously staged with Tc-99m methylene diphosphonate planar BS. CT scan showed a sensitivity and specificity in predicting LNI of 8.8 and 98 %; subgroup analysis disclosed a significant association only for the high-risk subgroup of 334 patients (P 0.009) with a sensitivity of 11.8 % and positive predictive value (PPV) of 44.4 %. However, logistic multivariate regression analysis including preoperative risk factors excluded any additional predictive ability of CT even in the high-risk group (P 0.40). These data are confirmed by ROC curve analysis, showing a low AUC of 54 % for CT, compared with 69 % for Partin tables and 80 % for Briganti nomogram. BS showed some positivity in 74 cases, only four of whom progressed, while 49 patients with negative BS progressed during their follow-up, six of them immediately after surgery. According to our opinion, the role of CT and BS should be restricted to selected high-risk patients, while clinical predictive nomograms should be adopted for the surgical planning.

The Role of Positron Emission Tomography With (68)Gallium (Ga)-Labeled Prostate-specific Membrane Antigen (PSMA) in the Management of Patients With Organ-confined and Locally Advanced Prostate Cancer Prior to Radical Treatment and After Radical Prostatectomy.

PubMed

Rai, Bhavan Prasad; Baum, Richard Paul; Patel, Amit; Hughes, Robert; Alonzi, Roberto; Lane, Tim; Adshead, Jim; Vasdev, Nikhil

2016-09-01

The role of positron emission tomography (PET) with (68)Gallium (Ga)-labeled prostate-specific membrane antigen (PSMA) imaging for prostate cancer is gaining prominence. Current imaging strategies, despite having progressed significantly, have limitations, in particular their ability to diagnose metastatic lymph node involvement. Preliminary results of PET with (68)Ga-labeled PSMA have shown encouraging results, particularly in the recurrent prostate cancer setting. Furthermore, the ability of PET with (68)Ga-labeled PSMA of playing a dual diagnostic and therapeutic setting (theranostics) is currently being investigated as well. PET with (68)Ga-labeled PSMA certainly has a role to play in bridging some of the voids in contemporary prostate cancer imaging tools. Copyright © 2016 Elsevier Inc. All rights reserved.

Androgen deprivation with or without radiation therapy for clinically node-positive prostate cancer. Lin CC, Gray PJ, Jemal A, Efstathiou JA, Surveillance and Health Services Research Program, Intramural Research, American Cancer Society, Atlanta, GA (CCL, AJ); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (PJG, JAE); e-mail: jefstathiou@partners.org. J Natl Cancer Inst. 2015 May 9;107(7). pii: djv119. [Print 2015 Jul]. doi: 10.1093/jnci/djv119.

PubMed

Scott, Eggener

2017-03-01

Clinically lymph node-positive (cN+) prostate cancer (PCa) is an often-fatal disease. Its optimal management remains largely undefined given a lack of prospective, randomized data to inform practice. We sought to describe modern practice patterns in the management of cN+PCa and assess the effect of adding radiation therapy (RT) to androgen deprivation therapy (ADT) on survival using the National Cancer Data Base. Patients with cN+PCa and without distant metastases diagnosed between 2004 and 2011 were included. Five-year overall survival for patients diagnosed between 2004 and 2006 and treated with ADT alone or ADT+RT were compared. Propensity score (PS) matching was used to balance baseline characteristics, and Cox multivariate regression analysis was used to estimate hazard ratios (HRs) for all-cause mortality. Of 3,540 total patients, 32.2% were treated with ADT alone and 51.4% received ADT+RT. Compared with ADT alone, patients treated with ADT+RT were younger and more likely to have private insurance, lower comorbidity scores, higher Gleason scores, and lower PSA values. After PS matching, 318 patients remained in each group. Compared with ADT alone, ADT+RT was associated with a 50% decreased risk of five-year all-cause mortality (HR = 0.50, 95% CI: 0.37-0.67, two-sided P<0.001; crude OS rate: 71.5% vs. 53.2%). Using a large national database, we have identified a statistically significant survival benefit for patients with cN+PCa treated with ADT+RT. These data, if appropriately validated by randomized trials, suggest that a substantial proportion of such patients at high risk for prostate cancer death may be undertreated, warranting a reevaluation of current practice guidelines. Copyright © 2017. Published by Elsevier Inc.

Alignment focus of daily image guidance for concurrent treatment of prostate and pelvic lymph nodes.

PubMed

Ferjani, Samah; Huang, Guangshun; Shang, Qingyang; Stephans, Kevin L; Zhong, Yahua; Qi, Peng; Tendulkar, Rahul D; Xia, Ping

2013-10-01

To determine the dosimetric impact of daily imaging alignment focus on the prostate soft tissue versus the pelvic bones for the concurrent treatment of the prostate and pelvic lymph nodes (PLN) and to assess whether multileaf collimator (MLC) tracking or adaptive planning (ART) is necessary with the current clinical planning margins of 8 mm/6 mm posterior to the prostate and 5 mm to the PLN. A total of 124 kilovoltage cone-beam computed tomography (kV-CBCT) images from 6 patients were studied. For each KV-CBCT, 4 plans were retrospectively created using an isocenter shifting method with 2 different alignment focuses (prostate, PLN), an MLC shifting method, and the ART method. The selected dosimetric endpoints were compared among these plans. For the isoshift contour, isoshift bone, MLC shift, and ART plans, D99 of the prostate was ≥97% of the prescription dose in 97.6%, 73.4%, 98.4%, and 96.8% of 124 fractions, respectively. Accordingly, D99 of the PLN was ≥97% of the prescription dose in 98.4%, 98.4%, 98.4%, and 100% of 124 fractions, respectively. For the rectum, D5 exceeded 105% of the planned D5 (and D5 of ART plans) in 11% (4%), 10% (2%), and 13% (5%) of 124 fractions, respectively. For the bladder, D5 exceeded 105% of the planned D5 (and D5 of ART) plans in 0% (2%), 0% (2%), and 0% (1%) of 124 fractions, respectively. For concurrent treatment of the prostate and PLN, with a planning margin to the prostate of 8 mm/6 mm posterior and a planning margin of 5 mm to the PLN, aligning to the prostate soft tissue can achieve adequate dose coverage to the both target volumes; aligning to the pelvic bone would result in underdosing to the prostate in one-third of fractions. With these planning margins, MLC tracking and ART methods have no dosimetric advantages. Copyright © 2013 Elsevier Inc. All rights reserved.

CPA-7 influences immune profile and elicits anti-prostate cancer effects by inhibiting activated STAT3.

PubMed

Liang, Meihua; Zhan, Fei; Zhao, Juan; Li, Qi; Wuyang, Jiazi; Mu, Guannan; Li, Dianjun; Zhang, Yanqiao; Huang, Xiaoyi

2016-07-19

Platinum-based chemotherapy is emerging as the first line of treatment for castration resistant prostate cancer. Among the family of platinum (IV)-based compounds, a member known as CPA-7 inhibits the growth of multiple cancer cell lines. However, how and to what extent CPA-7 elicits its anti-prostate cancer effects in vivo is largely unknown. In this study, we firstly assessed the potential toxicity of the synthesized CPA-7 in a prostate cancer model as well as in normal mice. Next, we evaluated the in vitro effects of CPA-7 on the growth of prostate cancer cells using cell counting assay, and calculated the tumor sizes and cumulative survival rate of the tumor bearing mice by Kaplan-Meier method during CPA-7 treatment. Then we measured the expression level of the activated form of STAT3 (one targets of CPA-7) and its transcriptive activity post CPA-7 treatment by synergistically using western blot, IHC, and firefly luciferase reporter assays. Finally, effects of CPA-7 on immune cell trafficking in the tumor draining lymph nodes and in the spleens are evaluated with flow cytometry. Treatment with CPA-7 significantly inhibited growth of prostate cancer cells in vitro, and also in mice resulting in a prolonged survival and a decreased recurrence rate. These therapeutic effects are due, at least in part, to functional depletion of STAT3 in prostate tumor tissue as well as in the surrounding areas of tumor cell invasion. CPA-7 treatment also resulted in a reduced level of regulatory T cells and increased levels of cytotoxic T and T helper cells in the spleen and in tumor infiltrating lymph nodes. This favorable effect on immune cell trafficking may account for the amnestic immune response against recurrent prostate cancer. CPA-7 is a promising new therapeutic agent for prostate cancer that both inhibits tumor cell proliferation and stimulates anti-tumor immunity. It has potential as first line treatment and/or as an adjuvant for refractory prostate cancer.

Potential impact of 68Ga-PSMA-11 PET/CT on prostate cancer definitive radiation therapy planning.

PubMed

Calais, Jérémie; Kishan, Amar U; Cao, Minsong; Fendler, Wolfgang P; Eiber, Matthias; Herrmann, Ken; Ceci, Francesco; Reiter, Robert E; Rettig, Matthew B; Hegde, John V; Shaverdian, Narek; King, Christopher R; Steinberg, Michael L; Czernin, Johannes; Nickols, Nicholas G

2018-04-13

Background: Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) detects PCa metastasis with superior accuracy with potential impact definitive radiation therapy (RT) planning for non-metastatic PCa. Objectives: i) To determine how often definitive PCa RT planning based on standard target volumes cover 68 Ga-PSMA-11 PET/CT defined disease, and ii) To assess the potential impact of 68 Ga-PSMA-11 PET/CT on definitive PCa RT planning. Patients and Methods: This is a post-hoc analysis of an intention to treat population of 73 patients with localized PCa without prior local therapy who underwent 68 Ga-PSMA PET/CT for initial staging as part of an Investigational New Drug trial. 11/73 were intermediate-risk (15%), 33/73 were high-risk (45%), 22/73 were very high risk (30%), and 7/73 were N1 (9.5%). Clinical target volumes (CTVs) that included the prostate, seminal vesicles, and pelvic lymph nodes (LNs) using Radiation Therapy Oncology Group (RTOG) consensus guidelines were contoured on the CT portion of the PET/CT by a radiation oncologist blinded to the PET findings. 68 Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. PSMA-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. Results: All patients had PSMA-positive primary prostate lesion(s). 25/73 (34%) and 7/73 (9.5%) had PSMA-positive pelvic nodal and distant metastases, respectively. The sites of nodal metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper-diaphragm (4%), and presacral (1.5%). The median size of the nodal lesions was 6 mm (range 4-24 mm). RT planning based on the CTVs covered 69/73 (94.5%) of primary disease and 20/25 (80%) of pelvic nodal disease, on a per-patient analysis. Conclusion: 68 Ga-PSMA-11 PET/CT had a major impact on intended definitive PCa RT planning in 12/73 of patients (16.5%) when RT fields covered the prostate, seminal vesicles and the pelvic LNs, and in 25/66 of patients (37%) when RT fields covered only the prostate and seminal vesicles (without pelvic LNs). Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Amino-terminal enhancer of split gene AES encodes a tumor and metastasis suppressor of prostate cancer.

PubMed

Okada, Yoshiyuki; Sonoshita, Masahiro; Kakizaki, Fumihiko; Aoyama, Naoki; Itatani, Yoshiro; Uegaki, Masayuki; Sakamoto, Hiromasa; Kobayashi, Takashi; Inoue, Takahiro; Kamba, Tomomi; Suzuki, Akira; Ogawa, Osamu; Taketo, M Mark

2017-04-01

A major cause of cancer death is its metastasis to the vital organs. Few effective therapies are available for metastatic castration-resistant prostate cancer (PCa), and progressive metastatic lesions such as lymph nodes and bones cause mortality. We recently identified AES as a metastasis suppressor for colon cancer. Here, we have studied the roles of AES in PCa progression. We analyzed the relationship between AES expression and PCa stages of progression by immunohistochemistry of human needle biopsy samples. We then performed overexpression and knockdown of AES in human PCa cell lines LNCaP, DU145 and PC3, and determined the effects on proliferation, invasion and metastasis in culture and in a xenograft model. We also compared the PCa phenotypes of Aes/Pten compound knockout mice with those of Pten simple knockout mice. Expression levels of AES were inversely correlated with clinical stages of human PCa. Exogenous expression of AES suppressed the growth of LNCaP cells, whereas the AES knockdown promoted it. We also found that AES suppressed transcriptional activities of androgen receptor and Notch signaling. Notably, AES overexpression in AR-defective DU145 and PC3 cells reduced invasion and metastasis to lymph nodes and bones without affecting proliferation in culture. Consistently, prostate epithelium-specific inactivation of Aes in Pten flox/flox mice increased expression of Snail and MMP9, and accelerated growth, invasion and lymph node metastasis of the mouse prostate tumor. These results suggest that AES plays an important role in controlling tumor growth and metastasis of PCa by regulating both AR and Notch signaling pathways. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Lack of an Association between Neutrophil-to-Lymphocyte Ratio and PSA Failure of Prostate Cancer Patients Who Underwent Radical Prostatectomy.

PubMed

Maeda, Yoko; Kawahara, Takashi; Koizumi, Mitsuyuki; Ito, Hiroki; Kumano, Yohei; Ohtaka, Mari; Kondo, Takuya; Mochizuki, Taku; Hattori, Yusuke; Teranishi, Jun-Ichi; Yumura, Yasushi; Miyoshi, Yasuhide; Yao, Masahiro; Miyamoto, Hiroshi; Uemura, Hiroji

2016-01-01

Introduction. The neutrophil-to-lymphocyte ratio (NLR), which can be easily calculated from routine complete blood counts of the peripheral blood, has been suggested to serve as a prognostic factor for some solid malignancies. In the present study, we aimed to determine the relationship between NLR in prostate cancer patients undergoing radical prostatectomy (RP) and their prognosis. Materials and Methods. We assessed NLR in 73 men (patients) who received RP for their prostate cancer. We also performed immunohistochemistry for CD8 and CD66b in a separate set of RP specimens. Results. The median NLR in the 73 patients was 1.85. There were no significant correlations of NLR with tumor grade (p = 0.834), pathological T stage (p = 0.082), lymph node metastasis (p = 0.062), or resection margin status (p = 0.772). Based on the area under the receiver operator characteristic curve (AUROC) to predict biochemical recurrence after RP, potential NLR cut-off point was determined to be 2.88 or 3.88. However, both of these cut-off points did not precisely predict the prognosis. There were no statistically significant differences in the number of CD66b-positive neutrophils or CD8-positive lymphocytes between stromal tissues adjacent to cancer glands and stromal tissues away from cancer glands and between different grades or stages of tumors. Conclusions. There was no association between NLR and biochemical failure after prostatectomy.

High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edelman, Scott; Liauw, Stanley L.; Rossi, Peter J.

2012-08-01

Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADTmore » and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.« less

Whole-Pelvis Radiotherapy in Combination With Interstitial Brachytherapy: Does Coverage of the Pelvic Lymph Nodes Improve Treatment Outcome in High-Risk Prostate Cancer?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bittner, Nathan; Merrick, Gregory S., E-mail: gmerrick@UrologicResearchInstitute.or; Wallner, Kent E.

2010-03-15

Purpose: To compare biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) rates among high-risk prostate cancer patients treated with brachytherapy and supplemental external beam radiation (EBRT) using either a mini-pelvis (MP) or a whole-pelvis (WP) field. Methods and Materials: From May 1995 to October 2005, 186 high-risk prostate cancer patients were treated with brachytherapy and EBRT with or without androgen-deprivation therapy (ADT). High-risk prostate cancer was defined as a Gleason score of >=8 and/or a prostate-specific antigen (PSA) concentration of >=20 ng/ml. Results: With a median follow-up of 6.7 years, the 10-year bPFS, CSS, and OS ratesmore » for the WP vs. the MP arms were 91.7% vs. 84.4% (p = 0.126), 95.5% vs. 92.6% (p = 0.515), and 79.5% vs. 67.1% (p = 0.721), respectively. Among those patients who received ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 93.6% vs. 90.1% (p = 0.413), 94.2% vs. 96.0% (p = 0.927), and 73.7% vs. 70.2% (p = 0.030), respectively. Among those patients who did not receive ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 82.4% vs. 75.0% (p = 0.639), 100% vs. 88% (p = 0.198), and 87.5% vs. 58.8% (p = 0.030), respectively. Based on multivariate analysis, none of the evaluated parameters predicted for CSS, while bPFS was best predicted by ADT and percent positive biopsy results. OS was best predicted by age and percent positive biopsy results. Conclusions: For high-risk prostate cancer patients receiving brachytherapy, there is a nonsignificant trend toward improved bPFS, CSS, and OS rates when brachytherapy is given with WPRT. This trend is most apparent among ADT-naive patients, for whom a significant improvement in OS was observed.« less

Immunohistochemical expression of Hsp60 correlates with tumor progression and hormone resistance in prostate cancer.

PubMed

Castilla, Carolina; Congregado, Belén; Conde, José M; Medina, Rafael; Torrubia, Francisco J; Japón, Miguel A; Sáez, Carmen

2010-10-01

To investigate the expression of Hsp60 protein in prostate cancer biopsy samples, and its association with prognostic clinical parameters and hormone resistance and survival. Molecular chaperones are involved in protein folding, protein degradation, and protein trafficking among subcellular compartments. We selected 107 patients with localized and locally advanced prostate cancer at our hospital from 1999 through 2004. We performed an analysis by western blot and immunohistochemistry on paraffin-embedded tissue sections. Clinical data were used to determine associations between immunohistochemical expression of Hsp60 and tumor behavior. The expression level of Hsp60 was significantly increased in tumors with high Gleason score (P < .001). Hsp60 expression was also significantly associated with initial serum PSA levels (P < .01) and with the presence of lymph node metastasis (P < .003). In 50 locally advanced cancers treated by androgen ablation we found an association between high Hsp60-expressing tumors and an early onset of hormone refractory disease (P < .02) and reduced cancer-specific survival (P < .05). Hsp60 protein is overexpressed in poorly differentiated prostate cancers. Hsp60 expression is strongly associated with prognostic clinical parameters, such as Gleason score, initial serum PSA levels, and lymph node metastasis and with the onset of hormone-refractory disease and reduced cancer-specific survival. Identification of such markers could be of relevance in the clinical management of prostate cancer. Copyright © 2010 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bednarz, Natalia; Eltze, Elke; Semjonow, Axel

A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating thosemore » patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs. Small subpopulations of PCa cells bearing BRCA1 losses might be one confounding factor initiating tumor dissemination and might provide an early indicator of shortened disease-free survival.« less

Histological changes associated with neoadjuvant chemotherapy are predictive of nodal metastases in high-risk prostate cancer patients

PubMed Central

O’Brien, Catherine; True, Lawrence D.; Higano, Celestia S.; Rademacher, Brooks L. S.; Garzotto, Mark; Beer, Tomasz M.

2011-01-01

Clinical trials are evaluating the effect of neoadjuvant chemotherapy on men with high risk prostate cancer. Little is known about the clinical significance of post-chemotherapy tumor histopathology. We assessed the prognostic and predictive value of histological features (intraductal carcinoma, vacuolated cell morphology, inconspicuous glands, cribriform architecture, and inconspicuous cancer cells) observed in 50 high-risk prostate cancers treated with pre-prostatectomy docetaxel and mitoxantrone. At a median follow-up of 65 months, the overall relapse-free survival (RFS) at 2 and 5 years was 65% and 49%, respectively. In univariate analyses (using Kaplan-Meier method and log-rank tests) intraductal (p=0.001) and cribriform (p=0.014) histologies were associated with shorter RFS. In multivariate analyses, using Cox’s proportional hazards regression, baseline PSA (p=0.004), lymph node metastases (p<0.001), and cribriform histology (p=0.007) were associated with shorter RFS. In multivariable logistic regression analysis, only intraductal pattern (p=0.007) predicted lymph node metastases. Intraductal and cribriform histologies apparently predict post-chemotherapy outcome. PMID:20231619

A novel canine model for prostate cancer.

PubMed

Keller, Jill M; Schade, George R; Ives, Kimberly; Cheng, Xu; Rosol, Thomas J; Piert, Morand; Siddiqui, Javed; Roberts, William W; Keller, Evan T

2013-06-01

No existing animal model fully recapitulates all features of human prostate cancer. The dog is the only large mammal, besides humans, that commonly develops spontaneous prostate cancer. Canine prostate cancer features many similarities with its human counterpart. We sought to develop a canine model of prostate cancer that would more fully represent the features of human prostate cancer than existing models. The Ace-1 canine prostate cancer cell line was injected transabdominally under transrectal ultrasound (TRUS) guidance into the prostates of immunosuppressed, intact, adult male dogs. Tumor progression was monitored by TRUS imaging. Some dogs were subjected to positron emission tomography (PET) for tumor detection. Time of euthanasia was determined based on tumor size, impingement on urethra, and general well-being. Euthanasia was followed by necropsy and histopathology. Ace-1 tumor cells grew robustly in every dog injected. Tumors grew in subcapsular and parenchymal regions of the prostate. Tumor tissue could be identified using PET. Histological findings were similar to those observed in human prostate cancer. Metastases to lungs and lymph nodes were detected, predominantly in dogs with intraprostatic tumors. We have established a minimally invasive dog model of prostate cancer. This model may be valuable for studying prostate cancer progression and distant metastasis. Copyright © 2013 Wiley Periodicals, Inc.

Reader Training for the Restaging of Biochemically Recurrent Prostate Cancer Using 18F-Fluciclovine PET/CT.

PubMed

Miller, Matthew P; Kostakoglu, Lale; Pryma, Daniel; Yu, Jian Qin; Chau, Albert; Perlman, Eric; Clarke, Bonnie; Rosen, Donald; Ward, Penelope

2017-10-01

18 F-Fluciclovine is a novel PET/CT tracer. This blinded image evaluation (BIE) sought to demonstrate that, after limited training, readers naïve to 18 F-fluciclovine could interpret 18 F-fluciclovine images from subjects with biochemically recurrent prostate cancer with acceptable diagnostic performance and reproducibility. The primary objectives were to establish individual readers' diagnostic performance and the overall interpretation (2/3 reader concordance) compared with standard-of-truth data (histopathology or clinical follow-up) and to evaluate interreader reproducibility. Secondary objectives included comparison to the expert reader and assessment of intrareader reproducibility. Methods: 18 F-Fluciclovine PET/CT images ( n = 121) and corresponding standard-of-truth data were collected from 110 subjects at Emory University using a single-time-point static acquisition starting 5 min after injection of approximately 370 MBq of 18 F-fluciclovine. Three readers were trained using standardized interpretation methodology and subsequently evaluated the images in a blinded manner. Analyses were conducted at the lesion, region (prostate, including bed and seminal vesicle, or extraprostatic, including all lymph nodes, bone, or soft-tissue metastasis), and subject level. Results: Lesion-level overall positive predictive value was 70.5%. The readers' positive predictive value and negative predictive value were broadly consistent with each other and with the onsite read. Sensitivity was highest for readers 1 and 2 (68.5% and 63.9%, respectively) whereas specificity was highest for reader 3 (83.6%). Overall, prostate-level sensitivity was high (91.4%), but specificity was moderate (48.7%). Interreader agreement was 94.7%, 74.4%, and 70.3% for the lesion, prostate, and extraprostatic levels, respectively, with associated Fleiss' κ-values of 0.54, 0.50, and 0.57. Intrareader agreement was 97.8%, 96.9%, and 99.1% at the lesion level; 100%, 100%, and 91.7% in the prostate region; and 83.3%, 75.0%, and 83.3% in the extraprostatic region for readers 1, 2, and 3, respectively. Concordance between the BIE and the onsite reader exceeded 75% for each reader at the lesion, region, and subject levels. Conclusion: Specific training in the use of standardized interpretation methodology for assessment of 18 F-fluciclovine PET/CT images enables naïve readers to achieve acceptable diagnostic performance and reproducibility when staging recurrent prostate cancer. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

PubMed

Walker, Steven M; Knight, Laura A; McCavigan, Andrena M; Logan, Gemma E; Berge, Viktor; Sherif, Amir; Pandha, Hardev; Warren, Anne Y; Davidson, Catherine; Uprichard, Adam; Blayney, Jaine K; Price, Bethanie; Jellema, Gera L; Steele, Christopher J; Svindland, Aud; McDade, Simon S; Eden, Christopher G; Foster, Chris; Mills, Ian G; Neal, David E; Mason, Malcolm D; Kay, Elaine W; Waugh, David J; Harkin, D Paul; Watson, R William; Clarke, Noel W; Kennedy, Richard D

2017-10-01

Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation. The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

African Americans with pancreatic ductal adenocarcinoma exhibit gender differences in Kaiso expression

PubMed Central

Mukherjee, Angana; Jones, Jacqueline; Karanam, Balasubramanyam; Davis, Melissa; Jaynes, Jesse; Reams, R. Renee; Dean-Colomb, Windy; Yates, Clayton

2016-01-01

Kaiso, a bi-modal transcription factor, regulates gene expression, and is elevated in breast, prostate, and colon cancers. Depletion of Kaiso in other cancer types leads to a reduction in markers for the epithelial–mesenchymal transition (EMT) (Jones et al., 2014), however its clinical implications in pancreatic ductal adenocarcinoma (PDCA) have not been widely explored. PDCA is rarely detected at an early stage but is characterized by rapid progression and invasiveness. We now report the significance of the subcellular localization of Kaiso in PDCAs from African Americans. Kaiso expression is higher in the cytoplasm of invasive and metastatic pancreatic cancers. In males, cytoplasmic expression of Kaiso correlates with cancer grade and lymph node positivity. In male and female patients, cytoplasmic Kaiso expression correlates with invasiveness. Also, nuclear expression of Kaiso increases with increased invasiveness and lymph node positivity. Further, analysis of the largest PDCA dataset available on ONCOMINE shows that as Kaiso increases, there is an overall increase in Zeb1, which is the inverse for E-cadherin. Hence, these findings suggest a role for Kaiso in the progression of PDCAs, involving the EMT markers, E-cadherin and Zeb1. PMID:27424525

EphA2 enhances the proliferation and invasion ability of LNCaP prostate cancer cells.

PubMed

Chen, Peijie; Huang, Yan; Zhang, Bo; Wang, Qiuquan; Bai, Peiming

2014-07-01

EphA2 is persistently overexpressed and functionally changed in numerous human cancers. However, to the best of our knowledge, the role that EphA2 plays in prostate cancer is not entirely clear. To investigate the roles of EphA2 in the development and progression of prostate cancer, the present study initially evaluated the roles of the EphA2 protein in LNCaP prostate cancer cells using recombinant plasmid, western blot analysis, flow cytometry, Matrigel invasion chamber and the cell counting kit-8 assay. An immunohistochemistry assay was also conducted to observe the effects of EphA2 in prostate cancer tissues. The results demonstrated that the LNCaP human prostate cancer cells that were transfected with pcDNA3.1(+) plasmid-mediated pcDNA3.1(+)-EphA2, markedly enhanced the cell growth and invasion in vitro . Additionally, EphA2 was overexpressed in prostate cancer specimens and the expression of EphA2 was significantly associated with Gleason grade, total prostate-specific antigen, advanced clinical stage and lymph node metastasis. Collectively, these results demonstrate that EphA2 is involved in malignant cell behavior and is a potential therapeutic target in human prostate cancer.

Locus-specific gene repositioning in prostate cancer

PubMed Central

Leshner, Marc; Devine, Michelle; Roloff, Gregory W.; True, Lawrence D.; Misteli, Tom; Meaburn, Karen J.

2016-01-01

Genes occupy preferred spatial positions within interphase cell nuclei. However, positioning patterns are not an innate feature of a locus, and genes can alter their localization in response to physiological and pathological changes. Here we screen the radial positioning patterns of 40 genes in normal, hyperplasic, and malignant human prostate tissues. We find that the overall spatial organization of the genome in prostate tissue is largely conserved among individuals. We identify three genes whose nuclear positions are robustly altered in neoplastic prostate tissues. FLI1 and MMP9 position differently in prostate cancer than in normal tissue and prostate hyperplasia, whereas MMP2 is repositioned in both prostate cancer and hyperplasia. Our data point to locus-specific reorganization of the genome during prostate disease. PMID:26564800

The impact of the United States Preventive Services Task Force (USPTSTF) recommendations against prostate-specific antigen (PSA) testing on PSA testing in Australia.

PubMed

Zargar, Homayoun; van den Bergh, Roderick; Moon, Daniel; Lawrentschuk, Nathan; Costello, Anthony; Murphy, Declan

2017-01-01

To assess the impact of the United States Preventive Services Task Force (USPTSTF) recommendations on prostate-specific antigen (PSA) testing, prostate biopsy, and prostatectomy in Australian men based on the available Medicare data. Events were identified using Medicare item numbers for PSA testing (66655, 66659), prostate biopsy (37219), prostatectomy (37210), and prostatectomy with lymph node dissection (37211). The occurrences of each procedure was queried per 100 000 capita for consecutive financial years over the period 2000-2015. For each item number, reports were also generated for all Australian States. For PSA testing the data was stratified into three age groups of 45-54, 55-64, and 65-74 years. For assessing the rate of prostatectomy the capita rate values for two item numbers of prostatectomy (37210) and prostatectomy with lymph node dissection (37211) were combined. Steady declines in per capita incidences of all five item numbers assessed were seen for the three consecutive financial years (2013-2015) since the publication of the USPTSTF recommendation statement. These declines were seen across all Australian States. When examining the rate of PSA testing for the three age brackets 45-54, 55-64, and 65-74 years, similar trends were identified. Since the introduction of the USPTSTF recommendation statement there has been a steady nationwide decline in per capita incidences of PSA testing, prostate biopsy, and prostatectomy based on the Australian Medicare data. Whether these declines are in the right direction toward reduction in over-diagnosis and overtreatment of clinically insignificant prostate cancer or stage migration toward more locally advanced disease due to lost opportunity in diagnosing and treating early clinically significant prostate cancer will remain to be seen. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients.

PubMed

Zang, Shiming; Shao, Guoqiang; Cui, Can; Li, Tian-Nv; Huang, Yue; Yao, Xiaochen; Fan, Qiu; Chen, Zejun; Du, Jin; Jia, Ruipeng; Sun, Hongbin; Hua, Zichun; Tang, Jun; Wang, Feng

2017-02-14

We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images. Only 3 patients with stable mCRPC after chemotherapy were negative for PSMA. The sensitivity, specificity and accuracy of 68Ga-PSMA-11 imaging were 97.3%, 100.0% and 97.5%, respectively. The maximum standardized uptake (SUVmax) of prostatic lesions was 17.09 ± 11.08 and 13.33 ± 12.31 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 revealed 105 metastatic lymph nodes in 15 patients; the SUVmax was 16.85 ± 9.70 and 7.54 ± 5.20 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 PET/CT also newly detected visceral metastasis in 9 patients (22.5%) and bone metastasis in 29 patients (72.5%). 68Ga-PSMA-11 PET/CT exhibits potential for staging and risk stratification in naïve PCa, as well as improved sensitivity for detection of lymph node and remote metastasis.

68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients

PubMed Central

Cui, Can; Li, Tian-Nv; Huang, Yue; Yao, Xiaochen; Fan, Qiu; Chen, Zejun; Du, Jin; Jia, Ruipeng; Sun, Hongbin; Hua, Zichun; Tang, Jun; Wang, Feng

2017-01-01

We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images. Only 3 patients with stable mCRPC after chemotherapy were negative for PSMA. The sensitivity, specificity and accuracy of 68Ga-PSMA-11 imaging were 97.3%, 100.0% and 97.5%, respectively. The maximum standardized uptake (SUVmax) of prostatic lesions was 17.09 ± 11.08 and 13.33 ± 12.31 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 revealed 105 metastatic lymph nodes in 15 patients; the SUVmax was 16.85 ± 9.70 and 7.54 ± 5.20 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 PET/CT also newly detected visceral metastasis in 9 patients (22.5%) and bone metastasis in 29 patients (72.5%). 68Ga-PSMA-11 PET/CT exhibits potential for staging and risk stratification in naïve PCa, as well as improved sensitivity for detection of lymph node and remote metastasis. PMID:28103574

Is computed tomography a necessary part of a metastatic evaluation for castration-resistant prostate cancer? Results from the Shared Equal Access Regional Cancer Hospital Database.

PubMed

Hanyok, Brian T; Howard, Lauren E; Amling, Christopher L; Aronson, William J; Cooperberg, Matthew R; Kane, Christopher J; Terris, Martha K; Posadas, Edwin M; Freedland, Stephen J

2016-01-15

Metastatic lesions in prostate cancer beyond the bone have prognostic importance and affect clinical therapeutic decisions. Few data exist regarding the prevalence of soft-tissue metastases at the initial diagnosis of metastatic castration-resistant prostate cancer (mCRPC). This study analyzed 232 men with nonmetastatic (M0) castration-resistant prostate cancer (CRPC) who developed metastases detected by a bone scan or computed tomography (CT). All bone scans and CT scans within the 30 days before or after the mCRPC diagnosis were reviewed. The rate of soft-tissue metastases among those undergoing CT was determined. Then, predictors of soft-tissue metastases and visceral and lymph node metastases were identified. Compared with men undergoing CT (n = 118), men undergoing only bone scans (n = 114) were more likely to have received primary treatment (P = .048), were older (P = .013), and less recently developed metastases (P = .018). Among those undergoing CT, 52 (44%) had soft-tissue metastases, including 20 visceral metastases (17%) and 41 lymph node metastases (35%), whereas 30% had no bone involvement. In a univariable analysis, only prostate-specific antigen (PSA) predicted soft-tissue metastases (odds ratio [OR], 1.27; P = .047), and no statistically significant predictors of visceral metastases were found. A higher PSA level was associated with an increased risk of lymph node metastases (OR, 1.38; P = .014), whereas receiving primary treatment was associated with decreased risk (OR, 0.36; P = .015). The data suggest that there is a relatively high rate of soft-tissue metastasis (44%) among CRPC patients undergoing CT at the initial diagnosis of metastases, including some men with no bone involvement. Therefore, forgoing CT during a metastatic evaluation may lead to an underdiagnosis of soft-tissue metastases and an underdiagnosis of metastases in general. Cancer 2015. © 2015 American Cancer Society. Cancer 2016;122:222-229. © 2015 American Cancer Society. © 2015 American Cancer Society.

Performance characteristics of prostate-specific antigen density and biopsy core details to predict oncological outcome in patients with intermediate to high-risk prostate cancer underwent robot-assisted radical prostatectomy.

PubMed

Yashi, Masahiro; Nukui, Akinori; Tokura, Yuumi; Takei, Kohei; Suzuki, Issei; Sakamoto, Kazumasa; Yuki, Hideo; Kambara, Tsunehito; Betsunoh, Hironori; Abe, Hideyuki; Fukabori, Yoshitatsu; Nakazato, Yoshimasa; Kaji, Yasushi; Kamai, Takao

2017-06-23

Many urologic surgeons refer to biopsy core details for decision making in cases of localized prostate cancer (PCa) to determine whether an extended resection and/or lymph node dissection should be performed. Furthermore, recent reports emphasize the predictive value of prostate-specific antigen density (PSAD) for further risk stratification, not only for low-risk PCa, but also for intermediate- and high-risk PCa. This study focused on these parameters and compared respective predictive impact on oncologic outcomes in Japanese PCa patients. Two-hundred and fifty patients with intermediate- and high-risk PCa according to the National Comprehensive Cancer Network (NCCN) classification, that underwent robot-assisted radical prostatectomy at a single institution, and with observation periods of longer than 6 months were enrolled. None of the patients received hormonal treatments including antiandrogens, luteinizing hormone-releasing hormone analogues, or 5-alpha reductase inhibitors preoperatively. PSAD and biopsy core details, including the percentage of positive cores and the maximum percentage of cancer extent in each positive core, were analyzed in association with unfavorable pathologic results of prostatectomy specimens, and further with biochemical recurrence. The cut-off values of potential predictive factors were set through receiver-operating characteristic curve analyses. In the entire cohort, a higher PSAD, the percentage of positive cores, and maximum percentage of cancer extent in each positive core were independently associated with advanced tumor stage ≥ pT3 and an increased index tumor volume > 0.718 ml. NCCN classification showed an association with a tumor stage ≥ pT3 and a Gleason score ≥8, and the attribution of biochemical recurrence was also sustained. In each NCCN risk group, these preoperative factors showed various associations with unfavorable pathological results. In the intermediate-risk group, the percentage of positive cores showed an independent predictive value for biochemical recurrence. In the high-risk group, PSAD showed an independent predictive value. PSAD and biopsy core details have different performance characteristics for the prediction of oncologic outcomes in each NCCN risk group. Despite the need for further confirmation of the results with a larger cohort and longer observation, these factors are important as preoperative predictors in addition to the NCCN classification for a urologic surgeon to choose a surgical strategy.

Up regulation of the steroid hormone synthesis regulator HSD3B2 is linked to early PSA recurrence in prostate cancer.

PubMed

Neubauer, Emily; Latif, Morwari; Krause, Jenny; Heumann, Asmus; Armbrust, Moritz; Luehr, Clara; Fraune, Christoph; Hube-Magg, Claudia; Kluth, Martina; Möller-Koop, Christina; Sauter, Guido; Simon, Ronald; Beyer, Burkhard; Pompe, Raisa S; Thederan, Imke; Schlomm, Thorsten; Büscheck, Franziska

2018-05-24

HSD3B2 plays a crucial role in steroid hormone biosynthesis and is thus of particular interest in hormone dependent tumors such as prostate cancer. To clarify the clinical relevance of HSD3B2 expression in prostate cancer, we analyzed HSD3B2 protein expression by immunohistochemistry on our preexisting tissue microarray with 12.247 annotated cancers. Compared with normal tissue cytoplasmic HSD3B2 staining was stronger in prostate cancers. In 9371 interpretable cancers, HSD3B2 expression was found in 95.5% of cancers and was considered weak in 29.9%, moderate in 40.7% and strong in 24.9%. HSD3B2 up regulation was linked to advanced pathological tumor stage (pT), high Gleason grade, elevated preoperative PSA levels (p < 0.0001 each), lymph node metastasis (p = 0.0019), accelerated cell proliferation (p < 0.0001), androgen receptor (AR) expression (p < 0.0001), and early biochemical recurrence (p < 0.0001). HSD3B2 up regulation was only marginally more frequent in ERG positive (98%) than in ERG negative cancers (94%; p < 0.0001) and was strongly linked to deletions of 5q and 6q (p < 0.0001 each). Multivariate analyses showed that the prognostic impact of HSD3B2 expression was independent of established preoperative, but not of postoperative prognostic parameters. In summary, the results of our study demonstrate that HSD3B2 is strongly up regulated in a fraction of prostate cancers that are characterized by increased AR signaling, adverse tumor phenotype and early biochemical recurrence. Copyright © 2018 Elsevier Inc. All rights reserved.

Survival Outcomes of Whole-Pelvic Versus Prostate-Only Radiation Therapy for High-Risk Prostate Cancer Patients With Use of the National Cancer Data Base

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amini, Arya; Jones, Bernard L.; Yeh, Norman

Purpose/Objectives: The addition of whole pelvic (WP) compared with prostate-only (PO) radiation therapy (RT) for clinically node-negative prostate cancer remains controversial. The purpose of our study was to evaluate the survival benefit of adding WPRT versus PO-RT for high-risk, node-negative prostate cancer, using the National Cancer Data Base (NCDB). Methods and Materials: Patients with high-risk prostate cancer treated from 2004 to 2006, with available data for RT volume, coded as prostate and pelvis (WPRT) or prostate alone (PO-RT) were included. Multivariate analysis (MVA) and propensity-score matched analysis (PSM) were performed. Recursive partitioning analysis (RPA) based on overall survival (OS) usingmore » Gleason score (GS), T stage, and pretreatment prostate-specific antigen (PSA) was also conducted. Results: A total of 14,817 patients were included: 7606 (51.3%) received WPRT, and 7211 (48.7%) received PO-RT. The median follow-up time was 81 months (range, 2-122 months). Under MVA, the addition of WPRT for high-risk patients had no OS benefit compared with PO-RT (HR 1.05; P=.100). On subset analysis, patients receiving dose-escalated RT also did not benefit from WPRT (HR 1.01; P=.908). PSM confirmed no survival benefit with the addition of WPRT for high-risk patients (HR 1.05; P=.141). In addition, RPA was unable to demonstrate a survival benefit of WPRT for any subset. Other prognostic factors for inferior OS under MVA included older age (HR 1.25; P<.001), increasing comorbidity scores (HR 1.46; P<.001), higher T stage (HR 1.17; P<.001), PSA (HR 1.81; P<.001), and GS (HR 1.29; P<.001), and decreasing median county household income (HR 1.15; P=.011). Factors improving OS included the addition of androgen deprivation therapy (HR 0.92; P=.033), combination external beam RT plus brachytherapy boost (HR 0.71; P<.001), and treatment at an academic/research institution (HR 0.84; P=.002). Conclusion: In the largest reported analysis of WPRT for patients with high-risk prostate cancer treated in the dose-escalated era, the addition of WPRT demonstrated no survival advantage compared with PO-RT.« less

Immunohistochemical expression of interleukin-2 receptor and interleukin-6 in patients with prostate cancer and benign prostatic hyperplasia: association with asymptomatic inflammatory prostatitis NIH category IV.

PubMed

Engelhardt, Paul Friedrich; Seklehner, Stephan; Brustmann, Hermann; Lusuardi, Lukas; Riedl, Claus R

2015-04-01

This study prospectively investigated the immunohistochemical expression of interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6) in patients with prostate cancer and benign prostatic hyperplasia (BPH), and a possible association of these conditions with asymptomatic inflammatory prostatitis National Institutes of Health (NIH) category IV. The study included 139 consecutive patients who underwent transurethral resection of the prostate and transvesical enucleation of the prostate (n = 82) or radical prostatectomy (n = 57). To characterize inflammatory changes the criteria proposed by Irani et al. [J Urol 1997;157:1301-3] were used. IL-2R and IL-6 expression was studied by a standard immunohistochemical method. Results were correlated with tumour, node, metastasis stage, Gleason scores, total prostate-specific antigen, International Prostate Symptom Score and body mass index. IL-2R and IL-6 expression was significantly higher in neoplastic prostate cancer tissue than in normal tissue of prostate cancer patients (p < 0.001 and p < 0.04, respectively). Prostate cancer patients with prostatitis showed significantly higher IL-2R expression than those without inflammation (p < 0.03). In patients with BPH, expression of IL-2R as well as IL-6 was higher in patients with prostatitis than in those without (p < 0.01 and p < 0.02, respectively). IL-2R and IL-6 expression was significantly higher in prostate cancer tissue than in normal tissue. Patients with asymptomatic inflammatory prostatitis NIH category IV showed significantly greater activity.

Offline multiple adaptive planning strategy for concurrent irradiation of the prostate and pelvic lymph nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, Peng; Xia, Ping, E-mail: xiap@ccf.org; Pouliot, Jean

2014-02-15

Purpose: Concurrent irradiation of the prostate and pelvic lymph nodes (PLNs) can be challenging due to the independent motion of the two target volumes. To address this challenge, the authors have proposed a strategy referred to as Multiple Adaptive Planning (MAP). To minimize the number of MAP plans, the authors’ previous work only considered the prostate motion in one major direction. After analyzing the pattern of the prostate motion, the authors investigated a practical number of intensity-modulated radiotherapy (IMRT) plans needed to accommodate the prostate motion in two major directions simultaneously. Methods: Six patients, who received concurrent irradiation of themore » prostate and PLNs, were selected for this study. Nine MAP-IMRT plans were created for each patient with nine prostate contours that represented the prostate at nine locations with respect to the PLNs, including the original prostate contour and eight contours shifted either 5 mm in a single anterior-posterior (A-P), or superior-inferior (S-I) direction, or 5 mm in both A-P and S-I directions simultaneously. From archived megavoltage cone beam CT (MV-CBCT) and a dual imaging registration, 17 MV-CBCTs from 33 available MV-CBCT from these patients showed large prostate displacements (>3 mm in any direction) with respect to the pelvic bones. For each of these 17 fractions, one of nine MAP-IMRT plans was retrospectively selected and applied to the MV-CBCT for dose calculation. For comparison, a simulated isocenter-shifting plan and a reoptimized plan were also created for each of these 17 fractions. The doses to 95% (D95) of the prostate and PLNs, and the doses to 5% (D5) of the rectum and bladder were calculated and analyzed. Results: For the prostate, D95 > 97% of the prescription dose was observed in 16, 16, and 17 of 17 fractions for the MAP, isocenter-shifted, and reoptimized plans, respectively. For PLNs, D95 > 97% of the prescription doses was observed in 10, 3, and 17 of 17 fractions for the three types of verification plans, respectively. The D5 (mean ± SD) of the rectum was 45.78 ± 5.75, 45.44 ± 4.64, and 44.64 ± 2.71 Gy, and the D5 (mean ± SD) of the bladder was 45.18 ± 2.70, 46.91 ± 3.04, and 45.67 ± 3.61 Gy for three types of verification plans, respectively. Conclusions: The MAP strategy with nine IMRT plans to accommodate the prostate motions in two major directions achieved good dose coverage to the prostate and PLNs. The MAP approach can be immediately used in clinical practice without requiring extra hardware and software.« less

A quantitative study of IMRT delivery effects in commercial planning systems for the case of oesophagus and prostate tumours.

PubMed

Seco, J; Clark, C H; Evans, P M; Webb, S

2006-05-01

This study focuses on understanding the impact of intensity-modulated radiotherapy (IMRT) delivery effects when applied to plans generated by commercial treatment-planning systems such as Pinnacle (ADAC Laboratories Inc.) and CadPlan/Helios (Varian Medical Systems). These commercial planning systems have had several version upgrades (with improvements in the optimization algorithm), but the IMRT delivery effects have not been incorporated into the optimization process. IMRT delivery effects include head-scatter fluence from IMRT fields, transmission through leaves and the effect of the rounded shape of the leaf ends. They are usually accounted for after optimization when leaf sequencing the "optimal" fluence profiles, to derive the delivered fluence profile. The study was divided into two main parts: (a) analysing the dose distribution within the planning-target volume (PTV), produced by each of the commercial treatment-planning systems, after the delivered fluence had been renormalized to deliver the correct dose to the PTV; and (b) studying the impact of the IMRT delivery technique on the surrounding critical organs such as the spinal cord, lungs, rectum, bladder etc. The study was performed for tumours of (i) the oesophagus and (ii) the prostate and pelvic nodes. An oesophagus case was planned with the Pinnacle planning system for IMRT delivery, via multiple-static fields (MSF) and compensators, using the Elekta SL25 with a multileaf collimator (MLC) component. A prostate and pelvic nodes IMRT plan was performed with the Cadplan/Helios system for a dynamic delivery (DMLC) using the Varian 120-leaf Millennium MLC. In these commercial planning systems, since IMRT delivery effects are not included into the optimization process, fluence renormalization is required such that the median delivered PTV dose equals the initial prescribed PTV dose. In preparing the optimum fluence profile for delivery, the PTV dose has been "smeared" by the IMRT delivery techniques. In the case of the oesophagus, the critical organ, spinal cord, received a greater dose than initially planned, due to the delivery effects. The increase in the spinal cord dose is of the order of 2-3 Gy. In the case of the prostate and pelvic nodes, the IMRT delivery effects led to an increase of approximately 2 Gy in the dose delivered to the secondary PTV, the pelvic nodes. In addition to this, the small bowel, rectum and bladder received an increased dose of the order of 2-3 Gy to 50% of their total volume. IMRT delivery techniques strongly influence the delivered dose distributions for the oesophagus and prostate/pelvic nodes tumour sites and these effects are not yet accounted for in the Pinnacle and the CadPlan/Helios planning systems. Currently, they must be taken into account during the optimization stage by altering the dose limits accepted during optimization so that the final (sequenced) dose is within the constraints.

Multiparametric magnetic resonance imaging for the assessment of extracapsular invasion and other staging parameters in patients with prostate cancer candidates for radical prostatectomy.

PubMed

Lista, F; Gimbernat, H; Cáceres, F; Rodríguez-Barbero, J M; Castillo, E; Angulo, J C

2014-06-01

the proper evaluation of the extracapsular extension (ECE), the invasion of seminal vesicles and regional lymph nodes are necessary to plan the treatment of localized prostate cancer. A model that assesses the risk of ECE in the specimen considering the clinical, histological and imaging findings is defined. prospective study in 85 patients with prostate cancer treated with radical prostatectomy. Prostate biopsy was performed 4 weeks before multiparametric study (mpMRI). mpMRI included T2-weighted endorectal magnetic resonance imaging (T2W-MRI), diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The apparent diffusion coefficient (ADC) was also measured. A study of consistency (k) was assessed comparing receiver operating characteristic (ROC) curve and area under the curve (AUC), which were obtained in each case (Z). Finally, a regression model was performed to predict ECE. the mean age was 63.7 ± 6.9 years and the mean value of PSA 12.6 ± 13.8. In 31.7% of cases, digital rectal examination was suspicious for malignancy. Prostatectomy specimen showed pT2a in 12 cases (14%), pT2b in 3 (3%), pT2c in 37 (43%), pT3a in 19(22%) and pT3b 14 cases (17%). ECE was evidenced in 33 (39%) of the specimens, seminal vesicle invasion in 14 (16.5%) and pelvic node involvement in 5 patients (6%). The consistency in the evaluation of ECE (image and pathological studies) was .35 for MRI (sensitivity .33, specificity .96) and .62 for mpMRI (sensitivity .58, specificity .98). Mean value of ADC was .76 ± .2 in patients with ECE. This value was not associated with Gleason score (P = .2) or with PSA value (P = .6). AUC value as predictor of ECE was of 65% for MRI, 78% for mpMRI and 50% ADC (Z = .008). Univariate analysis demonstrated that ECE probability increases with each Gleason score point, whilst this probability increases 1.06 times with each PSA point, and decreases .3 times with each point of ADC. Multivariate analysis confirmed that ADC value is a slight protective factor against ECE (OR = .01; CI 95% .002-.14). The consistency in the evaluation of seminal vesicles was .43 for MRI and .67 for mpMRI. AUC was 69% and 82% respectively (Z = .02). The consistency in the evaluation of positive lymph nodes was .4 for MRI and .7 for mpMRI. AUC was 68% and 88% respectively (Z = .36). multiparametric study allows to carry out a more proper preoperative evaluation of ECE than convectional MRI. The most reliable predictors of ECE are DW-MRI combined with DCE-MRI, ADC coefficient and Gleason score. The superiority of mpMRI is also demonstrated for detection of seminal vesicles invasion, but not for the evaluation of lymph nodes invasion. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Contribution of 11C-Choline PET/CT in prostate carcinoma biochemical relapse with serum PSA level below 1 ng/ml.

PubMed

Gómez-de la Fuente, F J; Martínez-Rodríguez, I; de Arcocha-Torres, M; Quirce, R; Jiménez-Bonilla, J; Martínez-Amador, N; Banzo, I

11 C-choline PET/CT has demonstrated good results in the restaging of prostate cancer (PCa) with high serum prostate specific antigen (PSA), but its use in patients with low serum PSA is controversial. Our aim was to evaluate the contribution of 11 C-choline PET/CT in patients with PCa, biochemical relapse and PSA <1 ng/ml. Fifty consecutive patients (mean age: 65.9±5.6 years) with biochemical relapse of PCa and serum PSA <1ng/ml were evaluated retrospectively. PET/CT was performed 20min after intravenous administration of 555-740 MBq of 11 C-choline. Minimum follow up time was 30 months. Twenty-one out of 50 patients (42%) had an abnormal 11 C-choline PET/CT. In 7 out of 21 patients (14%) tumor was confirmed (4 in prostatic bed, 4 in pelvic lymph nodes, 2 in mediastinal lymph nodes and one synchronous sigmoid carcinoma), and in all cases the initial therapeutic planning was modified. In 2 patients (4%) subsequent tests diagnosed a benign disease (one sarcoidosis, one tuberculosis sequelae) and in 3 patients (6%) they ruled out pathology. The other 9 patients (18%) had no further assessment (7 mediastinal and 4 pelvic lymph nodes). Twenty-nine out of 50 patients (58%) had a normal PET/CT. At 30 months, follow up recurrence was confirmed only in 2 of these patients. 11 C-choline PET/CT proved its usefulness in demonstrating tumor in 14% of patients with BR of PCa and serum PSA <1ng/ml, with therapeutic implications. In 4% of patients a benign condition was detected. A normal 11 C-choline PET/CT was associated with a very low rate of recurrence at 30 months. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

EphA2 enhances the proliferation and invasion ability of LNCaP prostate cancer cells

PubMed Central

CHEN, PEIJIE; HUANG, YAN; ZHANG, BO; WANG, QIUQUAN; BAI, PEIMING

2014-01-01

EphA2 is persistently overexpressed and functionally changed in numerous human cancers. However, to the best of our knowledge, the role that EphA2 plays in prostate cancer is not entirely clear. To investigate the roles of EphA2 in the development and progression of prostate cancer, the present study initially evaluated the roles of the EphA2 protein in LNCaP prostate cancer cells using recombinant plasmid, western blot analysis, flow cytometry, Matrigel invasion chamber and the cell counting kit-8 assay. An immunohistochemistry assay was also conducted to observe the effects of EphA2 in prostate cancer tissues. The results demonstrated that the LNCaP human prostate cancer cells that were transfected with pcDNA3.1(+) plasmid-mediated pcDNA3.1(+)-EphA2, markedly enhanced the cell growth and invasion in vitro. Additionally, EphA2 was overexpressed in prostate cancer specimens and the expression of EphA2 was significantly associated with Gleason grade, total prostate-specific antigen, advanced clinical stage and lymph node metastasis. Collectively, these results demonstrate that EphA2 is involved in malignant cell behavior and is a potential therapeutic target in human prostate cancer. PMID:24959216

Recurrent Medullary Thyroid Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET/CT: Exploring New Theranostic Avenues.

PubMed

Arora, Saurabh; Damle, Nishikant Avinash; Parida, Girish Kumar; Singhal, Abhinav; Nalli, Harish; Dattagupta, Shreya; Bal, Chandrasekar

2018-05-01

The prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells. Few other malignancies have shown expression of PSMA. We present a case of 35-year-old man with medullary thyroid carcinoma, post total thyroidectomy and bilateral neck dissection, now presenting with rising calcitonin levels (doubling time 9 months) and local neck recurrence with negative I-MIBG scan. We decided to perform Ga-PSMA-HBED-CC PET/CT scan to assess PSMA expression and explore the therapeutic option in view of rising serum calcitonin. It revealed intense PSMA uptake in the soft tissue mass in left thyroid bed and cervical lymph nodes.

Salvage Radiotherapy After Postprostatectomy Biochemical Failure: Does Pretreatment Radioimmunoscintigraphy Help Select Patients with Locally Confined Disease?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liauw, Stanley L.; Weichselbaum, Ralph R.; Zagaja, Gregory P.

2008-08-01

Purpose: Radioimmunoscintigraphy (RIS) has the potential to demonstrate early recurrences after prostatectomy and might be useful in selecting patients for salvage radiotherapy (RT). Methods: A total of 82 patients with adenocarcinoma of the prostate were treated with salvage RT between 1988 and 2005, for an elevated prostate-specific antigen (PSA) level after prostatectomy. Of the 82 patients, 32% had Gleason score 6 or less disease, 54% Gleason score 7 disease, 70% had Stage pT3 disease, 55% had positive margins, and 5% had pathologic lymph node involvement. The median pre-RT PSA level was 0.63 ng/mL. Of the 82 patients, 47 (57%) hadmore » a pre-RT RIS (ProstaScint) scan, which was used for both patient selection and target delineation. The RT regimen was a median dose of 66 Gy to the prostate bed. Also, 64% received androgen deprivation therapy. Biochemical failure was defined as a PSA level >0.1 ng/mL and increasing. Results: Patients with a pre-RT RIS scan had a lower preoperative PSA level (p = 0.0240) and shorter follow-up (p = 0.0221) than those without RIS. With a median follow-up of 44 months, the biochemical control rate was 56% at 3 years and 48% at 5 years. Margin status was the only factor associated with biochemical control on univariate (p = 0.0055) and multivariate (p = 0.0044) analysis. Patients who had prostate bed-only uptake on RIS (n = 38) did not have improved outcomes, with biochemical control rates of 51% at 3 years and 40% at 5 years. Conclusion: Patients treated with salvage RT had modest responses. Patients who were selected for treatment with RIS did not have better biochemical outcomes. Our results indicated that patients with positive margins were most likely to benefit from salvage RT.« less

Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for prostate cancer 2017.

PubMed

Aljubran, Ali; Abusamra, Ashraf; Alkhateeb, Sultan; Alotaibi, Mohammed; Rabah, Danny; Bazarbashi, Shouki; Alkushi, Hussain; Al-Mansour, Mubarak; Alharbi, Hulayel; Eltijani, Amin; Alghamdi, Abdullah; Alsharm, Abdullah; Ahmad, Imran; Murshid, Esam

2018-01-01

This is an update to the previously published Saudi guidelines for the evaluation and medical and surgical management of patients diagnosed with prostate cancer. Prostate cancer is categorized according to the stage of the disease using the tumor node metastasis staging system 7 th edition. The guidelines are presented with supporting evidence levels based on a comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Local factors, such as availability, logistic feasibility, and familiarity of various treatment modalities, have been taken into consideration. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health-care policymakers in the management of patients diagnosed with adenocarcinoma of the prostate.

Robust gene network analysis reveals alteration of the STAT5a network as a hallmark of prostate cancer.

PubMed

Reddy, Anupama; Huang, C Chris; Liu, Huiqing; Delisi, Charles; Nevalainen, Marja T; Szalma, Sandor; Bhanot, Gyan

2010-01-01

We develop a general method to identify gene networks from pair-wise correlations between genes in a microarray data set and apply it to a public prostate cancer gene expression data from 69 primary prostate tumors. We define the degree of a node as the number of genes significantly associated with the node and identify hub genes as those with the highest degree. The correlation network was pruned using transcription factor binding information in VisANT (http://visant.bu.edu/) as a biological filter. The reliability of hub genes was determined using a strict permutation test. Separate networks for normal prostate samples, and prostate cancer samples from African Americans (AA) and European Americans (EA) were generated and compared. We found that the same hubs control disease progression in AA and EA networks. Combining AA and EA samples, we generated networks for low low (<7) and high (≥7) Gleason grade tumors. A comparison of their major hubs with those of the network for normal samples identified two types of changes associated with disease: (i) Some hub genes increased their degree in the tumor network compared to their degree in the normal network, suggesting that these genes are associated with gain of regulatory control in cancer (e.g. possible turning on of oncogenes). (ii) Some hubs reduced their degree in the tumor network compared to their degree in the normal network, suggesting that these genes are associated with loss of regulatory control in cancer (e.g. possible loss of tumor suppressor genes). A striking result was that for both AA and EA tumor samples, STAT5a, CEBPB and EGR1 are major hubs that gain neighbors compared to the normal prostate network. Conversely, HIF-lα is a major hub that loses connections in the prostate cancer network compared to the normal prostate network. We also find that the degree of these hubs changes progressively from normal to low grade to high grade disease, suggesting that these hubs are master regulators of prostate cancer and marks disease progression. STAT5a was identified as a central hub, with ~120 neighbors in the prostate cancer network and only 81 neighbors in the normal prostate network. Of the 120 neighbors of STAT5a, 57 are known cancer related genes, known to be involved in functional pathways associated with tumorigenesis. Our method is general and can easily be extended to identify and study networks associated with any two phenotypes.

Moderate hypofractionated radiotherapy with volumetric modulated arc therapy and simultaneous integrated boost for pelvic irradiation in prostate cancer.

PubMed

Franzese, C; Fogliata, A; D'Agostino, G R; Di Brina, L; Comito, T; Navarria, P; Cozzi, L; Scorsetti, M

2017-07-01

The optimal treatment for unfavourable intermediate/high-risk prostate cancer is still debated. In the present study, the pattern of toxicity and early clinical outcome of patients with localized prostate cancer was analyzed. A cohort of 90 patients treated on pelvic lymph nodes from 2010 to 2015 was selected. All patients were treated with Volumetric Modulated Arc Therapy (VMAT), and Simultaneous integrated boost (SIB) in 28 fractions; the prostate, the seminal vesicle and the pelvic lymph node received total doses of 74.2, 65.5, and 51.8 Gy, respectively. End points were the detection of acute and late toxicities graded according to the Common Toxicity Criteria CTCAE version 3, evaluating the rectal, genito-urinary and gastro-intestinal toxicity. Correlation of OARs dose parameters and related toxicities was explored. Preliminary overall survival and Progression-free survival (PFS) were evaluated. With a median follow-up of 25 months, no interruptions for treatment-related toxicity were recorded. Univariate analysis among dosimetric data and acute toxicities showed no correlations. Regarding late toxicity: the dose received by a rectal volume of 90 cm 3 was found to be significant for toxicity prediction (p = 0.024). PFS was 90.6% and 60.2% at 2 and 4 years, respectively. PFS correlates with age (p = 0.011) and Gleason score (p = 0.011). Stratifying the PSA nadir in quartiles, its value was significant (p = 0.016) in predicting PFS, showing a reduction of PFS of 2 months for each PSA-nadir increase of 0.1 ng/ml. HRT with VMAT and SIB on the whole pelvis in unfavourable prostate cancer patients is effective with a mild pattern of toxicity.

Vasculogenic Mimicry in Prostate Cancer: The Roles of EphA2 and PI3K.

PubMed

Wang, Hua; Lin, Hao; Pan, Jincheng; Mo, Chengqiang; Zhang, Faming; Huang, Bin; Wang, Zongren; Chen, Xu; Zhuang, Jintao; Wang, Daohu; Qiu, Shaopeng

2016-01-01

Aggressive tumor cells can form perfusable networks that mimic normal vasculature and enhance tumor growth and metastasis. A number of molecular players have been implicated in such vasculogenic mimicry, among them the receptor tyrosine kinase EphA2, which is aberrantly expressed in aggressive tumors. Here we study the role and regulation of EphA2 in vasculogenic mimicry in prostate cancer where this phenomenon is still poorly understood. Vasculogenic mimicry was characterized by tubules whose cellular lining was negative for the endothelial cell marker CD34 but positive for periodic acid-Schiff staining, and/or contained red blood cells. Vasculogenic mimicry was assessed in 92 clinical samples of prostate cancer and analyzed in more detail in three prostate cancer cell lines kept in three-dimensional culture. Tissue samples and cell lines were also assessed for total and phosphorylated levels of EphA2 and its potential regulator, Phosphoinositide 3-Kinase (PI3K). In addition, the role of EphA2 in vasculogenic mimicry and in cell migration and invasion were investigated by manipulating the levels of EphA2 through specific siRNAs. Furthermore, the role of PI3K in vasculogenic mimicry and in regulating EphA2 was tested by application of an inhibitor, LY294002. Immunohistochemistry of prostate cancers showed a significant correlation between vasculogenic mimicry and high expression levels of EphA2, high Gleason scores, advanced TNM stage, and the presence of lymph node and distant metastases. Likewise, two prostate cancer cell lines (PC3 and DU-145) formed vasculogenic networks on Matrigel and expressed high EphA2 levels, while one line (LNCaP) showed no vasculogenic networks and lower EphA2 levels. Specific silencing of EphA2 in PC3 and DU-145 cells decreased vasculogenic mimicry as well as cell migration and invasion. Furthermore, high expression levels of PI3K and EphA2 phosphorylation at Ser897 significantly correlated with the presence of vasculogenic mimicry and in vitro inhibition of PI3K by LY294002 disrupted vasculogenic mimicry, potentially through a reduction of EphA2 phosphorylation at Ser897. The expression levels of PI3K and EphA2 are positively correlated with vasculogenic mimicry both in vivo and in vitro. Moreover, phosphorylation levels of EphA2 regulated by PI3K are also significantly associated with vasculogenic mimicry in vivo. Based on its functional implication in vasculogenic mimicry in vitro, EphA2 signaling may be a potential therapeutic target in advanced prostate cancer.

Efficacy, Predictive Factors, and Prediction Nomograms for 68Ga-labeled Prostate-specific Membrane Antigen-ligand Positron-emission Tomography/Computed Tomography in Early Biochemical Recurrent Prostate Cancer After Radical Prostatectomy.

PubMed

Rauscher, Isabel; Düwel, Charlotte; Haller, Bernhard; Rischpler, Christoph; Heck, Matthias M; Gschwend, Jürgen E; Schwaiger, Markus; Maurer, Tobias; Eiber, Matthias

2018-05-01

Recently, 68 Ga-labeled prostate-specific membrane antigen (PSMA)-ligand positron-emission tomography (PET) imaging has been shown to improve detection rates in recurrent prostate cancer (PC). However, published studies include only small patient numbers at low prostate-specific antigen (PSA) values. For this study, 272 consecutive patients with biochemical recurrence after radical prostatectomy and PSA value between 0.2 and 1ng/ml were included. The 68 Ga-PSMA-ligand PET/computed tomography (CT) was evaluated, and detection rates were determined and correlated to various clinical variables using univariate and multivariable analyses. Subgroups of patients with very low (0.2-0.5ng/ml) and low (>0.5-1.0ng/ml) PSA values were analyzed. In total, lesions indicative of PC recurrence were detected in 55% (74/134) and 74% (102/138) with very low and low PSA values, respectively. Main sites of recurrence were pelvic or retroperitoneal lymph nodes metastases, followed by local recurrence and bone metastases with higher probability in the low versus very low PSA subgroup. Detection rates significantly increased with higher PSA values, primary pT≥3a, primary pN+ disease, grade group ≥4, previous radiation therapy, and concurrent androgen deprivation therapy (ADT) in univariate analysis. In a multivariable logistic regression model, concurrent ADT and PSA values were identified as most relevant predictors of positive 68 Ga-PSMA-ligand PET/CT. Further, prediction nomograms were established, which may help in estimating pretest PSMA-ligand PET positivity in clinical practice. In our study, 68 Ga-labeled prostate-specific membrane antigen (PSMA)-ligand positron-emission tomography (PET)/computed tomography (CT) detected recurrent disease after radical prostatectomy in 55% (74/134) and 74% (102/138) of patients with very low (0.2-0.5ng/ml) and low (>0.5-1.0ng/ml) prostate-specific antigen values, respectively. On the basis of these data, it seems reasonable to perform 68 Ga-PSMA-ligand PET/CT also in patients with early biochemical recurrence, as it can tailor further therapy decisions (eg, local vs systemic treatment). The established prediction nomograms can further assist urologists in discussions on the use of 68 Ga-PSMA-ligand PET/CT with their patients in specific clinical settings. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Glycosylation potential of human prostate cancer cell lines

PubMed Central

Gao, Yin; Chachadi, Vishwanath B.; Cheng, Pi-Wan

2014-01-01

Altered glycosylation is a universal feature of cancer cells and altered glycans can help cancer cells escape immune surveillance, facilitate tumor invasion, and increase malignancy. The goal of this study was to identify specific glycoenzymes, which could distinguish prostate cancer cells from normal prostatic cells. We investigated enzymatic activities and gene expression levels of key glycosyl- and sulfotransferases responsible for the assembly of O- and N-glycans in several prostatic cells. These cells included immortalized RWPE-1 cells derived from normal prostatic tissues, and prostate cancer cells derived from metastasis in bone (PC-3), brain (DU145), lymph node (LNCaP), and vertebra (VCaP). We found that all cells were capable of synthesizing complex N-glycans and O-glycans with the core 1 structure, and each cell line had characteristic bio-synthetic pathways to modify these structures. The in vitro measured activities corresponded well to the mRNA levels of glycosyltransferases and sulfotransferases. Lectin and antibody binding to whole cells supported these results, which form the basis for the development of tumor cell-specific targeting strategies. PMID:22843320

Investigation of c-KIT and Ki67 expression in normal, preneoplastic and neoplastic canine prostate.

PubMed

Fonseca-Alves, Carlos Eduardo; Kobayashi, Priscilla Emiko; Palmieri, Chiara; Laufer-Amorim, Renée

2017-12-06

c-KIT expression has been related to bone metastasis in human prostate cancer, but whether c-KIT expression can be similarly classified in canine prostatic tissue is unknown. This study assessed c-KIT and Ki67 expression in canine prostate cancer (PC). c-KIT gene and protein expression and Ki67 expression were evaluated in forty-four canine prostatic tissues by immunohistochemistry, RT-qPCR and western blot. Additionally, we have investigated c-KIT protein expression by immunoblotting in two primary canine prostate cancer cell lines. Eleven normal prostates, 12 proliferative inflammatory atrophy (PIA) prostates, 18 PC, 3 metastatic lesions and two prostate cancer cell cultures (PC1 and PC2) were analysed. The prostatic tissue exhibited varying degrees of membranous, cytoplasmic or membranous/cytoplasmic c-KIT staining. Four normal prostates, 4 PIA and 5 prostatic carcinomas showed positive c-KIT expression. No c-KIT immunoexpression was observed in metastases. Canine prostate cancer and PIA samples contained a higher number of Ki67-positive cells compared to normal samples. The median relative quantification (RQ) for c-KIT expression in normal, PIA and prostate cancer and metastatic samples were 0.6 (0.1-2.5), 0.7 (0.09-2.1), 0.7 (0.09-5.1) and 0.1 (0.07-0.6), respectively. A positive correlation between the number of Ki67-positive cells and c-KIT transcript levels was observed in prostate cancer samples. In the cell line, PC1 was negative for c-KIT protein expression, while PC2 was weakly positive. The present study identified a strong correlation between c-KIT expression and proliferative index, suggesting that c-KIT may influence cell proliferation. Therefore, c-KIT heterogeneous protein expression among the samples (five positive and thirteen negative prostate cancer samples) indicates a personalized approach for canine prostate cancer.

Effect of DNA methylation on identification of aggressive prostate cancer.

PubMed

Alumkal, Joshi J; Zhang, Zhe; Humphreys, Elizabeth B; Bennett, Christina; Mangold, Leslie A; Carducci, Michael A; Partin, Alan W; Garrett-Mayer, Elizabeth; DeMarzo, Angelo M; Herman, James G

2008-12-01

Biochemical (prostate-specific antigen) recurrence of prostate cancer after radical prostatectomy remains a major problem. Better biomarkers are needed to identify high-risk patients. DNA methylation of promoter regions leads to gene silencing in many cancers. In this study, we assessed the effect of DNA methylation on the identification of recurrent prostate cancer. We studied the methylation status of 15 pre-specified genes using methylation-specific polymerase chain reaction on tissue samples from 151 patients with localized prostate cancer and at least 5 years of follow-up after prostatectomy. On multivariate logistic regression analysis, a high Gleason score and involvement of the capsule, lymph nodes, seminal vesicles, or surgical margin were associated with an increased risk of biochemical recurrence. Methylation of CDH13 by itself (odds ratio 5.50, 95% confidence interval [CI] 1.34 to 22.67; P = 0.02) or combined with methylation of ASC (odds ratio 5.64, 95% CI 1.47 to 21.7; P = 0.01) was also associated with an increased risk of biochemical recurrence. The presence of methylation of ASC and/or CDH13 yielded a sensitivity of 72.3% (95% CI 57% to 84.4%) and negative predictive value of 79% (95% CI 66.8% to 88.3%), similar to the weighted risk of recurrence (determined from the lymph node status, seminal vesicle status, surgical margin status, and postoperative Gleason score), a powerful clinicopathologic prognostic score. However, 34% (95% CI 21% to 49%) of the patients with recurrence were identified by the methylation profile of ASC and CDH13 rather than the weighted risk of recurrence. The results of our study have shown that methylation of CDH13 alone or combined with methylation of ASC is independently associated with an increased risk of biochemical recurrence after radical prostatectomy even considering the weighted risk of recurrence score. These findings should be validated in an independent, larger cohort of patients with prostate cancer who have undergone radical prostatectomy.

IMPACT OF STAGE MIGRATION AND PRACTICE CHANGES ON HIGH RISK PROSTATE CANCER: RESULTS FROM PATIENTS TREATED WITH RADICAL PROSTATECTOMY OVER THE LAST TWO DECADES

PubMed Central

Fossati, N.; Passoni, N. M.; Moschini, M.; Gandaglia, G.; Larcher, A.; Freschi, M.; Guazzoni, G.; Sjoberg, D. D.; Vickers, A. J.; Montorsi, F.; Briganti, A.

2016-01-01

Background Phenotype of prostate cancer at diagnosis has changed through the years. We aim to evaluate the impact of year of surgery on clinical, pathologic and oncologic outcomes of high-risk prostate cancer patients. Patients and methods We evaluated 1,033 clinically high-risk patients, defined as the presence of at least one of the following risk factors: pre-operative prostate specific antigen (PSA) level >20 ng/ml, and/or clinical stage ≥T3, and/or biopsy Gleason score ≥8. Patients were treated between 1990 and 2013 at a single Institution. Year-per-year trends of clinical and pathologic characteristics were examined. Multivariable Cox regression analysis was used to test the relationship between year of surgery and oncologic outcomes. Results We observed a decrease over time in the proportion of high-risk patients with a pre-operative PSA level >20 ng/ml or clinical stage cT3. An opposite trend was seen for biopsy Gleason score ≥8. We observed a considerable increase in the median number of lymph nodes removed that was associated with an increased rate of LNI. At multivariable Cox regression analysis, year of surgery was associated with a reduced risk of biochemical recurrence (HR per 5-year: 0.90; 95% CI: 0.84–0.96; p=0.01) and distant metastasis (HR per 5-year: 0.91; 95% CI: 0.83–0.99; p=0.039), after adjusting for age, pre-operative PSA, pathologic stage, lymph node invasion, surgical margin status, and pathological Gleason score. Conclusions In this single center study, an increased diagnosis of localized and less extensive high-grade prostate cancer was observed over the last two decades. High-risk patients selected for radical prostatectomy showed better cancer control over time. Better definitions of what constitutes high-risk prostate cancer among contemporary patients are needed. PMID:25787671

Technique of after-loading interstitial implants.

PubMed

Syed, A M; Feder, B H

1977-01-01

Interstitial implants are either removable or permanent (and occasionally a combination of both). Permanent implants are generally utilized where tumors are not accessible enough to permit easy removal of sources or where accurate source distribution is less critical. They are useful for cancers of the lung, pancreas, prostate, bladder, lymph nodes, etc. Radon and gold-198 have been largely replaced by iodine-125. Our major interests are in the removable after-loading iridium-192 implant techniques. Template (steel guide) and non-template (plastic tube) techniques are utilized. Templates are preferred where the tumor volume can only be approached from one side and where accurate positioning of sources would otherwise be difficult. They are useful for cancers of the cervix, vagina, urethra, and rectum. Non-template (plastic tube) techniques are preferred where the tumor volume can be approached from at least two sides and where templates are either not feasible or not essential for accurate positioning of sources. The single needle non-template approach is useful for cancers of lip, nodes, and breast (plastic button) and for cancers of the oral cavity and oropharynx (gold button). The paired needle non-template approach is useful for cancers of the gum, retromolar trigone, and base of tongue (loop technique) and for cancers of the palate (arch technique). Procedures for each technique are described in detail.

Treatment Outcomes from 68Ga-PSMA PET/CT-Informed Salvage Radiation Treatment in Men with Rising PSA After Radical Prostatectomy: Prognostic Value of a Negative PSMA PET.

PubMed

Emmett, Louise; van Leeuwen, Pim J; Nandurkar, Rohan; Scheltema, Matthijs J; Cusick, Thomas; Hruby, George; Kneebone, Andrew; Eade, Thomas; Fogarty, Gerald; Jagavkar, Raj; Nguyen, Quoc; Ho, Bao; Joshua, Anthony M; Stricker, Phillip

2017-12-01

68 Ga-PSMA (prostate-specific membrane antigen) PET/CT is increasingly used in men with prostate-specific antigen (PSA) failure after radical prostatectomy (RP) to triage those who will benefit from salvage radiation treatment (SRT). This study examines the value of PSMA-informed SRT in improving treatment outcomes in the context of biochemical failure after RP. Methods: We analyzed men with rising PSA after RP with PSA readings between 0.05 and 1.0 ng/mL, considered eligible for SRT at the time of PSMA. For each patient, clinical and pathologic features as well as scan results, including site of PSMA-positive disease, number of lesions, and a certainty score, were documented. Subsequent management, including SRT, and most recent PSA were recorded using medical records. Treatment response was defined as both PSA ≤ 0.1 ng/mL and >50% reduction in PSA. Multivariate logistic regression analysis was performed for association of clinical variables and treatment response to SRT. Results: One hundred sixty-four men were included. PSMA was positive in 62% ( n = 102/164): 38 of 102 in the prostatic fossa, 41 of 102 in pelvic nodes, and 23 of 102 distantly. Twenty-four patients received androgen-deprivation therapy (ADT) and were excluded for outcomes analysis. In total, 99 of 146 received SRT with a median follow-up after radiation treatment of 10.5 mo (interquartile range, 6-14 mo). Overall treatment response after SRT was 72% ( n = 71/99). Forty-five percent ( n = 27/60) of patients with a negative PSMA underwent SRT whereas 55% (33/60) did not. In men with a negative PSMA who received SRT, 85% ( n = 23/27) demonstrated a treatment response, compared with a further PSA increase in 65% (22/34) in those not treated. In 36 of 99 patients with disease confined to the prostate fossa on PSMA, 81% ( n = 29/36) responded to SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% ( n = 16/26) had treatment response after SRT. On multivariate logistic regression analysis, PSMA and serum PSA significantly correlated with treatment response, whereas pT stage, Gleason score, and surgical margin status did not. Conclusion: PSMA PET is independently predictive of treatment response to SRT and stratifies men into a high treatment response to SRT (negative or fossa-confined PSMA) versus men with poor response to SRT (nodes or distant-disease PSMA). In particular, a negative PSMA PET result predicts a high response to salvage fossa radiotherapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Value of PET/CT and MR Lymphography in Treatment of Prostate Cancer Patients With Lymph Node Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fortuin, Ansje S., E-mail: A.Fortuin@rad.umcn.nl; Deserno, Willem M.L.L.G.; Meijer, Hanneke J.M.

2012-11-01

Purpose: To determine the clinical value of two novel molecular imaging techniques: {sup 11}C-choline positron emission tomography (PET)/computed tomography (CT) and ferumoxtran-10 enhanced magnetic resonance imaging (magnetic resonance lymphography [MRL]) for lymph node (LN) treatment in prostate cancer (PCa) patients. Therefore, we evaluated the ability of PET/CT and MRL to assess the number, size, and location of LN metastases in patients with primary or recurrent PCa. Methods and Materials: A total of 29 patients underwent MRL and PET/CT for LN evaluation. The MRL and PET/CT data were analyzed independently. The number, size, and location of the LN metastases were determined.more » The location was described as within or outside the standard clinical target volume for elective pelvic irradiation as defined by the Radiation Therapy Oncology Group. Subsequently, the results from MRL and PET/CT were compared. Results: Of the 738 LNs visible on MRL, 151 were positive in 23 of 29 patients. Of the 132 LNs visible on PET/CT, 34 were positive in 13 of 29 patients. MRL detected significantly more positive LNs (p < 0.001) in more patients than PET/CT (p = 0.002). The mean diameter of the detected suspicious LNs on MRL was significantly smaller than those detected by PET/CT, 4.9 mm and 8.4 mm, respectively (p < 0.0001). In 14 (61%) of 23 patients, suspicious LNs were found outside the clinical target volume with MRL and in 4 (31%) of 13 patients with PET/CT. Conclusion: In patients with PCa, both molecular imaging techniques, MRL and {sup 11}C-choline PET/CT, can detect LNs suspicious for metastasis, irrespective of the existing size and shape criteria for CT and conventional magnetic resonance imaging. On MRL and PET/CT, 61% and 31% of the suspicious LNs were located outside the conventional clinical target volume. Therefore, these techniques could help to individualize treatment selection and enable image-guided radiotherapy for patients with PCa LN metastases.« less

Metabolomic signatures of aggressive prostate cancer.

PubMed

McDunn, Jonathan E; Li, Zhen; Adam, Klaus-Peter; Neri, Bruce P; Wolfert, Robert L; Milburn, Michael V; Lotan, Yair; Wheeler, Thomas M

2013-10-01

Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings. A state of the art metabolomics platform analyzed prostatectomy tissues (331 prostate tumor, 178 cancer-free prostate tissues) from two independent sites. Biochemicals were analyzed by gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-tandem mass spectrometry. Statistical analyses identified metabolites associated with cancer aggressiveness: Gleason score, extracapsular extension, and seminal vesicle and lymph node involvement. Prostate tumors had significantly altered metabolite profiles compared to cancer-free prostate tissues, including biochemicals associated with cell growth, energetics, stress, and loss of prostate-specific biochemistry. Many metabolites were further associated with clinical findings of aggressive disease. Aggressiveness-associated metabolites stratified prostate tumor tissues with high abundances of compounds associated with normal prostate function (e.g., citrate and polyamines) from more clinically advanced prostate tumors. These aggressive prostate tumors were further subdivided by abundance profiles of metabolites including NAD+ and kynurenine. When added to multiparametric nomograms, metabolites improved prediction of organ confinement (AUROC from 0.53 to 0.62) and 5-year recurrence (AUROC from 0.53 to 0.64). These findings support and extend earlier metabolomic studies in prostate cancer and studies where metabolic enzymes have been associated with carcinogenesis and/or outcome. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests. Copyright © 2013 Wiley Periodicals, Inc.

Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies.

PubMed

Hansel, D E; DeMarzo, A M; Platz, E A; Jadallah, S; Hicks, J; Epstein, J I; Partin, A W; Netto, G J

2007-05-01

Early prostate cancer antigen is a nuclear matrix protein that was recently shown to be expressed in prostate adenocarcinoma and adjacent benign tissue. Previous studies have demonstrated early prostate cancer antigen expression in benign prostate tissue up to 5 years before a diagnosis of prostate carcinoma, suggesting that early prostate cancer antigen could be used as a potential predictive marker. We evaluated early prostate cancer antigen expression by immunohistochemistry using a polyclonal antibody (Onconome Inc., Seattle, Washington) on benign biopsies from 98 patients. Biopsies were obtained from 4 groups that included 39 patients with first time negative biopsy (group 1), 24 patients with persistently negative biopsies (group 2), 8 patients with initially negative biopsies who were subsequently diagnosed with prostate carcinoma (group 3) and negative biopsies obtained from 27 cases where other concurrent biopsies contained prostate carcinoma (group 4). Early prostate cancer antigen staining was assessed by 2 of the authors who were blind to the group of the examined sections. Staining intensity (range 0 to 3) and extent (range 1 to 3) scores were assigned. The presence of intensity 3 staining in any of the blocks of a biopsy specimen was considered as positive for early prostate cancer antigen for the primary outcome in the statistical analysis. In addition, as secondary outcomes we evaluated the data using the proportion of blocks with intensity 3 early prostate cancer antigen staining, the mean of the product of staining intensity and staining extent of all blocks within a biopsy, and the mean of the product of intensity 3 staining and extent. Primary outcome analysis revealed the proportion of early prostate cancer antigen positivity to be highest in group 3 (6 of 8, 75%) and lowest in group 2 (7 of 24, 29%, p=0.04 for differences among groups). A relatively higher than expected proportion of early prostate cancer antigen positivity was present in group 1 (23 of 39, 59%). Early prostate cancer antigen was negative in 41% of group 4 who were known to harbor prostate carcinoma. The proportion of early prostate cancer antigen positivity was statistically significantly lower in group 2 than in each of the other groups when compared pairwise. A lower proportion of early prostate cancer antigen positivity was encountered in older archival tissue blocks (p<0.0001) pointing to a potential confounding factor. Corrected for block age, group 3 was the only group to remain statistically significantly different in early prostate cancer antigen positivity compared to the reference group 2. Similar findings were obtained when adjustments for patient age were made and when analysis was based on secondary outcome measurements. Our study showed a higher proportion of early prostate cancer antigen expression in initial negative prostate biopsy of patients who were diagnosed with prostate carcinoma on subsequent followup biopsies. We found a relatively high proportion of early prostate cancer antigen positivity (59%) in the group with first time negative biopsies and a potential 41% rate of false-negative early prostate cancer antigen staining in benign biopsies from cases with documented prostate carcinoma on concurrent cores. The lower early prostate cancer antigen positivity in cases with older blocks raises the question of a confounding effect of block age. Additional studies on the antigenic properties of early prostate cancer antigen in archival material are required to further delineate the usefulness of early prostate cancer antigen immunostaining on biopsy material.

Pilot Comparison of ⁶⁸Ga-RM2 PET and ⁶⁸Ga-PSMA-11 PET in Patients with Biochemically Recurrent Prostate Cancer.

PubMed

Minamimoto, Ryogo; Hancock, Steven; Schneider, Bernadette; Chin, Frederick T; Jamali, Mehran; Loening, Andreas; Vasanawala, Shreyas; Gambhir, Sanjiv Sam; Iagaru, Andrei

2016-04-01

Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA-11) is a PET tracer that can detect prostate cancer relapses and metastases by binding to the extracellular domain of PSMA. (68)Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 ((68)Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptors. We present pilot data on the biodistribution of these PET tracers in a small cohort of patients with biochemically recurrent prostate cancer. Seven men (mean age ± SD, 74.3 ± 5.9 y) with biochemically recurrent prostate cancer underwent both (68)Ga-PSMA-11 PET/CT and (68)Ga-RM2 PET/MRI scans. SUVmax and SUVmean were recorded for normal tissues and areas of uptake outside the expected physiologic biodistribution. All patients had a rising level of prostate-specific antigen (mean ± SD, 13.5 ± 11.5) and noncontributory results on conventional imaging. (68)Ga-PSMA-11 had the highest physiologic uptake in the salivary glands and small bowel, with hepatobiliary and renal clearance noted, whereas (68)Ga-RM2 had the highest physiologic uptake in the pancreas, with renal clearance noted. Uptake outside the expected physiologic biodistribution did not significantly differ between (68)Ga-PSMA-11 and (68)Ga-RM2; however, (68)Ga-PSMA-11 localized in a lymph node and seminal vesicle in a patient with no abnormal (68)Ga-RM2 uptake. Abdominal periaortic lymph nodes were more easily visualized by(68)Ga-RM2 in two patients because of lack of interference by radioactivity in the small intestine. (68)Ga-PSMA-11 and (68)Ga-RM2 had distinct biodistributions in this small cohort of patients with biochemically recurrent prostate cancer. Additional work is needed to understand the expression of PSMA and gastrin-releasing peptide receptors in different types of prostate cancer. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Agent Orange and long-term outcomes after radical prostatectomy.

PubMed

Ovadia, Aaron E; Terris, Martha K; Aronson, William J; Kane, Christopher J; Amling, Christopher L; Cooperberg, Matthew R; Freedland, Stephen J; Abern, Michael R

2015-07-01

To investigate the association between Agent Orange (AO) exposure and long-term prostate cancer (PC) outcomes. Data from 1,882 men undergoing radical prostatectomy for PC between 1988 and 2011 at Veterans Affairs Health Care Facilities were analyzed from the Shared Equal Access Regional Cancer Hospital database. Men were stratified by AO exposure (binary). Associations between AO exposure and biopsy and pathologic Gleason sum (GS) and pathologic stage were determined by logistic regression models adjusted for preoperative characteristics. Hazard ratios for biochemical recurrence (BCR), secondary treatment, metastases, and PC-specific mortality were determined by Cox models adjusted for preoperative characteristics. There were 333 (17.7%) men with AO exposure. AO-exposed men were younger (median 59 vs. 62 y), had lower preoperative prostate-specific antigen levels (5.8 vs. 6.7 ng/ml), lower clinical category (25% vs. 38% palpable), and higher body mass index (28.2 vs. 27.6 kg/m(2)), all P<0.01. Biopsy GS, pathologic GS, positive surgical margins, lymph node positivity, and extracapsular extension did not differ with AO exposure. At a median follow-up of 85 months, 702 (37.4%) patients had BCR, 603 (32.2%) patients received secondary treatment, 78 (4.1%) had metastases, and 39 (2.1%) died of PC. On multivariable analysis, AO exposure was not associated with BCR, secondary treatment, metastases, or PC mortality. AO exposure was not associated with worse preoperative characteristics such as elevated prostate-specific antigen levels or biopsy GS nor with BCR, secondary treatment, metastases, or PC death. Thus, as data on AO-exposed men mature, possible differences in PC outcomes observed previously are no longer apparent. Copyright © 2015 Elsevier Inc. All rights reserved.

18F-choline PET/MRI in suspected recurrence of prostate carcinoma.

PubMed

Riola-Parada, C; Carreras-Delgado, J L; Pérez-Dueñas, V; Garcerant-Tafur, M; García-Cañamaque, L

2018-05-21

To evaluate the usefulness of simultaneous 18 F-choline PET/MRI in the suspicion of prostate cancer recurrence and to relate 18 F-choline PET/MRI detection rate with analytical and pathological variables. 27 patients with prostate cancer who received local therapy as primary treatment underwent a 18 F-choline PET/MRI due to suspicion of recurrence (persistently rising serum PSA level). 18 F-choline PET/MRI findings were validated by anatomopathological analysis, other imaging tests or by biochemical response to oncological treatment. 18 F-choline PET/MRI detected disease in 15 of 27 patients (detection rate 55.56%). 4 (15%) presented exclusively local recurrence, 5 (18%) lymph node metastases and 7 (26%) bone metastases. Mean PSA (PSA med ) at study time was 2.94ng/mL (range 0.18-10ng/mL). PSA med in patients with positive PET/MRI was 3.70ng/mL (range 0.24-10ng/mL), higher than in patients with negative PET/MRI, PSA med 1.97ng/mL (range 0.18-4.38ng/mL), although without statistically significant differences. Gleason score at diagnosis in patients with a positive study was 7.33 (range 6-9) and in patients with a negative study was 7 (range 6-9), without statistically significant differences. 18 F-choline PET/MRI detection rate was considerable despite the relatively low PSA values in our sample. The influence of Gleason score and PSA level on 18 F-choline PET/MRI detection rate was not statistically significant. Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.

An image-guided radiotherapy decision support framework incorporating a Bayesian network and visualization tool.

PubMed

Hargrave, Catriona; Deegan, Timothy; Bednarz, Tomasz; Poulsen, Michael; Harden, Fiona; Mengersen, Kerrie

2018-05-17

To describe a Bayesian network (BN) and complementary visualization tool that aim to support decision-making during online cone-beam computed tomography (CBCT)-based image-guided radiotherapy (IGRT) for prostate cancer patients. The BN was created to represent relationships between observed prostate, proximal seminal vesicle (PSV), bladder and rectum volume variations, an image feature alignment score (FAS TV _ OAR ), delivered dose, and treatment plan compliance (TPC). Variables influencing tumor volume (TV) targeting accuracy such as intrafraction motion, and contouring and couch shift errors were also represented. A score of overall TPC (FAS global ) and factors such as image quality were used to inform the BN output node providing advice about proceeding with treatment. The BN was quantified using conditional probabilities generated from published studies, FAS TV _ OAR /global modeling, and a survey of IGRT decision-making practices. A new IGRT visualization tool (IGRT REV ), in the form of Mollweide projection plots, was developed to provide a global summary of residual errors after online CBCT-planning CT registration. Sensitivity and scenario analyses were undertaken to evaluate the performance of the BN and the relative influence of the network variables on TPC and the decision to proceed with treatment. The IGRT REV plots were evaluated in conjunction with the BN scenario testing, using additional test data generated from retrospective CBCT-planning CT soft-tissue registrations for 13/36 patients whose data were used in the FAS TV _ OAR /global modeling. Modeling of the TV targeting errors resulted in a very low probability of corrected distances between the CBCT and planning CT prostate or PSV volumes being within their thresholds. Strength of influence evaluation with and without the BN TV targeting error nodes indicated that rectum- and bladder-related network variables had the highest relative importance. When the TV targeting error nodes were excluded from the BN, TPC was sensitive to observed PSV and rectum variations while the decision to treat was sensitive to observed prostate and PSV variations. When root nodes were set so the PSV and rectum variations exceeded thresholds, the probability of low TPC increased to 40%. Prostate and PSV variations exceeding thresholds increased the likelihood of repositioning or repeating patient preparation to 43%. Scenario testing using the test data from 13 patients, demonstrated two cases where the BN provided increased high TPC probabilities, despite some of the prostate and PSV volume variation metrics not being within tolerance. The IGRT REV tool was effective in highlighting and quantifying where TV and OAR variations occurred, supporting the BN recommendation to reposition the patient or repeat their bladder and bowel preparation. In another case, the IGRT REV tool was also effective in highlighting where PSV volume variation significantly exceeded tolerance when the BN had indicated to proceed with treatment. This study has demonstrated that both the BN and IGRT REV plots are effective tools for inclusion in a decision support system for online CBCT-based IGRT for prostate cancer patients. Alternate approaches to modeling TV targeting errors need to be explored as well as extension of the BN to support offline IGRT decisions related to adaptive radiotherapy. © 2018 American Association of Physicists in Medicine.

The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer.

PubMed

Thompson, J E; van Leeuwen, P J; Moses, D; Shnier, R; Brenner, P; Delprado, W; Pulbrook, M; Böhm, M; Haynes, A M; Hayen, A; Stricker, P D

2016-05-01

We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific antigen/digital rectal examination. A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of individual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 [2.9%]), and the significant prostate cancer area in the radical prostatectomy specimen (3 [3.3%]). In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A three-dimensional definition of nodal spaces on the basis of CT images showing enlarged nodes for pelvic radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Portaluri, Maurizio; Bambace, Santa; Perez, Celeste

2005-11-15

Purpose: To demonstrate that margins of each pelvic chain may be derived by verifying the bony and soft tissue structures around abnormal nodes on computed tomography (CT) slices. Methods and Materials: Twenty consecutive patients (16 males, 4 females; mean age, 66 years; range, 43-80 years) with radiologic diagnosis of nodal involvement by histologically proved cervix carcinoma (two), rectum carcinoma (three), prostate carcinoma (four), lymphoma (five), penis carcinoma (one), corpus uteri carcinoma (one), bladder carcinoma (two), cutis tumor (one), and soft-tissue sarcoma (one) were retrospectively reviewed. One hundred CT scans showing 85 enlarged pelvic nodes were reviewed by two radiation oncologistsmore » (M.P., S.B.), and two radiologists (C.P., G.A.). Results: The more proximal structures to each enlarged node or group of nodes were thus recorded in a clockwise direction. Conclusion: According to their frequency and visibility, craniocaudal, anterior, lateral, posterior and medial margins of common iliac, external and internal iliac nodal chains, obturator and pudendal nodes, and deep and superficial inguinal nodes were derived from CT observations.« less

Radiobiologically optimized couch shift: A new localization paradigm using cone-beam CT for prostate radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Yimei, E-mail: yhuang2@hfhs.org; Gardner, Stephen J.; Wen, Ning

2015-10-15

Purpose: To present a novel positioning strategy which optimizes radiation delivery by utilizing radiobiological response knowledge and evaluate its use during prostate external beam radiotherapy. Methods: Five patients with low or intermediate risk prostate cancer were evaluated retrospectively in this IRB-approved study. For each patient, a VMAT plan with one 358° arc was generated on the planning CT (PCT) to deliver 78 Gy in 39 fractions. Five representative pretreatment cone beam CTs (CBCT) were selected for each patient. The CBCT images were registered to PCT by a human observer, which consisted of an initial automated registration with three degrees-of-freedom, followedmore » by manual adjustment for agreement at the prostate/rectal wall interface. To determine the optimal treatment position for each CBCT, a search was performed centering on the observer-matched position (OM-position) utilizing a score function based on radiobiological and dosimetric indices (EUD{sub prostate}, D99{sub prostate}, NTCP{sub rectum}, and NTCP{sub bladder}) for the prostate, rectum, and bladder. We termed the optimal treatment position the radiobiologically optimized couch shift position (ROCS-position). Results: The dosimetric indices, averaged over the five patients’ treatment plans, were (mean ± SD) 79.5 ± 0.3 Gy (EUD{sub prostate}), 78.2 ± 0.4 Gy (D99{sub prostate}), 11.1% ± 2.7% (NTCP{sub rectum}), and 46.9% ± 7.6% (NTCP{sub bladder}). The corresponding values from CBCT at the OM-positions were 79.5 ± 0.6 Gy (EUD{sub prostate}), 77.8 ± 0.7 Gy (D99{sub prostate}), 12.1% ± 5.6% (NTCP{sub rectum}), and 51.6% ± 15.2% (NTCP{sub bladder}), respectively. In comparison, from CBCT at the ROCS-positions, the dosimetric indices were 79.5 ± 0.6 Gy (EUD{sub prostate}), 77.3 ± 0.6 Gy (D99{sub prostate}), 8.0% ± 3.3% (NTCP{sub rectum}), and 46.9% ± 15.7% (NTCP{sub bladder}). Excessive NTCP{sub rectum} was observed on Patient 5 (19.5% ± 6.6%) corresponding to localization at OM-position, compared to the planned value of 11.7%. This was mitigated with radiobiologically optimized localization, resulting in a reduced NTCP{sub rectum} value of 11.3% ± 3.5%. Overall, the treatment position optimization resulted in similar target dose coverage with reduced risk to rectum. Conclusions: These encouraging results illustrate the potential advantage of applying radiobiologically optimized correction for online image-guided radiotherapy of prostate patients.« less

Effect of endorectal balloon positioning errors on target deformation and dosimetric quality during prostate SBRT

NASA Astrophysics Data System (ADS)

Jones, Bernard L.; Gan, Gregory; Kavanagh, Brian; Miften, Moyed

2013-11-01

An inflatable endorectal balloon (ERB) is often used during stereotactic body radiation therapy (SBRT) for treatment of prostate cancer in order to reduce both intrafraction motion of the target and risk of rectal toxicity. However, the ERB can exert significant force on the prostate, and this work assessed the impact of ERB position errors on deformation of the prostate and treatment dose metrics. Seventy-one cone-beam computed tomography (CBCT) image datasets of nine patients with clinical stage T1cN0M0 prostate cancer were studied. An ERB (Flexi-Cuff, EZ-EM, Westbury, NY) inflated with 60 cm3 of air was used during simulation and treatment, and daily kilovoltage (kV) CBCT imaging was performed to localize the prostate. The shape of the ERB in each CBCT was analyzed to determine errors in position, size, and shape. A deformable registration algorithm was used to track the dose received by (and deformation of) the prostate, and dosimetric values such as D95, PTV coverage, and Dice coefficient for the prostate were calculated. The average balloon position error was 0.5 cm in the inferior direction, with errors ranging from 2 cm inferiorly to 1 cm superiorly. The prostate was deformed primarily in the AP direction, and tilted primarily in the anterior-posterior/superior-inferior plane. A significant correlation was seen between errors in depth of ERB insertion (DOI) and mean voxel-wise deformation, prostate tilt, Dice coefficient, and planning-to-treatment prostate inter-surface distance (p < 0.001). Dosimetrically, DOI is negatively correlated with prostate D95 and PTV coverage (p < 0.001). For the model of ERB studied, error in ERB position can cause deformations in the prostate that negatively affect treatment, and this additional aspect of setup error should be considered when ERBs are used for prostate SBRT. Before treatment, the ERB position should be verified, and the ERB should be adjusted if the error is observed to exceed tolerable values.

Elastomeric negative acoustic contrast particles for affinity capture assays.

PubMed

Cushing, Kevin W; Piyasena, Menake E; Carroll, Nick J; Maestas, Gian C; López, Beth Ann; Edwards, Bruce S; Graves, Steven W; López, Gabriel P

2013-02-19

This report describes the development of elastomeric capture microparticles (ECμPs) and their use with acoustophoretic separation to perform microparticle assays via flow cytometry.We have developed simple methods to form ECμPs by cross-linking droplets of common commercially available silicone precursors in suspension followed by surface functionalization with biomolecular recognition reagents. The ECμPs are compressible particles that exhibit negative acoustic contrast in ultrasound when suspended in aqueous media, blood serum, or diluted blood. In this study, these particles have been functionalized with antibodies to bind prostate specific antigen and immunoglobulin (IgG). Specific separation of the ECμPs from blood cells is achieved by flowing them through a microfluidic acoustophoretic device that uses an ultrasonic standing wave to align the blood cells, which exhibit positive acoustic contrast, at a node in the acoustic pressure distribution while aligning the negative acoustic contrast ECμPs at the antinodes. Laminar flow of the separated particles to downstream collection ports allows for collection of the separated negative contrast (ECμPs) and positive contrast particles (cells). Separated ECμPs were analyzed via flow cytometry to demonstrate nanomolar detection for prostate specific antigen in aqueous buffer and picomolar detection for IgG in plasma and diluted blood samples. This approach has potential applications in the development of rapid assays that detect the presence of low concentrations of biomarkers in a number of biological sample types.

Elastomeric Negative Acoustic Contrast Particles for Affinity Capture Assays

PubMed Central

Cushing, Kevin W.; Piyasena, Menake E.; Carroll, Nick J.; Maestas, Gian C.; López, Beth Ann; Edwards, Bruce S.; Graves, Steven W.; López, Gabriel P.

2013-01-01

This report describes the development of elastomeric capture microparticles (ECμPs) and their use with acoustophoretic separation to perform microparticle assays via flow cytometry. We have developed simple methods to form ECμPsby crosslinking droplets of common commercially available silicone precursors in suspension followed by surface functionalization with biomolecular recognition reagents. The ECμPs are compressible particles that exhibit negative acoustic contrast in ultrasound when suspended in aqueous media, blood serum or diluted blood. In this study, these particles have been functionalized with antibodies to bind prostate specific antigen and immunoglobulin (IgG). Specific separation of the ECμPs from blood cells is achieved by flowing them through a microfluidic acoustophoretic device that uses an ultrasonic standing wave to align the blood cells, which exhibit positive acoustic contrast, at a node in the acoustic pressure distribution while aligning the negative acoustic contrast ECμPs at the antinodes. Laminar flow of the separated particles to downstream collection ports allows for collection of the separated negative contrast (ECμPs) and positive contrast particles (cells). Separated ECμPs were analyzed via flow cytometry to demonstrate nanomolar detection for prostate specific antigen in aqueous buffer and picomolar detection for IgG in plasma and diluted blood samples. This approach has potential applications in the development of rapid assays that detect the presence of low concentrations of biomarkers in a number of biological sample types. PMID:23331264

Comparison of hybrid (68)Ga-PSMA PET/MRI and (68)Ga-PSMA PET/CT in the evaluation of lymph node and bone metastases of prostate cancer.

PubMed

Freitag, Martin T; Radtke, Jan P; Hadaschik, Boris A; Kopp-Schneider, A; Eder, Matthias; Kopka, Klaus; Haberkorn, Uwe; Roethke, Matthias; Schlemmer, Heinz-Peter; Afshar-Oromieh, Ali

2016-01-01

To evaluate the reproducibility of the combination of hybrid PET/MRI and the (68)Ga-PSMA-11 tracer in depicting lymph node (LN) and bone metastases of prostate cancer (PC) in comparison with that of PET/CT. A retrospective analysis of 26 patients who were subjected to (68)Ga-PSMA PET/CTlow-dose (1 h after injection) followed by PET/MRI (3 h after injection) was performed. MRI sequences included T1-w native, T1-w contrast-enhanced, T2-w fat-saturated and diffusion-weighted sequences (DWIb800). Discordant PET-positive and morphological findings were evaluated. Standardized uptake values (SUV) of PET-positive LNs and bone lesions were quantified and their morphological size and conspicuity determined. Comparing the PET components, the proportion of discordant PSMA-positive suspicious findings was very low (98.5 % of 64 LNs concordant, 100 % of 28 bone lesions concordant). Two PET-positive bone metastases could not be confirmed morphologically using CTlow-dose, but could be confirmed using MRI. In 12 of 20 patients, 47 PET-positive LNs (71.9 %) were smaller than 1 cm in short axis diameter. There were significant linear correlations between PET/MRI SUVs and PET/CT SUVs in the 64 LN metastases (p < 0.0001) and in the 28 osseous metastases (p < 0.0001) for SUVmean and SUVmax, respectively. The LN SUVs were significantly higher on PET/MRI than on PET/CT (p SUVmax < 0.0001; p SUVmean < 0.0001) but there was no significant difference between the bone lesion SUVs (p SUVmax = 0.495; p SUVmean = 0.381). Visibility of LNs was significantly higher on MRI using the T1-w contrast-enhanced fat-saturated sequence (p = 0.013), the T2-w fat-saturated sequence (p < 0.0001) and the DWI sequence (p < 0.0001) compared with CTlow-dose. For bone lesions, only the overall conspicuity was higher on MRI compared with CTlow-dose (p < 0.006). Nodal and osseous metastases of PC are accurately and reliably depicted by hybrid PET/MRI using (68)Ga-PSMA-11 with very low discordance compared with PET/CT including PET-positive LNs of normal size. The correlation between PET/MRI SUVs and PET/CT SUVs was linear in LN and bone metastases but was significantly lower in control (non-metastatic) tissue.

99m Tc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer.

PubMed

Schmidkonz, Christian; Hollweg, Claudia; Beck, Michael; Reinfelder, Julia; Goetz, Theresa I; Sanders, James C; Schmidt, Daniela; Prante, Olaf; Bäuerle, Tobias; Cavallaro, Alexander; Uder, Michael; Wullich, Bernd; Goebell, Peter; Kuwert, Torsten; Ritt, Philipp

2018-01-01

99m Tc-MIP-1404 (Progenics Pharmaceuticals, Inc., New York, NY) is a novel, SPECT-compatible 99m Tc-labeled PSMA inhibitor for the detection of prostate cancer. We present results of its clinical use in a cohort of 225 men with histologically confirmed prostate cancer referred for workup of biochemical relapse. From April 2013 to April 2017, 99m Tc-MIP1404-scintigraphy was performed in 225 patients for workup of PSA biochemical relapse of prostate cancer. Whole-body planar and SPECT/CT images of the lower abdomen and thorax were obtained 3-4 h p.i. of 710 ± 64 MBq 99m Tc-MIP-1404. Images were visually analyzed for presence and location of abnormal uptake. In addition, quantitative analysis of the SPECT/CT data was carried out on a subset of 125 patients. Follow-up reports of subsequent therapeutic interventions were available for 59% (139) of all patients. Tracer-positive lesions were detected in 77% (174/225) of all patients. Detections occurred at the area of local recurrence in the prostate in 25% of patients (or a total of 56), with metastases in lymph nodes in 47% (105), bone in 27% (60), lung in 5% (12), and other locations in 2% (4) of patients. Detection rates were 90% at PSA levels ≥2 ng/mL and 54% below that threshold. Lesional SUVmax values were, on average, 32.2 ± 29.6 (0.8-142.2), and tumor-to-normal ratios 146.6 ± 160.5 (1.9-1482.4). The PSA level correlated significantly with total uptake of MIP-1404 in tumors (P < 0.001). Furthermore, total tumor uptake was significantly higher in patients with Gleason scores ≥8 compared to those with Gleason scores ≤7 (P < 0.05). In patients with androgen deprivation therapy, the detection rate was significantly higher compared to patients without androgen deprivation therapy (86% vs 71%, P < 0.001). Based on 99m Tc-MIP-1404-imaging and other information, an interdisciplinary tumor board review recommended changes to treatment plans in 74% (104/139) of those patients for whom the necessary documentation was available. SPECT/CT with 99m Tc-labeled MIP-1404 has a high probability in detecting PSMA-positive lesions in patients with elevated PSA. Statistical analysis disclosed significant relationship between quantitative 99m Tc-MIP-1404 uptake, PSA level, and Gleason score. © 2017 Wiley Periodicals, Inc.

Robotic radical prostatectomy in patients with high-risk disease: a review of short-term outcomes from a high-volume center.

PubMed

Jayram, Gautam; Decastro, Guarionex J; Large, Michael C; Razmaria, Aria; Zagaja, Gregory P; Shalhav, Arieh L; Brendler, Charles B

2011-03-01

Patients with high-risk prostate cancer have historically been treated with multimodal therapy and considered poor candidates for minimally invasive surgery. We reviewed our experiences with robot-assisted radical prostatectomy (RARP) in patients with high-risk clinical features. Clinical database review identified high-risk patients undergoing RARP by two high-volume robotic surgeons. D'Amico's criteria for high-risk prostate cancer were utilized: prostate-specific antigen ≥ 20 ng/mL, clinical stage ≥ T2c, or preoperative Gleason grade ≥ 8. About 148 patients were identified in the study group. Mean age at surgery was 60.9 years, and mean body mass index was 27.9. Mean estimated blood loss was 150 cc and the transfusion rate was 2.7%. Median hospital stay was 1 day and the rate of major complications (Clavien grade ≥ 3) was 3.4%. Bilateral nerve preservation was feasible in 28.4%, and the rate of positive surgical margins was 20.9%. Final pathology demonstrated extra-capsular disease in 54.1% of patients and 12.3% had lymph node involvement. At 2 years of follow-up, 21.3% of patients had experienced biochemical recurrence or had persistent disease after treatment. Continence was 91.2% (1 pad or less) and total impotence (inability to masturbate) was 48.3%. RARP does not compromise oncologic or functional outcomes in patients with high-risk prostate cancer. Although long-term study is necessary to validate oncologic and functional outcomes, our data suggest that the presence of high-risk disease is not a contraindication to a minimally invasive approach for radical prostatectomy at experienced centers.

Phase 1 trial of neoadjuvant radiation therapy before prostatectomy for high-risk prostate cancer.

PubMed

Koontz, Bridget F; Quaranta, Brian P; Pura, John A; Lee, W R; Vujaskovic, Zeljko; Gerber, Leah; Haake, Michael; Anscher, Mitchell S; Robertson, Cary N; Polascik, Thomas J; Moul, Judd W

2013-09-01

To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Validation of the prognostic grouping of the seventh edition of the tumor-nodes-metastasis classification using a large-scale prospective cohort study database of prostate cancer treated with primary androgen deprivation therapy.

PubMed

Kimura, Tomokazu; Onozawa, Mizuki; Miyazaki, Jun; Kawai, Koji; Nishiyama, Hiroyuki; Hinotsu, Shiro; Akaza, Hideyuki

2013-09-01

In the TNM seventh edition, a prognostic grouping for prostate cancer incorporating prostate-specific antigen and Gleason score was advocated. The present study was carried out to evaluate and validate prognostic grouping in prostate cancer patients. The 15 259 study patients treated with primary androgen deprivation therapy were enrolled in the Japan Study Group of Prostate Cancer. Overall survival was stratified by tumor-nodes-metastasis, Gleason score and prostate-specific antigen, and extensively analyzed. The accuracy of grouping systems was evaluated by the concordance index. The 5-year overall survival in prognostic grouping-I, IIA, IIB, III and IV was 90.0%, 88.3%, 84.8%, 80.6% and 57.1%, respectively. When considering subgroup stratification, the 5-year overall survival of subgroups prognostic grouping-IIA, IIB, III and IV was 80.9∼90.5%, 75.4∼91.8%, 75.7∼89.0% and 46.9∼86.2%, respectively. When prognostic grouping-IIB was subclassified into IIB1 (except IIB2) and IIB2 (T1-2b, prostate-specific antigen >20, Gleason score ≥8, and T2c, Gleason score ≥8), the 5-year overall survival of IIB2 was significantly lower than that of IIB1 (79.4% and 87.3%, P < 0.0001). Also, when prognostic grouping-IV was subclassified into IV1 (except IV2) and IV2 (M1, prostate-specific antigen >100 or Gleason score ≥8), the 5-year overall survival of prognostic grouping-IV1 was superior to that of IV2 (72.9% and 49.5%, P < 0.0001). Prognostic groupings were reclassified into modified prognostic groupings, divided into modified prognostic grouping-A (prognostic grouping-I, IIA, and IIB1), modified prognostic grouping-B (prognostic grouping-IIB2 and III), modified prognostic grouping-C (prognostic grouping-IV1) and modified prognostic grouping-D (prognostic grouping-IV2). The concordance index of prognostic grouping and modified prognostic grouping for overall survival was 0.670 and 0.685, respectively. Prognostic grouping could stratify the prognosis of prostate cancer patients. However, there is considerable variation among the prognostic grouping subgroups. Thus, the use of a modified prognostic grouping for patients treated with primary androgen deprivation therapy is advisable. © 2013 The Japanese Urological Association.

Surface-based prostate registration with biomechanical regularization

NASA Astrophysics Data System (ADS)

van de Ven, Wendy J. M.; Hu, Yipeng; Barentsz, Jelle O.; Karssemeijer, Nico; Barratt, Dean; Huisman, Henkjan J.

2013-03-01

Adding MR-derived information to standard transrectal ultrasound (TRUS) images for guiding prostate biopsy is of substantial clinical interest. A tumor visible on MR images can be projected on ultrasound by using MRUS registration. A common approach is to use surface-based registration. We hypothesize that biomechanical modeling will better control deformation inside the prostate than a regular surface-based registration method. We developed a novel method by extending a surface-based registration with finite element (FE) simulation to better predict internal deformation of the prostate. For each of six patients, a tetrahedral mesh was constructed from the manual prostate segmentation. Next, the internal prostate deformation was simulated using the derived radial surface displacement as boundary condition. The deformation field within the gland was calculated using the predicted FE node displacements and thin-plate spline interpolation. We tested our method on MR guided MR biopsy imaging data, as landmarks can easily be identified on MR images. For evaluation of the registration accuracy we used 45 anatomical landmarks located in all regions of the prostate. Our results show that the median target registration error of a surface-based registration with biomechanical regularization is 1.88 mm, which is significantly different from 2.61 mm without biomechanical regularization. We can conclude that biomechanical FE modeling has the potential to improve the accuracy of multimodal prostate registration when comparing it to regular surface-based registration.

Risk stratification and staging in prostate cancer with prostatic specific membrane antigen PET/CTObjective: A one-stop-shop.

PubMed

Gupta, Manoj; Choudhury, Partha Sarathi; Rawal, Sudhir; Goel, Harish Chandra; Singh, Amitabh; Talwar, Vineet; Sahoo, Saroj Kumar

2017-01-01

Current imaging modalities for prostate cancer (PC) had limitations for risk stratification and staging. Magnetic resonance imaging (MRI) frequently underestimated lymphatic metastasis while bone scintigraphy often had diagnostic dilemmas. Prostatic specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) has been remarkable in diagnosing PC recurrence and staging. We hypothesized it can become one-stop-shop for initial risk stratification and staging. Ninety seven PSMA PET-CT studies were re analysed for tumor node metastases (TNM) staging and risk stratification of lymphatic and distant metastases proportion. The histopathology of 23/97 patients was available as gold standard. Chi-square test was used for proportion comparison. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), over-estimation, under-estimation and correct-estimation of T and N stages were calculated. Cohen's kappa coefficient (k) was derived for inter-rater agreement. Lymphic or distant metastases detection on PSMA PET/CT increased significantly with increase in risk category. PSMA PET/CT sensitivity, specificity, PPV and NPV for extra prostatic extension (EPE), seminal vesicle invasion (SVI) and lymphatic metastases were 63.16%, 100%, 100%, 36.36% & 55%, 100%, 100%, 25% and 65.62%, 99.31%, 87.50%, 97.53%, respectively. Cohen's kappa coefficient showed substantial agreement between PSMA PET/CT and histopathological lymphic metastases (κ 0.734) however, it was just in fair agreement (κ 0.277) with T stage. PSMA PET/CT over-estimated, under-estimated and correct-estimated T and N stages in 8.71%, 39.13%, 52.17% and 8.71%, 4.35%, 86.96% cases, respectively. We found that PSMA PET/CT has potential for initial risk stratifications with reasonable correct estimation for N stage. However, it can underestimate T stage. Hence, we suggest that PSMA PET/CT should be used for staging and initial risk stratification of PC as one-stop-shop with regional MRI in surgically resectable cases.

Extraprostatic Extension Is Extremely Rare for Contemporary Gleason Score 6 Prostate Cancer.

PubMed

Anderson, Blake B; Oberlin, Daniel T; Razmaria, Aria A; Choy, Bonnie; Zagaja, Gregory P; Shalhav, Arieh L; Meeks, Joshua J; Yang, Ximing J; Paner, Gladell P; Eggener, Scott E

2017-09-01

A significant proportion of men with Gleason score 6 (GS6) prostate cancer undergo treatment with radiation or surgery. To assess pathologic stage of pure GS6 at radical prostatectomy (RP). In the period 2003-2014, 7817 patients underwent RP at two institutions. Of 2502 patients with GS6 at surgery, 60 were identified as stage pT3a-b on initial pathologic review, 55 with pT3a (extraprostatic extension, EPE), and five with pT3b (seminal vesicle invasion; SVI). All cases of GS6 with pT3 disease underwent contemporary pathologic evaluation for Gleason grade, stage, and extent of EPE. At one institution, all GS≥7 pT3b cases were re-reviewed for downgrading. The 2014 International Society of Urological Pathology (ISUP) Gleason grading criteria and 2009 ISUP recommendations on pT3 staging were applied. Calculated incidence (%) of pT3a, pT3b, pT4, and lymph node-positive disease. Of the 60 GS6 pT3a-b cases identified in the period 2003-2014, seven (0.28% of entire GS6 cohort) with GS6 and pT3a were identified after re-review, all focal EPE. Among the re-examined cohort, no cases of GS6 with pT3b were observed. None of the 132 GS≥7 pT3b cases were downgraded to GS6. Limitations include partial embedding of specimens and separate pathologic review at each institution. In a large prostatectomy cohort, GS6 never had seminal vesicle invasion (0%) and was very rarely (0.28%) associated with extraprostatic extension. GS6 prostate cancer rarely spreads outside the prostate. A new finding in this study was that GS6 prostate cancer never spread to the seminal vesicles. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Inhibitory effect of amiloride on the urokinase plasminogen activators in prostatic cancer.

PubMed

Ray, P; Bhatti, R; Gadarowski, J; Bell, N; Nasruddin, S

1998-01-01

The diuretic drug amiloride (AMLD), which competitively inhibits the catalytic activity of urokinase plasminogen activators (UPA), was used to study its effects on the proteolytic enzymes implicated in the invasiveness and metastases in a prostatic tumor model carrying two different sublines of adenocarcinoma of the prostate. Our data showed that UPA activity was significantly higher, both in the cytosol and pellet of R3327-AT3, a fast-growing highly metastatic and androgen-insensitive tumor, as compared to the G3327-G subline, a slow-growing nonmetastatic tumor of the prostate. The UPA activity in AT3 tumor dropped when the rats were treated with AMLD for 3 weeks. The UPA activity in the sera and tumor effusions from rats with AT3 tumor was significantly higher as compared to those with G subline tumor. The number of pulmonary metastatic foci was the same in untreated rats as compared to those treated with AMLD. The lymph node inspection after 3 weeks revealed no secondary tumor in the AMLD-treated group. The role of UPA in the metastases of prostate cancer is discussed.

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer.

PubMed

Evans, Christopher P; Higano, Celestia S; Keane, Thomas; Andriole, Gerald; Saad, Fred; Iversen, Peter; Miller, Kurt; Kim, Choung-Soo; Kimura, Go; Armstrong, Andrew J; Sternberg, Cora N; Loriot, Yohann; de Bono, Johann; Noonberg, Sarah B; Mansbach, Hank; Bhattacharya, Suman; Perabo, Frank; Beer, Tomasz M; Tombal, Bertrand

2016-10-01

Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naïve metastatic castration-resistant prostate cancer. To assess the effects of enzalutamide versus placebo in patients from PREVAIL based on site and extent of baseline disease. One thousand seven hundred and seventeen asymptomatic or minimally symptomatic patients were randomized to enzalutamide (n=872) or placebo (n=845). Subgroup analyses included nonvisceral (only bone and/or nodal; n=1513), visceral (lung and/or liver; n=204), low-volume bone disease (<4 bone metastases; n=867), high-volume bone disease (≥4 bone metastases; n=850), lymph node only disease (n=195). Oral enzalutamide (160mg) or placebo once daily while continuing androgen deprivation therapy. Coprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc. Enzalutamide improved rPFS versus placebo in patients with nonvisceral disease (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.14-0.22), visceral disease (HR, 0.28; 95% CI, 0.16-0.49), low- or high-volume bone disease (HR, 0.16; 95% CI, 0.11-0.22; HR, 0.22; 95% CI, 0.16-0.29, respectively), and lymph node only disease (HR, 0.09; 95% CI, 0.04-0.19). For OS, HRs favored enzalutamide (<1) across all disease subgroups, although 95% CI was >1 in patients with visceral disease (HR, 0.82; 95% CI, 0.55-1.23). Enzalutamide was well tolerated in patients with or without visceral disease. Enzalutamide provided clinically significant benefits in men with chemotherapy-naïve metastatic castration-resistant prostate cancer, with or without visceral disease, low- or high-volume bone disease, or lymph node only disease. Patients with metastatic castration-resistant prostate cancer-including those with or without visceral disease or widespread bone disease-benefitted from enzalutamide, an active well-tolerated therapy. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

68Ga PSMA-11 PET with CT urography protocol in the initial staging and biochemical relapse of prostate cancer.

PubMed

Iravani, Amir; Hofman, Michael S; Mulcahy, Tony; Williams, Scott; Murphy, Declan; Parameswaran, Bimal K; Hicks, Rodney J

2017-12-21

68 Ga-labelled prostate specific membrane antigen (PSMA) ligand PET/CT is a promising modality in primary staging (PS) and biochemical relapse (BCR) of prostate cancer (PC). However, pelvic nodes or local recurrences can be difficult to differentiate from radioactive urine. CT urography (CT-U) is an established method, which allows assessment of urological malignancies. The study presents a novel protocol of 68 Ga-PSMA-11 PET/CT-U in PS and BCR of PC. A retrospective review of PSMA PET/CT-U preformed on 57 consecutive patients with prostate cancer. Fifty mL of IV contrast was administered 10 min (range 8-15) before the CT component of a combined PET/CT study, acquired approximately 60 min (range 40-85) after administration of 166 MBq (range 91-246) of 68 Ga-PSMA-11. PET and PET/CT-U were reviewed by two nuclear medicine physicians and CT-U by a radiologist. First, PET images were reviewed independently followed by PET/CT-U images. Foci of activity which could not unequivocally be assessed as disease or urinary activity were recorded. PET/CT-U was considered of potential benefit in final interpretation when the equivocal focal activity in PET images corresponded to opacified ureter, bladder, prostate bed, seminal vesicles, or urethra. Student's T test and Pearson's correlation coefficient was used for assessment of variables including lymph node size and standardized uptake value. Overall 50 PSMA PET/CT-U studies were performed for BCR and 7 for PS. Median PSA with BCR and PS were 2.0 ± 11.4 ng/ml (0.06-57.3 ng/ml) and 18 ± 35.3 ng/ml (6.8-100 ng/ml), respectively. The median Gleason-score for both groups was 7 (range 6-10). In BCR group, PSMA PET was reported positive in 36 (72%) patients, CT-U in 11(22%) patients and PET/CT-U in 33 (66%) patients. In PS group, PSMA PET detected the primary site in all seven patients, of which one patient with metastatic nodal disease had negative CT finding. Of 40 equivocal foci (27/57 patients) on PET, 11 foci (10/57 patients, 17.5%) were localized to enhanced urine on PET/CT-U, hence considered of potential benefit in interpretation. Of those, 3 foci (3 patients) were solitary sites of activity on PSMA imaging including two local and one nodal site and 4 foci (3 patients) were in different nodal fields. PET/CT-U protocol is a practical approach and may assist in interpretation of 68 Ga-PSMA-11 imaging by delineation of the contrast opacified genitourinary system and matching focal PSMA activity with urinary contrast.

Image guided radiation therapy applications for head and neck, prostate, and breast cancers using 3D ultrasound imaging and Monte Carlo dose calculations

NASA Astrophysics Data System (ADS)

Fraser, Danielle

In radiation therapy an uncertainty in the delivered dose always exists because anatomic changes are unpredictable and patient specific. Image guided radiation therapy (IGRT) relies on imaging in the treatment room to monitor the tumour and surrounding tissue to ensure their prescribed position in the radiation beam. The goal of this thesis was to determine the dosimetric impact on the misaligned radiation therapy target for three cancer sites due to common setup errors; organ motion, tumour tissue deformation, changes in body habitus, and treatment planning errors. For this purpose, a novel 3D ultrasound system (Restitu, Resonant Medical, Inc.) was used to acquire a reference image of the target in the computed tomography simulation room at the time of treatment planning, to acquire daily images in the treatment room at the time of treatment delivery, and to compare the daily images to the reference image. The measured differences in position and volume between daily and reference geometries were incorporated into Monte Carlo (MC) dose calculations. The EGSnrc (National Research Council, Canada) family of codes was used to model Varian linear accelerators and patient specific beam parameters, as well as to estimate the dose to the target and organs at risk under several different scenarios. After validating the necessity of MC dose calculations in the pelvic region, the impact of interfraction prostate motion, and subsequent patient realignment under the treatment beams, on the delivered dose was investigated. For 32 patients it is demonstrated that using 3D conformal radiation therapy techniques and a 7 mm margin, the prescribed dose to the prostate, rectum, and bladder is recovered within 0.5% of that planned when patient setup is corrected for prostate motion, despite the beams interacting with a new external surface and internal tissue boundaries. In collaboration with the manufacturer, the ultrasound system was adapted from transabdominal imaging to neck imaging. Two case studies of nasopharyngeal cancer are discussed. The deformation of disease-positive cervical lymph nodes was monitored throughout treatment. Node volumes shrunk to 17% of the initial volume, moved up 1.3 cm, and received up to a 12% lower dose than that prescribed. It is shown that difficulties in imaging soft tissue in the neck region are circumvented with ultrasound imaging, and after dosimetric verification it is argued that adaptive replanning may be more beneficial than patient realignment when intensity modulated radiation therapy techniques are used. Some of the largest dose delivery errors were found in external electron beam treatments for breast cancer patients who underwent breast conserving surgery. Inaccuracies in conventional treatment planning resulted in substantial target dose discrepancies of up to 88%. When patient setup errors, interfraction tumour bed motion, and tissue remodeling were considered, inadequate target coverage was exacerbated. This thesis quantifies the dose discrepancy between that prescribed and that delivered. I delve into detail for common IGRT treatment sites, and illuminate problems that have not received much attention for less common IGRT treatment sites.

Association of anti-sperm antibodies with chronic prostatitis: A systematic review and meta-analysis.

PubMed

Jiang, Yumei; Cui, Dong; Du, Yuefeng; Lu, Jun; Yang, Lin; Li, Jinmei; Zhang, Jing; Bai, Xiaojing

2016-11-01

Chronic prostatitis is a risk factor for impaired male fertility potential, and anti-sperm antibodies (ASAs) cause the autoimmune disease immune infertility, which has a negative effect on semen parameters. Current studies have investigated the ASA-positive relationship between chronic prostatitis versus normal controls, but have shown inconsistent results. Hence, we systematic searched the PubMed, EMBASE, Science Direct/Elsevier, Medline, and the Cochrane Library up to October 2015 for case-control studies that involved the ASA-positive relationship between chronic prostatitis patients versus normal controls. The meta-analysis was performed with Review Manager and Stata software. After literature search, six studies were identified, including 721 cases of chronic prostatitis and 160 normal controls. Our results illustrated a significant correlation of the ASA-positive relationship between chronic prostatitis patients versus normal controls. The combined odds ratio of the ASA-positive rate in chronic prostatitis patients and normal controls was 3.26 (1.86-5.71). There was also a significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) III versus normal controls, and the combined OR was 2.46 (1.10-5.51). However, there was no significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) II versus normal controls. The present study illustrates that the positive rate of ASAs in chronic prostatitis patients was significantly higher than in the control group, suggesting that chronic prostatitis has a negative effect on male reproductive function. However, studies with larger samples are needed to better illuminate the correlation between ASAs and chronic prostatitis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

PubMed

Hatano, Koji; Nonomura, Norio; Nishimura, Kazuo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Tsujimura, Akira; Okuyama, Akihiko

2011-02-01

To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

Gene signatures distinguish stage-specific prostate cancer stem cells isolated from transgenic adenocarcinoma of the mouse prostate lesions and predict the malignancy of human tumors.

PubMed

Mazzoleni, Stefania; Jachetti, Elena; Morosini, Sara; Grioni, Matteo; Piras, Ignazio Stefano; Pala, Mauro; Bulfone, Alessandro; Freschi, Massimo; Bellone, Matteo; Galli, Rossella

2013-09-01

The relevant social and economic impact of prostate adenocarcinoma, one of the leading causes of death in men, urges critical improvements in knowledge of the pathogenesis and cure of this disease. These can also be achieved by implementing in vitro and in vivo preclinical models by taking advantage of prostate cancer stem cells (PCSCs). The best-characterized mouse model of prostate cancer is the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice develop a progressive lesion called prostatic intraepithelial neoplasia that evolves into adenocarcinoma (AD) between 24 and 30 weeks of age. ADs often metastasize to lymph nodes, lung, bones, and kidneys. Eventually, approximately 5% of the mice develop an androgen-independent neuroendocrine adenocarcinoma. Here we report the establishment of long-term self-renewing PCSC lines from the different stages of TRAMP progression by application of the neurosphere assay. Stage-specific prostate cell lines were endowed with the critical features expected from malignant bona fide cancer stem cells, namely, self-renewal, multipotency, and tumorigenicity. Notably, transcriptome analysis of stage-specific PCSCs resulted in the generation of well-defined, meaningful gene signatures, which identify distinct stages of human tumor progression. As such, TRAMP-derived PCSCs represent a novel and valuable preclinical model for elucidating the pathogenetic mechanisms leading to prostate adenocarcinoma and for the identification of molecular mediators to be pursued as therapeutic targets.

Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers.

PubMed Central

Krajewska, M.; Krajewski, S.; Epstein, J. I.; Shabaik, A.; Sauvageot, J.; Song, K.; Kitada, S.; Reed, J. C.

1996-01-01

Proteins encoded by bcl-2 family genes are important regulators of programmed cell death and apoptosis. Alterations in the expression of these apoptosis-regulating genes can contribute to the origins of cancer, as well as adversely influence tumor responses to chemo- and radiotherapy. Using antibodies specific for the Bcl-2, Bax, Bcl-X, and Mcl-1 proteins in combination with immunohistochemical methods, we examined for the first time the expression of these bcl-2 family genes in 64 cases of adenocarcinoma of the prostate, including 10 Gleason grade 2 to 4 tumors, 21 grade 5 to 7 tumors, 17 grade 8 to 10 tumors, 8 lymph node metastases, and 8 bone metastases. In addition, 24 cases of prostatic intraepithelial neoplasia (PIN) or PIN coexisting with carcinoma were also evaluated. All immunostaining results were scored with regard to approximate percentage of positive tumor cells and relative immunostaining intensity. Expression of the anti-apoptotic protein Bcl-2 was present in 16 of 64 (25%) adenocarcinomas and tended to be more frequent in high grade tumors (Gleason grade 8 to 10; 41%) and nodal metastases (38%) than in lower grade (Gleason 2 to 7) primary tumors (16%; P < 0.05). Bcl-X was expressed in all 64 (100%) tumors evaluated. Bcl-X immunointensity was generally stronger in high grade primary tumors (grade 8 to 10) and metastases compared with PIN and low grade neoplasms (P < 0.0001). In addition, the proportion of specimens with > 50% Bcl-X-immunopositive tumor cells also was higher in advanced grade primary tumors (Gleason 8 to 10) and metastases than in PIN and low grade tumors (Gleason 2 to 7; P < 0.005). The anti-apoptotic protein Mcl-1 was expressed in 52 of 64 (81%) tumors, compared with only 9 of 24 (38%) cases of PIN (P < 0.001). In addition, the percentage of Mcl-1-positive cells was typically higher in Gleason grade 8 to 10 tumors and metastases than in PIN or lower grade tumors (P = 0.025). In contrast, the pro-apoptotic protein Bax was expressed in all prostate cancers evaluated, with high percentages of immunopositive cells and strong immunointensity typically occurring regardless of tumor grade. The findings suggest that expression of several anti-apoptotic members of the bcl-2 gene family, including bcl-2, bcl-X, and mcl-1 increases during progression of prostate cancers, a finding that may be relevant to the hormone-insensitive, metastatic phenotype of most advanced adenocarcinomas of the prostate. Images Figure 2 PMID:8623925

Clinical applications of sentinel lymph-node biopsy for the staging and treatment of solid neoplasms.

PubMed

Gipponi, M

2005-08-01

A review of the clinical applications of sentinel lymph node (sN) biopsy has been performed with the aim of defining the rationale, the methods of detection, the accuracy, and the current indications to sN biopsy in different solid neoplasms. In melanoma patients, sN biopsy represents a standard procedure for staging purpose, although its therapeutic value is still under examination. The sN is an accurate method for the pathologic staging of the axilla in patients with early stage breast cancer, and it can be useful for the selection of patients with axillary metastasis who should undergo standard axillary dissection. In gynecologic malignancies, appreciable results are available in patients with vulvar and cervical cancer only. Patients with squamous cell vulvar cancer may benefit by sN biopsy because a complete bilateral inguino-femoral lymph-node dissection may be avoided whenever the sN is free of metastasis. As regards to cervical cancer, further studies are required with the combined technique (blue dye injection and gamma-probe guided surgery), which seems more promising, before abandoning pelvic lymphadenectomy in patients with histologically-negative sN. The experience in urologic cancer deals mainly with penile and prostate cancer; the modern procedures for the dynamic detection of sN are going to clarify its role in the surgical management of penile cancer; as regards to prostate cancer, very preliminary results suggest that the sN biopsy may enhance the pathologic staging of this neoplasm compared to modified pelvic lymphadenectomy, due to the individual variability of the lymphatic drainage of this cancer. In patients with clinically node-negative squamous head and neck cancer, the reliability of sN-guided neck lymph node dissection seems promising. The sN biopsy is also technically feasible in patients with differentiated thyroid cancer; however, the future role of this procedure in the clinical decision-making of these patients remains to be defined due to the questionable biological meaning of nodal metastases. Patients with non-small-cell lung cancer should be investigated by means of radiotracers injected at the time of thoracotomy or under CT-scan guidance in order to achieve a satisfactory identification rate (over 80%); the focused histopathologic staging of the sN improves current pathologic staging by conventional bi-valve assessment of all the lymph nodes of the surgical specimen; moreover, the prognostic role of isolated N2 metastasis can be better elucidated. In patients with gastrointestinal malignancies, the intraoperative lymphatic mapping with sN biopsy have suggested that the lymphatic drainage of the gastrointestinal tract is much more complicated than other sites, skip metastasis being rather frequent. In patients with gastric cancer, current data show that it can be detected by means of peritumoral injection of indocyanine green; the detection of tumor positive lymph nodes beyond the perigastric area could select patients amenable to D2 lymphadenectomy. As regards to colorectal cancer patients, the focused analysis of the sN may reveal disease that might otherwise go undetected by conventional surgical and pathological methods, and those patients which are upstaged can benefit by adjuvant chemotherapy. Finally, in patients with Merkel cell carcinoma, notwithstanding the limited experiences with sN biopsy, sN histology seems to predict regional lymph node status and may aid in selecting which patients are amenable to therapeutic lymph node dissection.

[18F]FDG imaging of head and neck tumours: comparison of hybrid PET and morphological methods.

PubMed

Dresel, S; Grammerstorff, J; Schwenzer, K; Brinkbäumer, K; Schmid, R; Pfluger, T; Hahn, K

2003-07-01

The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose ([(18)F]FDG) imaging of head and neck tumours using a second- or third-generation hybrid PET device. Results were compared with the findings of spiral computed tomography (CT) and magnetic resonance imaging (MRI), and, as regards lymph node metastasis, the ultrasound findings. A total of 116 patients with head and neck tumours (83 males and 33 females aged 27-88 years) were examined using a hybrid PET scanner after injection of 185-350 MBq of [(18)F]FDG (Picker Prism 2000 XP-PCD, Marconi Axis gamma-PET(2) AZ). Hybrid PET examinations were performed in list mode using an axial filter. Reconstruction of data was performed iteratively. Ninety-six patients underwent CT using a multislice technique (Siemens Somatom Plus 4, Marconi MX 8000), 18 patients underwent MRI and 100 patients were examined by ultrasound. All findings were verified by histology, which was considered the gold standard, or, in the event of negative histology, by follow-up. Correct diagnosis of the primary or recurrent lesion was made in 73 of 85 patients using the hybrid PET scanner, in 50 of 76 patients on CT and in 7 of 10 patients on MRI. Hybrid PET successfully visualised metastatic disease in cervical lymph nodes in 28 of 34 patients, while 23 of 31 were correctly diagnosed with CT, 3 of 4 with MRI and 30 of 33 with ultrasound. False positive results regarding lymph node metastasis were seen in three patients with hybrid PET, in 14 patients with CT and in 13 patients with ultrasound. MRI yielded no false positive results concerning lymph node metastasis. In one patient, unrecognised metastatic lesions were seen on hybrid PET elsewhere in the body (lung: n=1; bone: n=1). Additional malignant lesions at sites other than the head and neck tumour were found in three patients (one patient with lung cancer, one patient with pelvic metastasis due to a carcinoma of the prostate and one patient with pulmonary metastasis due to breast cancer). It is concluded that [(18)F]FDG PET with hybrid PET scanners is superior to CT and MRI in the diagnosis of primary or recurrent lesions as well as in the assessment of lymph node involvement, whereas it is inferior to ultrasound in the detection of cervical lymph node metastasis.

Oncologic Outcomes After Robot-assisted Radical Prostatectomy: A Large European Single-centre Cohort with Median 10-Year Follow-up.

PubMed

Rajan, Prabhakar; Hagman, Anna; Sooriakumaran, Prasanna; Nyberg, Tommy; Wallerstedt, Anna; Adding, Christofer; Akre, Olof; Carlsson, Stefan; Hosseini, Abolfazl; Olsson, Mats; Egevad, Lars; Wiklund, Fredrik; Steineck, Gunnar; Wiklund, N Peter

2016-11-02

Robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) treatment has been widely adopted with limited evidence for long-term (>5 yr) oncologic efficacy. To evaluate long-term oncologic outcomes following RARP. Prospective cohort study of 885 patients who underwent RARP as monotherapy for PCa between 2002 and 2006 in a single European centre and followed up until 2016. RARP as monotherapy. Biochemical recurrence (BCR)-free survival (BCRFS), salvage therapy (ST)-free survival (STFS), prostate cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method, and event-time distributions were compared using the log-rank test. Variables predictive of BCR and ST were identified using Cox proportional hazards models. We identified 167 BCRs, 110 STs, 16 PCa-related deaths, and 51 deaths from other/unknown causes. BCRFS, STFS, CSS, and OS rates were 81.8%, 87.5%, 98.5%, and 93.0%, respectively, at median follow-up of 10.5 yr. On multivariable analysis, the strongest independent predictors of both BCR and ST were preoperative Gleason score, pathological T stage, positive surgical margins (PSMs), and preoperative prostate-specific antigen. PSM >3mm/multifocal but not ≤3mm independently affected the risk of both BCR and ST. Study limitations include a lack of centralised histopathologic reporting, lymph node and post-operative tumour volume data in a historical cohort, and patient-reported outcomes. RARP appears to confer effective long-term oncologic efficacy. The risk of BCR or ST is unaffected by ≤3mm PSM, but further follow-up is required to determine any impact on CSS. Robot-assisted surgery for prostate cancer is effective 10 yr after treatment. Very small (<3mm) amounts of cancer at the cut edge of the prostate do not appear to impact on recurrence risk and the need for additional treatment, but it is not yet known whether this affects the risk of death from prostate cancer. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

A Critical Analysis of the Current Knowledge of Surgical Anatomy of the Prostate Related to Optimisation of Cancer Control and Preservation of Continence and Erection in Candidates for Radical Prostatectomy: An Update.

PubMed

Walz, Jochen; Epstein, Jonathan I; Ganzer, Roman; Graefen, Markus; Guazzoni, Giorgio; Kaouk, Jihad; Menon, Mani; Mottrie, Alexandre; Myers, Robert P; Patel, Vipul; Tewari, Ashutosh; Villers, Arnauld; Artibani, Walter

2016-08-01

In 2010, we published a review summarising the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control and the functional outcome of prostatectomy. To provide an update based on new literature to help the surgeon improve oncologic and surgical outcomes of radical prostatectomy (RP). We searched the PubMed database using the keywords radical prostatectomy, anatomy, neurovascular bundle, nerve, fascia, pelvis, sphincter, urethra, urinary continence, and erectile function. Relevant articles and textbook chapters published since the last review were critically reviewed, analysed, and summarised. Moreover, we integrated aspects that were not addressed in the last review into this update. We found new evidence for several topics. Up to 40% of the cross-sectional surface area of the urethral sphincter tissue is laterally overlapped by the dorsal vascular complex and might be injured during en bloc ligation. Denonvilliers fascia is fused with the base of the prostate in a horizontal fashion dorsally/caudally of the seminal vesicles, requiring sharp detachment when preserved. During extended pelvic lymph node dissection, the erectile nerves are at risk in the presacral and internal iliac area. Dissection planes for nerve sparing can be graded according to the amount of tissue left on the prostate as a safety margin against positive surgical margins. Vascular structures can serve as landmarks. The urethral sphincter and its length after RP are influenced by the shape of the apex. Taking this shape into account allows preservation of additional sphincter length with improved postoperative continence. This update provides additional, detailed information about the surgical anatomy of the prostate and adjacent tissues involved in RP. This anatomy remains complex and widely variable. These details facilitate surgical orientation and dissection during RP and ideally should translate into improved outcomes. Based on recent anatomic findings regarding the prostate and its surrounding tissue, the urologist can individualise the dissection during RP according to cancer and patient characteristics to improve oncologic and functional results at the same time. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Correlation between molecular tumor volume evaluated with 68Ga-PSMA PET/CT and prostatic specific antigen levels.

PubMed

Medina-Ornelas Sevastián, S; García-Pérez Francisco, O; Hernández-Pedro Norma, Y; Arellano-Zarate Angélica, E; Abúndiz-López Blanca, L

2018-02-14

To investigate the association between prostatic-specific antigen (PSA) levels and molecular tumor volume (MTV) measured in the 68 Ga-PSMA PET/CT, both done in a short period of time, in prostate cancer patients with biochemical failure. Eighty-four patients who underwent 68 Ga-PSMA PET/CT and measurement of PSA levels in the same week (trigger-PSA) were studied in this retrospective analysis. MTV was calculated from the sum of the metastatic lesions. To determine the association between trigger-PSA level and PET/CT findings, Spearman rank correlation was used. The median MTV of metastatic bone disease (mBD) was significantly higher than in metastatic lymph-nodes (mLN) (139.5 versus 17.7; P<.05). Disease was limited to the prostate in 8 patients (9.5%), mLN in 21 patients (25%), mBD in 32 patients (38.1%) and the 3 sites (prostate, mLN, and mBD) in 17 patients (20.2%). In 6 patients (6.14%), 68 Ga-PSMA-PET/CT was not capable of detecting disease. The median trigger-PSA levels of patients with disease limited to the prostate (2.8ng/mL), mLN (6.8ng/mL), and for mBD (16.8ng/mL) was statically significant (P<.05). Positive patients had a mean trigger-PSA of 4.3ng/mL vs 1.5ng/mL in negative patients (P<.05). We established 3 threshold-points for trigger-PSA level detection rate:≤1ng/mL (47.3%), 1-4ng/mL (68.4%) and≥4ng/mL (96.7%). When trigger-PSA exceeded 4ng/mL, the MTV was higher (P<.001). The correlation of MTV with trigger-PSA is demonstrated, which may have an impact on management. However, trigger-PSA levels were not capable of distinguishing between localized or distant disease. An accurate detection of disease can lead to a better therapeutic strategy. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Vasculogenic Mimicry in Prostate Cancer: The Roles of EphA2 and PI3K

PubMed Central

Wang, Hua; Lin, Hao; Pan, Jincheng; Mo, Chengqiang; Zhang, Faming; Huang, Bin; Wang, Zongren; Chen, Xu; Zhuang, Jintao; Wang, Daohu; Qiu, Shaopeng

2016-01-01

BACKGROUND. Aggressive tumor cells can form perfusable networks that mimic normal vasculature and enhance tumor growth and metastasis. A number of molecular players have been implicated in such vasculogenic mimicry, among them the receptor tyrosine kinase EphA2, which is aberrantly expressed in aggressive tumors. Here we study the role and regulation of EphA2 in vasculogenic mimicry in prostate cancer where this phenomenon is still poorly understood. METHODS. Vasculogenic mimicry was characterized by tubules whose cellular lining was negative for the endothelial cell marker CD34 but positive for periodic acid-Schiff staining, and/or contained red blood cells. Vasculogenic mimicry was assessed in 92 clinical samples of prostate cancer and analyzed in more detail in three prostate cancer cell lines kept in three-dimensional culture. Tissue samples and cell lines were also assessed for total and phosphorylated levels of EphA2 and its potential regulator, Phosphoinositide 3-Kinase (PI3K). In addition, the role of EphA2 in vasculogenic mimicry and in cell migration and invasion were investigated by manipulating the levels of EphA2 through specific siRNAs. Furthermore, the role of PI3K in vasculogenic mimicry and in regulating EphA2 was tested by application of an inhibitor, LY294002. RESULTS. Immunohistochemistry of prostate cancers showed a significant correlation between vasculogenic mimicry and high expression levels of EphA2, high Gleason scores, advanced TNM stage, and the presence of lymph node and distant metastases. Likewise, two prostate cancer cell lines (PC3 and DU-145) formed vasculogenic networks on Matrigel and expressed high EphA2 levels, while one line (LNCaP) showed no vasculogenic networks and lower EphA2 levels. Specific silencing of EphA2 in PC3 and DU-145 cells decreased vasculogenic mimicry as well as cell migration and invasion. Furthermore, high expression levels of PI3K and EphA2 phosphorylation at Ser897 significantly correlated with the presence of vasculogenic mimicry and in vitro inhibition of PI3K by LY294002 disrupted vasculogenic mimicry, potentially through a reduction of EphA2 phosphorylation at Ser897. CONCLUSIONS. The expression levels of PI3K and EphA2 are positively correlated with vasculogenic mimicry both in vivo and in vitro. Moreover, phosphorylation levels of EphA2 regulated by PI3K are also significantly associated with vasculogenic mimicry in vivo. Based on its functional implication in vasculogenic mimicry in vitro, EphA2 signaling may be a potential therapeutic target in advanced prostate cancer. PMID:27326255

Impact of the Level of Urothelial Carcinoma Involvement of the Prostate on Survival after Radical Cystectomy.

PubMed

Moschini, Marco; Soria, Francesco; Susani, Martin; Korn, Stephan; Briganti, Alberto; Roupret, Morgan; Seitz, Christian; Gust, Killian; Haitel, Andrea; Montorsi, Francesco; Wirth, Gregory; Robinson, Brian D; Karakiewicz, Pierre I; Özsoy, Mehmet; Rink, Michael; Shariat, Shahrokh F

2017-07-27

Urothelial prostatic involvement (UPI) at the time of radical cystoprostatectomy (RCP) was found associated with worse survival outcomes by several previous reports. Our aim is to evaluate the impact of different levels of UPI on survival outcomes using a large series of male patients treated with RCP. Whole step section specimens from 995 male BCa patients were assessed for UPI defined as: no involvement vs. prostatic urethral carcinoma in situ (CIS) vs. lamina propria involvement vs. ductal CIS vs. prostate stromal involvement. Primary end point of the study was predictors of prostatic involvement at RCP and its impact on overall survival after surgery. Prostatic involvement was recorded in 307 (30.9%) patients: 28% with prostatic urethral CIS, 12% with lamina propria involvement, 13% with ductal CIS and 47% with stromal involvement. Median follow-up was 70 months. Patients with stromal involvement had a worse 5-year survival (12%) than those with prostatic urethra CIS (40%), lamina propria involvement (36%), and ductal CIS (35%). Considering predictors of prostatic involvement, multifocal tumor (Odds Ratio [OR]: 6.60, p  < 0.001), lymphovascular invasion (OR: 2.61, p  < 0.001), lymph node metastases (OR: 2.02, p  < 0.001) and CIS (OR: 2.02, p  < 0.001) were found associated. Similar predictors were found assessing stromal involvement. Approximately one third of RCP patients harbor prostatic involvement of urothelial carcinoma. While all UPI are associated with worse overall survival, stromal involvement confers the worst outcome supporting its classification as T4 in the TNM staging.

Non-invasive assessment of inter-and intrapatient variability of integrin expression in metastasized prostate cancer by PET.

PubMed

Beer, Ambros J; Schwarzenböck, Sarah M; Zantl, Niko; Souvatzoglou, Michael; Maurer, Tobias; Watzlowik, Petra; Kessler, Horst; Wester, Hans-Jürgen; Schwaiger, Markus; Krause, Bernd Joachim

2016-05-10

Due to the high expression of the integrin αvβ3 not only on endothelial cells, but also on mature osteoclasts and prostate cancer cells, imaging of osseous metastases with αvβ3-targeted tracers seems promising. However, little is known about the patterns of αvβ3-expression in metastasized prostate cancer lesions in-vivo. Thus we evaluated the uptake of the αvβ3-specific PET tracer [18F]Galacto-RGD for assessment of bone metastases in prostate cancer patients. [18F]Galacto-RGD PET identified 58/74 bone-lesions (detection rate of 78.4%) and lymph node metastases in 2/5 patients. The SUVmean was 2.12+/-0.94 (range 0.70-4.38; tumor/blood 1.36+/-0.53; tumor/muscle 2.82+/-1.31) in bone-lesions and 2.21+/-1.18 (range 0.75-3.56) in lymph node metastases. Good visualization and detection of bone metastases was feasible due to a low background activity of the surrounding normal bone tissue. 12 patients with known metastasized prostate cancer according to conventional staging (including bone-scintigraphy and contrast-enhanced CT; median PSA 68.63 ng/ml, range 3.72-1935) were examined with PET after i.v.-injection of [18F]Galacto-RGD. Two blinded nuclear-medicine physicians evaluated the PET-scans in consensus concerning lesion detectability. Volumes-of-interest were drawn in the PET-scans over all metastases defined by conventional staging (maximum of 11 lesions/patient), over the left ventricle, liver and muscle and standardized-uptake-values (SUVs) were calculated. Our data show generally elevated uptake of [18F]Galacto-RGD in bone metastases from prostate cancer with a marked inter- and intrapatient variability. While [18F]Galacto-RGD PET is inferior to bone scintigraphy for detection of osseous metastases, it might be valuable in patient screening and monitoring of αvβ3-targeted therapies due to the high variability of αvβ3-expression.

Intensity-modulated salvage radiotherapy with simultaneous integrated boost for local recurrence of prostate carcinoma: a pilot study on the place of PET-choline for guiding target volume delineation.

PubMed

Wahart, Aurélien; Guy, Jean-Baptiste; Vallard, Alexis; Geissler, Benjamin; Ben Mrad, Majed; Falk, Alexander T; Prevot, Nathalie; de Laroche, Guy; Rancoule, Chloé; Chargari, Cyrus; Magné, Nicolas

2016-01-01

The aim of this study was to report the first cases of salvage radiotherapy (RT) using the intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) targeted on choline positron emission tomography (PET) uptake in a local recurrent prostate cancer, after a radical prostatectomy. Four patients received salvage irradiation for biochemical relapse that occurred after the initial radical prostatectomy. The relapse occurred from 10 months to 6 years with PSA levels ranging from 2.35 to 4.86 ng ml(-1). For each patient, an (18)F-choline PET-CT showed a focal choline uptake in prostatic fossa, with standardized uptake value calculated on the basis of predicted lean body mass (SUL) max of 3.3-6.8. No involved lymph node or distant metastases were diagnosed. IMRT doses were of 62.7 Gy (1.9 Gy/fraction, 33 fractions), with a SIB of 69.3 Gy (2.1 Gy/fraction, 33 fractions) to a PET-guided target volume. Acute toxicities were limited. We observed no gastrointestinal toxicity ≥grade 2 and only one grade 2 genitourinary toxicity. At 1-month follow-up evaluation, no complication and a decrease in PSA level (6.8-43.8% of the pre-therapeutic level) were reported. After 4 months, a decrease in PSA level was obtained for all the patients, ranging from 30% to 70%. At a median follow-up of 15 months, PSA level was controlled for all the patients, but one of them experienced a distant lymph node recurrence. Salvage irradiation to the prostate bed with SIB guided by PET-CT is feasible, with biological efficacy and no major acute toxicity. IMRT with PET-oriented SIB for salvage treatment of prostate cancer is possible, without major acute toxicity.

CD147 expression predicts biochemical recurrence after prostatectomy independent of histologic and pathologic features.

PubMed

Bauman, Tyler M; Ewald, Jonathan A; Huang, Wei; Ricke, William A

2015-07-25

CD147 is an MMP-inducing protein often implicated in cancer progression. The purpose of this study was to investigate the expression of CD147 in prostate cancer (PCa) progression and the prognostic ability of CD147 in predicting biochemical recurrence after prostatectomy. Plasma membrane-localized CD147 protein expression was quantified in patient samples using immunohistochemistry and multispectral imaging, and expression was compared to clinico-pathological features (pathologic stage, Gleason score, tumor volume, preoperative PSA, lymph node status, surgical margins, biochemical recurrence status). CD147 specificity and expression were confirmed with immunoblotting of prostate cell lines, and CD147 mRNA expression was evaluated in public expression microarray datasets of patient prostate tumors. Expression of CD147 protein was significantly decreased in localized tumors (pT2; p = 0.02) and aggressive PCa (≥pT3; p = 0.004), and metastases (p = 0.001) compared to benign prostatic tissue. Decreased CD147 was associated with advanced pathologic stage (p = 0.009) and high Gleason score (p = 0.02), and low CD147 expression predicted biochemical recurrence (HR 0.55; 95 % CI 0.31-0.97; p = 0.04) independent of clinico-pathologic features. Immunoblot bands were detected at 44 kDa and 66 kDa, representing non-glycosylated and glycosylated forms of CD147 protein, and CD147 expression was lower in tumorigenic T10 cells than non-tumorigenic BPH-1 cells (p = 0.02). Decreased CD147 mRNA expression was associated with increased Gleason score and pathologic stage in patient tumors but is not associated with recurrence status. Membrane-associated CD147 expression is significantly decreased in PCa compared to non-malignant prostate tissue and is associated with tumor progression, and low CD147 expression predicts biochemical recurrence after prostatectomy independent of pathologic stage, Gleason score, lymph node status, surgical margins, and tumor volume in multivariable analysis.

One-stop shop whole-body 68Ga-PSMA-11 PET/MRI compared to clinical Nomograms for preoperative T- and N-Staging of High-Risk Prostate Cancer.

PubMed

Thalgott, Mark; Düwel, Charlotte; Rauscher, Isabel; Heck, Matthias M; Haller, Bernhard; Gafita, Andrei; Gschwend, Jürgen E; Schwaiger, Markus; Maurer, Tobias; Eiber, Matthias

2018-05-24

Our aim was to assess the diagnostic potential of one-stop shop Prostate-specific membrane antigen-ligand Positron Emission Tomography/Magnetic Resonance Imaging ( 68 Ga-PSMA-11 PET/MRI) compared to preoperative staging nomograms in patients with high-risk prostate cancer (PC). Methods: A total of 102 patients underwent 68 Ga-PSMA-11 PET/MRI before intended radical prostatectomy (RP) with lymph node dissection. Preoperative variables determined the probabilities for lymph node metastases (LNM), extracapsular extension (ECE) and seminal vesical involvement (SVI) using the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and Partin tables. Receiver operating characteristic (ROC) analyses were performed to determine best discriminatory cutoffs. On cohort base, positivity rates of imaging and nomograms were compared to pathological prevalence. On patient base, sensitivity, specificity and its area under the curves (AUCs) were calculated. Finally, the full concordance of each method to postoperative T- and N-stage was determined. Results: 73 patients were finally analysed. On cohort base, the MSKCC nomogram (39.7%) positivity rate was most concordant with pathological prevalence for LNM (34.3%) compared to Partin tables (14.1%) and imaging (20.6). Prevalence of ECE (72.6%) was best predicted by MSKCC nomograms and imaging (83.6% each), compared to Partin tables (38.4%). For prevalence of SVI (45.2%), imaging (47.9%) performed superior to MSKCC (37.6%) and Partin tables (19.3%). On patient base, AUCs for LNM, ECE and SVI did not differ significantly between tests (p>0.05). Imaging revealed a high specificity (100%) for LNM and a sensitivity (60%) comparable to the MSKCC nomogram (68%) and Partin tables (60%). For ECE, imaging revealed the highest sensitivity (94.3%) compared to the MSKCC nomogram (66%) and Partin tables (71.1%). For SVI, sensitivity and specificity of imaging and MSKCC nomogram were comparable (81.5% and 80% vs. 87.9% and 75%). The rate of concordance to the final pTN-stage was 60.3% for imaging, 52.1% for the MSKCC nomogram and 39.7% for Partin tables. Conclusion: In our analysis, preoperative one-stop shop 68 Ga-PSMA-11 PET/MRI performs at least equally for T- and N-stage prediction compared to nomograms in high-risk PC patients. Despite, an improved prediction of the full final stage and the yield of additional anatomical information, the use of 68 Ga-PSMA-11 PET/MRI warrants further prospective evaluation. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

SU-E-J-57: First Development of Adapting to Intrafraction Relative Motion Between Prostate and Pelvic Lymph Nodes Targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ge, Y; Colvill, E; O’Brien, R

2015-06-15

Purpose Large intrafraction relative motion of multiple targets is common in advanced head and neck, lung, abdominal, gynaecological and urological cancer, jeopardizing the treatment outcomes. The objective of this study is to develop a real-time adaptation strategy, for the first time, to accurately correct for the relative motion of multiple targets by reshaping the treatment field using the multi-leaf collimator (MLC). Methods The principle of tracking the simultaneously treated but differentially moving tumor targets is to determine the new aperture shape that conforms to the shifted targets. Three dimensional volumes representing the individual targets are projected to the beam’s eyemore » view. The leaf openings falling inside each 2D projection will be shifted according to the measured motion of each target to form the new aperture shape. Based on the updated beam shape, new leaf positions will be determined with optimized trade-off between the target underdose and healthy tissue overdose, and considerations of the physical constraints of the MLC. Taking a prostate cancer patient with pelvic lymph node involvement as an example, a preliminary dosimetric study was conducted to demonstrate the potential treatment improvement compared to the state-of- art adaptation technique which shifts the whole beam to track only one target. Results The world-first intrafraction adaptation system capable of reshaping the beam to correct for the relative motion of multiple targets has been developed. The dose in the static nodes and small bowel are closer to the planned distribution and the V45 of small bowel is decreased from 110cc to 75cc, corresponding to a 30% reduction by this technique compared to the state-of-art adaptation technique. Conclusion The developed adaptation system to correct for intrafraction relative motion of multiple targets will guarantee the tumour coverage and thus enable PTV margin reduction to minimize the high target dose to the adjacent organs-at-risk. The authors acknowledge funding support from the Australian NHMRC Australia Fellowship and NHMRC Project Grant No. APP1042375.« less

Prediction of Prostate Cancer Recurrence Using Quantitative Phase Imaging

NASA Astrophysics Data System (ADS)

Sridharan, Shamira; Macias, Virgilia; Tangella, Krishnarao; Kajdacsy-Balla, André; Popescu, Gabriel

2015-05-01

The risk of biochemical recurrence of prostate cancer among individuals who undergo radical prostatectomy for treatment is around 25%. Current clinical methods often fail at successfully predicting recurrence among patients at intermediate risk for recurrence. We used a label-free method, spatial light interference microscopy, to perform localized measurements of light scattering in prostatectomy tissue microarrays. We show, for the first time to our knowledge, that anisotropy of light scattering in the stroma immediately adjoining cancerous glands can be used to identify patients at higher risk for recurrence. The data show that lower value of anisotropy corresponds to a higher risk for recurrence, meaning that the stroma adjoining the glands of recurrent patients is more fractionated than in non-recurrent patients. Our method outperformed the widely accepted clinical tool CAPRA-S in the cases we interrogated irrespective of Gleason grade, prostate-specific antigen (PSA) levels and pathological tumor-node-metastasis (pTNM) stage. These results suggest that QPI shows promise in assisting pathologists to improve prediction of prostate cancer recurrence.

Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

PubMed Central

Hsiao, Wayland; Anastasia, Katrina; Hall, John; Goodman, Michael; Rimland, David; Ritenour, Chad W. M.; Issa, Muta M.

2009-01-01

HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs) and corresponding 95% confidence intervals (CI). The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5). In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients. PMID:19219374

Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques.

PubMed

Au, Bryan C; Lee, Chyan-Jang; Lopez-Perez, Orlay; Foltz, Warren; Felizardo, Tania C; Wang, James C M; Huang, Ju; Fan, Xin; Madden, Melissa; Goldstein, Alyssa; Jaffray, David A; Moloo, Badru; McCart, J Andrea; Medin, Jeffrey A

2016-02-19

Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag)-specific responses through direct injections of recombinant lentivectors (LVs) that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA)-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months-the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an "off-the-shelf" anti-cancer vaccine that could be made at large scale and injected into patients-even on an out-patient basis.

The relationship of TMPRSS2-ERG gene fusion between primary and metastatic prostate cancers.

PubMed

Guo, Charles C; Wang, Yan; Xiao, Li; Troncoso, Patricia; Czerniak, Bogdan A

2012-05-01

Recent studies have revealed the presence of TMPRSS2-ERG gene fusion in both primary and metastatic prostate cancers. However, the relationship between primary and corresponding metastatic prostate cancers with respect to the status of this gene fusion remains unclear. Using fluorescence in situ hybridization, we evaluated the rearrangement of the ERG gene in the radical prostatectomy specimens and corresponding lymph node metastases from 19 patients with prostate cancer. The mean age of the patients was 61 years, and the median Gleason score in the radical prostatectomy specimens was 7 (4 + 3). Prostate cancer was unifocal in 6 cases and multifocal in 13 cases, including 10 with 2 foci and 3 with 3 foci. In the primary prostate cancers, rearrangement of the ERG gene was observed in 13 cases and associated with deletion of the 5' ERG gene in 8 cases. In the metastases, the ERG rearrangement was present in 10 cases and associated with deletion of the 5' ERG gene in 6 cases. In unifocal prostate cancers, the status of the ERG rearrangement was concordant between the primary prostate cancer and metastasis in 5 of 6 cases. In multifocal prostate cancer, despite a significant interfocal discordance, the status of the ERG rearrangement was concordant between the index (largest) primary tumor focus and metastasis in all 13 cases. Our study demonstrates a close relationship of the TMPRSS2-ERG gene fusion status between primary and metastatic prostate cancer. The concordance of the ERG gene rearrangement status between the index primary tumor focus and metastasis suggests that metastasis most likely arises from the index tumor focus in multifocal prostate cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Predictive factors and oncological outcomes of persistently elevated prostate-specific antigen in patients following robot-assisted radical prostatectomy.

PubMed

Kumar, Anup; Samavedi, Srinivas; Mouraviev, Vladimir; Bates, Anthony S; Coelho, Rafael F; Rocco, Bernardo; Patel, Vipul R

2017-03-01

Our aim was to evaluate factors associated with persistently elevated prostate-specific antigen (PSA) and biochemical recurrence following robotic-assisted radical prostatectomy (RARP). The study population (N = 5300) consisted of consecutive patients who underwent RARP for localized prostate cancer by a single surgeon (VP) from January 2008 through July 2013. A query of our Institutional Review Board-approved registry identified 162 men with persistently elevated PSA (group A), defined as PSA level ≥0.1 ng/ml at 6 weeks after surgery, who were compared with rest of the cohort group having undetectable PSA, group B (<0.1 ng/ml). A univariate and multivariate logistic regression analysis was used to evaluate the significant association between various variables and the following: (1) persistently elevated PSA, (2) BCR (PSA value ≥0.2 ng/ml) on follow-up in the persistent PSA group. On multivariate analysis, only the following parameters were significantly associated with persistent PSA after RARP-preoperative [PSA >10 ng/ml (p = 0.01), Gleason Score ≥8 (p = 0.001) and clinical stage(p = 0.001)]; postoperative [pathologic stage (p = 0.001), extraprostatic extension (EPE, p = 0.01), lymph node positivity (p = 0.001), positive surgical margin (PSM, p = 0.02), Gleason score (p = 0.01) and tumor volume percent (p < 0.001)]. The mean follow-up was 38.1 months. The BCR was significantly higher in group A as compared to group B(52.47 vs 7.9 %) respectively; p = 0.01). The mean time to BCR was significantly lesser in group A as compared to group B(8.9 vs 21.1 months respectively; p = 0.01). The BCR-free survival rates at 1 year and 3 years were significantly lower statistically in the persistent PSA group in comparison to other groups (69.7 vs 97.3 % and 48.5 vs 92.1 %, respectively; p = 0.01). On multivariate logistic regression analysis in patients with persistent PSA on follow-up, preoperative PSA >10 ng/ml, postoperative Gleason score ≥8, postoperative stage ≥pT3, positive pelvic lymph nodes, PSM >3 mm and post-RARP PSA doubling time (DT) <10 months (p < 0.001) were significantly associated with BCR. In patients after RARP, factors associated with aggressive disease (high preoperative PSA, Gleason score ≥8, stage ≥T3, PSM, high tumor volume percent and EPE) predict PSA persistence. Although these patients with persistent PSA after RARP are more likely to have BCR and that too earlier than those patients with undetectable PSA after RARP, a significant proportion of these patients (47.53 %) remain free of BCR. This subset of patients is associated with these favorable parameters (preoperative PSA <10 ng/ml, post-RARP PSA DT ≥10 months, postoperative Gleason score <8, pathologic stage 

Telocytes play a key role in prostate tissue organisation during the gland morphogenesis.

PubMed

Sanches, Bruno D A; Maldarine, Juliana S; Zani, Bruno C; Tamarindo, Guilherme H; Biancardi, Manoel F; Santos, Fernanda C A; Rahal, Paula; Góes, Rejane M; Felisbino, Sérgio L; Vilamaior, Patricia S L; Taboga, Sebastião R

2017-12-01

Telocytes are CD34-positive interstitial cells, known to exert several functions, one of which is a role in tissue organisation, previously demonstrated by telocytes in the myocardium. The existence of telocytes in the prostate has recently been reported, however, there is a lack of information regarding the function of these cells in prostate tissue, and information regarding the possible role of these cells in prostatic development. This study used immunofluorescence techniques in prostate tissue and prostatic telocytes in culture to determine the relationship between telocytes and prostate morphogenesis. Furthermore, immunofluorescent labelling of telocytes was performed on prostate tissue at different stages of early postnatal development. Initially, CD34-positive cells are found at the periphery of the developing alveoli, later in the same region, c-kit-positive cells and cells positive for both factors are verified and CD34-positive cells were predominantly observed in the interalveolar stroma and the region surrounding the periductal smooth muscle. Fluorescence assays also demonstrated that telocytes secrete TGF-β1 and are ER-Beta (ERβ) positive. The results suggest that telocytes play a changing role during development, initially supporting the differentiation of periductal and perialveolar smooth muscle, and later, producing dense networks that separate alveoli groups and form a barrier between the interalveolar region and periurethral smooth muscle. We conclude that telocytes play a relevant role in prostate tissue organisation during postnatal development. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Expression of lnterleukin-8 Correlates with Angiogenesis, Tumorigenicity, and Metastasis of Human Prostate Cancer Cells Implanted Orthotopically in Nude Mice1

PubMed Central

Sun, Jin Kim; Uehara, Hisanori; Karashima, Takashi; Mccarty, Marya; Shih, Nancy; Fidler, Isaiah J

2001-01-01

Abstract We determined whether the expression of interleukin-8 (IL-8) by human prostate cancer cells correlates with induction of angiogenesis, tumorigenicity, and production of metastasis. Low and high IL-8-producing clones were isolated from the heterogeneous PC-3 human prostate cancer cell line. The secretion of IL-8 protein correlated with transcriptional activity and levels of IL-8 mRNA. All PC-3 cells expressed both IL-8 receptors, CXCR1 and CXCR2. The low and high IL-8-producing clones were injected into the prostate of nude mice. Titration studies indicated that PC-3 cells expressing high levels of IL-8 were highly tumorigenic, producing rapidly growing, highly vascularized prostate tumors with and a 100% incidence of lymph node metastasis. Low IL-8-expressing PC-3 cells were less tumorigenic, producing slower growing and less vascularized primary tumors and a significantly lower incidence of metastasis. In situ hybridization (ISH) analysis of the tumors for expression of genes that regulate angiogenesis and metastasis showed that the expression level of IL-8, matrix metalloproteinases, vascular endothelial growth factor (VEGF), and E-cadherin corresponded with microvascular density and biological behavior of the prostate cancers in nude mice. Collectively, the data show that the expression level of IL-8 in human prostate cancer cells is associated with angiogenesis, tumorigenicity, and metastasis. PMID:11326314

Feasibility study of a new RF coil design for prostate MRI

NASA Astrophysics Data System (ADS)

Ha, Seunghoon; Roeck, Werner W.; Cho, Jaedu; Nalcioglu, Orhan

2014-09-01

The combined use of a torso-pelvic RF array coil and endorectal RF coil is the current state-of-the-art in prostate MRI. The endorectal coil provides high detection sensitivity to acquire high-spatial resolution images and spectroscopic data, while the torso-pelvic coil provides large coverage to assess pelvic lymph nodes and pelvic bones for metastatic disease. However, the use of an endorectal coil is an invasive procedure that presents difficulties for both patients and technicians. In this study, we propose a novel non-invasive RF coil design that can provide both image signal to noise ratio and field of view coverage comparable to the combined torso-pelvic and endorectal coil configuration. A prototype coil was constructed and tested using a pelvic phantom. The results demonstrate that this new design is a viable alternative for prostate MRI

Unusual Presentation of Bladder Paraganglioma: Comparison of (131)I MIBG SPECT/CT and (68)Ga DOTANOC PET/CT.

PubMed

Jain, Tarun Kumar; Basher, Rajender Kumar; Gupta, Nitin; Shukla, Jaya; Singh, Shrawan Kumar; Mittal, Bhagwant Rai

2016-01-01

Extraadrenal chromaffin cell-related tumors or paragangliomas are rare, especially in the bladder, accounting for less than 1% of cases. We report a 16-year-old boy who presented with hematuria and paroxysmal headache and was found to have a prostatic growth infiltrating the urinary bladder on anatomical imaging. Iodine-131 ((131)I) metaiodobenzylguanidine (MIBG) whole-body scanning and subsequently gallium-68 ((68)Ga) DOTANOC positron emission tomography/computed tomography (PET/CT) were performed. The MIBG scan revealed a non-tracer-avid soft-tissue mass, while DOTANOC PET/CT revealed a tracer-avid primary soft-tissue mass involving the urinary bladder and prostate with metastasis to the iliac lymph nodes. He underwent surgical management; histopathology of the surgical specimen revealed a bladder paraganglioma, whereas the prostate was found to be free of tumor.

Executing scatter operation to parallel computer nodes by repeatedly broadcasting content of send buffer partition corresponding to each node upon bitwise OR operation

DOEpatents

Archer, Charles J [Rochester, MN; Ratterman, Joseph D [Rochester, MN

2009-11-06

Executing a scatter operation on a parallel computer includes: configuring a send buffer on a logical root, the send buffer having positions, each position corresponding to a ranked node in an operational group of compute nodes and for storing contents scattered to that ranked node; and repeatedly for each position in the send buffer: broadcasting, by the logical root to each of the other compute nodes on a global combining network, the contents of the current position of the send buffer using a bitwise OR operation, determining, by each compute node, whether the current position in the send buffer corresponds with the rank of that compute node, if the current position corresponds with the rank, receiving the contents and storing the contents in a reception buffer of that compute node, and if the current position does not correspond with the rank, discarding the contents.

Clinical significance of CXCL16/CXCR6 expression in patients with prostate cancer.

PubMed

Ha, Hong Koo; Lee, Wan; Park, Hyun Jun; Lee, Sang Don; Lee, Jeong Zoo; Chung, Moon Kee

2011-01-01

We hypothesized that the CXCL16-CXCR6 ligand-receptor system may play an important role in prostate cancer progression. Levels of CXCL16 and CXCR6 expression were evaluated in prostate cancer cell lines (PC-3 and LNCaP) and normal prostate epithelial cells (PrEC), as well as in tissues from 354 patients. The immunohistochemical expression of CXCL16/CXCR6 was greater in the PC-3/LNCaP cells than in the PrEC cell line. The expression of CXCL16/CXCR6 was significantly higher in prostate cancer than in benign prostatic hypertrophy. Using RT-PCR, the expression of CXCL16/CXCR6 was found to be greater in the PC-3/LNCaP cells than in the PrEC cell line. CXCL16/CXCR6 was weakly detected in lung and liver tissues, whereas CXCL16 was highly expressed in specimens of bone metastasis. CXCL16 immunostaining was related to Gleason score, T stage, tumor volume, perineural invasion and lymph node metastasis. However, biochemical PSA recurrence was not related to the expression of CXCL16/CXCR6. High CXCL16/CXCR6 expression may be related to aggressive cancer behavior, and high CXCL16 expression to bone metastases.

Advances in prostate-specific membrane antigen PET of prostate cancer.

PubMed

Bouchelouche, Kirsten; Choyke, Peter L

2018-05-01

In recent years, a large number of reports have been published on prostate-specific membrane antigen (PSMA)/PET in prostate cancer (PCa). This review highlights advances in PSMA PET in PCa during the past year. PSMA PET/computed tomography (CT) is useful in detection of biochemical recurrence, especially at low prostate-specific antigen (PSA) values. The detection rate of PSMA PET is influenced by PSA level. For primary PCa, PSMA PET/CT shows promise for tumour localization in the prostate, especially in combination with multiparametric MRI (mpMRI). For primary staging, PSMA PET/CT can be used in intermediate and high-risk PCa. Intraoperative PSMA radioligand guidance seems promising for detection of malignant lymph nodes. While the use of PSMA PET/MRI in primary localized disease is limited to high and intermediate-risk patients and localized staging, in the recurrence setting, PET/MRI can be particularly helpful when the lesions are subtle. PSMA PET/CT is superior to choline PET/CT and other conventional imaging modalities. Molecular imaging with PSMA PET continues to pave the way for personalized medicine in PCa.However, large prospective clinical studies are still needed to fully evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa.

Frequency of Propionibacterium acnes Infection in Prostate Glands with Negative Biopsy Results Is an Independent Risk Factor for Prostate Cancer in Patients with Increased Serum PSA Titers.

PubMed

Kakegawa, Tomoya; Bae, Yuan; Ito, Takashi; Uchida, Keisuke; Sekine, Masaki; Nakajima, Yutaka; Furukawa, Asuka; Suzuki, Yoshimi; Kumagai, Jiro; Akashi, Takumi; Eishi, Yoshinobu

2017-01-01

Propionibacterium acnes has recently been implicated as a cause of chronic prostatitis and this commensal bacterium may be linked to prostate carcinogenesis. The occurrence of intracellular P. acnes infection in prostate glands and the higher frequency of P. acnes-positive glands in radical prostatectomy specimens from patients with prostate cancer (PCa) than in those from patients without PCa led us to examine whether the P. acnes-positive gland frequency can be used to assess the risk for PCa in patients whose first prostate biopsy, performed due to an increased prostate-specific antigen (PSA) titer, was negative. We retrospectively collected the first and last prostate biopsy samples from 44 patients that were diagnosed PCa within 4 years after the first negative biopsy and from 36 control patients with no PCa found in repeated biopsy for at least 3 years after the first biopsy. We evaluated P. acnes-positive gland frequency and P. acnes-positive macrophage number using enzyme-immunohistochemistry with a P. acnes-specific monoclonal antibody (PAL antibody). The frequency of P. acnes-positive glands was higher in PCa samples than in control samples in both first biopsy samples and in combined first and last biopsy samples (P < 0.001). A frequency greater than the threshold (18.5 and 17.7, respectively) obtained by each receiver operating characteristic curve was an independent risk factor for PCa (P = 0.003 and 0.001, respectively) with odds ratios (14.8 and 13.9, respectively) higher than those of serum PSA titers of patients just before each biopsy (4.6 and 2.3, respectively). The number of P. acnes-positive macrophages did not differ significantly between PCa and control samples. These results suggested that the frequency of P. acnes-positive glands in the first negative prostate biopsy performed due to increased PSA titers can be supportive information for urologists in planning repeated biopsy or follow-up strategies.

Sentinel node biopsy in thin and thick melanoma.

PubMed

Mozzillo, Nicola; Pennacchioli, Elisabetta; Gandini, Sara; Caracò, Corrado; Crispo, Anna; Botti, Gerardo; Lastoria, Secondo; Barberis, Massimo; Verrecchia, Francesco; Testori, Alessandro

2013-08-01

Although sentinel node biopsy (SNB) has become standard of care in patients with melanoma, its use in patients with thin or thick melanomas remains a matter of debate. This was a retrospective analysis of patients with thin (≤1 mm) or thick (≥4 mm) melanomas who underwent SNB at two Italian centers between 1998 and 2011. The associations of clinicopathologic features with sentinel lymph node positive status and overall survival (OS) were analyzed. In 492 patients with thin melanoma, sentinel node was positive for metastatic melanoma in 24 (4.9 %) patients. No sentinel node positivity was detected in patients with primary tumor thickness <0.3 mm. Mitotic rate was the only factor significantly associated with sentinel node positivity (p = 0.0001). Five-year OS was 81 % for patients with positive sentinel node and 93 % for negative sentinel node (p = 0.001). In 298 patients with thick melanoma, 39 % of patients had positive sentinel lymph nodes (median Breslow thickness 5 mm). In patients with positive sentinel node, 93 % had mitotic rate >1/mm(2). Five-year OS was 49 % for patients with positive sentinel lymph nodes and 56 % for patients with negative sentinel nodes (p = 0.005). The rate of sentinel node positivity in patients with thin melanoma was 4.9 %. The only clinicopathologic factor related to node positivity was mitotic rate. Given its prognostic importance, SNB should be considered in such patients. SNB should also be the standard method for melanoma ≥4 mm, not only for staging, but also for guiding therapeutic decisions.

68Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA <0.5 ng/ml. Efficacy and impact on treatment strategy.

PubMed

Farolfi, Andrea; Ceci, Francesco; Castellucci, Paolo; Graziani, Tiziano; Siepe, Giambattista; Lambertini, Alessandro; Schiavina, Riccardo; Lodi, Filippo; Morganti, Alessio G; Fanti, Stefano

2018-06-15

The primary aim of this retrospective, single-centre analysis was to assess the performance of 68 Ga-PSMA-11 PET/CT in prostate cancer (PCa) patients in early PSA failure after radical prostatectomy (RP). The secondary aim was to assess the potential impact of 68 Ga-PSMA-11 PET/CT on treatment strategy. 68 Ga-PSMA-11 PET/CT is performed in our institution within an investigational new drug (IND) trial in PCa patients with biochemical recurrence (BCR). The records of all patients enrolled between March 2016 and July 2017 were evaluated. These records were retrospectively analysed according to the following inclusion criteria: (a) RP as primary therapy, (b) proven BCR, ©) PSA levels in the range 0.2-0.5 ng/ml at the time of the 68 Ga-PSMA-11 PET/CT investigation, and (d) no salvage radiotherapy (S-RT) performed after recurrence. The performance of 68 Ga-PSMA-11 PET/CT was evaluated in terms of detection rate on a per-patient and a per-region basis (local vs. distant lesions). We further performed an intention-to-treat (ITT) analysis. The patient cohort was grouped into three subpopulations, blinded to the 68 Ga-PSMA-11 PET/CT results, according to the patients' characteristics and different patterns of treatment: (1) S-RT (with or without systemic treatment), (2) stereotactic body radiotherapy (SBRT) (with or without systemic treatment), and (3) systemic treatment. The treatment strategy was re-evaluated for each patient taking into consideration the 68 Ga-PSMA-11 PET/CT images. We enrolled 119 PCa patients (mean age 66 years, range 44-78 years) with a mean PSA level at the time of 68 Ga-PSMA-11 PET/CT of 0.34 ng/ml (median 0.32 ng/ml, SD ±0.09, range 0.20-0.50 ng/ml). 68 Ga-PSMA-1 1 PET/CT was positive in 41 of the 119 patients, resulting in an overall detection rate of 34.4%. 68 Ga-PSMA-11 uptake was observed in the prostate bed (3 patients, 2.5%), in the pelvic lymph nodes (21, 17.6%), in the retroperitoneal lymph nodes (4, 3.4%) and in the skeleton (21, 17.6%). Regarding ITT, 81 patients (68.1%) were considered possible candidates for S-RT only in the prostate bed and none of the patients (0%) for SBRT. According to the 68 Ga-PSMA-11 PET/CT results, the intended treatment was changed in 36 patients (30.2%). According to the PET/CT results, S-RT was recommended in 70 patients (58.8%), only to the prostate bed in 58 (48.7%) and SBRT in 29 (24.4%). The intended RT planning was modified in 36 (87.8%) of 41 patients with a positive 68 Ga-PSMA-11 PET/CT result. In our patient series with PSA levels <0.5 ng/ml, 68 Ga-PSMA-11 PET/CT had a detection rate of 34.4%. In the ITT analysis, 30.2% of patients had a change in the intended treatment. These data support the hypothesis that 68 Ga-PSMA-11 PET/CT is a useful procedure in the management of PCa patients showing early recurrence after RP, and should be implemented in routine clinical practice.

Usefulness of GATA-3 as a marker of seminal epithelium in prostate biopsies.

PubMed

Ortiz-Rey, J A; Chantada-de la Fuente, D; Peteiro-Cancelo, M Á; Gómez-de María, C; San Miguel-Fraile, M P

2017-11-01

The incidental presence of seminal vesicle epithelium in prostate needle biopsies is generally recognisable through routine microscopy. However, the biopsy can sometimes be erroneously interpreted as malignant due to its architectural and cytological characteristics, and immunohistochemistry can be useful for correctly identifying the biopsy. Our objective was to analyse the potential usefulness of GATA-3 as a marker of seminal epithelium. Through immunohistochemistry with a monoclonal anti-GATA-3 antibody (clone L50-823), we studied seminal vesicle sections from 20 prostatectomy specimens, 12 prostate needle biopsies that contained seminal vesicle tissue and 68 prostate biopsies without seminal vesicle epithelium, 36 of which showed adenocarcinoma. Staining for GATA-3 was intense in the 20 seminal vesicles of the prostatectomy specimens and in the 12 prostate needle biopsies that contained seminal epithelium. In the 60 biopsies without a seminal vesicle, GATA-3 was positive in the prostate basal cells and even in the secretory cells (57 cases), although with less intensity in 55 of the cases. One of the 36 prostatic adenocarcinomas tested positive for GATA-3. The intense immunohistochemical expression of GATA-3 in the seminal vesicle epithelium can help identify the epithelium in prostate biopsies. This marker is also positive in the basal cells of healthy prostates and, with less intensity, in the secretory cells. Positivity, weak or moderate, is observed on rare occasions in prostatic adenocarcinomas. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Executing a gather operation on a parallel computer

DOEpatents

Archer, Charles J [Rochester, MN; Ratterman, Joseph D [Rochester, MN

2012-03-20

Methods, apparatus, and computer program products are disclosed for executing a gather operation on a parallel computer according to embodiments of the present invention. Embodiments include configuring, by the logical root, a result buffer or the logical root, the result buffer having positions, each position corresponding to a ranked node in the operational group and for storing contribution data gathered from that ranked node. Embodiments also include repeatedly for each position in the result buffer: determining, by each compute node of an operational group, whether the current position in the result buffer corresponds with the rank of the compute node, if the current position in the result buffer corresponds with the rank of the compute node, contributing, by that compute node, the compute node's contribution data, if the current position in the result buffer does not correspond with the rank of the compute node, contributing, by that compute node, a value of zero for the contribution data, and storing, by the logical root in the current position in the result buffer, results of a bitwise OR operation of all the contribution data by all compute nodes of the operational group for the current position, the results received through the global combining network.

Salvage Stereotactic Body Radiotherapy for Isolated Lymph Node Recurrent Prostate Cancer: Single Institution Series of 94 Consecutive Patients and 124 Lymph Nodes.

PubMed

Jereczek-Fossa, Barbara Alicja; Fanetti, Giuseppe; Fodor, Cristiana; Ciardo, Delia; Santoro, Luigi; Francia, Claudia Maria; Muto, Matteo; Surgo, Alessia; Zerini, Dario; Marvaso, Giulia; Timon, Giorgia; Romanelli, Paola; Rondi, Elena; Comi, Stefania; Cattani, Federica; Golino, Federica; Mazza, Stefano; Matei, Deliu Victor; Ferro, Matteo; Musi, Gennaro; Nolè, Franco; de Cobelli, Ottavio; Ost, Piet; Orecchia, Roberto

2017-08-01

The purpose of the study was to evaluate the prostate serum antigen (PSA) response, local control, progression-free survival (PFS), and toxicity of stereotactic body radiotherapy (SBRT) for lymph node (LN) oligorecurrent prostate cancer. Between May 2012 and October 2015, 124 lesions were treated in 94 patients with a median dose of 24 Gy in 3 fractions. Seventy patients were treated for a single lesion and 25 for > 1 lesion. In 34 patients androgen deprivation (AD) was combined with SBRT. We evaluated biochemical response according to PSA level every 3 months after SBRT: a 3-month PSA decrease from pre-SBRT PSA of more than 10% identified responder patients. In case of PSA level increase, imaging was performed to evaluate clinical progression. Toxicity was assessed every 6 to 9 months after SBRT. Median follow-up was 18.5 months. In 13 patients (14%) Grade 1 to 2 toxicity was reported without any Grade 3 to 4 toxicity. Biochemical response, stabilization, and progression were observed in 64 (68%), 10 (11%), and 20 (21%) of 94 evaluable patients. Clinical progression was observed in 31 patients (33%) after a median time of 8.1 months. In-field progression occurred in 12 lesions (9.7%). Two-year local control and PFS rates were 84% and 30%, respectively. Age older than 75 years correlated with better biochemical response rate. Age older than 75 years, concomitant AD administered up to 12 months, and pelvic LN involvement correlated with longer PFS. SBRT is safe and offers good in-field control. At 2 years after SBRT, 1 of 3 patients is progression-free. Further investigation is warranted to identify patients who benefit most from SBRT and to define the optimal combination with AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Prostate stem cell antigen (PSCA) mRNA expression in peripheral blood in patients with benign prostatic hyperplasia and/or prostate cancer.

PubMed

Fawzy, Mohamed S; Mohamed, Randa H; Elfayoumi, Abdel-Rahman R

2015-03-01

The aim of this study was to determine whether detection of prostate stem cell antigen (PSCA) expression in BPH might be associated with the subsequent presence of Prostate cancer (PCa) and also to determine whether detection of PSCA expression has potential for prognosis in PCa. This study was comprised of 112 PCa patients, 111 BPH patients and 120 control subjects. We employed reverse-transcriptase polymerase chain reaction (RT-PCR) to detect PSCA mRNA-bearing cells in peripheral blood. PSCA mRNA was detected in the peripheral blood of 71.4% PCa patients and in 13.5% of patients with BPH by RT-PCR. PSCA was positive in 80% of high-grade diseases compared with 20% of low-grade diseases (P = 0.01). Whereas only 38.8% of prostate-confined diseases were PSCA positive, 61.2% of extraprostatic diseases were PSCA positive (P < 0.001). Patients with a lymphovascular invasion of tumor emboli tended to be PSCA positive (P = 0.02). BPH patients with RT-PCR PSCA positive were significantly more likely to develop prostate cancer (OR = 16, 95% CI = 8.1-31.6, P < 0.001). In conclusion, RT-PCR PSCA positivity is significantly associated with the Gleason score, LV tumor emboli and whether or not the tumor was organ confined. In this study, RT-PCR PSCA detection may be a promising tumor marker of diagnostic and metastasis detection for patients with prostate cancer. Also, it may be an important test for predicting BPH patients who are at high risk of subsequent cancer development.

The diagnostic value of thyroglobulin concentration in fine-needle aspiration of the cervical lymph nodes in patients with differentiated thyroid cancer.

PubMed

Mikosiński, Sławomir; Pomorski, Lech; Oszukowska, Lidia; Makarewicz, Jacek; Adamczewski, Zbigniew; Sporny, Stanisław; Lewiński, Andrzej

2006-01-01

Recurrent differentiated thyroid cancer generally occurs first in the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but is not specific enough. Ultrasound-guided fine-needle biopsy increases the specificity but still may fail to detect a recurrence of the disease in the cystic metastatic lymph nodes. The aim of the study was to estimate the value of Tg concentration in the needle washout after fine-needle aspiration of suspicious lymph nodes. The 105 patients studied had presented one or more enlarged suspicious cervical lymph nodes. All had undergone total thyroidectomy and (131)I ablative therapy. Serum thyroglobulin (Tg) concentration was within the 0.15-711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94-100%. The positive Tg washout concentration cut-off value was established as equal to the mean plus two standard deviations of the Tg washout concentration of patients with negative cytology. Lymph node involvement was diagnosed by cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned out to have positive cytology had a positive Tg washout concentration. All lymph nodes with positive cytology were positive in pathology. Seven patients and 20 lymph nodes with negative cytology were positive in the Tg washout concentration test. All but one patients and all but two lymph nodes with a positive Tg washout concentration had positive pathology. 1. Ultrasound-guided fine-needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2. The Tg washout concentration test is 100% sensitive in the detection of metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is 100% specific. 4. The Tg washout concentration test carries a risk of false-positive results. 5. Both methods should be used for early detection of metastatic lymph nodes in patients with differentiated thyroid cancer.

Unusual Presentation of Bladder Paraganglioma: Comparison of 131I MIBG SPECT/CT and 68Ga DOTANOC PET/CT

PubMed Central

Jain, Tarun Kumar; Basher, Rajender Kumar; Gupta, Nitin; Shukla, Jaya; Singh, Shrawan Kumar; Mittal, Bhagwant Rai

2016-01-01

Extraadrenal chromaffin cell-related tumors or paragangliomas are rare, especially in the bladder, accounting for less than 1% of cases. We report a 16-year-old boy who presented with hematuria and paroxysmal headache and was found to have a prostatic growth infiltrating the urinary bladder on anatomical imaging. Iodine-131 (131I) metaiodobenzylguanidine (MIBG) whole-body scanning and subsequently gallium-68 (68Ga) DOTANOC positron emission tomography/computed tomography (PET/CT) were performed. The MIBG scan revealed a non-tracer-avid soft-tissue mass, while DOTANOC PET/CT revealed a tracer-avid primary soft-tissue mass involving the urinary bladder and prostate with metastasis to the iliac lymph nodes. He underwent surgical management; histopathology of the surgical specimen revealed a bladder paraganglioma, whereas the prostate was found to be free of tumor. PMID:26912984

Pim Kinases Promote Migration and Metastatic Growth of Prostate Cancer Xenografts

PubMed Central

Santio, Niina M.; Eerola, Sini K.; Paatero, Ilkka; Yli-Kauhaluoma, Jari; Anizon, Fabrice; Moreau, Pascale; Tuomela, Johanna; Härkönen, Pirkko; Koskinen, Päivi J.

2015-01-01

Background and methods Pim family proteins are oncogenic kinases implicated in several types of cancer and involved in regulation of cell proliferation, survival as well as motility. Here we have investigated the ability of Pim kinases to promote metastatic growth of prostate cancer cells in two xenograft models for human prostate cancer. We have also evaluated the efficacy of Pim-selective inhibitors to antagonize these effects. Results We show here that tumorigenic growth of both subcutaneously and orthotopically inoculated prostate cancer xenografts is enhanced by stable overexpression of either Pim-1 or Pim-3. Moreover, Pim-overexpressing orthotopic prostate tumors are highly invasive and able to migrate not only to the nearby prostate-draining lymph nodes, but also into the lungs to form metastases. When the xenografted mice are daily treated with the Pim-selective inhibitor DHPCC-9, both the volumes as well as the metastatic capacity of the tumors are drastically decreased. Interestingly, the Pim-promoted metastatic growth of the orthotopic xenografts is associated with enhanced angiogenesis and lymphangiogenesis. Furthermore, forced Pim expression also increases phosphorylation of the CXCR4 chemokine receptor, which may enable the tumor cells to migrate towards tissues such as the lungs that express the CXCL12 chemokine ligand. Conclusions Our results indicate that Pim overexpression enhances the invasive properties of prostate cancer cells in vivo. These effects can be reduced by the Pim-selective inhibitor DHPCC-9, which can reach tumor tissues without serious side effects. Thus, Pim-targeting therapies with DHPCC-9-like compounds may help to prevent progression of local prostate carcinomas to fatally metastatic malignancies. PMID:26075720

Frequency of Propionibacterium acnes Infection in Prostate Glands with Negative Biopsy Results Is an Independent Risk Factor for Prostate Cancer in Patients with Increased Serum PSA Titers

PubMed Central

Ito, Takashi; Uchida, Keisuke; Sekine, Masaki; Nakajima, Yutaka; Furukawa, Asuka; Suzuki, Yoshimi; Kumagai, Jiro; Akashi, Takumi

2017-01-01

Background Propionibacterium acnes has recently been implicated as a cause of chronic prostatitis and this commensal bacterium may be linked to prostate carcinogenesis. The occurrence of intracellular P. acnes infection in prostate glands and the higher frequency of P. acnes-positive glands in radical prostatectomy specimens from patients with prostate cancer (PCa) than in those from patients without PCa led us to examine whether the P. acnes-positive gland frequency can be used to assess the risk for PCa in patients whose first prostate biopsy, performed due to an increased prostate-specific antigen (PSA) titer, was negative. Methods We retrospectively collected the first and last prostate biopsy samples from 44 patients that were diagnosed PCa within 4 years after the first negative biopsy and from 36 control patients with no PCa found in repeated biopsy for at least 3 years after the first biopsy. We evaluated P. acnes-positive gland frequency and P. acnes-positive macrophage number using enzyme-immunohistochemistry with a P. acnes-specific monoclonal antibody (PAL antibody). Results The frequency of P. acnes-positive glands was higher in PCa samples than in control samples in both first biopsy samples and in combined first and last biopsy samples (P < 0.001). A frequency greater than the threshold (18.5 and 17.7, respectively) obtained by each receiver operating characteristic curve was an independent risk factor for PCa (P = 0.003 and 0.001, respectively) with odds ratios (14.8 and 13.9, respectively) higher than those of serum PSA titers of patients just before each biopsy (4.6 and 2.3, respectively). The number of P. acnes-positive macrophages did not differ significantly between PCa and control samples. Conclusions These results suggested that the frequency of P. acnes-positive glands in the first negative prostate biopsy performed due to increased PSA titers can be supportive information for urologists in planning repeated biopsy or follow-up strategies. PMID:28081259

Comparison of testicular dose delivered by intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, Jeffrey M.; Handorf, Elizabeth A.; Price, Robert A.

A small decrease in testosterone level has been documented after prostate irradiation, possibly owing to the incidental dose to the testes. Testicular doses from prostate external beam radiation plans with either intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) were calculated to investigate any difference. Testicles were contoured for 16 patients being treated for localized prostate cancer. For each patient, 2 plans were created: 1 with IMRT and 1 with VMAT. No specific attempt was made to reduce testicular dose. Minimum, maximum, and mean doses to the testicles were recorded for each plan. Of the 16 patients, 4 receivedmore » a total dose of 7800 cGy to the prostate alone, 7 received 8000 cGy to the prostate alone, and 5 received 8000 cGy to the prostate and pelvic lymph nodes. The mean (range) of testicular dose with an IMRT plan was 54.7 cGy (21.1 to 91.9) and 59.0 cGy (25.1 to 93.4) with a VMAT plan. In 12 cases, the mean VMAT dose was higher than the mean IMRT dose, with a mean difference of 4.3 cGy (p = 0.019). There was a small but statistically significant increase in mean testicular dose delivered by VMAT compared with IMRT. Despite this, it unlikely that there is a clinically meaningful difference in testicular doses from either modality.« less

A novel murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) induced by immunization with a spermine binding protein (p25) peptide

PubMed Central

Altuntas, Cengiz Z.; Veizi, Elias; Izgi, Kenan; Bicer, Fuat; Ozer, Ahmet; Grimberg, Kerry O.; Bakhautdin, Bakytzhan; Sakalar, Cagri; Tasdemir, Cemal; Tuohy, Vincent K.

2013-01-01

The pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is poorly understood. Inflammatory and autoimmune mechanisms may play a role. We developed a murine model of experimental autoimmune prostatitis (EAP) that mimics the human phenotype of CP/CPPS. Eight-week-old mice were immunized subcutaneously with prostate-specific peptides in an emulsion of complete Freund's adjuvant. Mice were euthanized 10 days after immunization, and lymph node cells were isolated and assessed for recall proliferation to each peptide. P25 99–118 was the most immunogenic peptide. T-cell and B-cell immunity and serum levels of C-reactive protein and nitrate/nitrite levels were evaluated over a 9-wk period. Morphometric studies of prostate, 24-h micturition frequencies, and urine volume per void were evaluated. Tactile referred hyperalgesia was measured using von Frey filaments to the pelvic region. The unpaired Student's t-test was used to analyze differences between EAP and control groups. Prostates from p25 99–118-immunized mice demonstrated elevated gene expression levels of TNF-α, IL-17A, IFN-γ, and IL-1β, not observed in control mice. Compared with controls, p25 99–118-immunized mice had significantly higher micturition frequency and decreased urine output per void, and they demonstrated elevated pelvic pain response. p25 99–118 immunization of male SWXJ mice induced prostate-specific autoimmunity characterized by prostate-confined inflammation, increased micturition frequency, and pelvic pain. This autoimmune prostatitis model provides a useful tool for exploring the pathophysiology and new treatments. PMID:23344231

Impact of knee support and shape of tabletop on rectum and prostate position

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steenbakkers, Roel; Duppen, Joop C.; Betgen, Anja

2004-12-01

Purpose: To evaluate the impact of different tabletops with or without a knee support on the position of the rectum, prostate, and bulb of the penis; and to evaluate the effect of these patient-positioning devices on treatment planning. Methods and materials: For 10 male volunteers, five MRI scans were made in four different positions: on a flat tabletop with knee support, on a flat tabletop without knee support, on a rounded tabletop with knee support, and on a rounded tabletop without knee support. The fifth scan was in the same position as the first. With image registration, the position differencesmore » of the rectum, prostate, and bulb of the penis were measured at several points in a sagittal plane through the central axis of the prostate. A planning target volume was generated from the delineated prostates with a margin of 10 mm in three dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each planning target volume. Dose-volume histograms were calculated for all rectal walls. Results: The shape of the tabletop did not affect the rectum and prostate position. Addition of a knee support shifted the anterior and posterior rectal walls dorsally. For the anterior rectal wall, the maximum dorsal shift was 9.9 mm (standard error of the mean [SEM] 1.7 mm) at the top of the prostate. For the posterior rectal wall, the maximum dorsal shift was 10.2 mm (SEM 1.5 mm) at the middle of the prostate. Therefore, the rectal filling was pushed caudally when a knee support was added. The knee support caused a rotation of the prostate around the left-right axis at the apex (i.e., a dorsal rotation) by 5.6 deg (SEM 0.8 deg ) and shifts in the caudal and dorsal directions of 2.6 mm (SEM 0.4 cm) and 1.4 mm (SEM 0.6 mm), respectively. The position of the bulb of the penis was not influenced by the use of a knee support or rounded tabletop. The volume of the rectal wall receiving the same dose range (e.g., 40-75 Gy) was reduced by 3.5% (SEM 0.9%) when a knee support was added. No significant differences were observed between the first and fifth scan (flat tabletop with knee support) for all measured points, thereby excluding time trends. Conclusions: The rectum and prostate were significantly shifted dorsally by the use of a knee support. The rectum shifted more than the prostate, resulting in a dose benefit compared with irradiation without knee support. The shape of the tabletop did not influence the rectum or prostate position.« less

Prostatic cancer. Treated at a categorical center, 1980-1983.

PubMed

Slack, N H; Lane, W W; Priore, R L; Murphy, G P

1986-03-01

This report covers the experience from 537 patients with prostatic cancer seen at Roswell Park Memorial Institute (RPMI) from 1980 through 1983. This is a look at experiences in the early 1980s and is a continuation of the series covering the decades of the 1950s, 1960s, and 1970s. Referrals continue to dominate the series (85% of cases) but are now only slightly younger (65 years) than in-house diagnoses (66 years), of which one third were diagnosed at autopsy. Survival rates in this series, although limited in follow-up, were similar at two years to those in the 1970s and in the extensive series collected by the survey of the American College of Surgeons. Multiple primary tumors were observed in 22 per cent of this series, most frequently involving the bladder in addition to the prostate. Treatments continue to involve chemotherapy earlier in the course of disease as part of a succession of therapeutic modalities that include transurethral resection of prostate (TURP) or prostatectomy, lymph node dissection, external irradiation, castration, and hormones.

Predicting Likelihood of Having Four or More Positive Nodes in Patient With Sentinel Lymph Node-Positive Breast Cancer: A Nomogram Validation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unal, Bulent; Gur, Akif Serhat; Beriwal, Sushil

2009-11-15

Purpose: Katz suggested a nomogram for predicting having four or more positive nodes in sentinel lymph node (SLN)-positive breast cancer patients. The findings from this formula might influence adjuvant radiotherapy decisions. Our goal was to validate the accuracy of the Katz nomogram. Methods and Materials: We reviewed the records of 309 patients with breast cancer who had undergone completion axillary lymph node dissection. The factors associated with the likelihood of having four or more positive axillary nodes were evaluated in patients with one to three positive SLNs. The nomogram developed by Katz was applied to our data set. The areamore » under the curve of the corresponding receiver operating characteristics curve was calculated for the nomogram. Results: Of the 309 patients, 80 (25.9%) had four or more positive axillary lymph nodes. On multivariate analysis, the number of positive SLNs (p < .0001), overall metastasis size (p = .019), primary tumor size (p = .0001), and extracapsular extension (p = .01) were significant factors predicting for four or more positive nodes. For patients with <5% probability, 90.3% had fewer than four positive nodes and 9.7% had four or more positive nodes. The negative predictive value was 91.7%, and sensitivity was 80%. The nomogram was accurate and discriminating (area under the curve, .801). Conclusion: The probability of four or more involved nodes is significantly greater in patients who have an increased number of positive SLNs, increased overall metastasis size, increased tumor size, and extracapsular extension. The Katz nomogram was validated in our patients. This nomogram will be helpful to clinicians making adjuvant treatment recommendations to their patients.« less

Automated Patient Positioning Guided by Cone-Beam CT for Prostate Radiotherapy

DTIC Science & Technology

2009-01-01

clinically implemented an automated patient positioning strategy and tested with phantom experiments; (2) developed image-to-projection deformable...31st, 2008). The goal of this project is to develop a clinically practical technique for prostate patient positioning based on newly emerged CBCT...tissue organs; Secondly, it considers both the prostate target and the organs at risk (OARs) simultaneously, thus a better clinical decision can be

The Oncogenic Role of WWP1 E3 Ubiquitin Ligase in Prostate Cancer Development

DTIC Science & Technology

2011-05-01

receptors are overexpressed and predict a low risk in human breast cancer. Cancer Res 1993;53:3736–40. 26. Koda M, Sulkowski S, Garofalo C, Kanczuga... Koda L, Sulkowska M, Surmacz E. Expression of the insulin-like growth factor-I recep- tor in primary breast cancer and lymph node metastases

Differential blood-based diagnosis between benign prostatic hyperplasia and prostate cancer: miRNA as source for biomarkers independent of PSA level, Gleason score, or TNM status.

PubMed

Leidinger, Petra; Hart, Martin; Backes, Christina; Rheinheimer, Stefanie; Keck, Bastian; Wullich, Bernd; Keller, Andreas; Meese, Eckart

2016-08-01

Since the benefit of prostate-specific antigen (PSA) screening remains controversial, new non-invasive biomarkers for prostate carcinoma (PCa) are still required. There is evidence that microRNAs (miRNAs) in whole peripheral blood can separate patients with localized prostate cancer from healthy individuals. However, the potential of blood-based miRNAs for the differential diagnosis of PCa and benign prostatic hyperplasia (BPH) has not been tested. We compared the miRNome from blood of PCa and BPH patients and further investigated the influence of the tumor volume, tumor-node-metastasis (TNM) classification, Gleason score, pretreatment risk status, and the pretreatment PSA value on the miRNA pattern. By microarray approach, we identified seven miRNAs that were significantly deregulated in PCa patients compared to BPH patients. Using quantitative real time PCR (qRT-PCR), we confirmed downregulation of hsa-miR-221* (now hsa-miR-221-5p) and hsa-miR-708* (now hsa-miR-708-3p) in PCa compared to BPH. Clinical parameters like PSA level, Gleason score, or TNM status seem to have only limited impact on the overall abundance of miRNAs in patients' blood, suggesting a no influence of these factors on the expression of deregulated miRNAs.

Prognostic Value of Protocadherin10 (PCDH10) Methylation in Serum of Prostate Cancer Patients.

PubMed

Deng, Qiu-Kui; Lei, Yong-Gang; Lin, Ying-Li; Ma, Jian-Guo; Li, Wen-Ping

2016-02-16

BACKGROUND Prostate cancer is a heterogeneous malignancy with outcome difficult to predict. Currently, there is an urgent need to identify novel biomarkers that can accurately predict patient outcome and improve the treatment strategy. The aim of this study was to investigate the methylation status of PCDH10 in serum of prostate cancer patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS The methylation status of PCDH10 in serum of 171 primary prostate cancer patients and 65 controls was evaluated by methylation-specific PCR (MSP), after which the relationship between PCDH10 methylation and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis were used to evaluate the correlation between PCDH10 methylation and prognosis. RESULTS PCDH10 methylation occurred frequently in serum of prostate cancer patients. Moreover, PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis, and biochemical recurrence (BCR). In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival than patients with unmethylated PCDH10. Univariate and multivariate Cox proportional hazards model analysis indicated that PCDH10 methylation in serum is an independent predictor of worse BCR-free survival and overall survival. CONCLUSIONS PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer.

PSCA expression is associated with favorable tumor features and reduced PSA recurrence in operated prostate cancer.

PubMed

Heinrich, Marie-Christine; Göbel, Cosima; Kluth, Martina; Bernreuther, Christian; Sauer, Charlotte; Schroeder, Cornelia; Möller-Koop, Christina; Hube-Magg, Claudia; Lebok, Patrick; Burandt, Eike; Sauter, Guido; Simon, Ronald; Huland, Hartwig; Graefen, Markus; Heinzer, Hans; Schlomm, Thorsten; Heumann, Asmus

2018-05-31

Prostate Stem Cell Antigen (PSCA) is frequently expressed in prostate cancer but its exact function is unclear. To clarify contradictory findings on the prognostic role of PSCA expression, a tissue microarray containing 13,665 prostate cancers was analyzed by immunohistochemistry. PSCA staining was absent in normal epithelial and stromal cells of the prostate. Membranous and cytoplasmic PSCA staining was seen in 53.7% of 9642 interpretable tumors. Staining was weak in 22.4%, moderate in 24.5% and strong in 6.8% of tumors. PSCA expression was associated with favorable pathological and clinical tumor features: Early pathological tumor stage (p < 0.0001), low Gleason grade (p < 0.0001), absence of lymph node metastasis (p < 0.0001), low pre-operative PSA level (p = 0.0118), negative surgical margin (p < 0.0001) and reduced PSA recurrence (p < 0.0001). PSCA expression was an independent predictor of prognosis in multivariate analysis (hazard ratio 0.84, p < 0.0001). The absence of statistical relationship to TMPRSS2:ERG fusion status, chromosomal deletion or high tumor cell proliferation argues against a major role of PSCA for regulation of cell cycle or genomic integrity. PSCA expression is linked to favorable prognosis. PSCA measurement is a candidate for inclusion in multi-parametric prognostic prostate cancer tests.

Interval sentinel lymph nodes in melanoma: a digital pathology analysis of Ki67 expression and microvascular density.

PubMed

Marinaccio, Christian; Giudice, Giuseppe; Nacchiero, Eleonora; Robusto, Fabio; Opinto, Giuseppina; Lastilla, Gaetano; Maiorano, Eugenio; Ribatti, Domenico

2016-08-01

The presence of interval sentinel lymph nodes in melanoma is documented in several studies, but controversies still exist about the management of these lymph nodes. In this study, an immunohistochemical evaluation of tumor cell proliferation and neo-angiogenesis has been performed with the aim of establishing a correlation between these two parameters between positive and negative interval sentinel lymph nodes. This retrospective study reviewed data of 23 patients diagnosed with melanoma. Bioptic specimens of interval sentinel lymph node were retrieved, and immunohistochemical reactions on tissue sections were performed using Ki67 as a marker of proliferation and CD31 as a blood vessel marker for the study of angiogenesis. The entire stained tissue sections for each case were digitized using Aperio Scanscope Cs whole-slide scanning platform and stored as high-resolution images. Image analysis was carried out on three selected fields of equal area using IHC Nuclear and Microvessel analysis algorithms to determine positive Ki67 nuclei and vessel number. Patients were divided into positive and negative interval sentinel lymph node groups, and the positive interval sentinel lymph node group was further divided into interval positive with micrometastasis and interval positive with macrometastasis subgroups. The analysis revealed a significant difference between positive and negative interval sentinel lymph nodes in the percentage of Ki67-positive nuclei and mean vessel number suggestive of an increased cellular proliferation and angiogenesis in positive interval sentinel lymph nodes. Further analysis in the interval positive lymph node group showed a significant difference between micro- and macrometastasis subgroups in the percentage of Ki67-positive nuclei and mean vessel number. Percentage of Ki67-positive nuclei was increased in the macrometastasis subgroup, while mean vessel number was increased in the micrometastasis subgroup. The results of this study suggest that the correlation between tumor cell proliferation and neo-angiogenesis in interval sentinel lymph nodes in melanoma could be used as a good predictive marker to distinguish interval positive sentinel lymph nodes with micrometastasis from interval positive lymph nodes with macrometastasis subgroups.

Role of monocyte-lineage cells in prostate cancer cell invasion and tissue factor expression.

PubMed

Lindholm, Paul F; Lu, Yi; Adley, Brian P; Vladislav, Tudor; Jovanovic, Borko; Sivapurapu, Neela; Yang, Ximing J; Kajdacsy-Balla, André

2010-11-01

Tissue factor (TF) is a cell surface glycoprotein intricately related to blood coagulation and inflammation. This study was performed to investigate the role of monocyte-lineage cells in prostate cancer cell TF expression and cell invasion. Prostate cancer cell invasion was tested with and without added peripheral blood monocytes or human monocyte-lineage cell lines. TF neutralizing antibodies were used to determine the TF requirement for prostate cancer cell invasion activity. Immunohistochemistry was performed to identify prostate tissue CD68 positive monocyte-derived cells and prostate epithelial TF expression. Co-culture of PC-3, DU145, and LNCaP cells with isolated human monocytes significantly stimulated prostate cancer cell invasion activity. TF expression was greater in highly invasive prostate cancer cells and was induced in PC-3, DU145, and LNCaP cells by co-culture with U-937 cells, but not with THP-1 cells. TF neutralizing antibodies inhibited PC-3 cell invasion in co-cultures with monocyte-lineage U-937 or THP-1 cells. Prostate cancer tissues contained more CD68 positive cells in the stroma and epithelium (145 ± 53/mm(2)) than benign prostate (108 ± 31/mm(2)). Samples from advanced stage prostate cancer tended to contain more CD68 positive cells when compared with lower stage lesions. Prostatic adenocarcinoma demonstrated significantly increased TF expression compared with benign prostatic epithelium. This study shows that co-culture with monocyte-lineage cells induced prostate cancer cell invasion activity. PC-3 invasion and TF expression was induced in co-culture with U-937 cells and partially inhibited with TF neutralizing antibodies.

Analysis of deformable image registration accuracy using computational modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhong Hualiang; Kim, Jinkoo; Chetty, Indrin J.

2010-03-15

Computer aided modeling of anatomic deformation, allowing various techniques and protocols in radiation therapy to be systematically verified and studied, has become increasingly attractive. In this study the potential issues in deformable image registration (DIR) were analyzed based on two numerical phantoms: One, a synthesized, low intensity gradient prostate image, and the other a lung patient's CT image data set. Each phantom was modeled with region-specific material parameters with its deformation solved using a finite element method. The resultant displacements were used to construct a benchmark to quantify the displacement errors of the Demons and B-Spline-based registrations. The results showmore » that the accuracy of these registration algorithms depends on the chosen parameters, the selection of which is closely associated with the intensity gradients of the underlying images. For the Demons algorithm, both single resolution (SR) and multiresolution (MR) registrations required approximately 300 iterations to reach an accuracy of 1.4 mm mean error in the lung patient's CT image (and 0.7 mm mean error averaged in the lung only). For the low gradient prostate phantom, these algorithms (both SR and MR) required at least 1600 iterations to reduce their mean errors to 2 mm. For the B-Spline algorithms, best performance (mean errors of 1.9 mm for SR and 1.6 mm for MR, respectively) on the low gradient prostate was achieved using five grid nodes in each direction. Adding more grid nodes resulted in larger errors. For the lung patient's CT data set, the B-Spline registrations required ten grid nodes in each direction for highest accuracy (1.4 mm for SR and 1.5 mm for MR). The numbers of iterations or grid nodes required for optimal registrations depended on the intensity gradients of the underlying images. In summary, the performance of the Demons and B-Spline registrations have been quantitatively evaluated using numerical phantoms. The results show that parameter selection for optimal accuracy is closely related to the intensity gradients of the underlying images. Also, the result that the DIR algorithms produce much lower errors in heterogeneous lung regions relative to homogeneous (low intensity gradient) regions, suggests that feature-based evaluation of deformable image registration accuracy must be viewed cautiously.« less

A subset of high Gleason grade prostate carcinomas contain a large burden of prostate cancer syndecan-1 positive stromal cells.

PubMed

Sharpe, Benjamin; Alghezi, Dhafer A; Cattermole, Claire; Beresford, Mark; Bowen, Rebecca; Mitchard, John; Chalmers, Andrew D

2017-05-01

There is a pressing need to identify prognostic and predictive biomarkers for prostate cancer to aid treatment decisions in both early and advanced disease settings. Syndecan-1, a heparan sulfate proteoglycan, has been previously identified as a potential prognostic biomarker by multiple studies at the tissue and serum level. However, other studies have questioned its utility. Anti-Syndecan-1 immunohistochemistry was carried out on 157 prostate tissue samples (including cancerous, adjacent normal tissue, and non-diseased prostate) from three independent cohorts of patients. A population of Syndecan-1 positive stromal cells was identified and the number and morphological parameters of these cells quantified. The identity of the Syndecan-1-positive stromal cells was assessed by multiplex immunofluorescence using a range of common cell lineage markers. Finally, the burden of Syndecan-1 positive stromal cells was tested for association with clinical parameters. We identified a previously unreported cell type which is marked by Syndecan-1 expression and is found in the stroma of prostate tumors and adjacent normal tissue but not in non-diseased prostate. We call these cells Prostate Cancer Syndecan-1 Positive (PCSP) cells. Immunofluorescence analysis revealed that the PCSP cell population did not co-stain with markers of common prostate epithelial, stromal, or immune cell populations. However, morphological analysis revealed that PCSP cells are often elongated and displayed prominent lamellipodia, suggesting they are an unidentified migratory cell population. Analysis of clinical parameters showed that PCSP cells were found with a frequency of 20-35% of all tumors evaluated, but were not present in non-diseased normal tissue. Interestingly, a subset of primary Gleason 5 prostate tumors had a high burden of PCSP cells. The current study identifies PCSP cells as a novel, potentially migratory cell type, which is marked by Syndecan-1 expression and is found in the stroma of prostate carcinomas, adjacent normal tissue, but not in non-diseased prostate. A subset of poor prognosis high Gleason grade 5 tumors had a particularly high PCSP cell burden, suggesting an association between this unidentified cell type and tumor aggressiveness. © 2017 Wiley Periodicals, Inc.

Prospective Randomized Phase 2 Trial of Intensity Modulated Radiation Therapy With or Without Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Intermediate-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freytag, Svend O., E-mail: sfreyta1@hfhs.org; Stricker, Hans; Lu, Mei

Purpose: To assess the safety and efficacy of combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer. Methods and Materials: Forty-four men with intermediate-risk prostate cancer were randomly assigned to receive either OAMCGT plus IMRT (arm 1; n=21) or IMRT only (arm 2; n=23). The primary phase 2 endpoint was acute (≤90 days) toxicity. Secondary endpoints included quality of life (QOL), prostate biopsy (12-core) positivity at 2 years, freedom from biochemical/clinical failure (FFF), freedom from metastases, and survival. Results: Men in arm 1 exhibited a greater incidence of low-grade influenza-like symptoms, transaminitis,more » neutropenia, and thrombocytopenia than men in arm 2. There were no significant differences in gastrointestinal or genitourinary events or QOL between the 2 arms. Two-year prostate biopsies were obtained from 37 men (84%). Thirty-three percent of men in arm 1 were biopsy-positive versus 58% in arm 2, representing a 42% relative reduction in biopsy positivity in the investigational arm (P=.13). There was a 60% relative reduction in biopsy positivity in the investigational arm in men with <50% positive biopsy cores at baseline (P=.07). To date, 1 patient in each arm exhibited biochemical failure (arm 1, 4.8%; arm 2, 4.3%). No patient developed hormone-refractory or metastatic disease, and none has died from prostate cancer. Conclusions: Combining OAMCGT with IMRT does not exacerbate the most common side effects of prostate radiation therapy and suggests a clinically meaningful reduction in positive biopsy results at 2 years in men with intermediate-risk prostate cancer.« less

Gastric Metastasis of Prostate Cancer as an Unusual Presentation Using 68Ga-Prostate-Specific Membrane Antigen PET/CT.

PubMed

Solis Lara, Hugo Enrique; Villarreal Del Bosque, Natalia; Sada Treviño, Miguel Antonio; Yamamoto Ramos, Masao; Argueta Ruiz, Rocío Del Carmen

2018-05-01

A 79-year-old man with prostate cancer underwent Ga prostate-specific membrane antigen (Ga-PSMA) dual-time-point PET/CT scan to evaluate tumor activity due to early satiety, unquantified weight loss, and elevation of prostate-specific antigen (PSA), demonstrating thickening of the gastric wall with intense tracer uptake. The immunohistochemistry of gastric biopsy showed CDX2 and CK20: negative; CK7, focal positive; PSA, positive, which confirmed metastatic disease. Metastatic disease was also found in bones, right lung, and retroperitoneal and pelvic lymphadenopathies.

Biological and Genomic Differences of ERG Oncoprotein-Stratified Prostate Cancers from African and Caucasian Americans

DTIC Science & Technology

2014-10-01

Tomlins SA, Mudaliar KM, et al: Antibody-based detection of ERG rearrangement-positive prostate cancer. Neoplasia 12: 590-598, 2010. 8. Braun M, Goltz D...detection of ERG rearrangement-positive prostate cancer. Neoplasia 12: 590-598, 2010. 16. Braun M, Goltz D, Shaikhibrahim Z, et al: ERG protein

Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia.

PubMed

Leidinger, Petra; Keller, Andreas; Milchram, Lisa; Harz, Christian; Hart, Martin; Werth, Angelika; Lenhof, Hans-Peter; Weinhäusel, Andreas; Keck, Bastian; Wullich, Bernd; Ludwig, Nicole; Meese, Eckart

2015-01-01

Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients' sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia.

Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer: Potential opportunities for synergistic targeted therapeutics.

PubMed

Udager, Aaron M; DeMarzo, Angelo M; Shi, Yang; Hicks, Jessica L; Cao, Xuhong; Siddiqui, Javed; Jiang, Hui; Chinnaiyan, Arul M; Mehra, Rohit

2016-06-01

Recurrent ERG gene fusions, the most common genetic alterations in prostate cancer, drive overexpression of the nuclear transcription factor ERG, and are early clonal events in prostate cancer progression. The nuclear transcription factor MYC is also frequently overexpressed in prostate cancer and may play a role in tumor initiation and/or progression. The relationship between nuclear ERG and MYC protein overexpression in prostate cancer, as well as the clinicopathologic characteristics and prognosis of ERG-positive/MYC high tumors, is not well understood. Immunohistochemistry (IHC) for ERG and MYC was performed on formalin-fixed, paraffin-embedded tissue from prostate cancer tissue microarrays (TMAs), and nuclear staining was scored semi-quantitatively (IHC product score range = 0-300). Correlation between nuclear ERG and MYC protein expression and association with clinicopathologic parameters and biochemical recurrence after radical prostatectomy was assessed. 29.1% of all tumor nodules showed concurrent nuclear ERG and MYC protein overexpression (i.e., ERG-positive/MYC high), including 35.0% of secondary nodules. Overall, there was weak positive correlation between ERG and MYC expression across all tumor nodules (rpb  = 0.149, P = 0.045), although this correlation was strongest in secondary nodules (rpb  = 0.520, P = 0.019). In radical prostatectomy specimens, ERG-positive/MYC high tumors were positively associated with the presence of extraprostatic extension (EPE), relative to all other ERG/MYC expression subgroups, however, there was no significant association between concurrent nuclear ERG and MYC protein overexpression and time to biochemical recurrence. Concurrent nuclear ERG and MYC protein overexpression is common in prostate cancer and defines a subset of locally advanced tumors. Recent data indicates that BET bromodomain proteins regulate ERG gene fusion and MYC gene expression in prostate cancer, suggesting possible synergistic targeted therapeutics in ERG-positive/MYC high tumors. Prostate 76:845-853, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

B-DIM impairs radiation-induced survival pathways independently of androgen receptor expression and augments radiation efficacy in prostate cancer.

PubMed

Singh-Gupta, Vinita; Banerjee, Sanjeev; Yunker, Christopher K; Rakowski, Joseph T; Joiner, Michael C; Konski, Andre A; Sarkar, Fazlul H; Hillman, Gilda G

2012-05-01

Increased consumption of cruciferous vegetables is associated with decreased risk in prostate cancer (PCa). The active compound in cruciferous vegetables appears to be the self dimerized product [3,3'-diindolylmethane (DIM)] of indole-3-carbinol (I3C). Nutritional grade B-DIM (absorption-enhanced) has proven safe in a Phase I trial in PCa. We investigated the anti-cancer activity of B-DIM as a new biological approach to improve the effects of radiotherapy for hormone refractory prostate cancer cells, which were either positive or negative for androgen receptor (AR) expression. B-DIM inhibited cell growth in a dose-dependent manner in both PC-3 (AR-) and C4-2B (AR+) cell lines. B-DIM was effective at increasing radiation-induced cell killing in both cell lines, independently of AR expression. B-DIM inhibited NF-κB and HIF-1α DNA activities and blocked radiation-induced activation of these transcription factors in both PC-3 and C4-2B cells. In C4-2B (AR+) cells, AR expression and nuclear localization were significantly increased by radiation. However, B-DIM abrogated the radiation-induced AR increased expression and trafficking to the nucleus, which was consistent with decreased PSA secretion. In vivo, treatment of PC-3 prostate tumors in nude mice with B-DIM and radiation resulted in significant primary tumor growth inhibition and control of metastasis to para-aortic lymph nodes. These studies demonstrate that B-DIM augments radiation-induced cell killing and tumor growth inhibition. B-DIM impairs critical survival signaling pathways activated by radiation, leading to enhanced cell killing. These novel observations suggest that B-DIM could be used as a safe compound to enhance the efficacy of radiotherapy for castrate-resistant PCa. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Tracer uptake in mediastinal and paraaortal thoracic lymph nodes as a potential pitfall in image interpretation of PSMA ligand PET/CT.

PubMed

Afshar-Oromieh, Ali; Sattler, Lars Peter; Steiger, Katja; Holland-Letz, Tim; da Cunha, Marcelo Livorsi; Mier, Walter; Neels, Oliver; Kopka, Klaus; Weichert, Wilko; Haberkorn, Uwe

2018-07-01

Since the introduction of 68 Ga-PSMA-11 PET/CT for imaging prostate cancer (PC) we have frequently observed mediastinal lymph nodes (LN) showing tracer uptake despite being classified as benign. The aim of this evaluation was to further analyze such LN. Two patient groups with biphasic 68 Ga-PSMA-11 PET/CT at 1 h and 3 h p.i. were included in this retrospective evaluation. Group A (n = 38) included patients without LN metastases, and group B (n = 43) patients with LN metastases of PC. SUV of mediastinal/paraaortal LN of group A (n = 100) were compared to SUV of LN metastases of group B (n = 91). Additionally, 22 randomly selected mediastinal and paraaortal LN of patients without PC were immunohistochemically (IHC) analyzed for PSMA expression. In group A, 7/38 patients (18.4%) presented with at least one PSMA-positive mediastinal LN at 1 h p.i. and 3/38 (7.9%) positive LN at 3 h p.i. with a SUVmax of 2.3 ± 0.7 at 1 h p.i. (2.0 ± 0.7 at 3 h p.i.). A total of 11 PSMA-positive mediastinal/paraaortal LN were detected in nine patients considering both imaging timing points. SUVmax of LN-metastases was 12.5 ± 13.2 at 1 h p.i. (15.8 ± 17.0 at 3 h p.i.). SUVmax increased clearly (> 10%) between 1 h and 3 h p.i. in 76.9% of the LN metastases, and decreased significantly in 72.7% of the mediastinal/paraaortal LN. By IHC, PSMA-expression was observed in intranodal vascular endothelia of all investigated LN groups and to differing degrees within germinal centers of 15/22 of them (68.1%). Expression was stronger in mediastinal nodes (p = 0.038) and when follicular hyperplasia was present (p = 0.050). PSMA-positive mediastinal/paraaortal benign LN were visible in a notable proportion of patients. PSMA-positivity on the histopathological level was associated with the activation state of the LN. However, in contrast to LN metastases of PC, they presented with significantly lower uptake, which, in addition, usually decreased over time.

Evaluation of tumor hypoxia prior to radiotherapy in intermediate-risk prostate cancer using 18F-fluoromisonidazole PET/CT: a pilot study.

PubMed

Supiot, Stéphane; Rousseau, Caroline; Dore, Mélanie; Cheze-Le-Rest, Catherine; Kandel-Aznar, Christine; Potiron, Vincent; Guerif, Stéphane; Paris, François; Ferrer, Ludovic; Campion, Loïc; Meingan, Philippe; Delpon, Gregory; Hatt, Mathieu; Visvikis, Dimitris

2018-02-09

Hypoxia is a major factor in prostate cancer aggressiveness and radioresistance. Predicting which patients might be bad candidates for radiotherapy may help better personalize treatment decisions in intermediate-risk prostate cancer patients. We assessed spatial distribution of 18 F-Misonidazole (FMISO) PET/CT uptake in the prostate prior to radiotherapy treatment. Intermediate-risk prostate cancer patients about to receive high-dose (>74 Gy) radiotherapy to the prostate without hormonal treatment were prospectively recruited between 9/2012 and 10/2014. Prior to radiotherapy, all patients underwent a FMISO PET/CT as well as a MRI and 18 F-choline-PET. 18 F-choline and FMISO-positive volumes were semi-automatically determined using the fuzzy locally adaptive Bayesian (FLAB) method. In FMISO-positive patients, a dynamic analysis of early tumor uptake was performed. Group differences were assessed using the Wilcoxon signed rank test. Parameters were correlated using Spearman rank correlation. Of 27 patients (median age 76) recruited to the study, 7 and 9 patients were considered positive at 2.5h and 3.5h FMISO PET/CT respectively. Median SUV max and SUV max tumor to muscle (T/M) ratio were respectively 3.4 and 3.6 at 2.5h, and 3.2 and 4.4 at 3.5h. The median FMISO-positive volume was 1.1 ml. This is the first study regarding hypoxia imaging using FMISO in prostate cancer showing that a small FMISO-positive volume was detected in one third of intermediate-risk prostate cancer patients.

Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter, retrospective analysis.

PubMed

Ghedini, Pietro; Bossert, I; Zanoni, L; Ceci, F; Graziani, T; Castellucci, P; Ambrosini, V; Massari, F; Nobili, E; Melotti, B; Musto, A; Zoboli, S; Antunovic, L; Kirienko, M; Chiti, A; Mosconi, C; Ardizzoni, A; Golfieri, R; Fanti, S; Nanni, C

2018-05-01

During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases. We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma). Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

Prostate-Specific Antigen and Prostate-Specific Antigen Velocity as Threshold Indicators in 11C-Acetate PET/CTAC Scanning for Prostate Cancer Recurrence

PubMed Central

Dusing, Reginald W.; Peng, Warner; Lai, Sue-Min; Grado, Gordon L.; Holzbeierlein, Jeffrey M.; Thrasher, J. Brantley; Hill, Jacqueline; Van Veldhuizen, Peter J.

2014-01-01

Purpose The aim of this study was to identify which patient characteristics are associated with the highest likelihood of positive findings on 11C-acetate PET/computed tomography attenuation correction (CTAC) (PET/CTAC) scan when imaging for recurrent prostate cancer. Methods From 2007 to 2011, 250 11C-acetate PET/CTAC scans were performed at a single institution on patients with prostate cancer recurrence after surgery, brachytherapy, or external beam radiation. Of these patients, 120 met our inclusion criteria. Logistic regression analysis was used to examine the relationship between predictability of positive findings and patients’ characteristics, such as prostate-specific antigen (PSA) level at the time of scan, PSA kinetics, Gleason score, staging, and type of treatment before scan. Results In total, 68.3% of the 120 11C-acetate PET/CTAC scans were positive. The percentage of positive scans and PSA at the time of scanning and PSA velocity (PSAV) had positive correlations. The putative sensitivity and specificity were 86.6% and 65.8%, respectively, when a PSA level greater than 1.24 ng/mL was used as the threshold for scanning. The putative sensitivity and specificity were 74% and 75%, respectively, when a PSAV level greater than 1.32 ng/mL/y was used as the threshold. No significant associations were found between scan positivity and age, PSA doubling time, Gleason score, staging, or type of treatment before scanning. Conclusions This retrospective study suggests that threshold models of PSA greater than 1.24 ng/mL or PSAV greater than 1.32 ng/mL per year are independent predictors of positive findings in 11C-acetate PET/CTAC imaging of recurrent prostate cancer. PMID:25036021

Calcium-Sensing Receptor Tumor Expression and Lethal Prostate Cancer Progression.

PubMed

Ahearn, Thomas U; Tchrakian, Nairi; Wilson, Kathryn M; Lis, Rosina; Nuttall, Elizabeth; Sesso, Howard D; Loda, Massimo; Giovannucci, Edward; Mucci, Lorelei A; Finn, Stephen; Shui, Irene M

2016-06-01

Prostate cancer metastases preferentially target bone, and the calcium-sensing receptor (CaSR) may play a role in promoting this metastatic progression. We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer. A validated CaSR immunohistochemistry assay was performed on tumor tissue microarrays. Vitamin D receptor (VDR) expression and phosphatase and tensin homolog tumor status were previously assessed in a subset of cases by immunohistochemistry. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and pathological tumor node metastasis stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer. The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study. We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009. Participants were followed up or cancer-specific mortality or development of metastatic disease. On average, men were followed up 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathological variables (HR 2.0; 95% CI 1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR 3.2; 95% CI 1.4-7.3) but not in cases with high tumor VDR expression (HR 0.8; 95% CI 0.2-3.0). Tumor CaSR expression is associated with an increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.

Elucidation of the Molecular Mechanisms Underlying Lymph Node Metastasis in Prostate Cancer

DTIC Science & Technology

2007-10-01

370: 737-749, 2003. 4. Dias S, Choy M, Alitalo K, and Rafii S. Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates...1992). Science, 255, 989–991. Denis L and Murphy GP. (1993). Cancer, 72, 3888–3895. Dias S, Choy M, Alitalo K and Rafii S. (2002). Blood, 99, 2179

Identifying aggressive prostate cancer foci using a DNA methylation classifier.

PubMed

Mundbjerg, Kamilla; Chopra, Sameer; Alemozaffar, Mehrdad; Duymich, Christopher; Lakshminarasimhan, Ranjani; Nichols, Peter W; Aron, Manju; Siegmund, Kimberly D; Ukimura, Osamu; Aron, Monish; Stern, Mariana; Gill, Parkash; Carpten, John D; Ørntoft, Torben F; Sørensen, Karina D; Weisenberger, Daniel J; Jones, Peter A; Duddalwar, Vinay; Gill, Inderbir; Liang, Gangning

2017-01-12

Slow-growing prostate cancer (PC) can be aggressive in a subset of cases. Therefore, prognostic tools to guide clinical decision-making and avoid overtreatment of indolent PC and undertreatment of aggressive disease are urgently needed. PC has a propensity to be multifocal with several different cancerous foci per gland. Here, we have taken advantage of the multifocal propensity of PC and categorized aggressiveness of individual PC foci based on DNA methylation patterns in primary PC foci and matched lymph node metastases. In a set of 14 patients, we demonstrate that over half of the cases have multiple epigenetically distinct subclones and determine the primary subclone from which the metastatic lesion(s) originated. Furthermore, we develop an aggressiveness classifier consisting of 25 DNA methylation probes to determine aggressive and non-aggressive subclones. Upon validation of the classifier in an independent cohort, the predicted aggressive tumors are significantly associated with the presence of lymph node metastases and invasive tumor stages. Overall, this study provides molecular-based support for determining PC aggressiveness with the potential to impact clinical decision-making, such as targeted biopsy approaches for early diagnosis and active surveillance, in addition to focal therapy.

Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes.

PubMed

Yan, Lisa; Da Silva, Diane M; Verma, Bhavna; Gray, Andrew; Brand, Heike E; Skeate, Joseph G; Porras, Tania B; Kanodia, Shreya; Kast, W Martin

2015-02-15

LIGHT, a ligand for lymphotoxin-β receptor (LTβR) and herpes virus entry mediator, is predominantly expressed on activated immune cells and LTβR signaling leads to the recruitment of lymphocytes. The interaction between LIGHT and LTβR has been previously shown to activate immune cells and result in tumor regression in a virally-induced tumor model, but the role of LIGHT in tumor immunosuppression or in a prostate cancer setting, where self antigens exist, has not been explored. We hypothesized that forced expression of LIGHT in prostate tumors would shift the pattern of immune cell infiltration toward an anti-tumoral milieu, would inhibit T regulatory cells (Tregs) and would induce prostate cancer tumor associated antigen (TAA) specific T cells that would eradicate tumors. Real Time PCR was used to evaluate expression of forced LIGHT and other immunoregulatory genes in prostate tumors samples. For in vivo studies, adenovirus encoding murine LIGHT was injected intratumorally into TRAMP-C2 prostate cancer cell tumor bearing mice. Chemokine and cytokine concentrations were determined by multiplex ELISA. Flow cytometry was used to phenotype tumor infiltrating lymphocytes and expression of LIGHT on the tumor cell surface. Tumor-specific lymphocytes were quantified via ELISpot assay. Treg induction and Treg suppression assays determined Treg functionality after LIGHT treatment. LIGHT in combination with a therapeutic vaccine, PSCA TriVax, reduced tumor burden. LIGHT expression peaked within 48 hr of infection, recruited effector T cells that recognized mouse prostate stem cell antigen (PSCA) into the tumor microenvironment, and inhibited infiltration of Tregs. Tregs isolated from tumor draining lymph nodes had impaired suppressive capability after LIGHT treatment. Forced LIGHT treatment combined with PSCA TriVax therapeutic vaccination delays prostate cancer progression in mice by recruiting effector T lymphocytes to the tumor and inhibiting Treg mediated immunosuppression. Prostate 75:280-291, 2015. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Prospective evaluation of 18F-FACBC PET/CT and PET/MRI versus multiparametric MRI in intermediate- to high-risk prostate cancer patients (FLUCIPRO trial).

PubMed

Jambor, Ivan; Kuisma, Anna; Kähkönen, Esa; Kemppainen, Jukka; Merisaari, Harri; Eskola, Olli; Teuho, Jarmo; Perez, Ileana Montoya; Pesola, Marko; Aronen, Hannu J; Boström, Peter J; Taimen, Pekka; Minn, Heikki

2018-03-01

The purpose of this study was to evaluate 18 F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa). Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq 18 F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUV max ) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans. Logan plots were used to calculate volume of distribution (V T ). The presence of PCa was estimated in 12 regions with radical prostatectomy findings as ground truth. For each imaging modality, area under the curve (AUC) for detection of PCa was determined to predict diagnostic performance. The clinical trial registration number is NCT02002455. In the visual analysis, 164/312 (53%) regions contained PCa, and 41 tumor foci were identified. PET/CT demonstrated the highest sensitivity at 87% while its specificity was low at 56%. The AUC of both PET/MRI and mpMRI significantly (p < 0.01) outperformed that of PET/CT while no differences were detected between PET/MRI and mpMRI. SUV max and V T of Gleason score (GS) >3 + 4 tumors were significantly (p < 0.05) higher than those for GS 3 + 3 and benign hyperplasia. A total of 442 lymph nodes were evaluable for staging, and PET/CT and PET/MRI demonstrated true-positive findings in only 1/7 patients with metastatic lymph nodes. Quantitative 18 F-FACBC imaging significantly correlated with GS but failed to outperform MRI in lesion detection. 18 F-FACBC may assist in targeted biopsies in the setting of hybrid imaging with MRI.

New Bacterial Infection in the Prostate after Transrectal Prostate Biopsy.

PubMed

Seo, Yumi; Lee, Gilho

2018-04-23

The prostate is prone to infections. Hypothetically, bacteria can be inoculated into the prostate during a transrectal prostate biopsy (TRPB) and progress into chronic bacterial prostatitis. Therefore, we examined new bacterial infections in biopsied prostates after TRPB and whether they affect clinical characteristics in the biopsied patients. Of men whose prostate cultures have been taken prior to TRPB, 105 men with bacteria-free benign prostate pathology underwent an additional repeated prostate culture within a year after TRPB. Twenty out of 105 men (19.05%) acquired new bacteria in their naïve prostates after TRPB. Except for one single case of Escherichia coli infection, 19 men had acquired gram-positive bacteria species. Between the culture-positive and negative groups, there were no significant differences in age, serum prostate-specific antigen (PSA) level, white blood cell (WBC) counts in expressed prostatic secretion (EPS), prostate volume, symptom severities in Korean version of the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) questionnaire, and patient-specific risk factors for biopsy associated infectious complications. Additionally, the TRPB procedure increased the WBC counts in post-biopsy EPS ( P = 0.031, McNemar test), but did not increase the serum PSA level and symptoms of NIH-CPSI in 20 men who acquired new bacteria after TRPB. The TRPB procedure was significantly associated with acquiring new bacterial infections in the biopsied prostate, but these localized bacteria did not affect patients' serum PSA level and symptoms after biopsy.

Using individual patient anatomy to predict protocol compliance for prostate intensity-modulated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caine, Hannah; Whalley, Deborah; Kneebone, Andrew

If a prostate intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) plan has protocol violations, it is often a challenge knowing whether this is due to unfavorable anatomy or suboptimal planning. This study aimed to create a model to predict protocol violations based on patient anatomical variables and their potential relationship to target and organ at risk (OAR) end points in the setting of definitive, dose-escalated IMRT/VMAT prostate planning. Radiotherapy plans from 200 consecutive patients treated with definitive radiation for prostate cancer using IMRT or VMAT were analyzed. The first 100 patient plans (hypothesis-generating cohort) were examined to identifymore » anatomical variables that predict for dosimetric outcome, in particular OAR end points. Variables that scored significance were further assessed for their ability to predict protocol violations using a Classification and Regression Tree (CART) analysis. These results were then validated in a second group of 100 patients (validation cohort). In the initial analysis of the hypothesis-generating cohort, percentage of rectum overlap in the planning target volume (PTV) (%OR) and percentage of bladder overlap in the PTV (%OB) were highlighted as significant predictors of rectal and bladder dosimetry. Lymph node treatment was also significant for bladder outcomes. For the validation cohort, CART analysis showed that %OR of < 6%, 6% to 9% and > 9% predicted a 13%, 63%, and 100% rate of rectal protocol violations respectively. For the bladder, %OB of < 9% vs > 9% is associated with 13% vs 88% rate of bladder constraint violations when lymph nodes were not treated. If nodal irradiation was delivered, plans with a %OB of < 9% had a 59% risk of violations. Percentage of rectum and bladder within the PTV can be used to identify individual plan potential to achieve dose-volume histogram (DVH) constraints. A model based on these factors could be used to reduce planning time, improve work flow, and strengthen plan quality and consistency.« less

A Phase 1/2 Trial of Brief Androgen Suppression and Stereotactic Radiation Therapy (FASTR) for High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bauman, Glenn, E-mail: Glenn.bauman@lhsc.on.ca; Ferguson, Michelle; Lock, Michael

2015-07-15

Purpose: To initiate a phase 1/2 trial to examine the tolerability of a condensed combined-modality protocol for high-risk prostate cancer. Methods and Materials: Men scoring ≥3 on the Vulnerable Elderly Scale (VES) or refusing conventionally fractionated treatment for high-risk prostate cancer were eligible to participate. Androgen suppression was delivered for 12 months, and radiation therapy was delivered using 25 Gy to pelvic nodes delivered synchronously with 40 Gy to the prostate given as 1 fraction per week over 5 weeks. The phase 1 component included predetermined stopping rules based on 6-month treatment-related toxicity, with trial suspension specified if there were ≥6 of 15more » patients (40%) or ≥3 of 15 (20%) who experienced grade ≥2 or ≥3 gastrointestinal (GI) or genitourinary (GU) toxicity, respectively. Results: Sixteen men were enrolled, with 7 men meeting the criteria of VES ≥3 and 9 men having a VES <3 but choosing the condensed treatment. One man was not treated owing to discovery of a synchronous primary rectal cancer. Four patients (26%) experienced grade ≥2 toxicity at 6 weeks after treatment. There were 9 of 15 (60%) who experienced grade ≥2 GI or GU toxicity and 4 of 15 (26%) grade ≥3 GI or GU toxicity at 6 months, and 5 of 15 (30%) grade ≥2 GI and GU toxicity at 6 months. A review of the 15 cases did not identify any remedial changes, thus the phase 1 criteria were not met. Conclusion: This novel condensed treatment had higher than anticipated late toxicities and was terminated before phase 2 accrual. Treatment factors, such as inclusion of pelvic lymph node radiation therapy, planning constraints, and treatment margins, or patient factors related to the specific frail elderly population may be contributing.« less

Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

PubMed

Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

2010-01-01

The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

Bone marrow-derived cells contribute to regeneration of injured prostate epithelium and stroma.

PubMed

Nakata, Wataru; Nakai, Yasutomo; Yoshida, Takahiro; Sato, Mototaka; Hatano, Koji; Nagahara, Akira; Fujita, Kazutoshi; Uemura, Motohide; Nonomura, Norio

2015-06-01

Recent studies have reported that bone marrow-derived cells (BMDCs), which are recruited to sites of tissue injury and inflammation, can differentiate into epithelial cells, such as liver, lung, gastrointestinal tract, and skin cells. We investigated the role of BMDCs in contributing to regeneration of injured prostate epithelium. Using chimera rats that received allogenic bone marrow grafts from green fluorescent protein (GFP) transgenic rats after lethal whole-body irradiation, we investigated the existence of epithelial marker-positive BMDCs in injured prostate tissue caused by transurethral injection of lipopolysaccharide. Prostate tissues were harvested 2 weeks after transurethral lipopolysaccharide injection. Immunofluorescence staining showed that some cells in the stroma co-expressed GFP and pan-cytokeratin, which suggested the existence of epithelial marker-positive BMDCs. To confirm the existence of such cells, we collected bone marrow-derived non-hematopoietic cells (GFP+/CD45- cells) from the prostate by fluorescence-activated cell sorter analysis and analyzed the characteristics of the GFP+/CD45- cells. The number of cells in this population significantly increased from 0.042% to 0.492% compared with normal prostate tissue. We found by immunofluorescent analysis and RT-PCR that GFP+/CD45- cells expressed cytokeratin, which suggested that these cells have some features of epithelial cells. In the prostate obtained from the chimera rats 34 weeks after lipopolysaccharide injection, GFP- and cytokeratin-positive cells were observed in the prostate gland, which suggested that some of the cells in the prostate gland regenerated after prostate inflammation derived from bone marrow. BMDCs might be able to differentiate into prostate epithelial cells after prostatic injury. © 2015 Wiley Periodicals, Inc.

Small size of metastatic lymph nodes with extracapsular spread greatly impacts treatment outcomes in oral squamous cell carcinoma patients.

PubMed

Michikawa, C; Izumo, T; Sumino, J; Morita, T; Ohyama, Y; Michi, Y; Uzawa, N

2018-07-01

Extracapsular spread (ECS) of metastatic lymph nodes from oral carcinoma is the most significant prognostic predictor of a poor treatment outcome. However, only a few reports on prognostic factors in ECS-positive cases have been investigated. To address this problem, a detailed examination of ECS pathology was conducted to determine the prognostic factors of oral squamous cell carcinoma (OSCC) with ECS of metastatic lymph nodes. This study involved 63 OSCC patients with at least one pathologically metastatic node with ECS. Among the 229 metastatic lymph nodes, 149 exhibited ECS. Univariate analysis revealed that a poor outcome and recurrence were significantly associated with the number of ECS-positive nodes, density of ECS, and the minor axis of the smallest ECS-positive node. However, multivariate analysis identified only small size of ECS-positive nodes as a significant and independent factor predicting recurrence and a poor outcome. Thus, small size of ECS-positive nodes is the most important prognostic indicator for OSCC with ECS in metastatic lymph nodes. The classification of ECS status using the minor axis of ECS-positive nodes may be useful for further prediction of a poorer prognosis in OSCC cases. Standardization of ECS diagnosis and multicenter prospective studies will be required to confirm and refine these findings. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

1.5-Tesla Multiparametric-Magnetic Resonance Imaging for the detection of clinically significant prostate cancer.

PubMed

Popita, Cristian; Popita, Anca Raluca; Sitar-Taut, Adela; Petrut, Bogdan; Fetica, Bogdan; Coman, Ioan

2017-01-01

Multiparametric-magnetic resonance imaging (mp-MRI) is the main imaging modality used for prostate cancer detection. The aim of this study is to evaluate the diagnostic performance of mp-MRI at 1.5-Tesla (1.5-T) for the detection of clinically significant prostate cancer. In this ethical board approved prospective study, 39 patients with suspected prostate cancer were included. Patients with a history of positive prostate biopsy and patients treated for prostate cancer were excluded. All patients were examined at 1.5-T MRI, before standard transrectal ultrasonography-guided biopsy. The overall sensitivity, specificity, positive predictive value and negative predictive value for mp-MRI were 100%, 73.68%, 80% and 100%, respectively. Our results showed that 1.5 T mp-MRI has a high sensitivity for detection of clinically significant prostate cancer and high negative predictive value in order to rule out significant disease.

Clinical and microbiological characteristics of spontaneous acute prostatitis and transrectal prostate biopsy-related acute prostatitis: Is transrectal prostate biopsy-related acute prostatitis a distinct acute prostatitis category?

PubMed

Kim, Jong Wook; Oh, Mi Mi; Bae, Jae Hyun; Kang, Seok Ho; Park, Hong Seok; Moon, Du Geon

2015-06-01

This study aimed to compare the clinical and microbiological characteristics between acute bacterial prostatitis and transrectal biopsy-related acute prostatitis. We retrospectively reviewed the records of 135 patients hospitalized for acute prostatitis in three urological centers between 2004 and 2013. Acute bacterial prostatitis was diagnosed according to typical symptoms, findings of physical examination, and laboratory test results. Clinical variables, laboratory test results, and anti-microbial susceptibility results were reviewed. Patients were classified into the spontaneous acute prostatitis group (S-ABP) or biopsy-related acute prostatitis (Bx-ABP) for comparison of their clinical, laboratory, and microbiological findings. The mean age of all patients was 61.7 ± 12.9 years. Compared with S-ABP patients, Bx-ABP patients were significantly older, had larger prostate volumes, higher PSA values, higher peak fever temperatures, and higher incidence of septicemia and antibiotic-resistant bacteria. Overall, of the 135 patients, 57.8% had positive bacterial urine and/or blood cultures. Bx-ABP patients had a higher incidence of bacterial (urine and/or blood) positive cultures compared to S-ABP patients (66.7% versus 55.6%). Escherichia coli was the predominant organism in both groups, but it was more common in Bx-ABP (88.9%) than in S-ABP (66.7%). Extended spectrum beta-lactamase -producing bacteria accounted for 64.7% of culture-positive patients in the Bx-ABP group compared to 13.3% in the S-ABP group. Bx-ABP patients showed a higher incidence of septicemia and antibiotic-resistant bacteria than S-ABP patients. These results have important implications for the management and antimicrobial treatment of Bx-ABP, which may well deserve to be considered a distinct prostatitis category. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Improving diagnostic accuracy of prostate carcinoma by systematic random map-biopsy.

PubMed

Szabó, J; Hegedûs, G; Bartók, K; Kerényi, T; Végh, A; Romics, I; Szende, B

2000-01-01

Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized.

Outcome following sentinel lymph node biopsy-guided decisions in breast cancer patients with conversion from positive to negative axillary lymph nodes after neoadjuvant chemotherapy.

PubMed

Kang, Young-Joon; Han, Wonshik; Park, Soojin; You, Ji Young; Yi, Ha Woo; Park, Sungmin; Nam, Sanggeun; Kim, Joo Heung; Yun, Keong Won; Kim, Hee Jeong; Ahn, Sei Hyun; Park, Seho; Lee, Jeong Eon; Lee, Eun Sook; Noh, Dong-Young; Lee, Jong Won

2017-11-01

Many breast cancer patients with positive axillary lymph nodes achieve complete node remission after neoadjuvant chemotherapy. The usefulness of sentinel lymph node biopsy in this situation is uncertain. This study evaluated the outcomes of sentinel biopsy-guided decisions in patients who had conversion of axillary nodes from clinically positive to negative following neoadjuvant chemotherapy. We reviewed the records of 1247 patients from five hospitals in Korea who had breast cancer with clinically axillary lymph node-positive status and negative conversion after neoadjuvant chemotherapy, between 2005 and 2012. Patients who underwent axillary operations with sentinel biopsy-guided decisions (Group A) were compared with patients who underwent complete axillary lymph node dissection without sentinel lymph node biopsy (Group B). Axillary node recurrence and distant recurrence-free survival were compared. There were 428 cases in Group A and 819 in Group B. Kaplan-Meier analysis showed that recurrence-free survivals were not significantly different between Groups A and B (4-year axillary recurrence-free survival: 97.8 vs. 99.0%; p = 0.148). Multivariate analysis also indicated the two groups had no significant difference in axillary and distant recurrence-free survival. For breast cancer patients who had clinical conversion of axillary lymph nodes from positive to negative following neoadjuvant chemotherapy, sentinel biopsy-guided axillary surgery, and axillary lymph node dissection without sentinel lymph node biopsy had similar rates of recurrence. Thus, sentinel biopsy-guided axillary operation in breast cancer patients who have clinically axillary lymph node positive to negative conversion following neoadjuvant chemotherapy is a useful strategy.

Impact of false-negative sentinel lymph node biopsy on survival in patients with cutaneous melanoma.

PubMed

Caracò, C; Marone, U; Celentano, E; Botti, G; Mozzillo, N

2007-09-01

Sentinel lymph node biopsy is widely accepted as standard care in melanoma despite lack of pertinent randomized trials results. A possible pitfall of this procedure is the inaccurate identification of the sentinel lymph node leading to biopsy and analysis of a nonsentinel node. Such a technical failure may yield a different prognosis. The purpose of this study is to analyze the incidence of false negativity and its impact on clinical outcome and to try to understand its causes. The Melanoma Data Base at National Cancer Institute of Naples was analyzed comparing results between false-negative and tumor-positive sentinel node patients focusing on overall survival and prognostic factors influencing the clinical outcome. One hundred fifty-one cases were diagnosed to be tumor-positive after sentinel lymph node biopsy and were subjected to complete lymph node dissection. Thirty-four (18.4%)patients with tumor-negative sentinel node subsequently developed lymph node metastases in the basin site of the sentinel procedure. With a median follow-up of 42.8 months the 5-year overall survival was 48.4% and 66.3% for false-negative and tumor-positive group respectively with significant statistical differences (P < .03). The sensitivity of sentinel lymph node biopsy was 81.6%, and a regional nodal basin recurrence after negative-sentinel node biopsy means a worse prognosis, compared with patients submitted to complete lymph node dissection after a positive sentinel biopsy. The evidence of higher number of tumor-positive nodes after delayed lymphadenectomy in false-negative group compared with tumor-positive sentinel node cases, confirmed the importance of an early staging of lymph nodal involvement. Further data will better clarify the role of prognostic factors to identify cases with a more aggressive biological behavior of the disease.

Structural Variation of Prostate Urethra Reflected by the Ratio Between Prostate Volume and Prostatic Urethral Length is Associated with the Degrees of Lower Urinary Tract Symptoms.

PubMed

Ko, Young Hwii; Song, Phil Hyun

2016-05-01

Because it is well known that the prostate volume is not directly associated with the degrees of lower urinary tract symptom (LUTS), we hypothesized that change of the prostatic urethra led by prostatic enlargement as missing links between them. To provide an integral description, we determined the ratio between prostate volume and prostatic urethral length (RPVL), and investigated its clinical implication. Prostate volume, prostatic urethral length, RPVL was measured from transrectal ultrasonography for 213 consecutive patients. The degree of LUTS was investigated using the international prostate symptom score (IPSS) and uroflowmetry, then the correlations were analyzed. While no variables were significantly linked with total IPSS, obstructive symptoms (IPSS Q247) showed a negative association (r = -0.3, P < 0.001) and irritative symptoms (IPSS Q1356) showed a positive association solely with RPVL (r = 0.186, P = 0.007). These relevancies were enhanced (r = -0.471 [P = <0.001] and 0.3 [P = 0.004], respectively) in patients with a larger prostate (over 30 g, n = 93), but disappeared in their smaller counterparts (below 30 g, n = 120), (r = -0.133 [P = 0.143] and 0.75 [P = 0.410], respectively). In uroflowmetry, prostate urethral length showed positive correlation (r = 0.319 [P < 0.001]), and RPVL showed negative correlation (r = -0.195 [P = 0.004]) with post voiding residual amount, but these relationships similarly vanished in men with a smaller prostate. The structural variation of the prostatic urethra within the prostate reflected by RPVL showed correlation with the degree of LUTS, with a tendency toward increasing prostatic urethra in obstructive and decreasing prostatic urethra in irritative symptoms, in men with a relatively large prostate. © 2014 Wiley Publishing Asia Pty Ltd.

Hypofractionated IMRT of the Prostate Bed After Radical Prostatectomy: Acute Toxicity in the PRIAMOS-1 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katayama, Sonja, E-mail: sonja.katayama@med.uni-heidelberg.de; Striecker, Thorbjoern; Kessel, Kerstin

Purpose: Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed. Methods and Materials: From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy inmore » 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy. Results: Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged. Conclusions: Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Legge, K; O’Connor, D J; Nguyen, D

Purpose: To determine prostate motion during SBRT boost treatments with a Rectafix rectal sparing device in place using kV imaging during treatment. Methods: Patients each had three gold fiducial markers inserted into the prostate and received two VMAT boost fractions of 9.5–10 Gy under the PROMETHEUS clinical trial protocol with a Rectafix rectal retractor in place. Two-dimensional kilovoltage images of fiducial markers were acquired continuously during delivery. Three patients were treated on a Varian Clinac iX linear accelerator (6X, 600 MU/min), where kV images were acquired at 5 Hz during treatment. Seven patients were treated on a Varian Truebeam linearmore » accelerator (10XFFF, 2400 MU/min) where kV images were acquired every 3 seconds. Images were processed off-line using the Kilovoltage Intrafraction Monitoring (KIM) software after treatment. KIM determines prostate position in three dimensions from 2D kV projections using a probability density model and a pre-treatment kV arc. The 3D displacement of the prostate was quantified as a function of time throughout each fraction. Results: From all fractions analyzed, it was found that the prostate had moved less than 1 mm in any direction from its initial position 84.6% of the time. The prostate was between 1 and 2 mm from its initial position 14.2% of the time, between 2 and 3 mm of its initial position 0.8% of the time and was greater than 3 mm from its initial position only 0.4% of the time. Conclusion: The amount of prostate motion observed during prostate SBRT boost treatments with a Rectafix device in place was minimal and lower than that observed in non-Rectafix studies. The Rectafix device reduces rectal dose as well as immobilizing the prostate. Kimberley Legge is the recipient of an Australian Postgraduate Award.« less

Rapid increase in multidrug-resistant enteric bacilli blood stream infection after prostate biopsy - A 10-year population-based cohort study.

PubMed

Aly, Markus; Dyrdak, Robert; Nordström, Tobias; Jalal, Shah; Weibull, Caroline E; Giske, Christian G; Grönberg, Henrik

2015-06-15

Bloodstream infection following a transrectal prostate biopsy is a well-known and feared complication. Previous studies have shown an increase in multi-resistant bacterial infections as a consequence of higher usage of antibiotics in investigated populations. Our aim was to analyze bacterial resistance patterns in positive blood cultures, after prostate biopsies in Stockholm, Sweden, where the use of antibiotics has been low and decreasing during the last 10 years. From the three pathology laboratories in Stockholm, reports of prostate examinations were retrieved (n = 56,076) from 2003 to 2012. By linking men to the National Patient Register all but prostate core biopsies were excluded (n = 12,024). Prostate biopsies in men younger than 30 years of age were excluded (n = 5) leaving 44,047 biopsies for analysis. From laboratory information systems data regarding blood cultures were retrieved. Proportions of blood cultures within 30 days by year were calculated. Crude and adjusted logistic regression models were used to estimate ORs. In total, 44,047 prostate biopsies were performed in 32,916 men over 10 years. On 620 occasions a blood culture was drawn within 30 days of the biopsy; 266 of these were positive. The proportions with positive blood cultures in 2003 and 2012 were 0.38 and 1.14%, respectively. The proportion of multidrug-resistant bacteria increased significantly during the study. In the crude and the adjusted analysis, the year of biopsy and Charlson Comorbidity Index were associated with the risk of having a positive blood culture. Multidrug-resistant enteric bacilli are becoming a problem in Sweden, despite low antimicrobial use. Men need to be informed about the increasing risks of infectious complications of transrectal prostate biopsy. One out of 50 men undergoing a prostate biopsy will develop symptoms suggestive of a bloodstream infection after the biopsy and one in 100 men will have a positive blood culture. © 2015 Wiley Periodicals, Inc.

Outcomes of active surveillance for the management of clinically localized prostate cancer in the prospective, multi-institutional Canary PASS cohort

PubMed Central

Newcomb, Lisa F.; Thompson, Ian M.; Boyer, Hilary D.; Brooks, James D.; Carroll, Peter R.; Cooperberg, Matthew R.; Dash, Atreya; Ellis, William J.; Fazli, Ladan; Feng, Ziding; Gleave, Martin E.; Kunju, Priya; Lance, Raymond S.; McKenney, Jesse K.; Meng, Maxwell V.; Nicolas, Marlo M.; Sanda, Martin G.; Simko, Jeffry; So, Alan; Tretiakova, Maria S.; Troyer, Dean A.; True, Lawrence D.; Vakar-Lopez, Funda; Virgin, Jeff; Wagner, Andrew A.; Wei, John T.; Zheng, Yingye; Nelson, Peter S.; Lin, Daniel W.

2016-01-01

Purpose Active surveillance represents a strategy to address the overtreatment of prostate cancer, yet uncertainty regarding individual patient outcomes remains a concern. We evaluated outcomes in a prospective multi-center study of active surveillance. Methods We studied 905 men in the prospective Canary Prostate cancer Active Surveillance Study (PASS) enrolled between 2008 to 2013. We collected clinical data at study entry and at pre-specified intervals and determined associations with adverse reclassification defined as increased Gleason grade or greater cancer volume on follow-up biopsy. We also evaluated the relationships of clinical parameters with pathology findings in participants who underwent surgery after a period of active surveillance. Results During a median follow-up of 28 months, 24% of participants experienced adverse reclassification, of whom 53% underwent treatment while 31% continued active surveillance. Overall, 19% of participants received treatment, 68% with adverse reclassification while 32% opted for treatment without disease reclassification. In multivariate Cox proportional hazards modeling, percent of biopsy cores with cancer, BMI, and PSA density were associated with adverse reclassification (P = 0.01, 0.04, 0.04). Of 103 participants subsequently treated by radical prostatectomy, 34% had adverse pathology, defined as primary pattern 4–5 or non-organ confined disease, including two with positive lymph nodes, with no significant relationship between risk category at diagnosis and findings at surgery (P = 0.76). Conclusion Most men remain on active surveillance at five years without adverse reclassification or adverse pathology at surgery. However, clinical factors had only modest association with disease reclassification, supporting the need for approaches that improve prediction of this outcome. PMID:26327354

11C-Choline PET/CT based Helical Tomotherapy as Treatment Approach for Bone Metastases in Recurrent Prostate Cancer Patients.

PubMed

Incerti, Elena; Gangemi, Vincenzo; Mapelli, Paola; Deantoni, Chiara Lucrezia; Giovacchini, Giampiero; Fallanca, Federico; Fodor, Andrei; Ciarmiello, Andrea; Baldari, Sergio; Gianolli, Luigi; Di Muzio, Nadia; Picchio, Maria

2017-11-10

To evaluate the efficacy of 11C-choline PET/CT (CHO-PET/CT) based helical tomotherapy (HTT) as a therapeutic approach for bone metastases in recurrent prostate cancer (PCa) patients. This retrospective study includes 20 PCa patients (median age: 67; range: 51-80 years) presenting biochemical relapse after primary treatment who underwent CHO-PET/CT based HTT on positive bone metastases from December 2007 to June 2014. The effectiveness of HTT has been assessed with biochemical response at 3/6/12 months, biochemical relapse free survival (bRFS) and overall survival (OS) at 2 years. Toxicity has also been considered and assessed according to Common Terminology Criteria for Adverse Events (CTCAE). All patients presented a relapse at the time of CHO-PET/CT at bone level. In addition 15/20 (75%) also at lymph nodes (LNs) level (total lesions= 54). All patients underwent HTT on bone metastases and 19/20 concomitantly on prostatic bed and LNs. The median follow-up from CHO-PET/CT was 2 years (range: 1-7 years). At 3 months after the beginning of HTT treatment complete or partial biochemical response occurred in 79% of patients, at 6 months in 82% and at 12 months in 63% of patients. bRFS and OS at 2 years were 50% and 55% of patients, respectively. Patients presented mostly grade 1 or 2 toxicity according to CTCAE. The only grade 3 late toxicity has been observed in one patient. CHO-PET/CT based HTT is a suitable therapeutic approach in patients with recurrent PCa presenting bone metastases with a medium-low toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Improved prediction of biochemical recurrence after radical prostatectomy by genetic polymorphisms.

PubMed

Morote, Juan; Del Amo, Jokin; Borque, Angel; Ars, Elisabet; Hernández, Carlos; Herranz, Felipe; Arruza, Antonio; Llarena, Roberto; Planas, Jacques; Viso, María J; Palou, Joan; Raventós, Carles X; Tejedor, Diego; Artieda, Marta; Simón, Laureano; Martínez, Antonio; Rioja, Luis A

2010-08-01

Single nucleotide polymorphisms are inherited genetic variations that can predispose or protect individuals against clinical events. We hypothesized that single nucleotide polymorphism profiling may improve the prediction of biochemical recurrence after radical prostatectomy. We performed a retrospective, multi-institutional study of 703 patients treated with radical prostatectomy for clinically localized prostate cancer who had at least 5 years of followup after surgery. All patients were genotyped for 83 prostate cancer related single nucleotide polymorphisms using a low density oligonucleotide microarray. Baseline clinicopathological variables and single nucleotide polymorphisms were analyzed to predict biochemical recurrence within 5 years using stepwise logistic regression. Discrimination was measured by ROC curve AUC, specificity, sensitivity, predictive values, net reclassification improvement and integrated discrimination index. The overall biochemical recurrence rate was 35%. The model with the best fit combined 8 covariates, including the 5 clinicopathological variables prostate specific antigen, Gleason score, pathological stage, lymph node involvement and margin status, and 3 single nucleotide polymorphisms at the KLK2, SULT1A1 and TLR4 genes. Model predictive power was defined by 80% positive predictive value, 74% negative predictive value and an AUC of 0.78. The model based on clinicopathological variables plus single nucleotide polymorphisms showed significant improvement over the model without single nucleotide polymorphisms, as indicated by 23.3% net reclassification improvement (p = 0.003), integrated discrimination index (p <0.001) and likelihood ratio test (p <0.001). Internal validation proved model robustness (bootstrap corrected AUC 0.78, range 0.74 to 0.82). The calibration plot showed close agreement between biochemical recurrence observed and predicted probabilities. Predicting biochemical recurrence after radical prostatectomy based on clinicopathological data can be significantly improved by including patient genetic information. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Number of positive preoperative biopsy cores is a predictor of positive surgical margins (PSM) in small prostates after robot-assisted radical prostatectomy (RARP).

PubMed

Tuliao, Patrick H; Koo, Kyo C; Komninos, Christos; Chang, Chien H; Choi, Young D; Chung, Byung H; Hong, Sung J; Rha, Koon H

2015-12-01

To determine the impact of prostate size on positive surgical margin (PSM) rates after robot-assisted radical prostatectomy (RARP) and the preoperative factors associated with PSM. In all, 1229 men underwent RARP by a single surgeon, from 2005 to August of 2013. Excluded were patients who had transurethral resection of the prostate, neoadjuvant therapy, clinically advanced cancer, and the first 200 performed cases (to reduce the effect of learning curve). Included were 815 patients who were then divided into three prostate size groups: <31 g (group 1), 31-45 g (group 2), >45 g (group 3). Multivariate analysis determined predictors of PSM and biochemical recurrence (BCR). Console time and blood loss increased with increasing prostate size. There were more high-grade tumours in group 1 (group 1 vs group 2 and group 3, 33.9% vs 25.1% and 25.6%, P = 0.003 and P = 0.005). PSM rates were higher in prostates of <45 g with preoperative PSA levels of >20 ng/dL, Gleason score ≥7, T3 tumour, and ≥3 positive biopsy cores. In group 1, preoperative stage T3 [odds ratio (OR) 3.94, P = 0.020] and ≥3 positive biopsy cores (OR 2.52, P = 0.043) were predictive of PSM, while a PSA level of >20 ng/dL predicted the occurrence of BCR (OR 5.34, P = 0.021). No preoperative factors predicted PSM or BCR for groups 2 and 3. A preoperative biopsy with ≥3 positive cores in men with small prostates predicts PSM after RARP. In small prostates with PSM, a PSA level of >20 ng/dL is a predictor of BCR. These factors should guide the choice of therapy and indicate the need for closer postoperative follow-up. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

Identifying logical planes formed of compute nodes of a subcommunicator in a parallel computer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, Kristan D.; Faraj, Daniel

In a parallel computer, a plurality of logical planes formed of compute nodes of a subcommunicator may be identified by: for each compute node of the subcommunicator and for a number of dimensions beginning with a first dimension: establishing, by a plane building node, in a positive direction of the first dimension, all logical planes that include the plane building node and compute nodes of the subcommunicator in a positive direction of a second dimension, where the second dimension is orthogonal to the first dimension; and establishing, by the plane building node, in a negative direction of the first dimension,more » all logical planes that include the plane building node and compute nodes of the subcommunicator in the positive direction of the second dimension.« less

Assessment of prostate cancer detection with a visual-search human model observer

NASA Astrophysics Data System (ADS)

Sen, Anando; Kalantari, Faraz; Gifford, Howard C.

2014-03-01

Early staging of prostate cancer (PC) is a significant challenge, in part because of the small tumor sizes in- volved. Our long-term goal is to determine realistic diagnostic task performance benchmarks for standard PC imaging with single photon emission computed tomography (SPECT). This paper reports on a localization receiver operator characteristic (LROC) validation study comparing human and model observers. The study made use of a digital anthropomorphic phantom and one-cm tumors within the prostate and pelvic lymph nodes. Uptake values were consistent with data obtained from clinical In-111 ProstaScint scans. The SPECT simulation modeled a parallel-hole imaging geometry with medium-energy collimators. Nonuniform attenua- tion and distance-dependent detector response were accounted for both in the imaging and the ordered-subset expectation-maximization (OSEM) iterative reconstruction. The observer study made use of 2D slices extracted from reconstructed volumes. All observers were informed about the prostate and nodal locations in an image. Iteration number and the level of postreconstruction smoothing were study parameters. The results show that a visual-search (VS) model observer correlates better with the average detection performance of human observers than does a scanning channelized nonprewhitening (CNPW) model observer.

Antiproliferative effect of a polysaccharide fraction of a 20% methanolic extract of stinging nettle roots upon epithelial cells of the human prostate (LNCaP).

PubMed

Lichius, J J; Lenz, C; Lindemann, P; Müller, H H; Aumüller, G; Konrad, L

1999-10-01

In Germany, plant extracts are often used in the treatment of early stages of benign prostate hyperplasia (BPH). The effects of different concentrations of the polysaccharide fraction of the 20% methanolic extract of stinging nettle roots (POLY-M) on the cellular proliferation of lymph node carcinoma of the prostate (LNCaP) cells were determined by measurement of the genomic DNA content of the samples. All concentrations of POLY-M showed an inhibitory effect on the growth of the LNCaP cells during 7 days except the two lowest concentrations. The reduced proliferation of POLY-M treated LNCaP cells was significantly (p < 0.05) different from the untreated control. The inhibition was time- and concentration-dependent with the maximum suppression (50%) on day 6 and at concentrations of 1.0E-9 and 1.0E-11 mg/ml. No cytotoxic effect of POLY-M on cell proliferation was observed. The in vitro results show for the first time an antiproliferative effect of Urtica compounds on human prostatic epithelium and confirm our previous in vivo findings.

Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona.

PubMed

Carrera, D; de la Flor, M; Galera, J; Amillano, K; Gomez, M; Izquierdo, V; Aguilar, E; López, S; Martínez, M; Martínez, S; Serra, J M; Pérez, M; Martin, L

2016-01-01

The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Outcomes of Node-positive Breast Cancer Patients Treated With Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.

PubMed

Kamrava, Mitchell; Kuske, Robert R; Anderson, Bethany; Chen, Peter; Hayes, John; Quiet, Coral; Wang, Pin-Chieh; Veruttipong, Darlene; Snyder, Margaret; Demanes, David J

2018-06-01

To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy in node-positive compared with node-negative patients. From 1992 to 2013, 1351 patients (1369 breast cancers) were treated with breast-conserving surgery and adjuvant APBI using interstitial multicatheter brachytherapy. A total of 907 patients (835 node negative, 59 N1a, and 13 N1mic) had >1 year of data available and nodal status information and are the subject of this analysis. Median age (range) was 59 years old (22 to 90 y). T stage was 90% T1 and ER/PR/Her2 was positive in 87%, 71%, and 7%. Mean number of axillary nodes removed was 12 (SD, 6). Cox multivariate analysis for local/regional control was performed using age, nodal stage, ER/PR/Her2 receptor status, tumor size, grade, margin, and adjuvant chemotherapy/antiestrogen therapy. The mean (SD) follow-up was 7.5 years (4.6). The 5-year actuarial local control (95% confidence interval) in node-negative versus node-positive patients was 96.3% (94.5-97.5) versus 95.8% (87.6-98.6) (P=0.62). The 5-year actuarial regional control in node-negative versus node-positive patients was 98.5% (97.3-99.2) versus 96.7% (87.4-99.2) (P=0.33). The 5-year actuarial freedom from distant metastasis and cause-specific survival were significantly lower in node-positive versus node-negative patients at 92.3% (82.4-96.7) versus 97.8% (96.3-98.7) (P=0.006) and 91.3% (80.2-96.3) versus 98.7% (97.3-99.3) (P=0.0001). Overall survival was not significantly different. On multivariate analysis age 50 years and below, Her2 positive, positive margin status, and not receiving chemotherapy or antiestrogen therapy were associated with a higher risk of local/regional recurrence. Patients who have had an axillary lymph node dissection and limited node-positive disease may be candidates for treatment with APBI. Further research is ultimately needed to better define specific criteria for APBI in node-positive patients.

Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer.

PubMed

Brocks, David; Assenov, Yassen; Minner, Sarah; Bogatyrova, Olga; Simon, Ronald; Koop, Christina; Oakes, Christopher; Zucknick, Manuela; Lipka, Daniel Bernhard; Weischenfeldt, Joachim; Feuerbach, Lars; Cowper-Sal Lari, Richard; Lupien, Mathieu; Brors, Benedikt; Korbel, Jan; Schlomm, Thorsten; Tanay, Amos; Sauter, Guido; Gerhäuser, Clarissa; Plass, Christoph

2014-08-07

Despite much evidence on epigenetic abnormalities in cancer, it is currently unclear to what extent epigenetic alterations can be associated with tumors' clonal genetic origins. Here, we show that the prostate intratumor heterogeneity in DNA methylation and copy-number patterns can be explained by a unified evolutionary process. By assaying multiple topographically distinct tumor sites, premalignant lesions, and lymph node metastases within five cases of prostate cancer, we demonstrate that both DNA methylation and copy-number heterogeneity consistently reflect the life history of the tumors. Furthermore, we show cases of genetic or epigenetic convergent evolution and highlight the diversity in the evolutionary origins and aberration spectrum between tumor and metastatic subclones. Importantly, DNA methylation can complement genetic data by serving as a proxy for activity at regulatory domains, as we show through identification of high epigenetic heterogeneity at androgen-receptor-bound enhancers. Epigenome variation thereby expands on the current genome-centric view on tumor heterogeneity. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

A statistical motion model based on biomechanical simulations for data fusion during image-guided prostate interventions.

PubMed

Hu, Yipeng; Morgan, Dominic; Ahmed, Hashim Uddin; Pendsé, Doug; Sahu, Mahua; Allen, Clare; Emberton, Mark; Hawkes, David; Barratt, Dean

2008-01-01

A method is described for generating a patient-specific, statistical motion model (SMM) of the prostate gland. Finite element analysis (FEA) is used to simulate the motion of the gland using an ultrasound-based 3D FE model over a range of plausible boundary conditions and soft-tissue properties. By applying principal component analysis to the displacements of the FE mesh node points inside the gland, the simulated deformations are then used as training data to construct the SMM. The SMM is used to both predict the displacement field over the whole gland and constrain a deformable surface registration algorithm, given only a small number of target points on the surface of the deformed gland. Using 3D transrectal ultrasound images of the prostates of five patients, acquired before and after imposing a physical deformation, to evaluate the accuracy of predicted landmark displacements, the mean target registration error was found to be less than 1.9 mm.

Deep learning as a tool for increased accuracy and efficiency of histopathological diagnosis

NASA Astrophysics Data System (ADS)

Litjens, Geert; Sánchez, Clara I.; Timofeeva, Nadya; Hermsen, Meyke; Nagtegaal, Iris; Kovacs, Iringo; Hulsbergen-van de Kaa, Christina; Bult, Peter; van Ginneken, Bram; van der Laak, Jeroen

2016-05-01

Pathologists face a substantial increase in workload and complexity of histopathologic cancer diagnosis due to the advent of personalized medicine. Therefore, diagnostic protocols have to focus equally on efficiency and accuracy. In this paper we introduce ‘deep learning’ as a technique to improve the objectivity and efficiency of histopathologic slide analysis. Through two examples, prostate cancer identification in biopsy specimens and breast cancer metastasis detection in sentinel lymph nodes, we show the potential of this new methodology to reduce the workload for pathologists, while at the same time increasing objectivity of diagnoses. We found that all slides containing prostate cancer and micro- and macro-metastases of breast cancer could be identified automatically while 30-40% of the slides containing benign and normal tissue could be excluded without the use of any additional immunohistochemical markers or human intervention. We conclude that ‘deep learning’ holds great promise to improve the efficacy of prostate cancer diagnosis and breast cancer staging.

[Prostatic granulomas revealing a peripheral T-cell lymphoma].

PubMed

Foguem, C; Curlier, E; Rouamba, M-M; Regent, A; Philippe, P

2009-02-01

The presence of granulomas on tissue biopsie has been reported in a wide range of disorders. The clinical presentation and the diagnostic work-up of granulomatosis can be difficult as it is illustrated in the following report. A 59-year-old patient was referred in 2002 for a granulomatous prostatitis. Physical examination was normal. Except for the increase of prostate-specific antigen (which motivated a biopsy), the laboratory results were normal. Thoracic CT-scan disclosed mediastinal lymph nodes. A minor salivary gland biopsy was consistent with the diagnosis of sarcoidosis. In 2004, the patient presented an epidermal necrolysis, and in 2005 the deterioration of general status raised suspicion of a lymphoproliferative disorder. Liver and bone marrow biopsies revealed a granulomatous process. Despite steroid therapy, the patient died. Autopsy discloses a anaplasic T cell lymphoma. This report illustrates the relationship between sarcoidosis and lymphoma as a mode of presentation, a complication, or an accidental but misleading association? The association between anaplastic lymphoma and sarcoidosis is exceptional.

Impact of obesity on the predictive accuracy of prostate-specific antigen density and prostate-specific antigen in native Korean men undergoing prostate biopsy.

PubMed

Kim, Jae Heon; Doo, Seung Whan; Yang, Won Jae; Lee, Kwang Woo; Lee, Chang Ho; Song, Yun Seob; Jeon, Yoon Su; Kim, Min Eui; Kwon, Soon-Sun

2014-10-01

To evaluate the impact of obesity on the biopsy detection of prostate cancer. We retrospectively reviewed data of 1182 consecutive Korean patients (≥50 years) with serum prostate-specific antigen levels of 3-10 ng/mL who underwent initial extended 12-cores biopsy from September 2009 to March 2013. Patients who took medications that were likely to influence the prostate-specific antigen level were excluded. Receiver operating characteristic curves were plotted for prostate-specific antigen and prostate-specific antigen density predicting cancer status among non-obese and obese men. A total of 1062 patients (mean age 67.1 years) were enrolled in the analysis. A total of 230 men (21.7%) had a positive biopsy. In the overall study sample, the area under the receiver operator characteristic curve of serum prostate-specific antigen for predicting prostate cancer on biopsy were 0.584 and 0.633 for non-obese and obese men, respectively (P = 0.234). However, the area under the curve for prostate-specific antigen density in predicting cancer status showed a significant difference (non-obese 0.696, obese 0.784; P = 0.017). There seems to be a significant difference in the ability of prostate-specific antigen density to predict biopsy results between non-obese and obese men. Obesity positively influenced the overall ability of prostate-specific antigen density to predict prostate cancer. © 2014 The Japanese Urological Association.

Modulation of paracrine signaling by CD9 positive small extracellular vesicles mediates cellular growth of androgen deprived prostate cancer

PubMed Central

Soekmadji, Carolina; Riches, James D.; Russell, Pamela J.; Ruelcke, Jayde E.; McPherson, Stephen; Wang, Chenwei; Hovens, Chris M.; Corcoran, Niall M.; Hill, Michelle M.; Nelson, Colleen C.

2017-01-01

Proliferation and maintenance of both normal and prostate cancer (PCa) cells is highly regulated by steroid hormones, particularly androgens, and the extracellular environment. Herein, we identify the secretion of CD9 positive extracellular vesicles (EV) by LNCaP and DUCaP PCa cells in response to dihydrotestosterone (DHT) and use nano-LC–MS/MS to identify the proteins present in these EV. Subsequent bioinformatic and pathway analyses of the mass spectrometry data identified pathologically relevant pathways that may be altered by EV contents. Western blot and CD9 EV TR-FIA assay confirmed a specific increase in the amount of CD9 positive EV in DHT-treated LNCaP and DUCaP cells and treatment of cells with EV enriched with CD9 after DHT exposure can induce proliferation in androgen-deprived conditions. siRNA knockdown of endogenous CD9 in LNCaPs reduced cellular proliferation and expression of AR and prostate specific antigen (PSA) however knockdown of AR did not alter CD9 expression, also implicating CD9 as an upstream regulator of AR. Moreover CD9 positive EV were also found to be significantly higher in plasma from prostate cancer patients in comparison with benign prostatic hyperplasia patients. We conclude that CD9 positive EV are involved in mediating paracrine signalling and contributing toward prostate cancer progression. PMID:28881726

Prediction of potential disease-associated microRNAs based on random walk.

PubMed

Xuan, Ping; Han, Ke; Guo, Yahong; Li, Jin; Li, Xia; Zhong, Yingli; Zhang, Zhaogong; Ding, Jian

2015-06-01

Identifying microRNAs associated with diseases (disease miRNAs) is helpful for exploring the pathogenesis of diseases. Because miRNAs fulfill function via the regulation of their target genes and because the current number of experimentally validated targets is insufficient, some existing methods have inferred potential disease miRNAs based on the predicted targets. It is difficult for these methods to achieve excellent performance due to the high false-positive and false-negative rates for the target prediction results. Alternatively, several methods have constructed a network composed of miRNAs based on their associated diseases and have exploited the information within the network to predict the disease miRNAs. However, these methods have failed to take into account the prior information regarding the network nodes and the respective local topological structures of the different categories of nodes. Therefore, it is essential to develop a method that exploits the more useful information to predict reliable disease miRNA candidates. miRNAs with similar functions are normally associated with similar diseases and vice versa. Therefore, the functional similarity between a pair of miRNAs is calculated based on their associated diseases to construct a miRNA network. We present a new prediction method based on random walk on the network. For the diseases with some known related miRNAs, the network nodes are divided into labeled nodes and unlabeled nodes, and the transition matrices are established for the two categories of nodes. Furthermore, different categories of nodes have different transition weights. In this way, the prior information of nodes can be completely exploited. Simultaneously, the various ranges of topologies around the different categories of nodes are integrated. In addition, how far the walker can go away from the labeled nodes is controlled by restarting the walking. This is helpful for relieving the negative effect of noisy data. For the diseases without any known related miRNAs, we extend the walking on a miRNA-disease bilayer network. During the prediction process, the similarity between diseases, the similarity between miRNAs, the known miRNA-disease associations and the topology information of the bilayer network are exploited. Moreover, the importance of information from different layers of network is considered. Our method achieves superior performance for 18 human diseases with AUC values ranging from 0.786 to 0.945. Moreover, case studies on breast neoplasms, lung neoplasms, prostatic neoplasms and 32 diseases further confirm the ability of our method to discover potential disease miRNAs. A web service for the prediction and analysis of disease miRNAs is available at http://bioinfolab.stx.hk/midp/. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A critical evaluation of lymph node ratio in head and neck cancer.

PubMed

de Ridder, M; Marres, C C M; Smeele, L E; van den Brekel, M W M; Hauptmann, M; Balm, A J M; van Velthuysen, M L F

2016-12-01

In head and neck squamous cell carcinoma (HNSCC), the search for better prognostic factors beyond TNM-stage is ongoing. Lymph node ratio (LNR) (positive lymph nodes/total lymph nodes) is gaining interest in view of its potential prognostic significance. All HNSCC patients at the Netherlands Cancer Institute undergoing neck dissection for lymph node metastases in the neck region between 2002 and 2012 (n = 176) were included. Based on a protocol change in specimen processing, the cohort was subdivided in two distinct consecutive periods (pre and post 2007). The prognostic value of LNR, N-stage, and number of positive lymph nodes for overall survival was assessed. The mean number of examined lymph nodes after 2007 was significantly higher (42.3) than before (35.8) (p = 0.024). The higher number concerned mostly lymph nodes in level V. The mean number of positive lymph nodes before 2007 was 3.3 vs. 3.6 after 2007 (p = 0.745). By multivariate analysis of both pre- and post-2007 cohort data, two factors remained associated with an increased hazard of dying: N2 [HR 2.1 (1.1-4.1) and 2.4 (1.0-5.8)] and >3 positive lymph nodes [HR 2.0 (1.1-3.5) and 3.1 (1.4-6.9)]. Hazard ratio for LNR >7 % was not significantly different: pre 2007 at 2.2 (1.3-3.8) and post 2007 at 2.1 (1.0-4.8, p = 0.053). In this study, changes in specimen processing influenced LNR values, but not the total number of tumor positive nodes found. Therefore, in HNSCC, the number of positive nodes seems a more reliable parameter than LNR, provided a minimum number of lymph nodes are examined.

Prevalence of Corynebacterial 16S rRNA Sequences in Patients with Bacterial and “Nonbacterial” Prostatitis

PubMed Central

Tanner, Michael A.; Shoskes, Daniel; Shahed, Asha; Pace, Norman R.

1999-01-01

The etiology of chronic prostatitis syndromes in men is controversial, particularly when positive cultures for established uropathogens are lacking. Although identification of bacteria in prostatic fluid has relied on cultivation and microscopy, most microorganisms in the environment, including some human pathogens, are resistant to cultivation. We report here on an rRNA-based molecular phylogenetic approach to the identification of bacteria in prostate fluid from prostatitis patients. Positive bacterial signals were seen for 65% of patients with chronic prostatitis overall. Seven of 11 patients with bacterial signals but none of 6 patients without bacterial signals were cured with antibiotic-based therapy. Results indicate the occurrence in the prostate fluid of a wide spectrum of bacterial species representing several genera. Most rRNA genes were closely related to those of species belonging to the genera Corynebacterium, Staphylococcus, Peptostreptococcus, Streptococcus, and Escherichia. Unexpectedly, a wide diversity of Corynebacterium species was found in high proportion compared to the proportions of other bacterial species found. A subset of these 16S rRNA sequences represent those of undescribed species on the basis of their positions in phylogenetic trees. These uncharacterized organisms were not detected in control samples, suggesting that the organisms have a role in the disease or are the consequence of the disease. These studies show that microorganisms associated with prostatitis generally occur as complex microbial communities that differ between patients. The results also indicate that microbial communities distinct from those associated with prostatitis may occur at low levels in normal prostatic fluid. PMID:10325338

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, Kristan D.; Faraj, Daniel A.

In a parallel computer, a plurality of logical planes formed of compute nodes of a subcommunicator may be identified by: for each compute node of the subcommunicator and for a number of dimensions beginning with a first dimension: establishing, by a plane building node, in a positive direction of the first dimension, all logical planes that include the plane building node and compute nodes of the subcommunicator in a positive direction of a second dimension, where the second dimension is orthogonal to the first dimension; and establishing, by the plane building node, in a negative direction of the first dimension,more » all logical planes that include the plane building node and compute nodes of the subcommunicator in the positive direction of the second dimension.« less

The Will Rogers phenomenon in urological oncology.

PubMed

Gofrit, Ofer N; Zorn, Kevin C; Steinberg, Gary D; Zagaja, Gregory P; Shalhav, Arieh L

2008-01-01

Improvement in the prognosis of patient groups due to stage or grade reclassification is called the Will Rogers phenomenon. We determined the significance of the Will Rogers phenomenon in urological oncology. Studies referring to the Will Rogers phenomenon in urological oncology were identified through a MEDLINE search. Samples of articles not referring to the phenomenon directly but likely to be biased by it, such as articles comparing contemporary data to historical controls, were also reviewed. In prostate cancer the Will Rogers phenomenon is the result of the late 1990s acceptance that Gleason scores 2 to 4 should not be assigned on prostate biopsy. Consequently grade inflation occurred and current readings are almost 1 Gleason grade higher compared to past readings of the same biopsy. The result is an illusion of improvement in grade adjusted prognosis. In bladder cancer the Will Rogers phenomenon arises from improvement in histopathological processing of cystectomy specimens enabling the identification of microscopic perivesical fat infiltration and lymph node metastases not recognized in the past. Up staging from pT2 to pT3 and N0 to N+ may partly explain the improved stage adjusted survival after radical cystectomy observed in contemporary series. The Will Rogers phenomenon may also explain the correlation between the total number of lymph nodes removed at radical cystectomy and survival. As more lymph nodes are removed the probability of identifying metastases and up staging to N+ increases. Comparison of contemporary results to historical controls may be biased by the Will Rogers phenomenon. Ignoring the possibility of stage or grade reclassification may lead to erroneous conclusions.

Imaging Prostate Cancer Microenvironment by collagen Hybridization

DTIC Science & Technology

2014-10-01

from enlarged lymph nodes. Figure 3. Ex vivo NIRF imaging of PC-3 PIP xenograft. AI = androgen independent, AR = androgen receptor negative, PSMA ...center O.D. rim/focal ROI PC-3 rapid 0.25 ± .09 1.21 ± 0.40 PC-3 ( PSMA +) PIP rapid 0.26 ± .12 NA DU-145 slow 0.01 ± 0.01 0.06 ± 0.02 HP LNCaP

Feasibility study using a Ni-Ti stent and electronic portal imaging to localize the prostate during radiotherapy.

PubMed

Carl, Jesper; Lund, Bente; Larsen, Erik Hoejkjaer; Nielsen, Jane

2006-02-01

A new method for localization of the prostate during external beam radiotherapy is presented. The method is based on insertion of a thermo-expandable Ni-Ti stent. The stent is originally developed for treatment of bladder outlet obstruction caused by benign hyperplasia. The radiological properties of the stent are used for precise prostate localization during treatment using electronic portal images. Patients referred for intended curative radiotherapy and having a length of their prostatic urethra in the range from 25 to 65 mm were included. Pairs of isocentric orthogonal portal images were used to determine the 3D position at eight different treatment sessions for each patient. Fourteen patients were enrolled in the study. The data obtained demonstrated that the stent position was representative of the prostate location. The stent may also improve delineation of the prostate GTV, and prevent obstruction of bladder outlet during treatment. Precision in localization of the stent was less than 1 mm. Random errors in stent position were left-right 1.6 mm, cranial-caudal 2.2 mm and anterior-posterior 3.2 mm. In four of 14 patients a dislocation of the stent to the bladder occurred. Dislocation only occurred in patients with length of prostatic urethra less than 40 mm. A new method for radiological high precision localization of the prostate during radiotherapy is presented. The method is based on insertion of a standard Ni-Ti thermo-expandable stent, designed for treatment of benign prostate hyperplasia.

Fiducial marker guided prostate radiotherapy: a review

PubMed Central

Jain, Suneil; Hounsell, Alan R; O'Sullivan, Joe M

2016-01-01

Image-guided radiotherapy (IGRT) is an essential tool in the accurate delivery of modern radiotherapy techniques. Prostate radiotherapy positioned using skin marks or bony anatomy may be adequate for delivering a relatively homogeneous whole-pelvic radiotherapy dose, but these surrogates are not reliable when using reduced margins, dose escalation or hypofractionated stereotactic radiotherapy. Fiducial markers (FMs) for prostate IGRT have been in use since the 1990s. They require surgical implantation and provide a surrogate for the position of the prostate gland. A variety of FMs are available and they can be used in a number of ways. This review aimed to establish the evidence for using prostate FMs in terms of feasibility, implantation procedures, types of FMs used, FM migration, imaging modalities used and the clinical impact of FMs. A search strategy was defined and a literature search was carried out in Medline. Inclusion and exclusion criteria were applied, which resulted in 50 articles being included in this review. The evidence demonstrates that FMs provide a more accurate surrogate for the position of the prostate than either external skin marks or bony anatomy. A combination of FM alignment and soft-tissue analysis is currently the most effective and widely available approach to ensuring accuracy in prostate IGRT. FM implantation is safe and well tolerated. FM migration is possible but minimal. Standardization of all techniques and procedures in relation to the use of prostate FMs is required. Finally, a clinical trial investigating a non-surgical alternative to prostate FMs is introduced. PMID:27585736

Indications for Pelvic Nodal Treatment in Prostate Cancer Should Change. Validation of the Roach Formula in a Large Extended Nodal Dissection Series

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdollah, Firas; Cozzarini, Cesare; Suardi, Nazareno

2012-06-01

Purpose: Previous studies have criticized the predicting ability of the Roach formula in assessing the risk of lymph node invasion (LNI) in contemporary patients with prostate cancer (PCa) due to a significant overestimation of LNI rates. However, all those studies included patients treated with limited pelvic lymph node dissection (PLND), which is associated with high rates of false negative findings. We hypothesized that the Roach formula is still an accurate tool for LNI predictions if an extended PLND (ePLND) is performed. Methods and Materials: We included 3,115 consecutive patients treated with radical prostatectomy and ePLND between 2000 and 2010 atmore » a single tertiary referral center. Extended PLND consisted of removal of obturator, external iliac, and hypogastric lymph nodes. We externally validated the Roach formula by using the area under the receiver operating characteristics curve and calibration plot method. Moreover, we tested the performance characteristics of different formula-generated cutoff values ranging from 1% to 20%. Results: The accuracy of the Roach formula was 80.3%. The calibration showed only a minor underestimation of the LNI risk in high-risk patients (6.7%). According to the Roach formula, the use of 15% cut off would have allowed 74.2% (2,311/3,115) of patients to avoid nodal irradiation, while up to 32.7% (111/336) of all patients with LNI would have been missed. When the cut off was lowered to 6%, nodal treatment would have been spared in 1,541 (49.5%) patients while missing 41 LNI patients. The sensitivity, specificity, and negative predictive values associated with the 6% cut off were 87.9%, 54%, and 97.3%, respectively. Conclusions: The Roach formula is still accurate and does not overestimate the rate of LNI in contemporary prostate cancer patients if they are treated with ePLND. However, the recommended cut off of 15% would miss approximately one-third of patients with LNI. Based on our results, the cut off should be lowered to 6%.« less

Small cell carcinoma of the prostate presenting with Cushing Syndrome. A narrative review of an uncommon condition.

PubMed

Rueda-Camino, José Antonio; Losada-Vila, Beatriz; De Ancos-Aracil, Cristina Lucía; Rodríguez-Lajusticia, Laura; Tardío, Juan Carlos; Zapatero-Gaviria, Antonio

2016-01-01

Small cell carcinoma (SCC) of the prostate is an uncommon condition; there are very few cases in which presenting symptoms are consistent with Cushing Syndrome (CS). We report a new case in which CS triggers the suspicion of an SCC of the prostate and a review of the published cases of SCC of the prostate presenting with CS. The origin of these neoplasms is still unclear. It may be suspected when laboratory features appear in patients diagnosed with prostatic adenocarcinoma which becomes resistant to specific therapy. SCC usually occurs after the 6th decade. Patients suffering SCC of the prostate presenting with CS usually present symptoms such as hypertension, hyperglycemia, alkalosis or hypokalemia; cushingoid phenotype is less frequent. Cortisol and ACTH levels are often high. Prostatic-specific antigen levels are usually normal. CT scan is the preferred imaging test to localize the lesion, but its performance may be improved by adding other tests, such as FDG-PET scan. All patients have metastatic disease at the time of diagnosis. Lymph nodes, liver and bone are the most frequent metastases sites. Surgery and Ketokonazole are the preferred treatments for CS. The prognosis is very poor: 2- and 5-year survival rates are 27.5 and 14.3%, respectively. Key messages When a patient presents with ectopic Cushing Syndrome but lungs are normal, an atypical localization should be suspected. We should suspect a prostatic origin if Cushing Syndrome is accompanied by obstructive inferior urinary tract symptoms or in the setting of a prostatic adenocarcinoma with rapid clinical and radiological progression with relatively low PSA levels. Although no imaging test is preferred to localize these tumors, FDG-PET-TC can be very useful. Hormone marker scintigraphy (e.g. somatostatin) could be used too. As Cushing Syndrome is a paraneoplastic phenomenon, treatment of the underlying disease may help control hypercortisolism manifestations. These tumors are usually metastatic by the time of diagnosis. They have very poor prognosis.

Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes

PubMed Central

Yan, Lisa; Da Silva, Diane M.; Verma, Bhavna; Gray, Andrew; Brand, Heike E.; Skeate, Joseph G.; Porras, Tania B.; Kanodia, Shreya; Kast, W. Martin

2014-01-01

Background LIGHT, a ligand for lymphotoxin-β receptor (LTβR) and herpes virus entry mediator, is predominantly expressed on activated immune cells and LTβR signaling leads to the recruitment of lymphocytes. The interaction between LIGHT and LTβR has been previously shown in a virus induced tumor model to activate immune cells and result in tumor regression, but the role of LIGHT in tumor immunosuppression or in a prostate cancer setting, where self antigens exist, has not been explored. We hypothesized that forced expression of LIGHT in prostate tumors would shift the pattern of immune cell infiltration, would inhibit T regulatory cells (Tregs) and would induce prostate cancer tumor associated antigen (TAA) specific T cells that would eradicate tumors. Methods Real Time PCR was used to evaluate expression of forced LIGHT and various other genes in prostate tumors samples. Adenovirus encoding murine LIGHT was injected intratumorally into TRAMP C2 prostate cancer cell tumor bearing mice for in vivo studies. Chemokine and cytokine concentrations were determined by multiplex ELISA. Flow cytometry was used to phenotype tumor infiltrating lymphocytes and expression of LIGHT on the tumor cell surface. Tumor specific lymphocytes were quantified via an ELISpot assay. Treg induction and Treg suppression assays determined Treg functionality after LIGHT treatment. Results LIGHT expression peaked within 48 hours of infection, recruited effector T cells into the tumor microenvironment that recognized mouse prostate stem cell antigen (PSCA) and inhibited the infiltration of Tregs. Tregs isolated from tumor draining lymph nodes had impaired suppressive capability after LIGHT treatment. LIGHT in combination with a therapeutic vaccine, PSCA TriVax, reduced tumor burden. Conclusion Forced LIGHT treatment combined with PSCA TriVax therapeutic vaccination delays prostate cancer progression in mice by recruiting effector T lymphocytes to the tumor and inhibiting Treg mediated immunosuppression. PMID:25399517

Positive surgical margins after robotic assisted radical prostatectomy: a multi-institutional study.

PubMed

Patel, Vipul R; Coelho, Rafael F; Rocco, Bernardo; Orvieto, Marcelo; Sivaraman, Ananthakrishnan; Palmer, Kenneth J; Kameh, Darien; Santoro, Luigi; Coughlin, Geoff D; Liss, Michael; Jeong, Wooju; Malcolm, John; Stern, Joshua M; Sharma, Saurabh; Zorn, Kevin C; Shikanov, Sergey; Shalhav, Arieh L; Zagaja, Gregory P; Ahlering, Thomas E; Rha, Koon H; Albala, David M; Fabrizio, Michael D; Lee, David I; Chauhan, Sanket

2011-08-01

Positive surgical margins are an independent predictive factor for biochemical recurrence after radical prostatectomy. We analyzed the incidence of and associative factors for positive surgical margins in a multi-institutional series of 8,418 robotic assisted radical prostatectomies. We analyzed the records of 8,418 patients who underwent robotic assisted radical prostatectomy at 7 institutions. Of the patients 323 had missing data on margin status. Positive surgical margins were categorized into 4 groups, including apex, bladder neck, posterolateral and multifocal. The records of 6,169 patients were available for multivariate analysis. The variables entered into the logistic regression models were age, body mass index, preoperative prostate specific antigen, biopsy Gleason score, prostate weight and pathological stage. A second model was built to identify predictive factors for positive surgical margins in the subset of patients with organ confined disease (pT2). The overall positive surgical margin rate was 15.7% (1,272 of 8,095 patients). The positive surgical margin rate for pT2 and pT3 disease was 9.45% and 37.2%, respectively. On multivariate analysis pathological stage (pT2 vs pT3 OR 4.588, p<0.001) and preoperative prostate specific antigen (4 or less vs greater than 10 ng/ml OR 2.918, p<0.001) were the most important independent predictive factors for positive surgical margins after robotic assisted radical prostatectomy. Increasing prostate weight was associated with a lower risk of positive surgical margins after robotic assisted radical prostatectomy (OR 0.984, p<0.001) and a higher body mass index was associated with a higher risk of positive surgical margins (OR 1.032, p<0.001). For organ confined disease preoperative prostate specific antigen was the most important factor that independently correlated with positive surgical margins (4 or less vs greater than 10 ng/ml OR 3.8, p<0.001). The prostatic apex followed by a posterolateral site was the most common location of positive surgical margins after robotic assisted radical prostatectomy. Factors that correlated with cancer aggressiveness, such as pathological stage and preoperative prostate specific antigen, were the most important factors independently associated with an increased risk of positive surgical margins after robotic assisted radical prostatectomy. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Biodistribution of [(68)Ga]PSMA-HBED-CC in Patients with Prostate Cancer: Characterization of Uptake in Normal Organs and Tumour Lesions.

PubMed

Prasad, Vikas; Steffen, Ingo G; Diederichs, Gerd; Makowski, Marcus R; Wust, Peter; Brenner, Winfried

2016-06-01

The aim of this study was to determine the physiological and pathophysiological biodistribution of [(68)Ga]PSMA-HBED-CC (PSMA-11) ([(68)Ga]PSMA) in patients with prostate cancer (PCA) to establish the range of normal uptake in relevant organs and primary prostate tumours, locally recurrent PCA, lymph and bone metastases and other metastatic lesions. Additionally, we aimed to determine a cut-off uptake value for differentiation of primary tumours from normal prostate tissue. Overall, [(68)Ga]PSMA positron emission tomography/x-ray computed tomography (PET/CT) of 101 patients (mean age 69.1 years) with PCA was analysed retrospectively. For assessment of tracer biodistribution, maximum standardized uptake values (SUVmax) were calculated for various normal organs, as well as for primary tumours (PT) and/or metastases. Results are presented as median, interquartile range (IQR; 25th quantil-75th quantil) and range (minimum-maximum). [(68)Ga]PSMA PET/CT was performed 50 min (range 30-126) after injection of 109 MBq (range 84-158). Regarding biodistribution, highest uptake (median/IQR/range) of the tracer was found in the kidneys (49.6/40.7-57.6/2.7-97.0) followed by the submandibular glands (17.3/13.7-21.2/7.5-30.4), parotid glands (16.1/12.2-19.8/5.5-30.9) and duodenum (13.8/10.5-17.2/5.8-26.9). The best cut-off value for differentiating physiological uptake in the primary tumour from that in the prostate was found to be an SUVmax of 3.2. The median SUVmax in the PT (n = 35), locally recurrent PCA (n = 8), lymph node (n = 166), bone (n = 157) and other metastases (n = 3) were 10.2, 5.9, 6.2, 7.4 and 3.8, respectively. The best cut-off values for differentiating non-pathological uptake in lymph nodes and bones from tumour uptake were found to be SUVmax of 3.2 and 1.9, respectively. Patients with PSA <2 had significantly lower SUVmax in bone metastases as compared to patients with PSA ≥2 (p < 0.01). This biodistribution study provided a broad range of uptake data of [(68)Ga]PSMA-11 for normal organs/tissues, primary prostate tumours and metastatic lesions based on a large patient cohort. Both PT and small metastatic lesions were detectable due to their high tracer uptake. Four-times-higher median uptake in PT in comparison to normal prostate stroma resulted in a high diagnostic accuracy that could potentially be used for multimodal image-guided biopsy with dedicated reconstruction software.

Diagnosis and treatment of bacterial prostatitis.

PubMed

Videčnik Zorman, Jerneja; Matičič, Mojca; Jeverica, Samo; Smrkolj, Tomaž

2015-01-01

Prostate inflammation is a common syndrome, especially in men under 50. It usually presents with voiding symptoms and pain in the genitourinary area, and sometimes as sexual dysfunction. Based on clinical and laboratory characteristics, prostatitis is classified as acute bacterial prostatitis, chronic bacterial prostatitis, chronic inflammatory and non-inflammatory prostatitis or chronic pelvic pain syndrome, and asymptomatic inflammatory prostatitis. Bacterial prostatitis is most often caused by infection with uropathogens, mainly Gram-negative bacilli, but Gram-positive and atypical microorganisms have also been identified as causative organisms of chronic prostatitis. According to reports by several authors, Chlamydia trachomatis and Trichomonas vaginalis are some of the most common pathogens, making chronic prostatitis a sexually transmitted disease. Diagnosis and treatment of acute and chronic bacterial prostatitis in particular can be challenging.

Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model.

PubMed

Wada, Satoshi; Yoshimura, Kiyoshi; Hipkiss, Edward L; Harris, Tim J; Yen, Hung-Rong; Goldberg, Monica V; Grosso, Joseph F; Getnet, Derese; Demarzo, Angelo M; Netto, George J; Anders, Robert; Pardoll, Drew M; Drake, Charles G

2009-05-15

To study the immune response to prostate cancer, we developed an autochthonous animal model based on the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse in which spontaneously developing tumors express influenza hemagglutinin as a unique, tumor-associated antigen. Our prior studies in these animals showed immunologic tolerance to hemagglutinin, mirroring the clinical situation in patients with cancer who are generally nonresponsive to their disease. We used this physiologically relevant animal model to assess the immunomodulatory effects of cyclophosphamide when administered in combination with an allogeneic, cell-based granulocyte-macrophage colony-stimulating factor-secreting cancer immunotherapy. Through adoptive transfer of prostate/prostate cancer-specific CD8 T cells as well as through studies of the endogenous T-cell repertoire, we found that cyclophosphamide induced a marked augmentation of the antitumor immune response. This effect was strongly dependent on both the dose and the timing of cyclophosphamide administration. Mechanistic studies showed that immune augmentation by cyclophosphamide was associated with a transient depletion of regulatory T cells in the tumor draining lymph nodes but not in the peripheral circulation. Interestingly, we also noted effects on dendritic cell phenotype; low-dose cyclophosphamide was associated with increased expression of dendritic cell maturation markers. Taken together, these data clarify the dose, timing, and mechanism of action by which immunomodulatory cyclophosphamide can be translated to a clinical setting in a combinatorial cancer treatment strategy.

Probability modeling of the number of positive cores in a prostate cancer biopsy session, with applications.

PubMed

Serfling, Robert; Ogola, Gerald

2016-02-10

Among men, prostate cancer (CaP) is the most common newly diagnosed cancer and the second leading cause of death from cancer. A major issue of very large scale is avoiding both over-treatment and under-treatment of CaP cases. The central challenge is deciding clinical significance or insignificance when the CaP biopsy results are positive but only marginally so. A related concern is deciding how to increase the number of biopsy cores for larger prostates. As a foundation for improved choice of number of cores and improved interpretation of biopsy results, we develop a probability model for the number of positive cores found in a biopsy, given the total number of cores, the volumes of the tumor nodules, and - very importantly - the prostate volume. Also, three applications are carried out: guidelines for the number of cores as a function of prostate volume, decision rules for insignificant versus significant CaP using number of positive cores, and, using prior distributions on total tumor size, Bayesian posterior probabilities for insignificant CaP and posterior median CaP. The model-based results have generality of application, take prostate volume into account, and provide attractive tradeoffs of specificity versus sensitivity. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Optimisation of fluorescence guidance during robot-assisted laparoscopic sentinel node biopsy for prostate cancer.

PubMed

KleinJan, Gijs H; van den Berg, Nynke S; Brouwer, Oscar R; de Jong, Jeroen; Acar, Cenk; Wit, Esther M; Vegt, Erik; van der Noort, Vincent; Valdés Olmos, Renato A; van Leeuwen, Fijs W B; van der Poel, Henk G

2014-12-01

The hybrid tracer was introduced to complement intraoperative radiotracing towards the sentinel nodes (SNs) with fluorescence guidance. Improve in vivo fluorescence-based SN identification for prostate cancer by optimising hybrid tracer preparation, injection technique, and fluorescence imaging hardware. Forty patients with a Briganti nomogram-based risk >10% of lymph node (LN) metastases were included. After intraprostatic tracer injection, SN mapping was performed (lymphoscintigraphy and single-photon emission computed tomography with computed tomography (SPECT-CT)). In groups 1 and 2, SNs were pursued intraoperatively using a laparoscopic gamma probe followed by fluorescence imaging (FI). In group 3, SNs were initially located via FI. Compared with group 1, in groups 2 and 3, a new tracer formulation was introduced that had a reduced total injected volume (2.0 ml vs. 3.2 ml) but increased particle concentration. For groups 1 and 2, the Tricam SLII with D-Light C laparoscopic FI (LFI) system was used. In group 3, the LFI system was upgraded to an Image 1 HUB HD with D-Light P system. Hybrid tracer-based SN biopsy, extended pelvic lymph node dissection, and robot-assisted radical prostatectomy. Number and location of the preoperatively identified SNs, in vivo fluorescence-based SN identification rate, tumour status of SNs and LNs, postoperative complications, and biochemical recurrence (BCR). Mean fluorescence-based SN identification improved from 63.7% (group 1) to 85.2% and 93.5% for groups 2 and 3, respectively (p=0.012). No differences in postoperative complications were found. BCR occurred in three pN0 patients. Stepwise optimisation of the hybrid tracer formulation and the LFI system led to a significant improvement in fluorescence-assisted SN identification. Preoperative SPECT-CT remained essential for guiding intraoperative SN localisation. Intraoperative fluorescence-based SN visualisation can be improved by enhancing the hybrid tracer formulation and laparoscopic fluorescence imaging system. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Immune response in melanoma: an in-depth analysis of the primary tumor and corresponding sentinel lymph node

PubMed Central

Ma, Michelle W.; Medicherla, Ratna C.; Qian, Meng; de Miera, Eleazar Vega-Saenz; Friedman, Erica B.; Berman, Russell S.; Shapiro, Richard L.; Pavlick, Anna C.; Ott, Patrick A.; Bhardwaj, Nina; Shao, Yongzhao; Osman, Iman; Darvishian, Farbod

2013-01-01

The sentinel lymph node is the initial site of metastasis. Down-regulation of anti-tumor immunity plays a role in nodal progression. Our objective was to investigate the relationship between immune modulation and sentinel lymph node positivity, correlating it with outcome in melanoma patients. Lymph node/primary tissues from melanoma patients prospectively accrued and followed at New York University Medical Center were evaluated for the presence of regulatory T-cells (Foxp3+) and dendritic cells (conventional: CD11c+, mature: CD86+) using immunohistochemistry. Primary melanoma immune cell profiles from sentinel lymph node-positive/-negative patients were compared. Logistic regression models inclusive of standard-of-care/immunologic primary tumor characteristics were constructed to predict the risk of sentinel lymph node positivity. Immunological responses in the positive sentinel lymph node were also compared to those in the negative non-sentinel node from the same nodal basin and matched negative sentinel lymph node. Decreased immune response was defined as increased regulatory T-cells or decreased dendritic cells. Associations between the expression of these immune modulators, clinicopathologic variables, and clinical outcome were evaluated using univariate/multivariate analyses. Primary tumor conventional dendritic cells and regression were protective against sentinel lymph node metastasis (odds ratio=0.714, 0.067; P=0.0099, 0.0816, respectively). Anti-tumor immunity was down-regulated in the positive sentinel lymph node with an increase in regulatory T-cells compared to the negative non-sentinel node from the same nodal basin (P=0.0005) and matched negative sentinel lymph node (P=0.0002). The positive sentinel lymph node also had decreased numbers of conventional dendritic cells compared to the negative sentinel lymph node (P<0.0001). Adding sentinel lymph node regulatory T-cell expression improved the discriminative power of a recurrence risk assessment model using clinical stage. Primary tumor regression was associated with prolonged disease-free (P=0.025) and melanoma-specific (P=0.014) survival. Our results support an assessment of local immune profiles in both the primary tumor and sentinel lymph node to help guide therapeutic decisions. PMID:22425909

Number and Location of Positive Nodes, Postoperative Radiotherapy, and Survival After Esophagectomy With Three-Field Lymph Node Dissection for Thoracic Esophageal Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Junqiang; Pan Jianji, E-mail: panjianji@126.com; Zheng Xiongwei

2012-01-01

Purpose: To analyze influences of the number and location of positive lymph nodes and postoperative radiotherapy on survival for patients with thoracic esophageal squamous cell carcinoma (TE-SCC) treated with radical esophagectomy with three-field lymphadenectomy. Methods and Materials: A total of 945 patients underwent radical esophagectomy plus three-field lymph node dissection for node-positive TE-SCC at Fujian Provincial Tumor Hospital between January 1993 and March 2007. Five hundred ninety patients received surgery only (S group), and 355 patients received surgery, followed 3 to 4 weeks later by postoperative radiotherapy (S+R group) to a median total dose of 50 Gy in 25 fractions.more » We assessed potential associations among patient-, tumor-, and treatment-related factors and overall survival. Results: Five-year overall survival rates were 32.8% for the entire group, 29.6% for the S group, and 38.0% for the S+R group (p = 0.001 for S vs. S+R). Treatment with postoperative radiotherapy was particularly beneficial for patients with {>=}3 positive nodes and for those with metastasis in the upper (supraclavicular and upper mediastinal) region or both the upper and lower (mediastinal and abdominal) regions (p < 0.05). Postoperative radiotherapy was also associated with lower recurrence rates in the supraclavicular and upper and middle mediastinal regions (p < 0.05). Sex, primary tumor length, number of positive nodes, pathological T category, and postoperative radiotherapy were all independent predictors of survival. Conclusions: Postoperative radiotherapy was associated with better survival for patients with node-positive TE-SCC, particularly those with three or more positive nodes and positive nodes in the supraclavicular and superior mediastinal regions.« less

Salvage cryotherapy for recurrent prostate cancer after radiation therapy: the Columbia experience.

PubMed

de la Taille, A; Hayek, O; Benson, M C; Bagiella, E; Olsson, C A; Fatal, M; Katz, A E

2000-01-01

Cryotherapy of the prostate represents a potential treatment for localized recurrent prostate cancer after radiation therapy. We report our experience and evaluate the predictive factors for prostate-specific antigen (PSA) recurrence. Between October 1994 and April 1999, 43 patients underwent salvage cryoablation. All patients had biopsy-proven recurrent prostate cancer without seminal vesicle invasion, negative bone scans, and negative lymph node dissection. Patients had received 3 months of combined hormonal therapy before cryosurgery. Biochemical recurrence-free survival (bRFS) was defined as a PSA value less than 0.1 ng/mL. Complications included incontinence (9%), obstruction (5%), urethral stricture (5%), rectal pain (26%), urinary infection (9%), scrotal edema (12%), and hematuria (5%). The mean follow-up was 21.9 months (range 1.2 to 54). Twenty-six patients (60%) reached a serum PSA nadir less than 0.1 ng/mL, 16 (37%) had a PSA less than 4 ng/mL, and 1 (3%) had a PSA less than 10 ng/mL. The bRFS rate was 79% at 6 months and 66% at 12 months. The bRFS rate was higher for patients who had an undetectable postcryotherapy PSA than for patients who did not reach a PSA less than 0. 1 ng/mL (73% versus 30%, P = 0.0076). Using multivariate analysis, a PSA nadir greater than 0.1 ng/mL was an independent predictor of PSA recurrence. Current salvage cryotherapy of the prostate can result in undetectable serum PSA levels with low morbidity. Our data support the current safety and efficacy profile. We believe that cryotherapy is a viable option in the treatment of patients who have biopsy-proven local failure after radiation therapy for prostate cancer. Further refinements in technique and equipment may enhance cryosurgical results.

[Primary malignant lymphoma of the prostate: report of a case achieving complete response to combination chemotherapy and review of 22 Japanese cases].

PubMed

Fukutani, Keiko; Koyama, Yasuhiro; Fujimori, Masahiro; Ishida, Toshimitsu

2003-09-01

A 70-year-old man presented with complaints of difficult urination, perineal pain and lassitude. An enlarged, hard and nodular prostate was palpable on digital rectal examination. Needle biopsy of the prostate was performed, which revealed diffuse large B-cell non-Hodgkin's lymphoma by immunohistochemical studies. Right internal and external iliac nodes were swollen on computed tomographic scan (CT) of the pelvis. No abnormal finding was seen on abdominal CT, upper gastrointestinal fiberscopy and bone marrow histology. Therefore, the disease was classified into the clinical stage II according to Ann Arbor's criteria. The patient achieved complete response (CR) to five cycles of combination chemotherapy, CHOP, and survives more than two years without recurrence. Primary malignant lymphoma of the prostate is a rare prostatic malignancy. Only 22 Japanese cases with primary prostatic lymphoma have been reported to our knowledge. In 23 cases including ours the majority of the patients were older than 60 years, and their histopathology was mostly diffuse lymphoma, which belongs to intermediate grade of non-Hodjkin's lymphoma according to the Working Formulation's Classification. Nineteen out of 23 cases (83%) were divided into localized stage i.e. stage I or II. In these reports, three of five cases treated with either radical prostatectomy or radiotherapy alone resulted in death or progressive disease. On the other hand, 11 out of 16 cases (69%) who received chemotherapy alone or with other therapy obtained CR. Primary lymphoma of prostate has previously been considered to have a poor prognosis. Our results, however, suggest that patients with this malignancy respond well to combined chemotherapy, and could possibly be cured when the disease is confined to the localized stage.

Relationships between serum PSA levels, Gleason scores and results of 68Ga-PSMAPET/CT in patients with recurrent prostate cancer.

PubMed

Sanli, Yasemin; Kuyumcu, Serkan; Sanli, Oner; Buyukkaya, Fikret; İribaş, Ayça; Alcin, Goksel; Darendeliler, Emin; Ozluk, Yasemin; Yildiz, Sevda Ozel; Turkmen, Cüneyt

2017-11-01

To investigate the relationship between serum PSA level, Gleason score of PCa and the outcomes of Ga 68 -PSMA PET/CT in patients with recurrent PCa. A total of 109 consecutive patients (median age 71 years; range 48-89 years) who had PSA recurrence after RP and/or hormonotherapy and/or radiotherapy were included in this study. Local recurrences, lymph node metastasis (pelvic, abdominal and/or supradiaphragmatic), bone metastases (oligometastatic/multimetastatic) and other metastatic sites (lung, liver, brain, etc) were documented. In 91(83.4%) patients at least one lesion characteristic for PCa was detected by 68 Ga-PSMA PET/CT. The median serum total PSA (tPSA) was 6.5 (0.2-640) ng/ml.There was a significant difference between 68 Ga-PSMA PET/CT positive and negative patients in terms of serum total PSA value. No statistical significance was found between positive and negative 68 Ga-PSMA PET/CT findings in terms of Gleason score. Local recurrence was detected in 56 patients. whereas lymph node metastases were demonstrated in 46 patients. Pelvic nodal disease was the most frequent presentation followed by abdominal and supradiaphragmaticnodal involvement. Bone metastases [oligometastasis, (n = 20); multimetastasis, (n = 35)⦌ were also detected in 55 patients. In the ROC analysis for the study cohort, the optimal cut-off value of total serum PSA was determined as 0.67 ng/ml for distinguishing between positive and negative 68 Ga-PSMA PET/CT images, with an area under curve of 0.952 (95% CI 0.911-0.993). 68 Ga-PSMA PET/CT was found to be an effective tool for the detection of recurrent PCa. Even though no relationship was detected between the GS and 68 Ga-PSMA PET/CT findings, serum total PSA values may be used for estimating the likelihood of positive 68 Ga-PSMA PET/CT results.

SU-F-J-11: Radiobiologically Optimized Patient Localization During Prostate External Beam Localization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Y; Gardner, S; Liu, C

2016-06-15

Purpose: To present a novel positioning strategy which optimizes radiation delivery with radiobiological response knowledge, and to evaluate its application during prostate external beam radiotherapy. Methods: Ten patients with low or intermediate risk prostate cancer were evaluated retrospectively in this IRB-approved study. For each patient, a VMAT plan was generated on the planning CT (PCT) to deliver 78 Gy in 39 fractions with PTV = prostate + 7 mm margin, except for 5mm in the posterior direction. Five representative pretreatment CBCT images were selected for each patient, and prostate, rectum, and bladder were delineated on all CBCT images. Each CBCTmore » was auto-registered to the corresponding PCT. Starting from this auto-matched position (AM-position), a search for optimal treatment position was performed utilizing a score function based on radiobiological and dosimetric indices (D98-DTV, NTCP-rectum, and NTCP-bladder) for the daily target volume (DTV), rectum, and bladder. DTV was defined as prostate + 4 mm margin to account for intra-fraction motion as well as contouring variability on CBCT. We termed the optimal treatment position the radiobiologically optimized couch shift position (ROCS-position). Results: The indices, averaged over the 10 patients’ treatment plans, were (mean±SD): 77.7±0.2 Gy (D98-PTV), 12.3±2.7% (NTCP-rectum), and 53.2±11.2% (NTCP-bladder). The corresponding values calculated on all 50 CBCT images at the AM-positions were 72.9±11.3 Gy (D98-DTV), 15.8±6.4% (NTCP-rectum), and 53.0±21.1% (NTCP-bladder), respectively. In comparison, calculated on CBCT at the ROCS-positions, the indices were 77.0±2.1 Gy (D98-DTV), 12.1±5.7% (NTCP-rectum), and 60.7±16.4% (NTCP-bladder). Compared to autoregistration, ROCS-optimization recovered dose coverage to target volume and lowered the risk to rectum. Moreover, NTCPrectum for one patient remained high after ROCS-optimization and therefore could potentially benefit from adaptive planning. Conclusion: These encouraging results illustrate the potential utility of applying radiobiologically optimized correction for online image-guided radiotherapy of prostate patients.« less

Prostate-specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer.

PubMed

Hashimoto, Takeshi; Ohori, Makoto; Shimodaira, Kenji; Kaburaki, Naoto; Hirasawa, Yosuke; Satake, Naoya; Gondo, Tatsuo; Nakagami, Yoshihiro; Namiki, Kazunori; Ohno, Yoshio

2018-06-01

To clarify the impact of prostate-specific antigen screening on surgical outcomes of prostate cancer. Patients who underwent radical prostatectomy were divided into two groups according to prostate-specific antigen testing opportunity (group 1, prostate-specific antigen screening; group 2, non-prostate-specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank-sum and χ 2 -tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence-free survival. In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate-specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5-year biochemical recurrence-free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate-specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate-specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate-specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study. Detection by screening results in favorable outcomes after surgery. Prostate-specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer. © 2018 The Japanese Urological Association.

1.5-Tesla Multiparametric-Magnetic Resonance Imaging for the detection of clinically significant prostate cancer

PubMed Central

POPITA, CRISTIAN; POPITA, ANCA RALUCA; SITAR-TAUT, ADELA; PETRUT, BOGDAN; FETICA, BOGDAN; COMAN, IOAN

2017-01-01

Background and aim Multiparametric-magnetic resonance imaging (mp-MRI) is the main imaging modality used for prostate cancer detection. The aim of this study is to evaluate the diagnostic performance of mp-MRI at 1.5-Tesla (1.5-T) for the detection of clinically significant prostate cancer. Methods In this ethical board approved prospective study, 39 patients with suspected prostate cancer were included. Patients with a history of positive prostate biopsy and patients treated for prostate cancer were excluded. All patients were examined at 1.5-T MRI, before standard transrectal ultrasonography–guided biopsy. Results The overall sensitivity, specificity, positive predictive value and negative predictive value for mp-MRI were 100%, 73.68%, 80% and 100%, respectively. Conclusion Our results showed that 1.5 T mp-MRI has a high sensitivity for detection of clinically significant prostate cancer and high negative predictive value in order to rule out significant disease. PMID:28246496

Elevated Prostate Health Index (phi) and Biopsy Reclassification During Active Surveillance of Prostate Cancer.

PubMed

Andreas, Darian; Tosoian, Jeffrey J; Landis, Patricia; Wolf, Sacha; Glavaris, Stephanie; Lotan, Tamara L; Schaeffer, Edward M; Sokoll, Lori J; Ross, Ashley E

2016-07-01

The Prostate Health Index (phi) has been FDA approved for decision-making regarding prostate biopsy. Phi has additionally been shown to positively correlate with tumor volume, extraprostatic disease and higher Gleason grade tumors. Here we describe a case in which an elevated phi encouraged biopsy of a gentleman undergoing active surveillance leading to reclassification of his disease as high risk prostate cancer.

Effects of organ motion on proton prostate treatments, as determined from analysis of daily CT imaging for patient positioning.

PubMed

Maeda, Yoshikazu; Sato, Yoshitaka; Shibata, Satoshi; Bou, Sayuri; Yamamoto, Kazutaka; Tamamura, Hiroyasu; Fuwa, Nobukazu; Takamatsu, Shigeyuki; Sasaki, Makoto; Tameshige, Yuji; Kume, Kyo; Minami, Hiroki; Saga, Yusuke; Saito, Makoto

2018-05-01

We quantified interfractional movements of the prostate, seminal vesicles (SVs), and rectum during computed tomography (CT) image-guided proton therapy for prostate cancer and studied the range variation in opposed lateral proton beams. We analyzed 375 sets of daily CT images acquired throughout the proton therapy treatment of ten patients. We analyzed daily movements of the prostate, SVs, and rectum by simulating three image-matching strategies: bone matching, prostate center (PC) matching, and prostate-rectum boundary (PRB) matching. In the PC matching, translational movements of the prostate center were corrected after bone matching. In the PRB matching, we performed PC matching and correction along the anterior-posterior direction to match the boundary between the prostate and the rectum's anterior region. In each strategy, we evaluated systematic errors (Σ) and random errors (σ) by measuring the daily movements of certain points on each anatomic structure. The average positional deviations in millimeter of each point were determined by the Van Herk formula of 2.5Σ + 0.7σ. Using these positional deviations, we created planning target volumes of the prostate and SVs and analyzed the daily variation in the water equivalent length (WEL) from the skin surface to the target along the lateral beam directions using the density converted from the daily CT number. Based on this analysis, we designed prostate cancer treatment planning and evaluated the dose volume histograms (DVHs) for these strategies. The SVs' daily movements showed large variations over the superior-inferior direction, as did the rectum's anterior region. The average positional deviations of the prostate in the anterior, posterior, superior, inferior, and lateral sides (mm) in bone matching, PC matching, and PRB matching were (8.9, 9.8, 7.5, 3.6, 1.6), (5.6, 6.1, 3.5, 4.5, 1.9), and (8.6, 3.2, 3.5, 4.5, 1.9) (mm), respectively. Moreover, the ones of the SV tip were similarly (22.5, 15.5, 11.0, 7.6, 6.0), (11.8, 8.4, 7.8, 5.2, 6.3), and (9.9, 7.5, 7.8, 5.2, 6.3). PRB matching showed the smallest positional deviations at all portions except for the anterior portion of the prostate and was able to markedly reduce the positional deviations at the posterior portion. The averaged WEL variations at the distal and proximal sides of planning target volumes were estimated 7-9 mm and 4-6 mm, respectively, and showed the increasing of a few millimeters in PC and PRB matching compared to bone matching. In the treatment planning simulation, the DVH values of the rectum in PRB matching were reduced compared to those obtained with other matching strategies. The positional deviations for the prostate on the posterior side and the SVs were smaller by PRB matching than the other strategies and effectively reduced the rectal dose. 3D dose calculations indicate that PRB matching with CT image guidance may do a better job relative to other positioning methods to effectively reduce the rectal complications. The WEL variation was quite large, and the appropriate margin (approx. 10 mm) must be adapted to the proton range in an initial planning to maintain the coverage of target volumes throughout entire treatment. © 2018 American Association of Physicists in Medicine.

Prostate Specific Membrane Antigen Positron Emission Tomography May Improve the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging in Localized Prostate Cancer.

PubMed

Rhee, H; Thomas, P; Shepherd, B; Gustafson, S; Vela, I; Russell, P J; Nelson, C; Chung, E; Wood, G; Malone, G; Wood, S; Heathcote, P

2016-10-01

Positron emission tomography using ligands targeting prostate specific membrane antigen has recently been introduced. Positron emission tomography imaging with (68)Ga-PSMA-HBED-CC has been shown to detect metastatic prostate cancer lesions at a high rate. In this study we compare multiparametric magnetic resonance imaging and prostate specific membrane antigen positron emission tomography of the prostate with whole mount ex vivo prostate histopathology to determine the true sensitivity and specificity of these imaging modalities for detecting and locating tumor foci within the prostate. In a prospective clinical trial setting 20 patients with localized prostate cancer and a planned radical prostatectomy were recruited. All patients underwent multiparametric magnetic resonance imaging and positron emission tomography before surgery, and whole mount histopathology slides were directly compared to the images. European Society of Urogenital Radiology guidelines for reporting magnetic resonance imaging were used as a template for regional units of analysis. The uropathologist and radiologists were blinded to individual components of the study, and the final correlation was performed by visual and deformable registration analysis. A total of 50 clinically significant lesions were identified from the whole mount histopathological analysis. Based on regional analysis the sensitivity, specificity, positive predictive value and negative predictive value for multiparametric magnetic resonance imaging were 44%, 94%, 81% and 76%, respectively. With prostate specific membrane antigen positron emission tomography the sensitivity, specificity, positive predictive value and negative predictive value were 49%, 95%, 85% and 88%, respectively. Prostate specific membrane antigen positron emission tomography yielded a higher specificity and positive predictive value. A significant proportion of cancers are potentially missed and underestimated by both imaging modalities. Prostate specific membrane antigen positron emission tomography may be used in addition to multiparametric magnetic resonance imaging to help improve local staging in those patients undergoing retropubic radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Prostate Exam

ERIC Educational Resources Information Center

Romero, Frederico R.; Romero, Antonio W.; Filho, Thadeu Brenny; Kulysz, David; Oliveira, Fernando C., Jr.; Filho, Renato Tambara

2012-01-01

Objective: To help students, residents, and general practitioners to improve the technique, skills, and reproducibility of their prostate examination. Methods: We developed a comprehensive guideline outlining prostate anatomy, indications, patient preparation, positioning, technique, findings, and limitations of this ancient art of urological…

Calcium, magnesium, and whole-milk intakes and high-aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project (PCaP).

PubMed

Steck, Susan E; Omofuma, Omonefe O; Su, L Joseph; Maise, Amanda A; Woloszynska-Read, Anna; Johnson, Candace S; Zhang, Hongmei; Bensen, Jeannette T; Fontham, Elizabeth T H; Mohler, James L; Arab, Lenore

2018-05-01

Calcium and dairy product intakes have been positively associated with prostate cancer risk. An imbalance in concentrations of calcium and magnesium has been associated with multiple chronic diseases, although few studies have examined the relation with prostate cancer aggressiveness. The goal of this study was to examine the association between dietary intakes of calcium and magnesium, the calcium-to-magnesium ratio (Ca:Mg), and dairy products and prostate cancer aggressiveness. Dietary intake was assessed with the use of an interviewer-administered modified National Cancer Institute Diet History Questionnaire in 996 African American and 1064 European American men with a recent histologically confirmed diagnosis of prostate cancer from the North Carolina-Louisiana Prostate Cancer Project (PCaP). High-aggressive disease was defined as Gleason sum ≥8, or prostate-specific antigen (PSA) >20 ng/mL, or Gleason score ≥7 and clinical stage T3-T4. The comparison group was all other prostate cancer cases. Logistic regression was used to determine the adjusted ORs and 95% CIs for high-aggressive prostate cancer by tertile of diet and supplement exposures. There was a positive association across tertiles of dietary Ca:Mg intake, with odds of high-aggressive prostate cancer in the upper tertiles as follows-OR for tertile 2 compared with tertile 1: 1.38 (95% CI: 1.01, 1.88); OR for tertile 3 compared with tertile 1: 1.46 (95% CI: 1.06, 2.02). When stratified by race, the positive association was more pronounced in African American men (OR for tertile 3 compared with tertile 2: 1.62; 95% CI: 1.04, 2.53). Men who reported the highest daily consumption of whole-fat milk had a 74% increased odds of high-aggressive prostate cancer compared with non-whole-fat milk drinkers, which was attenuated after adjustment for potential mediating factors, such as saturated fat and Ca:Mg intake. Among both African American and European American men diagnosed with prostate cancer, a higher Ca:Mg and whole-milk intake were associated with higher odds of high-aggressive prostate cancer. This study was registered at www.clinicaltrials.gov as NCT03289130.

Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer.

PubMed

Haffner, Michael C; Guner, Gunes; Taheri, Diana; Netto, George J; Palsgrove, Doreen N; Zheng, Qizhi; Guedes, Liana Benevides; Kim, Kunhwa; Tsai, Harrison; Esopi, David M; Lotan, Tamara L; Sharma, Rajni; Meeker, Alan K; Chinnaiyan, Arul M; Nelson, William G; Yegnasubramanian, Srinivasan; Luo, Jun; Mehra, Rohit; Antonarakis, Emmanuel S; Drake, Charles G; De Marzo, Angelo M

2018-06-01

Antibodies targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-L1) interaction have shown clinical activity in multiple cancer types. PD-L1 protein expression is a clinically validated predictive biomarker of response for such therapies. Prior studies evaluating the expression of PD-L1 in primary prostate cancers have reported highly variable rates of PD-L1 positivity. In addition, limited data exist on PD-L1 expression in metastatic castrate-resistant prostate cancer (mCRPC). Here, we determined PD-L1 protein expression by immunohistochemistry using a validated PD-L1-specific antibody (SP263) in a large and representative cohort of primary prostate cancers and prostate cancer metastases. The study included 539 primary prostate cancers comprising 508 acinar adenocarcinomas, 24 prostatic duct adenocarcinomas, 7 small-cell carcinomas, and a total of 57 cases of mCRPC. PD-L1 positivity was low in primary acinar adenocarcinoma, with only 7.7% of cases showing detectable PD-L1 staining. Increased levels of PD-L1 expression were noted in 42.9% of small-cell carcinomas. In mCRPC, 31.6% of cases showed PD-L1-specific immunoreactivity. In conclusion, in this comprehensive evaluation of PD-L1 expression in prostate cancer, PD-L1 expression is rare in primary prostate cancers, but increased rates of PD-L1 positivity were observed in mCRPC. These results will be important for the future clinical development of programmed cell death protein 1/PD-L1-targeting therapies in prostate cancer. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

[Partial delegation to radiation therapists of the control by cone beam CT of prostate positioning].

PubMed

Benhaïm, C; Loos, G; Achard, J L; Berger, L; Caillé, C; Frédéric-Moreau, T; Biau, J; Lapeyre, M

2017-02-01

Intensity modulated radiotherapy for prostate cancer involves daily monitoring of the positioning of the prostate, possible with cone beam CT (CBCT). It allows increased accuracy compared to readjustments but induces an increase in the time dedicated to these medical checks. The aim of the study was to evaluate the possibility of delegation of this task to the radiation therapists by comparing their readjustments to the doctors. Five consecutive patients treated with radiation for prostate cancer (76Gy) were analysed. All had a daily CBCT for position control. The movements of the prostate relative to the bony part, the positional variations of the prostate measured by the radiation therapists and the doctors and medical time required to analyse imagery (filling of the rectum and bladder and perform a recalibration) were measured. One hundred seventy-six CBCT were analysed or 980 steps in the three axes. The movements of the prostate relative to bony part were respectively at least 5mm in 19%, 7% and 3% in the anterior-posterior, upper-lower and right-left axes. Changes readjustments between radiation therapists and doctors were in 95% of cases at the most 4mm in the anterior-posterior and upper-lower axis, and 3mm in the left-right axis. The time for medical use of the CBCT averaged 8min 40 [4 to 22min]. The daily readjustment on the prostate using CBCT may be delegated to radiation therapists with acceptable concordance of less than 4mm for 95% of measurements. An initial and ongoing training will ensure treatment safety. Copyright © 2017. Published by Elsevier SAS.

ERG induces epigenetic activation of Tudor domain-containing protein 1 (TDRD1) in ERG rearrangement-positive prostate cancer.

PubMed

Kacprzyk, Lukasz A; Laible, Mark; Andrasiuk, Tatjana; Brase, Jan C; Börno, Stefan T; Fälth, Maria; Kuner, Ruprecht; Lehrach, Hans; Schweiger, Michal R; Sültmann, Holger

2013-01-01

Overexpression of ERG transcription factor due to genomic ERG-rearrangements defines a separate molecular subtype of prostate tumors. One of the consequences of ERG accumulation is modulation of the cell's gene expression profile. Tudor domain-containing protein 1 gene (TDRD1) was reported to be differentially expressed between TMPRSS2:ERG-negative and TMPRSS2:ERG-positive prostate cancer. The aim of our study was to provide a mechanistic explanation for the transcriptional activation of TDRD1 in ERG rearrangement-positive prostate tumors. Gene expression measurements by real-time quantitative PCR revealed a remarkable co-expression of TDRD1 and ERG (r(2) = 0.77) but not ETV1 (r(2)<0.01) in human prostate cancer in vivo. DNA methylation analysis by MeDIP-Seq and bisulfite sequencing showed that TDRD1 expression is inversely correlated with DNA methylation at the TDRD1 promoter in vitro and in vivo (ρ = -0.57). Accordingly, demethylation of the TDRD1 promoter in TMPRSS2:ERG-negative prostate cancer cells by DNA methyltransferase inhibitors resulted in TDRD1 induction. By manipulation of ERG dosage through gene silencing and forced expression we show that ERG governs loss of DNA methylation at the TDRD1 promoter-associated CpG island, leading to TDRD1 overexpression. We demonstrate that ERG is capable of disrupting a tissue-specific DNA methylation pattern at the TDRD1 promoter. As a result, TDRD1 becomes transcriptionally activated in TMPRSS2:ERG-positive prostate cancer. Given the prevalence of ERG fusions, TDRD1 overexpression is a common alteration in human prostate cancer which may be exploited for diagnostic or therapeutic procedures.

Positioning accuracy and daily dose assessment for prostate cancer treatment using in-room CT image guidance at a proton therapy facility.

PubMed

Maeda, Yoshikazu; Sato, Yoshitaka; Minami, Hiroki; Yasukawa, Yutaka; Yamamoto, Kazutaka; Tamamura, Hiroyasu; Shibata, Satoshi; Bou, Sayuri; Sasaki, Makoto; Tameshige, Yuji; Kume, Kyo; Ooto, Hiroshi; Kasahara, Shigeru; Shimizu, Yasuhiro; Saga, Yusuke; Omoya, Akira; Saitou, Makoto

2018-05-01

To evaluate the effectiveness of CT image-guided proton radiotherapy for prostate cancer by analyzing the positioning uncertainty and assessing daily dose change due to anatomical variations. Patients with prostate cancer were treated by opposed lateral proton beams based on a passive scattering method using an in-room CT image-guided system. The system employs a single couch for both CT scanning and beam delivery. The patient was positioned by matching the boundary between the prostate and the rectum's anterior region identified in the CT images to the corresponding boundary in the simulator images after bone matching. We acquired orthogonal kV x-ray images after couch movement and confirmed the body position by referring to the bony structure prior to treatment. In offline analyses, we contoured the targeted anatomical structures on 375 sets of daily in-room CT images for 10 patients. The uncertainty of the image-matching procedure was evaluated using the prostate contours and actual couch corrections. We also performed dose calculations using the same set of CT images, and evaluated daily change of dose-volume histograms (DVHs) to compare the effectiveness of the treatment using prostate matching to the bone-matching procedure. The isocenter shifts by prostate matching after bone matching were 0.5 ± 1.8 and -0.8 ± 2.6 mm along the superior-inferior (SI) and anterior-posterior (AP) directions, respectively. The body movement errors (σ) after couch movement were 0.7, 0.5, and 0.3 mm along the lateral, SI and AP direction, respectively, for 30 patients. The estimated errors (σ) in the prostate matching were 1.0 and 1.3 mm, and, in conjunction with the movement errors, the total positioning uncertainty was estimated to be 1.0 and 1.4 mm along the SI and AP directions, respectively. Daily DVH analyses showed that in the prostate matching, 98.7% and 86.1% of the total 375 irradiations maintained a dose condition of V 95%  > 95% for the prostate and a dose constraint of V 77%  < 18% for the rectum, whereas 90.4% and 66.1% of the total irradiations did so when bone matching was used. The dose constraint of the rectum and dose coverage of the prostate were better maintained by prostate matching than bone matching (P < 0.001). The daily variation in the dose to the seminal vesicles (SVs) was large, and only 40% of the total irradiations maintained the initial planned values of V 95% for high-risk treatment. Nevertheless, the deviations from the original value were -4 ± 7% and -5 ± 11% in the prostate and bone matching, respectively, and a better dose coverage of the SV was achieved by the prostate matching. The correction of repositioning along the AP and SI direction from conventional bone matching in CT image-guided proton therapy was found to be effective to maintain the dose constraint of the rectum and the dose coverage of the prostate. This work indicated that prostate cancer treatment by prostate matching using CT image guidance may be effective to reduce the rectal complications and achieve better tumor control of the prostate. However, an adaptive approach is desirable to maintain better dose coverage of the SVs. © 2018 American Association of Physicists in Medicine.

SU-F-J-34: Automatic Target-Based Patient Positioning Framework for Image-Guided Radiotherapy in Prostate Cancer Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sasahara, M; Arimura, H; Hirose, T

Purpose: Current image-guided radiotherapy (IGRT) procedure is bonebased patient positioning, followed by subjective manual correction using cone beam computed tomography (CBCT). This procedure might cause the misalignment of the patient positioning. Automatic target-based patient positioning systems achieve the better reproducibility of patient setup. Our aim of this study was to develop an automatic target-based patient positioning framework for IGRT with CBCT images in prostate cancer treatment. Methods: Seventy-three CBCT images of 10 patients and 24 planning CT images with digital imaging and communications in medicine for radiotherapy (DICOM-RT) structures were used for this study. Our proposed framework started from themore » generation of probabilistic atlases of bone and prostate from 24 planning CT images and prostate contours, which were made in the treatment planning. Next, the gray-scale histograms of CBCT values within CTV regions in the planning CT images were obtained as the occurrence probability of the CBCT values. Then, CBCT images were registered to the atlases using a rigid registration with mutual information. Finally, prostate regions were estimated by applying the Bayesian inference to CBCT images with the probabilistic atlases and CBCT value occurrence probability. The proposed framework was evaluated by calculating the Euclidean distance of errors between two centroids of prostate regions determined by our method and ground truths of manual delineations by a radiation oncologist and a medical physicist on CBCT images for 10 patients. Results: The average Euclidean distance between the centroids of extracted prostate regions determined by our proposed method and ground truths was 4.4 mm. The average errors for each direction were 1.8 mm in anteroposterior direction, 0.6 mm in lateral direction and 2.1 mm in craniocaudal direction. Conclusion: Our proposed framework based on probabilistic atlases and Bayesian inference might be feasible to automatically determine prostate regions on CBCT images.« less

Image Guided Planning for Prostate Carcinomas With Incorporation of Anti-3-[18F]FACBC (Fluciclovine) Positron Emission Tomography: Workflow and Initial Findings From a Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schreibmann, Eduard, E-mail: eschre2@emory.edu; Schuster, David M.; Rossi, Peter J.

Purpose: {sup 18}F-Fluciclovine (anti-1-amino-3-[{sup 18}F]fluorocyclobutane-1-carboxylic acid) is a novel positron emission tomography (PET)/computed tomography (CT) radiotracer that has demonstrated utility for detection of prostate cancer. Our goal is to report the initial results from a randomized controlled trial of the integration of {sup 18}F-fluciclovine PET-CT into treatment planning for defining prostate bed and lymph node target volumes. Methods and Materials: We report our initial findings from a cohort of 41 patients, of the first enrolled on a randomized controlled trial, who were randomized to the {sup 18}F-fluciclovine arm. All patients underwent {sup 18}F-fluciclovine PET-CT for the detection of metabolic abnormalitiesmore » and high-resolution CT for treatment planning. The 2 datasets were registered first by use of a rigid registration. If soft tissue displacement was observable, the rigid registration was improved with a deformable registration. Each {sup 18}F-fluciclovine abnormality was segmented as a percentage of the maximum standard uptake value (SUV) within a small region of interest around the lesion. The percentage best describing the SUV falloff was integrated in planning by expanding standard target volumes with the PET abnormality. Results: In 21 of 55 abnormalities, a deformable registration was needed to map the {sup 18}F-fluciclovine activity into the simulation CT. The most selected percentage was 50% of maximum SUV, although values ranging from 15% to 70% were used for specific patients, illustrating the need for a per-patient selection of a threshold SUV value. The inclusion of {sup 18}F-fluciclovine changed the planning volumes for 46 abnormalities (83%) of the total 55, with 28 (51%) located in the lymph nodes, 11 (20%) in the prostate bed, 10 (18%) in the prostate, and 6 (11%) in the seminal vesicles. Only 9 PET abnormalities were fully contained in the standard target volumes based on the CT-based segmentations and did not necessitate expansion. Conclusions: The use of {sup 18}F-fluciclovine in postprostatectomy radiation therapy planning was feasible and led to augmentation of the target volumes in the majority (30 of 41) of the patients studied.« less

Effectiveness of the combined evaluation of KLK3 genetics and free-to-total prostate specific antigen ratio for prostate cancer diagnosis.

PubMed

Zambon, Carlo-Federico; Prayer-Galetti, Tommaso; Basso, Daniela; Padoan, Andrea; Rossi, Elisa; Secco, Silvia; Pelloso, Michela; Fogar, Paola; Navaglia, Filippo; Moz, Stefania; Zattoni, Filiberto; Plebani, Mario

2012-10-01

Of serum prostate specific antigen variability 40% depends on inherited factors. We ascertained whether the knowledge of KLK3 genetics would enhance prostate specific antigen diagnostic performance in patients with clinical suspicion of prostate cancer. We studied 1,058 men who consecutively underwent prostate biopsy for clinical suspicion of prostate cancer. At histology prostate cancer was present in 401 cases and absent in 657. Serum total prostate specific antigen and the free-to-total prostate specific antigen ratio were determined. Four polymorphisms of the KLK3 gene (rs2569733, rs2739448, rs925013 and rs2735839) and 1 polymorphism of the SRD5A2 gene (rs523349) were studied. The influence of genetics on prostate specific antigen variability was evaluated by multivariate linear regression analysis. The performance of total prostate specific antigen and the free-to-total prostate specific antigen ratio alone or combined with a genetically based patient classification were defined by ROC curve analyses. For prostate cancer diagnosis the free-to-total prostate specific antigen ratio index alone (cutoff 11%) was superior to total prostate specific antigen (cutoff 4 ng/ml) and to free-to-total prostate specific antigen ratio reflex testing (positive predictive value 61%, 43% and 54%, respectively). Prostate specific antigen correlated with KLK3 genetics (rs2735839 polymorphism p = 0.001, and rs2569733, rs2739448 and rs925013 haplotype combination p = 0.003). In patients with different KLK3 genetics 2 optimal free-to-total prostate specific antigen ratio cutoffs (11% and 14.5%) were found. For free-to-total prostate specific antigen ratio values between 11% and 14.5% the prostate cancer probability ranged from 30.0% to 47.4% according to patient genetics. The free-to-total prostate specific antigen ratio is superior to total prostate specific antigen for prostate cancer diagnosis, independent of total prostate specific antigen results. Free-to-total prostate specific antigen ratio findings below 11% are positively associated with prostate cancer and those above 14.5% are negatively associated with prostate cancer, while the interpretation of those between 11% and 14.5% is improved by patient KLK3 genetic analysis. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor.

PubMed

Mounir, Zineb; Korn, Joshua M; Westerling, Thomas; Lin, Fallon; Kirby, Christina A; Schirle, Markus; McAllister, Gregg; Hoffman, Greg; Ramadan, Nadire; Hartung, Anke; Feng, Yan; Kipp, David Randal; Quinn, Christopher; Fodor, Michelle; Baird, Jason; Schoumacher, Marie; Meyer, Ronald; Deeds, James; Buchwalter, Gilles; Stams, Travis; Keen, Nicholas; Sellers, William R; Brown, Myles; Pagliarini, Raymond A

2016-05-16

The TMPRSS2:ERG gene fusion is common in androgen receptor (AR) positive prostate cancers, yet its function remains poorly understood. From a screen for functionally relevant ERG interactors, we identify the arginine methyltransferase PRMT5. ERG recruits PRMT5 to AR-target genes, where PRMT5 methylates AR on arginine 761. This attenuates AR recruitment and transcription of genes expressed in differentiated prostate epithelium. The AR-inhibitory function of PRMT5 is restricted to TMPRSS2:ERG-positive prostate cancer cells. Mutation of this methylation site on AR results in a transcriptionally hyperactive AR, suggesting that the proliferative effects of ERG and PRMT5 are mediated through attenuating AR's ability to induce genes normally involved in lineage differentiation. This provides a rationale for targeting PRMT5 in TMPRSS2:ERG positive prostate cancers. Moreover, methylation of AR at arginine 761 highlights a mechanism for how the ERG oncogene may coax AR towards inducing proliferation versus differentiation.

Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience.

PubMed

Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R; Chagpar, Anees B; Killelea, Brigid K; Lannin, Donald R

2017-01-01

Background . Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods . Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results . At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1-15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion . Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient.

Radionavigated detection of sentinel nodes in breast carcinoma--first experiences of our department.

PubMed

Duchaj, B; Chvalny, P; Vesely, J; Makaiova, I; Durdik, S; Straka, V; Palaj, J; Procka, V; Aksamitova, K; Skraskova, S; Banki, P; Kovacova, S; Galbavy, S

2010-01-01

Biopsy and histological evaluation of sentinel lymphatic node limits the axillary node dissection only in cases of positive histological finding and decreases the occurrence of postoperative complications related to the axillary node dissection. We used radiotracer SentiScint, Medi-Radiopharma Ltd, Hungary and preoperatively administered blue dye--Blue Patenté V, Guebert, Aulnay-Sous-Bios, France. 11 (18%) patients were subdued to deep peritimorous application of radiotracer, 10 (16.4%) to sub/intradermal application over the lesions and n 40 (65.6%) patients the application was sub/intradermal and periareolar. The patients underwent an operation protocol of corresponding quadrantectomy, radionavigated blue-dye sentinel node biopsy and axillary dissection. From May 2006 to June 2008, we examined 61 patients with breast carcinoma. They underwent radionavigated and blue-dye sentinel node biopsy. We detected 57 (93.4%) sentinel nodes with preoperative scintigraphy, of which only 51 (83.6%) were detected peroperatively and underwent histological evaluation. In six (9.8%) cases, the "frozen cut" histology of the primary lesion had shown a benign lesion; hence no sentinel node biopsy or axillary disection was performed. 12 (19.7%) of 51 histologically evaluated sentinel nodes had metastatic invasion. We retrospectively compared the histological fund in sentinel and axillary nodes in patients with metastatic sentinel nodes. In 6 (16.6%) cases, the sentinel node was positive of metastatic invasion but axillary nodes were histologically negative, in 6 (16.6%) cases the sentinel node and axillary nodes were positive for metastatic invasion. We observed falsely negative findings in 3 (8.3%) patients with negative histological fund in the sentinel node, but positive axillary nodes (Tab. 3, Fig. 2, Ref. 11). Full Text (Free, PDF) www.bmj.sk.

Magnetic resonance imaging-directed transperineal limited-mapping prostatic biopsies to diagnose prostate cancer: a Scottish experience.

PubMed

Mukherjee, Ankur; Morton, Simon; Fraser, Sioban; Salmond, Jonathan; Baxter, Grant; Leung, Hing Y

2014-11-01

Transperineal prostatic biopsy is firmly established as an important tool in the diagnosis of prostate cancer. The benefit of additional imaging (magnetic resonance imaging) to target biopsy remains to be fully addressed. Using a cohort of consecutive patients undergoing transperineal template mapping biopsies, we studied positive biopsies in the context of magnetic resonance imaging findings and examined the accuracy of magnetic resonance imaging in predicting the location of transperineal template mapping biopsies-detected prostate cancer. Forty-four patients (mean age: 65 years, range 53-78) underwent transperineal template mapping biopsies. Thirty-four patients had 1-2 and 10 patients had ≥3 previous transrectal ultrasound scan-guided biopsies. The mean prostate-specific antigen was 15 ng/mL (range 2.5-79 ng/mL). High-grade prostatic intraepithelial neoplasia was found in 12 (27%) patients and prostate cancer with Gleason <7, 7 and >7 in 13, 10 and 8 patients, respectively. Suspicious lesions on magnetic resonance imaging scans were scored from 1 to 5. In 28 patients, magnetic resonance imaging detected lesions with score ≥3. Magnetic resonance imaging correctly localised transperineal template mapping biopsies-detected prostate cancer in a hemi-gland approach, particularly in a right to left manner (79% positive prediction rate), but not in a quadrant approach (33% positive prediction rate). Our findings support the notion of magnetic resonance imaging-based selection of patients for transperineal template mapping biopsies and that lesions revealed by magnetic resonance imaging are likely useful for targeted biopsies. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Distributed estimation of sensors position in underwater wireless sensor network

NASA Astrophysics Data System (ADS)

Zandi, Rahman; Kamarei, Mahmoud; Amiri, Hadi

2016-05-01

In this paper, a localisation method for determining the position of fixed sensor nodes in an underwater wireless sensor network (UWSN) is introduced. In this simple and range-free scheme, the node localisation is achieved by utilising an autonomous underwater vehicle (AUV) that transverses through the network deployment area, and that periodically emits a message block via four directional acoustic beams. A message block contains the actual known AUV position as well as a directional dependent marker that allows a node to identify the respective transmit beam. The beams form a fixed angle with the AUV body. If a node passively receives message blocks, it could calculate the arithmetic mean of the coordinates existing in each messages sequence, to find coordinates at two different time instants via two different successive beams. The node position can be derived from the two computed positions of the AUV. The major advantage of the proposed localisation algorithm is that it is silent, which leads to energy efficiency for sensor nodes. The proposed method does not require any synchronisation among the nodes owing to being silent. Simulation results, using MATLAB, demonstrated that the proposed method had better performance than other similar AUV-based localisation methods in terms of the rates of well-localised sensor nodes and positional root mean square error.

Dosimetric comparison of volumetric modulated Arc therapy, step-and-shoot, and sliding window IMRT for prostate cancer

NASA Astrophysics Data System (ADS)

Schnell, Erich; Herman, Tania De La Fuente; Young, Julie; Hildebrand, Kim; Algan, Ozer; Syzek, Elizabeth; Herman, Terence; Ahmad, Salahuddin

2012-10-01

This study aims to evaluate treatment plans generated by Step-and-Shoot (SS), Sliding Window (SW) and Volumetric Modulated Arc Therapy (VMAT) in order to assess the differences in dose volume histograms of planning target volume (PTV) and organs at risk (OAR), conformity indices, radiobiological evaluations, and plan quality for prostate cancer cases. Six prostate cancer patients treated in our center were selected for this retrospective study. Treatment plans were generated with Eclipse version 8.9 using 10 MV photon beams. For VMAT, Varian Rapid Arc with 1 or 2 arcs, and for SS and SW IMRT, 7-9 fields were used. Each plan had three PTVs with prescription doses of 81, 59.4, and 45 Gy to prostate, to prostate and lymph nodes, and to pelvis, respectively. Doses to PTV and OAR and the conformal indices (COIN) were compared among three techniques. The equivalent uniform dose (EUD), tumor control probability (TCP) and normal tissue complication probability (NTCP) were calculated and compared. The mean doses to the PTV prostate on average were 83 Gy and the percent differences of mean dose among all techniques were below 0.28. For bladder and rectum, the percent differences of mean dose among all techniques were below 2.2. The COIN did not favour any particular delivery method over the other. The TCP was higher with SS and SW for four patients and higher with VMAT for two patients. The NTCP for the rectum was the lowest with VMAT in five out of the six patients. The results show similar target coverage in general.

Phase I/II Study of Pre-operative Docetaxel and Mitoxantrone for High-risk Prostate Cancer

PubMed Central

Garzotto, Mark; Higano, Celestia S.; O’Brien, Catherine; Rademacher, Brooks L.S.; Janeba, Nicole; Fazli, Ladan; Lange, Paul H.; Lieberman, Stephen; Beer, Tomasz M.

2009-01-01

Background To determine the 5-year recurrence-free survival in patients with high-risk prostate cancer after neoadjuvant combination chemotherapy followed by surgery. Secondary endpoints included safety, pathologic effects of chemotherapy and predictors of disease recurrence. Patients and Methods Fifty seven patients were enrolled in a Phase I/II study of weekly docetaxel 35 mg/m2 and escalating mitoxantrone to 4 mg/m2 prior to prostatectomy. Patients were treated with 16 weeks of chemotherapy administered weekly on a 3 of every 4 week schedule. A tissue micro-array, constructed from the prostatectomy specimens served to facilitate the exploratory evaluation of biomarkers. The primary end point was relapse-free survival. Relapse was defined as a confirmed serum prostate-specific antigen (PSA) > 0.4 ng/ml. Results Of the 57 patients, 54 received 4 cycles of docetaxel and mitoxantrone prior to radical prostatectomy. Grade 4 toxicities were limited to leucopenia, neutropenia and hyperglycemia. Serum testosterone levels remained stable after chemotherapy. Negative surgical margins were attained in 67% of cases. Lymph node involvement was detected in 18.5% of cases. With a median follow-up of 63 months, 27 of 57 (47.4%) patients recurred. The Kaplan-Meier relapse-free survival at 2 years was 65.5% (95%CI 53.0% to 78.0%) and 49.8% at 5 years (95%CI 35.5% to 64.1%). Pretreatment serum PSA, lymph node involvement, and post-chemotherapy tissue VEGF expression were independent predictors of early relapse. Conclusions Preoperative chemotherapy with docetaxel and mitoxantrone is feasible. Approximately half of the high risk patients remain relapse free at 5 years and clinical and molecular predictors of early relapse were identified. PMID:20143429

The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy.

PubMed

Wu, Rui-Yi; Wang, Guo-Min; Xu, Lei; Zhang, Bo-Heng; Xu, Ye-Qing; Zeng, Zhao-Chong; Chen, Bing

2011-05-01

The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound (HIFU) combined with (+) low-dose external beam radiotherapy (LRT) as supplemental therapy for advanced prostate cancer (PCa) following hormonal therapy (HT). Our definition of HIFU+LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy (CRT). We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU+LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU+LRT treatment. There were significant differences among four groups with regard to overall survival (OS) and disease-specific survival (DSS) curves (P = 0.018 and 0.015). Further comparison between each pair of groups suggested that the long-term DSS of the HIFU+LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU+LRT group and the CRT group. Multivariable Cox's proportional hazard model showed that both HIFU+LRT and CRT were independently associated with DSS (P = 0.001 and 0.035) and had protective effects with regard to the risk of death. Compared with CRT, HIFU+LRT significantly decreased incidences of radiation-related late gastrointestinal (GI) and genitourinary (GU) toxicity grade ≥ II. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and regional lymph node metastases after HT. As an alternative to CRT, HIFU+LRT showed good efficacy and better safety.

Prospective, Randomized Controlled Trial Exploring the Effect of TachoSil® on Lymphocele Formation after Extended Pelvic Lymph Node Dissection in Prostate Cancer.

PubMed

Buelens, Sarah; Van Praet, Charles; Poelaert, Filip; Van Huele, Andries; Decaestecker, Karel; Lumen, Nicolaas

2018-05-15

To explore whether TachoSil®, a hemostatic patch, can reduce the incidence of lymphocele formation. Development of a lymphocele is a frequent complication after pelvic lymph node dissection (PLND) for nodal staging in prostate cancer. From 2013 - 2017, 100 patients with prostate cancer who were set to undergo a staging PLND before external beam radiotherapy (n = 50) or PLND concomitant with radical prostatectomy (RP) (n = 50) were prospectively randomized 1:1 between bilateral TachoSil® placement or not. Primary end points were radiographic lymphocele development, lymphocele volume (one week and one month postoperatively), the duration and volume of postoperative catheter drainage. Patient, tumor and surgical characteristics of the TachoSil® and control group did not differ significantly. In total 65 (65%) patients experienced a radiographic lymphocele up to three months after surgery, 29 (58%) in the TachoSil® and 36 (72%) in the control group (p = 0.34). Significantly less radiographic lymphoceles were observed one week postoperatively for patients undergoing sole PLND and one month postoperatively for PLND with RP in the TachoSil® compared to control group (16% versus 48%, p = 0.024 and 24% versus 52%, p = 0.047, respectively). The other postoperative characteristics presented no significant differences between both groups neither for patients undergoing sole PLND nor PLND with RP. Patients receiving bilateral TachoSil® placement after PLND seem less likely to develop a radiographic lymphocele early postoperative. Nevertheless, the clinical relevance of the use of TachoSil® remains highly debatable. Copyright © 2018 Elsevier Inc. All rights reserved.

Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival.

PubMed

Koen Talsma, A; Shapiro, Joel; Looman, Caspar W N; van Hagen, Pieter; Steyerberg, Ewout W; van der Gaast, Ate; van Berge Henegouwen, Mark I; Wijnhoven, Bas P L; van Lanschot, J Jan B; Hulshof, Maarten C C M; van Laarhoven, Hanneke W M; Nieuwenhuijzen, Grard A P; Hospers, Geke A P; Bonenkamp, Johannes J; Cuesta, Miguel A; Blaisse, Reinoud J B; Busch, Olivier R C; ten Kate, Fiebo J W; Creemers, Geert-Jan; Punt, Cornelis J A; Plukker, John T M; Verheul, Henk M W; van Dekken, Herman; van der Sangen, Maurice J C; Rozema, Tom; Biermann, Katharina; Beukema, Jannet C; Piet, Anna H M; van Rij, Caroline M; Reinders, Janny G; Tilanus, Hugo W

2014-11-01

We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98). The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

PREOPERATIVE MRI IMPROVES PREDICTION OF EXTENSIVE OCCULT AXILLARY LYMPH NODE METASTASES IN BREAST CANCER PATIENTS WITH A POSITIVE SENTINEL LYMPH NODE BIOPSY

PubMed Central

Loiselle, Christopher; Eby, Peter R.; Kim, Janice N.; Calhoun, Kristine E.; Allison, Kimberly H.; Gadi, Vijayakrishna K.; Peacock, Sue; Storer, Barry; Mankoff, David A.; Partridge, Savannah C.; Lehman, Constance D.

2014-01-01

Rationale and Objectives To test the ability of quantitative measures from preoperative Dynamic Contrast Enhanced MRI (DCE-MRI) to predict, independently and/or with the Katz pathologic nomogram, which breast cancer patients with a positive sentinel lymph node biopsy will have ≥ 4 positive axillary lymph nodes upon completion axillary dissection. Methods and Materials A retrospective review was conducted to identify clinically node-negative invasive breast cancer patients who underwent preoperative DCE-MRI, followed by sentinel node biopsy with positive findings and complete axillary dissection (6/2005 – 1/2010). Clinical/pathologic factors, primary lesion size and quantitative DCE-MRI kinetics were collected from clinical records and prospective databases. DCE-MRI parameters with univariate significance (p < 0.05) to predict ≥ 4 positive axillary nodes were modeled with stepwise regression and compared to the Katz nomogram alone and to a combined MRI-Katz nomogram model. Results Ninety-eight patients with 99 positive sentinel biopsies met study criteria. Stepwise regression identified DCE-MRI total persistent enhancement and volume adjusted peak enhancement as significant predictors of ≥4 metastatic nodes. Receiver operating characteristic (ROC) curves demonstrated an area under the curve (AUC) of 0.78 for the Katz nomogram, 0.79 for the DCE-MRI multivariate model, and 0.87 for the combined MRI-Katz model. The combined model was significantly more predictive than the Katz nomogram alone (p = 0.003). Conclusion Integration of DCE-MRI primary lesion kinetics significantly improved the Katz pathologic nomogram accuracy to predict presence of metastases in ≥ 4 nodes. DCE-MRI may help identify sentinel node positive patients requiring further localregional therapy. PMID:24331270

Node Self-Deployment Algorithm Based on an Uneven Cluster with Radius Adjusting for Underwater Sensor Networks

PubMed Central

Jiang, Peng; Xu, Yiming; Wu, Feng

2016-01-01

Existing move-restricted node self-deployment algorithms are based on a fixed node communication radius, evaluate the performance based on network coverage or the connectivity rate and do not consider the number of nodes near the sink node and the energy consumption distribution of the network topology, thereby degrading network reliability and the energy consumption balance. Therefore, we propose a distributed underwater node self-deployment algorithm. First, each node begins the uneven clustering based on the distance on the water surface. Each cluster head node selects its next-hop node to synchronously construct a connected path to the sink node. Second, the cluster head node adjusts its depth while maintaining the layout formed by the uneven clustering and then adjusts the positions of in-cluster nodes. The algorithm originally considers the network reliability and energy consumption balance during node deployment and considers the coverage redundancy rate of all positions that a node may reach during the node position adjustment. Simulation results show, compared to the connected dominating set (CDS) based depth computation algorithm, that the proposed algorithm can increase the number of the nodes near the sink node and improve network reliability while guaranteeing the network connectivity rate. Moreover, it can balance energy consumption during network operation, further improve network coverage rate and reduce energy consumption. PMID:26784193

The impact of race on prostate cancer detection and choice of treatment in men undergoing a contemporary extended biopsy approach.

PubMed

Swords, Kelly; Wallen, Eric M; Pruthi, Raj S

2010-01-01

African American men have a higher rate of prostate cancer mortality compared with their Caucasian American counterparts. However, it remains unclear as to whether such differences are due to biologic or socioeconomic influences. This study sought to determine if there are differences in demographic and clinical characteristics between African American and Caucasian American men in a modern cohort undergoing extended biopsy approach, and evaluated the subsequent choice of therapy in patients diagnosed with prostate cancer. A retrospective review was performed from a consecutive series of 500 men undergoing prostate biopsy at our institution between 2003 and 2005. All patients underwent a contemporary 10-12 biopsy scheme. Demographic, clinical, and pathologic variables as well as treatment choice (those with positive biopsy) were stratified and evaluated with regard to race-African American, Caucasian American, and other (Hispanic, Asian, American Indian). 65% were Caucasian American, 29% African American, and 7% other. The overall positive biopsy rate was 44%. African American men were significantly younger than Caucasian American but were not younger than "other" (61.6 vs. 64.3 vs. 61.5 years). No differences were observed with regard to prostate specific antigen density (PSAD), prostate volume, or rate of abnormal digital rectal exam (DRE). The positive biopsy rate was not different between Caucasian American and African American (46% vs. 46%), but significantly lower in other men (16%). These differences were maintained on odds ratio modeling, including age-adjusted and multivariate models. Of the 223 men with positive biopsies, information on treatment choice demonstrated that African American men had a significantly higher rate of choice of XRT (OR = 2.12) and rate of avoidance of surgery (OR = 0.35) than Caucasian American men. In men undergoing prostate biopsy using an extended (10-12 core) biopsy scheme, no differences were observed with regard to positive biopsy rate or other clinical or biochemical parameters [except for age and prostate specific antigen (PSA) level] between African American and Caucasian American men. Of those with a positive biopsy, African American men were more likely to avoid surgery and choose XRT in our population. Copyright (c) 2010 Elsevier Inc. All rights reserved.

TH-CD-207A-12: Impacts of Inter- and Intra-Fractional Organ Motion for High-Risk Prostate Cancer Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hassan Rezaeian, N; Chi, Y; Zhou, Y

2016-06-15

Purpose: We are conducting a clinical trial on stereotactic body radiation therapy (SBRT) for high-risk prostate cancer. Doses to three targets, prostate, intra-prostatic lesion, and pelvic lymph node (PLN) region, are escalated to three different levels via simultaneous integrated boost technique. Inter-/intra-fractional organ motions deteriorate planned dose distribution. This study aims at developing a dose reconstruction system to comprehensively understand the impacts of organ motion in our clinical trial. Methods: A 4D dose reconstruction system has been developed for this study. Using a GPU-based Monte-Carlo dose engine and delivery log file, the system is able to reconstruct dose on staticmore » or dynamic anatomy. For prostate and intra-prostatic targets, intra-fractional motion is the main concern. Motion trajectory acquired from Calypso in previously treated SBRT patients were used to perform 4D dose reconstructions. For pelvic target, inter-fractional motion is one concern. Eight patients, each with four cone beam CTs, were used to derive fractional motion. The delivered dose was reconstructed on the deformed anatomy. Dosimetric parameters for delivered dose distributions of the three targets were extracted and compared with planned levels. Results: For prostate intra-fractional motion, the mean 3D motion amplitude during beam delivery ranged from 1.5mm to 5.0mm and the average among all patients was 2.61mm. Inter-fractional motion for the PLN target was more significant. The average amplitude among patients was 4mm with the largest amplitude up to 9.6mm. The D95% deviation from planned level for prostate PTVs and GTVs are on average less than<0.1% and this deviation for intra-prostatic lesion PTVs and GTVs were more prominent. The dose at PLN was significantly affected with D{sub 95}% reduced by up to 44%. Conclusion: Intra-/inter-fractional organ motion is a concern for high-risk prostate SBRT, particularly for the PLN target. Our dose reconstruction approach can also serve as the basis to guide treatment adaptation.« less

Endothelin-1 Expression in Prostate Needle Biopsy Specimens Correlated With Aggressiveness of Prostatic Cancer

PubMed Central

Asgari, Mojgan; Eftekhar, Elham; Abolhasani, Maryam; Shahrokh, Hossein

2017-01-01

Background & Objective: As the prostate adenocarcinoma is one of the most common malignant tumors in males, looking for a marker to effectively predict aggressiveness and metastatic potential in an apparently localized cancer in initial needle biopsy specimens can help the clinicians to make more appropriate decision for treatment, planning, and choosing appropriate targeted therapy. The present study assessed the value of Endothelin-1 expression to predict prognosis of prostatic cancer Methods: In a cross sectional study, 83 patients who underwent radical prostatectomy in Hasheminejad Kidney Center in 2008 through 2012 were assigned to two groups including 43 with and 40 without extra-prostatic extension (EPE). Endothelin-1 staining was performed on Paraffin Embedded blocks of preoperative needle biopsies. Results: The expression of Endothelin-1 increased in 72% of patients in the group with EPE (P<0.001). The group with Endothelin-1 positivity showed higher serum level of prostate specific antigen (PSA) (p = 0.039). Endothelin-1 expression was positive in 67% of patients with perineurial invasion (P<0.001). Adjusting the baseline variables of PSA and PN in a multivariable logistic regression model, the Endothelin-1 positivity could effectively predict EPE in patients with prostatic cancer (OR: 5.46, p = 0.010). Conclusion: Correlation of Endothelin-1 expression in needle biopsy specimens in expected with extra-prostatic extension of tumor in radical prostatectomy specimens, perineurial invasion and serum PSA level at the time of diagnosis. PMID:29515640

Positive Response to Thermobalancing Therapy Enabled by Therapeutic Device in Men with Non-Malignant Prostate Diseases: BPH and Chronic Prostatitis.

PubMed

Aghajanyan, Ivan Gerasimovich; Allen, Simon

2016-04-18

The most common types of non-malignant prostate diseases are benign prostatic hyperplasia (BPH) and chronic prostatitis (CP). The aim of this study was to find out whether thermobalancing therapy with a physiotherapeutic device is effective for BPH and CP. During a 2.5-year period, 124 men with BPH over the age of 55 were investigated. Clinical parameters were tested twice: via the International Prostate Symptom Score (IPSS) and via ultrasound measurement of prostate volume (PV) and uroflowmetry maximum flow rate (Q max ), before and after six months of therapy. In 45 men with CP under the age of 55, the dynamics of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) were studied. The results of the investigated index tests in men with BPH confirmed a decrease in IPSS ( p < 0.001), a reduction in PV ( p < 0.001), an increase in Q max ( p < 0.001), and an improvement of quality of life (QoL) ( p < 0.001). NIH-CPSI scores in men with CP indicated positive dynamics. The observed positive changes in IPSS, PV, and Q max in men with BPH and the improvement in NIH-CPSI-QoL in patients with CP after using a physiotherapeutic device for six months as mono-therapy, support the view that thermobalancing therapy with the device can be recommended for these patients. Furthermore, the therapeutic device is free of side effects.

Continuous monitoring and intrafraction target position correction during treatment improves target coverage for patients undergoing SBRT prostate therapy.

PubMed

Lovelock, D Michael; Messineo, Alessandra P; Cox, Brett W; Kollmeier, Marisa A; Zelefsky, Michael J

2015-03-01

To compare the potential benefits of continuous monitoring of prostate position and intervention (CMI) using 2-mm displacement thresholds during stereotactic body radiation therapy (SBRT) treatment to those of a conventional image-guided procedure involving single localization prior to treatment. Eighty-nine patients accrued to a prostate SBRT dose escalation protocol were implanted with radiofrequency transponder beacons. The planning target volume (PTV) margin was 5 mm in all directions, except for 3 mm in the posterior direction. The prostate was kept within 2 mm of its planned position by the therapists halting dose delivery and, if necessary, correcting the couch position. We computed the number, type, and time required for interventions and where the prostate would have been during dose delivery had there been, instead, a single image-guided setup procedure prior to each treatment. Distributions of prostate displacements were computed as a function of time. After the initial setup, 1.7 interventions per fraction were required, with a concomitant increase in time for dose delivery of approximately 65 seconds. Small systematic drifts in prostate position in the posterior and inferior directions were observed in the study patients. Without CMI, intrafractional motion would have resulted in approximately 10% of patients having a delivered dose that did not meet our clinical coverage requirement, that is, a PTV D95 of >90%. The posterior PTV margin required for 95% of the dose to be delivered with the target positioned within the PTV was computed as a function of time. The margin necessary was found to increase by 2 mm every 5 minutes, starting from the time of the imaging procedure. CMI using a tight 2-mm displacement threshold was not only feasible but was found to deliver superior PTV coverage compared with the conventional image-guided procedure in the SBRT setting. Copyright © 2015 Elsevier Inc. All rights reserved.

Continuous Monitoring and Intrafraction Target Position Correction During Treatment Improves Target Coverage for Patients Undergoing SBRT Prostate Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lovelock, D. Michael, E-mail: lovelocm@mskcc.org; Messineo, Alessandra P.; Cox, Brett W.

2015-03-01

Purpose: To compare the potential benefits of continuous monitoring of prostate position and intervention (CMI) using 2-mm displacement thresholds during stereotactic body radiation therapy (SBRT) treatment to those of a conventional image-guided procedure involving single localization prior to treatment. Methods and Materials: Eighty-nine patients accrued to a prostate SBRT dose escalation protocol were implanted with radiofrequency transponder beacons. The planning target volume (PTV) margin was 5 mm in all directions, except for 3 mm in the posterior direction. The prostate was kept within 2 mm of its planned position by the therapists halting dose delivery and, if necessary, correcting themore » couch position. We computed the number, type, and time required for interventions and where the prostate would have been during dose delivery had there been, instead, a single image-guided setup procedure prior to each treatment. Distributions of prostate displacements were computed as a function of time. Results: After the initial setup, 1.7 interventions per fraction were required, with a concomitant increase in time for dose delivery of approximately 65 seconds. Small systematic drifts in prostate position in the posterior and inferior directions were observed in the study patients. Without CMI, intrafractional motion would have resulted in approximately 10% of patients having a delivered dose that did not meet our clinical coverage requirement, that is, a PTV D95 of >90%. The posterior PTV margin required for 95% of the dose to be delivered with the target positioned within the PTV was computed as a function of time. The margin necessary was found to increase by 2 mm every 5 minutes, starting from the time of the imaging procedure. Conclusions: CMI using a tight 2-mm displacement threshold was not only feasible but was found to deliver superior PTV coverage compared with the conventional image-guided procedure in the SBRT setting.« less

Implementation of a 5-Minute Magnetic Resonance Imaging Screening Protocol for Prostate Cancer in Men With Elevated Prostate-Specific Antigen Before Biopsy.

PubMed

Weiss, Jakob; Martirosian, Petros; Notohamiprodjo, Mike; Kaufmann, Sascha; Othman, Ahmed E; Grosse, Ulrich; Nikolaou, Konstantin; Gatidis, Sergios

2018-03-01

The aims of this study were to establish a 5-minute magnetic resonance (MR) screening protocol for prostate cancer in men before biopsy and to evaluate effects on Prostate Imaging Reporting and Data System (PI-RADS) V2 scoring in comparison to a conventional, fully diagnostic multiparametric MR imaging (mpMRI) approach. Fifty-two patients with elevated prostate-specific antigen levels and without prior biopsy were prospectively included in this institutional review board-approved study. In all patients, an mpMRI protocol according to the PI-RADS recommendations was acquired on a 3 T MRI system. In addition, an accelerated diffusion-weighted imaging sequence was acquired using simultaneous multislice technique (DW-EPISMS). Two readers independently evaluated the images for the presence/absence of prostate cancer according to the PI-RADS criteria and for additional findings. In a first reading session, only the screening protocol consisting of axial T2-weighted and DW-EPISMS images was made available. In a subsequent reading session, the mpMRI protocol was assessed blinded to the results of the first reading, serving as reference standard. Both readers successfully established a final diagnosis according to the PI-RADS criteria in the screening and mpMRI protocol. Mean lesion size was 1.2 cm in the screening and 1.4 cm in the mpMRI protocol (P = 0.4) with 35% (18/52) of PI-RADS IV/V lesions. Diagnostic performance of the screening protocol was excellent with a sensitivity and specificity of 100% for both readers with no significant differences in comparison to the mpMRI standard (P = 1.0). In 3 patients, suspicious lymph nodes were reported as additional finding, which were equally detectable in the screening and mpMRI protocol. A 5-minute MR screening protocol for prostate cancer in men with elevated prostate-specific antigen levels before biopsy is applicable for clinical routine with similar diagnostic performance as the full diagnostic mpMRI approach.

ZEB1-mediated vasculogenic mimicry formation associates with epithelial-mesenchymal transition and cancer stem cell phenotypes in prostate cancer.

PubMed

Wang, Hua; Huang, Bin; Li, Bai Mou; Cao, Kai Yuan; Mo, Chen Qiang; Jiang, Shuang Jian; Pan, Jin Cheng; Wang, Zong Ren; Lin, Huan Yi; Wang, Dao Hu; Qiu, Shao Peng

2018-05-12

The zinc finger E-box-binding homeobox 1 (ZEB1) induced the epithelial-mesenchymal transition (EMT) and altered ZEB1 expression could lead to aggressive and cancer stem cell (CSC) phenotypes in various cancers. Tissue specimens from 96 prostate cancer patients were collected for immunohistochemistry and CD34/periodic acid-Schiff double staining. Prostate cancer cells were subjected to ZEB1 knockdown or overexpression and assessment of the effects on vasculogenic mimicry formation in vitro and in vivo. The underlying molecular events of ZEB1-induced vasculogenic mimicry formation in prostate cancer were then explored. The data showed that the presence of VM and high ZEB1 expression was associated with higher Gleason score, TNM stage, and lymph node and distant metastases as well as with the expression of vimentin and CD133 in prostate cancer tissues. Furthermore, ZEB1 was required for VM formation and altered expression of EMT-related and CSC-associated proteins in prostate cancer cells in vitro and in vivo. ZEB1 also facilitated tumour cell migration, invasion and clonogenicity. In addition, the effects of ZEB1 in prostate cancer cells were mediated by Src signalling; that is PP2, a specific inhibitor of the Src signalling, dose dependently reduced the p-Src 527 level but not p-Src 416 level, while ZEB1 knockdown also down-regulated the level of p-Src 527 in PC3 and DU-145 cells. PP2 treatment also significantly reduced the expression of VE-cadherin, vimentin and CD133 in these prostate cancer cells. Src signalling mediated the effects of ZEB1 on VM formation and gene expression. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Mitotic rate is associated with positive lymph nodes in patients with thin melanomas.

PubMed

Wheless, Lee; Isom, Chelsea A; Hooks, Mary A; Kauffmann, Rondi M

2018-05-01

The American Joint Commission on Cancer will remove mitotic rate from its staging guidelines in 2018. Using a large nationally representative cohort, we examined the association between mitotic rate and lymph node positivity among thin melanomas. A total of 149,273 thin melanomas in the National Cancer Database were examined for their association of high-risk features of mitotic rate, ulceration, and Breslow depth with lymph node status. Among 17,204 patients with thin melanomas with data on Breslow depth, ulceration, and mitotic rate who underwent a lymph node biopsy, there was a strong linear relationship between odds of having a positive lymph node and mitotic rate (R 2  = 0.96, P < .0001, β = 3.31). The odds of having a positive node increased by 19% with each 1-point increase in mitotic rate (odds ratio, 1.19; 95% confidence interval, 1.17-1.21). Cases with negative nodes had a mean mitotic rate of 1.54 plus or minus 2.07 mitoses/mm 2 compared with 3.30 plus or minus 3.54 mitoses/mm 2 for those with positive nodes (P < .0001). The data collected do not allow for survival analyses. Mitotic rate was strongly associated with the odds of having a positive lymph node and should continue to be reported on pathology reports. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Prediction of non-biochemical recurrence rate after radical prostatectomy in a Japanese cohort: development of a postoperative nomogram.

PubMed

Okubo, Hidenori; Ohori, Makoto; Ohno, Yoshio; Nakashima, Jun; Inoue, Rie; Nagao, Toshitaka; Tachibana, Masaaki

2014-05-01

To develop a nomogram based on postoperative factors and prostate-specific antigen levels to predict the non-biochemical recurrence rate after radical prostatectomy ina Japanese cohort. A total of 606 Japanese patients with T1-3N0M0 prostate cancer who underwent radical prostatectomy and pelvic lymph node dissection at Tokyo Medical University hospital from 2000 to 2010 were studied. A nomogram was constructed based on Cox hazard regression analysis evaluating the prognostic significance of serum prostate-specific antigen and pathological factors in the radical prostatectomy specimens. The discriminating ability of the nomogram was assessed by the concordance index (C-index), and the predicted and actual outcomes were compared with a bootstrapped calibration plot. With a mean follow up of 60.0 months, a total of 187 patients (30.9%) experienced biochemical recurrence, with a 5-year non-biochemical recurrence rate of 72.3%. Based on a Cox hazard regression model, a nomogram was constructed to predict non-biochemical recurrence using serum prostate-specific antigen level and pathological features in radical prostatectomy specimens. The concordance index was 0.77, and the calibration plots appeared to be accurate. The postoperative nomogram described here can provide valuable information regarding the need for adjuvant/salvage radiation or hormonal therapy in patients after radical prostatectomy.

Clinicopathological importance of anterior prostate cancer in Japanese Men.

PubMed

Sato, Shun; Takahashi, Hiroyuki; Kimura, Takahiro; Egawa, Shin; Furusato, Bungo; Ikegami, Masahiro

2017-03-01

Prostate cancer of transition zone origin or anterior location has been recognized as infrequent, smaller in size and indolent, whereas, our previous report showed that transition zone/anterior cancer was frequently experienced in Japanese men. The current study was conducted to show clinicopathological characteristics of transition zone/anterior cancer. A total of 201 radical prostatectomy specimens were categorized as cancer of anterior or posterior prostate where more than two thirds of the tumor existed in the specific area. Clinicopathological characteristics including Gleason score, pathological stage, lymph node metastasis, extraprostatic extension, surgical incision into the prostate (shown as pT2+), and surgical margin status were compared between anterior and posterior cases. Cases were divided as 83, 73, and 45 of anterior, posterior cancer, and no dominance, respectively. Anterior cancers included significant numbers of high grade tumors (13/83 cases: 15.7%), which was less than posterior cancers (28.8%: 21/73). The cases in pT2+ were significantly more frequent in anterior cases than posterior ones (22.9% vs. 4.1%). No seminal vesicle invasion was shown in anterior cases. Thus, although anterior cancers are less aggressive than posterior cancers, a significant numbers of clinically important cancers were located in the anterior portion in Japanese men. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients With an Initial Diagnosis of Cytology-Proven Lymph Node-Positive Breast Cancer.

PubMed

Enokido, Katsutoshi; Watanabe, Chie; Nakamura, Seigo; Ogiya, Akiko; Osako, Tomo; Akiyama, Futoshi; Yoshimura, Akiyo; Iwata, Hiroji; Ohno, Shinji; Kojima, Yasuyuki; Tsugawa, Koichiro; Motomura, Kazuyoshi; Hayashi, Naoki; Yamauchi, Hideko; Sato, Nobuaki

2016-08-01

Sentinel lymph node biopsy (SNB) is the standard treatment of node-negative breast cancer; however, whether SNB should be performed for patients with node-positive disease before neoadjuvant chemotherapy (NAC) is controversial. We evaluated the accuracy of SNB after NAC in patients with breast cancer with nodal metastasis before chemotherapy to determine the false-negative rate (FNR) and detection rate for SNB. In the present multicenter prospective study performed from September 2011 to April 2013, 143 patients with breast cancer and positive axillary nodes, proved by fine needle aspiration cytology at the initial diagnosis (stage T1-T3N1M0), were enrolled. All patients underwent breast surgery with SNB and complete axillary lymph node dissection. After NAC, the pathologic complete nodal response rate was 52.4%. The sentinel lymph node could be identified in 130 cases (90.9%); the FNR was 16.0% (13 of 81). The FNR of each clinical subtype was 42.1% (8 of 19) for the estrogen receptor-positive and human epithelial growth factor 2 (HER2)-negative (luminal type), 16.7% (2 of 12) for ER-positive and HER2-positive (luminal-HER2 type), 3.2% (1 of 31) for HER2-positive (HER2-enriched type), and 10.5% (2 of 19) for ER-negative and HER2-negative (triple-negative breast cancer; P = .003). The FNR was significantly greater in the luminal than in the nonluminal type (odds ratio, 9.91; 95% confidence interval, 6.77-14.52). SNB after NAC in patients with initially node-positive breast cancer was technically feasible but should not be recommended for the luminal subtype. However, the tumor subtype can guide patient selection, and axillary lymph node dissection could be omitted for the luminal-HER2, HER2-enriched, and triple-negative breast cancer subtypes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Prognostic Significance of the Location of Lymph Node Metastases in Patients With Adenocarcinoma of the Distal Esophagus or Gastroesophageal Junction.

PubMed

Anderegg, Maarten C J; Lagarde, Sjoerd M; Jagadesham, Vamshi P; Gisbertz, Suzanne S; Immanuel, Arul; Meijer, Sybren L; Hulshof, Maarten C C M; Bergman, Jacques J G H M; van Laarhoven, Hanneke W M; Griffin, S Michael; van Berge Henegouwen, Mark I

2016-11-01

To identify the prognostic significance of the location of lymph node metastases in patients with esophageal or gastroesophageal junction (GEJ) adenocarcinoma treated with neoadjuvant therapy followed by esophagectomy. Detection of lymph node metastases in the upper mediastinum and around the celiac trunk after neoadjuvant therapy and resection does not alter the TNM classification of esophageal carcinoma. The impact of these distant lymph node metastases on survival remains unclear. Between March 2003 and September 2013, 479 consecutive patients with adenocarcinoma of the distal esophagus or GEJ who underwent transthoracic esophagectomy with en bloc 2-field lymphadenectomy after neoadjuvant therapy were included, and survival was analyzed according to the location of positive lymph nodes in the resection specimen. Two hundred fifty-three patients had nodal metastases in the resection specimen. Of these patients, 92 patients had metastases in locoregional nodes, 114 patients in truncal nodes, 21 patients in the proximal field of the chest, and 26 patients had both positive truncal and proximal field nodes. Median disease-free survival was 170 months in the absence of nodal metastases, 35 months for metastases limited to locoregional nodes, 16 months for positive truncal nodes, 15 months for positive nodes in the proximal field, and 8 months for nodal metastases in both truncal and the proximal field. On multivariate analysis, location of lymph node metastases was independently associated with survival. Location of lymph node metastases is an independent predictor for survival. Relatively distant lymph node metastases along the celiac axis and/or the proximal field have a negative impact on survival. Location of lymph node metastases should therefore be considered in future staging systems of esophageal and GEJ adenocarcinoma.

Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience

PubMed Central

Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R.; Chagpar, Anees B.

2017-01-01

Background. Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods. Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results. At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1–15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion. Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient. PMID:28492062

Relationship between human papillomavirus infection and overexpression of p53 protein in cervical carcinomas and lymph node metastases.

PubMed

Cavuslu, S; Goodlad, J; Hobbs, C; Connor, A M; Raju, K S; Best, J M; Cason, J

1997-10-01

Overexpression of p53 protein is common in cervical carcinoma. We investigated archival biopsies from 26 cervical cancer patients (24 with available lymph nodes) to determine the relationship between p53 overexpression and HPV infection at the cervix and lymph nodes. Twelve cervical carcinoma patients had p53 protein in cervical biopsies detectable by immunohistochemistry using monoclonal antibody DO-1, and 22 were positive for HPV DNA in polymerase chain reaction assays (16, contained HPV-16; 3, HPV-18; and, 3 HPV-X). Seven cervical cancer patients had one or more lymph nodes positive for p53 protein, and all but one of these were concordantly p53 positive at the cervix. However, detection of p53 protein in cervical biopsies was predictive neither of the expression of p53 at draining lymph nodes (P > 0.1) nor of the occurrence of metastases (P > 0.1). Fourteen patients were positive at one or more lymph nodes for HPV DNA. Cervical positivity for HPV DNA was associated significantly with concordant HPV positivity at the lymph nodes (P = 0.039) and was predictive of metastases (P = 0.019). There was no association between positivity for p53 and for HPV DNA at primary cervical carcinomas or at the lymph nodes (all P > 0.1). We conclude that, although detectable p53 protein is a common feature of cervical carcinomas, it is not predictive of metastases and is independent of HPV infection.

Comparative financial analysis of laparoscopic pelvic lymph node dissection performed in 1990-1992 v 1993-1994.

PubMed

Troxel, S A; Winfield, H N

1996-08-01

In 1994, it was reported that laparoscopic pelvic lymph node dissection (L-PLND) was US $1350 more expensive than open pelvic lymph node dissection (O-PLND) for the staging of prostate cancer. Despite the lower postoperative expenses associated with L-PLND, the intraoperative expenditures were 52% higher, primarily because of the prolonged operating time and the cost of disposable instrumentation. The objective of the present study was to determine if, with increasing laparoscopic experience and a more competitive surgical supply market, the intraoperative as well as the overall hospital expenses would diminish. The study population consisted of 105 men who underwent staging L-PLND for cancer of the prostate. Group I was composed of 50 patients who underwent surgery between 1990 and 1992, and Group II consisted of 55 patients operated on in 1993 and 1994. All hospital-related expenses were reorganized into preoperative, intraoperative, and postoperative and subsequently corrected for inflationary changes to a base year of 1993-1994. The total overall expenses of the two groups were similar, differing by only $65. Despite a lowering of preoperative and postoperative expenses in the 1993-1994 group by 112% and 31%, respectively, the intraoperative expenses were still $571 higher. The operative time decreased by 19 minutes in the contemporary group, but the expense of surgical supplies continued to increase up to $910 (104%) more than the 1990-1992 group. It is hoped that the use of "laparoscopic kits" as well hospital equipment consortiums will help slow the escalating costs of surgical care. However, it is the responsibility of the laparoscopic surgeon to demonstrate that these procedures are as safe, efficient, and cost-effective as their open counterpart.

Acute toxicity and its dosimetric correlates for high-risk prostate cancer treated with moderately hypofractionated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arunsingh, Moses; Mallick, Indranil, E-mail: imallick@gmail.com; Prasath, Sriram

Aims: To report the acute toxicity and the dosimetric correlates after moderately hypofractionated radiotherapy for localized prostate cancer. Methods: A total of 101 patients with localized prostate cancer were treated with image-guided intensity-modulated radiation therapy. Patients were treated to 65 Gy/25 Fr/5 weeks (n = 18), or 60 Gy/20 Fr/4 weeks (n = 83). Most (82.2%) had high-risk or pelvic node-positive disease. Acute toxicity was assessed using Radiation Therapy Oncology Group (RTOG) acute morbidity scoring criteria. Dose thresholds for acute rectal and bladder toxicity were identified. Results: The incidence of acute grade 2 GI toxicity was 20.8%, and grade 2more » genitourinary (GU) toxicity was 6.9%. No Grade 3 to 4 toxicity occurred. Small bowel toxicity was uncommon (Gr 2 = 4%). The 2 Gy equivalent doses (EQD2) to the rectum and bladder (α/β = 3) calculated showed that the absolute doses were more consistent predictors of acute toxicities than the relative volumes. Those with grade 2 or more GI symptoms had significantly higher V{sub EQD2-60} {sub Gy} (13.2 vs 9.9 cc, p = 0.007) and V{sub EQD2-50} {sub Gy} (20.6 vs 15.4 cc, p = 0.005). Those with grade 2 or more GU symptoms had significantly higher V{sub EQD2-70} {sub Gy} (30.4 vs 18.4 cc, p = 0.001) and V{sub EQD2-65} {sub Gy} (44.0 vs 28.8 cc, p = 0.001). The optimal cutoff value for predicting grade 2 acute proctitis, for V{sub EQD2-60} {sub Gy} was 9.7 cc and for V{sub EQD2-50} {sub Gy} was 15.9 cc. For grade 2 GU symptoms, the threshold values were 23.6 cc for V{sub EQD2-70} {sub Gy} and 38.1 cc for V{sub EQD2-65} {sub Gy}. Conclusions: Hypofractionated radiotherapy for prostate cancer is well tolerated and associated with manageable acute side effects. The absolute dose-volume parameters of rectum and bladder predict for acute toxicities.« less

Effect of Neoadjuvant Chemotherapy on Axillary Lymph Node Positivity and Numbers in Breast Cancer Cases.

PubMed

Uyan, Mikail; Koca, Bulent; Yuruker, Savas; Ozen, Necati

2016-01-01

The aim of this study is to compare the numbers of axillary lymph nodes (ALN) taken out by dissection between patients with breast cancer operated on after having neoadjuvant chemotherapy (NAC) treatment and otherswithout having neoadjuvant chemotherapy, and to investigate factors affecting lymph node positivity. A total of 49 patients operated due to advanced breast cancer after neoadjuvant chemotherapy and 144 patients with a similar stage of the cancer having primary surgical treatment without chemotherapy at the general surgery clinic of Ondokuz Mayis University Medicine Faculty between the dates 01.01.2006 and 31.10.2012 were included in the study. The total number of lymph nodes taken out by axillary dissection (ALND) was categorized as the number of positive lymph nodes and divided into <10 and ≥10. The variables to be compared were analysed using the program SPSS 15.0 with P<0.05 accepted as significant. Median number of dissected lymph nodes from the patient group having neoadjuvant chemotherapy was 16 (16-33) while it was 20 (5-55) without chemotherapy. The respective median numbers of positive lymph nodes were 5 ( 0-19) and 10 (0-51). In 8 out of 49 neoadjuvant chemotherapy patients (16.3%), the number of dissected lymph nodes was below 10, and it was below 10 in 17 out of 144 primary surgery patients. Differences in numbers of dissected total and positive lymph nodes between two groups were significant, but this was not the case for numbers of <10 lymph nodes. The number of dissected lymph nodes from the patients with breast cancer having neoadjuvant chemotherapy may be less than without chemotherapy. This may not always be attributed to an inadequate axillary dissection. More research to evaluate the numbers of positive lymph nodes are required in order to increase the reliability of staging in the patients with breast cancer undergoing neoadjuvant chemotherapy.

High-fat Diet-induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling.

PubMed

Hayashi, Takuji; Fujita, Kazutoshi; Nojima, Satoshi; Hayashi, Yujiro; Nakano, Kosuke; Ishizuya, Yu; Wang, Cong; Yamamoto, Yoshiyuki; Kinouchi, Toshiro; Matsuzaki, Kyosuke; Jingushi, Kentaro; Kato, Taigo; Kawashima, Atsunari; Nagahara, Akira; Ujike, Takeshi; Uemura, Motohide; Rodriguez Pena, Maria Del Carmen; Gordetsky, Jennifer B; Morii, Eiichi; Tsujikawa, Kazutake; Netto, George J; Nonomura, Norio

2018-05-18

High-fat diet (HFD) could induce prostate cancer progression. The aim of this study is to identify mechanisms of HFD-induced prostate cancer progression, focusing on inflammation. We administered HFD and celecoxib to autochthonous immunocompetent Pb-Cre+; Pten(fl/fl) model mice for prostate cancer. Tumor growth was evaluated by tumor weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age. Cytokines which correlated with tumor growth were identified, and the changes of tumor growth and local immune cells after inhibition of the cytokine signals were evaluated in the mice. Immunohistochemical analyses using prostatectomy specimens of obese patients were performed. HFD accelerated tumor growth, and increased the myeloid-derived suppressor cells (MDSCs) fraction and M2/M1 macrophage ratio in the model mice. Celecoxib suppressed tumor growth, and decreased both local MDSCs and M2/M1 macrophage ratio in HFD-fed mice. HFD-induced tumor growth was associated with IL6 secreted by prostatic macrophages, as were phosphorylated signal transducer and activator of transcription 3 (pSTAT3)-positive tumor cells. Anti-IL6 receptor antibody administration suppressed tumor growth, and decreased local MDSCs and pSTAT3-positive cell fractions in HFD-fed mice. The tumor-infiltrating CD11b-positive cell count was significantly higher in prostatectomy specimens of obese than those of non-obese prostate cancer patients. HFD increased MDSCs and accelerated prostate cancer tumor growth via IL6/pSTAT3 signaling in the mice. This mechanism could exist in obese prostate cancer patients. IL6-mediated inflammation could be a therapeutic target for prostate cancer. Copyright ©2018, American Association for Cancer Research.

Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

PubMed

Parwani, Anil V; Marlow, Cameron; Demarzo, Angelo M; Mikolajczyk, Stephen D; Rittenhouse, Harry G; Veltri, Robert W; Chan, Theresa Y

2006-10-01

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

Prostate stromal cells express the progesterone receptor to control cancer cell mobility.

PubMed

Yu, Yue; Lee, Jennifer Suehyun; Xie, Ning; Li, Estelle; Hurtado-Coll, Antonio; Fazli, Ladan; Cox, Michael; Plymate, Stephen; Gleave, Martin; Dong, Xuesen

2014-01-01

Reciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cancer cells to grow and metastasize. Our previous work showed that the progesterone receptor (PR) was expressed specifically in prostate stromal fibroblasts and smooth muscle cells. However, the expression levels of PR and its impact to tumor microenvironment in prostate tumors are poorly understood. Immunohistochemistry assays are applied to human prostate tissue biopsies. Cell migration, invasion and proliferation assays are performed using human prostate cells. Real-time PCR and ELISA are applied to measure gene expression at molecular levels. Immunohistochemistry assays showed that PR protein levels were decreased in cancer associated stroma when compared with paired normal prostate stroma. Using in vitro prostate stromal cell models, we showed that conditioned media collected from PR positive stromal cells inhibited prostate cancer cell migration and invasion, but had minor suppressive impacts on cancer cell proliferation. PR suppressed the secretion of stromal derived factor-1 (SDF-1) and interlukin-6 (IL-6) by stromal cells independent to PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1 or IL-6 to conditioned media from PR positive stromal cells counteracted the inhibitory effects of PR to cancer cell migration and invasion. Decreased expression of the PR in cancer associated stroma may contribute to the elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor progression.

Coplanar intensity-modulated radiotherapy class solution for patients with prostate cancer with bilateral hip prostheses with and without nodal involvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Young K., E-mail: Young.Lee@rmh.nhs.uk; McVey, Gerard P.; South, Chris P.

2013-07-01

Dose distributions for prostate radiotherapy are difficult to predict in patients with bilateral hip prostheses in situ, due to image distortions and difficulty in dose calculation. The feasibility of delivering curative doses to prostate using intensity-modulated radiotherapy (IMRT) in patients with bilateral hip prostheses was evaluated. Planning target volumes for prostate only (PTV1) and pelvic nodes (PTV2) were generated from data on 5 patients. PTV1 and PTV2 dose prescriptions were 70 Gy and 60 Gy, respectively, in 35 fractions, and an additional nodal boost of 65 Gy was added for 1 plan. Rectum, bladder, and bowel were also delineated. Beammore » angles and segments were chosen to best avoid entering through the prostheses. Dose-volume data were assessed with respect to clinical objectives. The plans achieved the required prescription doses to the PTVs. Five-field IMRT plans were adequate for patients with relatively small prostheses (head volumes<60 cm{sup 3}) but 7-field plans were required for patients with larger prostheses. Bowel and bladder doses were clinically acceptable for all patients. Rectal doses were deemed clinically acceptable, although the V{sub 50} {sub Gy} objective was not met for 4/5 patients. We describe an IMRT solution for patients with bilateral hip prostheses of varying size and shape, requiring either localized or whole pelvic radiotherapy for prostate cancer.« less

Feasibility of metronomic chemotherapy with tegafur-uracil, cisplatin, and dexamethasone for docetaxel-refractory prostate cancer

PubMed Central

Kubota, Hiroki; Fukuta, Katsuhiro; Yamada, Kenji; Hirose, Masahito; Naruyama, Hiromichi; Yanai, Yoshimasa; Yamada, Yasuyuki; Watase, Hideki; Kawai, Noriyasu; Tozawa, Keiichi; Yasui, Takahiro

2017-01-01

Objectives: To evaluate the efficacy of tegafur–uracil (UFT), a prodrug of 5-fluorouracil, plus cisplatin and dexamethasone in patients with docetaxel-refractory prostate cancers. Methods: Twenty-five patients with docetaxel-refractory prostate cancer were administered oral UFT plus intravenous cisplatin (UFT-P therapy) and dexamethasone. Treatment responses were assessed monthly via prostate-specific antigen (PSA) level measurements. Treatment-related adverse events and overall survival were also assessed. Results: UFT-P therapy resulted in decreased PSA levels in 14 (56%) patients and increased PSA levels in 11 (44%). In patients with increased PSA levels, 7 (64%) of the 11 patients displayed decreased PSA doubling times. The UFT-P therapy response rate was 84% (21/25 patients). Imaging studies revealed that tumor shrinkage during UFT-P therapy occurred in 1 patient in whom bilateral hydronephrosis caused by lymph node metastasis improved. The median survival time from docetaxel initiation was 36 months. In UFT-P-treated patients, the median PSA progression and overall survival times were 6 and 14 months, respectively. UFT-P treatment-related adverse events were mild diarrhea, general fatigue, and anorexia. Treatment was not discontinued for any of the patients. UFT-P therapy did not cause serious hepatic or renal dysfunction or pancytopenia. Conclusions: UFT-P therapy is a safe and effective treatment for patients with docetaxel-refractory prostate cancer, although large-scale, multicenter, prospective studies are needed to validate these findings. PMID:29255528

Tripartite motif-containing 29 (TRIM29) is a novel marker for lymph node metastasis in gastric cancer.

PubMed

Kosaka, Yoshimasa; Inoue, Hiroshi; Ohmachi, Takahiro; Yokoe, Takeshi; Matsumoto, Toshifumi; Mimori, Koshi; Tanaka, Fumiaki; Watanabe, Masahiko; Mori, Masaki

2007-09-01

Tripartite motif-containing 29 (TRIM29) belongs to the TRIM protein family, which has unique structural characteristics, including multiple zinc finger motifs and a leucine zipper motif. TRIM29, also known as ataxia telangiectasia group D complementing gene, possesses radiosensitivity suppressor functions. Although TRIM29 has been reported to be underexpressed in prostate and breast cancer, its expression in gastrointestinal cancer has not been studied. By use of real-time reverse transcriptase-polymerase chain reaction, we analyzed TRIM29 mRNA expression status with respect to various clinicopathological parameters in 124 patients with gastric cancer. An immunohistochemical study was also conducted. The expression of TRIM29 was far higher in gastric cancer tumor tissue. Increased TRIM29 mRNA expression was markedly associated with such parameters as histological grade, large tumor size, extent of tumor invasion, and lymph node metastasis. In the TRIM29 high-expression group, it was an independent predictor for lymph node metastasis. Furthermore, patients with high TRIM29 mRNA expression showed a far poorer survival rate than those with low TRIM29 mRNA expression. TRIM29 expression may serve as a good marker of lymph node metastasis in gastric cancer.

68Ga-PSMA PET/MR-Positive, Histopathology-Proven Prostate Cancer in a Patient With Negative Multiparametric Prostate MRI.

PubMed

Muehlematter, Urs J; Rupp, Niels J; Mueller, Julian; Eberli, Daniel; Burger, Irene A

2018-05-25

Multiparametric MRI incorporating T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced sequences is currently used for detection and localization of clinically important prostate cancer (PCa). The Ga-labeled PET tracer targeting the prostate-specific membrane antigen (PSMA, Ga-PSMA-11) is a promising diagnostic approach for staging and restating PCa. Recent studies suggest that Ga-PSMA could also be used for primary PCa detection and localization. We report a case of a Ga-PSMA PET/MR-positive lesion of the peripheral zone in a 73-year-old man with a negative preceding multiparametric MRI. Radical prostatectomy and subsequent histopathologic examination confirmed a Gleason 4 + 4 PCa.

Deciphering the Translational Determinants of Prostate Cancer Initiation and Progression

DTIC Science & Technology

2012-07-01

TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U...basal epithelial cells respectively. Yellow triangles = invasive front. b. Immunofluorescent images of 14-month-old PTENL/L lymph node ( LN ...j.ccr.2009.03.017 (2009). 15 Lahat, G. et al. Vimentin is a novel anti-cancer therapeutic target; insights from in vitro and in vivo mice xenograft

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 4: seminal vesicles and lymph nodes.

PubMed

Berney, Daniel M; Wheeler, Thomas M; Grignon, David J; Epstein, Jonathan I; Griffiths, David F; Humphrey, Peter A; van der Kwast, Theo; Montironi, Rodolfo; Delahunt, Brett; Egevad, Lars; Srigley, John R

2011-01-01

The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the infiltration of tumor into the seminal vesicles and regional lymph nodes were coordinated by working group 4. There was a consensus that complete blocking of the seminal vesicles was not necessary, although sampling of the junction of the seminal vesicles and prostate was mandatory. There was consensus that sampling of the vas deferens margins was not obligatory. There was also consensus that muscular wall invasion of the extraprostatic seminal vesicle only should be regarded as seminal vesicle invasion. Categorization into types of seminal vesicle spread was agreed by consensus to be not necessary. For examination of lymph nodes, there was consensus that special techniques such as frozen sectioning were of use only in high-risk cases. There was no consensus on the optimal sampling method for pelvic lymph node dissection specimens, although there was consensus that all lymph nodes should be completely blocked as a minimum. There was also a consensus that a count of the number of lymph nodes harvested should be attempted. In view of recent evidence, there was consensus that the diameter of the largest lymph node metastasis should be measured. These consensus decisions will hopefully clarify the difficult areas of pathological assessment in radical prostatectomy evaluation and improve the concordance of research series to allow more accurate assessment of patient prognosis.

Patient Positioning Based on a Radioactive Tracer Implanted in Patients With Localized Prostate Cancer: A Performance and Safety Evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kruijf, Willy J.M. de, E-mail: kruijf.de.w@bvi.nl; Verstraete, Jan; Neustadter, David

2013-02-01

Purpose: To evaluate the performance and safety of a radiation therapy positioning system (RealEye) based on tracking a radioactive marker (Tracer) implanted in patients with localized prostate cancer. Methods and Materials: We performed a single-arm multi-institutional trial in 20 patients. The iridium-192 ({sup 192}Ir)-containing Tracer was implanted in the patient together with 4 standard gold seed fiducials. Patient prostate-related symptoms were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Computed tomography (CT) was performed for treatment planning, during treatment, and after treatment to evaluate the migration stability of the Tracer. At 5 treatment sessions, cone beam CT was performedmore » to test the positioning accuracy of the RealEye. Results: The Tracer was successfully implanted in all patients. No device or procedure-related adverse events occurred. Changes in IPSS scores were limited. The difference between the mean change in Tracer-fiducial distance and the mean change in fiducial-fiducial distance was -0.39 mm (95% confidence interval [CI] upper boundary, -0.22 mm). The adjusted mean difference between Tracer position according to RealEye and the Tracer position on the CBCT for all patients was 1.34 mm (95% CI upper boundary, 1.41 mm). Conclusions: Implantation of the Tracer is feasible and safe. Migration stability of the Tracer is good. Prostate patients can be positioned and monitored accurately by using RealEye.« less

Patient positioning based on a radioactive tracer implanted in patients with localized prostate cancer: a performance and safety evaluation.

PubMed

de Kruijf, Willy J M; Verstraete, Jan; Neustadter, David; Corn, Benjamin W; Hol, Sandra; Venselaar, Jack L M; Davits, Rob J; Wijsman, Bart P; Van den Bergh, Laura; Budiharto, Tom; Oyen, Raymond; Haustermans, Karin; Poortmans, Philip M P

2013-02-01

To evaluate the performance and safety of a radiation therapy positioning system (RealEye) based on tracking a radioactive marker (Tracer) implanted in patients with localized prostate cancer. We performed a single-arm multi-institutional trial in 20 patients. The iridium-192 ((192)Ir)-containing Tracer was implanted in the patient together with 4 standard gold seed fiducials. Patient prostate-related symptoms were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Computed tomography (CT) was performed for treatment planning, during treatment, and after treatment to evaluate the migration stability of the Tracer. At 5 treatment sessions, cone beam CT was performed to test the positioning accuracy of the RealEye. The Tracer was successfully implanted in all patients. No device or procedure-related adverse events occurred. Changes in IPSS scores were limited. The difference between the mean change in Tracer-fiducial distance and the mean change in fiducial-fiducial distance was -0.39 mm (95% confidence interval [CI] upper boundary, -0.22 mm). The adjusted mean difference between Tracer position according to RealEye and the Tracer position on the CBCT for all patients was 1.34 mm (95% CI upper boundary, 1.41 mm). Implantation of the Tracer is feasible and safe. Migration stability of the Tracer is good. Prostate patients can be positioned and monitored accurately by using RealEye. Copyright © 2013 Elsevier Inc. All rights reserved.

Immunostaining of the androgen receptor and sequence analysis of its DNA-binding domain in canine prostate cancer.

PubMed

Lai, Chen-Li; van den Ham, René; Mol, Jan; Teske, Erik

2009-09-01

Prostate cancer in the dog (cPC) has many features in common with hormone refractory human prostate cancer. As cPC is seen more often in castrated dogs, the contribution of the androgen receptor (AR) to the development of prostate cancer remains questionable. The aim of the present study was to evaluate the presence of the AR by immunohistochemistry in cPC. AR staining was observed in most tumors from intact and castrated dogs, but the proportion of positive cells and the staining intensity were much lower than in the prostate of healthy, non-castrated dogs. Most of the positive staining was seen in the cytoplasm rather than in the nuclei of the tumor cells. The predominant cytoplasmic localization was not related to mutations in exon 3 of the DNA-binding domain of the AR, as shown by sequence analysis of microdissected AR positive tumor cells. Other mechanisms that lead to an impaired androgen-AR signaling or a basal/stem cell like origin may explain the low cytoplasmic AR staining in cPC.

Influence of Lymphatic Invasion on Locoregional Recurrence Following Mastectomy: Indication for Postmastectomy Radiotherapy for Breast Cancer Patients With One to Three Positive Nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsunuma, Ryoichi, E-mail: r-matsunuma@nifty.com; First Department of Surgery, Hamamatsu University School of Medicine, Shizuoka; Oguchi, Masahiko

2012-07-01

Purpose: The indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status. Methods and Materials: Retrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and lymore » status. Results: Multivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p < 0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p < 0.001 vs. p = 0.295). Conclusion: Among postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT.« less

Clinical impact of PSMA-based 18F-DCFBC PET/CT imaging in patients with biochemically recurrent prostate cancer after primary local therapy.

PubMed

Mena, Esther; Lindenberg, Maria L; Shih, Joanna H; Adler, Stephen; Harmon, Stephanie; Bergvall, Ethan; Citrin, Deborah; Dahut, William; Ton, Anita T; McKinney, Yolanda; Weaver, Juanita; Eclarinal, Philip; Forest, Alicia; Afari, George; Bhattacharyya, Sibaprasad; Mease, Ronnie C; Merino, Maria J; Pinto, Peter; Wood, Bradford J; Jacobs, Paula; Pomper, Martin G; Choyke, Peter L; Turkbey, Baris

2018-01-01

The purpose of our study was to assess 18 F-DCFBC PET/CT, a PSMA targeted PET agent, for lesion detection and clinical management of biochemical relapse in prostate cancer patients after primary treatment. This is a prospective IRB-approved study of 68 patients with documented biochemical recurrence after primary local therapy consisting of radical prostatectomy (n = 50), post radiation therapy (n = 9) or both (n = 9), with negative conventional imaging. All 68 patients underwent whole-body 18 F-DCFBC PET/CT, and 62 also underwent mpMRI within one month. Lesion detection with 18 F-DCFBC was correlated with mpMRI findings and pre-scan PSA levels. The impact of 18 F-DCFBC PET/CT on clinical management and treatment decisions was established after 6 months' patient clinical follow-up. Forty-one patients (60.3%) showed at least one positive 18 F-DCFBC lesion, for a total of 79 lesions, 30 in the prostate bed, 39 in lymph nodes, and ten in distant sites. Tumor recurrence was confirmed by either biopsy (13/41 pts), serial CT/MRI (8/41) or clinical follow-up (15/41); there was no confirmation in five patients, who continue to be observed. The 18 F-DCFBC and mpMRI findings were concordant in 39 lesions (49.4%), and discordant in 40 lesions (50.6%); the majority (n = 32/40) of the latter occurring because the recurrence was located outside the mpMRI field of view. 18 F-DCFBC PET positivity rates correlated with PSA values and 15%, 46%, 83%, and 77% were seen in patients with PSA values <0.5, 0.5 to <1.0, 1.0 to <2.0, and ≥2.0 ng/mL, respectively. The optimal cut-off PSA value to predict a positive 18 F-DCFBC scan was 0.78 ng/mL (AUC = 0.764). A change in clinical management occurred in 51.2% (21/41) of patients with a positive 18 F-DCFBC result, generally characterized by starting a new treatment in 19 patients or changing the treatment plan in two patients. 18 F-DCFBC detects recurrences in 60.3% of a population of patients with biochemical recurrence, but results are dependent on PSA levels. Above a threshold PSA value of 0.78 ng/mL, 18 F-DCFBC was able to identify recurrence with high reliability. Positive 18 F-DCFBC PET imaging led clinicians to change treatment strategy in 51.2% of patients.

Acoustic Microfluidics for Bioanalytical Application

NASA Astrophysics Data System (ADS)

Lopez, Gabriel

2013-03-01

This talk will present new methods the use of ultrasonic standing waves in microfluidic systems to manipulate microparticles for the purpose of bioassays and bioseparations. We have recently developed multi-node acoustic focusing flow cells that can position particles into many parallel flow streams and have demonstrated the potential of such flow cells in the development of high throughput, parallel flow cytometers. These experiments show the potential for the creation of high throughput flow cytometers in applications requiring high flow rates and rapid detection of rare cells. This talk will also present the development of elastomeric capture microparticles and their use in acoustophoretic separations. We have developed simple methods to form elastomeric particles that are surface functionalized with biomolecular recognition reagents. These compressible particles exhibit negative acoustic contrast in ultrasound when suspended in aqueous media, blood serum or diluted blood. These particles can be continuously separated from cells by flowing them through a microfluidic device that uses an ultrasonic standing wave to align the blood cells, which exhibit positive acoustic contrast, at a node in the acoustic pressure distribution while aligning the negative acoustic contrast elastomeric particles at the antinodes. Laminar flow of the separated particles to downstream collection ports allows for collection of the separated negative contrast particles and cells. Separated elastomeric particles were analyzed via flow cytometry to demonstrate nanomolar detection for prostate specific antigen in aqueous buffer and picomolar detection for IgG in plasma and diluted blood samples. This approach has potential applications in the development of rapid assays that detect the presence of low concentrations of biomarkers (including biomolecules and cells) in a number of biological sample types. We acknowledge support through the NSF Research Triangle MRSEC.

Nomogram for prediction of level 2 axillary lymph node metastasis in proven level 1 node-positive breast cancer patients.

PubMed

Jiang, Yanlin; Xu, Hong; Zhang, Hao; Ou, Xunyan; Xu, Zhen; Ai, Liping; Sun, Lisha; Liu, Caigang

2017-09-22

The current management of the axilla in level 1 node-positive breast cancer patients is axillary lymph node dissection regardless of the status of the level 2 axillary lymph nodes. The goal of this study was to develop a nomogram predicting the probability of level 2 axillary lymph node metastasis (L-2-ALNM) in patients with level 1 axillary node-positive breast cancer. We reviewed the records of 974 patients with pathology-confirmed level 1 node-positive breast cancer between 2010 and 2014 at the Liaoning Cancer Hospital and Institute. The patients were randomized 1:1 and divided into a modeling group and a validation group. Clinical and pathological features of the patients were assessed with uni- and multivariate logistic regression. A nomogram based on independent predictors for the L-2-ALNM identified by multivariate logistic regression was constructed. Independent predictors of L-2-ALNM by the multivariate logistic regression analysis included tumor size, Ki-67 status, histological grade, and number of positive level 1 axillary lymph nodes. The areas under the receiver operating characteristic curve of the modeling set and the validation set were 0.828 and 0.816, respectively. The false-negative rates of the L-2-ALNM nomogram were 1.82% and 7.41% for the predicted probability cut-off points of < 6% and < 10%, respectively, when applied to the validation group. Our nomogram could help predict L-2-ALNM in patients with level 1 axillary lymph node metastasis. Patients with a low probability of L-2-ALNM could be spared level 2 axillary lymph node dissection, thereby reducing postoperative morbidity.

Cell type specific gene expression analysis of prostate needle biopsies resolves tumor tissue heterogeneity

PubMed Central

Krönig, Malte; Walter, Max; Drendel, Vanessa; Werner, Martin; Jilg, Cordula A.; Richter, Andreas S.; Backofen, Rolf; McGarry, David; Follo, Marie; Schultze-Seemann, Wolfgang; Schüle, Roland

2015-01-01

A lack of cell surface markers for the specific identification, isolation and subsequent analysis of living prostate tumor cells hampers progress in the field. Specific characterization of tumor cells and their microenvironment in a multi-parameter molecular assay could significantly improve prognostic accuracy for the heterogeneous prostate tumor tissue. Novel functionalized gold-nano particles allow fluorescence-based detection of absolute mRNA expression levels in living cells by fluorescent activated flow cytometry (FACS). We use of this technique to separate prostate tumor and benign cells in human prostate needle biopsies based on the expression levels of the tumor marker alpha-methylacyl-CoA racemase (AMACR). We combined RNA and protein detection of living cells by FACS to gate for epithelial cell adhesion molecule (EPCAM) positive tumor and benign cells, EPCAM/CD45 double negative mesenchymal cells and CD45 positive infiltrating lymphocytes. EPCAM positive epithelial cells were further sub-gated into AMACR high and low expressing cells. Two hundred cells from each population and several biopsies from the same patient were analyzed using a multiplexed gene expression profile to generate a cell type resolved profile of the specimen. This technique provides the basis for the clinical evaluation of cell type resolved gene expression profiles as pre-therapeutic prognostic markers for prostate cancer. PMID:25514598

Toxicity Assessment of Pelvic Intensity-Modulated Radiotherapy With Hypofractionated Simultaneous Integrated Boost to Prostate for Intermediate- and High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCammon, Robert; Rusthoven, Kyle E.; Kavanagh, Brian

Purpose: To evaluate the toxicity of pelvic intensity-modulated radiotherapy (IMRT) with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with intermediate- to high-risk prostate cancer. Methods and Materials: A retrospective toxicity analysis was performed in 30 consecutive patients treated definitively with pelvic SIB-IMRT, all of whom also received androgen suppression. The IMRT plans were designed to deliver 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate while simultaneously delivering 50.4 Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to scoremore » toxicity. Results: The most common acute Grade 2 events were cystitis (36.7%) and urinary frequency/urgency (26.7%). At a median follow-up of 24 months, late toxicity exceeding Grade 2 in severity was uncommon, with two Grade 3 events and one Grade 4 event. Grade 2 or greater acute bowel toxicity was associated with signficantly greater bowel volume receiving {>=}25 Gy (p = .04); Grade 2 or greater late bowel toxicity was associated with a higher bowel maximal dose (p = .04) and volume receiving {>=}50 Gy (p = .02). Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric parameters examined. Conclusion: Pelvic IMRT with SIB to the prostate was well tolerated in this series, with low rates of Grade 3 or greater acute and late toxicity. SIB-IMRT combines pelvic radiotherapy and hypofractionation to the primary site and offers an accelerated approach to treating intermediate- to high-risk disease. Additional follow-up is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined with androgen suppression.« less

The Role of BRCA1 in Lethal Prostate Cancer

DTIC Science & Technology

2013-08-01

Positive 5% Positive 12% -15- Figure II. Correlation coefficients of mRNA expression of 28,000 genes within technical replicates for an 11-year old tissue...Transdisciplinary Prostate Cancer Partnership (ToPCaP, topcapteam.org) 1Division of Urology, McMaster University, Hamilton, ON, Canada 2Department of

Number of evaluated lymph nodes and positive lymph nodes, lymph node ratio, and log odds evaluation in early-stage pancreatic ductal adenocarcinoma: numerology or valid indicators of patient outcome?

PubMed

Lahat, G; Lubezky, N; Gerstenhaber, F; Nizri, E; Gysi, M; Rozenek, M; Goichman, Y; Nachmany, I; Nakache, R; Wolf, I; Klausner, J M

2016-09-29

We evaluated the prognostic significance and universal validity of the total number of evaluated lymph nodes (ELN), number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in a relatively large and homogenous cohort of surgically treated pancreatic ductal adenocarcinoma (PDAC) patients. Prospectively accrued data were retrospectively analyzed for 282 PDAC patients who had pancreaticoduodenectomy (PD) at our institution. Long-term survival was analyzed according to the ELN, PLN, LNR, and LODDS. Of these patients, 168 patients (59.5 %) had LN metastasis (N1). Mean ELN and PLN were 13.5 and 1.6, respectively. LN positivity correlated with a greater number of evaluated lymph nodes; positive lymph nodes were identified in 61.4 % of the patients with ELN ≥ 13 compared with 44.9 % of the patients with ELN < 13 (p = 0.014). Median overall survival (OS) and 5-year OS rate were higher in N0 than in N1 patients, 22.4 vs. 18.7 months and 35 vs. 11 %, respectively (p = 0.008). Mean LNR was 0.12; 91 patients (54.1 %) had LNR < 0.3. Among the N1 patients, median OS was comparable in those with LNR ≥ 0.3 vs. LNR < 0.3 (16.7 vs. 14.1 months, p = 0.950). Neither LODDS nor various ELN and PLN cutoff values provided more discriminative information within the group of N1 patients. Our data confirms that lymph node positivity strongly reflects PDAC biology and thus patient outcome. While a higher number of evaluated lymph nodes may provide a more accurate nodal staging, it does not have any prognostic value among N1 patients. Similarly, PLN, LNR, and LODDS had limited prognostic relevance.

Glycogen synthase kinase-3 inhibitors suppress the AR-V7-mediated transcription and selectively inhibit cell growth in AR-V7-positive prostate cancer cells.

PubMed

Nakata, Daisuke; Koyama, Ryokichi; Nakayama, Kazuhide; Kitazawa, Satoshi; Watanabe, Tatsuya; Hara, Takahito

2017-06-01

Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system. The effects of a glycogen synthase kinase-3 (GSK3) inhibitor, LY-2090314, on endogenous AR-V7 signaling were evaluated in an AR-V7-positive cell line, JDCaP-hr, by quantitative reverse transcription polymerase chain reaction. The relationship between AR-V7 signaling and β-catenin signaling was assessed using RNA interference. The effect of LY-2090314 on cell growth in various prostate cancer cell lines was also evaluated. We identified GSK3 inhibitors as transcriptional suppressors of AR-V7 using a high-throughput screen with an AR-V7 reporter system. LY-2090314 suppressed the reporter activity and endogenous AR-V7 activity in JDCaP-hr cells. Because silencing of β-catenin partly rescued the suppression, it was evident that the suppression was mediated, at least partially, via the activation of β-catenin signaling. AR-V7 signaling and β-catenin signaling reciprocally regulate each other in JDCaP-hr cells, and therefore, GSK3 inhibition can repress AR-V7 transcriptional activity by accumulating intracellular β-catenin. Notably, LY-2090314 selectively inhibited the growth of AR-V7-positive prostate cancer cells in vitro. Our findings demonstrate the potential of GSK3 inhibitors in treating advanced prostate cancer driven by AR splice variants. In vivo evaluation of AR splice variant-positive prostate cancer models will help illustrate the overall significance of GSK3 inhibitors in treating prostate cancer. © 2017 Wiley Periodicals, Inc.

Association of quantitative magnetic resonance imaging parameters with histological findings from MRI/ultrasound fusion prostate biopsy.

PubMed

Dianat, Seyed Saeid; Carter, H Ballentine; Schaeffer, Edward M; Hamper, Ulrik M; Epstein, Jonathan I; Macura, Katarzyna J

2015-10-01

Purpose of this pilot study was to correlate quantitative parameters derived from the multiparametric magnetic resonance imaging (MP-MRI) of the prostate with results from MRI guided transrectal ultrasound (MRI/TRUS) fusion prostate biopsy in men with suspected prostate cancer. Thirty-nine consecutive patients who had 3.0T MP-MRI and subsequent MRI/TRUS fusion prostate biopsy were included and 73 MRI-identified targets were sampled by 177 cores. The pre-biopsy MP-MRI consisted of T2-weighted, diffusion weighted (DWI), and dynamic contrast enhanced (DCE) images. The association of quantitative MRI measurements with biopsy histopathology findings was assessed by Mann-Whitney U- test and Kruskal-Wallis test. Of 73 targets, biopsy showed benign prostate tissue in 46 (63%), cancer in 23 (31.5%), and atypia/high grade prostatic intraepithelial neoplasia in four (5.5%) targets. The median volume of cancer-positive targets was 1.3 cm3. The cancer-positive targets were located in the peripheral zone (56.5%), transition zone (39.1%), and seminal vesicle (4.3%). Nine of 23 (39.1%) cancer-positive targets were higher grade cancer (Gleason grade > 6). Higher grade targets and cancer-positive targets compared to benign lesions exhibited lower mean apparent diffusion coefficient (ADC) value (952.7 < 1167.9 < 1278.9), and lower minimal extracellular volume fraction (ECF) (0.13 < 0.185 < 0.213), respectively. The difference in parameters was more pronounced between higher grade cancer and benign lesions. Our findings from a pilot study indicate that quantitative MRI parameters can predict malignant histology on MRI/TRUS fusion prostate biopsy, which is a valuable technique to ensure adequate sampling of MRI-visible suspicious lesions under TRUS guidance and may impact patient management. The DWI-based quantitative measurement exhibits a stronger association with biopsy findings than the other MRI parameters.

Kilovoltage Intrafraction Monitoring for Prostate Intensity Modulated Arc Therapy: First Clinical Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, Jin Aun; Institute of Medical Physics, School of Physics, University of Sydney, New South Wales; Booth, Jeremy T.

2012-12-01

Purpose: Most linear accelerators purchased today are equipped with a gantry-mounted kilovoltage X-ray imager which is typically used for patient imaging prior to therapy. A novel application of the X-ray system is kilovoltage intrafraction monitoring (KIM), in which the 3-dimensional (3D) tumor position is determined during treatment. In this paper, we report on the first use of KIM in a prospective clinical study of prostate cancer patients undergoing intensity modulated arc therapy (IMAT). Methods and Materials: Ten prostate cancer patients with implanted fiducial markers undergoing conventionally fractionated IMAT (RapidArc) were enrolled in an ethics-approved study of KIM. KIM involves acquiringmore » kV images as the gantry rotates around the patient during treatment. Post-treatment, markers in these images were segmented to obtain 2D positions. From the 2D positions, a maximum likelihood estimation of a probability density function was used to obtain 3D prostate trajectories. The trajectories were analyzed to determine the motion type and the percentage of time the prostate was displaced {>=}3, 5, 7, and 10 mm. Independent verification of KIM positional accuracy was performed using kV/MV triangulation. Results: KIM was performed for 268 fractions. Various prostate trajectories were observed (ie, continuous target drift, transient excursion, stable target position, persistent excursion, high-frequency excursions, and erratic behavior). For all patients, 3D displacements of {>=}3, 5, 7, and 10 mm were observed 5.6%, 2.2%, 0.7% and 0.4% of the time, respectively. The average systematic accuracy of KIM was measured at 0.46 mm. Conclusions: KIM for prostate IMAT was successfully implemented clinically for the first time. Key advantages of this method are (1) submillimeter accuracy, (2) widespread applicability, and (3) a low barrier to clinical implementation. A disadvantage is that KIM delivers additional imaging dose to the patient.« less

Prevalence of Flp Pili-Encoding Plasmids in Cutibacterium acnes Isolates Obtained from Prostatic Tissue

PubMed Central

Davidsson, Sabina; Carlsson, Jessica; Mölling, Paula; Gashi, Natyra; Andrén, Ove; Andersson, Swen-Olof; Brzuszkiewicz, Elzbieta; Poehlein, Anja; Al-Zeer, Munir A.; Brinkmann, Volker; Scavenius, Carsten; Nazipi, Seven; Söderquist, Bo; Brüggemann, Holger

2017-01-01

Inflammation is one of the hallmarks of prostate cancer. The origin of inflammation is unknown, but microbial infections are suspected to play a role. In previous studies, the Gram-positive, low virulent bacterium Cutibacterium (formerly Propionibacterium) acnes was frequently isolated from prostatic tissue. It is unclear if the presence of the bacterium represents a true infection or a contamination. Here we investigated Cutibacterium acnes type II, also called subspecies defendens, which is the most prevalent type among prostatic C. acnes isolates. Genome sequencing of type II isolates identified large plasmids in several genomes. The plasmids are highly similar to previously identified linear plasmids of type I C. acnes strains associated with acne vulgaris. A PCR-based analysis revealed that 28.4% (21 out of 74) of all type II strains isolated from cancerous prostates carry a plasmid. The plasmid shows signatures for conjugative transfer. In addition, it contains a gene locus for tight adherence (tad) that is predicted to encode adhesive Flp (fimbrial low-molecular weight protein) pili. In subsequent experiments a tad locus-encoded putative pilin subunit was identified in the surface-exposed protein fraction of plasmid-positive C. acnes type II strains by mass spectrometry, indicating that the tad locus is functional. Additional plasmid-encoded proteins were detected in the secreted protein fraction, including two signal peptide-harboring proteins; the corresponding genes are specific for type II C. acnes, thus lacking from plasmid-positive type I C. acnes strains. Further support for the presence of Flp pili in C. acnes type II was provided by electron microscopy, revealing cell appendages in tad locus-positive strains. Our study provides new insight in the most prevalent prostatic subspecies of C. acnes, subsp. defendens, and indicates the existence of Flp pili in plasmid-positive strains. Such pili may support colonization and persistent infection of human prostates by C. acnes. PMID:29201018

Preventive effects of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats.

PubMed

Bisson, Jean-François; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

2007-12-01

Plant extracts are useful in the management of benign prostatic hyperplasia (BPH). This study investigates whether ACTICOA (Barry Callebaut France, Louviers, France) powder (AP), a cocoa polyphenolic extract, could prevent prostate hyperplasia induced by testosterone propionate (TP) in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one negative control group receiving subcutaneous injections of corn oil and treated with vehicle and three groups injected subcutaneously with TP and treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments were given orally and started 2 weeks before the induction of prostate hyperplasia. The influence of TP and AP on body weights and food and water consumption of rats was examined. On day 36, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumption, while AP at both doses tested reduced significantly these differences. TP significantly increased prostate size ratio (P < .001), and this induced increase was significantly inhibited in AP-treated rats in comparison with positive controls (P < .001) in a dose-dependent manner. We conclude that AP can prevent TP-induced prostate hyperplasia and therefore may be beneficial in the management of BPH.

Automatic abdominal lymph node detection method based on local intensity structure analysis from 3D x-ray CT images

NASA Astrophysics Data System (ADS)

Nakamura, Yoshihiko; Nimura, Yukitaka; Kitasaka, Takayuki; Mizuno, Shinji; Furukawa, Kazuhiro; Goto, Hidemi; Fujiwara, Michitaka; Misawa, Kazunari; Ito, Masaaki; Nawano, Shigeru; Mori, Kensaku

2013-03-01

This paper presents an automated method of abdominal lymph node detection to aid the preoperative diagnosis of abdominal cancer surgery. In abdominal cancer surgery, surgeons must resect not only tumors and metastases but also lymph nodes that might have a metastasis. This procedure is called lymphadenectomy or lymph node dissection. Insufficient lymphadenectomy carries a high risk for relapse. However, excessive resection decreases a patient's quality of life. Therefore, it is important to identify the location and the structure of lymph nodes to make a suitable surgical plan. The proposed method consists of candidate lymph node detection and false positive reduction. Candidate lymph nodes are detected using a multi-scale blob-like enhancement filter based on local intensity structure analysis. To reduce false positives, the proposed method uses a classifier based on support vector machine with the texture and shape information. The experimental results reveal that it detects 70.5% of the lymph nodes with 13.0 false positives per case.

Mastery, Isolation, or Acceptance: Gay and Bisexual Men's Construction of Aging in the Context of Sexual Embodiment After Prostate Cancer.

PubMed

Ussher, Jane M; Rose, Duncan; Perz, Janette

2017-01-01

Age is the predominant risk factor for developing prostate cancer, leading to its description as an "older man's disease." Changed sexual embodiment is a concern for men who develop prostate cancer, often compounding experiences of age-related sexual decline. Although research has examined heterosexual men's experiences of aging in the context of sexual embodiment after prostate cancer, gay and bisexual men have received little attention. This qualitative study used a material-discursive analysis, drawing on positioning theory and intersectionality, to explore constructions of aging following prostate cancer in 46 gay or bisexual men. Thematic decomposition of one-to-one interviews identified three subject positions: "mastering youth," involving maintaining an active sex life through biomedical interventions, accessing commercial sex venues, or having sex with younger men; "the lonely old recluse," involving self-positioning as prematurely aged and withdrawal from a gay sexual scene; and "accepting embodied aging," involving the incorporation of changed sexual function into intimate relationships and finding pleasure through nonsexual activities. These subject positions are conceptualized as the product of intersecting masculine and gay identities, interpreted in relation to broader cultural discourses of "new aging" and "sexual health," in which sexual activity is conceptualized as a lifelong goal.

Radiolabeled choline PET/CT before salvage lymphadenectomy dissection: a systematic review and meta-analysis.

PubMed

Evangelista, Laura; Zattoni, Fabio; Karnes, Robert J; Novara, Giacomo; Lowe, Val

2016-12-01

To provide a systematic review of recently published reports and carry out a meta-analysis on the use of radiolabeled choline PET/computed tomography (CT) as a guide for salvage lymph node dissection (sLND) in prostate cancer patients with biochemical recurrence after primary treatments. Bibliographic database searches, from 2005 to May 2015, including Pubmed, Web of Science, and TripDatabase, were performed to find studies that included only patients who underwent sLND after radiolabeled choline PET/CT alone or in combination with other imaging modalities. For the qualitative assessment, all studies including the selected population were considered. Conversely, for the quantitative assessment, articles were included only if absolute numbers of true positive, true negative, false positive, and false negative test results were available or derivable from the text for lymph node metastases. Reviews, clinical reports, and editorial articles were excluded from analyses. Eighteen studies fulfilled the inclusion criteria and were assessed qualitatively. A total of 750 patients underwent radiolabeled choline (such as C-choline or F-choline) PET/CT before sLND. A quantitative evaluation was performed in nine studies. A patient-based, a lesion-based, and a site-based analysis was carried out in nine, four, and five studies, respectively. The pooled sensitivities were 85.3% [95% confidence interval (CI): 78.5-90.3%], 56.2% (95% CI: 41.6-69.7%), 75.3% (95% CI: 56.6-87.7%), and 63.7% (95% CI: 41-81.6%), respectively, for patient-based, lesion-based, pelvic site-based, and retroperitoneal site-based analysis. The pooled positive predictive values (PPVs) were 75% (95% CI: 68-80.9%), 85.8% (95% CI: 66.8-94.8%), 81.2% (95% CI: 70.1-88.9%), and 75.2% (95% CI: 58.7-86.7%), respectively, in the same analyses. High heterogeneities among the studies were found for sensitivities and PPVs ranging between 61.7-93.3% and 60.6-94.5%, respectively. Radiolabeled choline PET/CT has only a moderate sensitivity for the detection of metastatic lymph nodes in patients who are candidates for sLND, although the pooled PPVs ranged between 75 and 85.8% for all type of subanalyses. The presence of high heterogeneity among the studies should be considered carefully.

Endourethral MRI Guidance for Prostatic RF Ablation

DTIC Science & Technology

2005-06-01

head (3 cm wide) attached to a 24-cm plastic handle,. Copper tape and then covered with a coat of protective plastic. In addition, bazooka baluns made...in the perineum , advanced posterior surface. This arrangement was used to mimic the into the prostatic urethra, and fixated in the prostate by...are inserted through the perineum placed in the left lateral decubitus position to maximize and into the prostate gland, commonly under ultrasound

Prostatic Artery Embolization After Failed Urological Interventions for Benign Prostatic Obstruction: A Case Series of Three Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhatia, Shivank S., E-mail: sbhatia1@med.miami.edu; Dalal, Ravi, E-mail: rdalal@med.miami.edu; Gomez, Christopher, E-mail: Cgomez7@med.miami.edu

Benign prostate obstruction with associated lower urinary tract symptoms is a common diagnosis with multiple minimally invasive treatment options available. Herein, the authors describe three patients who failed prior different urological interventions who underwent prostate artery embolization with a subsequent improvement in symptoms. The positive response suggests that embolization may be an effective treatment alternative in this subset of patients.

Therapeutic effect of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats.

PubMed

Bisson, Jean-François; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

2007-12-01

Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Plant extracts are frequently used to treat BPH rather than therapeutics that can cause severe side effects. ACTICOA() (Ba0rry Callebaut France, Louviers, France) powder (AP) is a cocoa polyphenolic extract, and we have shown in a previous study that oral treatment with AP prevented prostate hyperplasia. This study investigated whether AP could improve established prostate hyperplasia using the same testosterone propionate (TP)-induced prostate hyperplasia model in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one group injected with corn oil and orally treated with the vehicle (negative control) and three groups injected subcutaneously with TP and orally treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments started 1 week after the start of the induction of prostate hyperplasia and lasted for 2 weeks. The influence of TP and AP on body weights, food and water consumptions, plasma polyphenolic concentration, and serum dihydrotestoterone (DHT) level of rats was examined. At completion of the study, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumptions, while AP reduced significantly these differences in a dose-dependent manner. AP significantly reduced serum DHT level and prostate size ratio in comparison with positive controls also dose-dependently. In conclusion, AP orally administered was effective for reducing established prostate hyperplasia, especially at the dose of 48 mg/kg/day.

AZD1152-HQPA induces growth arrest and apoptosis in androgen-dependent prostate cancer cell line (LNCaP) via producing aneugenic micronuclei and polyploidy.

PubMed

Zekri, Ali; Ghaffari, Seyed H; Ghanizadeh-Vesali, Samad; Yaghmaie, Marjan; Salmaninejad, Arash; Alimoghaddam, Kamran; Modarressi, Mohammad H; Ghavamzadeh, Ardeshir

2015-02-01

Prostate cancer is the frequent non-cutaneous tumor with high mortality in men. Prostate tumors contain cells with different status of androgen receptor. Androgen receptor plays important roles in progression and treatment of prostate cancer. Aurora B kinase, with oncogenic potential, is involved in chromosome segregation and cytokinesis, and its inhibition is a promising anti-cancer therapy. In the present study, we aimed to investigate the effects of Aurora B inhibitor, AZD1152-HQPA, on survival and proliferation of androgen receptor (AR)-positive prostate cancer cells. LNCaP was used as androgen-dependent prostate cancer cell line. We explored the effects of AZD1152-HQPA on cell viability, DNA content, micronuclei formation, and expression of genes involved in apoptosis and cell cycle. Moreover, the expression of Aurora B and AR were investigated in 23 benign prostatic hyperplasia and 38 prostate cancer specimens. AZD1152-HQPA treatment induced defective cell survival, polyploidy, and cell death in LNCaP cell line. Centromeric labeling with fluorescence in situ hybridization (FISH) showed that the loss of whole chromosomes is the origin of micronuclei, indicating on aneugenic action of AZD1152-HQPA. Treatment of AZD1152-HQPA decreased expression of AR. Moreover, we found weak positive correlations between the expression of Aurora B and AR in both benign prostatic hyperplasia and prostate cancer specimens (r = 0.25, r = 0.41). This is the first time to show that AZD1152-HQPA can be a useful therapeutic strategy for the treatment of androgen-dependent prostate cancer cell line. AZD1152-HQPA induces aneugenic mechanism of micronuclei production. Taken together, this study provides new insight into the direction to overcome the therapeutic impediments against prostate cancer.

[Quantification of prostate movements during radiotherapy].

PubMed

Artignan, X; Rastkhah, M; Balosso, J; Fourneret, P; Gilliot, O; Bolla, M

2006-11-01

Decrease treatment uncertainties is one of the most important challenge in radiation oncology. Numerous techniques are available to quantify prostate motion and visualise prostate location day after day before each irradiation: CT-scan, cone-beam-CT-Scan, ultrason, prostatic markers... The knowledge of prostate motion is necessary to define the minimal margin around the target volume needed to avoid mispositioning during treatment session. Different kind of prostate movement have been studied and are reported in the present work: namely, those having a large amplitude extending through out the whole treatment period on one hand; and those with a shorter amplitude happening during treatment session one the other hand. The long lasting movement are mostly anterior-posterior (3 mm standard deviation), secondary in cranial-caudal (1-2 mm standard deviation) and lateral directions (0.5-1 mm standard deviation). They are mostly due to the rectal state of filling and mildly due to bladder filling or inferior limbs position. On the other hand, the shorter movement that occurs during the treatment session is mostly variation of position around a steady point represented by the apex. Ones again, the rectal filling state is the principle cause. This way, during the 20 minutes of a treatment session, including the positioning of the patient, a movement of less than 3 mm could be expected when the rectum is empty. Ideally, real time imaging tools should allow an accurate localisation of the prostate and the adaptation of the dosimetry before each treatment session in a time envelope not exceeding 20 minutes.

Epithelial architectural destruction is necessary for bone marrow derived cell contribution to regenerating prostate epithelium.

PubMed

Palapattu, Ganesh S; Meeker, Alan; Harris, Timothy; Collector, Michael I; Sharkis, Saul J; DeMarzo, Angelo M; Warlick, Christopher; Drake, Charles G; Nelson, William G

2006-08-01

Using various nonphysiological tissue injury/repair models numerous studies have demonstrated the capacity of bone marrow derived cells to contribute to the repopulation of epithelial tissues following damage. To investigate whether this phenomenon might also occur during periods of physiological tissue degeneration/regeneration we compared the ability of bone marrow derived cells to rejuvenate the prostate gland in mice that were castrated and then later treated with dihydrotestosterone vs mice with prostate epithelium that had been damaged by lytic virus infection. Using allogenic bone marrow grafts from female donor transgenic mice expressing green fluorescent protein transplanted into lethally irradiated males we were able to assess the contributions of bone marrow derived cells to recovery of the prostatic epithelium in 2 distinct systems, including 1) surgical castration followed 1 week later by dihydrotestosterone replacement and 2) intraprostatic viral injection. Eight to 10-week-old male C57/Bl6 mice were distributed among bone marrow donor-->recipient/prostate injury groups, including 5 with C57/Bl6-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/vehicle injection, 4 with green fluorescent protein-->C57/Bl6/virus injection and 3 each with green fluorescent protein-->C57/Bl6/castration without and with dihydrotestosterone, respectively. Prostate tissues were harvested 3 weeks after dihydrotestosterone replacement or 14 days following intraprostatic viral injection. Prostate tissue immunofluorescence was performed with antibodies against the epithelial marker cytokeratin 5/8, the hematopoietic marker CD45 and green fluorescent protein. Mice that sustained prostate injury from vaccinia virus infection with concomitant severe inflammation and glandular disruption showed evidence of bone marrow derived cell reconstitution of prostate epithelium, that is approximately 4% of all green fluorescent protein positive cells in the epithelial compartment 14 days after injury expressed cytokeratin 5/8, similar to the proportion of green fluorescent protein positive cells in the prostate that no longer expressed the hematopoietic marker CD45. When prostatic degeneration/regeneration was triggered by androgen deprivation and reintroduction, no green fluorescent protein positive prostate epithelial cells were detected. These findings are consistent with a requirement for inflammation associated architectural destruction for the bone marrow derived cell contribution to the regeneration of prostate epithelium.

In-Bore 3-T MR-guided Transrectal Targeted Prostate Biopsy: Prostate Imaging Reporting and Data System Version 2–based Diagnostic Performance for Detection of Prostate Cancer

PubMed Central

Tan, Nelly; Lin, Wei-Chan; Khoshnoodi, Pooria; Asvadi, Nazanin H.; Yoshida, Jeffrey; Margolis, Daniel J. A.; Lu, David S. K.; Wu, Holden; Lu, David Y.; Huang, Jaioti

2017-01-01

Purpose To determine the diagnostic yield of in-bore 3-T magnetic resonance (MR) imaging–guided prostate biopsy and stratify performance according to Prostate Imaging Reporting and Data System (PI-RADS) versions 1 and 2. Materials and Methods This study was HIPAA compliant and institution review board approved. In-bore 3-T MR-guided prostate biopsy was performed in 134 targets in 106 men who (a) had not previously undergone prostate biopsy, (b) had prior negative biopsy findings with increased prostate-specific antigen (PSA) level, or (c) had a prior history of prostate cancer with increasing PSA level. Clinical, diagnostic 3-T MR imaging was performed with in-bore guided prostate biopsy, and pathology data were collected. The diagnostic yields of MR-guided biopsy per patient and target were analyzed, and differences between biopsy targets with negative and positive findings were determined. Results of logistic regression and areas under the curve were compared between PI-RADS versions 1 and 2. Results Prostate cancer was detected in 63 of 106 patients (59.4%) and in 72 of 134 targets (53.7%) with 3-T MR imaging. Forty-nine of 72 targets (68.0%) had clinically significant cancer (Gleason score ≥ 7). One complication occurred (urosepsis, 0.9%). Patients who had positive target findings had lower apparent diffusion coefficient values (875 × 10−6 mm2/sec vs 1111 × 10−6 mm2/sec, respectively; P < .01), smaller prostate volume (47.2 cm3 vs 75.4 cm3, respectively; P < .01), higher PSA density (0.16 vs 0.10, respectively; P < .01), and higher proportion of PI-RADS version 2 category 3–5 scores when compared with patients with negative target findings. MR targets with PI-RADS version 2 category 2, 3, 4, and 5 scores had a positive diagnostic yield of three of 23 (13.0%), six of 31 (19.4%), 39 of 50 (78.0%), and 24 of 29 (82.8%) targets, respectively. No differences were detected in areas under the curve for PI-RADS version 2 versus 1. Conclusion In-bore 3-T MR-guided biopsy is safe and effective for prostate cancer diagnosis when stratified according to PI-RADS versions 1 and 2. ©RSNA, 2016 PMID:27861110

Prognostic and Predictive Value of the 21-Gene Recurrence Score Assay in a Randomized Trial of Chemotherapy for Postmenopausal, Node-Positive, Estrogen Receptor-Positive Breast Cancer

PubMed Central

Albain, Kathy S.; Barlow, William E.; Shak, Steven; Hortobagyi, Gabriel N.; Livingston, Robert B.; Yeh, I-Tien; Ravdin, Peter; Bugarini, Roberto; Baehner, Frederick L.; Davidson, Nancy E.; Sledge, George W.; Winer, Eric P.; Hudis, Clifford; Ingle, James N.; Perez, Edith A.; Pritchard, Kathleen I.; Shepherd, Lois; Gralow, Julie R.; Yoshizawa, Carl; Allred, D. Craig; Osborne, C. Kent; Hayes, Daniel F.

2010-01-01

SUMMARY Background The 21-gene Recurrence Score assay (RS) is prognostic for women with node-negative, estrogen receptor (ER)-positive breast cancer (BC) treated with tamoxifen. A low RS predicts little benefit of chemotherapy. For node-positive BC, we investigated whether RS was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher recurrence risks. Methods The phase III trial S8814 for postmenopausal women with node-positive, ER-positive BC showed that CAF chemotherapy prior to tamoxifen (CAF-T) added survival benefit to tamoxifen alone. Optional tumor banking yielded specimens for RS determination by RT-PCR. We evaluated the effect of RS on disease-free survival (DFS) by treatment group (tamoxifen versus CAF-T) using Cox regression adjusting for number of positive nodes. Findings There were 367 specimens (40% of parent trial) with sufficient RNA (tamoxifen, 148; CAF-T, 219). The RS was prognostic in the tamoxifen arm (p=0.006). There was no CAF benefit in the low RS group (logrank p=0.97; HR=1.02, 95% CI (0.54,1.93)), but major DFS improvement for the high RS subset (logrank p=.03; HR=0.59, 95% CI (0.35, 1.01)), adjusting for number of positive nodes. The RS-by-treatment interaction was significant in the first 5 years (p=0.029), with no additional prediction beyond 5 years (p=0.58), though the cumulative benefit remained at 10 years. Results were similar for overall survival and BC-specific survival. Interpretation In this retrospective analysis, the RS is prognostic for tamoxifen-treated patients with positive nodes and predicts significant CAF benefit in tumors with a high RS. A low RS identifies women who may not benefit from anthracycline-based chemotherapy despite positive nodes. PMID:20005174

Stratified analysis of 800 Asian patients after robot-assisted radical prostatectomy with a median 64 months of follow up.

PubMed

Abdel Raheem, Ali; Kim, Dae Keun; Santok, Glen Denmer; Alabdulaali, Ibrahim; Chung, Byung Ha; Choi, Young Deuk; Rha, Koon Ho

2016-09-01

To report the 5-year oncological outcomes of robot-assisted radical prostatectomy from the largest series ever reported from Asia. A retrospective analysis of 800 Asian patients who were treated with robot-assisted radical prostatectomy from July 2005 to May 2010 in the Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea was carried out. The primary end-point was to evaluate the biochemical recurrence. The secondary end-point was to show the biochemical recurrence-free survival, metastasis-free survival and cancer-specific survival. A total of 197 (24.65%), 218 (27.3%), and 385 (48.1%) patients were classified as low-, intermediate- and high-risk patients according to the D'Amico risk stratification risk criteria, respectively. The median follow-up period was 64 months (interquartile range 28-71 months). The overall incidence of positive surgical margin was 36.6%. There was biochemical recurrence in 183 patients (22.9%), 38 patients (4.8%) developed distant metastasis and 24 patients (3%) died from prostate cancer. Actuarial biochemical recurrence-free survival, metastasis-free survival, and cancer-specific survival rates at 5 years were 76.4%, 94.6% and 96.7%, respectively. Positive lymph node was associated with lower 5-year biochemical recurrence-free survival (9.1%), cancer-specific survival (75.7%) and metastasis-free survival (61.9%) rates (P < 0.001). On multivariable analysis, among all the predictors, positive lymph node was the strongest predictor of biochemical recurrence, cancer-specific survival and metastasis-free survival (P < 0.001). Herein we report the largest robot-assisted radical prostatectomy series from Asia. Robot-assisted radical prostatectomy is confirmed to be an oncologically safe procedure that is able to provide effective 5-year cancer control, even in patients with high-risk disease. © 2016 The Japanese Urological Association.

Radical lymph node dissection and assessment: Impact on gallbladder cancer prognosis

PubMed Central

Liu, Gui-Jie; Li, Xue-Hua; Chen, Yan-Xin; Sun, Hui-Dong; Zhao, Gui-Mei; Hu, San-Yuan

2013-01-01

AIM: To investigate the lymph node metastasis patterns of gallbladder cancer (GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor. METHODS: From May 1995 to December 2010, a total of 78 consecutive patients with GBC underwent a radical resection at Liaocheng People’s Hospital. A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder. Demographic, operative and pathologic data were recorded. The lymph nodes retrieved were examined histologically for metastases routinely from each node. The positive lymph node count (PLNC) as well as the total lymph node count (TLNC) was recorded for each patient. Then the metastatic to examined lymph nodes ratio (LNR) was calculated. Disease-specific survival (DSS) and predictors of outcome were analyzed. RESULTS: With a median follow-up time of 26.50 mo (range, 2-132 mo), median DSS was 29.00 ± 3.92 mo (5-year survival rate, 20.51%). Nodal disease was found in 37 patients (47.44%). DSS of node-negative patients was significantly better than that of node-positive patients (median DSS, 40 mo vs 17 mo, χ2 = 14.814, P < 0.001), while there was no significant difference between N1 patients and N2 patients (median DSS, 18 mo vs 13 mo, χ2 = 0.741, P = 0.389). Optimal TLNC was determined to be four. When node-negative patients were divided according to TLNC, there was no difference in DSS between TLNC < 4 subgroup and TLNC ≥ 4 subgroup (median DSS, 37 mo vs 54 mo, χ2 = 0.715, P = 0.398). For node-positive patients, DSS of TLNC < 4 subgroup was worse than that of TLNC ≥ 4 subgroup (median DSS, 13 mo vs 21 mo, χ2 = 11.035, P < 0.001). Moreover, for node-positive patients, a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into 2 separate survival groups (< 6 or ≥ 6, respectively; median DSS, 15 mo vs 33 mo, χ2 = 11.820, P < 0.001). DSS progressively worsened with increasing PLNC and LNR, but no definite cut-off value could be identified. Multivariate analysis revealed histological grade, tumor node metastasis staging, TNLC and LNR to be independent predictors of DSS. Neither location of positive lymph nodes nor PNLC were identified as an independent variable by multivariate analysis. CONCLUSION: Both TLNC and LNR are strong predictors of outcome after curative resection for GBC. The retrieval and examination of at least 6 nodes can influence staging quality and DSS, especially in node-positive patients. PMID:23964151

Radical lymph node dissection and assessment: Impact on gallbladder cancer prognosis.

PubMed

Liu, Gui-Jie; Li, Xue-Hua; Chen, Yan-Xin; Sun, Hui-Dong; Zhao, Gui-Mei; Hu, San-Yuan

2013-08-21

To investigate the lymph node metastasis patterns of gallbladder cancer (GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor. From May 1995 to December 2010, a total of 78 consecutive patients with GBC underwent a radical resection at Liaocheng People's Hospital. A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder. Demographic, operative and pathologic data were recorded. The lymph nodes retrieved were examined histologically for metastases routinely from each node. The positive lymph node count (PLNC) as well as the total lymph node count (TLNC) was recorded for each patient. Then the metastatic to examined lymph nodes ratio (LNR) was calculated. Disease-specific survival (DSS) and predictors of outcome were analyzed. With a median follow-up time of 26.50 mo (range, 2-132 mo), median DSS was 29.00 ± 3.92 mo (5-year survival rate, 20.51%). Nodal disease was found in 37 patients (47.44%). DSS of node-negative patients was significantly better than that of node-positive patients (median DSS, 40 mo vs 17 mo, χ² = 14.814, P < 0.001), while there was no significant difference between N1 patients and N2 patients (median DSS, 18 mo vs 13 mo, χ² = 0.741, P = 0.389). Optimal TLNC was determined to be four. When node-negative patients were divided according to TLNC, there was no difference in DSS between TLNC < 4 subgroup and TLNC ≥ 4 subgroup (median DSS, 37 mo vs 54 mo, χ² = 0.715, P = 0.398). For node-positive patients, DSS of TLNC < 4 subgroup was worse than that of TLNC ≥ 4 subgroup (median DSS, 13 mo vs 21 mo, χ² = 11.035, P < 0.001). Moreover, for node-positive patients, a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into 2 separate survival groups (< 6 or ≥ 6, respectively; median DSS, 15 mo vs 33 mo, χ² = 11.820, P < 0.001). DSS progressively worsened with increasing PLNC and LNR, but no definite cut-off value could be identified. Multivariate analysis revealed histological grade, tumor node metastasis staging, TNLC and LNR to be independent predictors of DSS. Neither location of positive lymph nodes nor PNLC were identified as an independent variable by multivariate analysis. Both TLNC and LNR are strong predictors of outcome after curative resection for GBC. The retrieval and examination of at least 6 nodes can influence staging quality and DSS, especially in node-positive patients.

[Cost analysis of ultrasound-guided transrectal needle biopsy in prostatic carcinoma].

PubMed

Bissoli, E; Fandella, A; La Torre, E; Faggiano, L; Anselmo, G; Frasson, F

1998-04-01

The literature mortality and morbidity rates from prostatic carcinoma prompt to the better use of some routine diagnostic tools such as transrectal ultrasound-guided biopsy. We evaluated the overall cost of transrectal ultrasound biopsy (TRUSB) of the prostate and investigated the economic impact of the procedures currently used to diagnose prostatic carcinoma. The total cost of TRUSB was calculated with reference to 247 procedures performed in 1996. The following cost factors were evaluated: personnel, materials, maintenance-equipment depreciation, energy consumption and hospital overheads. A literature review was also carried out to check if our extrapolated costs corresponded to those of other authors worldwide and to consider them in the wider framework of the cost effectiveness of the strategies for the early diagnosis of prostatic cancer. The overall cost of TRUSB was Itl. 249,000, obtained by adding together the costs of: personnel (Itl. 160,000); materials (Itl. 59,000); equipment maintenance and depreciation (Itl. 12,400); energy consumption (Itl. 100); hospital overheads (Itl. 17,500). The literature review points out TRUSB as a clinically invasive tool for diagnosing prostatic carcinoma whose cost-effectiveness is debated. Cadaver studies report the presence of cancer cells in the prostate of 50% of 70-year-old men, while extrapolations calculate a morbidity from prostatic carcinoma in 9.5% of 50-year-old men. It is therefore obvious that randomized prostatic biopsies, methods apart, are very likely to be positive. This probability varies with the patient's age, the level of prostate specific antigen (PSA), the density of PSA/cm3 of prostate volume (PSAD), and the positivity of exploration and/or transrectal ultrasound findings. Despite the strict application of all these criteria and the critical assessment of the patient's general conditions, TRUSB is indicated for 16% of the male population over 50, with obvious implications. It has been recently suggested that the ratio between free PSA (antigen fraction of the total serum PSA) and total PSA could be clinically useful as an effective predict of TRUSB positivity or negativity. Free PSA evaluation might thus help reduce the number of TRUSB.

Profile of cell proliferation and apoptosis activated by the intrinsic and extrinsic pathways in the prostate of aging rats.

PubMed

Gonzaga, Amanda C R; Campolina-Silva, Gabriel H; Werneck-Gomes, Hipácia; Moura-Cordeiro, Júnia D; Santos, Letícia C; Mahecha, Germán A B; Morais-Santos, Mônica; Oliveira, Cleida A

2017-06-01

Estrogens acting through the receptors ERα and ERβ participate in prostate normal growth and cancer. ERβ is highly expressed in the prostate epithelium, playing pro-apoptotic, anti-proliferative, and pro-differentiation roles. Apoptosis is activated by the intrinsic pathway after castration and by the extrinsic pathway after ERβ agonist treatment. This differential activation of apoptotic pathways is important since a major problem in the treatment of prostate cancer is the recurrence of tumors after androgen withdrawal. However, a comprehensive study about the pattern of apoptosis in the aging prostate is lacking, a knowledge gap that we aimed to address herein. Cellular age-related proliferative and apoptotic profiles of prostate tissue obtained from aging Wistar rats were evaluated. Cell death (caspase-3, -8, -9, TNFα) was assessed by immunohistochemistry, immunofluorescence, and TUNEL. Cell proliferation (MCM7) and cell survival factors (ERK1/2, p-ERK1/2, p-Akt, and NF-κB) were determined by immunohistochemistry. As the rats aged, the number of proliferating cells gradually reduced in the normal epithelium of all prostate lobes, while increasing in focal areas of intraepithelial proliferation. Interestingly, in areas of intraepithelial proliferation, we observed a reduction in the number of cells positive for caspase-3, -8, and -9. Regardless the animal's age, few prostate epithelial cells were positive for caspase-3, caspase-9, and TUNEL. In contrast, a progressive increase was seen in the positivity for caspase-8, especially in the atrophic epithelium of ventral prostate, which coincided with a reduction in TNFα immunoreaction. However, morphology of most caspase-8 positive cells suggests that they were not apoptotic. We also found reduced ERβ expression in the same areas. Possibly, low levels of the pro-apoptotic inductors TNFα and ERβ direct caspase-8 activity to an alternative pro-survival role in the atrophic epithelium. This hypothesis is supported by the increased expression of the key survival factors (ERK1/2, p-ERK1/2, p-Akt, and NF-κB) in these areas. Our findings reveal that, as the animals age, there is an increase of proliferation in restricted areas of the prostate epithelium, and a concomitant reduction of the apoptosis rate with an increase in cell survival induced by caspase-8, indicating a focused and spontaneous disruption of tissue homeostasis. © 2017 Wiley Periodicals, Inc.

Biological and Genomic Differences of ERG Oncoprotein-Stratified Prostate Cancers from African and Caucasian Americans

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-13-2-0096 TITLE: Biological and Genomic Differences of ERG Oncoprotein-Stratified Prostate Cancers from African and...Biological and Genomic Differences of ERG Oncoprotein-Stratified Prostate Cancers from African and Caucasian Americans Sb. GRANT NUMBER W81 XWH-13-2...differences in the distribution of key clinico-pathologic patient features and molecular determinants for both ERG positive and ERG negative prostate cancer

Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS):a randomised, multicentre, open-label, phase 3 non-inferiority trial

PubMed Central

Donker, Mila; van Tienhoven, Geertjan; Straver, Marieke E; Meijnen, Philip; van de Velde, Cornelis J H; Mansel, Robert E; Cataliotti, Luigi; Westenberg, A Helen; Klinkenbijl, Jean H G; Orzalesi, Lorenzo; Bouma, Willem H; van der Mijle, Huub C J; Nieuwenhuijzen, Grard A P; Veltkamp, Sanne C; Slaets, Leen; Duez, Nicole J; de Graaf, Peter W; van Dalen, Thijs; Marinelli, Andreas; Rijna, Herman; Snoj, Marko; Bundred, Nigel J; Merkus, Jos W S; Belkacemi, Yazid; Petignat, Patrick; Schinagl, Dominic A X; Coens, Corneel; Messina, Carlo G M; Bogaerts, Jan; Rutgers, Emiel J T

2014-01-01

Summary Background If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. Methods Patients with T1–2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. Findings Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6·1 years (IQR 4·1–8·0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0·43% (95% CI 0·00–0·92) after axillary lymph node dissection versus 1·19% (0·31–2·08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0·00–5·27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. Interpretation Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1–2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity. Funding EORTC Charitable Trust. PMID:25439688

Mobile agent location in distributed environments

NASA Astrophysics Data System (ADS)

Fountoukis, S. G.; Argyropoulos, I. P.

2012-12-01

An agent is a small program acting on behalf of a user or an application which plays the role of a user. Artificial intelligence can be encapsulated in agents so that they can be capable of both behaving autonomously and showing an elementary decision ability regarding movement and some specific actions. Therefore they are often called autonomous mobile agents. In a distributed system, they can move themselves from one processing node to another through the interconnecting network infrastructure. Their purpose is to collect useful information and to carry it back to their user. Also, agents are used to start, monitor and stop processes running on the individual interconnected processing nodes of computer cluster systems. An agent has a unique id to discriminate itself from other agents and a current position. The position can be expressed as the address of the processing node which currently hosts the agent. Very often, it is necessary for a user, a processing node or another agent to know the current position of an agent in a distributed system. Several procedures and algorithms have been proposed for the purpose of position location of mobile agents. The most basic of all employs a fixed computing node, which acts as agent position repository, receiving messages from all the moving agents and keeping records of their current positions. The fixed node, responds to position queries and informs users, other nodes and other agents about the position of an agent. Herein, a model is proposed that considers pairs and triples of agents instead of single ones. A location method, which is investigated in this paper, attempts to exploit this model.

Prostatic adenocarcinoma with glomeruloid features.

PubMed

Pacelli, A; Lopez-Beltran, A; Egan, A J; Bostwick, D G

1998-05-01

A wide variety of architectural patterns of adenocarcinoma may be seen in the prostate. We have recently encountered a hitherto-undescribed pattern of growth characterized by intraluminal ball-like clusters of cancer cells reminiscent of renal glomeruli, which we refer to as prostatic adenocarcinoma with glomeruloid features. To define the architectural features, frequency, and distribution of prostatic adenocarcinoma with glomeruloid features, we reviewed 202 totally embedded radical prostatectomy specimens obtained between October 1992 and April 1994 from the files of the Mayo Clinic. This series was supplemented by 100 consecutive needle biopsies with prostatic cancer from January to February 1996. Prostatic adenocarcinoma with glomeruloid features was characterized by round to oval epithelial tufts growing within malignant acini, often supported by a fibrovascular core. The epithelial cells were sometimes arranged in semicircular concentric rows separated by clefted spaces. In the radical prostatectomy specimens, nine cases (4.5%) had glomeruloid features. The glomeruloid pattern constituted 5% to 20% of each cancer (mean, 8.33%) and was usually located at the apex or in the peripheral zone of the prostate. Seven cases were associated with a high Gleason score (7 or 8), one with a score of 6, and one with a score of 5. All cases were associated with high-grade prostatic intraepithelial neoplasia and extensive perineural invasion. Pathological stages included T2c (three cases), T3b (four cases), and T3c (two cases); one of the T3b cases had lymph node metastases (N1). Three (3%) of 100 consecutive routine needle biopsy specimens with cancer showed glomeruloid features, and this pattern constituted 5% to 10% of each cancer (mean, 6.7%). The Gleason score was 6 for two cases and 8 for one case. Two cases were associated with high-grade prostatic intraepithelial neoplasia, and one case had perineural invasion. Glomeruloid features were not observed in any benign or premalignant lesions, including hyperplasia and intraepithelial neoplasia. Glomeruloid structures in the prostate represent an uncommon but distinctive pattern of growth that is specific for malignancy. Glomeruloid features may be a useful diagnostic clue for malignancy, particularly in some challenging needle biopsy specimens. This pattern of growth is usually seen in high-grade adenocarcinoma, often with extraprostatic extension. Further investigations are required to determine its independent predictive value and correlation with stage and Gleason score.

Prostate health index and prostate cancer gene 3 score but not percent-free Prostate Specific Antigen have a predictive role in differentiating histological prostatitis from PCa and other nonneoplastic lesions (BPH and HG-PIN) at repeat biopsy.

PubMed

De Luca, Stefano; Passera, Roberto; Fiori, Cristian; Bollito, Enrico; Cappia, Susanna; Mario Scarpa, Roberto; Sottile, Antonino; Franco Randone, Donato; Porpiglia, Francesco

2015-10-01

To determine if prostate health index (PHI), prostate cancer antigen gene 3 (PCA3) score, and percentage of free prostate-specific antigen (%fPSA) may be used to differentiate asymptomatic acute and chronic prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA levels and negative findings on digital rectal examination at repeat biopsy (re-Bx). In this prospective study, 252 patients were enrolled, undergoing PHI, PCA3 score, and %fPSA assessments before re-Bx. We used 3 multivariate logistic regression models to test the PHI, PCA3 score, and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the "gray zone" of PSA (4-10ng/ml) cohort (171 individuals). Of the 252 patients, 43 (17.1%) had diagnosis of PCa. The median PHI was significantly different between men with a negative biopsy and those with a positive biopsy (34.9 vs. 48.1, P<0.001), as for the PCA3 score (24 vs. 54, P<0.001) and %fPSA (11.8% vs. 15.8%, P = 0.012). The net benefit of using PCA3 and PHI to differentiate prostatitis and PCa was moderate, although it extended to a good range of threshold probabilities (40%-100%), whereas that from using %fPSA was negligible: this pattern was reported for the whole population as for the "gray zone" PSA cohort. In front of a good diagnostic performance of all the 3 biomarkers in distinguishing negative biopsy vs. positive biopsy, the clinical benefit of using the PCA3 score and PHI to estimate prostatitis vs. PCa was comparable. PHI was the only determinant for prostatitis vs. BPH, whereas no biomarkers could differentiate prostate inflammation from HG-PIN. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of ECE on the benefits of PMRT for breast cancer patients with positive axillary nodes.

PubMed

Geng, Wenwen; Zhang, Bin; Li, Danhua; Liang, Xinrui; Cao, Xunchen

2013-07-01

The purpose of the present study was to retrospectively evaluate the effects of extracapsular extension (ECE) on the benefits of post-mastectomy radiation therapy (PMRT) for groups of patients with varying numbers of positive axillary nodes (1-3, 4-9 and ≥10 positive axillary nodes). A total of 1220 axillary node-positive patients who had received mastectomy were involved in this study. Patients were grouped as 'Radio + /ECE + ', 'Radio-/ECE + ', 'Radio + /ECE-' or 'Radio-/ECE-' according to status of ECE and whether receiving PMRT or not, and were evaluated in terms of local region relapse (LRR) rate. The 5-year and 10-year Kaplan-Meier disease-free survival and overall survival (OS) rates were analyzed. ECE-positive differed from ECE-negative groups with statistical significance for all comparisons in favor of the ECE-negative group: 5-year locoregional failure-free survival (LRFFS) (82.69% vs 91.83%, P < 0.001), 10-year LRFFS (75.39% vs 90.02%, P < 0.001); 5-year OS (52.12% vs 74.46%, P < 0.001), 10-year OS (35.17% vs 67.63%, P < 0.001). There were no significant effects of ECE on the benefits of PMRT for patients with 1-3 (P = 0.5720), ≥10(P = 0.0614) positive axillary nodes. However, for the group of patients with 4-9 positive axillary nodes, ECE status had a significant effect on the benefits of PMRT with respect to 5-year and 10-year LRFFS (P < 0.05). In our study, regardless of the ECE status, PMRT didn't significantly improve the LRFFS for patients with 1-3 or ≥10 positive axillary nodes. However, for patients with 4-9 positive axillary nodes, ECE could be an important criterion to consider when deciding whether to receive PMRT.

Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

DTIC Science & Technology

2012-05-01

ijo.2011.953. Epub 2011 Feb 23. 6. Sharma PK, Singh R, Novakovic KR, Eaton JW, Grizzle WE, Singh S. CCR9 mediates PI3K/AKT-dependent antiapoptotic...Cooper, C.R., Novakovic , K.R., Grizzle, W.E., Lillard Jr., J.W., 2009. Serum CXCL13 positively correlates with prostatic disease, prostate-specific

Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

PubMed

Sung, Shian-Ying; Chang, Junn-Liang; Chen, Kuan-Chou; Yeh, Shauh-Der; Liu, Yun-Ru; Su, Yen-Hao; Hsueh, Chia-Yen; Chung, Leland W K; Hsieh, Chia-Ling

2016-01-01

Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E) containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc) into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK) was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

Conditional Expression of the Androgen Receptor Induces Oncogenic Transformation of the Mouse Prostate*

PubMed Central

Zhu, Chunfang; Luong, Richard; Zhuo, Ming; Johnson, Daniel T.; McKenney, Jesse K.; Cunha, Gerald R.; Sun, Zijie

2011-01-01

The androgen signaling pathway, mediated through the androgen receptor (AR), is critical in prostate tumorigenesis. However, the precise role of AR in prostate cancer development and progression still remains largely unknown. Specifically, it is unclear whether overexpression of AR is sufficient to induce prostate tumor formation in vivo. Here, we inserted the human AR transgene with a LoxP-stop-loxP (LSL) cassette into the mouse ROSA26 locus, permitting “conditionally” activated AR transgene expression through Cre recombinase-mediated removal of the LSL cassette. By crossing this AR floxed strain with Osr1-Cre (odd skipped related) mice, in which the Osr1 promoter activates at embryonic day 11.5 in urogenital sinus epithelium, we generated a conditional transgenic line, R26hARloxP:Osr1-Cre+. Expression of transgenic AR was detected in both prostatic luminal and basal epithelial cells and is resistant to castration. Approximately one-half of the transgenic mice displayed mouse prostatic intraepithelial neoplasia (mPIN) lesions. Intriguingly, four mice (10%) developed prostatic adenocarcinomas, with two demonstrating invasive diseases. Positive immunostaining of transgenic AR protein was observed in the majority of atypical and tumor cells in the mPIN and prostatic adenocarcinomas, providing a link between transgenic AR expression and oncogenic transformation. An increase in Ki67-positive cells appeared in all mPIN and prostatic adenocarcinoma lesions of the mice. Thus, we demonstrated for the first time that conditional activation of transgenic AR expression by Osr1 promoter induces prostate tumor formation in mice. This new AR transgenic mouse line mimics the human disease and can be used for study of prostate tumorigenesis and drug development. PMID:21795710

Analysis of the spatial distribution of prostate cancer obtained from histopathological images

NASA Astrophysics Data System (ADS)

Diaz, Kristians; Castaneda, Benjamin; Montero, Maria Luisa; Yao, Jorge; Joseph, Jean; Rubens, Deborah; Parker, Kevin J.

2013-03-01

Understanding the spatial distribution of prostate cancer and how it changes according to prostate specific antigen (PSA) values, Gleason score, and other clinical parameters may help comprehend the disease and increase the overall success rate of biopsies. This work aims to build 3D spatial distributions of prostate cancer and examine the extent and location of cancer as a function of independent clinical parameters. The border of the gland and cancerous regions from wholemount histopathological images are used to reconstruct 3D models showing the localization of tumor. This process utilizes color segmentation and interpolation based on mathematical morphological distance. 58 glands are deformed into one prostate atlas using a combination of rigid, affine, and b-spline deformable registration techniques. Spatial distribution is developed by counting the number of occurrences in a given position in 3D space from each registered prostate cancer. Finally a difference between proportions is used to compare different spatial distributions. Results show that prostate cancer has a significant difference (SD) in the right zone of the prostate between populations with PSA greater and less than 5ng/ml. Age does not have any impact in the spatial distribution of the disease. Positive and negative capsule-penetrated cases show a SD in the right posterior zone. There is SD in almost all the glands between cases with tumors larger and smaller than 10% of the whole prostate. A larger database is needed to improve the statistical validity of the test. Finally, information from whole-mount histopathological images may provide better insight into prostate cancer.

Breast cancer-specific survival in patients with lymph node-positive hormone receptor-positive invasive breast cancer and Oncotype DX Recurrence Score results in the SEER database.

PubMed

Roberts, Megan C; Miller, Dave P; Shak, Steven; Petkov, Valentina I

2017-06-01

The Oncotype DX ® Breast Recurrence Score™ (RS) assay is validated to predict breast cancer (BC) recurrence and adjuvant chemotherapy benefit in select patients with lymph node-positive (LN+), hormone receptor-positive (HR+), HER2-negative BC. We assessed 5-year BC-specific survival (BCSS) in LN+ patients with RS results in SEER databases. In this population-based study, BC cases in SEER registries (diagnosed 2004-2013) were linked to RS results from assays performed by Genomic Health (2004-2014). The primary analysis included only patients (diagnosed 2004-2012) with LN+ (including micrometastases), HR+ (per SEER), and HER2-negative (per RT-PCR) primary invasive BC (N = 6768). BCSS, assessed by RS category and number of positive lymph nodes, was calculated using the actuarial method. The proportion of patients with RS results and LN+ disease (N = 8782) increased over time between 2004 and 2013, and decreased with increasing lymph node involvement from micrometastases to ≥4 lymph nodes. Five-year BCSS outcomes for those with RS < 18 ranged from 98.9% (95% CI 97.4-99.6) for those with micrometastases to 92.8% (95% CI 73.4-98.2) for those with ≥4 lymph nodes. Similar patterns were found for patients with RS 18-30 and RS ≥ 31. RS group was strongly predictive of BCSS among patients with micrometastases or up to three positive lymph nodes (p < 0.001). Overall, 5-year BCSS is excellent for patients with RS < 18 and micrometastases, one or two positive lymph nodes, and worsens with additionally involved lymph nodes. Further analyses should account for treatment variables, and longitudinal updates will be important to better characterize utilization of Oncotype DX testing and long-term survival outcomes.

Antiproliferative mechanisms of the flavonoids 2,2'-dihydroxychalcone and fisetin in human prostate cancer cells.

PubMed

Haddad, Ahmed Q; Fleshner, Neil; Nelson, Colleen; Saour, Basil; Musquera, Mireia; Venkateswaran, Vasundara; Klotz, Laurence

2010-01-01

We have previously demonstrated the antiproliferative effect of two flavonoids-2,2'-dihydroxychalcone (DHC), a novel synthetic flavonoid, and fisetin, a naturally occurring flavonol-in prostate cancer cells. In this study, we further examine the mechanisms of these compounds on survival and proliferation pathways. DHC and fisetin (1-50 microM) caused a dose-dependent reduction in viability, a concomitant increase in apoptosis in PC3 cells at 72 h, and a decrease in clonogenic survival at 24 h treatment. DHC was considerably more potent than fisetin in these cytotoxicity assays. The mechanism of accelerated cellular senescence was not activated by either compound in PC3 or lymph node carcinoma of the prostate (LNCaP) cells. Gene expression alterations in PC3 and LNCaP cells treated with 15 muM DHC and 25 microM fisetin for 6 to 24 h were determined by oligonucleotide array. Amongst the most highly represented functional categories of genes altered by both compounds was the cell cycle category. In total, 100 cell cycle genes were altered by DHC and fisetin including 27 genes with key functions in G2/M phase that were downregulated by both compounds. Other functional categories altered included chromosome organization, apoptosis, and stress response. These results demonstrate the multiple mechanisms of antitumor activity of DHC and fisetin in prostate cancer cells in vitro.

FoxP3 and indoleamine 2,3-dioxygenase immunoreactivity in sentinel nodes from melanoma patients.

PubMed

Ryan, Marisa; Crow, Jennifer; Kahmke, Russel; Fisher, Samuel R; Su, Zuowei; Lee, Walter T

2014-01-01

1) Assess FoxP3/indoleamine 2,3-dioxygenase immunoreactivity in head and neck melanoma sentinel lymph nodes and 2) correlate FoxP3/indoleamine 2,3-dioxygenase with sentinel lymph node metastasis and clinical recurrence. Retrospective cohort study. Patients with sentinel lymph node biopsy for head and neck melanoma between 2004 and 2011 were identified. FoxP3/indoleamine 2,3-dioxygenase prevalence and intensity were determined from the nodes. Poor outcome was defined as local, regional or distant recurrence. The overall immunoreactivity score was correlated with clinical recurrence and sentinel lymph node metastasis using the chi-square test for trend. Fifty-six sentinel lymph nodes were reviewed, with 47 negative and 9 positive for melanoma. Patients with poor outcomes had a statistically significant trend for higher immunoreactivity scores (p=0.03). Positive nodes compared to negative nodes also had a statistically significant trend for higher immunoreactivity scores (p=0.03). Among the negative nodes, there was a statistically significant trend for a poor outcome with higher immunoreactivity scores (p=0.02). FoxP3/indoleamine 2,3-dioxygenase immunoreactivity correlates with sentinel lymph node positivity and poor outcome. Even in negative nodes, higher immunoreactivity correlated with poor outcome. Therefore higher immunoreactivity may portend a worse prognosis even without metastasis in the sentinel lymph node. This could identify a subset of patients that may benefit from future trials and treatment for melanoma through Treg and IDO suppression. Published by Elsevier Inc.

Survey of practicing urologists: robotic versus open radical prostatectomy.

PubMed

Lee, Eugene K; Baack, Janet; Duchene, David A

2010-04-01

The robotic assisted radical prostatectomy (RARP) has become the most common operative choice for localized prostate cancer. At our institution, we have also seen a substantial increase in the proportion of RARP. Possible patient factors may include marketing, increased Internet usage by patients, and patient-to-patient communication. We surveyed urologists from the central United States to determine possible surgeon factors for the popularity of the RARP. We mailed a survey to all urologists in the South Central Section of the American Urological Association. After demographic information was obtained, participants were asked to choose an operation for themselves based on two prostate cancer scenarios; low risk and high risk. For the low risk prostate cancer scenario, 54.3% chose RARP while 32.9% chose a radical retropubic prostatectomy (RRP). In the high risk scenario, 32.3% chose a RARP while 58.8% chose the RRP. The top reasons for choosing robotics included decreased blood loss, better pain control, and visualization of the apex. The most popular reasons for an open operation included improved lymph node dissection, better tactile sensation, and easier operation for the surgeon. The two most important factors for choosing a particular operation were cancer control and the urologist performing the operation. Also, urologists favored the operative choice in which he or she performed. Robotic assisted radical prostatectomy has become the favored operative approach for low risk prostate cancer. However, many urologists still feel an oncologic difference may exist between open and robotic surgery as evidenced by more urologists favoring an open approach for high risk prostate cancer.

Incidental prostate cancer in patients with muscle-invasive bladder cancer who underwent radical cystoprostatectomy.

PubMed

Tanaka, Toshikazu; Koie, Takuya; Ohyama, Chikara; Hashimoto, Yasuhiro; Imai, Atsushi; Tobisawa, Yuki; Hatakeyama, Shingo; Yamamoto, Hayato; Yoneyama, Tohru; Horiguchi, Hirotaka; Kodama, Hirotake; Yoneyama, Takahiro

2017-11-01

The aim of this study was to analyze the features of incidentally detected prostate cancer (PCa) in radical cystoprostatectomy (RCP) specimens to determine their pathological characteristics and clinical significance. In this retrospective study, we reviewed the clinical and pathological records of 431 consecutive patients with muscle-invasive bladder cancer who underwent RCP at Hirosaki University. Of these, we focused on 237 male patients with prostate-specific antigen (PSA) measurements and digital rectal examinations (DRE) that were recorded prior to the RCP. Significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, pathological T3 or higher stage, lymph node involvement or three or more multifocal lesions within the prostate specimen. We compared clinically significant and insignificant PCa. In this study, a total of 43 patients (18.1%) were diagnosed with incidental PCa via RCP specimens. Age, preoperative PSA levels and pathological T stage in patients with clinically significant PCa were considerably higher than in those with insignificant cancer. Apical involvement was found in 16 patients, including 11 of those with clinically significant PCa. By the end of the follow-up period, none of the enrolled patients had a biochemical recurrence after surgery or died from PCa. According to our findings, preoperative risk factors were not reliable enough to accurately predict clinically significant PCa. Although there was no biochemical relapse or clinical recurrence of PCa in this study, the potential oncologic risk of prostate-sparing RCP must be considered. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Multiple joint metastasis of a transitional cell carcinoma in a dog.

PubMed

Colledge, Sarah L; Raskin, Rose E; Messick, Joanne B; Tiffany Reed, L; Wigle, William L; Balog, Kelley A

2013-06-01

An 8-year-old castrated male hound mix was referred to the Purdue University Veterinary Teaching Hospital for severe lameness, pollakiuria, and dyschezia. On presentation, the dog was nonweight bearing on the right rear limb and the right carpus was diffusely swollen. Synovial fluid analysis from the right carpus revealed a population of epithelial cells displaying marked anisocytosis, anisokaryosis, multinucleation, and prominent, variably sized nucleoli. A metastatic carcinoma with presumed prostatic or urothelial origin was diagnosed based on cytomorphology. Subsequent cytologic evaluation of peripheral lymph nodes revealed the presence of a similar neoplastic population. The dog was euthanized and synovial fluid from both stifle joints, as well as impression smears of the prostate gland, were collected. Carcinoma cells were identified in each stifle joint and in the prostate gland. Immunocytochemistry was performed on synovial fluid smears from 2 of the joints (right stifle and right carpus) and on impression smears of the prostate gland. The neoplastic population in the joints and prostate gland showed strong immunoreactivity to uroplakin III, a urothelial marker, indicating metastasis of a transitional cell carcinoma to multiple joints. In addition, evidence for epithelial to mesenchymal transition was identified using cytokeratin, an epithelial marker, and vimentin, a mesenchymal marker. A necropsy was performed and histopathology confirmed the presence of metastatic transitional cell carcinoma in various tissues. This case illustrates the importance of considering metastatic disease when a patient is presented with severe lameness and joint pain, and the clinical utility of synovial fluid cytology for diagnosis of metastasis in these cases. © 2013 American Society for Veterinary Clinical Pathology.

Persistent, Biologically Meaningful Prostate Cancer After 1 Year of Androgen Ablation and Docetaxel Treatment

PubMed Central

Tzelepi, Vassiliki; Efstathiou, Eleni; Wen, Sijin; Troncoso, Patricia; Karlou, Maria; Pettaway, Curtis A.; Pisters, Louis L.; Hoang, Anh; Logothetis, Christopher J.; Pagliaro, Lance C.

2011-01-01

Purpose Clinicians are increasingly willing to treat prostate cancer within the primary site in the presence of regional lymph node or even limited distant metastases. However, no formal study on the merits of this approach has been reported. We used a preoperative clinical discovery platform to prioritize pathways for assessment as therapeutic targets and to test the hypothesis that the primary site harbors potentially lethal tumors after aggressive treatment. Patients and Methods Patients with locally advanced or lymph node–metastatic prostate cancer underwent 1 year of androgen ablation and three cycles of docetaxel therapy, followed by prostatectomy. All specimens were characterized for stage by accepted criteria. Expression of select molecular markers implicated in disease progression and therapy resistance was determined immunohistochemically and compared with that in 30 archived specimens from untreated patients with high-grade prostate cancer. Marker expression was divided into three groups: intracellular signaling pathways, stromal-epithelial interaction pathways, and angiogenesis. Results Forty patients were enrolled, 30 (75%) of whom underwent prostatectomy and two (5%) who underwent cystoprostatectomy. Twenty-nine specimens contained sufficient residual tumor for inclusion in a tissue microarray. Immunohistochemical analysis showed increased epithelial and stromal expression of CYP17, SRD5A1, and Hedgehog pathway components, and modulations of the insulin-like growth factor I pathway. Conclusion A network of molecular pathways reportedly linked to prostate cancer progression is activated after 1 year of therapy; biomarker expression suggests that potentially lethal cancers persist in the primary tumor and may contribute to progression. PMID:21606419

Fluorine-18-fluoroethylcholine PET/CT in the detection of prostate cancer: a South African experience.

PubMed

Vorster, Mariza; Modiselle, Moshe; Ebenhan, Thomas; Wagener, Carl; Sello, That; Zeevaart, Jan Rijn; Moshokwa, Evelyn; Sathekge, Mike Machaba

2015-01-01

Imaging with fluorine-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has, until recently provided disappointing results with low sensitivity ranging from 31%-64% in patients with well-differentiated prostate cancer (PC) at all prostatic specific antigen (PSA) levels while fluorine-18-fluoroethylcholine ((18)F-FECh) PET/CT showed about 85% sensitivity in restaging patients after relapse. We present our experience of the sensitivity of (18)F-FECh PET/CT in the early stages of PC. Fifty patients were prospectively recruited and imaged, of which 40 fulfilled all inclusion criteria. Our patients had an average age of 65.5 years. Fifteen patients were referred for initial staging, with the remaining 25 referred for restaging and all patients had histologically confirmed adenocarcinoma. Patients were imaged by (18)F-FECh PET/CT. Findings were evaluated qualitatively and quantitatively and compared to the results of histology, PSA, Gleason score and bone scintigraphy. The prostate SUVmax was also used. Thirty-one patients demonstrated abnormal pelvic- and or extra- pelvic findings on (18)F-FECh PET/CT, which was consistent with malignant or metastatic involvement. The prostate SUVmax could not be used to predict the presence or absence of metastatic disease. Findings of this paper suggest that (18)F-FECh PET/CT in 30/40 cases (estimated as 75%) was helpful in the initial staging, restaging and lymph node detection of patients with PC. The SUVmax was not helpful. We diagnosed more PC cases in our African-American patients as compared to the Caucasian patients.

Using an AMACR (P504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens.

PubMed

Jiang, Zhong; Li, Cuizhen; Fischer, Andrew; Dresser, Karen; Woda, Bruce A

2005-02-01

We assessed the usefulness of immunohistochemical analysis with a 3-antibody cocktail (alpha-methylacyl coenzyme A racemase [AMACR, or P504S], 34betaE12, p63) and a double-chromogen reaction for detection of limited prostate cancer in 138 needle biopsy specimens, including 82 with small foci of prostatic adenocarcinoma and 56 benign prostates. When carcinoma was present, red cytoplasmic granular staining (AMACR) in the malignant glands and cells and dark brown nuclear (p63) and cytoplasmic (34betaE12) staining in basal cells of adjacent nonmalignant glands were found. Of 82 cases of small foci of prostatic adenocarcinoma, 78 (95%) expressed AMACR; all malignant glands were negative for basal cell staining. All benign glands adjacent to malignant glands were recognized easily by basal cell marker positivity and little or no AMACR expression. No benign glands were simultaneously positive for AMACR and negative for basal cell markers (specificity, 100%). There were no differences in intensity and numbers of positive glands with double-chromogen staining compared with using 1-color staining. Our results indicate that immunohistochemistry with a 3-antibody cocktail and double chromogen is a simple and easy assay that can be used as a routine test, which overcomes the problems of studying small lesions in prostate needle biopsies with multiple immunohistochemical stains.

The role of blood neutrophil count and the neutrophil-to-lymphocyte ratio as a predictive factor for prostate biopsy results.

PubMed

Kamali, Koosha; Ashrafi, Mojtaba; Shadpour, Pejman; Ameli, Mojtaba; Khayyamfar, Amirmahdi; Abolhasani, Maryam; Azizpoor, Amin

2018-04-01

It is apparent that prostate cancer has harmful effects on the erythrocytes, leucocytes, and platelets. In addition, it has been suggested that the toxic granules in neutrophils lead to inflammation in the cancerous tissues besides the activation of monocytes, so in this study we aimed to evaluate the blood neutrophil count besides the neutrophil-to-lymphocyte ratio as a predictive factor for prostate biopsy results and their relationship with prostate cancer grade in patients undergoing biopsy of the prostate. For all men with irritative lower urinary tract symptoms visiting Hasheminezhad Hospital from January to July 2015, in case of having a suspicious digital rectal examination or aged above 40 years, prostate-specific antigen was requested and in case of abnormal results, they underwent prostate biopsy. In order to examine the study hypothesis, the blood neutrophil count and the neutrophil-to-lymphocyte ratio were measured and compared with the abnormal prostate-specific antigen results and suspicious digital rectal examination. Among the 500 referred samples for biopsy, 352 (70.4%) had a negative biopsy result, while it was positive in the other 148 (29.6). The mean neutrophil count showed no statistical difference regarding the biopsy results (p = 0.381). When measuring the neutrophil-to-lymphocyte ratio again with biopsy results, no statistically significant difference was obtained based on the biopsy results (p = 0.112). Neutrophil count and neutrophil-to-lymphocyte ratio cannot be predictive factors for positive prostate cancer biopsy.

Can integrated 18F-FDG PET/MR replace sentinel lymph node resection in malignant melanoma?

PubMed

Schaarschmidt, Benedikt Michael; Grueneisen, Johannes; Stebner, Vanessa; Klode, Joachim; Stoffels, Ingo; Umutlu, Lale; Schadendorf, Dirk; Heusch, Philipp; Antoch, Gerald; Pöppel, Thorsten Dirk

2018-06-06

To compare the sensitivity and specificity of 18F-fluordesoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), 18F-FDG PET/magnetic resonance (18F-FDG PET/MR) and 18F-FDG PET/MR including diffusion weighted imaging (DWI) in the detection of sentinel lymph node metastases in patients suffering from malignant melanoma. Fifty-two patients with malignant melanoma (female: n = 30, male: n = 22, mean age 50.5 ± 16.0 years, mean tumor thickness 2.28 ± 1.97 mm) who underwent 18F-FDG PET/CT and subsequent PET/MR & DWI for distant metastasis staging were included in this retrospective study. After hybrid imaging, lymphoscintigraphy including single photon emission computed tomography/CT (SPECT/CT) was performed to identify the sentinel lymph node prior to sentinel lymph node biopsy (SLNB). In a total of 87 sentinel lymph nodes in 64 lymph node basins visible on SPECT/CT, 17 lymph node metastases were detected by histopathology. In separate sessions PET/CT, PET/MR, and PET/MR & DWI were assessed for sentinel lymph node metastases by two independent readers. Discrepant results were resolved in a consensus reading. Sensitivities, specificities, positive predictive values and negative predictive values were calculated with histopathology following SPECT/CT guided SLNB as a reference standard. Compared with histopathology, lymph nodes were true positive in three cases, true negative in 65 cases, false positive in three cases and false negative in 14 cases in PET/CT. PET/MR was true positive in four cases, true negative in 63 cases, false positive in two cases and false negative in 13 cases. Hence, we observed a sensitivity, specificity, positive predictive value and negative predictive value of 17.7, 95.6, 50.0 and 82.3% for PET/CT and 23.5, 96.9, 66.7 and 82.3% for PET/MR. In DWI, 56 sentinel lymph node basins could be analyzed. Here, the additional analysis of DWI led to two additional false positive findings, while the number of true positive findings could not be increased. In conclusion, integrated 18F-FDG PET/MR does not reliably differentiate N-positive from N-negative melanoma patients. Additional DWI does not increase the sensitivity of 18F-FDG PET/MR. Hence, sentinel lymph node biopsy cannot be replaced by 18F-FDG-PE/MR or 18F-FDG-PET/CT.

[Risk factors of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph node ≤ 2].

PubMed

Gao, Yajun; He, Yingjian; Fan, Zhaoqing; Ouyang, Tao

2014-08-13

To explore retrospectively the risk factors of non-sentinel lymph node (NSLN) metastasis in breast cancer patients with sentinel lymph node metastasis ≤ 2 and examine the likelihood of non-sentinel lymph node prediction. A sentinel lymph node biopsy database containing 455 breast cancer patients admitted between July 2005 and February 2012 at Beijing Cancer Hospital was analyzed retrospectively. The patients had ≤ 2 positive sentinel lymph node and complete axillary lymph node dissection. The SLNS⁺/SLNS ratio (P = 0.001), histological grade (P = 0.075), size of mass (P = 0.023) and onset age (P = 0.074) were correlated with NSLN metastases. Only SLNS⁺/SLNS (OR 0.502 95% CI 0.322-0.7844) , histological grade ratio (histological grade ratio II, III and others vs grade I OR 2.696, 2.102, 3.662) were significant independent predictors for NSLN metastases . The ROC value was 0.62 (0.56, 0.68). For ≤ 2 positive sentinel lymph nodes of breast cancer, ratio of SLNS⁺/SLNS and histological grading are independent factors affecting NSLN metastases. However, the results remain unsatisfactory for predicting the status of NSLN.

Extended field intensity modulated radiation therapy with concomitant boost for lymph node-positive cervical cancer: analysis of regional control and recurrence patterns in the positron emission tomography/computed tomography era.

PubMed

Vargo, John A; Kim, Hayeon; Choi, Serah; Sukumvanich, Paniti; Olawaiye, Alexander B; Kelley, Joseph L; Edwards, Robert P; Comerci, John T; Beriwal, Sushil

2014-12-01

Positron emission tomography/computed tomography (PET/CT) is commonly used for nodal staging in locally advanced cervical cancer; however the false negative rate for para-aortic disease are 20% to 25% in PET-positive pelvic nodal disease. Unless surgically staged, pelvis-only treatment may undertreat para-aortic disease. We have treated patients with PET-positive nodes with extended field intensity modulated radiation therapy (IMRT) to address the para-aortic region prophylactically with concomitant boost to involved nodes. The purpose of this study was to assess regional control rates and recurrence patterns. Sixty-one patients with cervical cancer (stage IBI-IVA) diagnosed from 2003 to 2012 with PET-avid pelvic nodes treated with extended field IMRT (45 Gy in 25 fractions with concomitant boost to involved nodes to a median of 55 Gy in 25 fractions) with concurrent cisplatin and brachytherapy were retrospectively analyzed. The nodal location was pelvis-only in 41 patients (67%) and pelvis + para-aortic in 20 patients (33%). There were a total of 179 nodes, with a median number of positive nodes of 2 (range, 1-16 nodes) per patient and a median nodal size of 1.8 cm (range, 0.7-4.5 cm). Response was assessed by PET/CT at 12 to 16 weeks. Complete clinical and imaging response at the first follow-up visit was seen in 77% of patients. At a mean follow-up time of 29 months (range, 3-116 months), 8 patients experienced recurrence. The sites of persistent/recurrent disease were as follows: cervix 10 (16.3%), regional nodes 3 (4.9%), and distant 14 (23%). The rate of para-aortic failure in patients with pelvic-only nodes was 2.5%. There were no significant differences in recurrence patterns by the number/location of nodes, largest node size, or maximum node standardized uptake value. The rate of late grade 3+ adverse events was 4%. Extended field IMRT was well tolerated and resulted in low regional recurrence in node-positive cervical cancer. The dose of 55 Gy in 25 fractions was effective in eradicating disease in involved nodes, with acceptable late adverse events. Distant metastasis is the predominant mode of failure, and the OUTBACK trial may challenge the presented paradigms. Copyright © 2014 Elsevier Inc. All rights reserved.

Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement.

PubMed

Grossman, David C; Curry, Susan J; Owens, Douglas K; Bibbins-Domingo, Kirsten; Caughey, Aaron B; Davidson, Karina W; Doubeni, Chyke A; Ebell, Mark; Epling, John W; Kemper, Alex R; Krist, Alex H; Kubik, Martha; Landefeld, C Seth; Mangione, Carol M; Silverstein, Michael; Simon, Melissa A; Siu, Albert L; Tseng, Chien-Wen

2018-05-08

In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 13%, and the lifetime risk of dying of prostate cancer is 2.5%. The median age of death from prostate cancer is 80 years. Many men with prostate cancer never experience symptoms and, without screening, would never know they have the disease. African American men and men with a family history of prostate cancer have an increased risk of prostate cancer compared with other men. To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on prostate-specific antigen (PSA)-based screening for prostate cancer. The USPSTF reviewed the evidence on the benefits and harms of PSA-based screening for prostate cancer and subsequent treatment of screen-detected prostate cancer. The USPSTF also commissioned a review of existing decision analysis models and the overdiagnosis rate of PSA-based screening. The reviews also examined the benefits and harms of PSA-based screening in patient subpopulations at higher risk of prostate cancer, including older men, African American men, and men with a family history of prostate cancer. Adequate evidence from randomized clinical trials shows that PSA-based screening programs in men aged 55 to 69 years may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 men screened. Screening programs may also prevent approximately 3 cases of metastatic prostate cancer per 1000 men screened. Potential harms of screening include frequent false-positive results and psychological harms. Harms of prostate cancer treatment include erectile dysfunction, urinary incontinence, and bowel symptoms. About 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence, and 2 in 3 men will experience long-term erectile dysfunction. Adequate evidence shows that the harms of screening in men older than 70 years are at least moderate and greater than in younger men because of increased risk of false-positive results, diagnostic harms from biopsies, and harms from treatment. The USPSTF concludes with moderate certainty that the net benefit of PSA-based screening for prostate cancer in men aged 55 to 69 years is small for some men. How each man weighs specific benefits and harms will determine whether the overall net benefit is small. The USPSTF concludes with moderate certainty that the potential benefits of PSA-based screening for prostate cancer in men 70 years and older do not outweigh the expected harms. For men aged 55 to 69 years, the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one and should include discussion of the potential benefits and harms of screening with their clinician. Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men. However, many men will experience potential harms of screening, including false-positive results that require additional testing and possible prostate biopsy; overdiagnosis and overtreatment; and treatment complications, such as incontinence and erectile dysfunction. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the balance of benefits and harms on the basis of family history, race/ethnicity, comorbid medical conditions, patient values about the benefits and harms of screening and treatment-specific outcomes, and other health needs. Clinicians should not screen men who do not express a preference for screening. (C recommendation) The USPSTF recommends against PSA-based screening for prostate cancer in men 70 years and older. (D recommendation).

Effect of family history on outcomes in patients treated with definitive brachytherapy for clinically localized prostate cancer.

PubMed

Peters, Christopher A; Stock, Richard G; Blacksburg, Seth R; Stone, Nelson N

2009-01-01

To determine the impact familial prostate cancer has on prognosis in men treated with brachytherapy for clinically localized prostate cancer. A total of 1,738 consecutive patients with prostate cancer (cT1-3, N0/X, M0) received low-dose-rate brachytherapy alone or in combination with external beam radiation therapy or hormone ablation from 1992 to 2005. The primary end-point was freedom from biochemical failure (FFBF) using the Phoenix definition. Minimum follow-up was 2 years and the median follow-up was 60 months (range, 24-197 months). A total of 187 of 1,738 men (11%) had a family history of prostate cancer in a first-degree relative. For the low-risk patients, both groups had similar actuarial 5-year FFBF (97.2% vs. 95.5%, p = 0.516). For intermediate-risk patients, there was a trend toward improved biochemical control in men positive for family history (5-yr FFBF 100% vs. 93.6%, p = 0.076). For the high-risk patients, men with a positive family history had similar 5-year FFBF (92.8% vs. 85.2%, p = 0.124). On multivariate analysis, family history was not significant; use of hormones, high biologic effective dose, initial prostate-specific antigen value, and Gleason score were the significant variables predicting biochemical control. This is the first study to examine the relationship of familial prostate cancer and outcomed in men treated with brachytherapy alone or in combination therapy. Men with a positive family history have clinicopathologic characteristics and biochemical outcomes similar to those with sporadic disease.

Obesity and Prostate Cancer Risk According to Tumor TMPRSS2:ERG Gene Fusion Status

PubMed Central

Egbers, Lieke; Luedeke, Manuel; Rinckleb, Antje; Kolb, Suzanne; Wright, Jonathan L.; Maier, Christiane; Neuhouser, Marian L.; Stanford, Janet L.

2015-01-01

The T2E gene fusion, formed by fusion of the transmembrane protease, serine 2, gene (TMPRSS2) with the erythroblast transformation-specific (ETS)-related gene (ERG), is found in approximately 50% of prostate cancers and may characterize distinct molecular subtypes of prostate cancer with different etiologies. We investigated the relationship between body mass index (BMI; weight (kg)/height (m)2) and prostate cancer risk by T2E status. Study participants were residents of King County, Washington, recruited for 2 population-based case-control studies conducted in 1993–1996 and 2002–2005. Tumor T2E status was determined for 563 prostate cancer patients who underwent radical prostatectomy. Information on weight, height, and covariables was obtained through in-person interviews. We performed polytomous logistic regression to calculate odds ratios and 95% confidence intervals for T2E-positive and -negative prostate cancer. Comparing the highest BMI quartile with the lowest, inverse associations were observed between recent (≥29.7 vs. <24.5: odds ratio = 0.66, 95% confidence interval: 0.45, 0.97) and maximum (≥31.8 vs. <25.9: odds ratio = 0.69, 95% confidence interval: 0.47, 1.02) BMI and the risk of T2E-positive prostate cancer. No significant associations were seen for men with T2E-negative tumors. This study provides evidence that obesity is specifically associated with reduced risk of developing androgen-responsive T2E fusion–positive tumors. The altered steroid hormone profile in obese men may contribute to this inverse association. PMID:25852077

DUOX enzyme activity promotes AKT signalling in prostate cancer cells.

PubMed

Pettigrew, Christopher A; Clerkin, John S; Cotter, Thomas G

2012-12-01

Reactive oxygen species (ROS) and oxidative stress are related to tumour progression, and high levels of ROS have been observed in prostate tumours compared to normal prostate. ROS can positively influence AKT signalling and thereby promote cell survival. The aim of this project was to establish whether the ROS generated in prostate cancer cells positively regulate AKT signalling and enable resistance to apoptotic stimuli. In PC3 cells, dual oxidase (DUOX) enzymes actively generate ROS, which inactivate phosphatases, thereby maintaining AKT phosphorylation. Inhibition of DUOX by diphenylene iodium (DPI), intracellular calcium chelation and small-interfering RNA (siRNA) resulted in lower ROS levels, lower AKT and glycogen synthase kinase 3β (GSK3β) phosphorylation, as well as reduced cell viability and increased susceptibility to apoptosis stimulating fragment (FAS) induced apoptosis. This report shows that ROS levels in PC3 cells are constitutively maintained by DUOX enzymes, and these ROS positively regulate AKT signalling through inactivating phosphatases, leading to increased resistance to apoptosis.

Perceived Stress in Online Prostate Cancer Community Participants: Examining Relationships with Stigmatization, Social Support Network Preference, and Social Support Seeking.

PubMed

Rising, Camella J; Bol, Nadine; Burke-Garcia, Amelia; Rains, Stephen; Wright, Kevin B

2017-06-01

Men with prostate cancer often need social support to help them cope with illness-related physiological and psychosocial challenges. Whether those needs are met depends on receiving support optimally matched to their needs. This study examined relationships between perceived stress, prostate cancer-related stigma, weak-tie support preference, and online community use for social support in a survey of online prostate cancer community participants (n = 149). Findings revealed a positive relationship between stigma and perceived stress. This relationship, however, was moderated by weak-tie support preference and online community use for social support. Specifically, stigma was positively related to perceived stress when weak-tie support was preferred. Analyses also showed a positive relationship between stigma and perceived stress in those who used their online community for advice or emotional support. Health communication scholars should work collaboratively with diagnosed men, clinicians, and online community administrators to develop online interventions that optimally match social support needs.

Variation of M3 muscarinic receptor expression in different prostate tissues and its significance.

PubMed

Song, Wei; Yuan, Mingzhen; Zhao, Shengtian

2009-08-01

To detect the expression of the muscarinic receptor (M receptor) in different prostate tissues and analyze the role of its subtype in prostatic oncogenesis. Thirty-six cases of normal prostate and benign prostatic hyperplasia, and 8 cases of prostatic tumor, were used in this study from the Shandong University, Shandong, China, between 2003-2006. The protein expressions of M1, M2, and M3 receptors in each group were determined by Western-blotting. The gene expressions of the M3 receptor and vascular endothelial growth factors (VEGF) in each group were determined by reverse transcriptase-polymerase chain reaction. The protein and gene expressions of the M3 receptor in the prostatic carcinoma group were higher than that of benign prostatic hyperplasia group (p=0.0001) and normal prostate group (p=0.0001). The M3 receptor and VEGF showed positive straight-line correlations of gene expressions with the 3 groups (r=0.4999, p=0.0001). The M3 receptor may have a close relationship with prostatic oncogenesis.

Prostate Cancer Predictive Simulation Modelling, Assessing the Risk Technique (PCP-SMART): Introduction and Initial Clinical Efficacy Evaluation Data Presentation of a Simple Novel Mathematical Simulation Modelling Method, Devised to Predict the Outcome of Prostate Biopsy on an Individual Basis.

PubMed

Spyropoulos, Evangelos; Kotsiris, Dimitrios; Spyropoulos, Katherine; Panagopoulos, Aggelos; Galanakis, Ioannis; Mavrikos, Stamatios

2017-02-01

We developed a mathematical "prostate cancer (PCa) conditions simulating" predictive model (PCP-SMART), from which we derived a novel PCa predictor (prostate cancer risk determinator [PCRD] index) and a PCa risk equation. We used these to estimate the probability of finding PCa on prostate biopsy, on an individual basis. A total of 371 men who had undergone transrectal ultrasound-guided prostate biopsy were enrolled in the present study. Given that PCa risk relates to the total prostate-specific antigen (tPSA) level, age, prostate volume, free PSA (fPSA), fPSA/tPSA ratio, and PSA density and that tPSA ≥ 50 ng/mL has a 98.5% positive predictive value for a PCa diagnosis, we hypothesized that correlating 2 variables composed of 3 ratios (1, tPSA/age; 2, tPSA/prostate volume; and 3, fPSA/tPSA; 1 variable including the patient's tPSA and the other, a tPSA value of 50 ng/mL) could operate as a PCa conditions imitating/simulating model. Linear regression analysis was used to derive the coefficient of determination (R 2 ), termed the PCRD index. To estimate the PCRD index's predictive validity, we used the χ 2 test, multiple logistic regression analysis with PCa risk equation formation, calculation of test performance characteristics, and area under the receiver operating characteristic curve analysis using SPSS, version 22 (P < .05). The biopsy findings were positive for PCa in 167 patients (45.1%) and negative in 164 (44.2%). The PCRD index was positively signed in 89.82% positive PCa cases and negative in 91.46% negative PCa cases (χ 2 test; P < .001; relative risk, 8.98). The sensitivity was 89.8%, specificity was 91.5%, positive predictive value was 91.5%, negative predictive value was 89.8%, positive likelihood ratio was 10.5, negative likelihood ratio was 0.11, and accuracy was 90.6%. Multiple logistic regression revealed the PCRD index as an independent PCa predictor, and the formulated risk equation was 91% accurate in predicting the probability of finding PCa. On the receiver operating characteristic analysis, the PCRD index (area under the curve, 0.926) significantly (P < .001) outperformed other, established PCa predictors. The PCRD index effectively predicted the prostate biopsy outcome, correctly identifying 9 of 10 men who were eventually diagnosed with PCa and correctly ruling out PCa for 9 of 10 men who did not have PCa. Its predictive power significantly outperformed established PCa predictors, and the formulated risk equation accurately calculated the probability of finding cancer on biopsy, on an individual patient basis. Copyright © 2016 Elsevier Inc. All rights reserved.

Regional lymph node staging in breast cancer: the increasing role of imaging and ultrasound-guided axillary lymph node fine needle aspiration.

PubMed

Mainiero, Martha B

2010-09-01

The status of axillary lymph nodes is a key prognostic indicator in patients with breast cancer and helps guide patient management. Sentinel lymph node biopsy is increasingly being used as a less morbid alternative to axillary lymph node dissection. However, when sentinel lymph node biopsy is positive, axillary dissection is typically performed for complete staging and local control. Axillary ultrasound and ultrasound-guided fine needle aspiration (USFNA) are useful for detecting axillary nodal metastasis preoperatively and can spare patients sentinel node biopsy, because those with positive cytology on USFNA can proceed directly to axillary dissection or neoadjuvant chemotherapy. Internal mammary nodes are not routinely evaluated, but when the appearance of these nodes is abnormal on imaging, further treatment or metastatic evaluation may be necessary. Copyright © 2010 Elsevier Inc. All rights reserved.

Does brachytherapy of the prostate affect sperm quality and/or fertility in younger men?

PubMed

Mydlo, Jack H; Lebed, Brett

2004-01-01

Sperm banking prior to surgical procedures which may affect fertility, such as retroperitoneal lymph node dissection, has been well documented. However, such procedures are usually performed in young men. With older men marrying later in life, or remarrying, we wanted to investigate the effects of radiation on prostate cancer patients who wanted to have children afterwards. We encountered several patients with prostate cancer who decided to undergo brachytherapy and were planning to have more children. We performed a search using PubMed and Ovid for the period 1966-2001 using the key words "fertility", "sperm banking", "radiation effects", "prostate cancer" and "brachytherapy". Of the four young patients we encountered who underwent brachytherapy, we found no significant change in semen parameters post-therapy, and three of them were able to father a child subsequently without any deleterious side-effects. It has been demonstrated in several reports that external-beam radiation therapy is associated with decreased spermatogenesis due to Leydig cell dysfunction and decreased serum testosterone, as well as having a direct effect on spermatogonia. However, there is a scarcity of literature discussing the effects of prostate brachytherapy on spermatogenesis as the patients involved are usually older and usually do not desire to father any more children. As I has a half-life of 60 days, we used an exposure of 10 mR/h at the symphysis pubis and used integration to find the total dose exposed to the testis as follows: Limits 14 400 to 0, S 10e (-In2/1440.Tdt) where T = 14 400 and 20.75 R = 20.75 cGy. Therefore, the total dose was 20.75 cGy x 0.91 = 18.88 cGy. This value is considered too low to have any significant effect on testicular tissues. We speculate that the effects of prostate brachytherapy on spermatogenesis in prostate cancer patients are minimal. However, due to the half-life of I, we recommend that these patients should wait for at least 3-4 months before trying to conceive. Furthermore, younger men with prostate cancer may want to consider sperm banking prior to brachytherapy if they want to have children in the future.

Predictive Factors for Nonsentinel Lymph Node Metastasis in Patients With Positive Sentinel Lymph Nodes After Neoadjuvant Chemotherapy: Nomogram for Predicting Nonsentinel Lymph Node Metastasis.

PubMed

Ryu, Jai Min; Lee, Se Kyung; Kim, Ji Young; Yu, Jonghan; Kim, Seok Won; Lee, Jeong Eon; Han, Se Hwan; Jung, Yong Sik; Nam, Seok Jin

2017-11-01

Axillary lymph node (ALN) status is an important prognostic factor for breast cancer patients. With increasing numbers of patients undergoing neoadjuvant chemotherapy (NAC), issues concerning sentinel lymph node biopsy (SLNB) after NAC have emerged. We analyzed the clinicopathologic features and developed a nomogram to predict the possibility of nonsentinel lymph node (NSLN) metastases in patients with positive SLNs after NAC. A retrospective medical record review was performed of 140 patients who had had clinically positive ALNs at presentation, had a positive SLN after NAC on subsequent SLNB, and undergone axillary lymph node dissection (ALND) from 2008 to 2014. On multivariate stepwise logistic regression analysis, pathologic T stage, lymphovascular invasion, SLN metastasis size, and number of positive SLN metastases were independent predictors for NSLN metastases (P < .05). The NAC nomogram was based on these 4 variables. A receiver operating characteristic curve was plotted, and the area under the curve (AUC) was 0.791 for the NAC nomogram. In the internal validation of performance, the AUCs for the training and test sets were 0.801 and 0.760, respectively. The nomogram was validated in an external patient cohort, with an AUC of 0.705. The Samsung Medical Center NAC nomogram was developed to predict the likelihood of additional positive NSLNs. The Samsung Medical Center NAC nomogram could provide information to surgeons regarding whether to perform additional ALND when the permanent biopsy revealed positive findings, although the intraoperative SLNB findings were negative. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical and anatomical guidelines in pelvic cancer contouring for radiotherapy treatment planning.

PubMed

Portaluri, Maurizio; Bambace, Santa; Perez, Celeste; Giuliano, Giuseppe; Angone, Grazia; Scialpi, Michele; Pili, Giorgio; Didonna, Vittorio; Alloro, Emira

2004-08-01

Many observations on potential inadequate coverage of tumour volume at risk in advanced cervical cancer (CC) when conventional radiation fields are used, have further substantiated by investigators using MRI, CT or lymphangiographic imaging. This work tries to obtain three dimensional margins by observing enlarged nodes in CT scans in order to improve pelvic nodal chains clinical target volumes (CTVs) drawing, and by looking for corroborative evidence in the literature for a better delineation of tumour CTV. Eleven consecutive patients (seven males, four females, mean age 62 years, range 43-78) with CT diagnosis of nodal involvement caused by pathologically proved carcinoma of the cervix (n = 2), carcinoma of the rectum (n = 2), carcinoma of the prostate (n = 2), non-Hodgkin lymphoma (n = 2), Hodgkin lymphoma (n = 1), carcinoma of the penis (n = 1) and carcinoma of the corpus uteri (n = 1) were retrospectively reviewed. Sixty CT scans with 67 enlarged pelvic nodes were reviewed in order to record the more proximal structures (muscle, bone, vessels, cutis or subcutis and other organs) to each enlarged node or group of nodes according to the four surfaces (anterior, lateral, posterior and medial) in a clockwise direction. A summary of the observations of each nodal chain and the number of occurrences of every marginal structure on axial CT slices is presented. Finally, simple guidelines are proposed. Tumour CTV should be based on individual tumour anatomy-mainly for lateral beams as it results from sagittal T2 weighted MRI images. Boundaries of pelvic nodes CTVs can be derived from observations of enlarged lymph nodes in CT scans.

Effect of intrafractional prostate motion on simultaneous boost intensity-modulated radiotherapy to the prostate: A simulation study based on intrafractional motion in the prone position

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ikeda, Itaru; Mizowaki, Takashi, E-mail: mizo@kuhp.kyoto-u.ac.jp; Ono, Tomohiro

2015-01-01

Although the prostate displacement of patients in the prone position is affected by respiration-induced motion, the effect of intrafractional prostate motion in the prone position during “simultaneous integrated boost intensity-modulated radiotherapy” (SIB-IMRT) is unclear. The purpose of this study was to evaluate the dosimetric effects of intrafractional motion on SIB-IMRT to a dominant intraprostatic lesion (IPL) using measured motion data of patients in a prone position, fixed with a thermoplastic shell. We obtained 2 orthogonal x-ray fluoroscopic images at the same moment every 0.2 seconds for 30 seconds before and after treatment, once weekly, from 7 patients with localized prostatemore » cancer with detectable prostatic calcification. Prostate displacements in the left-right (LR), anteroposterior (AP), and superoinferior (SI) directions were calculated using the prostatic calcification as a fiducial marker. We defined the displacement between pretreatment and posttreatment as baseline drift (BD). An SIB-IMRT plan was generated in which each IPL + 3 mm received a dose of 94.5 Gy, whereas the remainder of the prostate + 7 mm received a dose of 75.6 Gy in 9 fields. A simulated plan of dose blurring was generated by the convolution of isocenter-shifted plans using measured motion data in 30 seconds and motion in 30 seconds + distance between pretreatment and posttreatment position (BD) for each of the 7 patients. The motion in 30 seconds mainly reflected respiration-induced motion. The mean displacements of BD were 1.4 mm (− 3.1 to 8.2 mm), − 2.2 mm (− 9.1 to 1.5 mm), and − 0.3 mm (− 5.0 to 1.8 mm) in the AP, SI, and LR directions, respectively. The differences in the target coverage with V{sub 90%} of the IPL and V{sub 100%} of the prostate between the simulated plan and original plan were − 3.9% to − 0.3% and − 0.6% to 1.1% for respiration-induced motion and 3.1% to − 67.8% and 3.6% to − 13.3% for BD with respiration-induced motion, respectively. The large motion of BD resulted in an inadequate coverage by the prescribed dose of the SIB-IMRT to the IPL. A 7-mm margin is recommended when real-time tracking techniques are not applied. The effect of respiration-induced motion was small, so long as a 3-mm margin was added.« less

Partial axillary lymph node dissection inferior to the intercostobrachial nerves complements sentinel node biopsy in patients with clinically node-negative breast cancer.

PubMed

Li, Jianyi; Jia, Shi; Zhang, Wenhai; Qiu, Fang; Zhang, Yang; Gu, Xi; Xue, Jinqi

2015-06-30

The practice of breast cancer diagnosis and treatment in China varies to that in western developed countries. With the unavailability of radioactive tracer technique for sentinel lymph nodes biopsy (SLNB), using blue dye alone has been the only option in China. Also, the diagnosis of breast malignant tumor in most Chinese centres heavily relies on intraoperative instant frozen histology which is normally followed by sentinel lymph nodes mapping, SLNB and the potential breast and axillary operations in one consecutive session. This practice appears to cause a high false negative rate (FNR) for SLNB. The present study aimed to investigate the impact of the current practice in China on the accuracy of SLNB, and whether partial axillary lymph node dissection (PALND), dissection of lymph nodes inferior to the intercostobrachial nerve (ICBN), was a good complementary procedure following SLNB using blue dye. 289 patients with clinically node-negative breast cancer were identified and recruited. Tumorectomy, intraoperative instant frozen histological diagnosis, SLNB using methylene blue dye, and PALND or complete axillary node dissection (ALND) were performed in one consecutive operative session. The choice of SLNB only, SLNB followed by PALND or by ALND was based on the pre-determined protocol and preoperative choice by the patient. Clinical parameters were analyzed and survival analysis was performed. 37% patients with clinically negative nodes were found nodes positive. 59 patients with positive SLN underwent ALND, including 47 patients with up to two positive nodes which were all located inferior to the ICBN. 9 patients had failed SLNB and underwent PALND. Among them, 3 (33.3%) patients were found to have one metastatic node. 149 patients showed negative SLNB but chose PALND. Among them, 30 (20.1%), 14 (9.4) and 1 (0.7%) patients were found to have one, two and three metastatic node(s), respectively. PALND detected 48 (30.4%) patients who had either failed SLNB or negative SLNB to have additional positive nodes. All the patients with up to two positive nodes had their nodes located inferior to the ICBN. The FNR of SLNB was 43%. The accuracy rate was 58%. The follow-up ranged 12-33 months. The incidence of lymphedema for SLNB, PALND, and ALND was 0%, 0%, and 25.4%, respectively (P < 0.005). The disease-free survivals for SLNB, PALND, and ALND groups were 95.8%, 96.8%, and 94.9%, respectively (p > 0.05). Under the circumstances of current practice in China, PALND is a good complementary procedure following SLNB in clinically node-negative breast cancer.

Role of Magnetic Resonance Imaging Targeted Biopsy in Detection of Prostate Cancer Harboring Adverse Pathological Features of Intraductal Carcinoma and Invasive Cribriform Carcinoma.

PubMed

Prendeville, Susan; Gertner, Mark; Maganti, Manjula; Pintilie, Melania; Perlis, Nathan; Toi, Ants; Evans, Andrew J; Finelli, Antonio; van der Kwast, Theodorus H; Ghai, Sangeet

2018-07-01

The aim of this study was to compare biopsy detection of intraductal and cribriform pattern invasive prostate carcinoma in multiparametric magnetic resonance imaging positive and negative regions of the prostate. We queried a prospectively maintained, single institution database to identify patients who underwent multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and concurrent systematic sextant biopsy of magnetic resonance imaging negative regions between January 2013 and May 2016. All multiparametric magnetic resonance imaging targets were reviewed retrospectively by 2 readers for the PI-RADS™ (Prostate Imaging-Reporting and Data System), version 2 score, the maximum dimension, the apparent diffusion coefficient parameter and whether positive or negative on dynamic contrast enhancement sequence. Biopsy slides were reviewed by 2 urological pathologists for Gleason score/Grade Group and the presence or absence of an intraductal/cribriform pattern. A total of 154 patients were included in study. Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and systematic sextant biopsy of magnetic resonance imaging negative regions were negative for prostate carcinoma in 51 patients, leaving 103 available for the correlation of multiparametric magnetic resonance imaging and the intraductal/cribriform pattern. Prostate carcinoma was identified by multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy in 93 cases and by systematic sextant biopsy of magnetic resonance imaging negative regions in 76 (p = 0.008). Intraductal/cribriform positive tumor was detected in 23 cases, including at the multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy site in 22 and at the systematic sextant biopsy of magnetic resonance imaging negative region site in 3 (p <0.001). The intraductal/cribriform pattern was significantly associated with a PI-RADS score of 5 and a decreasing apparent diffusion coefficient value (p = 0.008 and 0.005, respectively). In 19 of the 23 cases with the intraductal/cribriform pattern prior 12-core standard systematic biopsy was negative in 8 and showed Grade Group 1 disease in 11. Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy was associated with significantly increased detection of intraductal/cribriform positive prostate carcinoma compared to systematic sextant biopsy of multiparametric magnetic resonance imaging negative regions. This supports the role of magnetic resonance imaging to enhance the detection of clinically aggressive intraductal/cribriform positive prostate carcinoma. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Pelvic Nodal Radiotherapy in Patients With Unfavorable Intermediate and High-Risk Prostate Cancer: Evidence, Rationale, and Future Directions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morikawa, Lisa K.; Memorial Sloan-Kettering Cancer Center; Roach, Mack, E-mail: mroach@radonc.ucsf.ed

2011-05-01

Over the past 15 years, there have been three major advances in the use of external beam radiotherapy in the management of men with clinically localized prostate made. They include: (1) image guided (IG) three-dimensional conformal/intensity modulated radiotherapy; (2) radiation dose escalation; and (3) androgen deprivation therapy. To date only the last of these three advances have been shown to improve overall survival. The presence of occult pelvic nodal involvement could explain the failure of increased conformality and dose escalation to prolong survival, because the men who appear to be at the greatest risk of death from clinically localized prostatemore » cancer are those who are likely to have lymph node metastases. This review discusses the evidence for prophylactic pelvic nodal radiotherapy, including the key trials and controversies surrounding this issue.« less

Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis).

PubMed

Lokant, M T; Naz, R K

2015-04-01

Prostate-specific antigen (PSA), produced by the prostate, liquefies post-ejaculate semen. PSA is detected in semen and blood. Increased circulating PSA levels indicate prostate abnormality [prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis (PTIS)], with variance among individuals. As the prostate has been proposed as an immune organ, we hypothesise that variation in PSA levels among men may be due to presence of auto-antibodies against PSA. Sera from healthy men (n = 28) and men having prostatitis (n = 25), BPH (n = 30) or PC (n = 29) were tested for PSA antibody presence using enzyme-linked immunosorbent assay (ELISA) values converted to standard deviation (SD) units, and Western blotting. Taking ≥2 SD units as cut-off for positive immunoreactivity, 0% of normal men, 0% with prostatitis, 33% with BPH and 3.45% with PC demonstrated PSA antibodies. One-way analysis of variance (anova) performed on the mean absorbance values and SD units of each group showed BPH as significantly different (P < 0.01) compared with PC and prostatitis. All others were nonsignificant (P < 0.05). Men (33%) with BPH had PSA antibodies by ELISA and Western blot. These discoveries may find clinical application in differential diagnosis among prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis. © 2014 Blackwell Verlag GmbH.

[Correlation of IL-8 and IL-6 in prostatic fluid with serum prostate-specific antigen level in patients with benign prostatic hyperplasia complicated by prostatitis].

PubMed

Ren, Xingfei; Wu, Chunlei; Yu, Qinnan; Zhu, Feng; Liu, Pei; Zhang, Huiqing

2016-01-01

To investigate the correlation of the levels of interleukin-8 (IL-8) and IL-6 in the prostatic fluid with serum levels of serum prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. A series of 211 patients undergoing surgery of BPH were divided into BPH group (n=75) and BPH with prostatitis group (n=136) according to the white blood cell count in the prostatic fluid. The clinical and laboratory findings were compared between the two groups, and stepwise regression analysis was used to assess the association of IL-8 and IL-6 with serum PSA level. No significant differences were found in age, BMI, blood pressure, blood glucose, blood lipids, IPSS score, PSA-Ratio, or prostate volume between the two groups (P<0.05). The patients with prostatitis had significantly increased serum PSA and prostate fluid IL-8 and IL-6 levels compared with those without prostatitis (P<0.001). Multiple linear regression analysis showed that IL-8 and IL-6 levels and white blood cell count in the prostatic fluid were all positively correlated with serum PSA level. Prostatitis is an important risk factor for elevated serum PSA level in patients with BPH, and both IL-8 and IL-6 levels in the prostatic fluid are correlated with serum PSA level.

Elucidation of the Molecular Mechanisms Underlying Lymph Node Metastasis in Prostate Cancer

DTIC Science & Technology

2005-10-01

overexpressed (Figure 8B). This result is significant for two reasons. First, it provides a mechanistic explanation for how FOXO-1, activated by SIRT1 ...transcription (Figure 4c). This result was confirmed when we used the dominant-negative form of SIRT1 to inhibit its activity (Figure 4d). SIRT-1DN protein... activated by SIRT1 , can act to Figure 3 (a) Androgen increases the IGF-IR protein level in LNCaP. LNCaP cells were grown in the charcoal–dextran

Bacteriological Profile of Isolates From Urine Samples in Patients of Benign Prostatic Hyperplasia and or Prostatitis Showing Lower Urinary Tract Symptoms.

PubMed

Mishra, Prem Prakash; Prakash, Ved; Singh, Kashmir; Mog, H; Agarwal, Sumit

2016-10-01

The incidence of Benign Prostatic Hyperplasia (BPH) or Prostatitis is increasing considerably worldwide. The Lower Urinary Tract Symptoms (LUTS) due to bacterial aetiology are one of the common factors for the complications among the patients. To determine the bacterial agents and their antibiotic sensitivity pattern from the urine samples of patients of BPH or Prostatitis showing symptoms of LUTS. The cross-sectional study was carried out in the Department of Microbiology of Rohilkhand Medical College and Hospital of Northern India from June 2014 to May 2015. A total of 105 urine specimens from patients of BPH and/ or Prostatitis were cultured by a semi-quantitative method. The isolated bacteria were identified by colony morphology, Gram's staining, motility and biochemical tests. Antibiotic sensitivity was done according to the CLSI 2007 guidelines by disc diffusion method. Data was analysed by SPSS and Microsoft office 2007. Proportions and percentages were used as statistical measures. The urine cultures from patients with BPH and or chronic Prostatitis, showed n=66/105 (62.85%) culture positivity. Out of 66 isolates the frequency was in following order Escherichia coli 21/66 (31.81%), Klebsiella spp 19/66 (28.78%), Staphylococcus aureus 11/66 (16.66%), Pseudomonas aeruginosa (10.60%), Proteus spp, Enterococcus spp, Acinetobacter spp and Citrobacter spp. The most susceptible 1 st , 2 nd and 3 rd line antibiotics for Gram negative isolates were ampicillin, amikacin and tigecycline respectively. Amongst the Gram positive isolates, the susceptible 1 st , 2 nd and 3 rd line antibiotics were cefoxitin, vancomycin, teicoplanin and linezolid. Multidrug resistance was seen in Escherichia coli (n=6), Klebsiella spp (n=7), Pseudomonas aeruginosa (n=4) and Staphylococcus aureus (n=3). Based on the above findings we can say that accurate aetiology of the LUTS among the patients of BPH and/or Prostatitis is warranted to initiate the therapeutic management. Based on our study we state that the prime pathogens are E.coli , Klebsiella among Gram negative isolates and S. aureus among Gram positive. The most sensitive drugs are aminoglycosides, tetracyclines and carbepenems for Gram neagtive isolates and oxazolidinones and glycopeptides among Gram positive isolates.

Targeting the Neural Microenvironment in Prostate Cancer

DTIC Science & Technology

2015-10-01

nerve-prostate cancer cell interactions. Subtask 1: Sub-aim 2.1. DRG PNI studies with DU145 prostate cancer cells (months 4-15) We have received...Subtask 2: Sub-aim 2.2. DRG PNI studies with other prostate cancer cell lines (months 12- 36) This will be carried beginning in Year 2 Subtask 3: Sub...targets of these pathways such as p70S6 kinase. We are well positioned to proceed with DRG and in vivo mouse studies as well as immunohistochemistry

[Surgery of prostate cancer: Technical principles and perioperative complications].

PubMed

Salomon, L; Rozet, F; Soulié, M

2015-11-01

To describe the surgical procedure of localized prostate cancer treated by radical prostatectomy. Bibliography search was performed from the Medline database (National Library of Medicine, PubMed) selected according to the scientific relevance. The research was focused on historic of radical prostatectomy, surgical anatomy, surgical technics of radical prostatectomy and lymph nodes excision, and complications. During the last 30 years, evolution of radical prostatectomy was important, from open to mini-invasive surgery with or without robotic assistance. Anatomical knowledge of the prostate was useful to describe the different anatomical structure as urinary sphincter and fascias, and to develop different procedure of neurovascular bundles preservation to ameliorate functional results. Complications are well-known and their taking-over more precise. Results of radical prostatectomy depend less of the surgical approach but more of the attitude of the surgeon according to the characteristics of the tumor and the functional status of the patient. Radical prostatectomy is an elaborate and challenging procedure when carcinological risk balances with functional results. Nevertheless, complications are quite rare. Improvement of results is due to adequation between surgical procedure and oncological and functional status. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

SU-G-JeP1-09: Evaluation of Transperineal Ultrasound Imaging as a Potential Solution for Target Tracking During Ablative Body Radiotherapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Najafi, M; Han, B; Hancock, S

Purpose: Prostate SABR is emerging as a clinically viable, potentially cost effective alternative to prostate IMRT but its adoption is contingent on providing solutions for accurate tracking during beam delivery. Our goal is to evaluate the performance of the Clarity Autoscan ultrasound monitoring system for inter-fractional prostate motion tracking in both phantoms and in-vivo. Methods: In-vivo evaluation was performed under IRB protocol to allow data collection in prostate patients treated with VMAT whereby prostate was imaged through the acoustic window of the perineum. The probe was placed before KV imaging and real-time tracking was started and continued until the endmore » of treatment. Initial absolute 3D positions of fiducials were estimated from KV images. Fiducial positions in MV images subsequently acquired during beam delivery were compared with predicted positions based on Clarity estimated motion. Results: Phantom studies with motion amplitudes of ±1.5, ±3, ±6 mm in lateral direction and ±2 mm in longitudinal direction resulted in tracking errors of −0.03 ± 0.3, −0.04 ± 0.6, −0.2 ± 0.9 mm, respectively, in lateral direction and −0.05 ± 0.30 mm in longitudinal direction. In phantom, measured and predicted fiducial positions in MV images were within 0.1 ± 0.6 mm. Four patients consented to participate in the study and data was acquired over a total of 140 fractions. MV imaging tracking was possible in about 75% of the time (due to occlusion of fiducials) compared to 100% with Clarity. Overall range of estimated motion by Clarity was 0 to 4.0 mm. In-vivo fiducial localization error was 1.2 ± 1.0 mm compared to 1.8 ± 1.9 mm if not taking Clarity estimated motion into account. Conclusion: Real-time transperineal ultrasound tracking reduces uncertainty in prostate position due to intrafractional motion. Research was supported by Elekta.« less

Detection of sexually transmitted pathogens in patients with chronic prostatitis/chronic pelvic pain: a prospective clinical study.

PubMed

Papeš, Dino; Pasini, Miram; Jerončić, Ana; Vargović, Martina; Kotarski, Viktor; Markotić, Alemka; Škerk, Višnja

2017-05-01

In <10% of patients with prostatitis syndrome, a causative uropathogenic organism can be detected. It has been shown that certain organisms that cause sexually transmitted infections can also cause chronic bacterial prostatitis, which can be hard to diagnose and treat appropriately because prostatic samples obtained by prostatic massage are not routinely tested to detect them. We conducted a clinical study to determine the prevalence of Chlamydia, mycoplasma, and trichomonas infection in 254 patients that were previously diagnosed and treated for chronic prostatitis/chronic pelvic pain syndrome due to negative urethral swab, urine, and prostate samples. Urethral swabs and standard Meares-Stamey four-glass tests were done. Detailed microbiological analysis was conducted to detect the above organisms. Thirty-five (13.8%) patients had positive expressed prostatic secretions/VB3 samples, of which 22 (10.1%) were sexually transmitted organisms that were not detected on previous tests.

WE-A-17A-11: Implanted Brachytherapy Seed Movement Due to Transrectal Ultrasound Probe-Induced Prostate Deformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, D; Usmani, N; Sloboda, R

Purpose: To characterize the movement of implanted brachytherapy seeds due to transrectal ultrasound probe-induced prostate deformation and to estimate the effects on prostate dosimetry. Methods: Implanted probe-in and probe-removed seed distributions were reconstructed for 10 patients using C-arm fluoroscopy imaging. The prostate was delineated on ultrasound and registered to the fluoroscopy seeds using a visible subset of seeds and residual needle tracks. A linear tensor and shearing model correlated the seed movement with position. The seed movement model was used to infer the underlying prostate deformation and to simulate the prostate contour without probe compression. Changes in prostate and surrogatemore » urethra dosimetry were calculated. Results: Seed movement patterns reflecting elastic decompression, lateral shearing, and rectal bending were observed. Elastic decompression was characterized by anterior-posterior expansion and superior-inferior and lateral contractions. For lateral shearing, anterior movement up to 6 mm was observed for extraprostatic seeds in the lateral peripheral region. The average intra-prostatic seed movement was 1.3 mm, and the residual after linear modeling was 0.6 mm. Prostate D90 increased by 4 Gy on average (8 Gy max) and was correlated with elastic decompression. For selected patients, lateral shearing resulted in differential change in D90 of 7 Gy between anterior and posterior quadrants, and increase in whole prostate D90 of 4 Gy. Urethra D10 increased by 4 Gy. Conclusion: Seed movement upon probe removal was characterized. The proposed model captured the linear correlation between seed movement and position. Whole prostate dose coverage increased slightly, due to the small but systematic seed movement associated with elastic decompression. Lateral shearing movement increased dose coverage in the anterior-lateral region, at the expense of the posterior-lateral region. The effect on whole prostate D90 was smaller due to the subset of peripheral seeds involved, but lateral shearing movement can have greater consequences for local dose coverage.« less

Axillary lymph node metastases in patients with breast carcinomas: assessment with nonenhanced versus uspio-enhanced MR imaging.

PubMed

Memarsadeghi, Mazda; Riedl, Christopher C; Kaneider, Andreas; Galid, Arik; Rudas, Margaretha; Matzek, Wolfgang; Helbich, Thomas H

2006-11-01

To prospectively assess the accuracy of nonenhanced versus ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging for depiction of axillary lymph node metastases in patients with breast carcinoma, with histopathologic findings as reference standard. The study was approved by the university ethics committee; written informed consent was obtained. Twenty-two women (mean age, 60 years; range, 40-79 years) with breast carcinomas underwent nonenhanced and USPIO-enhanced (2.6 mg of iron per kilogram of body weight intravenously administered) transverse T1-weighted and transverse and sagittal T2-weighted and T2*-weighted MR imaging in adducted and elevated arm positions. Two experienced radiologists, blinded to the histopathologic findings, analyzed images of axillary lymph nodes with regard to size, morphologic features, and USPIO uptake. A third independent radiologist served as a tiebreaker if consensus between two readers could not be reached. Visual and quantitative analyses of MR images were performed. Sensitivity, specificity, and accuracy values were calculated. To assess the effect of USPIO after administration, signal-to-noise ratio (SNR) changes were statistically analyzed with repeated-measurements analysis of variance (mixed model) for MR sequences. At nonenhanced MR imaging, of 133 lymph nodes, six were rated as true-positive, 99 as true-negative, 23 as false-positive, and five as false-negative. At USPIO-enhanced MR imaging, 11 lymph nodes were rated as true-positive, 120 as true-negative, two as false-positive, and none as false-negative. In two metastatic lymph nodes in two patients with more than one metastatic lymph node, a consensus was not reached. USPIO-enhanced MR imaging revealed a node-by-node sensitivity, specificity, and accuracy of 100%, 98%, and 98%, respectively. At USPIO-enhanced MR imaging, no metastatic lymph nodes were missed on a patient-by-patient basis. Significant interactions indicating differences in the decrease of SNR values for metastatic and nonmetastatic lymph nodes were found for all sequences (P < .001 to P = .022). USPIO-enhanced MR imaging appears valuable for assessment of axillary lymph node metastases in patients with breast carcinomas and is superior to nonenhanced MR imaging.

A New Formula for Prostate Cancer Lymph Node Risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, James B., E-mail: james.b.yu@yale.ed; Yale Cancer Center, New Haven, CT; Makarov, Danil V.

2011-05-01

Introduction: The successful treatment of prostate cancer depends on the accurate estimation of the risk of regional lymph node (LN) involvement. The Roach formula (RF) has been criticized as overestimating LN risk. A modification of the RF has been attempted by other investigators using simplified adjustment ratios: the Nguyen formula (NF). Methods and Materials: The National Cancer Institute Surveillance, Epidemiology, and End Results database was investigated for patients treated in 2004 through 2006 for whom at least 10 LN were examined at radical prostatectomy, cT1c or cT2 disease, and prostate-specific antigen (PSA) <26 ng/ml (N = 2,930). The Yale formulamore » (YF) was derived from half of the sample (n = 1,460), and validated in the other half (n = 1,470). Results: We identified 2,930 patients. Only 4.6% of patients had LN+, and 72.6% had cT1c disease. Gleason (GS) 8-10 histology was found in 14.4% of patients. The YF for prediction of %LN+ risk is [GS - 5]x [PSA/3 + 1.5 x T], where T = 0, 1, and 2 for cT1c, cT2a, and cT2b/cT2c. Within each strata of predicted %LN+ risk, the actual %LN+ was closest to the YF. Using a >15% risk as an indicator of high-risk disease, the YF had increased sensitivity (39.0% vs. 13.6%) compared with the NF, without a significant reduction in specificity (94.9% vs. 98.8%). The NF was overly restrictive of the high-risk group, with only 2% of patients having a >15% risk of LN+ by that formula. Conclusion: The YF performed better than the RF and NF and was best at differentiating patients at high risk for LN+ disease.« less

The biology and natural history of prostate cancer: a short introduction.

PubMed

Holmberg, Lars; Van Hemelrijck, Mieke

2014-01-01

This chapter aims to serve as a quick glance outlining an overall picture of mainstream thoughts, and to serve as a point of departure for more thorough discussions. The introduction of PSA testing has immensely complicated research in prostate cancer epidemiology and biology and added new clinical and biological domains. As for many cancers, age and ethnic origin are the strongest known risk factors. While migrant studies imply that environment and/or personal life style is important, epidemiological studies have failed to establish any strong leads. Despite the known androgen dependence of prostate cancer, there is little to support that circulating levels of androgens, estrogens or 5-alpha-reductase are associated with risk of developing the disease. However, a consistent finding is a positive association with levels of Insulin-like Growth Factor-1 (IGF-1). Prostate cancer is one of the cancers most strongly related to inherited susceptibility, even when taking into account that family history of prostate cancer triggers PSA testing among relatives. A number of somatic genetic alterations (amplifications, deletions, point mutations, translocations) are associated with prostate cancer risk. Findings for alterations in FASN, HPN, AMACR and MYC have been fairly consistent. Recent research shows that the notion of "hormone-independent prostate cancer" has to be revised: most prostate cancers remain dependent on androgen receptor signalling also after progression despite traditional androgen deprivation therapy. Traditional markers of stage and type of disease still play a major role for prognostication and treatment decisions. Prostate cancer is one of the few cancers where patients have been recommended watchful waiting or active surveillance. This provides opportunities for studies of natural history of the disease. The understanding of prostate cancer aetiology and natural history has progressed slowly. However, the current situation is positively challenging and opens up possibilities for fruitful research.

Bisphenol A and other environmental risk factors for prostate cancer in Hong Kong.

PubMed

Tse, Lap Ah; Lee, Priscilla Ming Yi; Ho, Wing Ming; Lam, Augustine Tsan; Lee, Man Kei; Ng, Simon Siu Man; He, Yonghua; Leung, Ka-Sing; Hartle, Jennifer C; Hu, Howard; Kan, Haidong; Wang, Feng; Ng, Chi Fai

2017-10-01

Environmental exposures are contributing factors to prostate cancer etiology, but these remain unclear. We aimed to document the associations between environmental risk factors and prostate cancer in Chinese, with special reference to bisphenol A (BPA). We recruited 431 newly diagnosed prostate cancer cases and 402 age-matched controls from Prince of Wales Hospital in Hong Kong. We obtained each participant's clinical data and epidemiological information on chronic BPA exposure and other environmental risk factors (e.g., dietary habits, occupation and shift work) using a standard questionnaire. A new assessment tool of environmental BPA exposure was developed and replicated. Multiple logistic regression analysis was performed to examine odds ratio (OR) and 95% confidence interval (95% CI) for the association of prostate cancer with a novel cumulative BPA exposure index (CBPAI) and other environmental risk factors. Weekly consumption of deep fried food (OR=1.85, 95% CI: 1.15-2.95) and pickled vegetable (OR=1.87, 95% CI: 1.07-3.28) was significantly associated with excessive prostate cancer risk. Prostate cancer was positively associated with nightshift work (OR=1.76, 95% CI: 1.07-2.89) and it was negatively associated with green tea drinking (OR=0.56, 95% CI: 0.34-0.91). There was a positive exposure-response relationship between CBPAI and prostate cancer, with the greatest and significant risk in the high versus reference category (OR=1.57, 95% CI: 1.01-2.44). Frequent consumption of deep fried food and pickled vegetable, non-habitual green tea drinking and nightshift work are the contributing risk factors to prostate cancer in Hong Kong Chinese. More importantly, this study provides the first epidemiological evidence on carcinogenicity of BPA on the human prostate. Copyright © 2017. Published by Elsevier Ltd.

[Tuberculosis of the lymphatic nodes and coexisting invasion with Toxoplasma gondii].

PubMed

Kociecka, W; Simon, E; Szymaczek-Meyer, L; Pakuła, M

Six cases of the peripheral lymphatic nodes tuberculosis with positive serologic reactions to Toxoplasma gondii antigen are presented. It was shown, that independently of a complex of clinical examinations histologic examination is decisive for the diagnosis of lymphatic nodes tuberculosis with coexisting toxoplasmosis. A positive serologic reaction with T. gondii antigen in patients with lymphatic nodes tuberculosis may reflect inactive infection with T. gondii. Use of anti-toxoplasmosis drugs may be not necessary in such cases.

Positive associations between galectin-3 and PSA levels in prostate cancer patients: a prospective clinical study-I.

PubMed

Nakajima, Kosei; Heilbrun, Lance K; Hogan, Victor; Smith, Daryn; Heath, Elisabeth; Raz, Avraham

2016-12-13

Galectin-3 (Gal-3), an oncogenic pro-inflammatory protein, has been suggested as a possible complementary diagnostic candidate to prostate specific antigen (PSA) blood test for prostate cancer patients. The presence of the proteins in the circulation (biomarkers) may elicit an intrinsic humoral immune reaction by generating autoantibodies, which consequently could alter the detection levels. Here, we report the associations of the two prostate cancer biomarkers, Gal-3 and PSA in patients at different clinical states of prostate cancer while taking into account the autoantibody levels. A blind, prospective, single institution, pilot study was conducted. A total of 95 men were classified into 5 groups: healthy controls (Group1), newly diagnosed patients (Group2), no recurrence after local therapy (Group3), rising PSA after local therapy (Group4), and metastatic patients (Group5). Gal-3 and PSA level were divided by their respective autoantibodies, which yielded relative PSA and relative Gal-3 levels. After the adjustments, Spearman's rank correlations and linear regression modeling revealed the positive associations between relative Gal-3 and relative PSA levels among all 95 men combined (rho = 0.446, P < 0.0001; fitted slope 0.448, P < 0.0001), in Group2 (rho = 0.616, P = 0.0050; fitted slope 0.438, P =0.0011), and Group3 (rho = 0.484, P = 0.0360; fitted slope 0.470, P = 0.0187). The data show positive associations of relative Gal-3 and relative PSA levels in prostate cancer patients, notably at early clinical time course. Allowing for the influence of autoantibodies, Gal-3 level might be considered as a potential biomarker since it is positively associated with PSA level.

Chronic bacterial prostatitis in men with spinal cord injury.

PubMed

Krebs, Jörg; Bartel, Peter; Pannek, Jürgen

2014-12-01

Recurrent urinary tract infections (UTI) are a major problem affecting spinal cord injury (SCI) patients and may stem from chronic bacterial prostatitis. We have therefore investigated the presence of chronic bacterial prostatitis and its role in the development of recurrent symptomatic UTI in SCI men. This study is a prospective cross-sectional investigation of bacterial prostatitis in SCI men in a single SCI rehabilitation center. In 50 men with chronic SCI presenting for a routine urologic examination, urine samples before and after prostate massage were taken for microbiologic investigation and white blood cell counting. Furthermore, patient characteristics, bladder diary details, and the annual rate of symptomatic UTI were collected retrospectively. No participant reported current symptoms of UTI or prostatitis. In most men (39/50, 78 %), the microbiologic analysis of the post-massage urine sample revealed growth of pathogenic bacteria. The majority of these men (32/39, 82 %) also presented with mostly (27/39, 69 %) the same pathogenic bacteria in the pre-massage sample. There was no significant (p = 0.48) difference in the number of symptomatic UTI in men with a positive post-massage culture compared with those with a negative culture. No significant (p = 0.67) difference in the frequency distribution of positive versus negative post-massage cultures was detected between men with recurrent and sporadic UTI. Most SCI men are affected by asymptomatic bacterial prostatitis; however, bacterial prostatitis does not play a major role in the development of recurrent UTI. The indication for antibiotic treatment of chronic bacterial prostatitis in asymptomatic SCI men with recurrent UTI is questionable.

Prostate-specific membrane antigen PET/MRI validation of MR textural analysis for detection of transition zone prostate cancer.

PubMed

Bates, Anthony; Miles, Kenneth

2017-12-01

To validate MR textural analysis (MRTA) for detection of transition zone (TZ) prostate cancer through comparison with co-registered prostate-specific membrane antigen (PSMA) PET-MR. Retrospective analysis was performed for 30 men who underwent simultaneous PSMA PET-MR imaging for staging of prostate cancer. Thirty texture features were derived from each manually contoured T2-weighted, transaxial, prostatic TZ using texture analysis software that applies a spatial band-pass filter and quantifies texture through histogram analysis. Texture features of the TZ were compared to PSMA expression on the corresponding PET images. The Benjamini-Hochberg correction controlled the false discovery rate at <5%. Eighty-eight T2-weighted images in 18 patients demonstrated abnormal PSMA expression within the TZ on PET-MR. 123 images were PSMA negative. Based on the corrected p-value of 0.005, significant differences between PSMA positive and negative slices were found for 16 texture parameters: Standard deviation and mean of positive pixels for all spatial filters (p = <0.0001 for both at all spatial scaling factor (SSF) values) and mean intensity following filtration for SSF 3-6 mm (p = 0.0002-0.0018). Abnormal expression of PSMA within the TZ is associated with altered texture on T2-weighted MR, providing validation of MRTA for the detection of TZ prostate cancer. • Prostate transition zone (TZ) MR texture analysis may assist in prostate cancer detection. • Abnormal transition zone PSMA expression correlates with altered texture on T2-weighted MR. • TZ with abnormal PSMA expression demonstrates significantly reduced MI, SD and MPP.

Correlation of human papilloma virus status with quantitative perfusion/diffusion/metabolic imaging parameters in the oral cavity and oropharyngeal squamous cell carcinoma: comparison of primary tumour sites and metastatic lymph nodes.

PubMed

Han, M; Lee, S J; Lee, D; Kim, S Y; Choi, J W

2018-05-17

To investigate the differences in perfusion/diffusion/metabolic imaging parameters according to human papilloma virus (HPV) status in the oral cavity and oropharyngeal squamous cell carcinoma (OC-OPSCC), separately in primary tumour sites and metastatic lymph nodes. This retrospective study comprised 41 patients with primary OC-OPSCCs and 29 patients with metastatic lymph nodes. The perfusion/diffusion/metabolic imaging parameters were measured at the primary tumour and the largest ipsilateral metastatic lymph node. The quantitative parameters were compared between the HPV-positive and -negative groups. The HPV-positivity was 39% (16 patients) for the primary tumours and 51.7% (15 patients) for the metastatic lymph nodes. Patients with HPV-positive tumours had a lower T stage (p=0.034). The metastatic lymph nodes for the HPV-positive patients were bulkier (p=0.016) and more frequently had cystic morphology (p=0.005). The perfusion parameters were not different, regardless of HPV status. The diffusion parameter (ADC min , p=0.011) of the metastatic lymph nodes in the HPV-positive groups was lower and metabolic parameter (metabolic tumour volume p=0.035 and total lesion glycolysis p=0.037) were higher than those in HPV-negative groups. The diffusion and metabolic parameters of metastatic lymph nodes from OC-OPSCC were different according to HPV status. The perfusion parameters did not clearly represent HPV status. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Infrequent Loss of Luminal Differentiation in Ductal Breast Cancer Metastasis

PubMed Central

Calvo, Julia; Sánchez-Cid, Lourdes; Muñoz, Montserrat; Lozano, Juan José; Thomson, Timothy M.; Fernández, Pedro L.

2013-01-01

Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and –positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes. PMID:24205108

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer

PubMed Central

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening. PMID:22076164

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer.

PubMed

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening.

Lateral decubitus position vs. lithotomy position: which is the best way to minimize patient's pain perception during transrectal prostate biopsy?

PubMed

Song, Phil Hyun; Ko, Young Hwii

2017-01-01

Considering the distinctive nature in terms of psychological stress and anal tone of position which is generally selected between lithotomy and left lateral decubitus (LLD), we postulated its effect on pain perception during biopsy, and investigated their association. A prospective study for comparison of two biopsy positions which were perform in a different working day was conducted for 208 men (lithotomy position=86, LLD=122). The decision on the position was made solely based on the patient's preference for the biopsy day, and all procedures were performed according to the identical protocol (12-core biopsy with intrarectal lidocaine gel), probe, and needle. The maximal degree of pain during the entire process was assessed using a visual analogue scale (VAS), immediately after biopsy. After propensity matching, a total of 152 patients were finally selected (lithotomy group=76, LLD=76), then peri-biopsy parameters were compared. Between groups, no differences were observed across all variables including age, obesity, prostate volume, serum PSA, international prostate symptom score, and cancer detection rate, except mean (±standard deviation) VAS score (3.89±2.01 vs. 4.58±2.22, p=0.049). VAS score showed significant association solely with patient's position (Pearson's coefficient=-0.165, p=0.042). In multiple linear regression models regarding the effect of clinical variables on VAS score, patient position was a single independent predictor favoring lithotomy position to decrease perceived pain (B=-0.928, p=0.024). These data suggest lithotomy position as a proper way to perform transrectal prostate biopsy with routine use of topical lidocaine gel in comparison with conventional LLD position. Copyright® by the International Brazilian Journal of Urology.

How accurate is our clinical prediction of "minimal prostate cancer"?

PubMed

Leibovici, Dan; Shikanov, Sergey; Gofrit, Ofer N; Zagaja, Gregory P; Shilo, Yaniv; Shalhav, Arieh L

2013-07-01

Recommendations for active surveillance versus immediate treatment for low risk prostate cancer are based on biopsy and clinical data, assuming that a low volume of well-differentiated carcinoma will be associated with a low progression risk. However, the accuracy of clinical prediction of minimal prostate cancer (MPC) is unclear. To define preoperative predictors for MPC in prostatectomy specimens and to examine the accuracy of such prediction. Data collected on 1526 consecutive radical prostatectomy patients operated in a single center between 2003 and 2008 included: age, body mass index, preoperative prostate-specific antigen level, biopsy Gleason score, clinical stage, percentage of positive biopsy cores, and maximal core length (MCL) involvement. MPC was defined as < 5% of prostate volume involvement with organ-confined Gleason score < or = 6. Univariate and multivariate logistic regression analyses were used to define independent predictors of minimal disease. Classification and Regression Tree (CART) analysis was used to define cutoff values for the predictors and measure the accuracy of prediction. MPC was found in 241 patients (15.8%). Clinical stage, biopsy Gleason's score, percent of positive biopsy cores, and maximal involved core length were associated with minimal disease (OR 0.42, 0.1, 0.92, and 0.9, respectively). Independent predictors of MPC included: biopsy Gleason score, percent of positive cores and MCL (OR 0.21, 095 and 0.95, respectively). CART showed that when the MCL exceeded 11.5%, the likelihood of MPC was 3.8%. Conversely, when applying the most favorable preoperative conditions (Gleason < or = 6, < 20% positive cores, MCL < or = 11.5%) the chance of minimal disease was 41%. Biopsy Gleason score, the percent of positive cores and MCL are independently associated with MPC. While preoperative prediction of significant prostate cancer was accurate, clinical prediction of MPC was incorrect 59% of the time. Caution is necessary when implementing clinical data as selection criteria for active surveillance.

Melatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC) Therapy.

PubMed

Liu, Vincent Wing Sun; Yau, Wing Lung; Tam, Chun Wai; Yao, Kwok-Ming; Shiu, Stephen Yuen Wing

2017-05-31

A major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7), nuclear factor-kappa B (NF-κB) was activated and could result in up-regulated interleukin ( IL ) -6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC) pathogenesis. Importantly, both AR-V7-induced NF-κB activation and IL-6 gene transcription in LNCaP and 22Rv1 cells could be inhibited by melatonin. Furthermore, stimulation of AR-V7 mRNA expression in LNCaP cells by betulinic acid, a pharmacological NF-κB activator, was reduced by melatonin treatment. Our data support the presence of bi-directional positive interactions between AR-V7 expression and NF-κB activation in CRPC pathogenesis. Of note, melatonin, by inhibiting NF-κB activation via the previously-reported MT₁ receptor-mediated antiproliferative pathway, can disrupt these bi-directional positive interactions between AR-V7 and NF-κB and thereby delay the development of castration resistance in advanced prostate cancer. Apparently, this therapeutic potential of melatonin in advanced prostate cancer/CRPC management is worth translation in the clinic via combined androgen depletion and melatonin repletion.

Melatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC) Therapy

PubMed Central

Liu, Vincent Wing Sun; Yau, Wing Lung; Tam, Chun Wai; Yao, Kwok-Ming; Shiu, Stephen Yuen Wing

2017-01-01

A major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7), nuclear factor-kappa B (NF-κB) was activated and could result in up-regulated interleukin (IL)-6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC) pathogenesis. Importantly, both AR-V7-induced NF-κB activation and IL-6 gene transcription in LNCaP and 22Rv1 cells could be inhibited by melatonin. Furthermore, stimulation of AR-V7 mRNA expression in LNCaP cells by betulinic acid, a pharmacological NF-κB activator, was reduced by melatonin treatment. Our data support the presence of bi-directional positive interactions between AR-V7 expression and NF-κB activation in CRPC pathogenesis. Of note, melatonin, by inhibiting NF-κB activation via the previously-reported MT1 receptor-mediated antiproliferative pathway, can disrupt these bi-directional positive interactions between AR-V7 and NF-κB and thereby delay the development of castration resistance in advanced prostate cancer. Apparently, this therapeutic potential of melatonin in advanced prostate cancer/CRPC management is worth translation in the clinic via combined androgen depletion and melatonin repletion. PMID:28561752

Comparison of Positron Emission Tomography Scanning and Sentinel Node Biopsy in the Detection of Inguinal Node Metastases in Patients With Anal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mistrangelo, Massimiliano, E-mail: mistrangelo@katamail.co; Centre of Minimally Invasive Surgery, University of Turin; Pelosi, Ettore

2010-05-01

Background: Inguinal lymph node metastases in patients with anal cancer are an independent prognostic factor for local failure and overall mortality. Inguinal lymph node status can be adequately assessed with sentinel node biopsy, and the radiotherapy strategy can subsequently be changed. We compared this technique vs. dedicated 18F-fluorodeoxyglucose positron emission tomography (PET) to determine which was the better tool for staging inguinal lymph nodes. Methods and Materials: In our department, 27 patients (9 men and 18 women) underwent both inguinal sentinel node biopsy and PET-CT. PET-CT was performed before treatment and then at 1 and 3 months after treatment. Results:more » PET-CT scans detected no inguinal metastases in 20 of 27 patients and metastases in the remaining 7. Histologic analysis of the sentinel lymph node detected metastases in only three patients (four PET-CT false positives). HIV status was not found to influence the results. None of the patients negative at sentinel node biopsy developed metastases during the follow-up period. PET-CT had a sensitivity of 100%, with a negative predictive value of 100%. Owing to the high number of false positives, PET-CT specificity was 83%, and positive predictive value was 43%. Conclusions: In this series of patients with anal cancer, inguinal sentinel node biopsy was superior to PET-CT for staging inguinal lymph nodes.« less

A reported 20-gene expression signature to predict lymph node-positive disease at radical cystectomy for muscle-invasive bladder cancer is clinically not applicable.

PubMed

van Kessel, Kim E M; van de Werken, Harmen J G; Lurkin, Irene; Ziel-van der Made, Angelique C J; Zwarthoff, Ellen C; Boormans, Joost L

2017-01-01

Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) provides a small but significant survival benefit. Nevertheless, controversies on applying NAC remain because the limited benefit must be weight against chemotherapy-related toxicity and the delay of definitive local treatment. Therefore, there is a clear clinical need for tools to guide treatment decisions on NAC in MIBC. Here, we aimed to validate a previously reported 20-gene expression signature that predicted lymph node-positive disease at radical cystectomy in clinically node-negative MIBC patients, which would be a justification for upfront chemotherapy. We studied diagnostic transurethral resection of bladder tumors (dTURBT) of 150 MIBC patients (urothelial carcinoma) who were subsequently treated by radical cystectomy and pelvic lymph node dissection. RNA was isolated and the expression level of the 20 genes was determined on a qRT-PCR platform. Normalized Ct values were used to calculate a risk score to predict the presence of node-positive disease. The Cancer Genome Atlas (TCGA) RNA expression data was analyzed to subsequently validate the results. In a univariate regression analysis, none of the 20 genes significantly correlated with node-positive disease. The area under the curve of the risk score calculated by the 20-gene expression signature was 0.54 (95% Confidence Interval: 0.44-0.65) versus 0.67 for the model published by Smith et al. Node-negative patients had a significantly lower tumor grade at TURBT (p = 0.03), a lower pT stage (p<0.01) and less frequent lymphovascular invasion (13% versus 38%, p<0.01) at radical cystectomy than node-positive patients. In addition, in the TCGA data, none of the 20 genes was differentially expressed in node-negative versus node-positive patients. We conclude that a 20-gene expression signature developed for nodal staging of MIBC at radical cystectomy could not be validated on a qRT-PCR platform in a large cohort of dTURBT specimens.

CD8+ T-cell responses rapidly select for antigen-negative tumor cells in the prostate.

PubMed

Bak, S Peter; Barnkob, Mike Stein; Wittrup, K Dane; Chen, Jianzhu

2013-12-01

Stimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respectively. However, the long-term effects of immune responses on selection and outgrowth of antigen-negative tumor cells in specific tumor types must be determined to understand and achieve long-term therapeutic effects. In this study, we have investigated the expression of a tumor-specific antigen in situ after treatment with tumor-specific CD8(+) T cells in an autochthonous mouse model of prostate cancer. After T-cell treatment, aggregates of dead antigen-positive tumor cells were concentrated in the lumen of the prostate gland and were eventually eliminated from the prostate tissue. Despite the elimination of antigen-positive tumor cells, prostate tumor continued to grow in T-cell-treated mice. Interestingly, the remaining tumor cells were antigen negative and downregulated MHC class I expression. These results show that CD8(+) T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells. These findings provide insights into the requirements for an effective cancer immunotherapy within the prostate that not only induces potent immune responses but also avoids selection and outgrowth of antigen-negative tumor cells. ©2013 AACR.

Psychological Characteristics and Traits for Finding Benefit From Prostate Cancer: Correlates and Predictors.

PubMed

Pascoe, Elizabeth C; Edvardsson, David

Although beginning evidence suggests that the capacity to derive benefit from cancer-associated experiences may be influenced by some individual psychological characteristics and traits, little is known about predictors for finding benefit from prostate cancer. The aim of this study was to explore the correlates and predictors for finding benefit from prostate cancer among a sample of men undergoing androgen deprivation. Pearson correlation and multiple linear regression modeling were performed on data collected in an acute tertiary hospital outpatient setting (N = 209) between July 2011 and December 2013 to determine correlates and predictors for finding benefit from prostate cancer. Multiple linear regression modeling showed that while the 6 predictors of self-reported coping, depression, anxiety, distress, resilience, and hope explained 38% of the variance in finding benefit, coping provided the strongest and statistically significant predictive contribution. Self-reported coping was strongly predictive of finding benefit from prostate cancer, but questions remain about if subtypes of coping strategies can be more or less predictive of finding benefit. Self-reported levels of depression, anxiety, distress, resilience, and hope had a less predictive and nonsignificant role in finding benefit from prostate cancer and raise questions about their function in this subpopulation. The findings suggest that coping strategies can maximize finding benefit from prostate cancer. Knowledge of influential coping strategies for finding benefit from prostate cancer can be immensely valuable to support men in rebuilding positive meaning amid a changed illness reality. Developing practice initiatives that foster positive meaning-making coping strategies seems valuable.

Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression.

PubMed

Zhang, Yajia; Pitchiaya, Sethuramasundaram; Cieślik, Marcin; Niknafs, Yashar S; Tien, Jean C-Y; Hosono, Yasuyuki; Iyer, Matthew K; Yazdani, Sahr; Subramaniam, Shruthi; Shukla, Sudhanshu K; Jiang, Xia; Wang, Lisha; Liu, Tzu-Ying; Uhl, Michael; Gawronski, Alexander R; Qiao, Yuanyuan; Xiao, Lanbo; Dhanasekaran, Saravana M; Juckette, Kristin M; Kunju, Lakshmi P; Cao, Xuhong; Patel, Utsav; Batish, Mona; Shukla, Girish C; Paulsen, Michelle T; Ljungman, Mats; Jiang, Hui; Mehra, Rohit; Backofen, Rolf; Sahinalp, Cenk S; Freier, Susan M; Watt, Andrew T; Guo, Shuling; Wei, John T; Feng, Felix Y; Malik, Rohit; Chinnaiyan, Arul M

2018-06-01

The androgen receptor (AR) plays a critical role in the development of the normal prostate as well as prostate cancer. Using an integrative transcriptomic analysis of prostate cancer cell lines and tissues, we identified ARLNC1 (AR-regulated long noncoding RNA 1) as an important long noncoding RNA that is strongly associated with AR signaling in prostate cancer progression. Not only was ARLNC1 induced by the AR protein, but ARLNC1 stabilized the AR transcript via RNA-RNA interaction. ARLNC1 knockdown suppressed AR expression, global AR signaling and prostate cancer growth in vitro and in vivo. Taken together, these data support a role for ARLNC1 in maintaining a positive feedback loop that potentiates AR signaling during prostate cancer progression and identify ARLNC1 as a novel therapeutic target.

[Sentinel lymph node metastasis in patients with ductal breast carcinoma in situ].

PubMed

Ruvalcaba-Limón, Eva; de Jesús Garduño-Raya, María; Bautista-Piña, Verónica; Trejo-Martínez, Claudia; Maffuz-Aziz, Antonio; Rodríguez-Cuevas, Sergio

2014-01-01

Sentinel lymph node biopsy in patients with ductal carcinoma in situ still controversial, with positive lymph node in range of 1.4-12.5% due occult invasive breast carcinoma in surgical specimen. To know the frequency of sentimel node metastases in patients with ductal carcinoma in situ, identify differences between positive and negative cases. Retrospective study of patients with ductal carcinoma in situ treated with sentinel lymph node biopsy because mastectomy indication, palpable tumor, radiological lesion = 5 cm, non-favorable breast-tumor relation and/or patients whom surgery could affect lymphatic flow drainage. Of 168 in situ carcinomas, 50 cases with ductal carcinoma in situ and sentinel lymph node biopsy were included, with a mean age of 51.6 years, 30 (60%) asymptomatic. The most common symptoms were palpable nodule (18%), nipple discharge (12%), or both (8%). Microcalcifications were common (72%), comedonecrosis pattern (62%), grade-2 histology (44%), and 28% negative hormonal receptors. Four (8%) cases had intra-operatory positive sentinel lymph node and one patient at final histo-pathological study (60% micrometastases, 40% macrometastases), all with invasive carcinoma in surgical specimen. Patients with intra-operatory positive sentinel lymph node where younger (44.5 vs 51 years), with more palpable tumors (50% vs 23.1%), and bigger (3.5 vs 2 cm), more comedonecrosis pattern (75% vs 60.8%), more indifferent tumors (75% vs 39.1%), and less cases with hormonal receptors (50% vs 73.9%), compared with negative sentinel lymph node cases, all these differences without statistic significance. One of each 12 patients with ductal carcinoma in situ had affection in sentinel lymph node, so we recommend continue doing this procedure to avoid second surgeries due the presence of occult invasive carcinoma.

Sentinel lymph node biopsy is indicated for patients with thick clinically lymph node-negative melanoma.

PubMed

Yamamoto, Maki; Fisher, Kate J; Wong, Joyce Y; Koscso, Jonathan M; Konstantinovic, Monique A; Govsyeyev, Nicholas; Messina, Jane L; Sarnaik, Amod A; Cruse, C Wayne; Gonzalez, Ricardo J; Sondak, Vernon K; Zager, Jonathan S

2015-05-15

Sentinel lymph node biopsy (SLNB) is indicated for the staging of clinically lymph node-negative melanoma of intermediate thickness, but its use is controversial in patients with thick melanoma. From 2002 to 2012, patients with melanoma measuring ≥4 mm in thickness were evaluated at a single institution. Associations between survival and clinicopathologic characteristics were explored. Of 571 patients with melanomas measuring ≥4 mm in thickness and no distant metastases, the median age was 66 years and 401 patients (70.2%) were male. The median Breslow thickness was 6.2 mm; the predominant subtype was nodular (45.4%). SLNB was performed in 412 patients (72%) whereas 46 patients (8.1%) presented with clinically lymph node-positive disease and 113 patients (20%) did not undergo SLNB. A positive SLN was found in 161 of 412 patients (39.1%). For SLNB performed at the study institution, 14 patients with a negative SLNB developed disease recurrence in the mapped lymph node basin (false-negative rate, 12.3%). The median disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) for the entire cohort were 62.1 months, 42.5 months, and 21.2 months, respectively. The DSS and OS for patients with a negative SLNB were 82.4 months and 53.4 months, respectively; 41.2 months and 34.7 months, respectively, for patients with positive SLNB; and 26.8 months and 22 months, respectively, for patients with clinically lymph node-positive disease (P<.0001). The median RFS was 32.4 months for patients who were SLNB negative, 14.3 months for patients who were SLNB positive, and 6.8 months for patients with clinically lymph node-positive disease (P<.0001). With an acceptably low false-negative rate, patients with thick melanoma and a negative SLNB appear to have significantly prolonged RFS, DSS, and OS compared with those with a positive SLNB. Therefore, SLNB should be considered as indicated for patients with thick, clinically lymph node-negative melanoma. © 2015 American Cancer Society.

Does debulking of enlarged positive lymph nodes improve survival in different gynaecological cancers?

PubMed

Somashekhar, S P

2015-08-01

Lymph-node-positive gynaecological cancers remain a pharmacotherapeutic challenge, and patients with lymph-node-positive gynaecological cancers have poor survival. The purpose of this review is to determine whether a survival advantage arises from surgical debulking of enlarged positive lymph nodes in different types of gynaecological cancers. Information from studies published on the survival benefits from debulking lymph nodes in gynaecological cancers was investigated. Pertaining to therapeutic lymphadenectomy, survival benefit can be analysed in two ways, direct survival benefit following therapeutic lymphadenectomy of bulky positive metastatic lymph nodes and indirect survival benefit, which results after a sequela of systematic lymphadenectomy, proper, accurate staging of disease and stage migration and tailor-made adjuvant treatment. The direct hypothesis of therapeutic lymphadenectomy and survival benefit has been prospected in cervical cancers and vulval cancers and in post-chemotherapy residual paraarotic nodal mass in germ cell ovarian cancer. The indirect survival benefit of therapeutic paraarotic lymphadenectomy in high-risk endometrial cancers and advanced epithelial ovarian cancers needs to be tested in randomized controlled trials. More randomized controlled trials are required to investigate this research question. Further, indirect benefit due to tailor-made adjuvant treatment, secondary to accurate staging achieved as a sequela of systematic lymphadenectomy, needs to be analysed in future trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR).

PubMed

Sarkar, F H; Sakr, W A; Li, Y W; Sreepathi, P; Crissman, J D

1993-01-01

Human papillomavirus (HPV) infections are strongly linked to the pathogenesis of uterine cervical neoplasms, and have been implicated in other cancers of the female genital tract. In contrast, the association of HPV with the cancers of the male urogenital tract is less evident, except in anal and penile cancers. However, recent studies reporting the prevalence of HPV infections in human prostate cancers (60-100% HPV 16 positive vs. no infection of HPV) have raised controversies regarding the prevalence of HPV in benign and neoplastic human prostate. We investigated the prevalence of HPV infections in prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinomas in 23 surgically resected prostates. Polymerase chain reaction (PCR) was used to amplify HPV 6b/11, 16, and 18 specific DNA sequences, using type specific HPV primers selected from the transforming gene E6-E7. The areas of PIN and cancer in 6 microns H&E stained tissue sections were identified, and respective areas of PIN and cancer were isolated from the adjacent serial sections and used for DNA amplification and HPV detection (Fig. 1). Our results demonstrated the presence of HPV 16 in three carcinomas (13%), using type specific primers in PCR amplified samples. We were not able to demonstrate the presence of other HPV types (HPV 6b/11 or HPV 18) in any of the samples using specific primers. Two of these prostates showed relatively strong positive signals by dot blot analysis, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. One more sample showed weak positivity, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. Subsequently, we have confirmed these results by Southern hybridization of the samples transferred to nylon membrane after agarose gel electrophoresis and detected by HPV 16 type specific oligonucleotide probe, using chemiluminescent assay. We, therefore, conclude that HPV infections of the prostate in general are not as common as has been previously claimed by other investigators.

Protein arginine methyltransferase 5 functions as an epigenetic activator of the androgen receptor to promote prostate cancer cell growth.

PubMed

Deng, X; Shao, G; Zhang, H-T; Li, C; Zhang, D; Cheng, L; Elzey, B D; Pili, R; Ratliff, T L; Huang, J; Hu, C-D

2017-03-02

Protein arginine methyltransferase 5 (PRMT5) is an emerging epigenetic enzyme that mainly represses transcription of target genes via symmetric dimethylation of arginine residues on histones H4R3, H3R8 and H2AR3. Accumulating evidence suggests that PRMT5 may function as an oncogene to drive cancer cell growth by epigenetic inactivation of several tumor suppressors. Here, we provide evidence that PRMT5 promotes prostate cancer cell growth by epigenetically activating transcription of the androgen receptor (AR) in prostate cancer cells. Knockdown of PRMT5 or inhibition of PRMT5 by a specific inhibitor reduces the expression of AR and suppresses the growth of multiple AR-positive, but not AR-negative, prostate cancer cells. Significantly, knockdown of PRMT5 in AR-positive LNCaP cells completely suppresses the growth of xenograft tumors in mice. Molecular analysis reveals that PRMT5 binds to the proximal promoter region of the AR gene and contributes mainly to the enriched symmetric dimethylation of H4R3 in the same region. Mechanistically, PRMT5 is recruited to the AR promoter by its interaction with Sp1, the major transcription factor responsible for AR transcription, and forms a complex with Brg1, an ATP-dependent chromatin remodeler, on the proximal promoter region of the AR gene. Furthermore, PRMT5 expression in prostate cancer tissues is significantly higher than that in benign prostatic hyperplasia tissues, and PRMT5 expression correlates positively with AR expression at both the protein and mRNA levels. Taken together, our results identify PRMT5 as a novel epigenetic activator of AR in prostate cancer. Given that inhibiting AR transcriptional activity or androgen synthesis remains the major mechanism of action for most existing anti-androgen agents, our findings also raise an interesting possibility that targeting PRMT5 may represent a novel approach for prostate cancer treatment by eliminating AR expression.

Efficacy of Sentinel Lymph Node Biopsy in Detecting Axillary Metastasis in Breast Cancer Using Methylene Blue.

PubMed

Nandu, Vipul V; Chaudhari, Milind S

2017-06-01

Breast cancer is the leading malignancy and the second leading cause of cancer-related deaths. Axillary lymph node status is a very important prognostic factor in breast cancer patients; nodal evaluation is therefore a critical part of breast cancer management. Axillary lymph node dissection results in significant morbidity. Sentinel lymph node biopsy (SLNB) is being used in many centers to stage the axilla in planning axillary dissection management of patients and hence plays an important part in reducing morbidity among patients with carcinoma breast. The objectives of this paper is to study the (1) efficacy of sentinel lymph node biopsy in detecting axillary metastasis, (2) location of sentinel lymph node in the axilla, (3) rate of involvement of sentinel lymph nodes, and (4) incidence of skip metastasis. Thirty-five patients with breast cancer with clinically node-negative axilla were selected for the study. Methylene blue dye was injected intralesional and perilesional 20 min prior to surgery. All patients underwent modified radical mastectomy with sentinel lymph node biopsy and axillary dissection and after pathological examination diagnostic statics, namely sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were computed. Sentinel lymph node was identified in all of these patients. Sixty percent patients had pathologically positive lymph nodes in the axilla. 90.48% patients of these had sentinel lymph nodes positive for malignant cells. Incidence of skip metastasis is 9.52%. 88.57% patients had sentinel lymph node mapped to level I lymph nodes. Sensitivity of SLNB is 90.48%, specificity is 85.71%, PPV of is 90.48%, NPV is 85.71%, and accuracy is 88.57%. Sentinel lymph node biopsy is an effective method of staging the axilla and deciding on axillary clearance in patients of carcinoma breast. Unnecessary axillary dissection and associated complications can be prevented in most of patients due to sentinel lymph node biopsy.

Contribution of Caudal Müllerian Duct Mesenchyme to Prostate Development

PubMed Central

Brechka, Hannah; McAuley, Erin M.; Lamperis, Sophia M.; Paner, Gladell P.

2016-01-01

A fundamental understanding of prostate development and tissue homeostasis has the high potential to reveal mechanisms for prostate disease initiation and identify novel therapeutic approaches for disease prevention and treatment. Our current understanding of prostate lineage specification stems from the use of developmental model systems that rely upon the embryonic preprostatic urogenital sinus mesenchyme to induce the formation of mature prostate epithelial cells. It is unclear, however, how the urogenital sinus epithelium can derive both adult urethral glands and prostate epithelia. Furthermore, the vast disparity in disease initiation between these two glands highlights key developmental factors that predispose prostate epithelia to hyperplasia and cancer. In this study we demonstrate that the caudal Müllerian duct mesenchyme (CMDM) drives prostate epithelial differentiation and is a key determinant in cell lineage specification between urethral glands and prostate epithelia. Utilizing both human embryonic stem cells and mouse embryonic tissues, we document that the CMDM is capable of inducing the specification of androgen receptor, prostate-specific antigen, NKX3.1, and Hoxb13-positive prostate epithelial cells. These results help to explain key developmental differences between prostate and urethral gland differentiation, and implicate factors secreted by the caudal Müllerian duct as novel targets for prostate disease prevention and treatment. PMID:27595922