Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer.

PubMed

Cherrier, M M; Cross, D J; Higano, C S; Minoshima, S

2018-04-27

Androgen deprivation therapy (ADT) is a common treatment option for men with biochemical relapse from prostate cancer. ADT is associated with changes in mood, cognition, and quality of life, and most recently with increased risk for Alzheimer's disease (AD). This study examined changes in brain metabolism using positron emission tomography (PET) in men undergoing intermittent ADT. Nine men with prostate cancer and a rising PSA (biochemical recurrence) without evidence of metastases were treated with intermittent ADT consisting of 9 months of complete androgen blockade achieved with combined leuprolide acetate and flutamide. Patients underwent resting [Fuorine-18] fluorodeoxyglucose PET ( 18 F-FDGPET) at baseline (before treatment) and again after 9 months of ADT. Whole-brain mapping analysis after 9 months of androgen deprivation compared to pretreatment baseline revealed decreased regional cerebral glucose metabolism in the cerebellum, posterior cingulate, and medial thalamus bilaterally. Associations of brain metabolism with measurements of cognition and mood while on androgen deprivation revealed positive correlations between the posterior cingulate, left inferior parietal lobule (BA40), and left mid temporal gyrus (BA39) and spatial reasoning and a negative correlation between left inferior parietal lobule and verbal memory. Several mood indices were negatively correlated with hypothalamus and brainstem. These findings suggest that complete androgen deprivation may result in changes in regional brain metabolism associated with variation in mood, verbal memory, and spatial performance. Brain regions that were impacted from ADT are similar and overlap with brain regions with metabolic decline found in early AD and diabetes, suggesting possible common mechanisms.

Long-term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer.

PubMed

Shrestha, Bikram; Sun, Yifei; Faisal, Farzana; Kim, Victoria; Soares, Kevin; Blair, Alex; Herman, Joseph M; Narang, Amol; Dholakia, Avani S; Rosati, Lauren; Hacker-Prietz, Amy; Chen, Linda; Laheru, Daniel A; De Jesus-Acosta, Ana; Le, Dung T; Donehower, Ross; Azad, Nilofar; Diaz, Luis A; Murphy, Adrian; Lee, Valerie; Fishman, Elliot K; Hruban, Ralph H; Liang, Tingbo; Cameron, John L; Makary, Martin; Weiss, Matthew J; Ahuja, Nita; He, Jin; Wolfgang, Christopher L; Huang, Chiung-Yu; Zheng, Lei

2017-07-01

The use of neoadjuvant chemotherapy or radiation for borderline resectable pancreatic adenocarcinoma (BL-PDAC) is increasing. However, the impact of neoadjuvant chemotherapy and radiation therapy on the outcome of BL-PDAC remains to be elucidated. We performed a retrospective analysis of 93 consecutive patients who were diagnosed with BL-PDAC and primarily followed at Johns Hopkins Hospital between February 2007 and December 2012. Among 93 patients, 62% received upfront neoadjuvant chemotherapy followed by chemoradiation, whereas 20% received neoadjuvant chemoradiation alone and 15% neoadjuvant chemotherapy alone. Resectability following all neoadjuvant therapy was 44%. Patients who underwent resection with a curative intent had a median overall survival (mOS) of 25.8 months, whereas those who did not undergo surgery had a mOS of 11.9 months. However, resectability and overall survival were not significantly different between the three types of neoadjuvant therapy. Nevertheless, 22% (95% CI, 0.13-0.36) of the 58 patients who received upfront chemotherapy followed by chemoradiation remained alive for a minimum of 48 months compared to none of the 19 patients who received upfront chemoradiation. Among patients who underwent curative surgical resection, 32% (95% CI, 0.19-0.55) of those who received upfront chemotherapy remained disease free at least 48 months following surgical resection, whereas none of the eight patients who received upfront chemoradiation remained disease free beyond 24 months following surgical resection. Neoadjuvant therapy with upfront chemotherapy may result in long-term survival in a subpopulation of patients with BL-PDAC. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

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

Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley

Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years. Results: The 5-more » and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p = 0.002). In a multivariate analysis, statin use (hazard ratio [HR]0.69, p = 0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p = 0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p = 0.51). On multivariate analysis, lower NCCN risk group (p = 0.01) and ADT use (p = 0.005) predicted improved DMFS. Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer.« less

Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Department of Medicine; Department of Biostatistics and Computational Biology; Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston; Johns Hopkins University, Baltimore; University of Wisconsin Carbone Cancer Center; School of Medicine and Public Health; Madison; Fox Chase Cancer Center, Temple University Health System, Philadelphia; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis; Mayo Clinic, Rochester, MN; University Hospitals Case Medical Center, Seidman Cancer Center; Cleveland Clinic Taussig Cancer Institute; Both in Cleveland; University of Virginia Cancer Center, Charlottesville; Comprehensive Cancer Centers of Nevada, Las Vegas; Siteman Cancer Center, Washington University School of Medicine, St. Louis; NorthShore University Health System, Evanston, IL; University of Michigan Comprehensive Cancer Center, Ann Arbor; Rutgers Cancer Institute of New Jersey, New Brunswick.N Engl J Med. 2015 Aug 20;373(8):737-46. [Epub 2015 Aug 5]. doi: 10.1056/NEJMoa1503747.

PubMed

Scott, Eggener

2017-03-01

Androgen deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone. We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75mg per square meter of body-surface area every 3wk for 6 cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone. A total of 790 patients (median age, 63y) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 vs. 44.0mo; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI]: 0.47-0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI: 0.51-0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2ng/ml at 12 months was 27.7% in the combination group vs. 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%. Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.). Copyright © 2017. Published by Elsevier Inc.

Neoadjuvant chemotherapy for brain tumors in infants and young children.

PubMed

Iwama, Junya; Ogiwara, Hideki; Kiyotani, Chikako; Terashima, Keita; Matsuoka, Kentaro; Iwafuchi, Hideto; Morota, Nobuhito

2015-05-01

Because of their large size and high vascularity, complete removal of brain tumors in infants and young children is often difficult. In most cases the degree of resection is associated with prognosis. Neoadjuvant chemotherapy may facilitate resection by reducing the vascularity of the tumor. The authors evaluated the effectiveness of neoadjuvant chemotherapy in the management of these tumors. The authors performed a retrospective review of infants and young children who underwent tumor removal after neoadjuvant chemotherapy. Nine consecutive patients underwent resection after neoadjuvant chemotherapy during the period February 2004 to December 2012. The mean age at diagnosis was 18 months (range 2-50 months). The average largest tumor diameter was 71 mm (range 30-130 mm) at initial surgery. Five patients underwent partial resection, and 4 underwent biopsy as the initial surgery. The histopathological diagnoses were ependymoma in 2 patients, anaplastic ependymoma in 1, primitive neuroectodermal tumor (PNET) in 2, choroid plexus carcinoma in 1, atypical teratoid/rhabdoid tumor (AT/RT) in 1, glioblastoma in 1, and embryonal tumor with abundant neuropil and true rosettes in 1. After 2-4 courses of multiagent chemotherapy (mainly with vincristine, cyclophosphamide, etoposide, and cisplatin), the second-look surgery was performed. In 1 patient with a PNET, intratumoral hemorrhage was observed after 2 courses of chemotherapy. The mean interval between the initial and the second-look surgery was 3 months. The tumor volume was reduced to varying degrees in 5 patients (56%) after chemotherapy. Intraoperatively, the vascularity of the tumor was considerably reduced, and the tumor was more circumscribed in all cases. Gross-total resection was achieved in 8 patients (89%) and neartotal resection in 1 (11%). Histopathological examination demonstrated fibrotic tissue circumscribing the tumor in 6 of 9 cases (67%). The average blood loss was 20% of the estimated blood volume, and 3 patients (33%) required a blood transfusion. There was no surgical mortality. One patient had transient dysphasia postoperatively. The mean follow-up period was 28 months. At the last follow-up, 2 patients (22%) had died (1 died of tumor progression and 1 of sepsis), and 4 patients (44%) had no tumor recurrence. Neoadjuvant chemotherapy for brain tumors in infants and young children was effective in reduction of tumor vascularity and clarification of the tumor-brain interface, which significantly facilitated maximal tumor resection.

Circumferential resection margin (CRM) positivity after MRI assessment and adjuvant treatment in 189 patients undergoing rectal cancer resection.

PubMed

Simpson, G S; Eardley, N; McNicol, F; Healey, P; Hughes, M; Rooney, P S

2014-05-01

The management of rectal cancer relies on accurate MRI staging. Multi-modal treatments can downstage rectal cancer prior to surgery and may have an effect on MRI accuracy. We aim to correlate the findings of MRI staging of rectal cancer with histological analysis, the effect of neoadjuvant therapy on this and the implications of circumferential resection margin (CRM) positivity following neoadjuvant therapy. An analysis of histological data and radiological staging of all cases of rectal cancer in a single centre between 2006 and 2011 were conducted. Two hundred forty-one patients had histologically proved rectal cancer during the study period. One hundred eighty-two patients underwent resection. Median age was 66.6 years, and male to female ratio was 13:5. R1 resection rate was 11.1%. MRI assessments of the circumferential resection margin in patients without neoadjuvant radiotherapy were 93.6 and 88.1% in patients who underwent neoadjuvant radiotherapy. Eighteen patients had predicted positive margins following chemoradiotherapy, of which 38.9% had an involved CRM on histological analysis. MRI assessment of the circumferential resection margin in rectal cancer is associated with high accuracy. Neoadjuvant chemoradiotherapy has a detrimental effect on this accuracy, although accuracy remains high. In the presence of persistently predicted positive margins, complete resection remains achievable but may necessitate a more radical approach to resection.

Lymph node metastases near the celiac trunk should be considered separately from other nodal metastases in patients with cancer of the esophagus or gastroesophageal junction after neoadjuvant treatment and surgery

PubMed Central

Lagarde, Sjoerd M.; Anderegg, Martinus C. J.; Gisbertz, Suzanne S.; Meijer, Sybren L.; Hulshof, Maarten C. C. M.; Bergman, Jacques J. G. H. M.; van Laarhoven, Hanneke W. M.

2018-01-01

Background The aim of the present study is to identify the incidence and prognostic significance of lymph node metastases near the celiac trunk in patients who underwent neoadjuvant chemo(radio)therapy followed by esophagectomy. Methods Between March 1994 and September 2013 a total of 462 consecutive patients with cancer of the esophagus or gastroesophageal junction (GEJ) who underwent potentially curative esophageal resection after neoadjuvant chemotherapy (N=88; 19.0%) or neoadjuvant chemoradiotherapy (CRT) (N=374; 81.0%) were included. Results Seventy one (15.4%) patients had truncal node metastases in the resection specimen. Metastases to these nodes occurred more frequently in male patients with adenocarcinoma and in tumors at the gastro-esophageal junction. A lower response to neoadjuvant treatment, higher ypT and ypN stages and a poorer grade of differentiation were significantly related with truncal node metastases. Patients with tumor positive truncal nodes had a worse median overall survival (17 vs. 55 months). In multivariate analysis, truncal node metastases were independently associated with a worse survival. Only 22 (31.0%) of the 71 patients with tumor positive truncal nodes were identified preoperatively with EUS or CT. In contrast, 37 patients had suspicious truncal nodes on EUS or CT, but metastases in the pathology specimen were absent. Conclusions In the present study, it is demonstrated that positive truncal nodes in the resection specimen after neoadjuvant therapy, are associated with advanced tumor stages and are an independent factor for inferior survival. PMID:29707301

Lymph node metastases near the celiac trunk should be considered separately from other nodal metastases in patients with cancer of the esophagus or gastroesophageal junction after neoadjuvant treatment and surgery.

PubMed

Lagarde, Sjoerd M; Anderegg, Martinus C J; Gisbertz, Suzanne S; Meijer, Sybren L; Hulshof, Maarten C C M; Bergman, Jacques J G H M; van Laarhoven, Hanneke W M; van Berge Henegouwen, Mark I

2018-03-01

The aim of the present study is to identify the incidence and prognostic significance of lymph node metastases near the celiac trunk in patients who underwent neoadjuvant chemo(radio)therapy followed by esophagectomy. Between March 1994 and September 2013 a total of 462 consecutive patients with cancer of the esophagus or gastroesophageal junction (GEJ) who underwent potentially curative esophageal resection after neoadjuvant chemotherapy (N=88; 19.0%) or neoadjuvant chemoradiotherapy (CRT) (N=374; 81.0%) were included. Seventy one (15.4%) patients had truncal node metastases in the resection specimen. Metastases to these nodes occurred more frequently in male patients with adenocarcinoma and in tumors at the gastro-esophageal junction. A lower response to neoadjuvant treatment, higher ypT and ypN stages and a poorer grade of differentiation were significantly related with truncal node metastases. Patients with tumor positive truncal nodes had a worse median overall survival (17 vs. 55 months). In multivariate analysis, truncal node metastases were independently associated with a worse survival. Only 22 (31.0%) of the 71 patients with tumor positive truncal nodes were identified preoperatively with EUS or CT. In contrast, 37 patients had suspicious truncal nodes on EUS or CT, but metastases in the pathology specimen were absent. In the present study, it is demonstrated that positive truncal nodes in the resection specimen after neoadjuvant therapy, are associated with advanced tumor stages and are an independent factor for inferior survival.

External Beam Radiation Therapy or Brachytherapy With or Without Short Course Neoadjuvant Androgen Deprivation Therapy: Results of a Multi-Center, Prospective Study of Quality of Life

PubMed Central

Gay, Hiram Alberto; Sanda, Martin G.; Liu, Jingxia; Wu, Ningying; Hamstra, Daniel A.; Wei, John T.; Dunn, Rodney L.; Klein, Eric A.; Sandler, Howard M.; Saigal, Christopher S.; Litwin, Mark S.; Kuban, Deborah A.; Hembroff, Larry; Regan, Meredith M.; Chang, Peter; Michalski, Jeff M.

2017-01-01

PURPOSE The long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multi-center studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer. METHODS We analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam radiation therapy (EBRT) or brachytherapy (BT). HRQOL was measured with the EPIC-26 questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used Chi-square or Fisher’s Exact test to compare the shift percentages between groups that did or did not receive NADT. Analyses were conducted at the two-sided 5% significance level. RESULTS For subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing baseline versus 24 months, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared to 14%, 13% and 16% in the EBRT group, respectively. CONCLUSION Compared to baseline, at 2 years participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasms, quality of erections, and ability to function sexually. However, there was no difference in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, feeling depressed, lack of energy or change in body weight. The improved survival in intermediate and high-risk patients receiving ADT and EBRT necessitates pre-treatment counseling of the HRQOL impact of ADT and EBRT. PMID:28463150

Hypofractionated Proton Boost Combined with External Beam Radiotherapy for Treatment of Localized Prostate Cancer

PubMed Central

Johansson, Silvia; Åström, Lennart; Sandin, Fredrik; Isacsson, Ulf; Montelius, Anders; Turesson, Ingela

2012-01-01

Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity. PMID:22848840

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.

18F-FDG PET-CT after Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients to Optimize Surgical Decision Making

PubMed Central

Anderegg, Maarten C. J.; de Groof, Elisabeth J.; Gisbertz, Suzanne S.; Bennink, Roel J.; Lagarde, Sjoerd M.; Klinkenbijl, Jean H. G.; Dijkgraaf, Marcel G. W.; Bergman, Jacques J. G. H. M.; Hulshof, Maarten C. C. M.; van Laarhoven, Hanneke W. M.; van Berge Henegouwen, Mark I.

2015-01-01

Background Prognosis of esophageal cancer patients can be significantly improved by neoadjuvant chemoradiotherapy (nCRT). Given the aggressive nature of esophageal tumors, it is conceivable that in a significant portion of patients treated with nCRT, dissemination already becomes manifest during the period of nCRT. The aim of this retrospective study was to determine the value and diagnostic accuracy of PET-CT after neoadjuvant chemoradiotherapy to identify patients with metastases preoperatively in order to prevent non-curative surgery. Methods From January 2011 until February 2013 esophageal cancer patients deemed eligible for a curative approach with nCRT and surgical resection underwent a PET-CT after completion of nCRT. If abnormalities on PET-CT were suspected metastases, histological proof was acquired. A clinical decision model was designed to assess the cost-effectiveness of this diagnostic strategy. Results 156 patients underwent a PET-CT after nCRT. In 31 patients (19.9%) PET-CT showed abnormalities suspicious for dissemination, resulting in 17 cases of proven metastases (10.9%). Of the patients without proven metastases 133 patients were operated. In 6 of these 133 cases distant metastases were detected intraoperatively, corresponding to 4.5% false-negative results. The standard introduction of a post-neoadjuvant therapy PET-CT led to a reduction of overall health care costs per patient compared to a scenario without restaging with PET-CT ($34,088 vs. $36,490). Conclusion In 10.9% of esophageal cancer patients distant metastases were detected by standard PET-CT after neoadjuvant chemoradiotherapy. To avoid non-curative resections we advocate post-neoadjuvant therapy PET-CT as a cost-effective step in the standard work-up of candidates for surgery. PMID:26529313

Prevalence of Clostridium Difficile Infection in Patients After Radical Cystectomy and Neoadjuvant Chemotherapy.

PubMed

Cotter, Katherine J; Fan, Yunhua; Sieger, Gretchen K; Weight, Christopher J; Konety, Badrinath R

2017-10-27

Clostridium Difficile is the most common cause of nosocomial infectious diarrhea. This study evaluates the prevalence and predictors of Clostridium Difficile infections in patients undergoing radical cystectomy with or without neoadjuvant chemotherapy. Retrospective chart review was performed of all patients undergoing cystectomy and urinary diversion at a single institution from 2011-2017. Infection was documented in all cases with testing for Clostridium Difficile polymerase chain reaction toxin B. Patient and disease related factors were compared for those who received neoadjuvant chemotherapy vs. those who did not in order to identify potential risk factors associated with C. Difficile infections. Chi squared test and logistic regression analysis were used to determine statistical significance. Of 350 patients who underwent cystectomy, 41 (11.7%) developed Clostridium Difficile in the 30 day post-operative period. The prevalence of C. Difficile infection was higher amongst the patients undergoing cystectomy compared to the non-cystectomy admissions at our hospital (11.7 vs. 2.9%). Incidence was not significantly different among those who underwent cystectomy for bladder cancer versus those who underwent the procedure for other reasons. Median time to diagnosis was 6 days (range 3-28 days). The prevalence of C. Diff infections was not significantly different among those who received neoadjuvant chemotherapy vs. those who did not (11% vs. 10.4% p  = 0.72). A significant association between C. Difficile infection was not seen with proton pump inhibitor use ( p  = 0.48), patient BMI ( p  = 0.67), chemotherapeutic regimen ( p  = 0.94), individual surgeon ( p  = 0.54), type of urinary diversion (0.41), or peri-operative antibiotic redosing ( p  = 0.26). Clostridium Difficile infection has a higher prevalence in patients undergoing cystectomy. No significant association between prevalence and exposure to neoadjuvant chemotherapy was seen.

Robot-Assisted Mckeown Esophagectomy is Feasible After Neoadjuvant Chemoradiation. Our Initial Experience.

PubMed

Goel, Ashish; Shah, Swati H; Selvakumar, Veda Padma Priya; Garg, Shubha; Kumar, Kapil

2018-02-01

Neoadjuvant chemoradiation has become the standard of care for esophageal cancer, especially for middle third esophageal lesions and those with squamous histology. Although more and more thoracic surgeons and surgical oncologists have now shifted to video-assisted and robot-assisted thoracoscopic esophagectomy; there is still limited experience for the use of minimal-assisted approaches in patients undergoing surgery after neoadjuvant chemoradiation. Most surgeons have concerns of feasibility, safety, and oncological outcomes as well as issues related to difficult learning curve in adopting robotic esophagectomy in patients after chemoradiation. We present our initial experience of Robot-Assisted Mckeown Esophagectomy in 27 patients after neoadjuvant chemoradiation, from May 2013 to October 2014. All patients underwent neoadjuvant chemoradiation to a dose of 50.4 Gy/25Fr with concurrent weekly cisplatin, followed by reassessment with clinical examination and repeat FDG PET/CT 6 weeks after completion of chemoradiation. Patients with progressive disease underwent palliative chemotherapy while patients with either partial or significant response to chemoradiation underwent Robot-Assisted Mckeown Esophagectomy with esophageal replacement by gastric conduit and esophagogastric anastomosis in the left neck. Out of 27 patients, 92.5 % patients had stage cT3/T4 tumours and node-positive disease in 48.1 % on imaging. Most patients were middle thoracic esophageal cancers (23/27), with squamous histology in all except for one. All patients received neoadjuvant chemoradiation and subsequently underwent Robot Assisted Mckeown Esophagectomy. The average time for robot docking, thoracic mobilization and total surgical procedure was 13.2, 108.4 and 342.7 min, respectively. The procedure was well tolerated by all patients with only one case of peri-operative mortality. Average ICU stay was 6.35 days (range 3-9 days). R0 resection rate of 96.3 % and average lymph node yield of 18 could be achieved. Pathological node negativity rate (pN0) and complete response (pCR) were 66.6 and 44.4 %, respectively. In the initial cases, four patients had to be converted to open due technical reasons or intraoperative complications. The present study, with shorter operative times, similar ICU stay, overall low morbidity, and mortality and optimal oncological outcomes suggest that robot-assisted thoracic mobilization of esophagus in patients with prior chemoradiation is feasible and safe with acceptable oncological outcomes. It has a shorter learning curve and hence allows for a transthoracic minimally invasive transthoracic esophagectomy to more and more patients, otherwise unfit for conventional approach.

Initial incomplete surgery modifies prognosis in advanced ovarian cancer regardless of subsequent management.

PubMed

Bacalbasa, Nicolae; Balescu, Irina; Dima, Simona; Herlea, Vlad; David, Leonard; Brasoveanu, Vladislav; Popescu, Irinel

2015-04-01

Prognosis in ovarian cancer is determined by completeness of cytoreduction and proper management by specialized oncological gynecologists. Incomplete initial debulking surgery in non-specialized Centers is, however, a reality and there is ongoing discussion about the best subsequent management of such patients. Patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics--FIGO FIGO stages IIIC-IV) who had biopsy by laparotomy or incomplete cytoreduction followed or not by chemotherapy further referred to our Institution between January 2002 and May 2014 were included. The two groups of incomplete cytoreduction [followed by upfront surgery or followed by chemotherapy and interval debulking surgery (IDS)] were compared and also compared against a cohort of 197 patients with similar characteristics who underwent upfront maximal surgery according to the standard at our Iinstitution during the same period. A total of 99 eligible patients were identified. Sixty-seven of them underwent biopsies by laparotomy and 32 underwent incomplete cytoreduction in other institutions. Twenty-eight patients underwent direct re-operation while 71 patients underwent neoadjuvant chemotherapy followed by IDS. The mean overall survival duration for patients with upfront reoperation was 31 months and 54 months for patients with neoadjuvant chemotherapy and IDS, considerably lower than the 72 months obtained for the group of 197 patients with maximal up-front complete cytoreduction at our Institution. Primary biopsy or incomplete cytoreduction reduces survival regardless of the subsequent approach. However, if incomplete cytoreduction has occurred, neoadjuvant chemotherapy followed by IDS is preferable to up-front reoperation. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Prospective study of neoadjuvant chemoradiotherapy using intensity-modulated radiotherapy and 5 fluorouracil for locally advanced rectal cancer - toxicities and response assessment.

PubMed

Simson, David K; Mitra, Swarupa; Ahlawat, Parveen; Saxena, Upasna; Sharma, Manoj Kumar; Rawat, Sheh; Singh, Harpreet; Bansal, Babita; Sripathi, Lalitha Kameshwari; Tanwar, Aditi

2018-01-01

The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint. All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted. Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR. IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy.

Association of PTP1B with Outcomes of Breast Cancer Patients Who Underwent Neoadjuvant Chemotherapy.

PubMed

Rivera Franco, Monica M; Leon Rodriguez, Eucario; Martinez Benitez, Braulio; Villanueva Rodriguez, Luisa G; de la Luz Sevilla Gonzalez, Maria; Armengol Alonso, Alejandra

2016-01-01

PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR). Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5%) and overexpression (≥5%). Patients' responses were graded according to the Miller-Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR ( P = 0.2). However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens ( P = 0.02). Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B over-expression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded.

Benefits and Disadvantages of Neoadjuvant Radiochemotherapy (RCT) in the Multimodal Therapy of Squamous Esophageal Cancer (ESC).

PubMed

Hanna, Adrian; Birla, Rodica; Iosif, Cristina; Boeriu, Marius; Constantinoiu, Silviu

2016-01-01

The purpose of this paper is to present the advantages and disadvantages of neoadjuvant RCT in multimodal therapyof ESC. Between 1998-2014 221 patients were treated with ESC, 85 of whom received neoadjuvant RCT. For these we have made imaging and pathologic assessment of response using RECIST and MANDARD criteria and statistical data were interpreted in terms of the factors that influence the response. Also, they were evaluated statistical correlations between RCT and resectability, postoperative morbidity, mortality and long-term survival. 45 patients were imagistic responders and 34 underwent surgery, 40 non-responders of which 14 underwent surgery. Of the 48 surgical patients with preoperative RCT, histopathological evaluation showed that 32 were pathological responders and 16 non responders. There were performed statistical analyzes of correlations between RCT and resectability, stage, location of ESC, morbidity, mortality and survival. RCT increase resectability, improves survival and maximum duration of survival, more in responders than in nonresponders and does not affect postoperative complications and postoperative mortality, nor among the responders or nonresponders. Imaging evaluation result of the response to RCT overestimate responders. Celsius.

Effect of neoadjuvant chemotherapy on HER-2 expression in surgically treated gastric and oesophagogastric junction carcinoma: a multicentre Italian study.

PubMed

Chiari, Damiano; Orsenigo, Elena; Guarneri, Giovanni; Baiocchi, Gian Luca; Mazza, Elena; Albarello, Luca; Bissolati, Massimiliano; Molfino, Sarah; Staudacher, Carlo

2017-03-01

Predictors of response to neoadjuvant chemotherapy are not available for gastric and oesophago-gastric junction carcinoma. HER-2 over-expression in breast cancer correlates with poor prognosis and high incidence of recurrence. First aim of this study was to evaluate if the HER-2 expression/amplification is predictive of response to neoadjuvant chemotherapy in terms of pathologic regression. Secondary aim was to evaluate if HER-2 expression varies after neoadjuvant treatment. Thirty-five patients with locally advanced gastric or oesophago-gastric junction carcinoma underwent preoperative chemotherapy and surgical resection at San Raffaele Scientific Institute and Spedali Civili of Brescia. HER-2 expression/amplification was evaluated on every biopsy at diagnosis time and on every surgical sample after neoadjuvant chemotherapy. Pathologic response to chemotherapy was evaluated according to TNM classification (ypT status and ypN status) and Mandard's tumour regression grade classification. In our series 10 patients (28.6%) showed a reduction in HER-2 overexpression and in 6 of them (17.1%) HER-2 expression completely disappeared. Only three of the six patients with HER-2 disappearance had a complete pathological response to neoadjuvant chemotherapy. There was a strong correlation between HER-2 negativity on biopsy and absence of lymph node metastasis in surgical samples after neoadjuvant chemotherapy, irrespective of nodal status before chemotherapy. A direct correlation between HER-2 reduction after neoadjuvant chemotherapy and pathologic regression (primary tumour and lymph nodes) in surgical samples was found. HER-2 negativity may represent a predictor of pathologic response to neoadjuvant chemotherapy for gastric and oesophago-gastric junction adenocarcinoma. Neoadjuvant treatment can reduce HER-2 overexpression.

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

PubMed Central

Gaß, Paul; Fasching, Peter A.; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W.; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesselt, Thomas; Fischer, Gunnar; Henschen, Stephan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M.; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y.; Beckmann, Matthias W.; Wallwiener, Diethelm; Kümmel, Sherko; Löhberg, Christian R.

2016-01-01

Background Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues. PMID:27920623

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

PubMed

Gaß, Paul; Fasching, Peter A; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesselt, Thomas; Fischer, Gunnar; Henschen, Stephan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y; Beckmann, Matthias W; Wallwiener, Diethelm; Kümmel, Sherko; Löhberg, Christian R

2016-10-01

Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues.

Prospective study of neoadjuvant chemoradiotherapy using intensity-modulated radiotherapy and 5 fluorouracil for locally advanced rectal cancer – toxicities and response assessment

PubMed Central

Simson, David K; Mitra, Swarupa; Ahlawat, Parveen; Saxena, Upasna; Sharma, Manoj Kumar; Rawat, Sheh; Singh, Harpreet; Bansal, Babita; Sripathi, Lalitha Kameshwari; Tanwar, Aditi

2018-01-01

Aims and objectives The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint. Materials and methods All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted. Results Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR. Conclusion IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy. PMID:29593430

Prognostic value of neoadjuvant treatment response in locally advanced rectal cancer.

PubMed

Sada, Yvonne H; Tran Cao, Hop S; Chang, George J; Artinyan, Avo; Musher, Benjamin L; Smaglo, Brandon G; Massarweh, Nader N

2018-06-01

For locally advanced rectal cancer, response to neoadjuvant radiation has been associated with improved outcomes but has not been well characterized in general practice. The goals of this study were to describe disease response rates after neoadjuvant treatment and to evaluate the association between disease response and survival. Retrospective cohort study of patients aged 18-80 y with clinical stage II and III rectal adenocarcinoma in the National Cancer Database (2006-2012). All patients underwent radical resection after neoadjuvant treatment. Treatment responses were defined as follows: no tumor response; intermediate-T and/or N downstaging with residual disease; and complete-ypT0N0. Multivariable, multinomial regression was used to evaluate the association between neoadjuvant radiation use and disease response. Multivariable Cox regression was used to evaluate the association between disease response and overall risk of death. Among 12,024 patients, 12% had a complete and 30% an intermediate response. Neoadjuvant chemotherapy alone was less likely to achieve an intermediate (relative risk ratio: 0.70 [0.56-0.88]) or a complete response (relative risk ratio: 0.59 [0.41-0.84]) relative to neoadjuvant radiation. Tumor response was associated with improved 5-y overall survival (complete = 90.2%, intermediate = 82.0%, no response = 70.5%; log-rank, P < 0.001). Complete and intermediate pathologic responses were associated with decreases in risk of death (hazard ratio: 0.40 [0.34-0.48] and 0.63 [0.57-0.69], respectively) compared to no response. Primary tumor and nodal response were independently associated with decreased risk of death. Neoadjuvant radiation is associated with treatment response, and pathologic response is associated with improved survival. Pathologic response may be an early benchmark for the oncologic effectiveness of neoadjuvant treatment. Published by Elsevier Inc.

Gastric ulceration following oesophageal stent migration complicating surgical management of oesophageal cancer

PubMed Central

Markar, Sheraz R.; Ross, Andrew; Low, Donald E.

2012-01-01

Oesophageal, fully covered self-expanding metal stents (SEMS) allow palliation of dysphagia so as to support nutrition during neoadjuvant therapy. We present a 68-year old man with an oesophageal adenocarcinoma (T3N1M0) who had a fully covered oesophageal SEMS placed prior to neoadjuvant chemoradiotherapy. Repeat endoscopy 8 weeks later (for stent removal) showed that the stent had migrated and impacted upon the greater curvature of the stomach with a resultant ulcer. Surgery was delayed and, 10 weeks following the cessation of neoadjuvant chemoradiotherapy, this patient underwent a right thoracoabdominal oesophagogastrectomy. Operative findings included an erosion of the stent-induced gastric ulcer into the body of the pancreas and showed that the ulcerated tumour had become adherent to the thoracic aorta. This report demonstrates that the complications of stent migration can significantly impact upon surgical resection at multiple levels and provides a case for the routine removal of stents used in the neoadjuvant setting. PMID:22593562

Depressive symptomatology in men receiving androgen deprivation therapy for prostate cancer: a controlled comparison.

PubMed

Lee, Morgan; Jim, Heather S; Fishman, Mayer; Zachariah, Babu; Heysek, Randy; Biagioli, Matthew; Jacobsen, Paul B

2015-04-01

Prostate cancer patients who receive androgen deprivation therapy (ADT) often experience many physical and psychological side effects. ADT may be associated with increased risk for depression, but the relationship between ADT and depression is not fully understood. This study used a longitudinal design to assess depressive symptomatology in patients receiving ADT compared with two groups of matched controls. Participants were men initiating ADT treatment (ADT+ group; n = 61) and their matched controls: prostate cancer patients treated with radical prostatectomy (ADT- group; n = 61), and no-cancer controls (CA- group; n = 61). Depressive symptomatology was assessed using the Center for Epidemiological Studies Depression Scale at ADT initiation and again 6 months later. Differences in depressive symptomatology and rates of clinically significant depressive symptomatology were analyzed between groups at each time point and within groups over time. Between baseline and follow-up, ADT+ participants demonstrated increased depressive symptomatology and increased rates of clinically significant depressive symptomatology (ps < 0.05). ADT+ participants also reported greater depressive symptomatology than both control groups at follow-up (ps < 0.001). Rates of clinically significant depressive symptomatology were higher in the ADT+ group than the ADT- and CA- groups at both time points (baseline: 28%, 5%, 12%; follow-up: 39%, 9%, 11%). Findings support the hypothesis that ADT administration yields increases in depression and suggest that the mechanism behind ADT's association with depression should be explored and that prostate cancer patients treated with ADT should receive particular focus in depression screening and intervention. Copyright © 2014 John Wiley & Sons, Ltd.

Population-Based Study of Cardiovascular Mortality Among Patients With Prostate Cancer Treated With Radical External Beam Radiation Therapy With and Without Adjuvant Androgen Deprivation Therapy at the British Columbia Cancer Agency

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

Kim, Julian; Vaid, Moninder; Tyldesley, Scott, E-mail: styldesl@bccancer.bc.ca

2011-07-01

Purpose: There are conflicting studies of the impact of androgen deprivation therapy (ADT) on cardiovascular (CV) mortality among prostate cancer patients receiving curative intent external beam radiation therapy (EBRT). We assessed the impact of ADT on CV mortality in patients treated in British Columbia. Methods and Materials: Provincial pharmacy and radiotherapy databases were linked to the provincial cancer registry, and defined a cohort of patients treated with curative intent EBRT between 1998 and 2005. We determined the duration of ADT and the cumulative incidence of CV death. We compared death from CV disease with and without ADT, and by durationmore » of ADT using competing risk analysis and Fine and Gray multivariant analysis. A total of 600 randomly selected patients were reviewed to determine baseline CV disease, CV risk factors, and Charlson Index. Results: Of 5,948 prostate cancer patients treated with radical intent EBRT, of whom 1,933 were treated without ADT, 674 received ADT for {<=}6 months and 3,341 received > 6 months of ADT. The cumulative CV mortality at 7 years was 2.6% (95% confidence interval [CI] 1.9-3.5%), 2.1% (95% CI = 1.2-3.5%), and 1.4 (95% CI = 1.0-2.0%) for patients with no ADT, {<=}6 months of ADT, and >6 months of ADT, respectively (Gray's p = 0.002). Baseline CV disease and risk factors were more prevalent in the no-ADT group compared with the >6-month ADT group. Conclusions: This study demonstrated a lower CV mortality rate among patients treated with longer durations of ADT than those treated without ADT. These differences likely relate to selection of patients for ADT rather than effect of ADT itself.« less

Development of prostate cancer in a patient with primary hypogonadism: intratumoural steroidogenesis in prostate cancer tissues.

PubMed

Arai, S; Shibata, Y; Nakamura, Y; Kashiwagi, B; Uei, T; Tomaru, Y; Miyashiro, Y; Honma, S; Hashimoto, K; Sekine, Y; Ito, K; Sasano, H; Suzuki, K

2013-01-01

Intratumoural steroidogenesis may play a significant role in the progression of prostate cancer (PC) in the context of long-term ablation of circulating testosterone (T). To clarify the mechanism accounting for the progression of PC in a 74-year-old man who had undergone bilateral orchiectomy when he was 5 years old, we performed immunohistochemical studies of androgen receptor (AR) and steroidogenic enzymes in the prostate. We also measured steroid hormone levels in the serum and prostate, as well as mRNA levels of genes mediating androgen metabolism in the prostate. Positive nuclear staining of AR was detected in malignant epithelial cells. The levels of androstenedione (Adione), T, and 5-alpha dihydrotestosterone (DHT) in the serum of the patient were similar to those in PC patients receiving neoadjuvant androgen deprivation therapy (ADT), but were higher in the patient's prostate than in PC patients not receiving ADT. The gene expression of CYP17A1 and HSD3B1 was not detected, whereas that of STS, HSD3B2, AKR1C3, SRD5A1, and SRD5A2 was detected. Moreover, cytoplasmic staining of HSD3B2, AKR1C3, SRD5A1, and SRD5A2 was detected in malignant epithelial cells. Hence, in the present case (a man with primary hypogonadism), steroidogenesis in PC tissues from adrenal androgens, especially dehydroepiandrosterone sulphate, was the mechanism accounting for progression of PC. This mechanism might help elucidate the development of castration-resistant PC. © 2012 American Society of Andrology and European Academy of Andrology.

Neoadjuvant Chemotherapy for Facilitating Surgical Resection of Infantile Massive Intracranial Immature Teratoma.

PubMed

Kitahara, Takahiro; Tsuji, Yoshihito; Shirase, Tomoyuki; Yukawa, Hiroyuki; Takeichi, Yasuhiro; Yamazoe, Naohiro

2016-04-01

Immature teratoma (IMT) is the most frequent histological subtype of infantile intracranial teratoma, the most common congenital brain tumor. IMT contains incompletely differentiated components resembling fetal tissues. Infantile intracranial IMT has a dismal prognosis, because it is often inoperable due to its massive size and high vascularity. Neoadjuvant chemotherapy has been shown to be effective in decreasing tumor volume and vascularity to facilitate surgical resection in other types of infantile brain tumors. However, only one recent case report described the effectiveness of neoadjuvant chemotherapy for infantile intracranial IMT in the literature, even though it is common entity with a poor prognosis in infants. Here, we describe the case of a 2-month-old male infant with a very large intracranial IMT. Maximal surgical resection was first attempted but was unsuccessful because of severe intraoperative hemorrhage. Neoadjuvant carboplatin and etoposide (CARE) chemotherapy was then administered with the aim of shrinking and devascularizing the tumor. After neoadjuvant chemotherapy, tumor size did not decrease, but intraoperative blood loss significantly decreased and near-total resection was achieved by the second and third surgery. The patient underwent adjuvant CARE chemotherapy and has been alive for 3 years after surgery without tumor regrowth. Even when neoadjuvant chemotherapy does not decrease tumor volume of infantile intracranial IMT, surgical resection should be tried because chemotherapy can facilitate surgical resection and improve clinical outcome by reducing tumor vascularity.

Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma

PubMed Central

Jung, Jang Han; Lee, Hyun Jik; Lee, Hee Seung; Jo, Jung Hyun; Cho, In Rae; Chung, Moon Jae; Park, Jeong Youp; Park, Seung Woo; Song, Si Young; Bang, Seungmin

2017-01-01

AIM To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA). METHODS We retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging. RESULTS The median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01). CONCLUSION NACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability. PMID:28566890

Esophageal cancer: outcomes of surgery, neoadjuvant chemotherapy, and three-dimension conformal radiotherapy.

PubMed

Fréchette, Eric; Buck, David A; Kaplan, Brian J; Chung, Theodore D; Shaw, James E; Kachnic, Lisa A; Neifeld, James P

2004-08-01

Neoadjuvant chemotherapy and radiation are being utilized with increasing frequency in the multimodal treatment of esophageal cancer, although their effects on morbidity, mortality, and survival remain unclear. The objective of this study was to determine the outcome of multimodal treatment in patients with localized esophageal cancer treated at a single institution. Between 1995 and 2002, 118 patients underwent treatment for localized esophageal cancer, utilizing surgery alone, chemoradiation alone, or surgery following neoadjuvant chemoradiation. There was no statistically significant difference in morbidity, mortality, or length of stay between the patients who received multimodal therapy when compared to surgery alone. A surgical resection after down-staging was possible in 9 out of 28 patients (32%) with a clinically non-resectable tumor (T4 or M1a). Forty-seven percent of the patients who received neoadjuvant therapy had a complete pathologic response with a 3-year survival of 59% as compared to only 20 months in those patients who did not achieve a complete response (P = 0.037). Neoadjuvant chemotherapy administered concomitantly with conformal radiotherapy can be performed safely in the treatment of esophageal cancer, without increasing the operative morbidity, mortality, or length of stay. The higher complete response rates to neoadjuvant treatment (as compared to other reports) may be due to the use of three-dimensional conformal radiation therapy or the novel use of weekly carboplatin and paclitaxel. Copyright 2004 Wiley-Liss, Inc.

Long-term survival based on pathologic response to neoadjuvant therapy in esophageal cancer.

PubMed

Tiesi, Gregory; Park, Wungki; Gunder, Meredith; Rubio, Gustavo; Berger, Michael; Ardalan, Bach; Livingstone, Alan; Franceschi, Dido

2017-08-01

Neoadjuvant treatment is standard for locally advanced esophageal cancer. However, whether the addition of radiation to neoadjuvant regimen improves survival remains unclear. The aim of this study was to compare survival in locally advanced esophageal cancer treated with neoadjuvant chemotherapy versus chemoradiation. A prospectively maintained database of esophagectomies (1999-2012) was analyzed. We identified 297 patients with locally advanced esophageal cancer that underwent either neoadjuvant chemotherapy (n = 231) or chemoradiation (n = 66) followed by esophagectomy. Pretreatment and pathologic staging were compared to assess response. Overall survival was recorded. Most patients in the chemotherapy and chemoradiation groups had pretreatment stage III disease (66.7% versus 65.2%; P = 0.44). Median follow-up was 79.3 and 64.9 mo for chemotherapy and chemoradiation cohorts, respectively. Complete response rate was higher in chemoradiation than chemotherapy groups (30.3% versus 13.8%; P < 0.001). Overall survival was similar between complete responders in both groups (median not reached versus 121.1 mo; chemotherapy versus chemoradiation). However, partial responders in the chemotherapy cohort had improved median survival (147.2 mo) versus those in the chemoradiation cohort (83.7 mo, P < 0.03). Within the chemotherapy-only group, partial responders had improved survival compared with nonresponders (P = 0.041); however, there was no difference in survival between partial and complete responders (P = 0.36). In patients undergoing esophagectomy for locally advanced esophageal cancer, neoadjuvant chemotherapy was associated with an equivalent overall survival, when compared with neoadjuvant chemoradiotherapy. Adding neoadjuvant radiation may enhance complete response rates but does not appear to be associated with improved survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Psychological effects of androgen-deprivation therapy on men with prostate cancer and their partners.

PubMed

Donovan, Kristine A; Walker, Lauren M; Wassersug, Richard J; Thompson, Lora M A; Robinson, John W

2015-12-15

The clinical benefits of androgen-deprivation therapy (ADT) for men with prostate cancer (PC) have been well documented and include living free from the symptoms of metastases for longer periods and improved quality of life. However, ADT comes with a host of its own serious side effects. There is considerable evidence of the adverse cardiovascular, metabolic, and musculoskeletal effects of ADT. Far less has been written about the psychological effects of ADT. This review highlights several adverse psychological effects of ADT. The authors provide evidence for the effect of ADT on men's sexual function, their partner, and their sexual relationship. Evidence of increased emotional lability and depressed mood in men who receive ADT is also presented, and the risk of depression in the patient's partner is discussed. The evidence for adverse cognitive effects with ADT is still emerging but suggests that ADT is associated with impairment in multiple cognitive domains. Finally, the available literature is reviewed on interventions to mitigate the psychological effects of ADT. Across the array of adverse effects, physical exercise appears to have the greatest potential to address the psychological effects of ADT both in men who are receiving ADT and in their partners. © 2015 American Cancer Society.

Quality of Life During Treatment With Chemohormonal Therapy: Analysis of E3805 Chemohormonal Androgen Ablation Randomized Trial in Prostate Cancer.

PubMed

Morgans, Alicia K; Chen, Yu-Hui; Sweeney, Christopher J; Jarrard, David F; Plimack, Elizabeth R; Gartrell, Benjamin A; Carducci, Michael A; Hussain, Maha; Garcia, Jorge A; Cella, David; DiPaola, Robert S; Patrick-Miller, Linda J

2018-04-10

Purpose Chemohormonal therapy with docetaxel and androgen deprivation therapy (ADT+D) for metastatic hormone-sensitive prostate cancer improves overall survival as compared with androgen deprivation therapy (ADT) alone. We compared the quality of life (QOL) between patients with metastatic hormone-sensitive prostate cancer who were treated with ADT+D and those who were treated with ADT alone. Methods Men were randomly assigned to ADT+ D (six cycles) or to ADT alone. QOL was assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P), FACT-Taxane, Functional Assessment of Chronic Illness Therapy-Fatigue, and the Brief Pain Inventory at baseline and at 3, 6, 9, and 12 months. The Wilcoxon signed rank test was used to examine changes over time. Mixed-effect models compared the QOL between arms at each time point. Results Seven hundred ninety men were randomly assigned (ADT+D [n = 397] and ADT[ n = 393]) and completed FACT-P (90% at baseline, 86% at 3 months, 83% at 6 months, 78% at 9 months, and 77% at 12 months). ADT+D patients reported a statistically significant decline in FACT-P at 3 months ( P < .001) but FACT-P did not differ significantly between baseline and 12 months ( P = .38). ADT+D FACT-P scores were significantly lower at 3 months ( P = .02) but significantly higher at 12 months ( P = .04) when compared with ADT FACT-P scores. Differences did not exceed the minimal clinically important difference at any time point. ADT+D patients reported significantly lower Functional Assessment of Chronic Illness Therapy-Fatigue scores at 3 months than did ADT patients ( P < .001). Over time, both arms reported significantly poorer FACT-Taxane scores ( P < .001) when compared with baseline. Brief Pain Inventory scores were similar between arms. Conclusion Although ADT+D was associated with statistically worse QOL at 3 months, QOL was better at 12 months for ADT+D patients than for ADT patients. Both arms reported a similar minimally changed QOL over time, suggesting that ADT+D is not associated with a greater long-term negative impact on QOL.

Influence of age on androgen deprivation therapy-associated Alzheimer’s disease

NASA Astrophysics Data System (ADS)

Nead, Kevin T.; Gaskin, Greg; Chester, Cariad; Swisher-McClure, Samuel; Dudley, Joel T.; Leeper, Nicholas J.; Shah, Nigam H.

2016-10-01

We recently found an association between androgen deprivation therapy (ADT) and Alzheimer’s disease. As Alzheimer’s disease is a disease of advanced age, we hypothesize that older individuals on ADT may be at greatest risk. We conducted a retrospective multi-institutional analysis among 16,888 individuals with prostate cancer using an informatics approach. We tested the effect of ADT on Alzheimer’s disease using Kaplan-Meier age stratified analyses in a propensity score matched cohort. We found a lower cumulative probability of remaining Alzheimer’s disease-free between non-ADT users age ≥70 versus those age <70 years (p < 0.001) and between ADT versus non-ADT users ≥70 years (p = 0.034). The 5-year probability of developing Alzheimer’s disease was 2.9%, 1.9% and 0.5% among ADT users ≥70, non-ADT users ≥70 and individuals <70 years, respectively. Compared to younger individuals older men on ADT may have the greatest absolute Alzheimer’s disease risk. Future work should investigate the ADT Alzheimer’s disease association in advanced age populations given the greater potential clinical impact.

Neoadjuvant chemotherapy in technically unresectable carcinoma of external auditory canal

PubMed Central

Joshi, Amit; Tandon, Nidhi; Noronha, Vanita; Dhumal, Sachin; Patil, Vijay; Arya, Supreeta; Juvekar, Shashikant; Agarwal, Jaiprakash; DCruz, Anil; Pai, Prathmesh; Prabhash, Kumar

2015-01-01

Background: Carcinoma of external auditory canal (EAC) is a very rare malignancy with surgical resection as the main modality of treatment. The outcomes with nonsurgical modalities are very dismal. We present a retrospective analysis of 4 patients evaluating the role of neoadjuvant chemotherapy in technically unresectable cancers. Materials and Methods: This is a retrospective analysis of 4 patients from our institute from 2010 to 2014 with carcinoma EAC who were deemed unfit for surgery due to extensive disease involving occipital bone with soft tissue infiltration (n = 2), temporal dura (n = 1), left temporal lobe, and extensive soft tissue involvement (n = 1). All these patients received neoadjuvant chemotherapy with docetaxel, cisplatin and 5 fluorouracil (n = 3) and paclitaxel and cisplatin (n = 1). Results: Response evaluation showed a partial response (PR) in 3 and stable disease (SD) in 1 patient by Response Evaluation Criteria in Solid Tumors criteria. All 3 patients who received 3 drug chemotherapy had PR while 1 patient who received 2 drug chemotherapy had SD. Two of these patients underwent surgery, and other 2 underwent definitive chemoradiation. One of 3 patients who achieved PR underwent surgical resection; the other 2 remained unresectable in view of the persistent intradural extension and infratemporal fossa involvement. One patient who had SD could undergo surgery in view of clearance of infraatemporal fossa. Recent follow-up shows that 3 out of these 4 patients are alive. Conclusion: This indicates that there may be a role of induction chemotherapy in converting potentially unresectable tumors to resectable disease that could produce better outcomes in carcinoma EAC. PMID:26855526

Patterns of Declining Use and the Adverse Effect of Primary Androgen Deprivation on All-cause Mortality in Elderly Men with Prostate Cancer.

PubMed

Sammon, Jesse D; Abdollah, Firas; Reznor, Gally; Pucheril, Daniel; Choueiri, Toni K; Hu, Jim C; Kim, Simon P; Schmid, Marianne; Sood, Akshay; Sun, Maxine; Kibel, Adam S; Nguyen, Paul L; Menon, Mani; Trinh, Quoc-Dien

2015-07-01

Primary androgen deprivation therapy (pADT) is commonly used to treat elderly men diagnosed with localized prostate cancer (CaP), despite the lack of evidence supporting its use. To examine the effect of pADT on mortality and to assess contemporary trends of pADT use in elderly men with CaP. Men older than 65 yr residing in Surveillance, Epidemiology, and End Results (SEER) registry areas diagnosed with localized or locally advanced CaP between 1992 and 2009 and not receiving definitive therapy. Propensity score (PS)-weighted Cox proportional hazards models were used to estimate the effect of pADT use on overall survival among patients receiving pADT. The interaction between comorbidity-adjusted life expectancy (LE) and pADT use was assessed within the Cox and PS-weighted models. Contemporary (2004-2009) trends for pADT use were analyzed by linear regression. The primary cohort included 46 376 men, of whom 17 873 received pADT (39%). Patients with >10 yr LE had lower pADT utilization rates than patients with short LE. Between 2004 and 2009, the use of pADT in men with localized CaP decreased by 14% (from 36% to 22%). Relative to observation, pADT was associated with a survival disadvantage, with a hazard ratio for all-cause mortality of 1.37 (95% confidence interval 1.20-1.56). Limitations included biases not accounted for by the PS-weighted model, changes in CaP staging over the study period, the absence of prostate-specific antigen (PSA) data prior to 2004, and the limits of retrospective analysis to demonstrate causality. The use of pADT in elderly men with localized CaP has decreased over time. For men forgoing primary definitive therapy, the use of pADT is not associated with a survival benefit compared to observation, and denies men an opportunity for cure with definitive therapy. The deleterious effect of pADT is most pronounced in men with prolonged LE. In this report, we assessed the effect of primary androgen deprivation (pADT) on prostate cancer mortality and determined current trends in the use of pADT. We showed that use of pADT in men aged >65 yr with localized prostate cancer has decreased over time. We also found that pADT is detrimental to men with localized prostate cancer, and particularly men with longer life expectancy. Therefore, we conclude that ADT should not be used as a primary treatment for men with prostate cancer that has not spread beyond the prostate. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

A natural history of weight change in men with prostate cancer on androgen-deprivation therapy (ADT): results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

PubMed

Kim, Howard S; Moreira, Daniel M; Smith, Matthew R; Presti, Joseph C; Aronson, William J; Terris, Martha K; Kane, Christopher J; Amling, Christopher L; Freedland, Stephen J

2011-03-01

• To better understand the natural history of weight change with androgen-deprivation therapy (ADT), we investigated the effect of ADT on body weight among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. • Men undergoing ADT lose lean muscle but gain fat mass, contributing to an overall gain in weight. • We identified 132 men in SEARCH who received ADT after radical prostatectomy. • 'Weight change' was defined as the difference in weight before starting ADT (6 months before ADT) and the on-ADT weight (between 6 and 18 months after starting ADT). • In a subanalysis, baseline characteristics of weight-gainers and -losers were analysed using univariate and multivariate analysis to test association with weight change. • In all, 92 men (70%) gained weight, and 40 (30%) either lost or maintained a stable weight. • On average, weight on ADT was 2.2 kg higher than the weight before ADT, with the mean change for weight-gainers and -losers being +4.2 kg and -2.4 kg, respectively. • This compared with no significant weight change in the year before starting ADT (paired t-test, change -0.7 kg, P= 0.19) or in the second year on ADT (paired t-test, change -0.5 kg, P= 0.46) for 84 men in whom these additional weight values were recorded. • There was no significant association between any of the features examined and weight change on univariate and multivariate analysis. • In this longitudinal study, ADT was accompanied by significant weight gain (+2.2 kg). This change occurred primarily in the first year of therapy, with men neither losing nor gaining additional weight thereafter. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

Depressive Symptomatology in Men Receiving Androgen Deprivation Therapy for Prostate Cancer: A Controlled Comparison

PubMed Central

Lee, Morgan; Jim, Heather S.; Fishman, Mayer; Zachariah, Babu; Heysek, Randy; Biagioli, Matthew; Jacobsen, Paul B.

2014-01-01

Objective Prostate cancer patients who receive androgen deprivation therapy (ADT) often experience many physical and psychological side effects. ADT may be associated with increased risk for depression, but the relationship between ADT and depression is not fully understood. This study used a longitudinal design to assess depressive symptomatology in patients receiving ADT compared to two groups of matched controls. Methods Participants were men initiating ADT treatment (ADT+ group; n = 61) and their matched controls: prostate cancer patients treated with radical prostatectomy (ADT− group; n = 61) and no-cancer controls (CA− group; n = 61). Depressive symptomatology was assessed using the Center for Epidemiological Studies Depression Scale at ADT initiation and again six months later. Differences in depressive symptomatology and rates of clinically-significant depressive symptomatology were analyzed between groups at each time point and within groups over time. Results: Between baseline and follow-up, ADT+ participants demonstrated increased depressive symptomatology and increased rates of clinically-significant depressive symptomatology (ps < .05). ADT+ participants also reported greater depressive symptomatology than both control groups at follow-up (ps < .001). Rates of clinically-significant depressive symptomatology were higher in the ADT+ group than the ADT− and CA− groups at both time points (baseline: 28%, 5%, 12%; follow-up: 39%, 9%, 11%). Conclusions Findings support the hypothesis that ADT administration yields increases in depression and suggest that the mechanism behind ADT’s association with depression should be explored and that prostate cancer patients treated with ADT should receive particular focus in depression screening and intervention. PMID:24924331

Self-Expanding Metal Stents Improve Swallowing and Maintain Nutrition During Neoadjuvant Therapy for Esophageal Cancer.

PubMed

Smith, Zachary L; Gonzaga, Jason E; Haasler, George B; Gore, Elizabeth M; Dua, Kulwinder S

2017-06-01

Patients with locally advanced esophageal cancer can have significant dysphagia. Nutritional support during neoadjuvant therapy is often delivered via nasoenteric or percutaneous feeding tubes. These approaches do not allow for per-oral feeding. Evaluate the safety and efficacy of fully covered self-expanding metal esophageal stents for nutritional support during neoadjuvant therapy. This was a pilot, prospective study at a single tertiary center. From March 2012 to May 2013, consecutive patients with esophageal cancer eligible for neoadjuvant therapy were enrolled. Metal stents were placed prior to starting neoadjuvant therapy. Data were collected at baseline and predetermined intervals until an endpoint (surgery or disease progression). Outcomes included dysphagia grade, satisfaction of swallowing score, nutritional status (weight, serum albumin), impact on surgery, and adverse events. Fourteen stents were placed in 12 patients (59.1 ± 9.5 years, 11 men, 1 woman). Dysphagia grade (pre 3.4 ± 0.5 vs post 0.2 ± 0.4, p < 0.0001) and swallowing scores (20.2 ± 5.9 vs 6.3 ± 4.7, p < 0.0001) significantly improved after stent placement. Improvements were sustained throughout neoadjuvant therapy. Body weight and serum albumin levels remained stable. Adverse events included severe chest pain (2), food impaction (1), and delayed stent migration (2). Five patients underwent surgical resection. No significant chemoradiation or operative adverse events occurred due to the presence of a stent. During neoadjuvant therapy for esophageal cancer, self-expanding metal stents are safe and effective in relieving dysphagia and maintaining nutrition. They allow patients to eat orally, thereby improving patient satisfaction. The presence of an in situ stent did not interfere with surgery.

Temperature dependence of exciton and charge carrier dynamics in organic thin films

NASA Astrophysics Data System (ADS)

Platt, A. D.; Kendrick, M. J.; Loth, M.; Anthony, J. E.; Ostroverkhova, O.

2011-12-01

We report on physical mechanisms behind the temperature-dependent optical absorption, photoluminescence (PL), and photoconductivity in spin-coated films of a functionalized anthradithiophene (ADT) derivative, ADT-triethylsilylethynyl (TES)-F, and its composites with C60 and another ADT derivative, ADT-TIPS-CN. Measurements of absorption and PL spectra, PL lifetimes, and transient photocurrent were performed at temperatures between 98 and 300 K as a function of applied electric field. In pristine ADT-TES-F films, absorptive and emissive species were identified to be disordered H aggregates whose properties are affected by static and dynamic disorder. The exciton bandwidths were ≤0.06 and ˜0.115 eV for absorptive and emissive aggregates, respectively, indicative of higher disorder in the emissive species. The exciton in the latter was found to be delocalized over approximately four to five molecules. The PL properties were significantly modified upon adding a guest molecule to the ADT-TES-F host. In ADT-TES-F/C60 composites, the PL was considerably quenched due to photoinduced electron transfer from ADT-TES-F to C60, while in ADT-TES-F/ADT-TIPS-CN blends, the PL was dominated by emission from an exciplex formed between ADT-TES-F and ADT-TIPS-CN molecules. In all materials, the PL quantum yield dramatically decreased as the temperature increased due to thermally activated nonradiative recombination. Considerable electric-field-induced PL quenching was observed at low temperatures at electric fields above ˜105 V/cm due to tunneling into dark states. No significant contribution of ADT-TES-F emissive exciton dissociation to transient photocurrent was observed. In all materials, charge carriers were photogenerated at sub-500-ps time scales, limited by the laser pulse width, with temperature- and electric-field-independent photogeneration efficiency. In ADT-TES-F/C60 (2%) composites, the photogeneration efficiency was a factor of 2-3 higher than that in pristine ADT-TES-F films. In ADT-TES-F/ADT-TIPS-CN (2%) blends, an additional charge carrier photogeneration component was observed at room temperature at time scales of ˜20 ns due to exciplex dissociation. At ˜0.5-5 ns after photoexcitation, the carriers propagated via thermally and electric-field-activated hopping with an activation energy of ˜0.025 eV. At time scales longer than ˜5 ns, charge transport of carriers that are not frozen in traps proceeded through tunneling via isoenergetic sites.

Successful resection of a giant mediastinal non-seminomatous germ cell tumor showing fluorodeoxyglucose accumulation after neoadjuvant chemotherapy: report of a case.

PubMed

Takada, Kazuki; Morodomi, Yosuke; Okamoto, Tatsuro; Suzuki, Yuzo; Fujishita, Takatoshi; Kitahara, Hirokazu; Shimamatsu, Shinichiro; Kohno, Mikihiro; Kawano, Daigo; Hidaka, Noriko; Nakanishi, Yoichi; Maehara, Yoshihiko

2014-05-01

A 32-year-old man presented with a mediastinal non-seminomatous germ cell tumor showing fluorodeoxyglucose (FDG) accumulation (maximum standardized uptake value = 22.21) and extremely elevated blood alpha-fetoprotein (AFP) level (9203.0 ng/ml). The patient underwent 4 cycles of neoadjuvant chemotherapy (cisplatin, bleomycin, and etoposide), which normalized the AFP level and reduced the tumor size, allowing complete resection without a support of extracorporeal circulation. Despite preoperative positron emission tomography revealing increased FDG uptake in the residual tumor (maximum standardized uptake value = 3.59), the pathologic evaluation revealed that no viable germ cell tumor cells remained. We believe FDG uptake should not be used as a criterion for surgical resection after neoadjuvant chemotherapy. It is appropriate to resect the residual tumor regardless of FDG uptake after induction chemotherapy if a tumor is resectable and the AFP level normalizes.

Preoperative enteral access is not necessary prior to multimodality treatment of esophageal cancer.

PubMed

Jenkins, Thomas K; Lopez, Alexandra N; Sarosi, George A; Ben-David, Kfir; Thomas, Ryan M

2018-04-01

Surgical enteral access prior to multimodality treatment for esophageal cancer is controversial as dysphagia is often used for feeding tube referral. We hypothesized that enteral access before neoadjuvant chemoradiation for esophageal cancer provides no benefit compared to that placed during definitive esophagectomy. Patients undergoing esophagectomy for esophageal malignancy from 2007 - 2014 were retrospectively identified. Clinicopathologic factors were recorded including preoperative enteral access, weight change, nutritional laboratory works, and perioperative complications. Of 156 identified patients, 99 (63.5%) received neoadjuvant chemoradiation and comprised the study cohort. Fifty (50.5%) underwent enteral access (gastrostomy [14], jejunostomy [32], other [4]; "Access Group") prior to chemoradiation followed by esophagectomy and were compared to 49 "No-Access" patients who underwent enteral access during esophagectomy. Clinicopathologic variables were similar between cohorts. The Access and No-Access cohorts had similar reported dysphagia (86% vs 75.5%, respectively; P = .2) and mean preesophagectomy serum albumin (3.9 vs 4 gm/dL, respectively; P = .2). Weight loss ± 6-month periesophagectomy was similar between access versus No-Access cohorts (-11.2% vs -15.4%, respectively; P = .1). Weight loss during this period was likewise similar for patients with dysphagia in the Access (-11%) versus No-Access group (-15.2%, P = .1). No difference in complication rates was noted between Access (64%) and No-Access groups (51%, P = .2). Despite healthcare provider bias, there seems to be no nutritional or perioperative benefit for enteral access before neoadjuvant chemoradiation for esophageal malignancy. Patients with esophageal malignancy should therefore proceed to appropriate neoadjuvant and surgical therapy with enteral access performed during definitive resection or reserved for those with frank obstruction on endoscopy. Published by Elsevier Inc.

A Randomized Phase II Trial of Short-Course Androgen Deprivation Therapy With or Without Bevacizumab for Patients With Recurrent Prostate Cancer After Definitive Local Therapy

PubMed Central

McKay, Rana R.; Zurita, Amado J.; Werner, Lillian; Bruce, Justine Y.; Carducci, Michael A.; Stein, Mark N.; Heath, Elisabeth I.; Hussain, Arif; Tran, Hai T.; Sweeney, Christopher J.; Ross, Robert W.; Kantoff, Philip W.; Slovin, Susan F.

2016-01-01

Purpose Patients with recurrent prostate cancer after local treatment make up a heterogeneous population for whom androgen deprivation therapy (ADT) is the usual treatment. The purpose of this randomized phase II trial was to investigate the efficacy and toxicity of short-course ADT with or without bevacizumab in men with hormone-sensitive prostate cancer. Patients and Methods Eligible patients had an increasing prostate-specific antigen (PSA) of ≤ 50 ng/mL and PSA doubling time of less than 18 months. Patients had either no metastases or low burden, asymptomatic metastases (lymph nodes < 3 cm and five or fewer bone metastases). Patients were randomly assigned 2:1 to a luteinizing hormone-releasing hormone agonist, bicalutamide and bevacizumab or ADT alone, for 6 months. The primary end point was PSA relapse-free survival (RFS). Relapse was defined as a PSA of more than 0.2 ng/mL for prostatectomy patients or PSA of more than 2.0 ng/mL for primary radiation therapy patients. Results Sixty-six patients received ADT + bevacizumab and 36 received ADT alone. Patients receiving ADT + bevacizumab had a statistically significant improvement in RFS compared with patients treated with ADT alone (13.3 months for ADT + bevacizumab v 10.2 months for ADT alone; hazard ratio, 0.47; 95% CI, 0.29 to 0.77; log-rank P = .002). Hypertension was the most common adverse event in patients receiving ADT + bevacizumab (36%). Conclusion ADT combined with bevacizumab resulted in an improved RFS for patients with hormone-sensitive prostate cancer. Long-term follow-up is needed to determine whether some patients have a durable PSA response and are able to remain off ADT for prolonged periods. Our data provide rationale for combining vascular endothelial growth factor–targeting therapy with ADT in hormone-sensitive prostate cancer. PMID:27044933

Androgen deprivation therapy for prostate cancer: long-term safety and patient outcomes

PubMed Central

Ahmadi, Hamed; Daneshmand, Siamak

2014-01-01

Androgen deprivation therapy (ADT) constitutes the first-line treatment for patients with locally advanced tumors, recurrent or metastatic disease. Given its widespread use, clinicians should be familiar with common side effects of this treatment. This review focuses on common side effects of ADT and available treatment options to control the side effects. Also, it briefly compares continuous ADT with other therapeutic approaches for androgen deprivation in prostate cancer patients. Similar to hormonal medications, newer non-hormonal therapeutic options including gabapentin and acupuncture have at best moderate effect in controlling hot flashes in patients on ADT. Supervised and/or home exercise programs significantly improve ADT-related fatigue, metabolic/cardiovascular side effects, and cognitive dysfunction. Denosumab, a human monoclonal antibody against RANK-L, is more effective than bisphosphonates in preventing skeletal-related events in patients with metastatic or castrate-resistant prostate cancer and unlike bisphosphonates, it can also reduce the risk of vertebral fractures in men receiving ADT for non-metastatic prostate cancer. Toremifene, a selective estrogen receptor inhibitor, has dual beneficial effects on ADT-related osteoporosis and metabolic dysfunction. Metformin coupled with lifestyle modification is also a well-tolerated treatment for metabolic changes during ADT. While producing similar oncological outcomes, intermittent ADT is associated with higher quality of life in patients under ADT by improving bone health, less metabolic and hematologic complications, and fewer hot flashes and sexual dysfunction events. PMID:25045284

[Efficacy analysis of proximally extended resection for locally advanced rectal cancer after neoadjuvant chemoradiotherapy].

PubMed

Qin, Qiyuan; Kuang, Yingyi; Ma, Tenghui; Wu, Yali; Wang, Huaiming; Pi, Yanna; Wang, Hui; Wang, Lei

2017-11-25

To evaluate the short-term outcomes and perioperative safety of proximally extended resection for locally advanced rectal cancer after neoadjuvant chemoradiotherapy. From colorectal cancer database in The Sixth Affiliated Hospital of Sun Yat-sen University, a cohort of patients who underwent neoadjuvant chemoradiotherapy(1.8-2.0 Gy per day, 25-28 fractions, concurrent fluorouracil-based chemotherapy) followed by curative sphincter-preserving surgery for locally advanced rectal cancer between May 2016 and June 2017 were retrospectively identified. Exclusion criteria were synchronous colon cancer, intraoperatively confirmed distal metastasis, multiple visceral resection, and emergency operation. Thirty-one patients underwent proximal extended resection and two were excluded for incomplete extended resection, then 29 patients were enrolled as the extended group. Using propensity scores matching with 1/1 ration, 29 locally advanced rectal cancer patients who underwent conventional resection after neoadjuvant chemoradiotherapy at the same time were matched as the conventional group. Clinical data of two groups were analyzed, and the baseline characteristics and short-term outcomes were compared using the t test, χ 2 test, or Mann-Whitney U test. Two groups were well balanced with respect to the baseline characteristics after propensity score matching. As compared with conventional group, patients in extended group had longer surgical specimen [(18.8±5.1) cm vs.(11.6±3.4) cm, t=6.314, P=0.000] and longer proximal resection margin [(14.8±5.5) cm vs.(8.2±3.0) cm, t=5.725, P=0.000], but also had longer total operating time [(322.4±100.7) min vs.(254.6±70.3) min, t=2.975, P=0.004] and more intraoperative blood loss [100(225) ml vs. 100(50) ml, Z=-2.403, P=0.016]. No significant differences were observed in the length of distal resection margin, ratio of positive resection margin, number of retrieved lymph node, time of analgesic use, time of draining tube use, time to first flatus, time to first oral diet, and postoperative hospital stay. During the perioperative period of 30 days, the morbidity of complication in extended group and conventional group was 17.2%(5/29) and 34.5% (10/29), respectively (P=0.134). Proximally extended resection is a radical and safe surgical alternative for locally advanced rectal cancer after neoadjuvant chemoradiotherapy, which can potentially reduce the risk of anastomosis complication.

99mTc-sestamibi scintigraphy used to evaluate tumor response to neoadjuvant chemotherapy in locally advanced breast cancer: A quantitative analysis

PubMed Central

KOGA, KATIA HIROMOTO; MORIGUCHI, SONIA MARTA; NETO, JORGE NAHÁS; PERES, STELA VERZINHASSE; SILVA, EDUARDO TINÓIS DA; SARRI, ALMIR JOSÉ; MICHELIN, ODAIR CARLITO; MARQUES, MARIANGELA ESTHER ALENCAR; GRIVA, BEATRIZ LOTUFO

2010-01-01

To evaluate the tumor response to neoadjuvant chemotherapy, 99mTc-sestamibi breast scintigraphy was proposed as a quantitative method. Fifty-five patients with ductal carcinoma were studied. They underwent breast scintigraphy before and after neoadjuvant chemotherapy, along with clinical assessment and surgical specimen analysis. The regions of interest on the lesion and contralateral breast were identified, and the pixel counts were used to evaluate lesion uptake in relation to background radiation. The ratio of these counts before to after neoadjuvant chemotherapy was assessed. The decrease in uptake rate due to chemotherapy characterized the scintigraphy tumor response. The Kruskal-Wallis test was used to compare the mean scintigraphic tumor response and histological type. Dunn’s multiple comparison test was used to detect differences between histological types. The Mann-Whitney test was used to compare means between quantitative and qualitative variables: scintigraphic tumor response vs. clinical response and uptake before chemotherapy vs. scintigraphic tumor response. The Spearman’s test was used to correlate the quantitative variables of clinical reduction in tumor size and scintigraphic tumor response. All of the variables compared presented significant differences. The change in 99mTc-sestamibi uptake noted on breast scintigraphy, before to after neoadjuvant chemotherapy, may be used as an effective method for evaluating the response to neoadjuvant chemotherapy, since this quantification reflects the biological behavior of the tumor towards the chemotherapy regimen. Furthermore, additional analysis on the uptake rate before chemotherapy may accurately predict treatment response. PMID:22966312

Laparoscopic surgery is feasible for the treatment of rectal cancer after neoadjuvant chemoradiotherapy.

PubMed

Ju, Wencui; Luo, Xiaoyong; Han, Baowei

2016-09-01

This case-control study aimed to clarify the short- and long-term outcomes of laparoscopic surgery for rectal cancer after neoadjuvant chemo radiotherapy compared with conventional open resection. Between January 2008 and December 2014, a series of 227 patients with rectal cancer underwent radical surgery after neoadjuvant chemo radiotherapy. Age, gender, American Society of Anesthesiologists score, clinical stage, and type of resection were matched by propensity scoring and 106 patients (53 patients with laparoscopic total mesorectal excision and 53 patients with open resection) were selected for analysis. There were no significant differences in the clinicopathological features between the two groups. With regard to short-term outcomes, blood loss, postoperative analgesia and hospital stay were significantly shorter in the laparoscopy group than in the open group, whereas operative time was significantly longer in the laparoscopy group than in the open group. The overall morbidity was similar in the two groups. There were no significant differences in the 5-year overall and disease-free survival rates between the two groups. In summary, laparoscopic surgery may be both feasible and efficient compared with open resection for rectal cancer after neoadjuvant chemo radiotherapy.

Cardiovascular risk after androgen deprivation therapy for prostate cancer: an Asian perspective.

PubMed

Teoh, Jeremy Yuen Chun; Ng, Chi-Fai

2016-09-01

Androgen deprivation therapy (ADT) plays an important role in managing prostate cancer. However, ADT may result in major cardiovascular events and potentially lead to fatal consequences. Cardiovascular disease is the leading cause of mortality and it is a very important health condition to look into. Asians and Caucasians differ both physiologically and genetically, and they may have display different cardiovascular profiles. In this article, we reviewed the literature focusing on the cardiovascular risk after ADT for prostate cancer in the Asian population. We would discuss about the pathogenesis of ADT leading to cardiovascular events, summarize the findings concerning cardiac and stroke risks after ADT, compare between the different modalities of ADT and also provide genetic basics which are unique to Asians. We hope this article would provide more insights into the cardiovascular risk after ADT for prostate cancer in an Asian perspective.

Quality indicators for prostate radiotherapy: are patients disadvantaged by receiving treatment in a 'generalist' centre?

PubMed

Freeman, Amanda R; Roos, Daniel E; Kim, Laurence

2015-04-01

The purpose of this retrospective review was to evaluate concordance with evidence-based quality indicator guidelines for prostate cancer patients treated radically in a 'generalist' (as distinct from 'sub-specialist') centre. We were concerned that the quality of treatment may be lower in a generalist centre. If so, the findings could have relevance for many radiotherapy departments that treat prostate cancer. Two hundred fifteen consecutive patients received external beam radiotherapy (EBRT) and/or brachytherapy between 1.10.11 and 30.9.12. Treatment was deemed to be in line with evidence-based guidelines if the dose was: (i) 73.8-81 Gy at 1.8-2.0 Gy/fraction for EBRT alone (eviQ guidelines); (ii) 40-50 Gy (EBRT) for EBRT plus high-dose rate (HDR) brachytherapy boost (National Comprehensive Cancer Network (NCCN) guidelines); and (iii) 145 Gy for low dose rate (LDR) I-125 monotherapy (NCCN). Additionally, EBRT beam energy should be ≥6 MV using three-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT), and high-risk patients should receive neo-adjuvant androgen-deprivation therapy (ADT) (eviQ/NCCN). Treatment of pelvic nodes was also assessed. One hundred four high-risk, 84 intermediate-risk and 27 low-risk patients (NCCN criteria) were managed by eight of nine radiation oncologists. Concordance with guideline doses was confirmed in: (i) 125 of 136 patients (92%) treated with EBRT alone; (ii) 32 of 34 patients (94%) treated with EBRT + HDR BRT boost; and (iii) 45 of 45 patients (100%) treated with LDR BRT alone. All EBRT patients were treated with ≥6 MV beams using 3D-CRT (78%) or IMRT (22%). 84%, 21% and 0% of high-risk, intermediate-risk and low-risk patients received ADT, respectively. Overall treatment modality choice (including ADT use and duration where assessable) was concordant with guidelines for 176/207 (85%) of patients. The vast majority of patients were treated concordant with evidence-based guidelines suggesting that, within the limits of the selected criteria, prostate cancer patients are unlikely to be disadvantaged by receiving radiotherapy in this 'generalist' centre. © 2014 The Royal Australian and New Zealand College of Radiologists.

Reduced Arogenate Dehydratase Expression: Ramifications for Photosynthesis and Metabolism1[OPEN

PubMed Central

Höhner, Ricarda; Ito, Tetsuro; Amakura, Yoshiaki; Weitz, Karl

2018-01-01

Arogenate dehydratase (ADT) catalyzes the final step of phenylalanine (Phe) biosynthesis. Previous work showed that ADT-deficient Arabidopsis (Arabidopsis thaliana) mutants had significantly reduced lignin contents, with stronger reductions in lines that had deficiencies in more ADT isoforms. Here, by analyzing Arabidopsis ADT mutants using our phenomics facility and ultra-performance liquid chromatography-mass spectrometry-based metabolomics, we describe the effects of the modulation of ADT on photosynthetic parameters and secondary metabolism. Our data indicate that a reduced carbon flux into Phe biosynthesis in ADT mutants impairs the consumption of photosynthetically produced ATP, leading to an increased ATP/ADP ratio, the overaccumulation of transitory starch, and lower electron transport rates. The effect on electron transport rates is caused by an increase in proton motive force across the thylakoid membrane that down-regulates photosystem II activity by the high-energy quenching mechanism. Furthermore, quantitation of secondary metabolites in ADT mutants revealed reduced flavonoid, phenylpropanoid, lignan, and glucosinolate contents, including glucosinolates that are not derived from aromatic amino acids, and significantly increased contents of putative galactolipids and apocarotenoids. Additionally, we used real-time atmospheric monitoring mass spectrometry to compare respiration and carbon fixation rates between the wild type and adt3/4/5/6, our most extreme ADT knockout mutant, which revealed no significant difference in both night- and day-adapted plants. Overall, these data reveal the profound effects of altered ADT activity and Phe metabolism on secondary metabolites and photosynthesis with implications for plant improvement. PMID:29523714

Sleep disturbance in men receiving androgen deprivation therapy for prostate cancer: The role of hot flashes and nocturia.

PubMed

Gonzalez, Brian D; Small, Brent J; Cases, Mallory G; Williams, Noelle L; Fishman, Mayer N; Jacobsen, Paul B; Jim, Heather S L

2018-02-01

Patients with prostate cancer receiving androgen deprivation therapy (ADT) are at risk of sleep disturbance; however, to the authors' knowledge, the mechanisms by which ADT may affect sleep are not well understood. The current study compared objective and subjective sleep disturbance in ADT recipients and controls and examined whether sleep disturbance in ADT recipients is attributable to the influence of ADT on hot flashes and nocturia. Patients with prostate cancer were assessed before or within 1 month after the initiation of ADT as well as 6 months and 12 months later (78 patients). Patients with prostate cancer were treated with prostatectomy only (99 patients) and men with no history of cancer (108 men) were assessed at similar intervals. Participants self-reported their sleep disturbance (Insomnia Severity Index) and interference from hot flashes (Hot Flash Related Daily Interference Scale). One hundred participants also wore actigraphs for 3 days at the 6-month assessment to measure objective sleep disturbance and reported their nocturia frequency. ADT recipients reported worse sleep disturbance, higher rates of clinically significant sleep disturbance, and greater hot flash interference than controls (Ps≤.03). In cross-sectional analyses among those with actigraphy data, ADT recipients had greater objective sleep disturbance and more episodes of nocturia (Ps<.01). Cross-sectional mediation analyses demonstrated that the association between ADT and objectively and subjectively measured sleep disturbance was partly attributable to nocturia and hot flashes (Ps<.05). The results of the current study suggest that the association between ADT and sleep may be partly explained by nocturia and hot flash interference. Future studies should examine behavioral and pharmacologic interventions to address these symptoms among ADT recipients. Cancer 2018;124:499-506. © 2017 American Cancer Society. © 2017 American Cancer Society.

Hormonal response recovery after long-term androgen deprivation therapy in patients with prostate cancer.

PubMed

Planas, Jacques; Celma, Ana; Placer, José; Cuadras, Mercè; Regis, Lucas; Gasanz, Carlos; Trilla, Enrique; Salvador, Carlos; Lorente, David; Morote, Juan

2016-12-01

The aim of this study was to evaluate hormonal recovery after cessation of androgen deprivation therapy (ADT) in a group of elderly prostate cancer patients. Forty patients with locally advanced or metastatic prostate cancer, with a mean age of 71.5 years [95% confidence interval (CI) 69.1-73.9], were treated with ADT for a mean duration of 74.6 months (95% CI 59.7-89.5 months). Mean follow-up time after ADT cessation was 36.5 months (95% CI 30.6-42.3 months). Serum testosterone and luteinizing hormone (LH) were determined at 6 month intervals after ADT cessation. After 18 months of follow-up, all patients had recovered normal LH levels, while 38% of patients still presented castration levels of testosterone (< 50 ng/dl). A multivariate analysis was performed to find factors related to testosterone recovery (testosterone >50 ng/dl). Neither age at start of ADT nor clinical stage reached statistical significance. Only time under ADT was correlated with testosterone recovery (p = .031). Kaplan-Meier curves were obtained. Mean time for testosterone recovery was 14.5 months (95% CI 6.5-22.6 months) in patients treated with ADT for less than 60 months compared to 29.3 months (95% CI 19.6-39.1 months) in patients treated with ADT for more than 60 months (log-rank p = .029). Age did not correlate with testosterone recovery in a group of elderly prostate cancer patients in whom ADT was stopped. Testosterone recovery after ADT cessation was significantly correlated with time under ADT treatment. Significant implications related to economic aspects of the dosage schedule may be considered.

Adjuvant androgen-deprivation therapy following prostate total cryoablation in high-risk localized prostate cancer patients - Open-labeled randomized clinical trial.

PubMed

Chen, Chung-Hsin; Pu, Yeong-Shiau

2018-06-01

To investigate the efficacy and safety profile of 12-month adjuvant androgen-deprivation therapy (ADT) following total-gland cryoablation (TGC) in patients with high-risk localized prostate cancer (HRLPC). This open-label randomized trial included 38 HRLPC patients who received TGC between July 2011 and March 2013. Within 4 weeks after TGC, subjects were randomly assigned (1:1) to either the 12-month adjuvant ADT or non-adjuvant ADT group. The primary outcome was biochemical failure measured by the Phoenix definition. Adverse events were measured at month 1, 2, 3, 6, 9 and 12. In addition, a cohort of 145 HRLPC patients was selected retrospectively for outcome validation. The adjuvant ADT and non-adjuvant ADT groups did't differ in peri-operative characters, such as age, preoperative PSA, tumor stages, Gleason score, prostate size and cryoprobe number. Four patients with adjuvant ADT withdrew from this trial for personal reasons (N = 2), elevated liver function (N = 1) and poorly controlled hyperglycemia (N = 1). In contrast, none in non-adjuvant ADT group experienced adverse events. Biochemical failures were identified in 5 (26%) patients in each group during a median follow-up duration of 45 months. The median times to biochemical failure were 25 and 5.5 months for adjuvant ADT and non-adjuvant ADT groups, respectively. Biochemical-failure survival curves converged 24 months after TGC. Univariable and multivariable analyses revealed adjuvant ADT was not associated with biochemical recurrences in the validation cohort. Adjuvant ADT does not reduce biochemical failure for HRPLC patients undergoing TGC. It should be further confirmed by a larger cohort. Copyright © 2018. Published by Elsevier Inc.

Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

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

Gao, Yuan-Hong; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou; Lin, Jun-Zhong

Purpose: Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. Methods and Materials: Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consistingmore » of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. Results: All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. Conclusions: Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen as induction, concomitant, and consolidation chemotherapy to the conventional radiation is well tolerated. The strategy is highly effective in terms of pCR and major regression, which warrants further investigation.« less

Pretreatment Serum Testosterone and Androgen Deprivation: Effect on Disease Recurrence and Overall Survival in Prostate Cancer Patients Treated With Brachytherapy

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

Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.

Purpose: Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. Methods and Materials: From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined formore » each deceased patient. Results: Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). Conclusions: Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.« less

High-Risk Prostate Cancer With Gleason Score 8-10 and PSA Level {<=}15 ng/ mL Treated With Permanent Interstitial Brachytherapy

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

Fang, L. Christine; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org; Butler, Wayne M.

2011-11-15

Purpose: With widespread prostate-specific antigen (PSA) screening, there has been an increase in men diagnosed with high-risk prostate cancer defined by a Gleason score (GS) {>=}8 coupled with a relatively low PSA level. The optimal management of these patients has not been defined. Cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) were evaluated in brachytherapy patients with a GS {>=}8 and a PSA level {<=}15 ng/mL with or without androgen-deprivation therapy (ADT). Methods and Materials: From April 1995 to October 2005, 174 patients with GS {>=}8 and a PSA level {<=}15 ng/mL underwent permanent interstitial brachytherapy. Ofmore » the patients, 159 (91%) received supplemental external beam radiation, and 113 (64.9%) received ADT. The median follow-up was 6.6 years. The median postimplant Day 0 minimum percentage of the dose covering 90% of the target volume was 121.1% of prescription dose. Biochemical control was defined as a PSA level {<=}0.40 ng/mL after nadir. Multiple parameters were evaluated for impact on survival. Results: Ten-year outcomes for patients without and with ADT were 95.2% and 92.5%, respectively, for CSS (p = 0.562); 86.5% and 92.6%, respectively, for bPFS (p = 0.204); and 75.2% and 66.0%, respectively, for OS (p = 0.179). The median post-treatment PSA level for biochemically controlled patients was <0.02 ng/mL. Multivariate analysis failed to identify any predictors for CSS, whereas bPFS and OS were most closely related to patient age. Conclusions: Patients with GS {>=}8 and PSA level {<=}15 ng/mL have excellent bPFS and CSS after brachytherapy with supplemental external beam radiotherapy. The use of ADT did not significantly impact bPFS, CSS, or OS.« less

Protective effects of anethole dithiolethione against oxidative stress-induced cytotoxicity in human Jurkat T cells.

PubMed

Khanna, S; Sen, C K; Roy, S; Christen, M O; Packer, L

1998-07-01

The protective effects of anethole dithiolethione (ADT) against H2O2- or 4-hydroxynonenal (HNE)-induced cytotoxicity in human Jurkat T cells were investigated. Jurkat T cells were pretreated with ADT (10-50 microM) for 18 hr and then challenged with H202 or HNE for up to 4 hr. Cytotoxicity was assessed by measuring: 1) leakage of lactate dehydrogenase from cells to medium; and 2) exclusion of the DNA intercalating fluorescent probe propidium iodide by viable cells. Pretreatment of cells with ADT (10 or 25 microM) for 18 hr significantly protected cells against H202- or HNE-induced cytotoxicity. Treatment of cells with ADT (10-50 microM) for 72 hr significantly increased the activities of catalase and glutathione reductase. The maximum effect of ADT treatment on the activity of these enzymes was observed when cells were treated with 25 microM of ADT for 72 hr. A significant increase in cellular GSH was observed in cells that were treated with ADT for 72 hr. Using monobromobimane as a thiol probe, we consistently observed that cells pretreated for 18 hr with ADT (25 or 50 microM) had also increased total thiol content. Exposure of Jurkat T cells to H202 or HNE resulted in a time-dependent decrease in cellular GSH. ADT (10-50 microM, 18 hr) pretreatment circumvented H202-dependent lowering of cellular GSH. In conclusion, ADT proved to be a potent cytoprotective thiol antioxidant with multifaceted mechanisms of action, suggesting that the drug has a remarkable therapeutic potential.

Androgen deprivation therapy impact on quality of life and cardiovascular health, monitoring therapeutic replacement.

PubMed

Trost, Landon W; Serefoglu, Ege; Gokce, Ahmet; Linder, Brian J; Sartor, Alton O; Hellstrom, Wayne J G

2013-02-01

Androgen deprivation therapy (ADT) is commonly utilized in the management of both localized and advanced adenocarcinoma of the prostate. The use of ADT is associated with several adverse events, physical changes, and development of medical comorbidities/mortality. The current article reviews known adverse events associated with ADT as well as treatment options, where available. Current recommendations and guidelines are cited for ongoing monitoring of patients receiving ADT. A PubMed search of topics relating to ADT and adverse outcomes was performed, with select articles highlighted and reviewed based on level of evidence and overall contribution. Reported outcomes of studies detailing adverse effects of ADT were reviewed and discussed. Where available, randomized trials and meta-analyses were reported. ADT may result in several adverse events including decreased libido, erectile dysfunction, vasomotor symptoms, cognitive, psychological and quality of life impairments, weight gain, sarcopenia, increased adiposity, gynecomastia, reduced penile/testicular size, hair changes, periodontal disease, osteoporosis, increased fracture risk, diabetes and insulin resistance, hyperlipidemia, and anemia. The definitive impact of ADT on lipid profiles, cardiovascular morbidity/mortality, and all-cause mortality is currently unknown with available data. Treatment options to reduce ADT-related adverse events include changing to an intermittent treatment schedule, biophysical therapy, counseling, and pharmacotherapy. Patients treated with ADT are at increased risk of several adverse events and should be routinely monitored for the development of potentially significant morbidity/mortality. Where appropriate, physicians should reduce known risk factors and counsel patients as to known risks and benefits of therapy. © 2013 International Society for Sexual Medicine.

A randomized phase II trial evaluating different schedules of zoledronic acid on bone mineral density in patients with prostate cancer beginning androgen deprivation therapy.

PubMed

Lang, Joshua M; Wallace, Marianne; Becker, Jordan T; Eickhoff, Jens C; Buehring, Bjoern; Binkley, Neil; Staab, Mary Jane; Wilding, George; Liu, Glenn; Malkovsky, Miroslav; McNeel, Douglas G

2013-12-01

To assess the effects of timing and schedule of zoledronic acid (ZA) administration on bone mineral density (BMD) in patients beginning androgen deprivation therapy (ADT) for the treatment of recurrent prostate cancer. In this randomized, 3-arm trial, we evaluated changes in BMD after 3 different ZA administration schedules in men with recurrent prostate cancer who were beginning ADT. Forty-four patients were enrolled and randomized to receive a single dose of ZA given 1 week before beginning ADT (arm 1), a single dose of ZA given 6 months after beginning ADT (arm 2), or monthly administration of ZA starting 6 months after beginning ADT, for a total of 6 doses (arm 3). Patients who received ZA before ADT had a significant improvement in BMD at the total proximal femur and trochanter after 6 months compared with the other groups. In addition, only patients in the arm that received multiple doses improved lumbar spine BMD while on ADT, with these findings persisting to 24 months. However, this group also experienced more grade 1 adverse events. Analysis of these data suggests that ZA administration before initiation of ADT was superior to treatment 6 months after starting ADT in maintaining BMD. In addition, monthly ZA administration can increase BMD above baseline but is associated with more adverse events. Further study is needed to examine whether the timing and frequency of ZA therapy in patients on ADT can reduce fracture risk. Copyright © 2013 Elsevier Inc. All rights reserved.

Androgen deprivation therapy's impact on the mood of prostate cancer patients as perceived by patients and the partners of patients.

PubMed

Van Dam, Dexter; Wassersug, Richard J; Hamilton, Lisa Dawn

2016-07-01

To assess the relationship between of androgen deprivation therapy (ADT) and the mood of prostate cancer (PCa) patients and partners of PCa patients. PCa patients (n = 295) and partners of patients (n = 84) completed an online survey assessing the patients' current mood and mood prior to treatment, relationship adjustment, and sexual function. We compared men on ADT to men who received non-hormonal treatments for their PCa. Patients currently treated with ADT (n = 82) reported worsened mood as measured by the Profile of Mood States compared to those not on ADT (n = 213). The negative impact of ADT on mood, however, was reduced in older patients. Partners of patients on ADT (n = 42) reported similar declines in the patient's mood that patients reported, but to a greater degree than patient-reported levels. Our data support ADT's impact on PCa patients' mood and verify that partners concurrently see the effects. The psychological changes related to ADT can impact relationships and affect the quality of life of both PCa patients and partners. Patients and their partners are likely to benefit from being well informed about the psychological effects of androgen deprivation on men beginning ADT. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Large institutional variations in use of androgen deprivation therapy with definitive radiotherapy in a population-based cohort of men with intermediate- and high-risk prostate cancer.

PubMed

Ong, Wee Loon; Foroudi, Farshad; Evans, Sue; Millar, Jeremy

2017-11-01

To evaluate the pattern of use of androgen deprivation therapy (ADT) with definitive radiotherapy (RT) in men with prostate cancer (PCa) in a population-based study in Australia. This is a prospective cohort of men with intermediate- and high-risk PCa, captured in the population-based Prostate Cancer Outcome Registry Victoria, who were treated with definitive prostate RT between January 2010 and December 2015. The primary outcome of interest was ADT utilization. Chi-squared test for trend was used to evaluate the temporal trend in the use of ADT over the study period. Multivariate logistic regressions were used to evaluate the effects of patient-, tumour- and treatment-related factors, and treatment institutions (public/ private and metropolitan/ regional) on the likelihood of ADT utilization. A total of 1806 men were included in the study, 199 of whom (11%) had favourable National Comprehensive Cancer Network (NCCN) intermediate-risk disease (i.e. only one intermediate-risk feature, primary Gleason grade 3, and <50% biopsy core involved), 687 (38%) had unfavourable NCCN intermediate-risk disease, and 920 (51%) had high-risk disease. Of the 1806 men, 1155 (64%) received ADT with RT. Men with NCCN high-risk PCa (84%) were more likely to have ADT than men with favourable NCCN intermediate-risk (32%) and unfavourable NCCN intermediate-risk (46%) PCa (P < 0.001). Men treated in public institutions (66%, vs 47% in private institutions; P < 0.001) and regional centres (78%, vs 59% in metropolitan institutions; P < 0.001) were more likely to receive ADT. There was a trend towards an increase in ADT utilization from 50% in 2010 to 64% in 2015 (P < 0.001). In multivariate analyses (adjusting for age, tumour-related factors, year of treatment and use of brachytherapy boost), treatment institution (public and regional) remained independently associated with increased likelihood of ADT utilization. Men with intermediate-risk PCa treated in regional and public institutions were 2.7 times (95% confidence interval [CI] 1.9-3.9; P < 0.001) and 2.8 times (95% CI 1.4-5.3; P = 0.002), more likely to receive ADT with RT, respectively, while men with high-risk PCa treated in regional and public institutions were 3.1 times (95% CI 1.7-5.7; P < 0.001) and 3.0 times (95% CI 1.7-5.4; P < 0.001), more likely to receive ADT with RT, respectively. This is the largest Australasian contemporary series reporting on the pattern of use of ADT with definitive prostate RT. While there was an increasing trend towards use of ADT over time, ADT still appeared to be underutilized in certain groups of patients who may benefit from ADT, with approximately one in five men with high-risk and one in two with unfavourable intermediate-risk PCa not receiving ADT with RT. There was notable variation in the use of ADT between public vs private and metropolitan vs regional institutions. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

The Value of Restaging With Chest and Abdominal CT/MRI Scan After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

PubMed

Liu, Guo-Chen; Zhang, Xu; Xie, E; An, Xin; Cai, Pei-Qiang; Zhu, Ying; Tang, Jing-Hua; Kong, Ling-Heng; Lin, Jun-Zhong; Pan, Zhi-Zhong; Ding, Pei-Rong

2015-11-01

Little was known with regard to the value of preoperative systemic restaging for patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT). This study was designed to evaluate the role of chest and abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI) on preoperative restaging in LARC after neoadjuvant CRT and to assess the impact on treatment strategy.Between January 2007 and April 2013, 386 newly diagnosed consecutive patients with LARC who underwent neoadjuvant CRT and received restaging with chest and abdominal CT/MRI scan were included. Imaging results before and after CRT were analyzed.Twelve patients (3.1%) (6 liver lesions, 2 peritoneal lesions, 2 distant lymph node lesions, 1 lung lesions, 1 liver and lung lesions) were diagnosed as suspicious metastases on the restaging scan after radiotherapy. Seven patients (1.8%) were confirmed as metastases by pathology or long-term follow-up. The treatment strategy was changed in 5 of the 12 patients as a result of restaging CT/MRI findings. Another 10 patients (2.6%) who present with normal restaging imaging findings were diagnosed as metastases intra-operatively. The sensitivity, specificity accuracy, negative predictive value, and positive predictive values of restaging CT/MRI was 41.4%, 98.6%, 58.3%, and 97.3%, respectively.The low incidence of metastases and minimal consequences for the treatment plan question the clinical value of routine restaging of chest and abdomen after neoadjuvant CRT. Based on this study, a routine restaging CT/MRI of chest and abdomen in patients with rectal cancer after neoadjuvant CRT is not advocated, carcino-embryonic antigen (CEA) -guided CT/MRI restaging might be an alternative.

DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

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

Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu; Wang Xiaozhe; Niemierko, Andrzej

2012-05-01

Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, withmore » biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need confirmation in an independent data set.« less

Identification of residual breast carcinoma following neoadjuvant chemotherapy: diffusion-weighted imaging--comparison with contrast-enhanced MR imaging and pathologic findings.

PubMed

Woodhams, Reiko; Kakita, Satoko; Hata, Hirofumi; Iwabuchi, Keiichi; Kuranami, Masaru; Gautam, Shiva; Hatabu, Hiroto; Kan, Shinichi; Mountford, Carolyn

2010-02-01

To compare the capability of diffusion-weighted (DW) and contrast material-enhanced magnetic resonance (MR) imaging to provide diagnostic information on residual breast cancers following neoadjuvant chemotherapy and to assess apparent diffusion coefficients (ADCs) of the carcinoma prior to neoadjuvant chemotherapy to determine if the method could help predict response to chemotherapy. Institutional review board approval and informed consent were obtained. Three hundred ninety-eight patients underwent MR imaging of the breast, including DW MR (b values, 0 and 1500 sec/mm(2)) and contrast-enhanced MR imaging. Of these, the contralateral breast in 73 women was used as a control. Seventy-two patients with 73 lesions with malignant disease were treated by using neoadjuvant chemotherapy and were examined for residual disease following therapy. Three were excluded because of prolonged intervals between final MR imaging and surgery. Thus, 69 patients (70 lesions) with DW and contrast-enhanced MR imaging results were compared with postoperative histopathologic findings. The ADCs of the carcinoma prior to neoadjuvant chemotherapy were calculated for each patient, and those with complete response and residual disease were compared. The accuracy for depicting residual tumor was 96% for DW MR imaging, compared with an accuracy of 89% for contrast-enhanced MR imaging (P = .06). There was no significant difference in prechemotherapy ADCs between pathologic complete response cases and those with residual disease. DW MR imaging had at least as good of accuracy as did contrast-enhanced MR imaging for monitoring neoadjuvant chemotherapy. The ADCs prior to chemotherapy did not predict response to chemotherapy. The use of DW imaging to visualize residual breast cancer without the need for contrast medium could be advantageous in women with impaired renal function. (c) RSNA, 2010

Magnetic resonance imaging (MRI)-based indication for neoadjuvant treatment of rectal carcinoma and the surrogate endpoint CRM status.

PubMed

Strassburg, Joachim; Junginger, Theo; Trinh, Trong; Püttcher, Olaf; Oberholzer, Katja; Heald, Richard J; Hermanek, Paul

2008-11-01

Is it possible to reduce the frequency of neoadjuvant therapy for rectal carcinoma and nevertheless achieve a rate of more than 90% circumferential resection margin (CRM)-negative resection specimens by a novel concept of magnetic resonance imaging (MRI)-based therapy planning? One hundred eighty-one patients from Berlin and Mainz, Germany, with primary rectal carcinoma, without distant metastasis, underwent radical surgery with curative intention. Surgical procedures applied were anterior resection with total mesorectal excision (TME) or partial mesorectal excision (PME; PME for tumours of the upper rectum) or abdominoperineal excision with TME. With MRI selection of the highest-risk cases, neoadjuvant therapy was given to only 62 of 181 (34.3%). The rate of CRM-negative resection specimens on histology was 170 of 181 (93.9%) for all patients, and in Berlin, only 1 of 93 (1%) specimens was CRM-positive. Patients selected for primary surgery had CRM-negative specimens on histology in 114 of 119 (95.8%). Those selected for neoadjuvant therapy had a lower rate of clear margin: 56 of 62 (90%). By applying a MRI-based indication, the frequency of neoadjuvant treatment with its acute and late adverse effects can be reduced to 30-35% without reduction of pathologically CRM-negative resection specimens and, thus, without the danger of worsening the oncological long-term results. This concept should be confirmed in prospective multicentre observation studies with quality assurance of MRI, surgery and pathology.

Hepatoblastoma in Children With Congenital Portosystemic Shunts.

PubMed

Lautz, Timothy B; Shah, Sonam A; Superina, Riccardo A

2016-04-01

Two children developed hepatoblastoma concurrent with congenital portosystemic shunts (PSSs) (Abernethy malformations). Both underwent operative ligation of their PSSs. One received concurrent tumor resection, whereas the other was deemed initially unresectable and underwent biopsy followed by neoadjuvant chemotherapy. Although benign hepatic masses, such as focal nodular hyperplasia and nodular regenerative hyperplasia, are common in patients with Abernethy malformations, malignant tumors have also been documented and should always be considered in the differential diagnosis of a patient with a congenital PSS and a hepatic mass.

The Dehydratase ADT3 Affects ROS Homeostasis and Cotyledon Development1[OPEN

PubMed Central

Para, Alessia; Muhammad, DurreShahwar; Naldrett, Michael J.; Warpeha, Katherine M.

2016-01-01

During the transition from seed to seedling, emerging embryos strategically balance available resources between building up defenses against environmental threats and initiating the developmental program that promotes the switch to autotrophy. We present evidence of a critical role for the phenylalanine (Phe) biosynthetic activity of AROGENATE DEHYDRATASE3 (ADT3) in coordinating reactive oxygen species (ROS) homeostasis and cotyledon development in etiolated Arabidopsis (Arabidopsis thaliana) seedlings. We show that ADT3 is expressed in the cotyledon and shoot apical meristem, mainly in the cytosol, and that the epidermis of adt3 cotyledons contains higher levels of ROS. Genome-wide proteomics of the adt3 mutant revealed a general down-regulation of plastidic proteins and ROS-scavenging enzymes, corroborating the hypothesis that the ADT3 supply of Phe is required to control ROS concentration and distribution to protect cellular components. In addition, loss of ADT3 disrupts cotyledon epidermal patterning by affecting the number and expansion of pavement cells and stomata cell fate specification; we also observed severe alterations in mesophyll cells, which lack oil bodies and normal plastids. Interestingly, up-regulation of the pathway leading to cuticle production is accompanied by an abnormal cuticle structure and/or deposition in the adt3 mutant. Such impairment results in an increase in cell permeability and provides a link to understand the cell defects in the adt3 cotyledon epidermis. We suggest an additional role of Phe in supplying nutrients to the young seedling. PMID:27540109

Impact of novel histopathological factors on the outcomes of liver surgery for colorectal cancer metastases.

PubMed

Serrablo, A; Paliogiannis, P; Pulighe, F; Moro, S Saudi-Moro; Borrego-Estella, V; Attene, F; Scognamillo, F; Hörndler, C

2016-09-01

We evaluated the impacts of a series of novel histopathological factors on clinical-surgical outcomes and survival of patients who underwent surgery for colorectal cancer liver metastasis, with and without neoadjuvant chemotherapy. A prospective database including 150 consecutive patients who underwent 183 hepatic resections for metastatic colorectal cancer was evaluated. Among them, 74 (49.3%) received neoadjuvant chemotherapy before surgery. The histopathological factors studied were: a) microsatellitosis, b) type and pattern of tumour growth, c) nuclear grade and the number of mitoses/mm(2), d) perilesional pseudocapsule, e) intratumoural fibrosis, f) lesion cellularity, g) hypoxic-angiogenic perilesional growth pattern, and h) the tumour normal interface. Three or more metastatic lesions, R1 resection margins, and <50% tumour necrosis were prognostic factors for a worse OS, but only the former was confirmed to be an independent prognostic factor in the multivariate analysis. Furthermore, tumour fibrosis <40% and cellularity >10% were predictive of a worse neoadjuvant therapy response, but these findings were not confirmed in the multivariate analysis. Finally, tumour necrosis <50%, cellularity >10%, and TNI >0.5 mm were prognostic factors for a worse DFS and AS in the univariate but not in the multivariate analysis. Several factors seem to influence the outcomes of surgery for colorectal cancer liver metastasis, especially the number of the lesions, the margins of resection, the percentage of necrosis and fibrosis, as well as the cellularity and the TNI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Less than 12 lymph nodes in the surgical specimen after neoadjuvant chemo-radiotherapy: an indicator of tumor regression in locally advanced rectal cancer?

PubMed Central

Gurawalia, Jaiprakash; Nayak, Sandeep P.; Kurpad, Vishnu; Pandey, Arun

2016-01-01

Background The number of lymph node retrieved in the surgical specimen is important for tumor staging and has paramount impact on prognosis in colorectal cancer and imitates the adequacy of lymph node surgical clearance. The paucity of lymph node yields in patients undergoing resection after preoperative chemo radiotherapy (CRT) in rectal cancer has seen. Lower total number of lymph nodes in the total mesoractal excision (TME) specimen after CRT, could a marker of better tumor response. Methods We retrospectively reviewed the prospectively managed data of patients underwent excision for rectal cancer, who treated by neoadjuvant radiotherapy with or without chemotherapy in locally advanced rectal cancer. From 2010 to 2014, 364 patients underwent rectal cancer surgery, of which ninety-one treated with neoadjuvant treatment. Standard surgical and pathological protocols were followed. Patients were categorized into two groups based on the number of total harvested lymph nodes with group 1, having 12 or more nodes harvested, and group 2 including patients who had <12 lymph nodes harvested. The total number of lymph nodes retrieved from the surgical specimen was correlated with grade of tumor regression with neoadjuvant treatment. Results Out of 91 patients, 38 patients (42%) had less than 12 lymph nodes examined in specimen. The difference in median number of lymph nodes was observed significantly as 9 (range, 2–11) versus 16 (range, 12–32), in group 2 and 1, respectively (P<0.01). Patients with fewer lymph node group were comparable with respect to age, BMI, pre-operative staging, neoadjuvant treatment. Pathological complete response in tumor pCR was seen with significantly higher rate (40% vs. 26%, P<0.05) in group 2. As per Mandard criteria, there was significant difference in tumor regression grade (TRG) between both the groups (P<0.05). Among patients with metastatic lymph nodes, median LNR was lower in <12 lymph nodes group at 0.167 (range, 0.09–0.45) versus 0.187 (range, 0.05–0.54), difference was not statistically significant (P=0.81). Conclusions Retrieval of fewer than 12 lymph nodes in surgical specimen of rectal cancer who had received neo-adjuvant radiotherapy with or without chemotherapy should be considered as a good indicator of tumor response with better local disease control, and a good prognostic factor, rather than as a pointer of poor diligence of the surgical and pathological assessment. PMID:28078118

Evaluation of neoadjuvant chemotherapy effects on liver parenchyma in resected pediatric malignancies.

PubMed

Scuderi, Maria Grazia; Magro, Gaetano; Di Cataldo, Andrea; Pesce, Antonino; Scalora, Luisa; Vecchio, Giada Maria; Portale, Rosanna; Di Benedetto, Vincenzo; Puleo, Stefano

2013-08-01

Neoadjuvant chemotherapy for colorectal liver metastases in adults is responsible for chemotherapy-associated liver injury (CALI), characterized by steatosis, steatohepatitis, and sinusoidal obstruction syndrome. These alterations cause delayed operation to reduce the risk of hemorrhage, portal hypertension, and hepatic failure. Children with hepatic malignancies usually receive neoadjuvant chemotherapy prior to surgery. The aim of this study was to evaluate retrospectively whether the CALI occurs in this pediatric population. This study evaluated patients referred since 1996 for hepatic malignancies who received hepatectomy after chemotherapy. Liver resection material was reviewed, in order to investigate the presence of morphological changes compatible with the CALI in the peritumoral hepatic tissue. Twelve patients were recruited. All patients satisfied the inclusion criteria except one who did not receive neoadjuvant chemotherapy. Eleven children underwent surgery 1 month after the last chemotherapy cycle. All are alive disease-free. Histological examination of specimen revealed only mild changes such as diffuse swelling of hepatocytes and focal, mild portal inflammation. Severe hepatic changes such as steatosis, necrosis, or fibrosis were not identified. CALI-related morphological changes were not found in our patients. The absence of the CALI could be attributed to the younger age of patients (possible different response to stress) and/or to the different chemotherapy schedules compared to those in use for adults patients.

Neoadjuvant or adjuvant therapy for resectable esophageal cancer: is there a standard of care?

PubMed

Almhanna, Khaldoun; Shridhar, Ravi; Meredith, Kenneth L

2013-04-01

Carcinoma of the esophagus is an aggressive and lethal disease with an increasing incidence worldwide. Despite changes in the treatment approach over the past two decades and even following complete resection, most patients will eventually relapse and die as a result of their disease. Several clinical trials evaluated different modalities in treating locally advanced esophageal cancer; however, because of stage migration and the changes in disease epidemiology, applying these trials to clinical practice has become a daunting task. We searched Medline and conference abstracts for randomized studies published in the past three decades. We restricted our search to articles published in English. Neoadjuvant chemoradiotherapy followed by surgical resection is an accepted standard of care in the United States for patients with locally advanced esophageal cancer. Esophagectomy remains an essential component of treatment and can lead to improved overall survival, especially when performed at high-volume institutions. The role of adjuvant chemotherapy following curative resection in patients who underwent neoadjuvant chemotherapy and radiation remains unclear. Several questions still need to be answered regarding the use of neoadjuvant or adjuvant therapy for patients with resectable esophageal cancer. The optimal chemotherapy regimen has not yet been identified for these patients, although newer therapies show promise.

[Treatment of pelvic Ewing's sarcoma in children and the effect on the skeletal growth and development].

PubMed

Fu, Jun; Guo, Zheng; Wang, Zhen; Li, Xiang-dong; Li, Jing; Chen, Guo-jing; Wu, Zhi-gang

2012-12-01

To explore the effect of neo-adjuvant chemotherapy and computer-assisted surgery on children and adolescents with primary pelvic Ewing's sarcoma, and assess the therapeutic effect on the pelvic skeletal growth and development. This is a retrospective analysis of 10 children with primary pelvic Ewing's sarcoma treated between Jan 2001 and Oct 2010 at the Department of Oncologic Orthopaedics at Xijing Hospital. There were 3 girls and 7 boys in the age of 7 to 16 years (average 12.7 years). All patients were pathologically diagnosed as Ewing's sarcoma. There were two cases in the sacroiliac joint, one in the ilium, one in the pubic bone, and 6 cases in peri-acetabular area including 5 below the triradiate cartilage and one above the triradiate cartilage, without cartilage invasion. All patients underwent neo-adjuvant chemotherapy, resection and reconstruction surgery and postoperative chemotherapy. CDP, ADM and IFO regimen chemotherapy were given as the main treatment. Five cases were treated by traditional resection and reconstruction, and after 2008, five cases were treated by computer-assisted surgery. During the reconstruction, the hip rotation center was put at a depressed location. All of the 10 cases underwent postoperative radiotherapy in a dose of 45-55 Gy. All patients were followed-up for 12-72 months (mean: 37.8 months). One child had tumor recurrence and lung metastasis and 9 patients had no evidence of disease (NED). After neo-adjuvant chemotherapy, the oncologic statuses (RECIST) were: 1 CR, 8 PR and 1 SD. The functional recoveries after surgery (Enneking's) were: 4 cases excellent, 4 good, 1 fair and 1 poor. Five cases who underwent computer-assisted surgery achieved a good reconstruction without local recurrence. There were no effects on skeletal growth in 8 cases. An unbalanced hip rotational center occurred in one case, and a compemsatory scoliosis was found in another case. There were no serious complications in all patients. The comprehensive treatment including neo-adjuvant chemotherapy, resection-reconstruction surgery and postoperative chemoradiotherapy may give a good control to primary pelvic Ewing's sarcomas in children and adolescents. The computer-assisted surgery used for accurate tumor resection and pelvic reconstruction is a good alternative when treating young patients with malignant pelvic tumors. The triradiate cartilage in children's acetabulum could be a natural barrier resistant to the invasion of Ewing's sarcomas.

Age-dependent effects of topiramate on the acquisition and the retention of rapid kindling.

PubMed

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2007-04-01

To examine antiepileptogenic, disease modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Afterdischarge threshold (ADT) and duration (ADD) were examined in 2-, 3-, and 5-week-old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10-s trains, bipolar 20 Hz square wave pulses delivered every 5 min). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 h after the protocol were compared between topiramate and vehicle-treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. In 2-week-old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In 3-week-old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of 5-week-old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty-four h after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle-treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages.

Age-Dependent Effects of Topiramate on the Acquisition and the Retention of Rapid Kindling

PubMed Central

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2008-01-01

Summary Purpose To examine antiepileptogenic, disease-modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Methods Afterdischarge threshold (ADT) and duration (ADD) were examined in two-, three-, and five-week old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10 second trains, bipolar 20 Hz square wave pulses delivered every five minutes). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 hours after the protocol were compared between topiramate and vehicle treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. Results In two-week old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In three-week old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of five-week old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty four hours after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Conclusions Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages. PMID:17319916

LHRH Agonists for the Treatment of Prostate Cancer: 2012

PubMed Central

Lepor, Herbert; Shore, Neal D

2012-01-01

The most recent guidelines on prostate cancer screening from the American Urological Association (2009), the National Comprehensive Cancer Network (2011), and the European Association of Urology (2011), as well as treatment and advances in disease monitoring, have increased the androgen deprivation therapy (ADT) population and the duration of ADT usage as the first-line treatment for metastatic prostate cancer. According to the European Association of Urology, gonadotropin-releasing hormone (GnRH) agonists have become the leading therapeutic option for ADT because they avoid the physical and psychological discomforts associated with orchiectomy. However, GnRH agonists display several shortcomings, including testosterone (T) surge (“clinical flare”) and microsurges. T surge delays the intended serologic endpoint of T suppression and may exacerbate clinical symptoms. Furthermore, ADT manifests an adverse-event spectrum that can impact quality of life with its attendant well-documented morbidities. Strategies to improve ADT tolerability include a holistic management approach, improved diet and exercise, and more specific monitoring to detect and prevent T depletion toxicities. Intermittent ADT, which allows hormonal recovery between treatment periods, has become increasingly utilized as a methodology for improving quality of life while not diminishing chronic ADT efficacy, and may also provide healthcare cost savings. This review assesses the present and potential future role of GnRH agonists in prostate cancer and explores strategies to minimize the adverse-event profile for patients receiving ADT. PMID:23172994

Changes in physical functioning and muscle strength in men receiving androgen deprivation therapy for prostate cancer: a controlled comparison.

PubMed

Gonzalez, Brian D; Jim, Heather S L; Small, Brent J; Sutton, Steven K; Fishman, Mayer N; Zachariah, Babu; Heysek, Randy V; Jacobsen, Paul B

2016-05-01

The purpose of the study is to examine changes in muscle strength and self-reported physical functioning in men receiving androgen deprivation therapy (ADT) for prostate cancer compared to matched controls. Prostate cancer patients scheduled to begin ADT (n = 62) were assessed within 20 days of starting ADT and 6 and 12 months later. Age and geographically matched prostate cancer controls treated with prostatectomy only (n = 86) were assessed at similar time intervals. Grip strength measured upper body strength, the Chair Rise Test measured lower body strength, and the SF-12 Physical Functioning scale measured self-reported physical functioning. As expected, self-reported physical functioning and upper body muscle strength declined in ADT recipients but remained stable in prostate cancer controls. Contrary to expectations, lower body muscle strength remained stable in ADT recipients but improved in prostate cancer controls. Higher Gleason scores, more medical comorbidities, and less exercise at baseline predicted greater declines in physical functioning in ADT recipients. ADT is associated with declines in self-reported physical functioning and upper body muscle strength as well as worse lower body muscle strength relative to prostate cancer controls. These findings should be included in patient education regarding the risks and benefits of ADT. Findings also underscore the importance of conducting research on ways to prevent or reverse declines in physical functioning in this patient population.

Vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving chemotherapy and conservative surgery.

PubMed

Mabuchi, Yasushi; Yahata, Tamaki; Kobayashi, Aya; Tanizaki, Yuko; Minami, Sawako; Ino, Kazuhiko

2015-06-01

Vaginal carcinoma is a rare gynecological malignancy that is usually treated by radiation therapy and/or surgery combined with chemotherapy. Here, we report a case of invasive vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving neoadjuvant chemotherapy and conservative surgery. A 36-year-old non-parous woman had a solid tumor in the vagina. Positron emission tomography/computed tomography showed a tumor in the vagina with high FDG uptake (SUV = 17.33) but no metastatic lesions. The patient was diagnosed with vaginal squamous cell carcinoma, FIGO stage I, T1N0M0. Because she wished to retain her fertility, neoadjuvant chemotherapy consisting of irinotecan hydrochloride and nedaplatin was initiated. After four courses of chemotherapy, partial vaginectomy was carried out and the pathological diagnosis of the residual lesion was VAIN 3. Following two further courses of the same chemotherapy, she obtained complete response, and has shown no evidence of disease for 14 months. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Upfront Androgen Deprivation Therapy With Salvage Radiation May Improve Biochemical Outcomes in Prostate Cancer Patients With Post-Prostatectomy Rising PSA

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

Jang, Joanne W.; Hwang, Wei-Ting; Guzzo, Thomas J.

2012-08-01

Purpose: The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT. Methods and Materials: Of nearly 2,000 post-prostatectomy patients, we reviewed the medical records of 191 patients who received salvage RT at University of Pennsylvania between 1987 and 2007. Follow-up data were obtained by chart review and electronic polling of the institutional laboratory database and Social Securitymore » Death Index. Biochemical failure after salvage RT was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir or the initiation of ADT after completion of salvage RT. Results: One hundred twenty-nine patients received salvage RT alone, and 62 patients received combined ADT and salvage RT. Median follow-up was 5.4 years. Patients who received combined ADT and salvage RT were younger, had higher pathologic Gleason scores, and higher rates of seminal vesicle invasion, lymph node involvement, and pelvic nodal irradiation compared with patients who received salvage RT alone. Patients who received combined therapy had improved biochemical progression-free survival (bPFS) compared with patients who received RT alone (p = 0.048). For patients with pathologic Gleason scores {<=}7, combined RT and ADT resulted in significantly improved bPFS compared to RT alone (p = 0.013). Conclusions: These results suggest that initiating ADT during salvage RT in the post-prostatectomy setting may improve bPFS compared with salvage RT alone. However, prospective randomized data are necessary to definitively determine whether hormonal manipulation should be used with salvage RT. Furthermore, the optimal nature and duration of ADT and the patient subgroups in which ADT could provide the most benefit remain open questions.« less

[Neoadjuvant Radiochemotherapy Followed by Curative Resection in Patients with Advanced Non-Small Cell Lung Cancer in Stage IIIA/IIIB: Prognostic Factors and Results].

PubMed

Schreiner, W; Dudek, W; Lettmaier, S; Gavrychenkova, S; Rieker, R; Fietkau, R; Sirbu, H

2016-06-01

The role of surgical lung resection following neo-adjuvant radio-chemotherapy (RCT) in patients with locally advanced non-small cell lung cancer (NSCLC) is yet not clearly defined. The aim of our study was to analyze the postoperative survival and to identify relevant prognostic factors. 46 patients underwent curative resections after neo-adjuvant RCT for locally advanced NSCLC (IIIA/IIIB) between February 2008 and February 2015. A retrospective data analysis regarding preoperative regression status, perioperative mortality, postoperative survival, patho-histological remission, relapse pattern and other prognostic factors was performed. A neo-adjuvant RCT with a median radiation dose of 50.4 [range, 45-60] Gy was performed in 44 (96 %) patients. Partial and/or complete regression was observed in 32 (70 %) patients. R0-resection was achieved in 44 (96 %) patients. The 30-day mortality was 4 % and the perioperative morbidity was 37 %. The overall and progression free 5-year survival rate was 47 % and respectively 45 % [in median 58 months]. The 5-year survival rate of 64 % in the "responder"-group was significantly better when compared with 24 % in the "non-responder"-group (p = 0.038). The tri-modality therapy improved the prognosis in patients with locally advanced NSCLC (stage IIIA/IIIB). The complete patho-histological remission is an important prognostic factor for better long term survival. Dividing the patients in "responder" and "non-responder" after neo-adjuvant RCT may have large therapeutically consequences in the future. Georg Thieme Verlag KG Stuttgart · New York.

Neoadjuvant radiation therapy prior to total mesorectal excision for rectal cancer is not associated with postoperative complications using current techniques.

PubMed

Milgrom, Sarah A; Goodman, Karyn A; Nash, Garrett M; Paty, Philip B; Guillem, José G; Temple, Larissa K; Weiser, Martin R; Garcia-Aguilar, Julio

2014-07-01

Neoadjuvant radiation therapy (RT) downstages rectal cancer but may increase postoperative morbidity. This study aims to quantify 30-day complication rates after total mesorectal excision (TME) using current techniques and to assess for an association of these complications with neoadjuvant RT. Stage I-III rectal cancer patients who underwent TME from 2005 to 2010 were identified. Complications occurring within 30 days after TME were retrieved from a prospectively maintained institutional database of postoperative adverse events. The cohort consisted of 461 patients. Median age was 59 years (range 18-90), and 274 patients (59 %) were male. Comorbid conditions included obesity (n = 147; 32 %), coronary artery disease (n = 83; 18 %), diabetes (n = 65; 14 %), and inflammatory bowel disease (n = 19; 4 %). A low anterior resection (LAR) was performed in 383 cases (83 %), an abdominoperineal resection (APR) was performed in 72 cases (16 %), and a Hartmann's procedure was performed in 6 cases (1 %). Preoperative RT was delivered to 310 patients (67 %; median dose of 50.4 Gy, range 27-55.8 Gy). The 30-day incidence of postoperative mortality was 0.4 % (n = 2), any complication 25 % (n = 117), grade 3 or more complication 5 % (n = 24), intra-abdominal infection 3 % (n = 12), abdominal wound complication 9 % (n = 42), perineal wound complication after APR 11 % (n = 8/72), and anastomotic leak after LAR 2 % (n = 6/383). These events were not associated with neoadjuvant RT. In a cohort undergoing TME using current techniques, neoadjuvant RT was not associated with 30-day postoperative morbidity or mortality.

Hormone Therapy Plus Chemotherapy for Metastatic Prostate Cancer

Cancer.gov

A trial of androgen deprivation therapy (ADT) plus six cycles of docetaxel versus ADT alone found that after a median follow-up of nearly 29 months, median overall survival was 13.6 months longer with the combination therapy than with ADT alone.

Concurrent Androgen Deprivation Therapy During Salvage Prostate Radiotherapy Improves Treatment Outcomes in High-Risk Patients

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

Soto, Daniel E., E-mail: dsoto2@partners.org; Passarelli, Michael N.; Daignault, Stephanie

2012-03-01

Purpose: To determine whether concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes. Methods and Materials: A total of 630 postprostatectomy patients were retrospectively identified who were treated with three-dimensional conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical failure was defined as prostate-specific antigen (PSA) of 0.2 ng/mL or greater above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of biochemical failure, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression, or distant failure. Multivariate-adjustedmore » Cox proportional hazards modeling was performed to determine which factors predict PFS. Results: Low-, intermediate-, and high-risk patients made up 10%, 24%, and 66% of patients, respectively. The mean RT dose was 68 Gy. Twenty-four percent of patients received concurrent ADT (cADT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-year PFS was 4.0 years for cADT vs. 3.4 years for cADT patients (p = 0.22). Multivariate analysis showed that concurrent ADT (p = 0.05), Gleason score (p < 0.001), and pre-RT PSA (p = 0.03) were independent predictors of PFS. When patients were stratified by risk group, the benefits of cADT (hazard ratio, 0.65; p = 0.046) were significant only for high-risk patients. Conclusions: This retrospective study showed a PFS benefit of concurrent ADT during salvage prostate RT. This benefit was observed only in high-risk patients.« less

Androgen deprivation therapy for prostate cancer: recommendations to improve patient and partner quality of life.

PubMed

Elliott, Stacy; Latini, David M; Walker, Lauren M; Wassersug, Richard; Robinson, John W

2010-09-01

Because of improved prostate cancer detection, more patients begin androgen deprivation therapy (ADT) earlier and remain on it longer than before. Patients now may be androgen deprived for over a decade, even when they are otherwise free of cancer symptoms. An ADT Survivorship Working Group was formed to develop and evaluate interventions to limit the physiological and emotional trauma patients and their partners experience from this treatment. The multidisciplinary Working Group met for 2 days to define the challenges couples face when patients commence ADT. A writing sub-group was formed. It compiled the meeting's proceedings, reviewed the literature and, in consultation with the other members of the working group, wrote the manuscript. Expert opinion of the side effects of ADT that affect the quality of life (QOL) of patients and their partners and the recommendations for managing ADT to optimize QOL were based on the best available literature, clinical experience, and widespread internal discussions among Working Group members. Side effects identified as particularly challenging include: (i) body feminization; (ii) changes in sexual performance; (iii) relationship changes; (iv) cognitive and affective symptoms; and (v) fatigue, sleep disturbance, and depression. Recommendations for managing ADT include providing information about ADT side effects before administration of ADT, and, where appropriate, providing referrals for psychosocial support. Sexual rehabilitation principles for persons with chronic illness may prove useful. Psychological interventions for sexual sequelae need to be offered and individualized to patients, regardless of their age or partnership. Support should also be offered to partners. Our hope is that this plan will serve as a guide for optimizing how ADT is carried out and improve the lives of androgen-deprived men and their intimate partners. © 2010 International Society for Sexual Medicine.

Response of the surface tropical Atlantic Ocean to wind forcing

NASA Astrophysics Data System (ADS)

Castellanos, Paola; Pelegrí, Josep L.; Campos, Edmo J. D.; Rosell-Fieschi, Miquel; Gasser, Marc

2015-05-01

We use 10 years of satellite data (sea level pressure, surface winds and absolute dynamic topography [ADT]) together with Argo-inferred monthly-mean values of near-surface velocity and water transport, to examine how the tropical system of near-surface zonal currents responds to wind forcing. The data is analyzed using complex Hilbert empirical orthogonal functions, confirming that most of the variance has annual periodicity, with maximum amplitudes in the region spanned by the seasonal displacement of the Inter-Tropical Convergence Zone (ITCZ). The ADT mirrors the shape of the upper isopycnals, hence becoming a good indicator of the amount of water stored in the upper ocean. Within about 3° from the Equator, where the Coriolis force is small, there is year-long meridional Ekman-transport divergence that would lead to the eastward transport of the Equatorial Undercurrent and its northern and southern branches. Beyond 3° of latitude, and at least as far as 20°, the convergence of the Ekman transport generally causes a poleward positive ADT gradient, which sustains the westward South Equatorial Current (SEC). The sole exception occurs in summer, between 8°N and 12°N, when an Ekman-transport divergence develops and depletes de amount of surface water, resulting in an ADT ridge-valley system which reverses the ADT gradient and drives the eastward North Equatorial Countercurrent (NECC) at latitudes 4-9°N; in late fall, divergence ceases and the NECC drains the ADT ridge, so the ADT gradient again becomes positive and the SEC reappears. The seasonal evolution of a tilted ITCZ controls the surface water fluxes: the wind-induced transports set the surface divergence-convergence, which then drive the ADT and, through the ADT gradients, create the geostrophic jets that close the water balance.

Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice.

PubMed

Poulsen, Christian Bo; Mortensen, Martin Bødtker; Koechling, Wolfgang; Sørensen, Charlotte Brandt; Bentzon, Jacob Fog

2016-02-23

Treatment of prostate cancer often involves androgen deprivation therapy (ADT) by gonadotropin-releasing hormone (GnRH) receptor agonists, GnRH receptor antagonists, or orchiectomy. ADT may increase the rate of cardiovascular disease events, but recent clinical studies suggested that not all means of ADT carry the same risk, raising the possibility of non-testosterone-mediated effects of different forms of ADT on atherosclerosis. Here we compared effects of ADT on atherosclerosis in intact and orchiectomized Apoe-deficient mice. Chow-fed Apoe-deficient mice were allocated to orchiectomy and/or monthly injections with the GnRH receptor agonist leuprolide or the GnRH receptor antagonist degarelix. Atherosclerosis was quantified at 26 weeks of age in the aortic arch by en face examination and in the aortic root by histology. In intact Apoe-deficient mice, all types of ADT reduced testosterone production to castration levels. Although hypercholesterolemia was accentuated in leuprolide-treated mice, the amount and composition of atherosclerosis was not different between the different types of ADT. In orchiectomized Apoe-deficient mice, leuprolide, but not degarelix, augmented hypercholesterolemia, changed body, thymus, and spleen weights, and increased atherosclerosis in the aortic root. No direct effects of the drugs were detectable on cytokine secretion from murine bone marrow-derived macrophages or on splenocyte proliferation. No differences in the development of atherosclerosis were detected among groups of intact Apoe-deficient mice treated with different types of ADT. A pro-atherogenic, possibly cholesterol-mediated, effect of leuprolide was seen in orchiectomized mice that might be relevant for understanding the potential cardiovascular risk associated with GnRH agonist-based ADT. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Androgen deprivation therapy of self-identifying, help-seeking pedophiles in the Dunkelfeld.

PubMed

Amelung, Till; Kuhle, Laura F; Konrad, Anna; Pauls, Alfred; Beier, Klaus M

2012-01-01

Androgen deprivation therapy (ADT) is considered an effective strategy in sexual offender treatment. However, the evidence base concerning its effects on sexual arousal control is limited. Past research has focused almost exclusively on men in forensic contexts. The present retrospective observational study provided data on ADT in a sample of self-identifying, help-seeking pedohebephilic men applying for a one-year group therapy program. Factors possibly influencing the readiness to take up or discontinue ADT were presented. Effects of a combination of ADT and group psychotherapy program on changes in paraphilic sexual behavior and associated psychological factors were examined. The proportion of men having taken up ADT was rather small (n=15). Greater awareness of potentially risky situations to commit child sexual offenses and self-rated uncontrollability of sexual urges were identified as characterizing men resorting to ADT. Additionally, these men were initially more open to include medical treatment. Examination of the effects of ADT and psychotherapy was limited to a sample of six men providing complete data sets. Descriptive data demonstrated a reduction of paraphilic sexual behaviors, an increase of risk-awareness and self-efficacy, and a decrease of offense-supportive cognitions and self-esteem. The present study underlined the importance of careful education and monitoring of self-identifying, help-seeking pedohebephilic patients interested in ADT concerning the effects and side effects of the treatment in a clinical context. Copyright © 2012 Elsevier Ltd. All rights reserved.

RNAi suppression of Arogenate Dehydratase1 reveals that phenylalanine is synthesized predominantly via the arogenate pathway in petunia petals.

PubMed

Maeda, Hiroshi; Shasany, Ajit K; Schnepp, Jennifer; Orlova, Irina; Taguchi, Goro; Cooper, Bruce R; Rhodes, David; Pichersky, Eran; Dudareva, Natalia

2010-03-01

l-Phe, a protein building block and precursor of numerous phenolic compounds, is synthesized from prephenate via an arogenate and/or phenylpyruvate route in which arogenate dehydratase (ADT) or prephenate dehydratase, respectively, plays a key role. Here, we used Petunia hybrida flowers, which are rich in Phe-derived volatiles, to determine the biosynthetic routes involved in Phe formation in planta. Of the three identified petunia ADTs, expression of ADT1 was the highest in petunia petals and positively correlated with endogenous Phe levels throughout flower development. ADT1 showed strict substrate specificity toward arogenate, although with the lowest catalytic efficiency among the three ADTs. ADT1 suppression via RNA interference in petunia petals significantly reduced ADT activity, levels of Phe, and downstream phenylpropanoid/benzenoid volatiles. Unexpectedly, arogenate levels were unaltered, while shikimate and Trp levels were decreased in transgenic petals. Stable isotope labeling experiments showed that ADT1 suppression led to downregulation of carbon flux toward shikimic acid. However, an exogenous supply of shikimate bypassed this negative regulation and resulted in elevated arogenate accumulation. Feeding with shikimate also led to prephenate and phenylpyruvate accumulation and a partial recovery of the reduced Phe level in transgenic petals, suggesting that the phenylpyruvate route can also operate in planta. These results provide genetic evidence that Phe is synthesized predominantly via arogenate in petunia petals and uncover a novel posttranscriptional regulation of the shikimate pathway.

Effects of perineural invasion on biochemical recurrence and prostate cancer-specific survival in patients treated with definitive external beam radiotherapy.

PubMed

Peng, Luke C; Narang, Amol K; Gergis, Carol; Radwan, Noura A; Han, Peijin; Marciscano, Ariel E; Robertson, Scott P; He, Pei; Trieu, Janson; Ram, Ashwin N; McNutt, Todd R; Griffith, Emily; DeWeese, Theodore A; Honig, Stephanie; Singh, Harleen; Greco, Stephen C; Tran, Phuoc T; Deville, Curtiland; DeWeese, Theodore L; Song, Daniel Y

2018-06-01

Perineural invasion (PNI) has not yet gained universal acceptance as an independent predictor of adverse outcomes for prostate cancer treated with external beam radiotherapy (EBRT). We analyzed the prognostic influence of PNI for a large institutional cohort of prostate cancer patients who underwent EBRT with and without androgen deprivation therapy (ADT). We, retrospectively, reviewed prostate cancer patients treated with EBRT from 1993 to 2007 at our institution. The primary endpoint was biochemical failure-free survival (BFFS), with secondary endpoints of metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Univariate and multivariable Cox proportional hazards models were constructed for all survival endpoints. Hazard ratios for PNI were analyzed for the entire cohort and for subsets defined by NCCN risk level. Additionally, Kaplan-Meier survival curves were generated for all survival endpoints after stratification by PNI status, with significant differences computed using the log-rank test. Of 888 men included for analysis, PNI was present on biopsy specimens in 187 (21.1%). PNI was associated with clinical stage, pretreatment PSA level, biopsy Gleason score, and use of ADT (all P<0.01). Men with PNI experienced significantly inferior 10-year BFFS (40.0% vs. 57.8%, P = 0.002), 10-year MFS (79.7% vs. 89.0%, P = 0.001), and 10-year PCSS (90.9% vs. 95.9%, P = 0.009), but not 10-year OS (67.5% vs. 77.5%, P = 0.07). On multivariate analysis, PNI was independently associated with inferior BFFS (P<0.001), but not MFS, PCSS, or OS. In subset analysis, PNI was associated with inferior BFFS (P = 0.04) for high-risk patients and with both inferior BFFS (P = 0.01) and PCSS (P = 0.05) for low-risk patients. Biochemical failure occurred in 33% of low-risk men with PNI who did not receive ADT compared to 8% for low-risk men with PNI treated with ADT (P = 0.01). PNI was an independently significant predictor of adverse survival outcomes in this large institutional cohort, particularly for patients with NCCN low-risk disease. PNI should be carefully considered along with other standard prognostic factors when treating these patients with EBRT. Supplementing EBRT with ADT may be beneficial for select low-risk patients with PNI though independent validation with prospective studies is recommended. Copyright © 2018 Elsevier Inc. All rights reserved.

Complete remission in a colon cancer patient with a large, irresectable liver metastasis after XELOX/cetuximab/bevacizumab treatment.

PubMed

Weihrauch, Martin R; Stippel, Dirk; Fries, Jochen W U; Arnold, Dirk; Bovenschulte, Henning; Coutelle, Oliver; Hacker, Ulrich

2008-09-01

Stage IV colorectal cancer is usually an incurable disease. However, patients with resectable metastases have 5-year disease-free survival rates of up to 30%. Even with primarily irresectable disease, cure can be achieved in patients who become operable after neoadjuvant treatment. To improve the prognosis of these patients, highly effective neoadjuvant regimens need to be developed. Here, we report the case of a 62-year-old male patient who had been diagnosed with International Union against Cancer (UICC) stage III colon cancer 7 years previously and now presented with a large, irresectable liver metastasis and enlarged perihepatic lymph nodes. After neoadjuvant treatment with cetuximab, bevacizumab and XELOX, the patient showed a complete remission and underwent surgery. Histopathologically, the resected tissue and lymph nodes were free of residual tumor. To our knowledge, this is the first report of a complete pathological response in a patient with irresectable colorectal cancer after intensive chemotherapy/anti-EGFR/ VEGF antibody therapy. This combination regimen may help to improve the survival rates for patients with irresectable disease. Copyright 2008 S. Karger AG, Basel.

Quality of life effects of androgen deprivation therapy in a prostate cancer cohort in New Zealand: can we minimize effects using a stratification based on the aldo-keto reductase family 1, member C3 rs12529 gene polymorphism?

PubMed

Karunasinghe, Nishi; Zhu, Yifei; Han, Dug Yeo; Lange, Katja; Zhu, Shuotun; Wang, Alice; Ellett, Stephanie; Masters, Jonathan; Goudie, Megan; Keogh, Justin; Benjamin, Benji; Holmes, Michael; Ferguson, Lynnette R

2016-08-02

Androgen deprivation therapy (ADT) is an effective palliation treatment in men with advanced prostate cancer (PC). However, ADT has well documented side effects that could alter the patient's health-related quality of life (HRQoL). The current study aims to test whether a genetic stratification could provide better knowledge for optimising ADT options to minimize HRQoL effects. A cohort of 206 PC survivors (75 treated with and 131 without ADT) was recruited with written consent to collect patient characteristics, clinical data and HRQoL data related to PC management. The primary outcomes were the percentage scores under each HRQoL subscale assessed using the European Organisation for Research and Treatment of Cancer Quality of Life questionnaires (QLQ-C30 and PR25) and the Depression Anxiety Stress Scales developed by the University of Melbourne, Australia. Genotyping of these men was carried out for the aldo-keto reductase family 1, member C3 (AKR1C3) rs12529 single nucleotide polymorphism (SNP). Analysis of HRQoL scores were carried out against ADT duration and in association with the AKR1C3 rs12529 SNP using the generalised linear model. P-values <0 · 05 were considered significant, and were further tested for restriction with Bonferroni correction. Increase in hormone treatment-related effects were recorded with long-term ADT compared to no ADT. The C and G allele frequencies of the AKR1C3rs12529 SNP were 53·4 % and 46·6 % respectively. Hormone treatment-related symptoms showed an increase with ADT when associated with the AKR1C3 rs12529 G allele. Meanwhile, decreasing trends on cancer-specific symptoms and increased sexual interest were recorded with no ADT when associated with the AKR1C3 rs12529 G allele and reverse trends with the C allele. As higher incidence of cancer-specific symptoms relate to cancer retention it is possible that associated with the C allele there could be higher incidence of unresolved cancers under no ADT options. If these findings can be reproduced in larger homogeneous cohorts, a genetic stratification based on the AKR1C3 rs12529 SNP, can minimize ADT-related HRQoL effects in PC patients. Our data additionally show that with this stratification it could also be possible to identify men needing ADT for better oncological advantage.

Surgical Resection for Hepatoblastoma-Updated Survival Outcomes.

PubMed

Sunil, Bhanu Jayanand; Palaniappan, Ravisankar; Venkitaraman, Balasubramanian; Ranganathan, Rama

2017-09-30

Hepatoblastoma is the most common liver malignancy in the pediatric age group. The management of hepatoblastoma involves multidisciplinary approach. Patients with hepatoblastoma who underwent liver resection between 2000 and 2013 were analyzed and survival outcomes were studied. The crude incidence rate of hepatoblastoma at the Madras Metropolitan Tumor Registry (MMTR) is 0.4/1,00,000 population per year. Twelve patients underwent liver resection for hepatoblastoma during the study period; this included eight males and four females. The median age at presentation was 1.75 years (Range 5 months to 3 years). The median serum AFP in the study population was 20,000 ng/ml (Range 4.5 to 1,40,000 ng/ml). Three patients had stage I, one patient had stage II, and eight patients had stage III disease as per the PRETEXT staging system. Two patients were categorized as high risk and ten patients were categorized as standard risk. Seven of these patients received two to four cycles of neoadjuvant chemotherapy (PLADO regimen), and one patient received neoadjuvant radiation up to 84 Gy. Major liver resection was performed in nine patients. Nine patients received adjuvant chemotherapy. The most common histological subtype was embryonal type. Microscopic margin was positive in three cases. One patient recurred 7 months after surgery and the site of failure was the lung. The 5-year overall survival of the case series was 91%. The median survival was 120 months. Liver resections can be safely performed in pediatric populations after neoadjuvant treatment. Patients undergoing surgery had good disease control and long-term survival.

Cellular Basis for ADT-Induced Acceleration of Sarcopenia

DTIC Science & Technology

2015-10-01

fractures due to 1) the already high incidence of bone metastasis and 2) ADT-induced acceleration in osteoporosis emphasizes the need for other therapies...acceleration in osteoporosis emphasizes the need for other therapies. In order to devise effective therapies, an understanding as to how ADT results in severe

Quality of Life in a Prospective, Multicenter Phase 2 Trial of Neoadjuvant Full-Dose Gemcitabine, Oxaliplatin, and Radiation in Patients With Resectable or Borderline Resectable Pancreatic Adenocarcinoma

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

Serrano, Pablo E.; Herman, Joseph M.; Griffith, Kent A.

Purpose: To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma. Methods and Materials: Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores weremore » compared with baseline. A change >10% was considered a minimal clinically important difference. Results: Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (−8, P=.02). This was in parallel with deterioration in physical functioning (−14.1, P=.001), increase in diarrhea (+16.7, P=.044), and an improvement in pancreatic pain (−13, P=.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit. Conclusions: The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical resection, most domains returned back to baseline levels by 6 months.« less

Perceived barriers and facilitators to physical activity in men with prostate cancer: possible influence of androgen deprivation therapy.

PubMed

Keogh, J W L; Patel, A; MacLeod, R D; Masters, J

2014-03-01

While physical activity is beneficial for men with prostate cancer, too few perform sufficient activity for such benefit. This study examined perceptions of men with prostate cancer of their barriers and facilitators to physical activity, and how androgen deprivation therapy (ADT) may influence these perceptions. Two focus groups were conducted, involving six ADT and eight non-ADT patients respectively. Data were transcribed verbatim and themes developed using a general inductive thematic approach. Facilitators to physical activity common to both groups of cancer survivors included clinician and spousal involvement, with pre-existing co-morbidities and increased age cited as barriers by both groups. The ADT subgroup cited personal involvement as a facilitator to physical activity, with fatigue, reduced motivation and a relative lack of specific advice from their clinician as additional barriers. The non-ADT subgroup had no additional facilitators to physical activity but cited time constraints as a barrier. These results highlight the important role that cancer clinicians and spouses play in promoting physical activity for men with prostate cancer and how ADT may influence their other facilitators and barriers. As physical activity is beneficial for prostate cancer survivors, especially those on ADT, cancer clinicians should regularly discuss physical activity with their patients. © 2013 John Wiley & Sons Ltd.

Abiraterone acetate/androgen deprivation therapy combination versus docetaxel/androgen deprivation therapy combination in advanced hormone-sensitive prostate cancer: a network meta-analysis on safety and efficacy.

PubMed

Kassem, Loay; Shohdy, Kyrillus S; Abdel-Rahman, Omar

2018-05-01

A major, yet precisely studied, shift has occurred in the treatment of advanced hormone-sensitive prostate cancer (HSPC) by the addition of docetaxel to androgen deprivation therapy (ADT) in the first line. Recently, two landmark trials showed that abiraterone acetate (AA) can be an effective alternative along with ADT in the same setting. We implemented a network meta-analysis to compare the safety and efficacy of the two combinations. PubMed database, ASCO and ESMO meeting library databases of all results published until June 2017 were searched using the keywords: "prostate cancer" AND "docetaxel" OR "abiraterone acetate". Efficacy endpoints including progression-free survival (PFS) and overall survival (OS), and safety endpoints (including treatment related deaths and selected adverse events) were assessed. Twenty relevant studies were retrieved and assessed for eligibility. Of those trials, eight were found potentially eligible. Inconsistent reporting of efficacy outcomes limited our analysis to M1 HSPC. The pooled hazard ratios (HRs) of OS and PFS of the direct comparison of abiraterone acetate plus ADT versus ADT were 0.63 (95% CI: 0.545-0.717) and 0.38 (95% CI: 0.34-0.43), respectively. Meanwhile, in the trials of docetaxel plus ADT the pooled HRs of OS and PFS were 0.75 (95% CI: 0.65-0.86) and 0.634 (95% CI: 0.57-0.70), respectively. The indirect comparison showed that the HRs of OS and PFS in DOC + ADT in comparison to AA + ADT were 1.2 (95% CI: 0.98-1.46) and 1.65 (1.40-1.94), respectively. The pooled RR of treatment-related mortality in docetaxel + ADT versus AA + ADT was 1.438 (95% CI: 0.508-4.075). Patients with metastatic HSPC (mHSPC) who received abiraterone acetate with ADT had better PFS and less toxicity compared to those receiving docetaxel with ADT. A trend towards superior OS and fewer treatment-related deaths was also observed, but was statistically non-significant. In view of lacking clear OS advantage, the choice between docetaxel and AA should include a discussion with the patient about the potential toxicities and impact on quality of life of each regimen.

Decrease in lean body mass in men with prostate cancer receiving androgen deprivation therapy: mechanism and biomarkers.

PubMed

Hara, Noboru; Ishizaki, Fumio; Saito, Toshihiro; Nishiyama, Tsutomu; Kawasaki, Takashi; Takahashi, Kota

2013-02-01

To elucidate the mechanism of the androgen deprivation therapy (ADT)-related decrease in lean body mass (LBM). The LBM and blood samples were studied before and after 6 months of ADT in 72 patients with localized prostate cancer. The LBM was assessed using a foot-to-foot bioelectrical impedance analyzer. Before ADT, the LBM correlated with none of the serum sex steroid levels; however, it correlated closely with serum 5α-androstane-3α,17β-diol glucuronide (Spearman's rank correlation coefficient = 0.409, P = .001) and insulin-like growth factor-1 (IGF-I, Spearman's rank correlation coefficient = 0.329, P = .005). After ADT, the LBM decreased by 0.9% (P = .036), and the serum testosterone and dihydrotestosterone had decreased by 96.8% and 94.3%, respectively (P <.001 for both), and the IGF-I had increased by 11.6% (from 19.9 to 22.2 nmol/L, P = .001). The serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D] levels decreased after ADT by 9.8% (from 66.2 to 59.7 pg/mL, P = .008), and the post-treatment LBM correlated inversely with 1,25(OH)2D (Spearman's rank correlation coefficient = -0.343, P = .003). The post-treatment LBM was dissociated with 5α-androstane-3α,17β-diol glucuronide and IGF-I. The pretreatment and post-treatment LBMs both correlated inversely with serum sex hormone-binding globulin (P = .024 and P = .016, respectively). The deficiency in androgen levels was suggested to be a link to the ADT-related decrease in LBM; the androgen metabolite 5α-androstane-3α,17β-diol glucuronide has a potential value for assessing the LBM in untreated men. IGF-I also promotes muscle building and is positively regulated during ADT. Sex hormone-binding globulin possibly accelerates the ADT-related decrease in LBM. Although the mechanism for the decrease in 1,25(OH)2D and its inverse correlation with LBM during ADT is unclear, 1,25(OH)2D might be a biomarker reflecting the ADT-related decrease in LBM. Copyright © 2013 Elsevier Inc. All rights reserved.

Androgen deprivation therapy and risk of rheumatoid arthritis in patients with localized prostate cancer.

PubMed

Yang, D D; Krasnova, A; Nead, K T; Choueiri, T K; Hu, J C; Hoffman, K E; Yu, J B; Spratt, D E; Feng, F Y; Trinh, Q-D; Nguyen, P L

2018-02-01

Androgens are generally immunosuppressive, and men with untreated hypogonadism are at increased risk for autoimmune conditions. To date, there has been no evidence linking androgen deprivation therapy (ADT) to autoimmune diseases, including rheumatoid arthritis (RA). We investigated the association between ADT and RA in patients with prostate cancer. We identified 105 303 men age 66 years or older who were diagnosed with stages I-III prostate cancer from 1992 through 2006 using the Surveillance, Epidemiology, and End Results-Medicare linked database, excluding patients with a history of RA. χ2 test was used to compare 5-year Kaplan-Meier rates of RA diagnoses. Competing risk Cox regression using inverse probability of treatment weighting was utilized to examine the association between pharmacologic ADT and diagnosis of RA. The 43% of patients (N = 44 785) who received ADT experienced a higher 5-year rate of RA diagnoses compared with men who did not (5.4% versus 4.4%, P < 0.001). Receipt of any ADT was associated with a 23% increased risk of being diagnosed with RA (hazard ratio 1.23, 95% confidence interval 1.09-1.40, P = 0.001). The risk of being diagnosed with RA increased with a longer duration of ADT, from 19% with 1-6 months and 29% with 7-12 months to 33% with ≥13 months (Ptrend < 0.001). Consistent with the immunosuppressive properties of androgens, we demonstrated for the first time that ADT was associated with an elevated risk of being diagnosed with RA in this large cohort of elderly men with prostate cancer. The risk was higher with a longer duration of ADT. Linking ADT to an increased risk of being diagnosed with an autoimmune condition adds to mounting evidence of the adverse effects of ADT that should prompt physicians to thoughtfully weigh its risks and benefits. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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.

Sexual healing in patients with prostate cancer on hormone therapy.

PubMed

Schover, Leslie R

2015-01-01

Since prostate cancer becomes more common with age, at least one-third of men have sexual problems at diagnosis. All localized treatments for prostate cancer greatly increase the prevalence of sexual dysfunction, which include loss of desire, erectile dysfunction, and changes in orgasm. Even men on active surveillance have a higher rate of problems than matched peers without prostate cancer. However, men given androgen deprivation therapy (ADT) have the worst rates of sexual dysfunction. Even after 3 to 4 months of ADT, men's desire for sex is decreased and irreversible damage may occur to the erectile tissue in the penis. Erections do not recover in about one-half of men, even if ADT is discontinued. Although intermittent ADT allows some recovery of sexual function, serum testosterone requires 9 to 12 months off ADT to recover. Again, one-half of men have permanent erectile dysfunction. If ADT causes atrophy of the erectile tissue, blood leaks out of the venous system during erection. This syndrome is difficult to treat except with surgery to implant a penile prosthesis. Despite the high rate of sexual problems in men on ADT, a small group stays sexually active and is able to have reliable erections. To improve men's sexual satisfaction on ADT, it may be important to educate them about getting extra mental and physical sexual stimulation, as well as using penile rehabilitation during hormone therapy. Information on reaching orgasm and coping with problems such as dry orgasm, pain with orgasm, and urinary incontinence during sex also should be provided.

Cognitive decline in prostate cancer patients undergoing ADT: a potential role for exercise training.

PubMed

Mundell, Niamh L; Daly, Robin M; Macpherson, Helen; Fraser, Steve F

2017-04-01

Androgen deprivation therapy (ADT) is an effective and widely prescribed treatment for prostate cancer (PCa), but it is associated with multiple treatment-induced adverse effects that impact on various musculoskeletal and cardiometabolic health outcomes. Emerging research has shown that ADT is also associated with cognitive impairment, which has been linked to a loss of independence, increased falls and fracture risk and greater use of medical services. The aim of this review is to outline the evidence related to the effect of ADT use on cognitive function, and propose a role for exercise training as part of usual care to prevent and/or manage cognitive impairments for PCa survivors on ADT. The following results have been obtained from this study. ADT has been shown to adversely affect specific cognitive domains, particularly verbal memory, visuomotor function, attention and executive function. However, current clinical guidelines do not recommend routine assessment of cognitive function in these men. No studies have examined whether exercise training can preserve or improve cognitive function in these men, but in healthy adults', multimodal exercise training incorporating aerobic training, progressive resistance training (PRT) and challenging motor control exercises have the potential to attenuate cognitive decline. In conclusion, as treatment with ADT for men with PCa has been associated with a decline in cognition, it is recommended that cognitive function be routinely monitored in these men and that regular exercise training be prescribed to preserve (or improve) cognitive function. Assessment of cognition and individualised exercise training should be considered in the usual treatment plan of PCa patients receiving ADT. © 2017 Society for Endocrinology.

The Effect of Lateral Ankle Ligament Repair in Muscle Reaction Time in Patients with Mechanical Ankle Instability.

PubMed

Li, H-Y; Zheng, J-J; Zhang, J; Hua, Y-H; Chen, S-Y

2015-11-01

Studies have shown that functional ankle instability can result in prolonged muscle reaction time. However, the deficit in muscle reaction time in patients with mechanical ankle instability (MAI) and the effect of lateral ankle ligament repair on muscle reaction time are unclear. The purpose of this study was to identify the deficit in muscle reaction time, and to evaluate the role of lateral ligament repair in improving muscle reaction time in MAI patients. Sixteen MAI patients diagnosed with lateral ankle ligament tears by ultrasonography and magnetic resonance imaging underwent arthroscopic debridement and open lateral ankle ligament repair with a modified Broström procedure. One day before the operation, reaction times of the tibialis anterior and peroneus longus muscles were recorded following sudden inversion perturbation while walking on a custom walkway, and anterior drawer test (ADT) and American Orthopaedic Foot and Ankle Society (AOFAS) scale score were evaluated. Six months postoperatively, muscle reaction time, ADT and AOFAS scale score were reevaluated, and muscle reaction times in 15 healthy controls were also recorded. Preoperatively, the affected ankles in the MAI group had significantly delayed tibialis anterior and peroneus longus muscles reaction times compared with controls. Six months after the operation, median AOFAS scale scores were significantly greater than preoperatively, and ADT was negative in the MAI group. However, the affected ankles in the MAI group showed no difference in muscle reaction time compared with preoperative values. MAI patients had prolonged muscle reaction time. The modified Broström procedure produced satisfactory clinical outcomes in MAI patients, but did not shorten reaction times of the tibialis anterior and peroneus longus muscles. © Georg Thieme Verlag KG Stuttgart · New York.

Cognitive Effects of Androgen Deprivation Therapy in Men With Advanced Prostate Cancer.

PubMed

Gunlusoy, Bulent; Ceylan, Yasin; Koskderelioglu, Aslı; Gedizlioglu, Muhtesem; Degirmenci, Tansu; Ortan, Pınar; Kozacioglu, Zafer

2017-05-01

To evaluate the prostate cancer effects of androgen deprivation therapy (ADT) by using a systematic set of methods to calculate specific cognitive functions in men with locally advanced or metastatic prostate cancer. From April 2014 to February 2016, a prospective, comparative study was done to evaluate the cognitive effects of hormone therapy. Group 1 consisted of 78 patients with locally advanced or metastatic prostate cancer who received complete ADT treatment continuously for 12 months and group 2 (control group) consisted of 78 patients who underwent radical prostatectomy without any additional treatment. The Montreal Cognitive Assessment (MoCA) test and the Frontal Assessment Battery (FAB) test with Turkish language version were used to evaluate multiple domains of cognitive function. Post-treatment results of both tests revealed that patients in group 1 achieved lower mean total scores than group 2. In MoCA test, the deficits were especially prominent in the areas of language ability and short-term memory capacity (P < .05 and P < .05). No significant differences could be identified between groups in respect to attention, executive functions, visuospatial abilities, abstract thinking, calculating abilities, and orientation. In FAB test, the deficits were especially prominent in the areas of mental flexibility and inhibitory control (P < .05 and P < .05). No significant differences could be identified between groups in conceptualization, motor series, conflicting instructions, and environmental autonomy. ADT affects cognitive functions such as language ability, short-term memory capacity, mental flexibility, and inhibitory control. Urologists should keep in mind these side effects and inform the patients and their families for the early symptoms of cognitive dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

Fertility preservation with ovarian stimulation and time to treatment in women with stage II-III breast cancer receiving neoadjuvant therapy.

PubMed

Chien, A Jo; Chambers, Julia; Mcauley, Fiona; Kaplan, Tessa; Letourneau, Joseph; Hwang, Jimmy; Kim, Mi-Ok; Melisko, Michelle E; Rugo, Hope S; Esserman, Laura J; Rosen, Mitchell P

2017-08-01

To determine whether fertility preservation with ovarian stimulation (OS) results in treatment delay in breast cancer (BC) patients receiving neoadjuvant therapy (NAT). This is a retrospective study of women screened for the prospective neoadjuvant ISPY2 trial at the University of California San Francisco. All patients were <43, had stage II-III BC, and received neoadjuvant therapy. Time to initiation of NAT was compared between women who underwent OS (STIM) and women who did not (control). Patient and tumor characteristics, as well as oncologic outcomes, were compared between STIM and control groups. 82 patients were included (34 STIM and 48 control). STIM patients were overall younger (mean = 35 vs. 36.9 years old, p = 0.06), and more likely to be childless (79.4 vs 31.2%, p < 0.0001) than controls. Mean time from diagnosis to initiation of NAT was 40 days, with no significant difference between STIM and control groups (mean 39.8 days vs 40.9 days, p = 0.75). Mean time from diagnosis to fertility consultation was 16.3 days. With median follow-up of 79 months, 16 (19.5%) patients have recurred or died from BC. Rates of pCR, recurrence, and death were similar in both groups. Six of 34 STIM patients have undergone embryo transfer, resulting in one patient with two live births. Fertility preservation with OS can be performed in the neoadjuvant setting without delay in initiation of systemic therapy and should be discussed with all early-stage BC patients of reproductive age.

Letrozole in the neoadjuvant setting: the P024 trial

PubMed Central

Ma, Cynthia

2007-01-01

Neoadjuvant chemotherapy trials have consistently reported lower response rates in hormone receptor-positive (HR+) breast cancer when compared with HR− cases. Preoperative endocrine therapy has therefore become a logical alternative and has gained considerable momentum from the finding that aromatase inhibitors (AIs) are more effective than tamoxifen for HR+ breast cancer in both the neoadjuvant and adjuvant settings. The most convincing neoadjuvant trial to demonstrate the superiority of an AI versus tamoxifen was the P024 study, a large multinational double-blind trial in postmenopausal women with HR+ breast cancer ineligible for breast-conserving surgery. The overall response rate (ORR) was 55% for letrozole and 36% for tamoxifen (P < 0.001). Significantly more letrozole-treated patients underwent breast-conserving surgery (45 vs. 35%, respectively; P = 0.022). In addition, ORR was significantly higher with letrozole than tamoxifen in the human epidermal growth factor receptor HER1/HER2+ subgroup (P = 0.0004). The clinical efficacy of letrozole in HER2+ breast cancer was confirmed by fluorescent in situ hybridization analysis and was found to be comparable to that of HER2− cases (ORR 71% in both subsets). Biomarker studies confirmed the superiority of letrozole in centrally assessed estrogen receptor-positive (ER+) tumors and found a strong relationship with the degree of ER positivity for both agents. Interestingly, letrozole was effective even in marginally ER+ tumors and, unlike tamoxifen, consistently reduced the expression from estrogen-regulated genes (progesterone receptor and trefoil factor 1). Furthermore, when analyzed by Ki67 immunohistochemistry, letrozole was significantly more effective than tamoxifen in reducing tumor proliferation (P = 0.0009). Thus, neoadjuvant letrozole is safe and superior to tamoxifen in the treatment of postmenopausal women with HR+ locally advanced breast cancer. PMID:17912634

The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

2012-04-01

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

Bipolar Androgen Therapy for Men With Androgen Ablation Naïve Prostate Cancer: Results From the Phase II BATMAN Study.

PubMed

Schweizer, Michael T; Wang, Hao; Luber, Brandon; Nadal, Rosa; Spitz, Avery; Rosen, D Marc; Cao, Haiyi; Antonarakis, Emmanuel S; Eisenberger, Mario A; Carducci, Michael A; Paller, Channing; Denmeade, Samuel R

2016-09-01

We have previously documented a paradoxical anti-tumor effect when castration-resistant prostate cancer patients were treated with intermittent, high-dose testosterone (i.e., Bipolar Androgen Therapy; BAT). Because, an adaptive increase in androgen receptor expression following chronic androgen deprivation therapy (ADT) may underlie this effect, we tested whether men with hormone-sensitive (HS) prostate cancer (PC) would also respond to BAT if given following a 6-month ADT lead-in. Asymptomatic HS PC patients with low metastatic burden or non-metastatic biochemically recurrent disease were enrolled. Following 6-month of ADT, those with a PSA <4 ng/ml went on to receive alternating 3-month cycles of BAT and ADT. BAT was administered as intramuscular testosterone (T) cypionate or enanthate 400 mg on Days (D) 1, 29, and 57. ADT was continued throughout the study to allow rapid cycling from near castrate to supraphysiologic range T following T injections. The primary endpoint was the percent of patients with a PSA <4 ng/ml after 18 months. Secondary endpoints included radiographic response and quality of life (QoL). Twenty-nine of 33 patients received BAT following the ADT lead-in. The primary endpoint was met, with 17/29 men (59%, 90% confidence interval: 42-74%) having a PSA <4 ng/ml at 18 months. Ten patients receiving BAT had RECIST evaluable disease, and eight (80%) objective responses were observed (four complete; four partial). Three patients progressed per RECIST criteria and three had unconfirmed progression on bone scan. Men treated with 6-month of ADT had improved QoL following the first cycle of BAT as measured by the SF-36, FACT-P, and IIEF surveys. BAT demonstrated preliminary efficacy in men with HS PC following 6-month of ADT. BAT may improve QoL in men treated with ADT. Prostate 76:1218-1226, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

SLCO2B1 and SLCO1B3 May Determine Time to Progression for Patients Receiving Androgen Deprivation Therapy for Prostate Cancer

PubMed Central

Yang, Ming; Xie, Wanling; Mostaghel, Elahe; Nakabayashi, Mari; Werner, Lillian; Sun, Tong; Pomerantz, Mark; Freedman, Matthew; Ross, Robert; Regan, Meredith; Sharifi, Nima; Figg, William Douglas; Balk, Steven; Brown, Myles; Taplin, Mary-Ellen; Oh, William K.; Lee, Gwo-Shu Mary; Kantoff, Philip W.

2011-01-01

Purpose Androgen deprivation therapy (ADT), an important treatment for advanced prostate cancer, is highly variable in its effectiveness. We hypothesized that genetic variants of androgen transporter genes, SLCO2B1 and SLCO1B3, may determine time to progression on ADT. Patients and Methods A cohort of 538 patients with prostate cancer treated with ADT was genotyped for SLCO2B1 and SLCO1B3 single nucleotide polymorphisms (SNP). The biologic function of a SLCO2B1 coding SNP in transporting androgen was examined through biochemical assays. Results Three SNPs in SLCO2B1 were associated with time to progression (TTP) on ADT (P < .05). The differences in median TTP for each of these polymorphisms were about 10 months. The SLCO2B1 genotype, which allows more efficient import of androgen, enhances cell growth and is associated with a shorter TTP on ADT. Patients carrying both SLCO2B1 and SLCO1B3 genotypes, which import androgens more efficiently, exhibited a median 2-year shorter TTP on ADT, demonstrating a gene-gene interaction (Pinteraction = .041). Conclusion Genetic variants of SLCO2B1 and SLCO1B3 may function as pharmacogenomic determinants of resistance to ADT in prostate cancer. PMID:21606417

Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation therapy?

PubMed

Chondrogiannis, Sotirios; Marzola, Maria Cristina; Ferretti, Alice; Grassetto, Gaia; Maffione, Anna Margherita; Rampin, Lucia; Fanti, Stefano; Giammarile, Francesco; Rubello, Domenico

2014-07-01

To evaluate if the detection rate (DR) of (18)F-choline (18F-CH) PET/CT is influenced by androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) already treated with radical intent and presenting biochemical relapse. We have retrospectively evaluated (18)F-CH PET/CT scans of 325 consecutive PC patients enrolled in the period November 2009 to December 2012 previously treated with radical intent and referred to our centre to perform (18)F-CH PET/CT for biochemical relapse. Two different groups of patients were evaluated. group A included the whole sample of 325 patients (mean age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49-86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of patients in terms of PSA values also excluding both very low and very high PSA levels avoiding the "a priori" higher probability of negative or positive PET scan, respectively. At the time of examination, 139 patients from group A and 72 patients from group B were under ADT: these patients were considered to be hormone-resistant PC patients because from their oncologic history (>18 months) an increase of PSA levels emerged despite the ongoing ADT. The relationship between (18)F-CH PET/CT findings and possible clinical predictors was investigated using both univariate and multivariate binary logistic regression analyses, including trigger PSA and ADT. Considering the whole population, overall DR of (18)F-CH PET was 58.2 % (189/325 patients). In the whole sample of patients (group A), both at the univariate and multivariate logistic regression analysis, trigger PSA and ADT were significantly correlated with the DR of (18)F-CH PET (p < 0.05). Moreover, the DR in patients under ADT (mean PSA 7.8 ng/ml) was higher than in patients not under ADT (mean PSA 3.9 ng/ml), (DR was 70.5 % and 48.9 %, respectively; p < 0.001), therefore, demonstrating the existence of a significant correlation between the DR of (18)F-CH PET and ADT. In group B patients only trigger PSA resulted a reliable predictor of the (18)F-CH positivity, since ADT was not correlated to the DR of (18)F-CH PET (p = 0.061). Also in group B the DR of (18)F-CH PET in patients under ADT was higher than in patients not under ADT (65.3 % and 51.3 %, respectively) but the difference was not significant without a statistically significant correlation in the Mann Whitney test (p = 0.456) therefore, suggesting the lack of correlation between DR (18)F-CH PET/CT and ADT. Similarly to previous published studies, in our series the overall DR of (18)F-CH PET/CT was 58 % and was significantly correlated to trigger PSA. The most important finding of the present study is that ADT does not negatively influence DR of (18)F-CH PET/CT in PC patients with biochemical relapse; therefore, it can be suggested that it is not necessary to withdraw ADT before performing (18)F-CH PET/CT.

Lack of Benefit for the Addition of Androgen Deprivation Therapy to Dose-Escalated Radiotherapy in the Treatment of Intermediate- and High-Risk Prostate Cancer

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

Krauss, Daniel, E-mail: dkrauss@beaumont.edu; Kestin, Larry; Ye, Hong

2011-07-15

Purpose: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). Methods and Materials: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA {>=}20, or Stage T3. Patients were additionally divided specifically by Gleason score, presencemore » of palpable disease, and PSA level to further define subgroups benefitting from ADT. Results: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason {>=}8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. Conclusion: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.« less

Androgen Deprivation Therapy Use in the Setting of High-dose Radiation Therapy and the Risk of Prostate Cancer–Specific Mortality Stratified by the Extent of Competing Mortality

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

Rose, Brent S., E-mail: brose44@gmail.com; Chen, Ming-Hui; Wu, Jing

Purpose: The addition of androgen deprivation therapy (ADT) to radiation therapy (RT) is the standard of care for men with intermediate- and high-risk prostate cancer (PC). However, whether competing mortality (CM) affects the ability of ADT to improve, survival remains unanswered. Methods and Materials: We calculated a CM risk score using a Fine-Gray semiparametric model that included age and cardiometabolic comorbidities from a cohort of 17,669 men treated with high-dose RT with or without supplemental ADT for nonmetastatic PC. Fine and Gray competing risk regression analysis was used to assess whether ADT reduced the risk of PC-specific mortality for menmore » with a low versus a high risk of CM among the 4550 patients within the intermediate- and high-risk cohort after adjustment for established PC prognostic factors, year of treatment, site, and ADT propensity score. Results: After a median follow-up of 8.4 years, 1065 men had died, 89 (8.36%) of PC. Among the men with a low CM score, ADT use was associated with a significant reduction in the risk of PC-specific mortality (adjusted hazard ratio 0.35, 95% confidence interval 0.14-0.87, P=.02) but was not for men with high CM (adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.30, P=.30). Conclusions: Adding ADT to high-dose RT appears to be associated with decreased PC-specific mortality risk in men with a low but not a high CM score. These data should serve to heighten awareness about the importance of considering competing risks when determining whether to add ADT to RT for older men with intermediate- or high-risk PC.« less

Obese frailty, physical performance deficits, and falls in older men with biochemical recurrence of prostate cancer on androgen deprivation therapy: a case-control study

PubMed Central

Bylow, Kathryn; Hemmerich, Joshua; Mohile, Supriya G.; Stadler, Walter M.; Sajid, Saleha; Dale, William

2010-01-01

Objectives Early androgen deprivation therapy (ADT) has no proven survival advantage in older men with biochemical recurrence (BCR) of prostate cancer (PCa), and it may contribute to geriatric frailty; we tested this hypothesis. Methods We conducted a case-control study of men aged 60+ with BCR on ADT (n=63) versus PCa survivors without recurrence (n=71). Frailty prevalence, “obese” frailty, Short Physical Performance Battery (SPPB) scores and falls were compared. An exploratory analysis of frailty biomarkers (CRP, ESR, hemoglobin, albumin, and total cholesterol) was performed. Summary statistics, univariate and multivariate regression analyses were conducted. Results More patients on ADT were obese (BMI >30; 46.2% vs. 20.6%; p=0.03). There were no statistical differences in SPPB (p=0.41) or frailty (p=0.20). Using a proposed “obese” frailty criteria, 8.7% in ADT group were frail and 56.5% were “prefrail”, compared with 2.9% and 48.8% of controls (p=0.02). Falls in the last year were higher in ADT group (14.3% vs. 2.8%; p=0.02). In analyses controlling for age, clinical characteristics, and comorbidities, the ADT group trended toward significance for “obese” frailty (p = 0.14) and falls (OR = 4.74, p = 0.11). Comorbidity significantly increased the likelihood of “obese” frailty (p=0.01) and falls (OR 2.02, p = 0.01). Conclusions Men with BCR on ADT are frailer using proposed modified “obese” frailty criteria. They may have lower performance status and more falls. A larger, prospective trial is necessary to establish a causal link between ADT use and progression of frailty and disability. PMID:21269665

Promoting calcium and vitamin D intake to reduce the risk of osteoporosis in men on androgen deprivation therapy for recurrent prostate cancer.

PubMed

Davison, B Joyce; Wiens, Kristin; Cushing, Meredith

2012-10-01

The aim of this study was to measure the impact of a patient education intervention aimed at increasing dietary intake of calcium and vitamin D in patients currently on androgen deprivation therapy (ADT) for the treatment of prostate cancer. Sixty-one participants attended a one-time dietitian-delivered group education session focusing on diet and lifestyle strategies to reduce the risk of bone loss while on ADT. Dietary intake was assessed using the diet history questionnaire at baseline and again at approximately 1 year post-intervention. Demographics, medical history (including comorbidities), awareness of developing bone loss while on ADT, and information resources utilized were recorded at baseline. Fifty-one participants completed both time points. Over one third of men did not meet minimum current clinical guidelines for calcium or vitamin D intake at baseline. Sixty-three percent of men reported they were aware that osteoporosis was a known side effect of ADT therapy. Only supplemental calcium intake was significantly increased after the intervention. Men aware of their risk of developing bone loss while on ADT reported higher baseline calcium intake (p ≤ 0.05). Men undergoing ADT for less than 1 year at the time of intervention had significantly higher total calcium intake at follow-up compared to men on ADT for longer than 1 year (p = 0.038). Nonsignificant trends indicated that calcium and vitamin D intakes changed to a greater degree in those undergoing ADT for less than 1 year as well. Total calcium and vitamin D did not change significantly as a result of the intervention. Results suggest that promotion of dietary changes may be more effective if delivered closer to the initiation of therapy.

Selective targeting of bioengineered platelets to prostate cancer vasculature: new paradigm for therapeutic modalities

PubMed Central

Montecinos, Viviana P; Morales, Claudio H; Fischer, Thomas H; Burns, Sarah; San Francisco, Ignacio F; Godoy, Alejandro S; Smith, Gary J

2015-01-01

Androgen deprivation therapy (ADT) provides palliation for most patients with advanced prostate cancer (CaP); however, greater than 80% subsequently fail ADT. ADT has been indicated to induce an acute but transient destabilization of the prostate vasculature in animal models and humans. Human re-hydrated lyophilized platelets (hRL-P) were investigated as a prototype for therapeutic agents designed to target selectively the tumour-associated vasculature in CaP. The ability of hRL-P to bind the perturbed endothelial cells was tested using thrombin- and ADP-activated human umbilical vein endothelial cells (HUVEC), as well as primary xenografts of human prostate tissue undergoing acute vascular involution in response to ADT. hRL-P adhered to activated HUVEC in a dose-responsive manner. Systemically administered hRL-P, and hRL-P loaded with super-paramagnetic iron oxide (SPIO) nanoparticles, selectively targeted the ADT-damaged human microvasculature in primary xenografts of human prostate tissue. This study demonstrated that hRL-P pre-loaded with chemo-therapeutics or nanoparticles could provide a new paradigm for therapeutic modalities to prevent the rebound/increase in prostate vasculature after ADT, inhibiting the transition to castration-recurrent growth. PMID:25736582

Interval Between Surgery and Neoadjuvant Chemoradiation Therapy for Distal Rectal Cancer: Does Delayed Surgery Have an Impact on Outcome?

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

Habr-Gama, Angelita; Perez, Rodrigo Oliva; Proscurshim, Igor

Background: The optimal interval between neoadjuvant chemoradiation therapy (CRT) and surgery in the treatment of patients with distal rectal cancer is controversial. The purpose of this study is to evaluate whether this interval has an impact on survival. Methods and Materials: Patients who underwent surgery after CRT were retrospectively reviewed. Patients with a sustained complete clinical response (cCR) 1 year after CRT were excluded from this study. Clinical and pathologic characteristics and overall and disease-free survival were compared between patients undergoing surgery 12 weeks or less from CRT and patients undergoing surgery longer than 12 weeks from CRT completion andmore » between patients with a surgery delay caused by a suspected cCR and those with a delay for other reasons. Results: Two hundred fifty patients underwent surgery, and 48.4% had CRT-to-surgery intervals of 12 weeks or less. There were no statistical differences in overall survival (86% vs. 81.6%) or disease-free survival rates (56.5% and 58.9%) between patients according to interval ({<=}12 vs. >12 weeks). Patients with intervals of 12 weeks or less had significantly higher rates of Stage III disease (34% vs. 20%; p = 0.009). The delay in surgery was caused by a suspected cCR in 23 patients (interval, 48 {+-} 10.3 weeks). Five-year overall and disease-free survival rates for this subset were 84.9% and 51.6%, not significantly different compared with the remaining group (84%; p = 0.96 and 57.8%; p = 0.76, respectively). Conclusions: Delay in surgery for the evaluation of tumor response after neoadjuvant CRT is safe and does not negatively affect survival. These results support the hypothesis that shorter intervals may interrupt ongoing tumor necrosis.« less

Pathologic fracture in childhood and adolescent osteosarcoma: A single-institution experience.

PubMed

Haynes, Lindsay; Kaste, Sue C; Ness, Kirsten K; Wu, Jianrong; Ortega-Laureano, Lucia; Bishop, Michael; Neel, Michael; Rao, Bhaskar; Fernandez-Pineda, Israel

2017-04-01

Pathologic fractures occur in 5-10% of pediatric osteosarcoma (OS) cases and have historically been considered a contraindication to limb salvage. Our purpose was to describe the radiographic features of pathologic fracture and examine its impact on local recurrence rates, functional outcomes, and overall survival. We retrospectively analyzed patients at our institution from 1990 to 2015 with pathologic fracture at diagnosis or during neoadjuvant chemotherapy. We selected a control group of 50 OS patients of similar age and gender without pathologic fracture from 1990 to 2015. Functional outcomes were scored using Musculoskeletal Tumor Society criteria. Chi-square test was used for comparative analysis of groups. Thirty-six patients with 37 pathologic fractures form the study cohort. Of patients who received surgery, 18 of 34 patients with fracture underwent amputation compared to 8 of 48 patients in the nonfracture group (P = 0.007). Indications for amputation in fracture patients were tumor size (n = 7), neurovascular involvement (n = 6), and tumor progression during neoadjuvant chemotherapy (n = 5). Only one patient (2.9%) in the fracture group who underwent limb salvage suffered local recurrence. Of patients who received neoadjuvant chemotherapy, 25 of 34 fracture patients showed poor histological response compared to 24 of 47 nonfracture patients (P = 0.044). There was no statistically significant difference in overall survival (P = 0.96). Functional outcomes were significantly lower in fracture patients (median = 17.5) than nonfracture patients (median = 24) (P = 0.023). Radiographic features of pathologic fractures were highly variable in this population. Limb salvage surgery can be performed without increased risk of local recurrence. Patients with pathologic fracture suffer worse functional outcomes but no decrease in overall survival. © 2016 Wiley Periodicals, Inc.

Immediate radical trachelectomy versus neoadjuvant chemotherapy followed by conservative surgery for patients with stage IB1 cervical cancer with tumors 2cm or larger: A literature review and analysis of oncological and obstetrical outcomes.

PubMed

Pareja, Rene; Rendón, Gabriel J; Vasquez, Monica; Echeverri, Lina; Sanz-Lomana, Carlos Millán; Ramirez, Pedro T

2015-06-01

Radical trachelectomy is the treatment of choice in women with early-stage cervical cancer wishing to preserve fertility. Radical trachelectomy can be performed with a vaginal, abdominal, or laparoscopic/robotic approach. Vaginal radical trachelectomy (VRT) is generally not offered to patients with tumors 2cm or larger because of a high recurrence rate. There are no conclusive recommendations regarding the safety of abdominal radical trachelectomy (ART) or laparoscopic radical trachelectomy (LRT) in such patients. Several investigators have used neoadjuvant chemotherapy in patients with tumors 2 to 4cm to reduce tumor size so that fertility preservation may be offered. However, to our knowledge, no published study has compared outcomes between patients with cervical tumors 2cm or larger who underwent immediate radical trachelectomy and those who underwent neoadjuvant chemotherapy followed by radical trachelectomy. We conducted a literature review to compare outcomes with these 2 approaches. Our main endpoints for evaluation were oncological and obstetrical outcomes. The fertility preservation rate was 82.7%, 85.1%, 89%; and 91.1% for ART (tumors larger than >2cm), ART (all sizes), NACT followed by surgery and VRT (all sizes); respectively. The global pregnancy rate was 16.2%, 24% and 30.7% for ART, VRT, and NACT followed by surgery; respectively. The recurrence rate was 3.8%, 4.2%, 6%, 7.6% and 17% for ART (all sizes), VRT (all sizes), ART (tumors>2cm), NACT followed by surgery, and VRT (tumors>2cm). These outcomes must be considered when offering a fertility sparing technique to patients with a tumor larger than 2cm. Copyright © 2015 Elsevier Inc. All rights reserved.

C. elegans ADAMTS ADT-2 regulates body size by modulating TGFβ signaling and cuticle collagen organization

PubMed Central

Fernando, Thilini; Flibotte, Stephane; Xiong, Sheng; Yin, Jianghua; Yzeiraj, Edlira; Moerman, Donald G.; Meléndez, Alicia; Savage-Dunn, Cathy

2011-01-01

Organismal growth and body size are influenced by both genetic and environmental factors. We have utilized the strong molecular genetic techniques available in the nematode C. elegans to identify genetic determinants of body size. In C. elegans, DBL-1, a member of the conserved family of secreted growth factors known as the Transforming Growth Factor β superfamily, is known to play a major role in growth control. The mechanisms by which other determinants of body size function, however, is less well understood. To identify additional genes involved in body size regulation, a genetic screen for small mutants was previously performed. One of the genes identified in that screen was sma-21. We now demonstrate that sma-21 encodes ADT-2, a member of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family of secreted metalloproteases. ADAMTS proteins are believed to remodel the extracellular matrix and may modulate the activity of extracellular signals. Genetic interactions suggest that ADT-2 acts in parallel with or in multiple size regulatory pathways. We demonstrate that ADT-2 is required for normal levels of expression of a DBL-1-responsive transcriptional reporter. We further demonstrate that adt-2 regulatory sequences drive expression in glial-like and vulval cells, and that ADT-2 activity is required for normal cuticle collagen fibril organization. We therefore propose that ADT-2 regulates body size both by modulating TGFβ signaling activity and by maintaining normal cuticle structure. PMID:21256840

[Neoadjuvant Chemotherapy Using S-1 for Pancreatic Cancer - Mid-Term Results].

PubMed

Homma, Yuki; Honda, Goro; Sakamoto, Katsunori; Kurata, Masanao; Honjo, Masahiko; Hirata, Yoshihiro; Shinya, Satoshi

2016-10-01

Although surgical resection is the only curative strategy for pancreatic cancer, the prognosis of patients with pancreatic cancer remains poor. Recently, neoadjuvant treatment has been frequently employed as a promising treatment. Here, the mid-term results of neoadjuvant chemoradiotherapy(NACRT)using S-1, which has been performed in our hospital since 2008, are reported. Seventy-nine patients with resectable or borderline resectable pancreatic ductal adenocarcinoma, who had been intended to undergo NACRT treatment using S-1, were enrolled. The NACRT comprised radiotherapy( 1.8 Gy×28 days)and full-dose twice-daily oral S-1 given on the same days as the radiotherapy. The results of the NACRT and pancreatectomy and the patients' prognoses were evaluated. Fifty-five patients(69.6%)underwent pancreatectomy, with no case of mortality. The curative resection rate was 94.5%. Postoperative adjuvant chemotherapy was administered in 46 patients(83.6%). The 3-year survival rates of all 79 patients and 55 pancreatectomy patients were 40.1% and 50.4%, respectively. NACRT using S-1 was found to be feasible, and good mid-term outcomes were obtained. However, analysis of the long-term outcomes and comparisons with other novel anti-cancer drugs are still required.

Neoadjuvant sirolimus for a large hepatic perivascular epithelioid cell tumor (PEComa).

PubMed

Bergamo, Francesca; Maruzzo, Marco; Basso, Umberto; Montesco, Maria Cristina; Zagonel, Vittorina; Gringeri, Enrico; Cillo, Umberto

2014-02-27

Perivascular epithelioid cell tumors (PEComas) are rare soft-tissue tumors with an extremely heterogeneous clinical behavior. They may arise in different organs and may behave indolently or sometimes metastasize with different grades of biological aggressiveness. We report the case of a young woman with a primary inoperable PEComa of the liver with malignant histological features. Since the mTOR pathway is often altered in PEComas and responses have been reported with mTOR-inhibitors such as sirolimus or temsirolimus, we decided to start a neoadjuvant treatment with sirolimus. The patient tolerated the treatment fairly well and after 8 months a favorable tumor shrinkage was obtained. The patient then stopped sirolimus and 2 weeks later underwent partial liver resection, with complete clinical recovery and normal liver function. The histological report confirmed a malignant PEComa with vascular invasion and negative margins. Then 6 additional months of post-operative sirolimus treatment were administered, followed by regular radiological follow-up. For patients with a large and histologically aggressive PEComa, we think that neoadjuvant treatment with mTOR-inhibitor sirolimus may be considered to facilitate surgery and allow early control of a potentially metastatic disease. For selected high-risk patients, the option of adjuvant treatment may be discussed.

CaMKKβ-Dependent Activation of AMP-Activated Protein Kinase Is Critical to Suppressive Effects of Hydrogen Sulfide on Neuroinflammation

PubMed Central

Zhou, Xiaomei; Cao, Yongjun; Ao, Guizhen; Hu, Lifang; Liu, Hui; Wu, Jian; Wang, Xiaoyu; Jin, Mengmeng; Zheng, Shuli; Zhen, Xuechu; Alkayed, Nabil J.

2014-01-01

Abstract Aims: The manner in which hydrogen sulfide (H2S) suppresses neuroinflammation is poorly understood. We investigated whether H2S polarized microglia to an anti-inflammatory (M2) phenotype by activating AMP-activated protein kinase (AMPK). Results: Three structurally unrelated H2S donors (5-(4-hydroxyphenyl)-3H-1,2-dithiocyclopentene-3-thione [ADT-OH], (p-methoxyphenyl) morpholino-phosphinodithioic acid [GYY4137], and sodium hydrosulfide [NaHS]) enhanced AMPK activation in BV2 microglial cells in the presence and absence of lipopolysaccharide (LPS). The overexpression of the H2S synthase cystathionine β-synthase (CBS) in BV2 cells enhanced endogenous H2S production and AMPK activation regardless of LPS stimulation. On LPS stimulation, overexpression of both ADT-OH and CBS promoted M2 polarization of BV2 cells, as evidenced by suppressed M1 and elevated M2 signature gene expression. The promoting effects of ADT-OH on M2 polarization were attenuated by an AMPK inhibitor or AMPK knockdown. Liver kinase B1 (LKB1) and calmodulin-dependent protein kinase kinase β (CaMKKβ) are upstream kinases that activate AMPK. ADT-OH activated AMPK in Hela cells lacking LKB1. In contrast, both the CaMKKβ inhibitor and siRNA abolished ADT-OH activation of AMPK in LPS-stimulated BV2 cells. Moreover, the CaMKKβ inhibitor and siRNA blunted ADT-OH suppression on M1 gene expression and enhancement of M2 gene expression in LPS-stimulated BV2 cells. Moreover, ADT-OH promoted M2 polarization of primary microglia in an AMPK activation- and CaMKKβ-dependent manner. Finally, in an LPS-induced in vivo neuroinflammation model, both ADT-OH and NaHS enhanced AMPK activation in the brain area where microglia were over-activated on LPS stimulation. Furthermore, ADT-OH suppressed M1 and promoted M2 gene expression in this in vivo model. Innovation and Conclusion: CaMKKβ-dependent AMPK activation is an unrecognized mechanism underlying H2S suppression on neuroinflammation. Antioxid. Redox Signal. 21, 1741–1758. PMID:24624937

Present and changing trends in surgical modalities and neoadjuvant chemotherapy administration for female breast cancer in Beijing, China: A 10-year (2006-2015) retrospective hospitalization summary report-based study.

PubMed

Bao, Xiaoyuan; Sun, Kexin; Tian, Xin; Yin, Qiongzhou; Jin, Meng; Yu, Na; Jiang, Hanfang; Zhang, Jun; Hu, Yonghua

2018-06-01

This study was conducted to describe present and changing trends in surgical modalities and neoadjuvant chemotherapy (NACT) in female breast cancer patients in China from 2006 to 2015. Data of 44 299 female breast cancer patients from 15 tertiary hospitals in Beijing were extracted from hospitalization summary reports. Surgeries were categorized into five modalities: breast-conserving surgery (BCS), simple mastectomy (SM), modified radical mastectomy (MRM), radical mastectomy (RM), and extensive radical mastectomy (ERM). In total, 38 471 (86.84%) breast cancer patients underwent surgery: 22.64% BCS, 8.22% SM, 63.97% MRM, 4.24% RM, and 0.93% ERM. Older patients (> 60) underwent surgery more frequently than younger patients (< 60). The proportion of patients who underwent BCS was highest in the age ≥ 80 (39.24%) and < 40 (28.69%) subgroups and in patients with papillary carcinoma (35.48%), and lowest in the age 60- subgroup (18.17%) and in patients with Paget's disease (19.05%). SM was most frequently performed in patients with Paget's disease (29.00%), and MRM for ductal (64.99%), and lobular (63.78%) carcinomas. During the study period, the proportion of patients who underwent MRM dropped by 29.04%, SM and BCS increased from 15.78% and 30.83%, respectively, and NACT increased in all subgroups, particularly in patients with lymph node involvement (26.72%). Surgical modalities varied significantly by age and histologic group. The use of BCS and SM increased dramatically, while MRM declined significantly. The proportion of patients treated with NACT has increased significantly, especially in patients with lymph node involvement. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Delineation of soil temperature regimes from HCMM data

NASA Technical Reports Server (NTRS)

Day, R. L.; Petersen, G. W. (Principal Investigator)

1982-01-01

The subsetting of HCMM data into ORSER format was completed for four dates using a modified SUBSET program. Large areas (approximately 2500 scan lines, 1680 elements) were selected to increase the occurrence of suitable control points for registration. Average daily temperatures (ADT) were calculated for each date. The MERGE program combined registered daytime temperature (DAY-IR) with nighttime temperature (NIGHT-IR) to form a separate two-channel data set. The SUBTRAN program averaged the DAY-IR and NIGHT-IR creating a third ADT channel. Registration equations for the four ADT data sets were generated. A one dimensional soil heat flow equation was modified to allow for mean annual soil temperature predictions using merged ADT data sets.

Stochastic Modeling and Analysis of Multiple Nonlinear Accelerated Degradation Processes through Information Fusion

PubMed Central

Sun, Fuqiang; Liu, Le; Li, Xiaoyang; Liao, Haitao

2016-01-01

Accelerated degradation testing (ADT) is an efficient technique for evaluating the lifetime of a highly reliable product whose underlying failure process may be traced by the degradation of the product’s performance parameters with time. However, most research on ADT mainly focuses on a single performance parameter. In reality, the performance of a modern product is usually characterized by multiple parameters, and the degradation paths are usually nonlinear. To address such problems, this paper develops a new s-dependent nonlinear ADT model for products with multiple performance parameters using a general Wiener process and copulas. The general Wiener process models the nonlinear ADT data, and the dependency among different degradation measures is analyzed using the copula method. An engineering case study on a tuner’s ADT data is conducted to demonstrate the effectiveness of the proposed method. The results illustrate that the proposed method is quite effective in estimating the lifetime of a product with s-dependent performance parameters. PMID:27509499

A General Accelerated Degradation Model Based on the Wiener Process.

PubMed

Liu, Le; Li, Xiaoyang; Sun, Fuqiang; Wang, Ning

2016-12-06

Accelerated degradation testing (ADT) is an efficient tool to conduct material service reliability and safety evaluations by analyzing performance degradation data. Traditional stochastic process models are mainly for linear or linearization degradation paths. However, those methods are not applicable for the situations where the degradation processes cannot be linearized. Hence, in this paper, a general ADT model based on the Wiener process is proposed to solve the problem for accelerated degradation data analysis. The general model can consider the unit-to-unit variation and temporal variation of the degradation process, and is suitable for both linear and nonlinear ADT analyses with single or multiple acceleration variables. The statistical inference is given to estimate the unknown parameters in both constant stress and step stress ADT. The simulation example and two real applications demonstrate that the proposed method can yield reliable lifetime evaluation results compared with the existing linear and time-scale transformation Wiener processes in both linear and nonlinear ADT analyses.

Stochastic Modeling and Analysis of Multiple Nonlinear Accelerated Degradation Processes through Information Fusion.

PubMed

Sun, Fuqiang; Liu, Le; Li, Xiaoyang; Liao, Haitao

2016-08-06

Accelerated degradation testing (ADT) is an efficient technique for evaluating the lifetime of a highly reliable product whose underlying failure process may be traced by the degradation of the product's performance parameters with time. However, most research on ADT mainly focuses on a single performance parameter. In reality, the performance of a modern product is usually characterized by multiple parameters, and the degradation paths are usually nonlinear. To address such problems, this paper develops a new s-dependent nonlinear ADT model for products with multiple performance parameters using a general Wiener process and copulas. The general Wiener process models the nonlinear ADT data, and the dependency among different degradation measures is analyzed using the copula method. An engineering case study on a tuner's ADT data is conducted to demonstrate the effectiveness of the proposed method. The results illustrate that the proposed method is quite effective in estimating the lifetime of a product with s-dependent performance parameters.

A General Accelerated Degradation Model Based on the Wiener Process

PubMed Central

Liu, Le; Li, Xiaoyang; Sun, Fuqiang; Wang, Ning

2016-01-01

Accelerated degradation testing (ADT) is an efficient tool to conduct material service reliability and safety evaluations by analyzing performance degradation data. Traditional stochastic process models are mainly for linear or linearization degradation paths. However, those methods are not applicable for the situations where the degradation processes cannot be linearized. Hence, in this paper, a general ADT model based on the Wiener process is proposed to solve the problem for accelerated degradation data analysis. The general model can consider the unit-to-unit variation and temporal variation of the degradation process, and is suitable for both linear and nonlinear ADT analyses with single or multiple acceleration variables. The statistical inference is given to estimate the unknown parameters in both constant stress and step stress ADT. The simulation example and two real applications demonstrate that the proposed method can yield reliable lifetime evaluation results compared with the existing linear and time-scale transformation Wiener processes in both linear and nonlinear ADT analyses. PMID:28774107

The Use of Dietary Supplements to Alleviate Androgen Deprivation Therapy Side Effects during Prostate Cancer Treatment

PubMed Central

Dueregger, Andrea; Heidegger, Isabel; Ofer, Philipp; Perktold, Bernhard; Ramoner, Reinhold; Klocker, Helmut; Eder, Iris E.

2014-01-01

Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT. PMID:25338271

Sarcopenia during androgen-deprivation therapy for prostate cancer.

PubMed

Smith, Matthew R; Saad, Fred; Egerdie, Blair; Sieber, Paul R; Tammela, Teuvo L J; Ke, Chunlei; Leder, Benjamin Z; Goessl, Carsten

2012-09-10

To characterize changes in lean body mass (LBM) in men with prostate cancer receiving androgen-deprivation therapy (ADT). We prospectively evaluated LBM in a prespecified substudy of a randomized controlled trial of denosumab to prevent fractures in men receiving ADT for nonmetastatic prostate cancer. LBM was measured by total-body dual-energy x-ray absorptiometry at study baseline and at 12, 24, and 36 months. The analyses included 252 patients (132, denosumab; 120, placebo) with a baseline and at least one on-study LBM assessment. Patients were stratified by age (< 70 v ≥ 70 years) and by ADT duration (≤ 6 v > 6 months). Median ADT duration was 20.4 months at study baseline. Mean LBM decreased significantly from baseline, by 1.0% at month 12 (95% CI, 0.4% to 1.5%; P < .001; n = 248), by 2.1% at month 24 (95% CI, 1.5% to 2.7%; P < .001; n = 205), and by 2.4% at month 36 (95% CI, 1.6% to 3.2%; P < .001; n = 168). Men age ≥ 70 years (n = 127) had significantly greater changes in LBM at all measured time points than younger men. At 36 months, LBM decreased by 2.8% in men age ≥ 70 years and by 0.9% in younger men (P = .035). Men with ≤ 6 months of ADT at study entry (n = 36) had a greater rate of decrease in LBM compared with men who had received more than 6 months of ADT at study entry (3.7% v 2.0%; P = .0645). In men receiving ADT, LBM decreased significantly after 12, 24, and 36 months.

Anethole dithiolethione, a putative neuroprotectant, increases intracellular and extracellular glutathione levels during starvation of cultured astroglial cells.

PubMed

Dringen, R; Hamprecht, B; Drukarch, B

1998-12-01

Astroglial cells protect neurons against oxidative damage. The antioxidant glutathione plays a pivotal role in the neuroprotective action of astroglial cells which is impaired following loss of glutathione. Anethole dithiolethione (ADT), a sulfur-containing compound which is used in humans as a secretagogue, increases glutathione levels in cultured astroglial cells under "physiological" conditions and is thought thereby to protect against oxidative damage. Presently, we report the effect of ADT (3-100 microM) on glutathione content of and efflux from rat primary astroglia-rich cultures under "pathological" conditions, i.e., extended deprivation of glucose and amino acids. Although cellular viability was not affected significantly, starvation of these cultures for 24 h in a bicarbonate buffer lacking glucose and amino acids led to a decrease in glutathione and protein content of approximately 43% and 40%, respectively. Although no effect on the protein loss occurred, the presence of ADT during starvation counteracted the starvation-induced loss of intracellular glutathione in a concentration-dependent way. At a concentration of 100 microM ADT even a significant increase in astroglial glutathione content was noted after 24 h of starvation. Alike intracellular glutathione levels, the amount of glutathione found in the buffer was elevated substantially if ADT was present during starvation. This ADT-mediated, apparent increase in glutathione efflux was additive to the stimulatory effect on extracellular glutathione levels of acivicin (100 microM), an inhibitor of extracellular enzymatic glutathione breakdown. However, the ADT-induced elevation of both intra- and extracellular glutathione content during starvation was prevented completely by coincubation with buthionine sulfoximine (10 microM), an inhibitor of glutathione synthesis. These results demonstrate that, most likely through stimulation of glutathione synthesis, ADT enables astroglial cells to maintain higher intra- and extracellular levels of glutathione under adverse conditions. Considering the lowered glutathione levels in neurodegenerative syndromes, we conclude that further evaluation of the therapeutic potential of the compound is warranted.

Assessment of the Rate of Adherence to International Guidelines for Androgen Deprivation Therapy with External-beam Radiation Therapy: A Population-based Study.

PubMed

Dell'Oglio, Paolo; Abou-Haidar, Hiba; Leyh-Bannurah, Sami-Ramzi; Tian, Zhe; Larcher, Alessandro; Gandaglia, Giorgio; Fossati, Nicola; Shariat, Shahrokh F; Capitanio, Umberto; Briganti, Alberto; Montorsi, Francesco; Graefen, Markus; Saad, Fred; Karakiewicz, Pierre I

2016-09-01

The National Comprehensive Cancer Network and the European Association of Urology guidelines recommend using radiation therapy (RT) with androgen deprivation therapy (ADT) to treat high-risk and locally advanced prostate cancer patients. To evaluate the degree of adherence to these guidelines. Between 2003 and 2009, in the Surveillance Epidemiology and End Results (SEER)-Medicare database, 14 180 patients were diagnosed with high-risk (T1-T2 with World Health Organization histologic grade 3) or locally advanced (T3-T4 with any histologic grade) prostatic adenocarcinoma. Administration of RT-ADT versus RT alone. We assessed the rate of adherence to guidelines with respect to use of RT-ADT in the overall population and after stratification according to stage-grade groupings (T1-T2 G3 vs T3-T4 any grade), age (66-69, 70-74, 75-79, ≥80 yr), Charlson Comorbidity Index (CCI) (0, 1, ≥2), and preexisting baseline cardiovascular (CV) disease. We depicted the rate of RT-ADT administration graphically over the study period. Multivariable logistic regression analyses were performed to assess the predictors of RT-ADT use. RT-ADT rates and guideline adherence were 58-75%, with the highest rate (75%) in 2003 and the lowest (58%) in 2009. When stratified according to stage-grade groupings, age, CCI, and preexisting baseline CV disease, similar results were obtained. In multivariable analyses, year of diagnosis (p<0.001), patient age (p<0.001), stage-grade groupings (p<0.001), CCI (p=0.036), race (p<0.001), marital status (p<0.001), population density (p<0.001), and US regions (p<0.001) were independent predictors of RT-ADT use. The limitations of our study include age >65 yr and exclusive Medicare coverage. The rate of guideline adherence regarding the use of RT-ADT is suboptimal and decreases with time instead of increasing. This population-based study provides evidence of low adherence to international urologic guidelines regarding the combination of radiation therapy (RT) with androgen deprivation therapy (ADT) for high-risk and locally advanced prostate cancer (PCa) patients. Despite the increasing number of randomized controlled trials over time that showed a survival benefit for patients with high-risk and locally advanced PCa treated with RT-ADT compared with RT alone, the rate of adherence to guidelines decreased with time. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Time on androgen deprivation therapy and adaptations to exercise: secondary analysis from a 12-month randomized controlled trial in men with prostate cancer.

PubMed

Taaffe, Dennis R; Buffart, Laurien M; Newton, Robert U; Spry, Nigel; Denham, James; Joseph, David; Lamb, David; Chambers, Suzanne K; Galvão, Daniel A

2018-02-01

To explore if duration of previous exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a year-long exercise programme moderates the exercise response with regard to body composition and muscle performance, and also to explore the moderator effects of baseline testosterone, time since ADT, and baseline value of the outcome. In a multicentre randomized controlled trial, 100 men who had previously undergone either 6 months (short-term) or 18 months (long-term) of ADT in combination with radiotherapy, as part of the TROG 03.04 RADAR trial, were randomized to 6 months supervised exercise, followed by a 6-month home-based maintenance programme, or to printed physical activity educational material for 12 months across 13 university-affiliated exercise clinics in Australia and New Zealand. The participants were long-term survivors of PCa with a mean age of 71.7 ± 6.4 years, and were assessed for lower extremity performance (repeated chair rise), with a subset of men (n = 57) undergoing additional measures for upper and lower body muscle strength and body composition (lean mass, fat mass, appendicular skeletal muscle [ASM]) by dual X-ray absorptiometry. Data were analysed using generalized estimating equations. Time on ADT significantly moderated the exercise effects on chair rise (β interaction = -1.3 s, 95% confidence interval [CI] -2.6 to 0.0), whole-body lean mass (β interaction = 1194 g, 95% CI 234 to 2153) and ASM mass (β interaction = 562 g, 95% CI 49 to 1075), and approached significance for fat mass (β interaction = -1107 g, 95% CI -2346 to 132), with greater benefits for men previously on long-term ADT. At 6 months, the intervention effects on chair rise time -1.5 s (95% CI -2.5 to -0.5), whole-body lean mass 824 g (95% CI 8 to 1640), ASM mass 709 g (95% CI 260 to 1158), and fat mass -1377 g (95% CI -2156 to -598) were significant for men previously on long-term ADT, but not for men on short-term ADT. At 12 months, the intervention effects for men on long-term ADT remained significant for the chair rise, with improved performance (-2.0 s, 95% CI -3.0 to -1.0) and increased ASM (537 g, 95% CI 153 to 921). Time on ADT did not moderate the exercise effects on muscle strength, nor did time since ADT cessation moderate any intervention effects. Similarly, testosterone and baseline values of the outcome had negligible moderator effects. Men with PCa previously treated long-term with ADT respond more favourably to exercise in terms of lower body muscle performance and body composition (lean and fat mass, and ASM) than those with short-term ADT exposure. As a result, men who were formerly on long-term androgen suppression regimens should be especially prescribed exercise medicine interventions to alleviate residual treatment-related adverse effects. © 2017 The Authors. BJU International.

National Trends and Predictors of Androgen Deprivation Therapy Use in Low-Risk Prostate Cancer

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

Yang, David D.; Muralidhar, Vinayak; Brigham and Women's Hospital, Boston, Massachusetts

Purpose: Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease. Methods and Materials: Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level <10 ng/mL, and cT1-T2a) diagnosed from 2004 to 2012 with complete demographic and treatment information. We used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality. Results: Overall ADT use decreased from 17.6% in 2004more » to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; P<.001; incidence, 14.0% vs 6.0% in 2012); treatment in the South (AOR, 1.51), Midwest (AOR, 1.81), or Northeast (AOR, 1.90) versus West (P<.001); and brachytherapy use versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; P<.001). Among 25,196 patients who did not receive local therapy, predictors of primary ADT use included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; P<.001); and treatment in the South (AOR, 1.26), Midwest (AOR, 1.52), or Northeast (AOR, 1.28) versus West (P≤.008). Primary ADT use was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; P<.001) after adjustment for age and comorbidity. Conclusions: ADT use in low-risk prostate cancer has declined nationally but may remain an issue of concern in certain populations and regions.« less

Changed processing of visual sexual stimuli under GnRH-therapy--a single case study in pedophilia using eye tracking and fMRI.

PubMed

Jordan, Kirsten; Fromberger, Peter; Laubinger, Helge; Dechent, Peter; Müller, Jürgen L

2014-05-17

Antiandrogen therapy (ADT) has been used for 30 years to treat pedophilic patients. The aim of the treatment is a reduction in sexual drive and, in consequence, a reduced risk of recidivism. Yet the therapeutic success of antiandrogens is uncertain especially regarding recidivism. Meta-analyses and reviews report only moderate and often mutually inconsistent effects. Based on the case of a 47 year old exclusively pedophilic forensic inpatient, we examined the effectiveness of a new eye tracking method and a new functional magnetic resonance imaging (fMRI)-design in regard to the evaluation of ADT in pedophiles. We analyzed the potential of these methods in exploring the impact of ADT on automatic and controlled attentional processes in pedophiles. Eye tracking and fMRI measures were conducted before the initial ADT as well as four months after the onset of ADT. The patient simultaneously viewed an image of a child and an image of an adult while eye movements were measured. During the fMRI-measure the same stimuli were presented subliminally. Eye movements demonstrated that controlled attentional processes change under ADT, whereas automatic processes remained mostly unchanged. We assume that these results reflect either the increased ability of the patient to control his eye movements while viewing prepubertal stimuli or his better ability to manipulate his answer in a socially desirable manner. Unchanged automatic attentional processes could reflect the stable pedophilic preference of the patient. Using fMRI, the subliminal presentation of sexually relevant stimuli led to changed activation patterns under the influence of ADT in occipital and parietal brain regions, the hippocampus, and also in the orbitofrontal cortex. We suggest that even at an unconscious level ADT can lead to changed processing of sexually relevant stimuli, reflecting changes of cognitive and perceptive automatic processes. We are convinced that our experimental designs using eye tracking and fMRI could prospectively add additional and valuable information in the evaluation of ADT in paraphilic patients and sex offenders. But with respect to the limited significance of this single case study, these first results are preliminary and further studies have to be conducted with healthy subjects and patients.

Changed processing of visual sexual stimuli under GnRH-therapy – a single case study in pedophilia using eye tracking and fMRI

PubMed Central

2014-01-01

Background Antiandrogen therapy (ADT) has been used for 30 years to treat pedophilic patients. The aim of the treatment is a reduction in sexual drive and, in consequence, a reduced risk of recidivism. Yet the therapeutic success of antiandrogens is uncertain especially regarding recidivism. Meta-analyses and reviews report only moderate and often mutually inconsistent effects. Case presentation Based on the case of a 47 year old exclusively pedophilic forensic inpatient, we examined the effectiveness of a new eye tracking method and a new functional magnetic resonance imaging (fMRI)-design in regard to the evaluation of ADT in pedophiles. We analyzed the potential of these methods in exploring the impact of ADT on automatic and controlled attentional processes in pedophiles. Eye tracking and fMRI measures were conducted before the initial ADT as well as four months after the onset of ADT. The patient simultaneously viewed an image of a child and an image of an adult while eye movements were measured. During the fMRI-measure the same stimuli were presented subliminally. Eye movements demonstrated that controlled attentional processes change under ADT, whereas automatic processes remained mostly unchanged. We assume that these results reflect either the increased ability of the patient to control his eye movements while viewing prepubertal stimuli or his better ability to manipulate his answer in a socially desirable manner. Unchanged automatic attentional processes could reflect the stable pedophilic preference of the patient. Using fMRI, the subliminal presentation of sexually relevant stimuli led to changed activation patterns under the influence of ADT in occipital and parietal brain regions, the hippocampus, and also in the orbitofrontal cortex. We suggest that even at an unconscious level ADT can lead to changed processing of sexually relevant stimuli, reflecting changes of cognitive and perceptive automatic processes. Conclusion We are convinced that our experimental designs using eye tracking and fMRI could prospectively add additional and valuable information in the evaluation of ADT in paraphilic patients and sex offenders. But with respect to the limited significance of this single case study, these first results are preliminary and further studies have to be conducted with healthy subjects and patients. PMID:24885644

The Scaffold Attachment Factor SAFB1: A New Player in G2/M Checkpoint Control

DTIC Science & Technology

2007-04-01

RNA was obtained from locally advanced breast tumors in 24 patients before they underwent four cycles of neoadjuvant docetaxel treatment . Gene...expression analysis was performed and correlated to the treatment response to determine genes that are differentially expressed in docetaxel-sensitive...decreased sensitivity to drugs, depending on the chemotherapeutic agent used 2) Association of SAFB1 loss with resistance to docetaxel treatment , both

Hepatoblastoma.

PubMed

Sharma, Divya; Subbarao, Girish; Saxena, Romil

2017-03-01

Hepatoblastoma is the most common primary malignant hepatic tumor of infancy and childhood, occurring predominantly in the first two years of life. The management of hepatoblastoma has changed markedly over the last 3 decades; neoadjuvant chemotherapy is now standard, particularly in unresectable tumors resulting in considerable preoperative tumor shrinkage and sometimes near total ablation of the tumor. A 20 month old infant was incidentally found to have a 7.6cm right sided retroperitoneal tumor on routine screening ultrasonography for left ureteral stenosis. Serum alpha fetoprotein was elevated. Biopsy revealed hepatoblastoma, mixed epithelial and embryonal type without mesenchymal elements. He underwent neoadjuvant chemotherapy. Although the tumor had decreased considerably in size, close proximity to major vascular structures precluded safe resection. Liver transplantation was performed; the explanted liver showed complete tumor necrosis with no residual malignancy. The postoperative course was uncomplicated and he is continuing on sixth cycle of chemotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

A case of pneumatosis intestinalis during neoadjuvant chemotherapy with cisplatin and 5-fluorouracil for esophageal cancer†.

PubMed

Kouzu, Keita; Tsujimoto, Hironori; Hiraki, Shuichi; Takahata, Risa; Yaguchi, Yoshihisa; Kumano, Isao; Horiguchi, Hiroyuki; Nomura, Shinsuke; Nagata, Ken; Harada, Manabu; Nagata, Hiromi; Sugihara, Takao; Ishibashi, Yusuke; Itazaki, Yujiro; Tsuchiya, Satoshi; Aosasa, Suefumi; Hase, Kazuo; Yamamoto, Junji; Ueno, Hideki

2017-11-01

Pneumatosis intestinalis (PI) is a relatively rare disease. A 70-year-old man with stage II squamous cell carcinoma of the middle thoracic esophagus was administered cisplatin plus 5-fluorouracil (CF) therapy as neoadjuvant chemotherapy. On Day 14 of the first course of CF therapy, he complained of acute abdominal pain. Computed tomography (CT) revealed PI of the entire colon and a small air bubble in the mesentery. A colonoscopy revealed that there was no finding suggestive of ischemia. Because there was no sign of peritoneal irritation, conservative treatment was selected. On Day 7 after PI diagnosis, CT indicated the disappearance of PI. The patient underwent a radical esophagectomy. Intraoperative laparoscopic findings showed the serosa of the colon to be intact. The patient was discharged without any complications. It is important to take into account that CF therapy may cause PI and that PI can be treated conservatively.

Elevated platelet count as predictor of recurrence in rectal cancer patients undergoing preoperative chemoradiotherapy followed by surgery.

PubMed

Toiyama, Yuji; Inoue, Yasuhiro; Kawamura, Mikio; Kawamoto, Aya; Okugawa, Yoshinaga; Hiro, Jyunichiro; Saigusa, Susumu; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

2015-02-01

The impact of systemic inflammatory response (SIR) on prognostic and predictive outcome in rectal cancer after neoadjuvant chemoradiotherapy (CRT) has not been fully investigated. This retrospective study enrolled 89 patients with locally advanced rectal cancer who underwent neoadjuvant CRT and for whom platelet (PLT) counts and SIR status [neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR)] were available. Both clinical values of PLT and SIR status in rectal cancer patients were investigated. Elevated PLT, NLR, PLR, and pathologic TNM stage III [ypN(+)] were associated with significantly poor overall survival (OS). Elevated PLT, NLR, and ypN(+) were shown to independently predict OS. Elevated PLT and ypN(+) significantly predicted poor disease-free survival (DFS). Elevated PLT was identified as the only independent predictor of DFS. PLT counts are a promising pre-CRT biomarker for predicting recurrence and poor prognosis in rectal cancer.

Multimodality Management of "Borderline Resectable" Pancreatic Neuroendocrine Tumors: Report of a Single-Institution Experience.

PubMed

Ambe, Chenwi M; Nguyen, Phuong; Centeno, Barbara A; Choi, Junsung; Strosberg, Jonathan; Kvols, Larry; Hodul, Pamela; Hoffe, Sarah; Malafa, Mokenge P

2017-01-01

Pancreatic neuroendocrine tumors (PanNETs) constitute approximately 3% of pancreatic neoplasms. Like patients with pancreatic ductal adenocarcinoma (PDAC), some of these patients present with "borderline resectable disease." For these patients, an optimal treatment approach is lacking. We report our institution's experience with borderline resectable PanNETs using multimodality treatment. We identified patients with borderline resectable PanNETs who had received neoadjuvant therapy at our institution between 2000 and 2013. The definition of borderline resectability was based on National Comprehensive Cancer Network criteria for PDAC. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal retrieval, number of positive nodes, and recurrence were documented. Statistics were descriptive. Of 112 patients who underwent surgical resection for PanNETs during the study period, 23 received neoadjuvant therapy, 6 of whom met all inclusion criteria and had borderline resectable disease. These 6 patients received at least 1 cycle of temozolomide and capecitabine, with 3 also receiving radiation. All had radiographic evidence of treatment response. Four (67%) had negative-margin resections. Four patients had histologic evidence of a moderate response. Follow-up (3.0-4.3 years) indicated that all patients were alive, with 5/6 free of disease (1 patient with metastatic disease still on treatment without progression). A multimodality treatment strategy (neoadjuvant temozolomide and capecitabine ± radiation) can be successfully applied to patients with PanNETs who meet NCCN borderline resectable criteria for PDAC. To our knowledge, this is the first report of the use of a multimodality protocol in the treatment of patients with borderline resectable PanNETs.

Influence of Irradiated Lung Volumes on Perioperative Morbidity and Mortality in Patients After Neoadjuvant Radiochemotherapy for Esophageal Cancer

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

Daehn, Doreen; Martell, Joachim; Vorwerk, Hilke

Purpose: In some randomized trials, the treatment outcome of locally advanced esophageal cancer has been significantly improved by neoadjuvant radiochemotherapy (RCT). However, increased perioperative pulmonary toxicity in terms of acute respiratory distress syndrome (ARDS) has been linked to radiation exposure of the lungs. In our study we evaluated perioperative morbidity and mortality in patients with cancer Stages IIA-IVA treated with curative intent either with surgery alone (S) or with neoadjuvant RCT followed by surgery (RCTS). Patients and Methods: Between 1996 and 2003, 55 patients received S, and 98 received RCTS. In the RCTS group, most patients received two cycles ofmore » 5-fluorouracil plus cisplatinum simultaneously with normofractionated radiotherapy (40Gy). Four weeks later they underwent surgery. Endpoints were the incidence of acute lung injury (ALI), ARDS, other postoperative complications, and mortality within 31 days. Results: Between both groups there were no significant differences between the incidence and severity of ALI and ARDS (RCTS: 42.9%, 42.9%; S: 45.5%, 38.2%). Furthermore, there were no significant differences in the incidences of pneumonia, pleural effusion, and pneumothorax (RCTS 29.6% vs. S 16.4%, p = 0.07). Perioperative complication rates and mortality did not vary significantly (mortality after RCTS 5.1% vs. S 3.6%). A detailed analysis of 54 RCTS patients according to lung dose-volume histograms did not show any correlation between ARDS and pulmonary exposure. In univariate analysis, only respiratory comorbidity correlated with ARDS. Conclusion: Neoadjuvant cisplatinum and 5-fluorouracil-based RCT apparently has no detrimental impact on the postoperative course.« less

Do the conventional clinicopathologic parameters predict for response and survival in head and neck cancer patients undergoing neoadjuvant chemotherapy?

PubMed

Fonseca, E; Cruz, J J; Dueñas, A; Gómez, A; Sánchez, P; Martín, G; Nieto, A; Soria, P; Muñoz, A; Gómez, J L; Pardal, J L

1996-01-01

Neoadjuvant chemotherapy for head and neck carcinoma is still an important treatment modality. The prognostic value of patient and tumor parameters has been extensively evaluated in several trials, yielding mixed results. We report the prognostic factors emerging from a group of patients undergoing neoadjuvant chemotherapy. From April 1986 to June 1992, 149 consecutive patients received cisplatin-5-fluorouracil-based neoadjuvant chemotherapy. After four courses of chemotherapy, patients underwent local-regional treatment with surgery, radiation or both. A variety of patient and tumor characteristics were evaluated as predictors for response to chemotherapy and survival. The complete response, partial response and no response rates to NAC were 52%, 33% and 15%, respectively. No parameters predicted response to chemotherapy. At a maximum follow-up of 87 months, overall survival was 39% and disease-free survival was 49%. Variables shown to be predictors of survival in univariate analyses were age, performance status, histology, site, T, N, stage, and response to chemotherapy. Using the Cox regression analysis, only complete response to induction chemotherapy (P = 0.0006), performance status (P = 0.03), stage (P = 0.01), age (P = 0.03) and primary tumor site (P = 0.04) emerged as independent prognostic factors for survival. Complete response to chemotherapy was confirmed as the strongest prognostic factor influencing survival. However, conventional clinicopathologic factors did not predict response, hence, potential prognostic biologic and molecular factors for response must be sought. At present, much effort must be made for the improvement of the complete response rate, which seems to be a requisite to prolong survival.

Impact of age on efficacy of postoperative oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy.

PubMed

Huang, Xuan-Zhang; Gao, Peng; Song, Yong-Xi; Sun, Jing-Xu; Chen, Xiao-Wan; Zhao, Jun-Hua; Ma, Bin; Wang, Jun; Wang, Zhen-Ning

2016-04-12

Clinical practice guidelines focusing on age-related adjuvant chemotherapy for rectal cancer are currently limited. The present study aimed to explore the impact of age on the efficacy of adjuvant oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy. We performed a retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results-Medicare-linked database from 1992-2009. We enrolled patients with yp stages I-III rectal cancer who received neoadjuvant chemoradiotherapy and underwent curative resection. The age-related survival benefit of adding oxaliplatin to adjuvant 5-fluorouracil (5-FU) chemotherapy was evaluated using Kaplan-Meier survival analysis with propensity score-matching and Cox proportional hazards models. Comparing the oxaliplatin group with the 5-FU group, there were significant interactions between age and chemotherapy efficacy in terms of overall survival (OS) (p for interaction = 0.017) among patients with positive lymph nodes (ypN+). Adding oxaliplatin to 5-FU could prolong survival in patients aged < 73 years and ypN+ category, and but did not translate into survival benefits in patients aged ≥ 73 years and ypN+ category. No significant interactions were observed among ypN- patients, and oxaliplatin did not significantly improve OS, regardless of age. In patients with rectal cancer who have already received neoadjuvant chemoradiotherapy and undergone curative resection, adding oxaliplatin to 5-FU could prolong OS in patients aged < 73 years and ypN+ category. However, adding oxaliplatin did not translate into survival benefits in patients age ≥ 73 years and ypN+ category, or in ypN- patients.

DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA's antidepressant action.

PubMed

Ben Dor, Rivka; Marx, Christine E; Shampine, Lawrence J; Rubinow, David R; Schmidt, Peter J

2015-09-01

Alterations in neurosteroid secretion have been implicated in the efficacy of antidepressants. In a previous study, the adrenal androgen DHEA, a precursor of the neurosteroid androsterone, produced antidepressant and libido-enhancing effects in patients with midlife depression. To investigate the mechanisms underlying DHEA's behavioral effects in this same patient group, we examined plasma levels of four additional neurosteroids implicated in the regulation of affective behavior. Blood samples were assayed for neurosteroids in men (n = 13) and women (n = 10) with midlife depression who previously participated in a crossover study in which DHEA and placebo were administered for 6 weeks each. Depression severity was measured by the Center for Epidemiologic Studies Depression Scale (CES-D). Plasma levels of androsterone (ADT), allopregnanolone, pregnanolone, and pregnenolone were measured by GC-MS at baseline and week 6 of each treatment phase. Data were analyzed with repeated measures analysis of variance (ANOVA-R) and Bonferroni t tests. ADT levels (but not allopregnanolone, pregnanolone, and pregnenolone) increased after DHEA but not after placebo (F 2,42 = 3.3, p < 0.05). Post-DHEA ADT levels were higher in women than men [t 63 = 2.9, p < 0.05]. However, in both men and women who met criteria for clinical response on the CES-D, baseline ADT levels significantly increased post-DHEA, and the magnitude of the ADT increase post-DHEA treatment was similar in men and women. Consequently, it was the non-responders who accounted for the sex difference in post-DHEA plasma ADT levels, a difference that was driven by values in two women (the only female non-responders). The small sample size notwithstanding, these data emphasize the potential behavioral relevance of ADT in humans, which may include contribution to the antidepressant effects of DHEA.

Sarcopenia During Androgen-Deprivation Therapy for Prostate Cancer

PubMed Central

Smith, Matthew R.; Saad, Fred; Egerdie, Blair; Sieber, Paul R.; Tammela, Teuvo L.J.; Ke, Chunlei; Leder, Benjamin Z.; Goessl, Carsten

2012-01-01

Purpose To characterize changes in lean body mass (LBM) in men with prostate cancer receiving androgen-deprivation therapy (ADT). Patients and Methods We prospectively evaluated LBM in a prespecified substudy of a randomized controlled trial of denosumab to prevent fractures in men receiving ADT for nonmetastatic prostate cancer. LBM was measured by total-body dual-energy x-ray absorptiometry at study baseline and at 12, 24, and 36 months. The analyses included 252 patients (132, denosumab; 120, placebo) with a baseline and at least one on-study LBM assessment. Patients were stratified by age (< 70 v ≥ 70 years) and by ADT duration (≤ 6 v > 6 months). Results Median ADT duration was 20.4 months at study baseline. Mean LBM decreased significantly from baseline, by 1.0% at month 12 (95% CI, 0.4% to 1.5%; P < .001; n = 248), by 2.1% at month 24 (95% CI, 1.5% to 2.7%; P < .001; n = 205), and by 2.4% at month 36 (95% CI, 1.6% to 3.2%; P < .001; n = 168). Men age ≥ 70 years (n = 127) had significantly greater changes in LBM at all measured time points than younger men. At 36 months, LBM decreased by 2.8% in men age ≥ 70 years and by 0.9% in younger men (P = .035). Men with ≤ 6 months of ADT at study entry (n = 36) had a greater rate of decrease in LBM compared with men who had received more than 6 months of ADT at study entry (3.7% v 2.0%; P = .0645). Conclusion In men receiving ADT, LBM decreased significantly after 12, 24, and 36 months. PMID:22649143

The perspective of prostate cancer patients and patients' partners on the psychological burden of androgen deprivation and the dyadic adjustment of prostate cancer couples.

PubMed

Hamilton, Lisa Dawn; Van Dam, Dexter; Wassersug, Richard J

2016-07-01

Prostate cancer and its treatments, particularly androgen deprivation therapy (ADT), affect both patients and partners. This study assessed how prostate cancer treatment type, patient mood, and sexual function related to dyadic adjustment from patient and partner perspectives. Men with prostate cancer (n = 206) and partners of men with prostate cancer (n = 66) completed an online survey assessing the patients' mood (profile of mood states short form), their dyadic adjustment (dyadic adjustment scale), and sexual function (expanded prostate cancer index composite). Analyses of covariance found that men on ADT reported better dyadic adjustment compared with men not on ADT. Erectile dysfunction was high for all patients, but a multivariate analysis of variance found that those on ADT experienced greater bother at loss of sexual function than patients not on ADT, suggesting that loss of libido when on ADT does not mitigate the psychological distress associated with loss of erections. In a multiple linear regression, patients' mood predicted their dyadic adjustment, such that worse mood was related to worse dyadic adjustment. However, more bother with patients' overall sexual function predicted lower relationship scores for the patients, while the patients' lack of sexual desire predicted lower dyadic adjustment for partners. Both patients and partners are impacted by the prostate cancer treatment effects on patients' psychological and sexual function. Our data help clarify the way that prostate cancer treatments can affect relationships and that loss of libido on ADT does not attenuate distress about erectile dysfunction. Understanding these changes may help patients and partners maintain a co-supportive relationship. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Systemic bias in the medical literature on androgen deprivation therapy and its implication to clinical practice.

PubMed

Phillips, J L; Wassersug, R J; McLeod, D L

2012-12-01

LHRH agonists are used for androgen deprivation therapy (ADT) to treat prostate cancer, but have many side effects that reduce of the quality of life of prostate cancer patients and their partners. Patients are poorly informed about the side effects of these drugs and how to manage them. To test the hypothesis that there is bias in the peer-reviewed literature on ADT that correlates with an association between authors and the luteinising hormone-releasing hormone (LHRH) agonists pharmaceutical industry. We assessed 155 articles on ADT published in English-language peer-reviewed journals in terms of how comprehensive they were in acknowledging LHRH agonists' side effects. Although the literature regarding ADT is substantial, the vast majority of articles failed to acknowledge many of the more stressful side effects of ADT for patients and their partners. Articles most likely to acknowledge the psychosocial impact of ADT were significantly less likely to have had industrial support than those articles that did not mention those side effects. Alternative treatments to the LHRH agonists were rarely mentioned. Authors who indicated some association with a pharmaceutical company tended to minimise the side effects of LHRH agonists and not acknowledge alternatives to the LHRH agonists for ADT. Industrial support is associated with a proliferation of articles published in the peer-reviewed literature directed at practising physicians. Such flooding of the literature may, in part, limit physicians' knowledge of the side effects of these drugs and, in turn, account for the poor knowledge that patients on LHRH agonists have about the drugs they are taking and ways to manage their side effects. © 2012 Blackwell Publishing Ltd.

Safety profile of a replication-deficient human adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle.

PubMed

Barrera, J; Brake, D A; Kamicker, B J; Purcell, C; Kaptur, R; Schieber, T; Lechtenberg, K; Miller, T D; Ettyreddy, D; Brough, D E; Butman, B T; Colby, M; Neilan, J G

2018-04-01

The safety of a replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was evaluated in five independent safety studies. The target animal safety studies were designed in compliance with United States (U.S.) regulatory requirements (Title 9, U.S. Code of Federal Regulation [9CFR]) and international standard guidelines (VICH Topic GL-44) for veterinary live vaccines. The first three studies were conducted in a total of 22 vaccinees and demonstrated that the AdtA24 master seed virus (MSV) was safe, did not revert to virulence and was not shed or spread from vaccinees to susceptible cattle or pigs. The fourth safety study conducted in 10 lactating cows using an AdtA24 vaccine serial showed that the vaccine was completely absent from milk. The fifth safety study was conducted under typical U.S. production field conditions in 500 healthy beef and dairy cattle using two AdtA24 vaccine serials. These results demonstrated that the vaccine was safe when used per the product label recommendations. Additional data collected during these five studies confirmed that AdtA24 vaccinees developed FMDV A24 and the HAd5 vaccine vector serum neutralization antibodies that test negative in a FMDV non-structural protein antibody test, confirming AdtA24 vaccine's capability to differentiate infected from vaccinated animals (DIVA). In conclusion, results from this comprehensive set of cattle studies demonstrated the safety of the replication-deficient AdtA24 vaccine and fulfilled safety-related requirements for U.S. regulatory requirements. © 2017 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

Auditory discrimination therapy (ADT) for tinnitus managment: preliminary results.

PubMed

Herraiz, C; Diges, I; Cobo, P; Plaza, G; Aparicio, J M

2006-12-01

This clinical assay has demonstrated the efficacy of auditory discrimination therapy (ADT) in tinnitus management compared with a waiting-list group. In all, 43% of the ADT patients improved their tinnitus, and its intensity together with its handicap were statistically decreased (EMB rating: B-2). To describe the effect of sound discrimination training on tinnitus. ADT designs a procedure to increase the cortical representation of trained frequencies (damaged cochlear areas with a secondary reduction of cortical stimulation) and to shrink the neighbouring over-represented ones (corresponding to tinnitus pitch). This prospective descriptive study included 14 patients with high frequency matched tinnitus. Tinnitus severity was measured according to a visual analogue scale (VAS) and the Tinnitus Handicap Inventory (THI). Patients performed a 10-min auditory discrimination task twice a day for 1 month. Discontinuous 8 kHz pure tones were randomly mixed with 500 ms 'white noise' sounds through a MP3 system. ADT group results were compared with a waiting-list group (n=21). In all, 43% of our patients had improvement in their tinnitus. A significant improvement in VAS (p=0.004) and THI mean scores was achieved (p=0.038). Statistical differences between ADT and the waiting-list group have been proved, considering patients' self-evaluations (p=0.043) and VAS scores (p=0.004). A non-significant reduction of THI was achieved (p=0.113).

Assessment of early response biomarkers in relation to long‐term survival in patients with HER2‐negative breast cancer receiving neoadjuvant chemotherapy plus bevacizumab: Results from the Phase II PROMIX trial

PubMed Central

Kimbung, Siker; Markholm, Ida; Bjöhle, Judith; Lekberg, Tobias; von Wachenfeldt, Anna; Azavedo, Edward; Saracco, Ariel; Hellström, Mats; Veerla, Srinivas; Paquet, Eric; Bendahl, Pär‐Ola; Fernö, Mårten; Bergh, Jonas; Loman, Niklas

2017-01-01

Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response‐guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One‐hundred‐and‐fifty patients with large, operable and locally advanced HER2‐negative breast cancer received epirubicin and docetaxel, with the addition of bevacizumab. Patients underwent tumor biopsies at baseline, after Cycle 2 and at the time of surgery. The primary end point, pCR, and its relation with the secondary endpoints event‐free survival (EFS), overall survival (OS) and gene expression profiles, are reported. The pCR rate was 13% (95% CI 8.6–20.2), with significantly more pCRs among triple‐negative [28% (95% CI 14.8–45.4)] than among hormone receptor positive (HR+) tumors [9% (95% CI 4.6–16.3); (OR = 3.9 [CI = 1.5–10.3])]. pCR rates were not associated with EFS or OS. PAM50 subtypes significantly changed after Cycle 2 (p = 0.03) and an index of absolute changes in PAM50 correlations between these time‐points was associated with EFS [HR = 0.62 (CI = 0.3–1.1)]. In univariable analyses, signatures for angiogenesis, proliferation, estrogen receptor signaling, invasion and metastasis, and immune response, measured after Cycle 2, were associated with pCR in HR+ tumors. Evaluation of changes in molecular subtypes and other signatures early in the course of neoadjuvant treatment may be predictive of pCR and EFS. These factors may help guide further treatment and should be considered when designing neoadjuvant trials. PMID:28940389

Relative value of physical examination, mammography, and breast sonography in evaluating the size of the primary tumor and regional lymph node metastases in women receiving neoadjuvant chemotherapy for locally advanced breast carcinoma.

PubMed

Herrada, J; Iyer, R B; Atkinson, E N; Sneige, N; Buzdar, A U; Hortobagyi, G N

1997-09-01

The purpose of this study was to correlate physical examination and sonographic and mammographic measurements of breast tumors and regional lymph nodes with pathological findings and to evaluate the effect of neoadjuvant chemotherapy on clinical Tumor-Node-Metastasis stage by noninvasive methods. This was a retrospective analysis of 100 patients with locally advanced breast cancer registered and treated in prospective trials of neoadjuvant chemotherapy. All patients received four cycles of a doxorubicin-containing regimen and had noninvasive evaluation of the primary tumor and regional lymph nodes before and after neoadjuvant chemotherapy by physical examination, sonography, and mammography and underwent breast surgery and axillary dissection within 5 weeks after completion of neoadjuvant chemotherapy. The correlations between clinical and pathological measurements were determined by Spearman rank correlation analysis. A proportional odds model was used to examine predictive values. Eighty-three patients had both a clinically detectable primary tumor and lymph node metastases. Sixty-four patients had a decrease in Tumor-Node-Metastasis stage after chemotherapy. For 54% of patients, there was concordance in clinical response between the primary tumor and lymph node compartment; for the rest, results were discordant. Physical examination correlated best with pathological findings in the measurement of the primary tumor (P = 0.0003), whereas sonography was the most accurate predictor of size for axillary lymph nodes (P = 0.0005). The combination of physical examination and mammography worked best for assessment of the primary tumor (P = 0.003), whereas combining physical examination with sonography gave optimal evaluation of regional lymph nodes (P = 0.0001). In conclusion, physical examination is the best noninvasive predictor of the real size of locally advanced primary breast cancer, whereas sonography correlates better with the real dimensions of axillary lymph nodes. The combination of physical examination with either mammography or sonography significantly improves the accuracy of noninvasive assessment of tumor dimensions.

Efficacy of assessing circulating cell-free DNA using a simple fluorescence assay in patients with triple-negative breast cancer receiving neoadjuvant chemotherapy: a prospective observational study

PubMed Central

Park, Kwonoh; Woo, Miyoung; Kim, Jeong Eun; Ahn, Jin-Hee; Jung, Kyung Hae; Roh, Jin; Gong, Gyungyub; Kim, Sung-Bae

2018-01-01

This study aims to assess cell-free DNA (CFD) by a fluorescence assay as a biomarker for early prediction of a pathologic complete response (pCR) and relapse in patients with triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy. Patients with clinical stage II or III TNBC scheduled for neoadjuvant chemotherapy were prospectively enrolled. All patients underwent four cycles of Adriamycin plus cyclophosphamide (AC), followed by four cycles of cisplatin or docetaxel chemotherapy and surgery. Blood samples were obtained before the initial chemotherapy (baseline-CFD) and after four AC neoadjuvant chemotherapy cycles (AC-CFD) to evaluate CFD levels. In total, 72 patients who met the inclusion criteria were enrolled. The mean baseline-CFD and AC-CFD levels were 239 ± 68 and 210 ± 66 ng/mL, respectively, with a significant decline in the CFD levels after AC neoadjuvant chemotherapy (P = 0.001). In the 33.6-month median follow-up, 18 cases of relapse were reported. A ROC curve analysis of baseline-CFD was performed to determine the predictive value for relapse, and an area under the curve of 0.62 (95% CI, 0.46–0.78) at 264 ng/mL was obtained. Patients with baseline-CFD >264 ng/mL were at a higher risk of relapse than those with baseline-CFD ≤264 ng/mL (HR, 2.84; 95% CI, 1.11–7.24; P = 0.029). Multivariate analysis established baseline-CFD as an independent predicting factor for relapse (HR, 3.74; 95% CI, 1.32–10.53; P = 0.013). In conclusion, baseline-CFD measured by a fluorescence assay might be a potential biomarker to predict relapse, which could be useful for risk stratification of TNBC. PMID:29423090

Pertuzumab/Trastuzumab/CT Versus Trastuzumab/CT Therapy for HER2+ Breast Cancer: Results from the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST).

PubMed

Beitsch, Peter; Whitworth, Pat; Baron, Paul; Rotkis, Michael C; Mislowsky, Angela M; Richards, Paul D; Murray, Mary K; Pellicane, James V; Dul, Carrie L; Nash, Charles H; Stork-Sloots, Lisette; de Snoo, Femke; Untch, Sarah; Lee, Laura A

2017-09-01

Pertuzumab became a standard part of neoadjuvant therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancers approximately halfway through Neoadjuvant Breast Registry Symphony Trial (NBRST) enrollment, providing a unique opportunity to determine biologically which clinical HER2+ patients benefit most from dual targeting. As a neoadjuvant phase 4 study, NBRST classifies patients by both conventional and molecular subtyping. Of 308 clinical HER2+ patients enrolled in NBRST between 2011 and 2014 from 62 U.S. institutions, 297 received neoadjuvant chemotherapy (NCT) with HER2-targeted therapy and underwent surgery. This study compared the pathologic complete response (pCR) rate of BluePrint versus clinical subtypes with treatment, specifically differences between trastuzumab (T) treatment and trastuzumab and pertuzumab (T/P) treatment. In this study, 60% of the patients received NCT-T, and 40% received NCT-T/P. The overall pCR rate (ypT0/isN0) was 47%. BluePrint classified 161 tumors (54%) as HER2 type, with a pCR rate of 65%. This was significantly higher than the pCR rate for the 91 HER2+ tumors (31%) classified as luminal (18%) (p = 0.00001) and the 45 tumors (15%) classified as basal (44%) (p = 0.0166). The patients treated with T/P had higher pCR rates than those treated with trastuzumab alone. The difference was most pronounced in the BluePrint luminal patients (8 vs. 31%). The highest pCR was reached by the BluePrint HER2-type patients treated with T/P (76%). The addition of pertuzumab leads to increased pCR rates for all HER2+ patient groups except for the BluePrint basal-type patients. This better response was most pronounced for the BluePrint luminal-type patients.

Value of FDG-PET/CT Volumetry After Chemoradiotherapy in Rectal Cancer.

PubMed

Okuno, Takayuki; Kawai, Kazushige; Koyama, Keitaro; Takahashi, Miwako; Ishihara, Soichiro; Momose, Toshimitsu; Morikawa, Teppei; Fukayama, Masashi; Watanabe, Toshiaki

2018-03-01

Neoadjuvant chemoradiotherapy followed by an optimal surgery is the standard treatment for patients with locally advanced rectal cancer. FDG-PET/CT is commonly used as the modality for assessing the effect of chemoradiotherapy. The purpose of this study was to investigate whether PET/CT-based volumetry could contribute to the prediction of pathological complete response or prognosis after neoadjuvant chemoradiotherapy. This was a retrospective cohort study. This study was conducted at a single research center. Ninety-one consecutive patients with locally advanced rectal cancer were enrolled between January 2005 and December 2015. Patients underwent PET/CT before and after neoadjuvant chemoradiotherapy. Maximum standardized uptake value and total lesion glycolysis on PET/CT before and after neoadjuvant chemoradiotherapy were calculated using isocontour methods. Correlations between these variables and clinicopathological factors and prognosis were assessed. PET/CT-associated variables before chemoradiotherapy were not correlated with either clinicopathological factors or prognosis. Maximum standardized uptake value was associated with pathological complete response, but total lesion glycolysis was not. Maximum standardized uptake value correlated with ypT, whereas total lesion glycolysis correlated with both ypT and ypN. High total lesion glycolysis was associated with a considerably poorer prognosis; the 5-year recurrence rate was 65% and the 5-year mortality rate 42%, whereas in lesions with low total lesion glycolysis, these were 6% and 2%. On multivariate analysis, high total lesion glycolysis was an independent risk factor for recurrence (HR = 4.718; p = 0.04). The gain in fluoro-2-deoxy-D-glucose uptake may differ between scanners, thus the general applicability of this threshold should be validated. In patients with locally advanced rectal cancer, high total lesion glycolysis after neoadjuvant chemoradiotherapy is strongly associated with a worse prognosis. Total lesion glycolysis after chemoradiotherapy may be a promising preoperative predictor of recurrence and death. See Video Abstract at http://links.lww.com/DCR/A464.

Current and future strategies for the nutritional management of cardiometabolic complications of androgen deprivation therapy for prostate cancer.

PubMed

Turner, Lauren; Poole, Karen; Faithfull, Sara; Griffin, Bruce A

2017-12-01

Androgen deprivation therapy (ADT) is used widely as part of a combined modality for the treatment of prostate cancer. However, ADT has also been associated with the development of cardiometabolic complications that can increase mortality from cardiovascular events. There is emerging evidence to suggest that ADT-related cardiometabolic risk can be mitigated by diet and lifestyle modification. While the clinical focus for a nutritional approach for achieving this effect is unclear, it may depend upon the timely assessment and targeting of dietary changes to the specific risk phenotype of the patient. The present review aims to address the metabolic origins of ADT-related cardiometabolic risk, existing evidence for the effects of dietary intervention in modifying this risk, and the priorities for future dietary strategies.

The number of cycles of neoadjuvant chemotherapy is associated with prognosis of stage IIIc-IV high-grade serous ovarian cancer.

PubMed

Xu, Xia; Deng, Fei; Lv, Mengmeng; Chen, Xiaoxiang

2017-02-01

No consensus exists on the number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced stage epithelial ovarian cancer. The present study aims to explore the optimal number of cycles of neoadjuvant chemotherapy (NAC) and post-operation chemotherapy to treat the International Federation of Gynecology and Obstetrics stage IIIc-IV high-grade serous ovarian cancer (HG-SOC). A total of 129 IIIc-IV stage HG-SOC cases were retrospectively analyzed. Cases were comprised of patients who underwent NAC followed by IDS and who achieved clinical complete response (CCR) at the end of primary therapy. Patients were recruited from the Jiangsu Institute of Cancer Research between 1993 and 2013. Optimal IDS-associated factors were explored with logistic regression. The association between progression-free survival (PFS), overall survival (OS) duration, and covariates was assessed by Cox proportional hazards model and log-rank test. The median number of NAC cycle was 3 (range 1-8). CA-125 decreasing kinetics (p = 0.01) was independently associated with optimal IDS. CA-125 decreasing kinetics, optimal IDS, and NAC cycles was independently associated with OS (p < 0.01, p < 0.01, p = 0.03, respectively) and PFS (p < 0.01, p < 0.01, p = 0.04, respectively). The PFS of patients who underwent ≥5 NAC cycles was shorter than those of patients who underwent <5 NAC cycles (12.3 versus 17.2 months). The PFS and OS of patients who underwent <5 cycles of adjuvant chemotherapy post-IDS were shorter than those of patients who underwent ≥5 cycles (14.2 and 20.3 versus 21.2 and 28.8 months). NAC cycles, CA-125 decreasing kinetics, and optimal debulking are independently associated with the prognosis of patients with advanced stage HG-SOC who underwent NAC/IDS and achieved CCR. The number of administered NAC cycles should not exceed 4.

Evolving Therapeutic Strategies in Mucosal Melanoma Have Not Improved Survival Over Five Decades

PubMed Central

KIRCHOFF, DANIEL D.; DEUTSCH, GARY B.; FOSHAG, LELAND J.; LEE, JI HEY; SIM, MYUNG-SHIN; FARIES, MARK B.

2016-01-01

Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neoadjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized. PMID:26802836

Evolving Therapeutic Strategies in Mucosal Melanoma Have Not Improved Survival Over Five Decades.

PubMed

Kirchoff, Daniel D; Deutsch, Gary B; Foshag, Leland J; Lee, Ji Hey; Sim, Myung-Shin; Faries, Mark B

2016-01-01

Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neoadjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized.

Individual response to neoadjuvant chemotherapy assessed with optical mammography in patients with breast cancer

NASA Astrophysics Data System (ADS)

Anderson, Pamela G.; Krishnamurthy, Nishanth; Kalli, Sirishma; Sassaroli, Angelo; Makim, Shital S.; Graham, Roger A.; Fantini, Sergio

2017-02-01

We report an optical mammography study on eight patients with breast cancer who underwent neoadjuvant chemotherapy. Of these eight patients, six were responders (tumor size decreased by more than 50%) and two were nonresponders (tumor size decreased by less than 50%). The goals of this study are (1) to characterize the temporal evolution of the hemoglobin concentration ([HbT]) and saturation (SO2) in breast tissue during the course of treatment in responders and non-responders, and (2) to define a quantitative index that is capable of identifying responders and nonresponders during treatment. We found that both [HbT] and SO2 decreased by a greater amount in responders than in non-responders during therapy. This result applied to both cancerous and healthy breast, but the discrimination of responders and non-responders was more significant with SO2 measurements in the cancerous breast. A cumulative response index defined in terms of SO2 measurements in the cancerous breast achieved a 100% sensitivity and 100% specificity for the identification of responders and non-responders at therapy midpoint. These results confirm the potential of optical mammography in assessing response to neoadjuvant chemotherapy during treatment, thus offering the opportunity to consider alternative options to ineffective treatment regimens.

Patient's Skeletal Muscle Radiation Attenuation and Sarcopenic Obesity are Associated with Postoperative Morbidity after Neoadjuvant Chemoradiation and Resection for Rectal Cancer.

PubMed

Berkel, Annefleur E M; Klaase, Joost M; de Graaff, Feike; Brusse-Keizer, Marjolein G J; Bongers, Bart C; van Meeteren, Nico L U

2018-06-13

To investigate the relation between skeletal muscle measurements (muscle mass, radiation attenuation, and sarcopenic obesity), postoperative morbidity, and survival after treatment of locally advanced rectal cancer. This explorative retrospective study identified 99 consecutive patients who underwent neoadjuvant chemoradiation and surgery between January 2007 and May 2012. Skeletal muscle mass was measured as total psoas area and total abdominal muscle area (TAMA) at 3 anatomical levels using the patient's preoperative computed tomography scan. Radiation attenuation was measured using corresponding mean Hounsfield units for TAMA. Sarcopenic obesity was defined as body mass index above 25 kg·m-2 combined with skeletal muscle mass index below the sex-specific median. Postoperative complications were graded by using the -Clavien-Dindo classification. Twenty-five patients (25.3%) developed a grade 3-5 complication. Lower radiation attenuation was independently associated with overall (p = 0.003) and grade 3-5 complications (p = 0.002). Sarcopenic obesity was associated with overall complications (all p < 0.05). Skeletal muscle measurements and survival were not significantly related. Radiation attenuation was associated with overall and grade 3-5 postoperative morbidity after neoadjuvant chemoradiation and non-laparoscopic resection for rectal cancer. Sarcopenic obesity was associated with overall complications. © 2018 S. Karger AG, Basel.

Germline Variation in HSD3B1 as a Novel Biomarker in Prostate Cancer

DTIC Science & Technology

2017-10-01

metastasis. Taken together, these results indicate that HSD3B1 genotype is a powerful genetic biomarker of resistance to ADT, and can be used to...salvage ADT. We analyzed differences in these endpoints according to genotype using an additive genetic model with the log-rank trend test...indicate that HSD3B1 genotype is a powerful genetic biomarker of resistance to ADT, and can be used to identify men who might benefit from escalated

High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

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

Ost, Piet, E-mail: piet.ost@ugent.be; Cozzarini, Cesare; De Meerleer, Gert

2012-07-01

Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was leftmore » at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.« less

Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

PubMed Central

Mason, Malcolm D.; Parulekar, Wendy R.; Sydes, Matthew R.; Brundage, Michael; Kirkbride, Peter; Gospodarowicz, Mary; Cowan, Richard; Kostashuk, Edmund C.; Anderson, John; Swanson, Gregory; Parmar, Mahesh K.B.; Hayter, Charles; Jovic, Gordana; Hiltz, Andrea; Hetherington, John; Sathya, Jinka; Barber, James B.P.; McKenzie, Michael; El-Sharkawi, Salah; Souhami, Luis; Hardman, P.D. John; Chen, Bingshu E.; Warde, Padraig

2015-01-01

Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer. PMID:25691677

Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality.

PubMed

Tsai, Henry K; D'Amico, Anthony V; Sadetsky, Natalia; Chen, Ming-Hui; Carroll, Peter R

2007-10-17

We investigated whether androgen deprivation therapy (ADT) use is associated with an increased risk of death from cardiovascular causes in patients treated for localized prostate cancer. From the Cancer of the Prostate Strategic Urologic Research Endeavor database, data on 3262 patients treated with radical prostatectomy and 1630 patients treated with external beam radiation therapy, brachytherapy, or cryotherapy for localized prostate cancer were included in this analysis. Competing risks regression analyses were performed to assess whether use of ADT was associated with a shorter time to death from cardiovascular causes after controlling for age (as a continuous variable) and the presence of baseline cardiovascular disease risk factors. All tests for statistical significance were two-sided. The median follow-up time was 3.8 years (range = 0.1-11.3 years). Among the 1015 patients who received ADT, the median duration of ADT use was 4.1 months (range = 1.0-32.9 months). In a competing risks regression analysis that controlled for age and risk factors for cardiovascular disease, both ADT use (adjusted hazard ratio [HR] = 2.6; 95% confidence interval [CI] = 1.4 to 4.7; P = .002) and age (adjusted HR = 1.07; 95% CI = 1.02 to 1.1; P = .003) were associated with statistically significantly increased risks of death from cardiovascular causes in patients treated with radical prostatectomy. Among patients 65 years or older treated with radical prostatectomy, the 5-year cumulative incidence of cardiovascular death was 5.5% (95% CI = 1.2% to 9.8%) in those who received ADT and 2.0% (95% CI = 1.1% to 3.0%) in those who did not. Among patients 65 years or older treated with external beam radiation therapy, brachytherapy, or cryotherapy, ADT use was associated with a higher cumulative incidence of death from cardiovascular causes, but the difference did not reach statistical significance. The use of ADT appears to be associated with an increased risk of death from cardiovascular causes in patients undergoing radical prostatectomy for localized prostate cancer.

Seven-Month Prostate-Specific Antigen Is Prognostic in Metastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation With or Without Docetaxel

PubMed Central

Harshman, Lauren C.; Chen, Yu-Hui; Liu, Glenn; Carducci, Michael A.; Jarrard, David; Dreicer, Robert; Hahn, Noah; Garcia, Jorge A.; Hussain, Maha; Shevrin, Daniel; Eisenberger, Mario; Kohli, Manish; Plimack, Elizabeth R.; Cooney, Matthew; Vogelzang, Nicholas J.; Picus, Joel; Dipaola, Robert

2018-01-01

Purpose We evaluated the relationship between prostate-specific antigen (PSA) and overall survival in the context of a prospectively randomized clinical trial comparing androgen-deprivation therapy (ADT) plus docetaxel with ADT alone for initial metastatic hormone-sensitive prostate cancer. Methods We performed a landmark survival analysis at 7 months using the E3805 Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) database (ClinicalTrials.gov identifier: NCT00309985). Inclusion required at least 7 months of follow-up and PSA levels at 7 months from ADT initiation. We used the prognostic classifiers identified in a previously reported trial (Southwest Oncology Group 9346) of PSA ≤ 0.2, > 0.2 to 4, and > 4 ng/mL. Results Seven hundred nineteen of 790 patients were eligible for this subanalysis; 358 were treated with ADT plus docetaxel, and 361 were treated with ADT alone. Median follow-up time was 23.1 months. On multivariable analysis, achieving a 7-month PSA ≤ 0.2 ng/mL was more likely with docetaxel, low-volume disease, prior local therapy, and lower baseline PSAs (all P ≤ .01). Across all patients, median overall survival was significantly longer if 7-month PSA reached ≤ 0.2 ng/mL compared with > 4 ng/mL (median survival, 60.4 v 22.2 months, respectively; P < .001). On multivariable analysis, 7-month PSA ≤ 0.2 and low volume disease were prognostic of longer overall survival (all P < 0.01). The addition of docetaxel increased the likelihood of achieving a PSA ≤ 0.2 ng/mL at 7 months (45.3% v 28.8% of patients on ADT alone). Patients on ADT alone who achieved a 7-month PSA ≤ 0.2 ng/mL had the best survival and were more likely to have low-volume disease (56.7%). Conclusion PSA ≤ 0.2 ng/mL at 7 months is prognostic for longer overall survival with ADT for metastatic hormone-sensitive prostate cancer irrespective of docetaxel administration. Adding docetaxel increased the likelihood of a lower PSA and improved survival. PMID:29261442

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

Castle, Katherine O., E-mail: kocastle@mdanderson.org; Hoffman, Karen E.; Levy, Lawrence B.

Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis basedmore » on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease. In patients with GS 4+3 or T2c disease, the addition of ADT to dose-escalated RT did improve FFF.« less

Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus

PubMed Central

Noble, Fergus; Nolan, Luke; Bateman, Adrian C; Byrne, James P; Kelly, Jamie J; Bailey, Ian S; Sharland, Donna M; Rees, Charlotte N; Iveson, Timothy J; Underwood, Tim J; Bateman, Andrew R

2013-01-01

AIM: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy. METHODS: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ≤ 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics. RESULTS: Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to NAC was associated with significantly increased DFS (mean DFS; TRG 1-2: 5.1 years, 95%CI: 4.6-5.6 vs TRG 3-5: 2.8 years, 95%CI: 2.2-3.3, P < 0.0001). Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC (median DFS; TRG 3-5 and nodal down-staging: 5.533 years, 95%CI: 3.558-7.531 vs TRG 3-5 and no nodal down-staging: 1.114 years, 95%CI: 0.961-1.267, P < 0.0001). CONCLUSION: Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS. PMID:24409055

Physical activity levels in locally advanced rectal cancer patients following neoadjuvant chemoradiotherapy and an exercise training programme before surgery: a pilot study.

PubMed

Loughney, Lisa; West, Malcolm A; Dimitrov, Borislav D; Kemp, Graham J; Grocott, Michael Pw; Jack, Sandy

2017-01-01

The aim of this pilot study was to measure changes in physical activity level (PAL) variables, as well as sleep duration and efficiency in people with locally advanced rectal cancer (1) before and after neoadjuvant chemoradiotherapy (CRT) and (2) after participating in a pre-operative 6-week in-hospital exercise training programme, following neoadjuvant CRT prior to major surgery, compared to a usual care control group. We prospectively studied 39 consecutive participants (27 males). All participants completed standardised neoadjuvant CRT: 23 undertook a 6-week in-hospital exercise training programme following neoadjuvant CRT. These were compared to 16 contemporaneous non-randomised participants (usual care control group). All participants underwent a continuous 72-h period of PA monitoring by SenseWear biaxial accelerometer at baseline, immediately following neoadjuvant CRT (week 0), and at week 6 (following the exercise training programme). Of 39 recruited participants, 23 out of 23 (exercise) and 10 out of 16 (usual care control) completed the study. In all participants ( n  = 33), there was a significant reduction from baseline (pre-CRT) to week 0 (post-CRT) in daily step count: median (IQR) 4966 (4435) vs. 3044 (3265); p  < 0.0001, active energy expenditure (EE) (kcal): 264 (471) vs. 154 (164); p  = 0.003, and metabolic equivalent (MET) (1.3 (0.6) vs. 1.2 (0.3); p  = 0.010). There was a significant improvement in sleep efficiency (%) between week 0 and week 6 in the exercise group compared to the usual care control group (80 (13) vs. 78 (15) compared to (69 ((24) vs. 76 (20); p  = 0.022), as well as in sleep duration and lying down time ( p  < 0.05) while those in active EE (kcal) (152 (154) vs. 434 (658) compared to (244 (198) vs. 392 (701) or in MET (1.3 (0.4) vs. 1.5 (0.5) compared to (1.1 (0.2) vs. 1.5 (0.5) were also of importance but did not reach statistical significance ( p  > 0.05). An apparent improvement in daily step count and overall PAL in the exercise group was not statistically significant. PAL variables, daily step count, EE and MET significantly reduced following neoadjuvant CRT in all participants. A 6-week pre-operative in-hospital exercise training programme improved sleep efficiency, sleep duration and lying down time when compared to participants receiving usual care. Clinicaltrials.gov NCT01325909.

A polymorphism in a transporter of testosterone is a determinant of androgen independence in prostate cancer.

PubMed

Sharifi, Nima; Hamada, Akinobu; Sissung, Tristan; Danesi, Romano; Venzon, David; Baum, Caitlin; Gulley, James L; Price, Douglas K; Dahut, William L; Figg, William D

2008-08-05

To determine if patients with advanced prostate cancer carrying a polymorphism that codes for a more active testosterone transporter have less durable responses to androgen-deprivation therapy (ADT) than patients not carrying this polymorphism. We previously determined that a polymorphism in SLCO1B3 affects testosterone transport and that those men who have at least one wild-type T allele at the 334 T > G polymorphism in this gene have a shorter survival. We hypothesized that the T allele which increases testosterone transport would be associated with a shorter interval from ADT to androgen independence. We examined the association between this SLCO1B3 polymorphism and time from ADT to androgen independence, ADT to prostate-specific antigen (PSA) nadir and PSA nadir to androgen independence in 68 Caucasian patients with advanced prostate cancer who were treated with ADT with metastatic disease (D2) or biochemical failure with no metastatic disease (D0). When examined separately, patients in the individual stages tended to have a shorter time to androgen independence with the T allele in the D0 (P = 0.11) and D2 (P = 0.18) groups. Combining these groups and stratifying by stage yielded a statistically significant shorter time to androgen independence with the T allele (P = 0.048). A polymorphism in a transporter that increases testosterone import is associated with a shorter time to androgen independence in patients with prostate cancer who are treated with ADT.

Microstructural control of charge transport in organic blend thin-film transistors

DOE PAGES

Hunter, Simon; Chen, Jihua; Anthopoulos, Thomas D.

2014-07-17

In this paper, the charge-transport processes in organic p-channel transistors based on the small-molecule 2,8-difluoro-5,11-bis(triethylsilylethynyl)anthradithiophene (diF-TES ADT), the polymer poly(triarylamine)(PTAA) and blends thereof are investigated. In the case of blend films, lateral conductive atomic force microscopy in combination with energy filtered transmission electron microscopy are used to study the evolution of charge transport as a function of blends composition, allowing direct correlation of the film's elemental composition and morphology with hole transport. Low-temperature transport measurements reveal that optimized blend devices exhibit lower temperature dependence of hole mobility than pristine PTAA devices while also providing a narrower bandgap trap distribution thanmore » pristine diF-TES ADT devices. These combined effects increase the mean hole mobility in optimized blends to 2.4 cm 2/Vs; double the value measured for best diF-TES ADT-only devices. The bandgap trap distribution in transistors based on different diF-TES ADT:PTAA blend ratios are compared and the act of blending these semiconductors is seen to reduce the trap distribution width yet increase the average trap energy compared to pristine diF-TES ADT-based devices. In conclusion, our measurements suggest that an average trap energy of <75 meV and a trap distribution of <100 meV is needed to achieve optimum hole mobility in transistors based on diF-TES ADT:PTAA blends.« less

An Update on Triptorelin: Current Thinking on Androgen Deprivation Therapy for Prostate Cancer.

PubMed

Merseburger, Axel S; Hupe, Marie C

2016-07-01

Androgen deprivation therapy (ADT) is the mainstay palliative treatment for men with locally advanced and metastatic prostate cancer, and aims to reduce testosterone to levels obtained by surgical castration. Use of gonadotropin-releasing hormone (GnRH) agonists predominates among the ADT options. The GnRH agonist, triptorelin is a first-line hormonal therapy that has demonstrated efficacy and safety in clinical trials of patients with locally advanced non-metastatic or metastatic disease. Sustained-release 1-, 3- and 6-month formulations of triptorelin, administered intramuscularly or subcutaneously, have been developed to provide improved flexibility and convenience for the patient. Head-to-head studies of GnRH agonists are lacking in the field of prostate cancer. Despite the inevitable progression to castration-resistant prostate cancer (CRPC) in most patients receiving ADT, monitoring of testosterone levels needs to improve in routine practice and physicians should not overlook the benefits of continued ADT in their patients when introducing one of the various new treatment options for CRPC. For improved survival outcomes, there remains a need to tailor ADT treatment regimens, novel hormonal agents and chemotherapy according to the individual patient with advanced prostate cancer.

Integrated performance and reliability specification for digital avionics systems

NASA Technical Reports Server (NTRS)

Brehm, Eric W.; Goettge, Robert T.

1995-01-01

This paper describes an automated tool for performance and reliability assessment of digital avionics systems, called the Automated Design Tool Set (ADTS). ADTS is based on an integrated approach to design assessment that unifies traditional performance and reliability views of system designs, and that addresses interdependencies between performance and reliability behavior via exchange of parameters and result between mathematical models of each type. A multi-layer tool set architecture has been developed for ADTS that separates the concerns of system specification, model generation, and model solution. Performance and reliability models are generated automatically as a function of candidate system designs, and model results are expressed within the system specification. The layered approach helps deal with the inherent complexity of the design assessment process, and preserves long-term flexibility to accommodate a wide range of models and solution techniques within the tool set structure. ADTS research and development to date has focused on development of a language for specification of system designs as a basis for performance and reliability evaluation. A model generation and solution framework has also been developed for ADTS, that will ultimately encompass an integrated set of analytic and simulated based techniques for performance, reliability, and combined design assessment.

A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients.

PubMed

Kiwata, J L; Dorff, T B; Schroeder, E T; Gross, M E; Dieli-Conwright, C M

2016-12-01

Androgen deprivation therapy (ADT), a primary treatment for locally advanced or metastatic prostate cancer, is associated with the adverse effects on numerous physiologic parameters, including alterations in cardiometabolic variables that overlap with components of the metabolic syndrome (MetS). As MetS is an established risk factor for cardiovascular mortality and treatment for prostate cancer has been associated with the development of MetS, interventions targeting cardiometabolic factors have been investigated in prostate cancer patients to attenuate the detrimental effects of ADT. Much support exists for exercise interventions in improving MetS variables in insulin-resistant adults, but less evidence is available in men with prostate cancer. Regular exercise, when performed at appropriate intensities and volumes, can elicit improvements in ADT-related adverse effects, including MetS, and contributes to the growing body of literature supporting the role of exercise in cancer survivorship. This review (1) discusses the biologic inter-relationship between prostate cancer, ADT and MetS, (2) evaluates the current literature in support of exercise in targeting MetS and (3) describes the physiological mechanisms by which exercise may favorably alter MetS risk factors in prostate cancer patients on ADT.

A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients

PubMed Central

Kiwata, J L; Dorff, T B; Schroeder, E T; Gross, M E; Dieli-Conwright, C M

2016-01-01

Androgen deprivation therapy (ADT), a primary treatment for locally advanced or metastatic prostate cancer, is associated with the adverse effects on numerous physiologic parameters, including alterations in cardiometabolic variables that overlap with components of the metabolic syndrome (MetS). As MetS is an established risk factor for cardiovascular mortality and treatment for prostate cancer has been associated with the development of MetS, interventions targeting cardiometabolic factors have been investigated in prostate cancer patients to attenuate the detrimental effects of ADT. Much support exists for exercise interventions in improving MetS variables in insulin-resistant adults, but less evidence is available in men with prostate cancer. Regular exercise, when performed at appropriate intensities and volumes, can elicit improvements in ADT-related adverse effects, including MetS, and contributes to the growing body of literature supporting the role of exercise in cancer survivorship. This review (1) discusses the biologic inter-relationship between prostate cancer, ADT and MetS, (2) evaluates the current literature in support of exercise in targeting MetS and (3) describes the physiological mechanisms by which exercise may favorably alter MetS risk factors in prostate cancer patients on ADT. PMID:27349496

Noether and Abbott-Deser-Tekin conserved quantities in scalar-tensor theory of gravity both in Jordan and Einstein frames

NASA Astrophysics Data System (ADS)

Bhattacharya, Krishnakanta; Das, Ashmita; Majhi, Bibhas Ranjan

2018-06-01

We revisit the thermodynamic aspects of the scalar-tensor theory of gravity in the Jordan and in the Einstein frame. Examining the missing links of this theory carefully, we establish the thermodynamic descriptions from the conserved currents and potentials by following both the Noether and the Abbott-Deser-Tekin (ADT) formalism. With the help of conserved Noether current and potential, we define the thermodynamic quantities, which we show to be conformally invariant. Moreover, the defined quantities are shown to fit nicely in the laws of (the first and the second) black hole thermodynamics formulated by the Wald's method. We stretch the study of the conformal equivalence of the physical quantities in these two frames by following the ADT formalism. Our further study reveals that there is a connection between the ADT and the Noether conserved quantities, which signifies that the ADT approach provide the equivalent thermodynamic description in the two frames as obtained in Noether prescription. Our whole analysis is very general as the conserved Noether and ADT currents and potentials are formulated off-shell and the analysis is exempted from any prior assumption or boundary condition.

Correlation between apparent diffusion coefficient and histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy.

PubMed

Wang, Jifei; Sun, Meili; Liu, Dawei; Hu, Xiaoshu; Pui, Margaret H; Meng, Quanfei; Gao, Zhenhua

2017-08-01

Background Neoadjuvant chemotherapy has made limb-salvage surgery possible for the patients with osteosarcoma. Diffusion-weighted magnetic resonance imaging (DWI) has been used to monitor chemotherapy response. Purpose To correlate the apparent diffusion coefficient (ADC) values with histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy. Material and Methods Twelve patients with osteoblastic (n = 7), chondroblastic (n = 4), and fibroblastic (n = 1) osteosarcomas underwent post-chemotherapy DWI before limb-salvage surgery. ADCs corresponding to 127 histological tissue samples from the 12 resected specimens were compared to histological features. Results The mean ADC value of non-cartilaginous viable tumor (38/91, ADC = 1.22 ± 0.03 × 10 -3  mm 2 /s) was significantly ( P < 0.001) lower than that of non-cartilaginous tumor cell necrosis without stroma disintegration (25/91, ADC =1.77 ± 0.03 × 10 -3  mm 2 /s), cartilaginous viable tumor (14/91, ADC = 2.19 ± 0.04 × 10 -3  mm 2 /s), and cystic areas including liquefied necrosis, blood space, and secondary aneurysmal bone cyst (14/91, ADC = 2.29 ± 0.05 × 10 -3  mm 2 /s). The mean ADC value of non-cartilaginous tumor cell necrosis was also significantly ( P < 0.001) smaller than those of viable cartilaginous tumor and cystic/hemorrhagic necrosis whereas the mean ADC values were not significantly ( P > 0.05) different between viable cartilaginous tumor and cystic/hemorrhagic necrosis. Conclusion DWI allows assessment of tumor necrosis after neoadjuvant chemotherapy by ADC differences between viable tumor and necrosis in fibroblastic and osteoblastic osteosarcomas whereas viable chondroblastic osteosarcoma has high ADC and cannot be distinguished reliably from necrosis.

Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

PubMed Central

Abdo, Joe; Bertellotti, Carrie A.; Cornell, David L.; Agrawal, Devendra K.; Mittal, Sumeet K.

2017-01-01

There has been an alarming rise in the incidence of esophageal adenocarcinoma which continues to have poor survival rates primarily due to lack of effective chemotherapy and presentation at advanced stages. Over a dozen chemotherapeutic agents are FDA approved for esophageal cancer (EC), and a two or three-drug combination is typically prescribed as first-line therapy for the majority of EC patients, administered either pre or post-operatively with esophageal resection. We have noticed significant variability in adjuvant and neoadjuvant regimens used in the community setting. The aim of this study was to review the various drug regimens used in the neoadjuvant setting for EC patients with adenocarcinoma undergoing resection at a single tertiary referral center in the Midwest. A total of 123 patients (stage II–III) underwent esophageal resection after neoadjuvant treatment at the center. Overall, 18 distinct drug regimens were used in 123 patients including two patients who received targeted therapy. Median survival post-surgery for this group was 11.2 months with no single regimen offering a survival advantage. These results reveal an unclear algorithm of how accepted regimens are prescribed in the community setting as well as a dire need for agents that are more effective. Additionally, it was noted that although proteomic markers have been found to predict drug response to 92% of the FDA-approved drugs in EC (12 of 13), according to pathology reports, molecular diagnostic testing was not used to direct treatment in this cohort. We therefore propose potential strategies to improve clinical outcomes including the use of a robust molecular oncology diagnostic panel and discuss the potential role for targeted chemotherapy and/or immunotherapy in the management of EC patients. PMID:28770168

Phase II study of neoadjuvant therapy with nab-paclitaxel and cisplatin followed by surgery in patients with locally advanced esophageal squamous cell carcinoma

PubMed Central

Fan, Yun; Jiang, Youhua; Zhou, Xinming; Chen, Qixun; Huang, Zhiyu; Xu, Yanjun; Gong, Lei; Yu, Haifeng; Yang, Haiyan; Liu, Jinshi; Lei, Tao; Zhao, Qiang; Mao, Weimin

2016-01-01

Background We carried out a phase II study to evaluate the efficiency and safety of the combination of nanoparticle albumin bound-paclitaxel (nab-paclitaxel) and cisplatin as preoperative chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) Results From Oct 2011 to Dec 2012, 35 patients were enrolled and received neoadjuvant chemotherapy. Thirty patients underwent surgery and achieved a 100% R0 resection. Pathological complete response (pCR) rate was 13.3% and near pCR rate was 6.7%. Down-staging was achieved in 19 patients. With median follow-up of 37.8 months, 16 patients were still alive. One-, 2- and 3- year overall survival (OS) rate was 90.0%, 70.0% and 43.3%, respectively. This treatment resulted in a median disease-free survival (DFS) of 34.7 months and a median OS of 37.8 months. Median DFS and OS of down-staged patients were significantly longer than those of non-downstaged patients. The grade 4 toxicities during neoadjuvant chemotherapy were limited to neutropenia (2.9%) and vomiting (2.9%). Methods Patients with locally advanced ESCC (stage IIA to IIIC) and performance status 0-1 were enrolled and received two cycles of nab-paclitaxel (100 mg/m2) on day 1, 8, 22 and 29, and cisplatin (75 mg/m2) on day 1 and 22, followed by resection. Two cycles of adjuvant chemotherapy with the same regimen were given. Postoperative radiotherapy was permitted and decided by radiation therapist. Conclusion Weekly nab-paclitaxel with three-weekly cisplatin seems effective and safe as a neoadjuvant chemotherapy strategy for locally advanced ESCC. Down-staged patients have favorable outcome. ClinicalTrials.gov Identifier NCT01258192 PMID:27244882

Neoadjuvant Interdigitated Chemoradiotherapy Using Mesna, Doxorubicin, and Ifosfamide for Large, High-grade, Soft Tissue Sarcomas of the Extremity: Improved Efficacy and Reduced Toxicity.

PubMed

Chowdhary, Mudit; Sen, Neilayan; Jeans, Elizabeth B; Miller, Luke; Batus, Marta; Gitelis, Steven; Wang, Dian; Abrams, Ross A

2018-05-18

Patients with large, high-grade extremity soft tissue sarcoma (STS) are at high risk for both local and distant recurrence. RTOG 95-14, using a regimen of neoadjuvant interdigitated chemoradiotherapy with mesna, doxorubicin, ifosfamide, and dacarbazine followed by surgery and 3 cycles of adjuvant mesna, doxorubicin, ifosfamide, and dacarbazine, demonstrated high rates of disease control at the cost of significant toxicity (83% grade 4, 5% grade 5). As such, this regimen has not been widely adopted. Herein, we report our institutional outcomes utilizing a modified interdigitated chemoradiotherapy regimen, without dacarbazine, and current radiotherapy planning and delivery techniques for high-risk STS. Adults with large (≥5 cm; median, 12.9 cm), grade 3 extremity STS who were prospectively treated as part of our institutional standard of care from 2008 to 2016 are included. Neoadjuvant chemoradiotherapy consisted of 3 cycles of mesna, doxorubicin, and ifosfamide (MAI) and 44 Gy (22 Gy in 11 fractions between cycles of MAI) after which patients underwent surgical resection and received 3 additional cycles of MAI. Twenty-six patients received the MAI treatment protocol. At a median follow-up of 47.3 months, 23 (88.5%) patients are still alive. Three year locoregional recurrence-free survival, disease-free survival, and overall survival are 95.0%, 64.0%, and 95.0%, respectively. There have been no therapy-related deaths or secondary malignancies. The nonhematologic grade 4 toxicity rate was 7.7%. Neoadjuvant interdigitated MAI radiotherapy followed by resection and 3 cycles of adjuvant MAI has resulted in acceptable and manageable toxicity and highly favorable survival in patients at greatest risk for treatment failure.

Surgical Outcomes of Patients Undergoing Extrafascial Hysterectomy After Neoadjuvant Radiotherapy With or Without Chemotherapy for Locally Advanced Endometrial Cancer Clinically Extending to the Cervix or Parametria.

PubMed

Boisen, Michelle M; Vargo, J Austin; Beriwal, Sushi; Sukumvanich, Paniti; Olawaiye, Alexander B; Kelley, Joseph L; Edwards, Robert P; Huang, Marilyn; Courtney-Brooks, Madeleine; Comerci, John T

2017-07-01

Recent data have shown high rates of clinical and pathologic responses to neoadjuvant radiation therapy for locally advanced endometrial cancer. There are limited data on the surgical outcomes of these patients in the era of modern radiation and surgical techniques. We sought to characterize surgical outcomes after extrafascial hysterectomy in this population. Patients with endometrial cancer of all histologies clinically involving the cervix or parametria treated with neoadjuvant brachytherapy followed by extrafascial hysterectomy from 1999 to 2014 were identified. Patient charts were reviewed for data regarding treatment characteristics and postoperative outcomes. Pearson χ and logistic regression analyses were used to assess correlations between surgical complications and treatment-related variables. Twenty-nine patients met inclusion criteria. Mean operating time for the cohort was 115 minutes. Mean estimated blood loss was 100 mL. No visceral injuries occurred. Mean length of hospital stay was 1 and 4 days for the minimally invasive and laparotomy groups, respectively. Rates of postoperative ileus, blood transfusion, wound infection, and readmission were 3%, 3%, 6%, and 3%, respectively. No case of prolonged urodynamic dysfunction was noted. The rate of vaginal complications was significantly higher in the group of patients who underwent minimally invasive surgery as compared with laparotomy (33% vs 5%, P < 0.041). These data support adjuvant extrafascial hysterectomy after neoadjuvant radiotherapy for endometrial cancer with cervical or parametrial involvement as a safe and viable procedure, with low rates of postoperative complications. Extra care should be taken when closing the vaginal cuff to reduce the risk of vaginal cuff complications.

Value of diffusion-weighted MRI and apparent diffusion coefficient measurements for predicting the response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy.

PubMed

Iannicelli, Elsa; Di Pietropaolo, Marco; Pilozzi, Emanuela; Osti, Mattia Falchetto; Valentino, Maria; Masoni, Luigi; Ferri, Mario

2016-10-01

The aim of our study was to assess the performance value of magnetic resonance imaging (MRI) in the restaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy (CRT) and in the identification of good vs. poor responders to neoadjuvant therapy. A total of 34 patients with locally advanced rectal cancer underwent MRI prior to and after CRT. T stage and tumor regression grade (TRG) on post-CRT MRI was compared with the pathological staging ypT and TRG. Tumor volume and the apparent diffusion coefficient (ADC) were measured using diffusion-weighted imaging (DWI) before and after neoadjuvant CRT; the percentage of tumor volume reduction and the change of ADC (ΔADC) was also calculated. ADC parameters and the percentage of tumor volume reduction were correlated to histopathological results. The diagnostic performance of ADC and volume reduction to assess tumor response was evaluated by calculating the area under the ROC curve and the optimal cut-off values. A significant correlation between the T stage and the TRG defined in DW-MRI after CRT and the ypT and the TRG observed on the surgical specimens was found (p = 0.001; p < 0.001). The mean post-CRT ADC and ΔADC in responder patients was significantly higher compared to non-responder ones (p = 0.001; p = 0.01). Furthermore, the mean post-CRT ADC values were significantly higher in tumors with T-downstage (p = 0.01). DW-MRI may have a significant role in the restaging and in the evaluation of post-CRT response of locally advanced rectal cancer. Quantitative analysis of DWI through ADC map may result in a promising noninvasive tool to evaluate the response to therapy.

Validating the Astronomy Diagnostics Test for Undergraduate Non-Science Majors

NASA Astrophysics Data System (ADS)

Slater, T. F.; Hufnagel, B.; Adams, J. P.

1999-05-01

The Astronomy Diagnostics Test (ADT) is a standard diagnostic test for undergraduate non-science majors taking introductory astronomy. Serving to compare the effectiveness of various instructional interventions, the ADT has been developed and field-tested over the last year by a multi-institutional team, known as the Collaboration for Astronomy Education Research (CAER). The team includes Jeff Adams, Rebecca Lindell Adrian, Christine Brick, Gina Brissenden, Grace Deming, Beth Hufnagel, Tim Slater, and Michael Zeilik, among others. The need for a nationally normed, valid, and reliable assessment instrument in astronomy has been articulated in a wide variety of forums. This need results from the simultaneous occurrence of several important phenomena over the last decade including: the inclusion of astronomy concepts in national science education standards; documentation of widespread astronomical misconceptions; the influence of the Force Concept Inventory guiding reform in physics; and the call for university faculty to document improvements in instruction. In a triangulated effort to validate the ADT for widespread use, the researchers used on a three-phase strategy. In this context, "validity" means that the ADT measures what it purports to measure. In other words, do students give the correct answer for the scientifically correct reasons or, alternatively, do students give the correct answer even though they have misunderstandings about the phenomena being tested? These three phases were: (1) conduct statistical item-analysis on each test question for a large and diverse student population (n=2000 from 21 institutions); (2) conduct 60 clinical student interviews using the test questions as the script; and (3) conduct an inductive analysis of 30 student supplied written responses to ADT questions posed without the multiple-choices provided. The ADT and its supporting comparative database is available at URL: http://solar.physics.montana.edu/aae/adt/. This research was supported in part by NSF DGE-9714489 (BH) and NASA Grant #CERES-NAG54576 (TS).

Hypoxia-Independent Downregulation of Hypoxia-Inducible Factor 1 Targets by Androgen Deprivation Therapy in Prostate Cancer

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

Ragnum, Harald Bull; Røe, Kathrine; Division of Medicine, Department of Oncology, Akershus University Hospital, Lørenskog

2013-11-15

Purpose: We explored changes in hypoxia-inducible factor 1 (HIF1) signaling during androgen deprivation therapy (ADT) of androgen-sensitive prostate cancer xenografts under conditions in which no significant change in immunostaining of the hypoxia marker pimonidazole had occurred. Methods and Materials: Gene expression profiles of volume-matched androgen-exposed and androgen-deprived CWR22 xenografts, with similar pimonidazole-positive fractions, were compared. Direct targets of androgen receptor (AR) and HIF1 transcription factors were identified among the differentially expressed genes by using published lists. Biological processes affected by ADT were determined by gene ontology analysis. HIF1α protein expression in xenografts and biopsy samples from 35 patients receiving neoadjuvantmore » ADT was assessed by immunohistochemistry. Results: A total of 1344 genes showed more than 2-fold change in expression by ADT, including 35 downregulated and 5 upregulated HIF1 targets. Six genes were shared HIF1 and AR targets, and their downregulation was confirmed with quantitative RT-PCR. Significant suppression of the biological processes proliferation, metabolism, and stress response in androgen-deprived xenografts was found, consistent with tumor regression. Nineteen downregulated HIF1 targets were involved in those significant biological processes, most of them in metabolism. Four of these were shared AR and HIF1 targets, including genes encoding the regulatory glycolytic proteins HK2, PFKFB3, and SLC2A1. Most of the downregulated HIF1 targets were induced by hypoxia in androgen-responsive prostate cancer cell lines, confirming their role as hypoxia-responsive HIF1 targets in prostate cancer. Downregulation of HIF1 targets was consistent with the absence of HIF1α protein in xenografts and downregulation in patients by ADT (P<.001). Conclusions: AR repression by ADT may lead to downregulation of HIF1 signaling independently of hypoxic fraction, and this may contribute to tumor regression. HIF1α expression is probably not a useful hypoxia biomarker during ADT in prostate cancer.« less

Benefits of Using Stereotactic Body Radiotherapy in Patients With Metachronous Oligometastases of Hormone-Sensitive Prostate Cancer Detected by [18F]fluoromethylcholine PET/CT.

PubMed

Bouman-Wammes, Esther W; van Dodewaard-De Jong, Joyce M; Dahele, Max; Cysouw, Matthijs C F; Hoekstra, Otto S; van Moorselaar, R Jeroen A; Piet, Maartje A H; Verberne, Hein J; Bins, Adriaan D; Verheul, Henk M W; Slotman, Ben J; Oprea-Lager, Daniela E; Van den Eertwegh, Alfons J M

2017-10-01

For patients with oligometastatic recurrence of prostate cancer (PC), stereotactic body radiation therapy (SBRT) represents an attractive treatment option, as it is safe without major side effects. The aim of this study was to investigate the impact of SBRT in delaying the start of androgen deprivation therapy (ADT). Forty-three patients treated with SBRT for oligometastatic recurrence (< 5 metastases) of hormone-sensitive PC, defined with [ 18 F]fluoromethylcholine positron emission tomography/computed tomography were included. As a control group, 20 patients with oligometastatic disease not treated with SBRT were identified from another hospital. Data were collected retrospectively. A post-SBRT prostate-specific antigen (PSA) response was seen in 29 (67.4%) of 43 patients. Median ADT-free survival (ADT-FS) was 15.6 months (95% confidence interval [CI], 11.7-19.5) for the whole group, and 25.7 months (95% CI, 9.0-42.4) for patients with a PSA response. Seven patients were treated with a second course of SBRT because of oligometastatic disease recurrence; the ADT-FS in this group was 32.1 months (95% CI, 7.8-56.5). Compared with the control group, the ADT-FS from first diagnosis of metastasis was significantly longer, with 17.3 (95% CI, 13.7-20.9) months versus 4.19 months (95% CI, 0.0-9.0), P < .001. Also, time between diagnosis of the metastasis until progression of disease during ADT use (castration resistance) was longer for the SBRT-treated patients (mean 66.6, 95% CI, 53.5-79.8, vs. 36.41, 95% CI, 26.0-46.8 months, P = .020). There were no grade III or IV adverse events reported. SBRT can safely and effectively be used to postpone ADT in appropriately selected patients with oligometastatic recurrence of PC. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of a Group-Mediated Exercise and Dietary Intervention in the Treatment of Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: Results From the IDEA-P Trial.

PubMed

Focht, Brian C; Lucas, Alexander R; Grainger, Elizabeth; Simpson, Christina; Fairman, Ciaran M; Thomas-Ahner, Jennifer M; Buell, Jackie; Monk, J Paul; Mortazavi, Amir; Clinton, Steven K

2018-04-19

Although androgen-deprivation therapy (ADT) is the foundation of treatment for prostate cancer, the physiological impacts of ADT result in functional decline and enhanced risk of chronic disease and metabolic syndrome. The Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) is a single-blind, randomized, pilot trial comparing the effects of a group-mediated, cognitive-behavioral (GMCB) exercise and dietary intervention (EX+D) with those of a standard-of-care (SC) control during the treatment of prostate cancer patients undergoing ADT. A total of 32 prostate cancer patients (M age = 66.28, SD = 7.79) undergoing ADT were randomly assigned to the 12-week EX+D intervention (n = 16) or control (n = 16). The primary outcome in IDEA-P was change in mobility performance with secondary outcomes including body composition and muscular strength. Blinded assessment of outcomes were obtained at baseline and at 2- and 3-month follow-ups. Favorable adherence and retention rates were observed, and no serious intervention-related adverse events were documented. Intent-to-treat ANCOVA controlling for baseline value and ADT duration demonstrated that EX+D resulted in significantly greater improvements in mobility performance (p < .02), muscular strength (p < .01), body fat percentage (p < .05), and fat mass (p < .03) at 3-month follow-up, relative to control. Findings from the IDEA-P trial suggest that a GMCB-based EX+D intervention resulted in significant, clinically meaningful improvements in mobility performance, muscular strength, and body composition, relative to controls. Collectively, these results suggest that the EX+D was a safe and well-tolerated intervention for prostate cancer patients on ADT. The utility of implementing this approach in the treatment of prostate cancer patients on ADT should be evaluated in future large-scale efficacy trials. NCT02050906.

Radiotherapy in cT3 prostatic carcinoma: retrospective comparison between neoadjuvant and adjuvant hormonotherapy.

PubMed

Cellini, Numa; Luzi, Stefano; Morganti, Alessio Giuseppe; Valentini, Vincenzo; Mantini, Giovanna; Racioppi, Marco; Smaniotto, Daniela; Leone, Mariavittoria; Mattiucci, Gian Carlo; Digesù, Cinzia; Giustacchini, Mario; Destito, Antonio; Alcini, Eugenio

2004-01-01

The aim of this study was to retrospectively compare the clinical outcomes achieved in 2 groups of patients with cT3 prostatic carcinoma undergoing neoadjuvant hormonotherapy and neoadjuvant hormonotherapy plus adjuvant hormonotherapy with external beam radiotherapy. One hundred patients with cT3N0M0 prostatic carcinoma underwent radiotherapy to pelvic lymph nodes (45 Gy, 1.8 Gy/fraction) with a booster dose (65-70 Gy) to the prostatic cavity. Forty-four patients received neoadjuvant hormonotherapy (goserelin, starting 2 months before radiotherapy and continuing until the end of irradiation); 56 patients received neoadjuvant hormonotherapy plus adjuvant goserelin until disease progression, if present. Patients undergoing adjuvant hormonotherapy as compared to those who received exclusive neoadjuvant therapy showed a higher reduction in PSA level below 1.0 ng/ml (p = 0.0211), a lower incidence of biochemical failures (p = 0.0170), a lower incidence of hematogenous metastases (p = 0.0320) and a trend suggestive of a better disease-free survival (p = 0.0660). At univariate analysis (logrank), Gleason score did not show a significant correlation with any of the end points analyzed. To the contrary, patients with tumor <15 mm showed a better local control (p = 0.0347) and biochemical failure-free survival (p = 0.0102). Furthermore, a trend between initial PSA level and incidence of hematogenous metastases was observed (p = 0.0519). Patients with a posttreatment PSA level <1.0 ng/ml had a lower incidence of metastases (p = 0.0237) and a better survival (p = 0.0178); patients with complete clinical response showed a lower incidence of biochemical failures (p = 0.0469). Radiotherapy doses >70 Gy showed a trend with biochemical failure-free survival (p = 0.0554). At multivariate analysis, a correlation between Gleason score and incidence of metastases (p = 0.0232), and between tumor diameter and local control (p = 0.0178) and biochemical failure-free survival (p = 0.0290) was recorded. In patients with cT3N0M0 prostate carcinoma, prolonged hormonotherapy was shown to be significantly correlated with biochemical failure-free survival and distant metastasis-free survival. Furthermore, tumor size had a significant impact on biochemical failure-free survival as well as on local control. Copyright 2004 S. Karger AG, Basel

Androgen Deprivation Therapy and maintenance of intimacy: a randomized controlled pilot study of an educational intervention for patients and their partners.

PubMed

Walker, Lauren M; Hampton, Amy J; Wassersug, Richard J; Thomas, Bejoy C; Robinson, John W

2013-03-01

Androgen Deprivation Therapy (ADT) for prostate cancer is associated with many treatment side effects that tend to erode couples' intimacy. We piloted a randomized controlled trial to investigate the effect of an educational intervention designed to preserve couples' intimacy in the face of ADT. Couples were recruited at the time the patient was first prescribed ADT and were randomized to a treatment or control group. Those in the treatment group were asked to read an educational guide and participate in an educational session designed to inform couples about possible ADT side effects and management strategies. To assess changes in the couples' relationships, they were administered the Dyadic Adjustment Scale and the Personal Assessment of Intimacy in Relationships questionnaire prior to randomization and again at 6 months. While results were not statistically significant, trends and effect sizes suggest that the educational intervention helped attenuate declines in intimacy for patients, but not for their partners. Couples who participated in the intervention were more successful at maintaining sexual activity than were couples in the control group. ADT places considerable strain on intimate relationships, particularly for the partners. It appears that patients who receive help in anticipating and managing ADT related changes report better dyadic adjustment and closer intimacy. More efforts are needed to develop interventions to benefit patients' partners. We conclude that the intervention holds promise and that a full-scale evaluation of the intervention is both feasible and warranted. Copyright © 2012 Elsevier Inc. All rights reserved.

TGFβ Superfamily Members Mediate Androgen Deprivation Therapy-Induced Obese Frailty in Male Mice

PubMed Central

Pan, Chunliu; Singh, Shalini; Sahasrabudhe, Deepak M.; Chakkalakal, Joe V.; Krolewski, John J.

2016-01-01

First line treatment for recurrent and metastatic prostate cancer is androgen deprivation therapy (ADT). Use of ADT has been increasing in frequency and duration, such that side effects increasingly impact patient quality of life. One of the most significant side effects of ADT is sarcopenia, which leads to a loss of skeletal muscle mass and function, resulting in a clinical disability syndrome known as obese frailty. Using aged mice, we developed a mouse model of ADT-induced sarcopenia that closely resembles the phenotype seen in patients, including loss of skeletal muscle strength, reduced lean muscle mass, and increased adipose tissue. Sarcopenia onset occurred about 6 weeks after castration and was blocked by a soluble receptor (ActRIIB-Fc) that binds multiple TGFβ superfamily members, including myostatin, growth differentiation factor 11, activin A, activin B, and activin AB. Analysis of ligand expression in both gastrocnemius and triceps brachii muscles demonstrates that each of these proteins is induced in response to ADT, in 1 of 3 temporal patterns. Specifically, activin A and activin AB levels increase and decline before onset of strength loss at 6 weeks after castration, and myostatin levels increase coincident with the onset of strength loss and then decline. In contrast, activin B and growth differentiation factor 11 levels increase after the onset of strength loss, 8–10 weeks after castration. The observed patterns of ligand induction may represent differential contributions to the development and/or maintenance of sarcopenia. We hypothesize that some or all of these ligands are targets for therapy to ameliorate ADT-induced sarcopenia in prostate cancer patients. PMID:27611336

Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.

PubMed

Swords, Douglas S; Firpo, Matthew A; Johnson, Kirsten M; Boucher, Kenneth M; Scaife, Courtney L; Mulvihill, Sean J

2017-07-01

Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of androgen deprivation therapy on intraprostatic tumour volume identified on 18F choline PET/CT for prostate dose painting radiotherapy.

PubMed

Chan, Joachim; Carver, Antony; Brunt, John N H; Vinjamuri, Sobhan; Syndikus, Isabel

2017-03-01

Prostate dose painting radiotherapy requires the accurate identification of dominant intraprostatic lesions (DILs) to be used as boost volumes; these can be identified on multiparametric MRI (mpMRI) or choline positron emission tomography (PET)/CT. Planning scans are usually performed after 2-3 months of androgen deprivation therapy (ADT). We examine the effect of ADT on choline tracer uptake and boost volumes identified on choline PET/CT. Fluoroethylcholine ( 18 F choline) PET/CT was performed for dose painting radiotherapy planning in patients with intermediate- to high-risk prostate cancer. Initially, they were performed at planning. Owing to low visual tracer uptake, PET/CT for subsequent patients was performed at staging. We compared these two approaches on intraprostatic lesions obtained on PET using both visual and automatic threshold methods [prostate maximum standardized uptake value (SUV max ) 60%] when compared with mpMRI. PET/CT was performed during ADT in 11 patients (median duration of 85 days) and before ADT in 29 patients. ADT significantly reduced overall prostate volume by 17%. During ADT, prostate SUV max was lower although it did not reach statistical significance (4.2 vs 6.6, p = 0.06); three patients had no visually identifiable PET DIL; and visually defined PET DILs were significantly smaller than corresponding mpMRI DILs (p = 0.03). However, all patients scanned before ADT had at least one visually identifiable PET DIL, with no significant size difference between MRI and visually defined PET DILs. In both groups, threshold PET produced larger DILs than visual PET. Both PET methods have moderate sensitivity (0.50-0.68) and high specificity (0.85-0.98) for identifying MRI-defined disease. For visual contouring of boost volumes in prostate dose painting radiotherapy, 18 F choline PET/CT should be performed before ADT. For threshold contouring of boost volumes using our PET/CT scanning protocol, threshold levels of above 60% prostate SUV max may be more suitable. Additional use of PET with MRI for radiotherapy planning can significantly change the overall boost volumes compared with using MRI alone. Advances in knowledge: For prostate dose painting radiotherapy, the additional use of 18 F choline PET with MRI can significantly change the overall boost volumes, and PET should be performed before hormone therapy, especially if boost volumes are visually identified.

Vascular responses to radiotherapy and androgen-deprivation therapy in experimental prostate cancer

PubMed Central

2012-01-01

Background Radiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC. Methods Using mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI. Results Compared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density ( VD), and vessel area fraction ( VF) from qIHC. Although total hypoxic fractions ( HF) did not change, estimated acute hypoxia scores ( AHS) – the proportion of hypoxia staining within 50 μm from perfusion staining – were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve ( AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size ( VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after pharmacokinetic modeling. Interestingly, such modeling also detected tumor necrosis very strongly. Conclusions DCE MRI reliably allows non-invasive assessment of tumors’ vascular function. The findings of increased tumor vascularization after ADT encourage further studies into whether these changes are beneficial for combined RT, or if treatment with anti-angiogenic therapy may be a strategy to improve the therapeutic efficacy of ADT in advanced PC. PMID:22621752

Surgical Outcomes of Primary Versus Post-Neoadjuvant Chemotherapy Breast Conservation Surgery: A Comparative Study from a Developing Country.

PubMed

Agarwal, Gaurav; Sonthineni, Chaitra; Mayilvaganan, Sabaretnam; Mishra, Anjali; Lal, Punita; Agrawal, Vinita

2018-05-01

In India and other developing countries, breast conservation surgery (BCS) rates in breast cancer patients are low due to advanced disease at presentation and misconceptions about BCS outcomes. Many patients presenting with large or locally advanced breast cancers (LABC) can be offered post-neoadjuvant chemotherapy (NACT) BCS, safety of which is not as well established as that of primary BCS. This retrospective study compared pathological and surgical outcome parameters in patients undergoing primary and post-NACT BCS. All non-metastatic breast cancer patients undergoing BCS during 2011-2015 with 1-year follow-up were included. Outcome parameters in form of margin infiltration, ipsilateral breast tumor recurrence (IBTR) rates and IBTR-free survival were compared between primary and post-NACT BCS patients groups. One hundred and twenty-nine patients underwent BCS; 95 underwent primary and 34 post-NACT BCS. Patients in both groups underwent similar multimodality treatment as per institutional protocols. Post-NACT patients more frequently required oncoplastic volume displacement or replacement surgery (p = 0.002). Re-excision of infiltrated margins was needed more frequently in primary BCS compared with post-NACT BCS group (14.4 vs. 8.8%; p = 0.40). IBTR (Mean follow-up = 30.7 months) was seen in 8.8% post-NACT patients compared with 2.1% primary BCS (p = 0.114). IBTR-free survival did not differ significantly between the groups in stage-wise comparison. Post-NACT BCS is safe even in large tumors and LABC, though many require oncoplastic procedures for satisfactory cosmesis. In a developing country where many patients present with large breast cancers or LABC, the benefits of BCS can be offered to a majority with the help of NACT, without compromising the chances of cure.

Application of neoadjuvant chemotherapy in occult breast cancer

PubMed Central

Yang, Haisong; Li, Ling; Zhang, Mengmeng; Zhang, Shiyong; Xu, Shu; Ma, Xiaoxia

2017-01-01

Abstract Rationale: Although rare, occult breast cancer (OBC) originates from breast tissue. Its primary lesions cannot be identified by clinical examination or imaging; therefore, the diagnosis, treatment, and prognosis remain controversial. Patient concerns: This study comprised 5 female OBC patients who were admitted to the Affiliated Hospital of Guizhou Medical University for painless axillary lumps. Diagnoses: 18F-flurodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) indicated metastasis in the ipsilateral axillary lymph nodes. No clear breast primary lesions were identified; other organs were also excluded as the primary site. Pathological biopsy confirmed axillary lymph node metastasis of adenocarcinoma. Immunohistochemical staining of the tumor to identify the source revealed that estrogen receptors (ERs) and progesterone receptors (PgRs) were positive in 2 cases, ER was positive and PR was negative in 1 case, and both were negative in 2 cases. Human epidermal growth factor receptor 2 was negative in all cases. All patients were diagnosed with OBC. Interventions: All patients underwent neoadjuvant chemotherapy (NAC). One patient did not undergo follow-up therapy. The other 4 underwent total mastectomy plus axillary lymph node dissection followed by radiotherapy. Two patients also underwent endocrine therapy. Outcomes: Patients were followed up for 9.0 to 72.0 months. Four achieved pathological complete response. One patient experienced metastasis to the ipsilateral supraclavicular lymph nodes 2.0 years later, which was cleared after additional treatment. The other patients were tumor free. Lessons: Here, we are reporting 5 cases of OBC treated with NAC that were evaluated by 18F-FDG PET/CT scans. This study suggests that NAC might lead to a positive outcome. PMID:28984771

Grain Boundary Induced Bias Instability in Soluble Acene-Based Thin-Film Transistors

PubMed Central

Nguyen, Ky V.; Payne, Marcia M.; Anthony, John E.; Lee, Jung Hun; Song, Eunjoo; Kang, Boseok; Cho, Kilwon; Lee, Wi Hyoung

2016-01-01

Since the grain boundaries (GBs) within the semiconductor layer of organic field-effect transistors (OFETs) have a strong influence on device performance, a substantial number of studies have been devoted to controlling the crystallization characteristics of organic semiconductors. We studied the intrinsic effects of GBs within 5,11-bis(triethylsilylethynyl) anthradithiophene (TES-ADT) thin films on the electrical properties of OFETs. The GB density was easily changed by controlling nulceation event in TES-ADT thin films. When the mixing time was increased, the number of aggregates in as-spun TES-ADT thin films were increased and subsequent exposure of the films to 1,2-dichloroethane vapor led to a significant increase in the number of nuleation sites, thereby increasing the GB density of TES-ADT spherulites. The density of GBs strongly influences the angular spread and crystallographic orientation of TES-ADT spherulites. Accordingly, the FETs with higher GB densities showed much poorer electrical characteristics than devices with lower GB density. Especially, GBs provide charge trapping sites which are responsible for bias-stress driven electrical instability. Dielectric surface treatment with a polystyrene brush layer clarified the GB-induced charge trapping by reducing charge trapping at the semiconductor-dielectric interface. Our study provides an understanding on GB induced bias instability for the development of high performance OFETs. PMID:27615358

Grain Boundary Induced Bias Instability in Soluble Acene-Based Thin-Film Transistors.

PubMed

Nguyen, Ky V; Payne, Marcia M; Anthony, John E; Lee, Jung Hun; Song, Eunjoo; Kang, Boseok; Cho, Kilwon; Lee, Wi Hyoung

2016-09-12

Since the grain boundaries (GBs) within the semiconductor layer of organic field-effect transistors (OFETs) have a strong influence on device performance, a substantial number of studies have been devoted to controlling the crystallization characteristics of organic semiconductors. We studied the intrinsic effects of GBs within 5,11-bis(triethylsilylethynyl) anthradithiophene (TES-ADT) thin films on the electrical properties of OFETs. The GB density was easily changed by controlling nulceation event in TES-ADT thin films. When the mixing time was increased, the number of aggregates in as-spun TES-ADT thin films were increased and subsequent exposure of the films to 1,2-dichloroethane vapor led to a significant increase in the number of nuleation sites, thereby increasing the GB density of TES-ADT spherulites. The density of GBs strongly influences the angular spread and crystallographic orientation of TES-ADT spherulites. Accordingly, the FETs with higher GB densities showed much poorer electrical characteristics than devices with lower GB density. Especially, GBs provide charge trapping sites which are responsible for bias-stress driven electrical instability. Dielectric surface treatment with a polystyrene brush layer clarified the GB-induced charge trapping by reducing charge trapping at the semiconductor-dielectric interface. Our study provides an understanding on GB induced bias instability for the development of high performance OFETs.

Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

PubMed Central

Dreussi, Eva; Cecchin, Erika; Polesel, Jerry; Canzonieri, Vincenzo; Agostini, Marco; Boso, Caterina; Belluco, Claudio; Buonadonna, Angela; Lonardi, Sara; Bergamo, Francesca; Gagno, Sara; De Mattia, Elena; Pucciarelli, Salvatore; De Paoli, Antonino; Toffoli, Giuseppe

2016-01-01

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses. PMID:27608007

Predictors of circumferential resection margin involvement in surgically resected rectal cancer: A retrospective review of 23,464 patients in the US National Cancer Database.

PubMed

Al-Sukhni, Eisar; Attwood, Kristopher; Gabriel, Emmanuel; Nurkin, Steven J

2016-04-01

The circumferential resection margin (CRM) is a key prognostic factor after rectal cancer resection. We sought to identify factors associated with CRM involvement (CRM+). A retrospective review was performed of the National Cancer Database, 2004-2011. Patients with rectal cancer who underwent radical resection and had a recorded CRM were included. Multivariable analysis of the association between clinicopathologic characteristics and CRM was performed. Tumor <1 mm from the cut margin defined CRM+. Of 23,464 eligible patients, 13.3% were CRM+. Factors associated with CRM+ were diagnosis later in the study period, lack of insurance, advanced stage, higher grade, undergoing APR, and receiving radiation. Nearly half of CRM+ patients did not receive neoadjuvant therapy. CRM+ patients who did not receive neoadjuvant therapy were more likely to be female, older, with more comorbidities, smaller tumors, earlier clinical stage, advanced pathologic stage, and CEA-negative disease compared to those who received it. Factors associated with CRM+ include features of advanced disease, undergoing APR, and lack of health insurance. Half of CRM+ patients did not receive neoadjuvant treatment. These represent cases where CRM status may be modifiable with appropriate pre-operative selection and multidisciplinary management. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic adenocarcinoma following neoadjuvant therapy.

PubMed

Baumgartner, Joel M; Krasinskas, Alyssa; Daouadi, Mustapha; Zureikat, Amer; Marsh, Wallis; Lee, Kenneth; Bartlett, David; Moser, A James; Zeh, Herbert J

2012-06-01

Celiac trunk encasement by adenocarcinoma of the pancreatic body is generally regarded as a contraindication for surgical resection. Recent studies have suggested that a subset of stage III patients will succumb to their disease in the absence of distant metastases. We hypothesized that patients with stage III tumors invading the celiac trunk, who are free of distant disease following neoadjuvant therapy, may derive prolonged survival benefit from aggressive surgical resection. We performed a retrospective review of distal pancreatectomies with en bloc celiac axis resection for pancreatic adenocarcinoma. Eleven patients underwent a distal pancreatectomy with en bloc celiac axis resection after completing neoadjuvant chemoradiation therapy. Median operative time was 8 h, 14 min, and median estimated blood loss was 700 ml. Median length of stay was 9 days. Five patients (45%) had postoperative complications; three were Clavien grade I. Four patients (35%) had pancreatic leaks; two were ISGPF grade B, and two were grade A. There were two 90-day perioperative deaths. Ten patients had R0 resections (91%). After a median follow-up of 41 weeks, six patients recurred. Four of the five patients with SMAD4 loss recurred, and two of the five patients with intact SMAD4 recurred. Median disease-free and overall survival were 21 weeks and 26 months, respectively. Resection of pancreatic body adenocarcinoma with celiac axis resection is technically feasible with acceptable perioperative morbidity and mortality.

Predictive factors and management of rectal bleeding side effects following prostate cancer brachytherapy.

PubMed

Price, Jeremy G; Stone, Nelson N; Stock, Richard G

2013-08-01

To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥ grade 2 proctitis. A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Actuarial risk of ≥ grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT. Copyright © 2013 Elsevier Inc. All rights reserved.

Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

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

Price, Jeremy G.; Stone, Nelson N.; Stock, Richard G., E-mail: Richard.Stock@mountsinai.org

2013-08-01

Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, andmore » treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT.« less

The effect of molecular subtype and body mass index on neo-adjuvant chemotherapy in breast cancer patients.

PubMed

Iwase, Toshiaki; Nakamura, Rikiya; Yamamoto, Naohito; Yoshi, Atushi; Itami, Makiko; Miyazaki, Masaru

2014-06-01

The aim of the present study was to analyze the effect of subtype and body mass index (BMI) on neo-adjuvant chemotherapy (NAC) and postoperative prognosis. Two-hundred and forty nine patients who underwent surgery after NAC were included. A multivariate analysis and survival analysis were used to clarify the relationship between BMI, subtype, and NAC. In the logistic regression model, the pCR rate had a significant relationship with the subtype and tumor stage. In the non-pCR group, more overweight patients had significantly a worse disease-free survival (DFS) compared to normal range patients (Log lank test, p < 0.05). In the Cox proportional hazards model, subtype and tumor stage were significantly associated with decreased DFS. In conclusion, patients with the ER (+), HER (-) type and a high BMI had a high risk for recurrence when they achieved non-pCR after NAC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sentinel Lymph Nodes for Breast Carcinoma: An Update on Current Practice

PubMed Central

Maguire, Aoife; Brogi, Edi

2016-01-01

Sentinel lymph node (SLN) biopsy has been established as the standard of care for axillary staging in patients with invasive breast carcinoma and clinically negative lymph nodes (cN0). Historically, all patients with a positive SLN underwent axillary lymph node dissection (ALND). The ACOSOG Z0011 trial showed that women with T1-T2 disease and cN0 who undergo breast conserving surgery and whole-breast radiotherapy can safely avoid ALND. The main goal of SLN examination should be to detect all macrometastases (>2mm). Gross sectioning SLNs at 2 mm intervals and microscopic examination of one H&E-stained section from each SLN block is the preferred method of pathologic evaluation of SLNs. The role and timing of SLN biopsy for patients having neoadjuvant chemotherapy is controversial and continues to be explored in clinical trials. SLN biopsies from patients with invasive breast carcinoma who have received neoadjuvant chemotherapy pose particular challenges for pathologists. PMID:26768036

Commentary on "Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial." Gravis G, Fizazi K, Joly F, Oudard S, Priou F, Esterni B, Latorzeff I, Delva R, Krakowski I, Laguerre B, Rolland F, Théodore C, Deplanque G, Ferrero JM, Pouessel D, Mourey L, Beuzeboc P, Zanetta S, Habibian M, Berdah JF, Dauba J, Baciuchka M, Platini C, Linassier C, Labourey JL, Machiels JP, El Kouri C, Ravaud A, Suc E, Eymard JC, Hasbini A, Bousquet G, Soulie M, Medical Oncology and Biostatistics, Institut Paoli-Calmettes, Marseille, France. Lancet Oncol 2013;14(2):149-58 [Epub 2013 Jan 8].

PubMed

Trump, Donald L

2013-11-01

Early chemotherapy might improve the overall outcomes of patients with metastatic non-castrate (i.e., hormone-sensitive) prostate cancer. We investigated the effects of the addition of docetaxel to androgen-deprivation therapy (ADT) for patients with metastatic non-castrate prostate cancer. In this randomised, open-label, phase 3 study, we enrolled patients in 29 centres in France and one in Belgium. Eligible patients were older than 18 years and had histologically confirmed adenocarcinoma of the prostate and radiologically proven metastatic disease; a Karnofsky score of at least 70%; a life expectancy of at least 3 months; and adequate hepatic, haematological, and renal function. They were randomly assigned to receive to ADT (orchiectomy or luteinising hormone-releasing hormone agonists, alone or combined with non-steroidal antiandrogens) alone or in combination with docetaxel (75 mg/m(2) intravenously on the first day of each 21-day cycle; up to nine cycles). Patients were randomised in a 1:1 ratio, with dynamic minimisation to minimise imbalances in previous systemic treatment with ADT, chemotherapy for local disease or isolated rising concentration of serum prostate-specific antigen, and Glass risk groups. Patients, physicians, and data analysts were not masked to treatment allocation. The primary endpoint was overall survival. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00104715. Between Oct 18, 2004, and Dec 31, 2008, 192 patients were randomly allocated to receive ADT plus docetaxel and 193 to receive ADT alone. Median follow-up was 50 months (IQR 39-63). Median overall survival was 58 9 months (95% CI 50 8-69 1) in the group given ADT plus docetaxel and 54 2 months (42 2-not reached) in that given ADT alone (hazard ratio 1 01, 95% CI 0 75-1 36). 72 serious adverse events were reported in the group given ADT plus docetaxel, of which the most frequent were neutropenia (40 [21%]), febrile neutropenia (six [3%]), abnormal liver function tests (three [2%]), and neutropenia with infection (two [1%]). Four treatment-related deaths occurred in the ADT plus docetaxel group (two of which were neutropenia-related), after which the data monitoring committee recommended treatment with granulocyte colony-stimulating factor. After this recommendation, no further treatment-related deaths occurred. No serious adverse events were reported in the ADT alone group. Docetaxel should not be used as part of first-line treatment for patients with non-castrate metastatic prostate cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Proton therapy may allow for comprehensive elective nodal coverage for patients receiving neoadjuvant radiotherapy for localized pancreatic head cancers.

PubMed

Lee, Richard Y; Nichols, Romaine C; Huh, Soon N; Ho, Meng W; Li, Zuofeng; Zaiden, Robert; Awad, Ziad T; Ahmed, Bestoun; Hoppe, Bradfors S

2013-12-01

Neoadjuvant radiotherapy has the potential to improve local disease control for patients with localized pancreatic cancers. Concern about an increased risk of surgical complications due to small bowel and gastric exposure, however, has limited enthusiasm for this approach. Dosimetric studies have demonstrated the potential for proton therapy to reduce intestinal exposure compared with X-ray-based therapy. We sought to determine if neoadjuvant proton therapy allowed for field expansions to cover high-risk nodal stations in addition to the primary tumor. Twelve consecutive patients with nonmetastatic cancers of the pancreatic head underwent proton-based planning for neoadjuvant radiotherapy. Gross tumor volume was contoured using diagnostic computed tomography (CT) scans with oral and intravenous contrast. Four-dimensional planning scans were utilized to define an internal clinical target volume (ICTV). Five-mm planning target volume (PTV) expansions on the ICTV were generated to establish an initial PTV (PTV1). A second PTV was created using the initial PTV but was expanded to include the high-risk nodal targets as defined by the RTOG contouring atlas (PTV2). Optimized proton plans were generated for both PTVs for each patient. All PTVs received a dose of 50.4 cobalt gray equivalent (CGE). Normal-tissue exposures to the small bowel space, stomach, right kidney, left kidney and liver were recorded. Point spinal cord dose was limited to 45 CGE. Median PTV1 volume was 308.75 cm(3) (range, 133.33-495.61 cm(3)). Median PTV2 volume was 541.75 cm(3) (range, 399.44-691.14 cm(3)). In spite of the substantial enlargement of the PTV when high-risk lymph nodes were included in the treatment volume, normal-tissue exposures (stomach, bowel space, liver, and kidneys) were only minimally increased relative to the exposures seen when only the gross tumor target was treated. Proton therapy appears to allow for field expansions to cover high-risk lymph nodes without significantly increasing critical normal-tissue exposure in the neoadjuvant setting.

Can we eliminate neoadjuvant chemoradiotherapy in favor of neoadjuvant multiagent chemotherapy for select stage II/III rectal adenocarcinomas: Analysis of the National Cancer Data base.

PubMed

Cassidy, Richard J; Liu, Yuan; Patel, Kirtesh; Zhong, Jim; Steuer, Conor E; Kooby, David A; Russell, Maria C; Gillespie, Theresa W; Landry, Jerome C

2017-03-01

Stage II and III rectal cancers have been effectively treated with neoadjuvant chemoradiotherapy (NCRT) followed by definitive resection. Advancements in surgical technique and systemic therapy have prompted investigation of neoadjuvant multiagent chemotherapy (NMAC) regimens with the elimination of radiation (RT). The objective of the current study was to investigate factors that predict for the use of NCRT versus NMAC and compare outcomes using the National Cancer Data Base (NCDB) for select stage II and III rectal cancers. In the NCDB, 21,707 patients from 2004 through 2012 with clinical T2N1 (cT2N1), cT3N0, or cT3N1 rectal cancers were identified who had received NCRT or NMAC followed by low anterior resection. Kaplan-Meier analyses, log-rank tests, and Cox-proportional hazards regression analyses were conducted along with propensity score matching analysis to reduce treatment selection bias. The 5-year actuarial overall survival (OS) rate was 75% for patients who received NCRT versus 67.2% for those who received NMAC (P < .01). On MVA, those who received NCRT had improved OS (hazard ratio, 0.77. P < .01), and this effect was confirmed on propensity score matching analysis (hazard ratio, 0.72; P = .01). In the same model, the following variables improved OS: age < 65 years, having private insurance, treatment at an academic center, living in an affluent zip code, a low comorbidity score, receipt of adjuvant chemotherapy, and a shorter interval before surgery (all P < .05). African Americans, men, patients with high-grade tumors, those with cT3N1 tumors, and those who underwent incomplete (R1) resection had worse OS (all P < .05). In this series, the elimination of neoadjuvant RT for select patients with stage II and III rectal adenocarcinoma was associated with worse OS and should not be recommended outside of a clinical trial. Cancer 2017;123:783-93. © 2016 American Cancer Society. © 2016 American Cancer Society.

Cytoreductive prostate radiotherapy in oligometastatic prostate cancer: a single centre analysis of toxicity and clinical outcome.

PubMed

Riva, Giulia; Marvaso, Giulia; Augugliaro, Matteo; Zerini, Dario; Fodor, Cristiana; Musi, Gennaro; De Cobelli, Ottavio; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja

2017-01-01

The current standard of care for patients with metastatic prostate cancer (mPCa) at diagnosis is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to define the role of a local radiotherapy (RT) treatment in the mPCa setting. We retrospectively reviewed data of patients with PCa and bone oligometastases at diagnosis treated in our institution with ADT followed by cytoreductive prostate-RT with or without RT on metastases. Biochemical and clinical failure (BF, CF), overall survival (OS) and RT-toxicity were assessed. We identified 22 patients treated with ADT and external-beam RT on primary between June 2008 and March 2016. All of them but four were also treated for bone metastases. RT on primary with moderately and extremely hypofractionated regimes started after 10.3 months (3.9-51.7) from ADT. After a median follow-up of 26.4 months (10.3-55.5), 20 patients are alive. Twelve patients showed BF after a median time of 23 months (14.5-104) and CF after a median of 23.6 months (15.3-106.1) from the start of ADT. Three patients became castration resistant, starting a new therapy; median time to castration resistance was 31.03 months (range: 29.9-31.5 months). According to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC), only one patient developed acute grade 3 genitourinary toxicity. No late grade >2 adverse events were observed. Prostate RT in oligometastatic patients is safe and offers long-lasting local control. When compared to ADT alone, RT on primary seems to improve biochemical control and long-term survival; however, this hypothesis should be investigated in prospective studies. Further research is warranted.

Falls and Frailty in Prostate Cancer Survivors: Current, Past, and Never Users of Androgen Deprivation Therapy.

PubMed

Winters-Stone, Kerri M; Moe, Esther; Graff, Julie N; Dieckmann, Nathan F; Stoyles, Sydnee; Borsch, Carolyn; Alumkal, Joshi J; Amling, Christopher L; Beer, Tomasz M

2017-07-01

To compare the prevalence of and association between falls and frailty of prostate cancer survivors (PCSs) who were current, past or never users of androgen deprivation therapy (ADT). Cross-sectional. Mail and electronic survey. PCSs (N = 280; mean age 72 ± 8). Cancer history, falls, and frailty status (robust, prefrail, frail) using traditionally defined and obese phenotypes. Current (37%) or past (34%) ADT users were more than twice as likely to have fallen in the previous year as never users (15%) (P = .002). ADT users had twice as many recurrent falls (P < .001) and more fall-related injuries than unexposed men (P = .01). Current (43%) or past (40%) ADT users were more likely to be classified as prefrail or frail than never users (15%) (P < .001), and the prevalence of combined obese frailty + prefrailty was even greater in current (59%) or past (62%) ADT users than never users (25%) (P < .001). Traditional and obese frailty significantly increased the likelihood of reporting falls in the previous year (odds ratio (OR) = 2.15, 95% CI = 1.18-3.94 and OR = 2.97, 95% CI = 1.62-5.58, respectively) and was also associated with greater risk of recurrent falls (OR = 3.10, 95% CI = 1.48-6.5 and OR = 3.99, 95% CI = 1.79-8.89, respectively). Current and past exposure to ADT is linked to higher risk of falls and frailty than no treatment. PCSs should be appropriately counseled on fall prevention strategies, and approaches to reduce frailty should be considered. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Genetic Predictors of Fatigue in Prostate Cancer Patients Treated with Androgen Deprivation Therapy: Preliminary Findings

PubMed Central

Jim, Heather S.L.; Park, Jong Y.; Permuth-Wey, Jennifer; Rincon, Maria A.; Phillips, Kristin M.; Small, Brent J.; Jacobsen, Paul B.

2012-01-01

Background Fatigue is a common and distressing side effect of androgen deprivation therapy (ADT) for prostate cancer. The goal of the current study was to examine the relationship between changes in fatigue following initiation of ADT and single nucleotide polymorphisms (SNPs) in three pro-inflammatory cytokine genes: interleukin-1 beta (IL1B), interleukin-6 (IL6), and tumor necrosis factor alpha (TNFA). Methods As part of a larger study, men with prostate cancer (n=53) were recruited prior to initiation of ADT. Fatigue was assessed at recruitment and six months after initiation of ADT. DNA was extracted from blood drawn at baseline. Results Patients with the IL6-174 (rs1800795) G/C or C/C genotype displayed greater increases in fatigue intrusiveness, frequency, and duration than the G/G genotype (p values≤0.05), although inclusion of age, race, and baseline depressive symptomatology in the model attenuated these relationships (p values≤0.09). Patients with the TNFA-308 (rs1800629) G/A genotype showed greater increases in fatigue severity than the G/G genotype (p=0.02). IL1B-511 (rs16944) genotype did not significantly predict changes in fatigue (p values>0.46). Patients with higher numbers of variants displayed greater increases in fatigue duration and interference (p values≤0.02) than patients with lower numbers of variants. Conclusions Prostate cancer patients treated with ADT who carry variant alleles of the IL6 and TNFA genes are susceptible to heightened fatigue. These preliminary data lend support for the role of genetic variation in the development of cancer-related fatigue secondary to ADT. Findings are relevant to attempts to develop personalized approaches to cancer treatment. PMID:22475653

Warm Anomaly Effects on California Current Phytoplankton

NASA Astrophysics Data System (ADS)

Gomez Ocampo, E.; Gaxiola-Castro, G.; Beier, E.; Durazo, R.

2016-02-01

Positive temperature anomalies were reported in the NE Pacific Ocean since the boreal winter of 2013-2014. Previous studies showed that these anomalies were caused by lower than normal rates of heat loss from the ocean to the atmosphere and by relatively weak cold water advection to the upper ocean. Anomalous Sea Surface Temperature (SST), Absolute Dynamic Topography (ADT), and Chlorophyll (CHL) obtained from monthly remote sensing data were registered in the California Current region during August 2014. Anomalies appeared around the coastal and oceanic zones, particularly in the onshore zone between Monterey Bay, California and Magdalena Bay, Baja California. High positive SST anomalous values up to 4ºC above the long-term mean, 20 cm in ADT, and less of 4.5 mg m-3 of CHL were registered. Changes of 20 cm in ADT above the average are equivalent to 50 m thermocline deepening considering typical values of stratification for the area, which in turn influenced the availability of nutrients and light for phytoplankton growth in the euphotic zone. To examine the influence of the warm anomaly on phytoplankton production, we fitted with Generalized Additive Models the relationship between monthly primary production satellite data and ADT. Primary production inferred from the model, showed during August 2014 high negative anomalies (up to 0.5 gC m-2 d1) in the coastal zone. The first empirical orthogonal function of ADT and PP revealed that the highest ADT anomalies and the lowest primary production occurred off the Baja California Peninsula, between Punta Eugenia and Cabo San Lucas. Preliminary conclusions showed that warm anomaly affected negatively to phytoplankton organisms during August 2014, being this evident by low biomass and negative primary production anomalies as result of pycnocline deepens.

The Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) in prostate cancer patients undergoing androgen deprivation therapy: study protocol for a randomized controlled trial.

PubMed

Focht, Brian C; Lucas, Alexander R; Grainger, Elizabeth; Simpson, Christina; Thomas-Ahner, Jennifer M; Clinton, Steven K

2014-09-09

Androgen deprivation therapy (ADT) is the foundation of treatment for men with metastatic prostate cancer and is now frequently incorporated into multimodality strategies for the curative treatment of locally advanced prostate cancer. Nevertheless, the catabolic effects of ADT result in meaningful adverse effects on physiological and quality of life outcomes, which may, in turn, increase the risk of functional decline, frailty, cardiovascular disease, and metabolic syndrome. Recent evidence demonstrates that lifestyle intervention promoting change in exercise and dietary behaviors is a promising approach, and may offset, or even reverse, the adverse effects accompanying ADT. Unfortunately, the limited existing studies of the effects of exercise and dietary interventions targeting patients with prostate cancer on ADT are characterized by high attrition rates and poor postintervention maintenance of treatment effects. Consequently, the Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) is designed to contrast the effects of a lifestyle intervention designed to promote independent self-management of exercise and dietary behavior with those of standard care disease management approach in the treatment of prostate cancer. A total of 40 patients with prostate cancer undergoing ADT will be randomly assigned to lifestyle intervention or standard care. Outcomes of interest in IDEA-P include changes in self-reported and objectively assessed physical function and physical activity, dietary behavior, body composition, muscular strength, and quality of life. Outcomes will be obtained at baseline, 2-month, and 3-month assessments by trial personnel blinded to participants' randomization assignment. Findings from this study will establish the feasibility and preliminary efficacy of an innovative lifestyle intervention designed to promote progressively independent self-regulated exercise and dietary behavior change in the treatment of patients with prostate cancer undergoing ADT. ClinicalTrials.gov NCT02050906.

Impact of Radiotherapy When Added to Androgen-Deprivation Therapy for Locally Advanced Prostate Cancer: Long-Term Quality-of-Life Outcomes From the NCIC CTG PR3/MRC PR07 Randomized Trial

PubMed Central

Brundage, Michael; Sydes, Matthew R.; Parulekar, Wendy R.; Warde, Padraig; Cowan, Richard; Bezjak, Andrea; Kirkbride, Peter; Parliament, Matthew; Moynihan, Clare; Bahary, Jean-Paul; Parmar, Mahesh K.B.; Sanders, Karen; Chen, Bingshu E.; Mason, Malcolm D.

2015-01-01

Purpose The NCIC CTG PR3/MRC PR07 randomized phase III trial compared androgen-deprivation therapy (ADT) alone versus ADT with radiotherapy (RT) for patients with locally advanced prostate cancer. This article reports the health-related quality-of-life (HRQOL) outcomes of this trial. Patients and Methods A total of 1,205 patients were randomly allocated to either ADT alone or ADT with RT. HRQOL was assessed at baseline and every 6 months thereafter using the European Organisation for Research and Treatment of Cancer Core Questionnaire and a prostate cancer–specific checklist or the Functional Assessment of Cancer Therapy–Prostate questionnaire. Mean changes from baseline scores for five function domains and nine symptom domains were analyzed as those most relevant to ADT and RT. The proportions of patients with improved, stable, or worsened HRQOL scores according to instrument-specific minimal important differences were calculated. Results Baseline questionnaires were completed by 1,028 patients (88%). At 6 months, RT had a statistically significant impact on mean score for bowel symptoms (P = .02), diarrhea (P < .001), urinary function (P = .003), and erectile dysfunction (P = .008); by 3 years, however, there were no significant between-group differences in any domain. Generalized linear mixed modeling revealed no significant between-arm differences in any of the function scales but showed significant deterioration in both arms over time for Functional Assessment of Cancer Therapy–Prostate total score, treatment outcome index, and physical and functional well-being. Conclusion The addition of RT to ADT for patients with locally advanced prostate cancer significantly improved overall survival and had only modest and transient negative impact on relevant domains of HRQOL. PMID:26014295

Androgen deprivation and stem cell markers in prostate cancers

PubMed Central

Tang, Yao; Hamburger, Anne W; Wang, Linbo; Khan, Mohammad Afnan; Hussain, Arif

2010-01-01

In our previous studies using human LNCaP xenografts and TRAMP (transgenic adenocarcinoma of mouse prostate) mice, androgen deprivation therapy (ADT) resulted in a temporary cessation of prostate cancer (PCa) growth, but then tumors grew faster with more malignant behaviour. To understand whether cancer stem cells might play a role in PCa progression in these animal models, we investigated the expressions of stem cell-related markers in tumors at different time points after ADT. In both animal models, enhanced expressions of stem cell markers were observed in tumors of castrated mice, as compared to non-castrated controls. This increased cell population that expressed stem cell markers is designated as stem-like cells (SLC) in this article. We also observed that the SLC peaked at relatively early time points after ADT, before tumors resumed their growth. These results suggest that the SLC population may play a role in tumor re-growth and disease progression, and that targeting the SLC at their peak-expression time point may prevent tumor recurrence following ADT. PMID:20126580

Analysis of the Astronomy Diagnostic Test

NASA Astrophysics Data System (ADS)

Brogt, Erik; Sabers, Darrell; Prather, Edward E.; Deming, Grace L.; Hufnagel, Beth; Slater, Timothy F.

Seventy undergraduate class sections were examined from the database of Astronomy Diagnostic Test (ADT) results of Deming and Hufnagel to determine if course format correlated with ADT normalized gain scores. Normalized gains were calculated for four different classroom scenarios: lecture, lecture with discussion, lecture with lab, and lecture with both lab and discussion. Statistical analysis shows that there are no significant differences in normalized gain among the self- reported classroom formats. Prerequisites related to mathematics courses did show differences in normalized gain. Of all reported course activities, only the lecture and the readings for the course correlate significantly with the normalized gain. This analysis suggests that the ADT may not have enough sensitivity to measure differences in the effectiveness of different course formats because of the wide range of topics that the ADT addresses with few questions. Different measures of gain and their biases are discussed. We argue that the use of the normalized gain is not always warranted because of its strong bias toward high pretest scores.

Analyses of transients for an 800 MW-class accelerator driven transmuter with fertile-free fuels

NASA Astrophysics Data System (ADS)

Maschek, Werner; Suzuki, Tohru; Chen, Xue-Nong; Rineiski, Andrei; Matzerath Boccaccini, Claudia; Mori, Magnus; Morita, Koji

2006-06-01

In the FUTURE Program, the development and application of fertile-free fuels for Accelerator Driven Transmuters (ADTs) has been advanced. To assess the reactor performance and safety behavior of an ADT with so-called dedicated fuels, various transient cases for an 800 MW-class Pb/Bi-cooled ADT were investigated using the SIMMER-III code. The FUTURE ADT also served as vehicle to develop and test ideas on a safety concept for such transmuters. After an extensive ranking procedure, a CERCER fuel with an MgO matrix and a CERMET fuel with a Mo-92 matrix were chosen. The transient scenarios shown here are: spurious beam trip (BT), unprotected loss of flow (ULOF) and unprotected blockage accident (UBA). Since the release of fission gas and helium after cladding failure could induce a significant positive reactivity, the gas-blowdown was investigated for the transient scenarios. The present analyses showed that power excursions could be avoided by the fuel sweep-out from the core under severe accident conditions.

Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated With Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease

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

Stenmark, Matthew H.; Blas, Kevin; Halverson, Schuyler

2011-11-15

Purpose: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). Methods and Materials: Between 1998 and 2008 at University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11-33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer-specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. Results: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8-3.9, p < 0.0001),more » salvage ADT use (HR 3.9-6.3, p < 0.0001), metastasis (HR 3.7-6.6, p < 0.0001), and PCSM (HR 3.7-16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19-0.38, p < 0.001) and PCSM (HR 0.38-0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3-4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25-0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. Conclusion: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.« less

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

Use of neoadjuvant electrochemotherapy to treat a large metastatic lesion of the cheek in a patient with melanoma.

PubMed

Mozzillo, Nicola; Caracò, Corrado; Mori, Stefano; Di Monta, Gianluca; Botti, Gerardo; Ascierto, Paolo A; Caracò, Corradina; Aloj, Luigi

2012-06-22

Approximately 200,000 new cases of melanoma are diagnosed worldwide each year. Skin metastases are a frequent event, occurring in 18.2% of cases. This can be distressing for the patient, as the number and size of cutaneous lesions increases, often worsened by ulceration, bleeding and pain. Electrochemotherapy (ECT) is a local modality for the treatment of cutaneous or subcutaneous tumors that allows delivery of low- and non-permeant drugs into cells. ECT has been used in palliative management of metastatic melanoma to improve patients' quality of life. This is, to our knowledge, the first application of ECT as neoadjuvant treatment of metastatic subcutaneous melanoma. A 44-year-old Caucasian woman underwent extensive surgical resection of a melanoma, with a Breslow thickness of 1.5 mm, located on the right side of her scalp. No further treatment was given and the woman remained well until she came to our attention with a large nodule in her right cheek. Whole-body fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) was performed for staging and treatment monitoring. Baseline FDG PET/CT showed the lesion in the cheek to have a maximal standardized uptake value (SUVmax) of 19.5 with no evidence of further disease spread. Fine needle aspiration cytology confirmed the presence of metastatic melanoma. The patient underwent two sessions of ECT with intravenous injections of bleomycin using a CliniporatorTM as neoadjuvant treatment permitting conservative surgery three months later.Follow-up PET/CT three months after the first ECT treatment showed a marked decrease in SUVmax to 5. Further monitoring was performed through monthly PET/CT studies. Multiple cytology examinations showed necrotic tissue. Conservative surgery was carried out three months after the second ECT. Reconstruction was easily achieved through a rotation flap. Pathological examination of the specimen showed necrotic tissue without residual melanoma. One year after the last ECT treatment, the patient was disease-free as determined by contrast-enhanced CT and PET/-CT scans with a good functional and aesthetic result. ECT represents a safe and effective therapeutic approach that is associated with clear benefits in terms of quality of life (minimal discomfort, mild post-treatment pain and short duration of hospital stay) and may, in the neoadjuvant setting as reported here, offer the option of more conservative surgery and an improved cosmetic effect with complete local tumor control.

Use of neoadjuvant electrochemotherapy to treat a large metastatic lesion of the cheek in a patient with melanoma

PubMed Central

2012-01-01

Background Approximately 200,000 new cases of melanoma are diagnosed worldwide each year. Skin metastases are a frequent event, occurring in 18.2% of cases. This can be distressing for the patient, as the number and size of cutaneous lesions increases, often worsened by ulceration, bleeding and pain. Electrochemotherapy (ECT) is a local modality for the treatment of cutaneous or subcutaneous tumors that allows delivery of low- and non-permeant drugs into cells. ECT has been used in palliative management of metastatic melanoma to improve patients’ quality of life. This is, to our knowledge, the first application of ECT as neoadjuvant treatment of metastatic subcutaneous melanoma. Methods and results A 44-year-old Caucasian woman underwent extensive surgical resection of a melanoma, with a Breslow thickness of 1.5 mm, located on the right side of her scalp. No further treatment was given and the woman remained well until she came to our attention with a large nodule in her right cheek. Whole-body fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) was performed for staging and treatment monitoring. Baseline FDG PET/CT showed the lesion in the cheek to have a maximal standardized uptake value (SUVmax) of 19.5 with no evidence of further disease spread. Fine needle aspiration cytology confirmed the presence of metastatic melanoma. The patient underwent two sessions of ECT with intravenous injections of bleomycin using a CliniporatorTM as neoadjuvant treatment permitting conservative surgery three months later. Follow-up PET/CT three months after the first ECT treatment showed a marked decrease in SUVmax to 5. Further monitoring was performed through monthly PET/CT studies. Multiple cytology examinations showed necrotic tissue. Conservative surgery was carried out three months after the second ECT. Reconstruction was easily achieved through a rotation flap. Pathological examination of the specimen showed necrotic tissue without residual melanoma. One year after the last ECT treatment, the patient was disease-free as determined by contrast-enhanced CT and PET/-CT scans with a good functional and aesthetic result. Conclusions ECT represents a safe and effective therapeutic approach that is associated with clear benefits in terms of quality of life (minimal discomfort, mild post-treatment pain and short duration of hospital stay) and may, in the neoadjuvant setting as reported here, offer the option of more conservative surgery and an improved cosmetic effect with complete local tumor control. PMID:22800396

Analysis of the Astronomy Diagnostic Test

ERIC Educational Resources Information Center

Brogt, Erik; Sabers, Darrell; Prather, Edward E.; Deming, Grace L.; Hufnagel, Beth; Slater, Timothy F.

2007-01-01

Seventy undergraduate class sections were examined from the database of Astronomy Diagnostic Test (ADT) results of Deming and Hufnagel to determine if course format correlated with ADT normalized gain scores. Normalized gains were calculated for four different classroom scenarios: lecture, lecture with discussion, lecture with lab, and lecture…

Auditory discrimination training for tinnitus treatment: the effect of different paradigms.

PubMed

Herraiz, Carlos; Diges, I; Cobo, P; Aparicio, J M; Toledano, A

2010-07-01

Acoustic deprivation, i.e. hearing loss, is responsible for a cascade of processes resulting in reorganisation of the cortex. Tinnitus mechanisms are explained by synchronization of the neural spontaneous activity and might be related to cortical re-mapping. Auditory discrimination training (ADT) has demonstrated in both animals and humans to induce tonotopical changes in the auditory pathways through neural plasticity. We hypothesize that ADT could have some effect on tinnitus perception. The objective of this study is to compare the effect on tinnitus following two paradigms of ADT. Only patients from 20 to 60 years of age were recruited. Inclusion criteria were pure tone tinnitus of mild or moderate handicap according to the Tinnitus Handicap Inventory score (<56). ADT patients were randomized in two groups: SAME (ADT in the same frequency of tinnitus pitch, 20 patients) and NONSAME (ADT in the frequency one-octave below tinnitus pitch, 21 patients). Groups of pair of tones (70% standard tones ST, 30% deviant tones ST + 0.1-0.5 kHz) were randomly mixed for 20 min/day during 1 month. Patient had to mark when the two sounds of the pair were similar or different. Control group included 26 patients from the waiting list (WLG). Patients were also divided according to the trained frequency and the deepest hearing-impaired frequency. Outcome parameters were set up according to the answer to the question "is your tinnitus better, same, or worse with the treatment?" (RESP), the tinnitus handicap inventory (THI) and the visual analogue scale from 1 to 10 on tinnitus intensity (VAS). Tinnitus improved in 42.2% of the patients (RESP). VAS and THI scores were reduced but only THI differences were statistically significant (P = 0.003). ADT patients improved significantly compared with WLG in RESP and THI scores (P < 0.01). Training frequencies one-octave below the tinnitus pitch (NONSAME) decreased significantly THI scores compared with patients trained frequencies similar to tinnitus pitch (SAME, P = 0.035). RESP and VAS scores decreased more in NONSAME group though differences were not significant. We did not find any differences when comparing the group training the deepest hearing-impaired frequency and the group who trained other frequencies. Auditory discrimination training significantly improved tinnitus handicap compared to a waiting list group. Those patients who trained frequencies one octave below the tinnitus pitch had better outcome than those who performed the ADT with frequencies similar to the tinnitus pitch (P = 0.035).

PSA Doubling Time Predicts for the Development of Distant Metastases for Patients Who Fail 3DCRT Or IMRT Using the Phoenix Definition.

PubMed

Klayton, Tracy L; Ruth, Karen; Buyyounouski, Mark K; Uzzo, Robert G; Wong, Yu-Ning; Chen, David Y T; Sobczak, Mark; Peter, Ruth; Horwitz, Eric M

2011-01-01

PURPOSE: PSA doubling time (PSADT) is commonly used as an indication for salvage androgen deprivation therapy (ADT) for PSA failure following RT. Previously, we had shown that PSADT of <12 months is an important predictor of distant metastasis following 3DCRT using the ASTRO definition of BF. We sought to determine if this approach is still valid using the Phoenix definition. METHODS: Eligible patients included 432 men with T1-3N0M0 prostate cancer who demonstrated PSA failure after completing definitive 3DCRT or IMRT from 1989-2005. Endpoints included freedom from distant metastasis (FDM), cause-specific survival (CSS) and overall survival (OS). PSADT was stratified by 0-6, 6-12, 12-18, 18-24, and >24 months. The median follow-up was 95 months (6-207 months). RESULTS: The 7 year FDM, CSS, and OS rates for the entire group were 73%, 77% and 52%, respectively. 7 year FDM was 50% for PSADT <6 months vs. 83% for PSADT >6 months (p=0.0001). 7 year CSS was 61% for PSADT <6 and 85% for PSADT >6 (p=0.0001). 7 year OS was 47% for PSADT <6 and 53% for PSADT >6 (p=0.04). The proportion of men with BF receiving salvage ADT with a PSADT <6 months was 59%, 6-12 was 45%, 12-18 was 42%, 18-24 was 36%, >24 was 28%. ADT was associated with improved 7 year CSS (68% vs. 46%, p=0.015). Of the 314 men with PSADT >6 months, 124 received ADT and 190 were observed. With a median follow-up of 38 months from BF, there was no demonstrable benefit to ADT in the 7 year CSS (87% vs. 79%, respectively; p=0.758). Independent predictors of FDM were PSADT (p<0.0001), GS (p=0.011), and the use of initial ADT (p=0.005). CONCLUSION: PSADT remains a significant predictor of clinical failure and CSS for men treated with 3DCRT or IMRT who fail according to the Phoenix definition. Immediate use of ADT in patients with PSADT <6 months is significantly associated with improved CSS, although the benefit is less apparent in patients with longer PSADT. These results further refine the role of PSADT in predicting which patients may benefit from salvage ADT and those who may be observed expectantly.

Lifetime prediction and reliability estimation methodology for Stirling-type pulse tube refrigerators by gaseous contamination accelerated degradation testing

NASA Astrophysics Data System (ADS)

Wan, Fubin; Tan, Yuanyuan; Jiang, Zhenhua; Chen, Xun; Wu, Yinong; Zhao, Peng

2017-12-01

Lifetime and reliability are the two performance parameters of premium importance for modern space Stirling-type pulse tube refrigerators (SPTRs), which are required to operate in excess of 10 years. Demonstration of these parameters provides a significant challenge. This paper proposes a lifetime prediction and reliability estimation method that utilizes accelerated degradation testing (ADT) for SPTRs related to gaseous contamination failure. The method was experimentally validated via three groups of gaseous contamination ADT. First, the performance degradation model based on mechanism of contamination failure and material outgassing characteristics of SPTRs was established. Next, a preliminary test was performed to determine whether the mechanism of contamination failure of the SPTRs during ADT is consistent with normal life testing. Subsequently, the experimental program of ADT was designed for SPTRs. Then, three groups of gaseous contamination ADT were performed at elevated ambient temperatures of 40 °C, 50 °C, and 60 °C, respectively and the estimated lifetimes of the SPTRs under normal condition were obtained through acceleration model (Arrhenius model). The results show good fitting of the degradation model with the experimental data. Finally, we obtained the reliability estimation of SPTRs through using the Weibull distribution. The proposed novel methodology enables us to take less than one year time to estimate the reliability of the SPTRs designed for more than 10 years.

Determinants of vitamin D levels in men receiving androgen deprivation therapy for prostate cancer.

PubMed

Mennen-Winchell, Lori J; Grigoriev, Victor; Alpert, Patricia; Dos Santos, Hildemar; Tonstad, Serena

2015-01-01

Studies found an association between decreased 25-OH vitamin D blood level and prostate cancer progression. Vitamin D supplementation is controversial and dosage recommendations inconsistent. This study identified factors associated with 25-OH vitamin D levels and whether vitamin D supplementation with 800 IU/day raised vitamin D levels in prostate cancer patients receiving androgen deprivation therapy (ADT). We recruited 108 men treated with ADT for ≥9 months from eight cancer and urology practices. Sections of the NHANES 2005-2006 questionnaire and Canadian Fitness Survey were completed identifying age, ethnicity, length of ADT use, calcium supplementation ≥1000 IU mg/day, body mass index, exercise, alcohol and tobacco use, and vitamin D supplementation ≥800 IU/daily. Blood was collected for 25-OH vitamin D analysis. The majority of men (66%) had blood levels of 25-OH vitamin D <32 ng/mL. Regression analysis showed vitamin D supplementation (β = 6.556, CI 1.463, 11.650; p = .012) and African American ethnicity (β = -7.816, CI -12.996, -2.635; p = .003) is associated with 25-OH vitamin D level after controlling age and tobacco use. Findings support current recommendations for supplementation with ≥800 IU vitamin D/day for men receiving ADT. Nurse practitioners caring for prostate cancer patients receiving ADT should include vitamin D monitoring and supplementation. ©2014 American Association of Nurse Practitioners 2014.

Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study.

PubMed

Noordman, Bo Jan; Spaander, Manon C W; Valkema, Roelf; Wijnhoven, Bas P L; van Berge Henegouwen, Mark I; Shapiro, Joël; Biermann, Katharina; van der Gaast, Ate; van Hillegersberg, Richard; Hulshof, Maarten C C M; Krishnadath, Kausilia K; Lagarde, Sjoerd M; Nieuwenhuijzen, Grard A P; Oostenbrug, Liekele E; Siersema, Peter D; Schoon, Erik J; Sosef, Meindert N; Steyerberg, Ewout W; van Lanschot, J Jan B

2018-05-31

After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations. The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin [area under the curve 2 mg/mL per min] plus paclitaxel [50 mg/m 2 of body-surface area] combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET-CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12-14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed. Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% [95% CI 17-50]) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% [95% CI 4-23]) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% [95% CI 17-44]). PET-CT missed six of 41 TRG3 or TRG4 tumours (15% [95% CI 7-28]). PET-CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas). After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET-CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803). Dutch Cancer Society. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analysis of vehicle classification data, including monthly and seasonal ADT factors, hourly distribution factors, and lane distribution factors

DOT National Transportation Integrated Search

1998-11-01

This report documents the development of monthly and seasonal average daily traffic (ADT) factors for performing estimating AADTs. It appears that seasonal factors can estimate AADT as well as monthly factors, and it is recommended that seasonal fact...

Restaging after neoadjuvant chemoradiation in rectal cancers: is histology the key in patient selection?

PubMed Central

Singhal, Nitin; Vallam, Karthik; Engineer, Reena; Ostwal, Vikas; Arya, Supreeta

2016-01-01

Background Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer. However, there is no clarity regarding the necessity for restaging scans to rule out systemic progression of disease post chemoradiation with existing literature being divided on the need for the same. Methods Data from a prospectively maintained database was retrospectively analysed. All locally advanced rectal cancers (node positive/T4/T3 with threatened or involved CRM) were included. Biopsy proof of adenocarcinoma and CT scan of abdomen and chest were mandatory. Grade of tumor and response to CTRT on restaging magnetic resonance imaging (MRI) were documented. Results Out of 119 patients subjected to CTRT, 72 underwent definitive total mesorectal excision while 13 patients progressed locoregionally on restaging MR pelvis and 15 other patients progressed systemically while the rest defaulted. Patients with poorly differentiated (PD) cancers were compared to those with well/moderately differentiated (WMD) tumors. PD tumors had a significantly higher rate of local progression (32.1% vs. 5.6% %, P=0.0011) and systemic progression (35.7% vs. 6.9%, P=0.0008) as compared to WMD tumors. Only one-third (9/28) of PD patients underwent TME while the rest progressed. Conclusions Selecting poorly differentiated tumors alone for restaging CECT abdomen and thorax will be a cost effective strategy as the rate of progression is very high. Also patients with PD tumors need to be consulted about the high probability of progression of disease. PMID:27284467

Is aortic lymphadenectomy indicated in locally advanced cervical cancer after neoadjuvant chemotherapy followed by radical surgery? A retrospective study on 261 women.

PubMed

Martinelli, F; Signorelli, M; Bogani, G; Ditto, A; Chiappa, V; Perotto, S; Scaffa, C; Lorusso, D; Raspagliesi, F

2016-10-01

The aim of this study was to estimate the rate of aortic lymph nodes (LN) metastases/recurrences among patients affected by locally advanced stage cancer patients (LACC), treated with neoadjuvant chemotherapy (NACT) and radical surgery. Retrospective evaluation of consecutive 261 patients affected by LACC (stage IB2-IIB), treated with NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990 and 2011. Stage at presentation included stage IB2, IIA and IIB in 100 (38.3%), 50 (19.2%) and 111 (42.5%) patients, respectively. Squamous cell carcinoma accounted for more than 80%, followed by adenocarcinoma or adenosquamous cancers (20%). Overall, 56 women (21.5%) had LN metastases. Four out of 83 women (5%) who underwent both pelvic and aortic LN dissection had aortic LN metastases, and all women had concomitant pelvic and aortic LN metastases. Only one woman out of 178 (0.5%) who underwent pelvic lymphadenectomy only, had an aortic LN recurrence. Overall 2% of women (5/261) had aortic LN metastases/recurrence. Our data suggest that aortic lymphadenectomy at the time of surgery is not routinely indicated in LACC after NACT, but should reserved in case of bulky LN in both pelvic and/or aortic area. The risk of isolated aortic LN relapse is negligible. Further prospective studies are warranted. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma.

PubMed

Leone, B; Vallejo, C; Perez, J; Cuevas, M A; Machiavelli, M; Lacava, J; Focaccia, G; Ferreyra, R; Suttora, G; Romero, A; Castaldi, J; Arroyo, A; Rabinovich, M

1996-04-01

A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

Neoadjuvant chemotherapy response influences outcomes in non-colorectal, non-neuroendocrine liver metastases.

PubMed

Lucchese, A M; Kalil, A N; Ruiz, A; Karam, V; Ciacio, O; Pittau, G; Castaing, D; Cherqui, D; Sa Cunha, A; Vibert, E; Adam, R

2018-06-12

Indications for surgical resection of non-colorectal, non-neuroendocrine (NCNNE) liver metastases are unclear. This study analysed the influence of response to neoadjuvant chemotherapy and the presence of extrahepatic disease (EHD) on outcomes. Patients who underwent hepatic resection for NCNNE liver metastases and who received neoadjuvant chemotherapy at a single centre between 1982 and 2016 were analysed retrospectively. Patients were classified as having no EHD, controlled EHD or non-controlled EHD. Hepatic resection was performed in 199 patients (81·2 per cent) after partial or complete response to chemotherapy or disease stabilization, and 46 patients (18·8 per cent) after tumour progression. Patients with progressive disease after chemotherapy had worse overall survival than those without (23 versus 50·4 per cent at 5 years; P = 0·004). Median survival was 63·6 (range 31·1-94·8) months for patients without EHD, 34·8 (19·2-49·2) months for those with controlled EHD and 7·2 (1·2-13·2) months for patients with non-controlled EHD (P = 0·004). In multivariable analysis, EHD (P = 0·004), response to chemotherapy (P = 0·004) and resection margins (P = 0·002) were all independent predictors of overall survival, regardless of primary tumour site. The prognosis of patients with NCNNE liver metastases is influenced by preoperative chemotherapy and resectability. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

Neoadjuvant chemotherapy in the treatment of locally advanced cervical carcinoma in pregnancy: a report of two cases and review of issues specific to the management of cervical carcinoma in pregnancy including planned delay of therapy.

PubMed

Tewari, K; Cappuccini, F; Gambino, A; Kohler, M F; Pecorelli, S; DiSaia, P J

1998-04-15

Women diagnosed with invasive cervical carcinoma during pregnancy are faced with difficult decisions regarding therapy and the fate of their unborn child. A modest treatment delay for International Federation of Gynecology and Obstetrics Stage I cervical lesions is considered acceptable in patients who wish to continue their pregnancy. Two patients with locally advanced cervical carcinoma diagnosed early in the second trimester strongly desired continuation of their pregnancies. They were treated with neoadjuvant chemotherapy until the third trimester, and then underwent delivery and definitive surgical treatment. The patients were evaluated during pregnancy for evidence of a clinical response to chemotherapy. Intraoperative findings and pathologic analysis of the surgical material provided further objective data regarding disease status. Both patients experienced a dramatic reduction in tumor volume, rendering radical hysterectomy feasible at the time of cesarean section. In addition, both patients tolerated chemotherapy well and there were no adverse fetal effects. Favorable neonatal outcomes were achieved. One patient experienced recurrence within 5 months of surgery, whereas the other patient remained without evidence of disease for 2 years. To the authors' knowledge, these reports constitute the first description of the use of neoadjuvant chemotherapy for invasive squamous cell carcinoma of the cervix in pregnancy (MEDLINE 1966-1997). This therapeutic option should be considered in selected women with locally advanced cervical carcinoma who do not want termination of their pregnancy.

Neoadjuvant chemotherapy evaluation by MRI volumetry in rectal cancer followed by chemoradiation and total mesorectal excision: Initial experience.

PubMed

Nougaret, Stephanie; Fujii, Shinya; Addley, Helen C; Bibeau, Frederic; Pandey, Himanshu; Mikhael, Hisham; Reinhold, Caroline; Azria, David; Rouanet, Philippe; Gallix, Benoit

2013-09-01

To evaluate rectal cancer volumetry in predicting initial neoadjuvant chemotherapy response. Sixteen consecutive patients who underwent neoadjuvant chemotherapy (CX) before chemoradiotherapy (CRT) and surgery were enrolled in this retrospective study. Tumor volume was evaluated at the first magnetic resonance imaging (MRI), after CX and after CRT. Tumor volume regression (TVR) and downstaging were compared with histological results according to Tumor Regression Grade (TRG) to assess CX and CRT response, respectively. The mean tumor volume was 132 cm(3) ± 166 before and 56 cm(3) ± 71 after CX. TVR after CX was significantly different between patients with poor histologic response (TRG1/2) and those with good histologic response (TRG3/4) (P = 0.001). An optimal cutoff of TVR >68% (area under the curve [AUC]: 0.9, 95% confidence interval [CI]: 0.65-0.98, P = 0.0001) to predict good histology response after CX was assessed by receiver operating characteristic curve. According to previous data and this study, we defined 70% as the best cutoff values according to sensitivity (86%), specificity (100%) of TVR for predicting good histology response. In contradistinction, MRI downstaging was associated with TRG only after CRT (P = 0.04). Our pilot study showed that MRI volumetry can predict early histological response after CX and before CRT. MRI volumetry could help the clinician to distinguish early responders in order to aid appropriate individually tailored therapies. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

Neoadjuvant oral vs. infusional chemoradiotherapy on locally advanced rectal cancer: Prognostic factors.

PubMed

Conde, Sofia; Borrego, Margarida; Teixeira, Tânia; Teixeira, Rubina; Sá, Anabela; Soares, Paula

2012-01-01

To evaluate the prognostic factors and impact on survival of neoadjuvant oral and infusional chemoradiotherapy in patients with locally advanced rectal cancer. There is still no definitive consensus about the prognostic factors and the impact of neoadjuvant chemoradiotherapy on survival. Some studies have pointed to an improvement in overall survival (OS) and progression-free survival (PFS) in patients with tumor downstaging (TD) and nodal downstaging (ND). A set of 159 patients with LARC were treated preoperatively. Group A - 112 patients underwent concomitant oral chemoradiotherapy: capecitabine or UFT + folinic acid. Group B - 47 patients submitted to concomitant chemoradiation with 5-FU in continuous infusion. 63.6% of patients were submitted to adjuvant chemotherapy. pathologic complete response (pCR) - 18.7%; TD - 55.1%; ND - 76%; loco-regional response - 74.8%. Group B: pCR - 11.4%; TD - 50%; ND - 55.8%; LRR - 54.5%. The loco-regional control was 95.6%. There was no difference in survival between both groups. Those with loco-regional response had better PFS. Tumor and nodal downstaging, loco-regional response and a normal CEA level turned out to be important prognostic factors in locally advanced rectal cancer. Nodal downstaging and loco-regional response were higher in Group A. Those with tumor downstaging and loco-regional response from Group A had better OS. Adjuvant chemotherapy had no impact on survival except in those patients with loco-regional response who achieved a higher PFS.

The Academic Diligence Task (ADT): Assessing Individual Differences in Effort on Tedious but Important Schoolwork

PubMed Central

Galla, Brian M.; Plummer, Benjamin D.; White, Rachel E.; Meketon, David; D’Mello, Sidney K.; Duckworth, Angela L.

2014-01-01

The current study reports on the development and validation of the Academic Diligence Task (ADT), designed to assess the tendency to expend effort on academic tasks which are tedious in the moment but valued in the long-term. In this novel online task, students allocate their time between solving simple math problems (framed as beneficial for problem solving skills) and, alternatively, playing Tetris or watching entertaining videos. Using a large sample of high school seniors (N = 921), the ADT demonstrated convergent validity with self-report ratings of Big Five conscientiousness and its facets, self-control and grit, as well as discriminant validity from theoretically unrelated constructs, such as Big Five extraversion, openness, and emotional stability, test anxiety, life satisfaction, and positive and negative affect. The ADT also demonstrated incremental predictive validity for objectively measured GPA, standardized math and reading achievement test scores, high school graduation, and college enrollment, over and beyond demographics and intelligence. Collectively, findings suggest the feasibility of online behavioral measures to assess noncognitive individual differences that predict academic outcomes. PMID:25258470

The Academic Diligence Task (ADT): Assessing Individual Differences in Effort on Tedious but Important Schoolwork.

PubMed

Galla, Brian M; Plummer, Benjamin D; White, Rachel E; Meketon, David; D'Mello, Sidney K; Duckworth, Angela L

2014-10-01

The current study reports on the development and validation of the Academic Diligence Task (ADT), designed to assess the tendency to expend effort on academic tasks which are tedious in the moment but valued in the long-term. In this novel online task, students allocate their time between solving simple math problems (framed as beneficial for problem solving skills) and, alternatively, playing Tetris or watching entertaining videos. Using a large sample of high school seniors ( N = 921), the ADT demonstrated convergent validity with self-report ratings of Big Five conscientiousness and its facets, self-control and grit, as well as discriminant validity from theoretically unrelated constructs, such as Big Five extraversion, openness, and emotional stability, test anxiety, life satisfaction, and positive and negative affect. The ADT also demonstrated incremental predictive validity for objectively measured GPA, standardized math and reading achievement test scores, high school graduation, and college enrollment, over and beyond demographics and intelligence. Collectively, findings suggest the feasibility of online behavioral measures to assess noncognitive individual differences that predict academic outcomes.

Androgen Receptor Roles in Insulin Resistance and Obesity in Males: The Linkage of Androgen-Deprivation Therapy to Metabolic Syndrome

PubMed Central

Yu, I-Chen; Lin, Hung-Yun; Sparks, Janet D.; Yeh, Shuyuan

2014-01-01

Prostate cancer (PCa) is one of the most frequently diagnosed malignancies in men. Androgen-deprivation therapy (ADT) is the first-line treatment and fundamental management for men with advanced PCa to suppress functions of androgen/androgen receptor (AR) signaling. ADT is effective at improving cancer symptoms and prolonging survival. However, epidemiological and clinical studies support the notion that testosterone deficiency in men leads to the development of metabolic syndrome that increases cardiovascular disease risk. The underlying mechanisms by which androgen/AR signaling regulates metabolic homeostasis in men are complex, and in this review, we discuss molecular mechanisms mediated by AR signaling that link ADT to metabolic syndrome. Results derived from various AR knockout mouse models reveal tissue-specific AR signaling that is involved in regulation of metabolism. These data suggest that steps be taken early to manage metabolic complications associated with PCa patients receiving ADT, which could be accomplished using tissue-selective modulation of AR signaling and by treatment with insulin-sensitizing agents. PMID:25249645

Race is associated with completion of neoadjuvant chemotherapy for breast cancer.

PubMed

Knisely, Anne T; Michaels, Alex D; Mehaffey, J Hunter; Hassinger, Taryn E; Krebs, Elizabeth D; Brenin, David R; Schroen, Anneke T; Showalter, Shayna L

2018-05-03

Completion of prescribed neoadjuvant chemotherapy for breast cancer is paramount to patients obtaining full benefit from the treatment; however, factors affecting neoadjuvant chemotherapy completion are not known. We hypothesized that race is a predictor of completion of neoadjuvant chemotherapy in patients with breast cancer. All patients with breast cancer treated with neoadjuvant chemotherapy 2009-2016 at a single institution were stratified by completion of neoadjuvant chemotherapy and by race. Univariate analysis and multivariable logistic regression were used to identify patient and tumor characteristics that affected the rate of neoadjuvant chemotherapy completion. A total of 92 (74%) of 124 patients completed their prescribed neoadjuvant chemotherapy. On univariate analysis, white patients were more likely to complete neoadjuvant chemotherapy than non-white patients (76% vs 50%, P = .006). Non-white patients were more likely to have government insurance and larger prechemotherapy tumors (both, P < .05), but these factors were not associated with rates of neoadjuvant chemotherapy completion. After controlling for age, insurance status, tumor size, and estrogen receptor status, whites remained associated with completion of neoadjuvant chemotherapy (OR 3.65, P = .014). At our institution, white patients with breast cancer were more likely than non-white patients to complete neoadjuvant chemotherapy. Further investigation into the underlying factors impacting this disparity is needed. Copyright © 2018 Elsevier Inc. All rights reserved.

Esophageal stent fixation with endoscopic suturing device improves clinical outcomes and reduces complications in patients with locally advanced esophageal cancer prior to neoadjuvant therapy: a large multicenter experience.

PubMed

Yang, Juliana; Siddiqui, Ali A; Kowalski, Thomas E; Loren, David E; Khalid, Ammara; Soomro, Ayesha; Mazhar, Syed M; Rosé, Julian; Isby, Laura; Kahaleh, Michel; Kalra, Ankush; Sarkisian, Alex M; Kumta, Nikhil A; Nieto, Jose; Sharaiha, Reem Z

2017-03-01

Endoscopic placement of fully covered self-expanding metal stents (FCSEMS) to treat malignant dysphagia in patients with esophageal cancer significantly improves dysphagia; however, these stents have a high migration rate. To determine whether FCSEMS fixation using an endoscopic suturing device treated malignant dysphagia and prevented stent migration in patients with locally advanced esophageal cancer receiving neoadjuvant therapy when compared to patients with FCSEMS placement alone. A review of patients with locally advanced esophageal cancer who underwent FCSEMS placement at 3 centers was performed. Patients were divided into two groups: Group A (n = 26) was composed of patients who underwent FCSEMS placement with suture placement, and Group B (n = 67) was composed of patients with FCSEMS placement alone. There were no significant differences between Groups A and B in demographics, and tumor characteristics. The technical success rate for stent placement was 100 %. There was no difference between Groups A and B in the median stent diameter and stent lengths. Mean dysphagia score obtained at 1 week after stent placement had improved significantly from baseline (2.4 and 1, respectively, p < 0.001). Patients had a median follow-up of 4 months. Immediate adverse events were mild chest discomfort in 4 patients in Group A and 2 patients in Group B (p = 0.05), and significant acid reflux in 3 patient in Group A compared to 2 patients in Group B (p = 0.1). The stent migration rate was significantly lower in Group A compared to compared to Group B (7.7 vs 26.9 %, respectively, p = 0.004). There was a delayed perforation in 1 patient and 1 death due to aspiration pneumonia in Group B. Fixation of esophageal FCSEMSs by using an endoscopic suturing device in patients receiving neoadjuvant therapy was shown to be feasible, safe, and relatively effective at preventing stent migration compared to those who had stent placed alone.

Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer.

PubMed

Vyfhuis, Melissa A L; Burrows, Whitney M; Bhooshan, Neha; Suntharalingam, Mohan; Donahue, James M; Feliciano, Josephine; Badiyan, Shahed; Nichols, Elizabeth M; Edelman, Martin J; Carr, Shamus R; Friedberg, Joseph; Henry, Gavin; Stewart, Shelby; Sachdeva, Ashutosh; Pickering, Edward M; Simone, Charles B; Feigenberg, Steven J; Mohindra, Pranshu

2018-06-01

To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT). At our institution, 355 patients with locally advanced non-small cell lung cancer were treated with curative intent with definitive CRT (January 2000-December 2013), of whom 111 underwent mediastinal reassessment for possible surgical resection. Ultimately 88 patients received trimodality therapy. Chi-squared analysis was used to compare categorical variables. The Kaplan-Meier analysis was performed to estimate OS and FFR, with Cox regression used to determine the absolute hazards. Using high-dose neoadjuvant CRT, we observed a mediastinal nodal clearance (MNC) rate of 74% (82 of 111 patients) and pCR rate of 48% (37 of 77 patients). With a median follow-up of 34.2 months (range, 3-177 months), MNC resulted in improved OS and FFR on both univariate (OS: hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.272-0.763, P = .004; FFR: HR 0.426, 95% CI 0.250-0.726, P = .002) and multivariate analysis (OS: HR 0.460, 95% CI 0.239-0.699, P = .001; FFR: HR 0.455, 95% CI 0.266-0.778, P = .004). However, pCR did not independently impact OS (P = .918) or FFR (P = .474). Mediastinal nodal clearance after CRT continues to be predictive of improved survival for patients undergoing trimodality therapy. However, a pCR at both the primary and mediastinum did not further improve survival outcomes. Future therapies should focus on improving MNC to encourage more frequent use of surgery and might justify use of preoperative CRT over chemotherapy alone. Copyright © 2018 Elsevier Inc. All rights reserved.

Higher-order formulas of amplitude-dependent tune shift caused by a sextupole magnetic field distribution

NASA Astrophysics Data System (ADS)

Soutome, Kouichi; Tanaka, Hitoshi

2017-06-01

Nowadays, designs for ring-based light sources use multibend lattices for achieving a very small emittance of around 100 pmrad. In this type of storage ring, the chromaticity correcting sextupoles generally have greater strengths than those used in typical third-generation light sources. Therefore, controlling lattice nonlinearity such as amplitude-dependent tune shift (ADTS) is important for enabling stable operations and smooth beam commissioning. As the strength of the sextupoles increases, their higher-order terms contribute significantly to ADTS, rendering well-known lowest-order formulas inadequate for describing tune variations at large horizontal amplitudes. In response, we have derived explicit expressions of ADTS up to the fourth order in sextupole strength based on the canonical perturbation theory, assuming that the amplitude of a vertical betatron oscillation is smaller compared with the horizontal one. The new formulas express the horizontal and vertical betatron tune variations as functions of the action variables: Jx and Jy up to O (Jx2) and O (Jy) . The derived formulas were applied to a five-bend achromat lattice designed for the SPring-8 upgrade. By comparing the calculated results with the tracking simulations, we found that (1) the formulas accurately express ADTS around a horizontal amplitude of ˜10 mm and (2) the nonlinear terms of the fourth order in sextupole strength govern the behaviors of circulating electrons at large horizontal amplitudes. In this paper, we present explicit expressions of fourth-order formulas of ADTS and provide some examples to illustrate their effectiveness.

Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells.

PubMed

Olson, Brian M; Gamat, Melissa; Seliski, Joseph; Sawicki, Thomas; Jeffery, Justin; Ellis, Leigh; Drake, Charles G; Weichert, Jamey; McNeel, Douglas G

2017-12-01

Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR . ©2017 American Association for Cancer Research.

Protective Effects of 2-Amino-5,6-dihydro-4H-1,3-thiazine and Its Derivative against Radiation-Induced Hematopoietic and Intestinal Injury in Mice.

PubMed

Li, Yuanyuan; Kong, Shaofan; Yang, Fujun; Xu, Wenqing

2018-05-21

Ionizing radiation (IR) acts as an external stimulating factor, when it acts on the body, it will activate NF- κ B and cause the up-regulation of inducible nitric oxide synthase (iNOS) and induce a large amount of nitric oxide (NO) production. NO and other reactive nitrogen and oxygen species (RNS and ROS) can cause damage to biological molecules and affect their physiological functions. Our study investigated the protective role of 2-amino-5,6-dihydro-4 H -1,3-thiazine hydrobromide (2-ADT) and 2-acetylamino-5,6-dihydro-4 H -1,3-thiazine hydrobromide (2-AADT), two nitric oxide synthase inhibitors, against radiation-induced hematopoietic and intestinal injury in mice. Pretreatment with 2-ADT and 2-AADT improved the survival of mice exposed to a lethal dose of radiation, especially, the survival rate of the 2-ADT 20 mg/kg group was significantly higher than that of the vehicle group ( p < 0.001). Our findings indicated that the radioprotective actions of 2-ADT and 2-AADT are achieved via accelerating hematopoietic system recovery, decreasing oxidative and nitrosative stress by enhancing the antioxidant defense system and reducing NO as well as peroxynitrite (ONOO − ) content, and mitigating the radiation-induced DNA damage evaluated by comet assay. These results suggest that 2-ADT and 2-AADT may have great application potential in ameliorating the damages of radiotherapy.

Androgen deprivation therapy for prostate cancer and the risk of hospitalisation for community-acquired pneumonia.

PubMed

Hicks, Blánaid M; Yin, Hui; Bladou, Franck; Ernst, Pierre; Azoulay, Laurent

2017-07-01

Androgens have been shown to influence both the immune system and lung tissue, raising the hypothesis that androgen deprivation therapy (ADT) for prostate cancer may increase the risk of pneumonia. Thus, the aim of this study was to determine whether ADT is associated with an increased risk of hospitalisation for community-acquired pneumonia in patients with prostate cancer. This was a population-based cohort study using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository. The cohort consisted of 20 310 men newly diagnosed with non-metastatic prostate cancer between 1 April 1998 and 31 March 2015. Time-dependent Cox proportional hazards models were used to estimate adjusted HRs and 95% CIs for hospitalisation for community-acquired pneumonia associated with current and past use of ADT compared with non-use. During a mean follow-up of 4.3 years, there were 621 incident hospitalisations for community-acquired pneumonia (incidence rate: 7.2/1000 person-years). Current ADT use was associated with an 81% increased risk of hospitalisation for community-acquired pneumonia (12.1 vs 3.8 per 1000 person-years, respectively; HR 1.81, 95% CI 1.47 to 2.23). The association was observed within the first six months of use (HR 1.73, 95% CI 1.23 to 2.42) and remained elevated with increasing durations of use (≥25 months; HR 1.79, 95% CI 1.39 to 2.30). In contrast, past ADT use was not associated with an increased risk (HR 1.23, 95% CI 0.95 to 1.60). The use of ADT is associated with an increased risk of hospitalisation for community-acquired pneumonia in men with prostate cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Redefining High-Risk Prostate Cancer Based on Distant Metastases and Mortality After High-Dose Radiotherapy With Androgen Deprivation Therapy

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

Tendulkar, Rahul D., E-mail: tendulr@ccf.org; Reddy, Chandana A.; Stephans, Kevin L.

2012-03-15

Purpose: Modern outcomes of high-dose external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT) for high-risk (HR) prostate cancer are not well described. Methods and Materials: We identified 585 patients who met HR criteria by 2010 National Comprehensive Cancer Network guidelines, who were treated with EBRT consisting of {>=}74 Gy from 1996 to 2008 at Cleveland Clinic, of whom 95% received ADT. We analyzed biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The median EBRT dose was 78 Gy, and median ADT duration was 6 months. At 10 years, the bRFS was 50.2%, themore » DMFS was 71.6%, and the PCSM was 14.4%. On multivariate analysis, significant predictors of bRFS were biopsy Gleason score (bGS) of 8 to 10, stage T3, and prostate-specific antigen (PSA) concentration; predictors of DMFS were bGS of 8 to 10 and stage T3; the only predictor of PCSM was bGS of 8 to 10. The duration of ADT was not predictive of any endpoint. We identified an unfavorable high-risk (UHR) group of stage T1-T2 tumors consisting of bGS of 8 with PSA of >10 ng/ml or bGS of 9 to 10 with any PSA level; the remaining clinically localized cancers comprised the favorable high-risk (FHR) group. Comparing FHR, UHR, and stage T3 groups, the DMFS rates were 81.4%, 57.8%, and 59.1% (p < 0.0001), and the PCSM rates were 7.5%, 28.4%, and 20.6% at 10 years, respectively (p = 0.006). Conclusion: A bGS of 8 to 10 is the strongest predictor of bRFS, DMFS, and PCSM after high-dose EBRT with ADT. The duration of ADT did not correlate with outcome. Future studies should account for the heterogeneity in HR prostate cancer.« less

A pilot randomised controlled trial of a periodised resistance training and protein supplementation intervention in prostate cancer survivors on androgen deprivation therapy

PubMed Central

Dorff, Tanya B; Todd Schroeder, E; Salem, George J; Lane, Christianne J; Rice, Judd C; Gross, Mitchell E; Dieli-Conwright, Christina M

2017-01-01

Introduction Prostate cancer survivors (PCS) receiving androgen deprivation therapy (ADT) experience deleterious side effects such as unfavourable changes in cardiometabolic factors that lead to sarcopenic obesity and metabolic syndrome (MetS). While loss of lean body mass (LBM) compromises muscular strength and quality of life, MetS increases the risk of cardiovascular disease and may influence cancer recurrence. Exercise can improve LBM and strength, and may serve as an alternative to the pharmacological management of MetS in PCS on ADT. Prior exercise interventions in PCS on ADT have been effective at enhancing strength, but only marginally effective at enhancing body composition and ameliorating cardiometabolic risk factors. This pilot trial aims to improve on existing interventions by employing periodised resistance training (RT) to counter sarcopenic obesity in PCS on ADT. Secondary aims compare intervention effects on cardiometabolic, physical function, quality of life and molecular skeletal muscle changes. An exploratory aim examines if protein supplementation (PS) in combination with RT elicits greater changes in these outcomes. Methods and analysis A 2×2 experimental design is used in 32 PCS on ADT across a 12-week intervention period. Participants are randomised to resistance training and protein supplementation (RTPS), RT, PS or control. RT and RTPS groups perform supervised RT three times per week for 12 weeks, while PS and RTPS groups receive 50 g whey protein per day. This pilot intervention applies a multilayered approach to ameliorate detrimental cardiometabolic effects of ADT while investigating molecular mechanisms underlying skeletal muscle changes in PCS. Ethics and dissemination This trial was approved by the University of Southern California Institutional Review Board (HS-13–00315). Results from this trial will be communicated in peer-reviewed publications and scientific presentations. Trial registration number NCT01909440; Pre-results. PMID:28698349

Phase II randomized clinical trial evaluating neoadjuvant chemotherapy regimens with weekly paclitaxel or eribulin followed by doxorubicin and cyclophosphamide in women with locally advanced HER2-negative breast cancer: NSABP Foundation Study FB-9.

PubMed

Abraham, Jame; Robidoux, André; Tan, Antoinette R; Limentani, Steven; Sturtz, Keren; Shalaby, Ibrahim; Alcorn, Hope; Buyse, Marc E; Wolmark, Norman; Jacobs, Samuel A

2015-07-01

Locally advanced breast cancer (LABC) is a good setting in which to monitor response to neoadjuvant chemotherapy, to downsize the tumor (which facilitates breast-conserving surgery), and to test newer agents in untreated patients. Eribulin (E) has shown activity in patients who have undergone previous taxane, anthracycline, and capecitabine treatment. We aimed to evaluate the neoadjuvant use of E followed by doxorubicin and cyclophosphamide (AC) in patients with HER2-negative LABC, using as a control a randomized group of women who received weekly paclitaxel (WP). Fifty women with LABC were accrued January-August 2013. Patients were randomized (1:2) to receive either WP (N = 19) for 12 treatments or E (N = 31) every 3 weeks for 4 cycles followed by AC every 3 weeks for 4 cycles before surgery. 17/19 patients who took WP and 25/30 who took E completed all cycles. Patients were evaluated by clinical examination and breast MRI at baseline and after completion of E or WP. Surgical pCR in breast and lymph nodes was determined by a local pathologist following chemotherapy. Forty-nine patients received ≥1 dose of neoadjuvant chemotherapy and are included in this analysis. Forty-eight underwent surgery; one had disease that was inoperable (on E) and is included as no-pCR patient. 17/19 of these patients who took WP completed 12 doses; 28/30 on E completed 4 cycles. Six discontinued treatment on WP, E, or AC. Both treatments were well tolerated. pCR on WP = 5/19(26 %) and on E = 5/30(17 %). Both regimens were equally well tolerated with no unexpected toxicities. pCR did not suggest higher activity with E than with other standard regimens in these LABC patients.

Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance)

PubMed Central

Boughey, Judy C.; Ballman, Karla V.; Hunt, Kelly K.; McCall, Linda M.; Mittendorf, Elizabeth A.; Ahrendt, Gretchen M.; Wilke, Lee G.; Le-Petross, Huong T.

2015-01-01

Purpose The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery. Patients and Methods Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed. Results Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery. Conclusion AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy. PMID:25646192

Predictive value of MRI-detected extramural vascular invasion in stage T3 rectal cancer patients before neoadjuvant chemoradiation.

PubMed

Sun, Yiqun; Li, Jianwen; Shen, Lijun; Wang, Xiaolin; Tong, Tong; Gu, Yajia

2018-01-01

We set out to explore the probability of MRI-detected extramural vascular invasion (mr-EMVI) before chemoradiation to predict responses to chemoradiation and survival in stage T3 rectal cancer patients. A total of 100 patients with T3 rectal cancer who underwent MRI examination and received neoadjuvant chemoradiation and surgery were enrolled. The correlation between mr-EMVI and other clinical factors were analyzed by chi-square. Logistic regression model was performed to select the potential factors influencing tumor responses to neoadjuvant chemoradiation. A Cox proportional hazards regression model was performed to explore potential predictors of survival. The positive mr-EMVI result was more likely to be present in patients with a higher T3 subgroup (T3a+b = 7.1% vs. T3c+d = 90.1%, P < 0.001) and more likely in patients with mesorectal fascia involvement than in those without MRF (65% vs. 38.8%, P = 0.034). Compared with mr-EMVI (+) patients, more mr-EMVI (-) patients showed a good response (staged ≤ ypT2N0) (odds ratio [OR], 3.020; 95% confidence interval [CI], 1.071-8.517; P = 0.037). In univariate analysis, mr-EMVI (+) (hazard ratio [HR], 5.374; 95% CI, 1.210-23.872; P = 0.027) and lower rectal cancers (HR, 3.326; 95% CI, 1.135-9.743; P = 0.028) were significantly associated with decreased disease-free survival. A positive mr-EMVI status (HR, 5.727; 95% CI, 1.286-25.594; P = 0.022) and lower rectal cancers (HR, 3.137; 95% CI, 1.127-8.729; P = 0.029) also served as prognostic factors related to decreased disease-free survival in multivariate analysis. The mr-EMVI status before chemoradiation is a significant prognostic factor and could be used for identifying T3 rectal cancer patients who might benefit from neoadjuvant chemoradiation.

Neoadjuvant Radiotherapy: A Risk Factor for Short-Term Wound Complications after Radical Resection for Rectal Cancer?

PubMed

Holubar, Stefan D; Brickman, Rachel K; Greaves, Spencer W; Ivatury, S Joga

2016-08-01

Neoadjuvant radiotherapy (RT) for rectal cancer may increase wound complications after oncologic proctectomy. We aimed to assess the relationship between neoadjuvant RT and 30-day wound complications after radical surgery for rectal cancer. We identified rectal cancer patients (International Classification of Diseases, revision-9 [ICD-9] code 154.1) who underwent radical resection, using NSQIP from 2005 to 2010. Patients were stratified into preoperative radiation vs no radiation groups. Our primary outcome was any wound complication. The association between preoperative RT and postoperative wound complication rate was assessed by univariate, multivariable, and propensity score analyses. Of 242,670 colorectal cases, 6,297 patients were included. Of these, 2,476 (39%) received RT within 90 days preoperatively. The RT group, compared with the no RT group, received more chemotherapy within 30 days preoperatively (15.0% vs 2.5%, p < 0.0001), and had less laparoscopic (18.9% vs 25.1%, p < 0.0001) or sphincter-preserving surgery (61.8% vs 67.1%, p < 0.0001). In the univariate analyses, there was no difference in wound complications (19.6% vs 18.7%, p = 0.42) between groups. Similarly, there was no difference in overall complications (29.6% vs 29.8%, p = 0.89), return to operating room (6.7% vs 6.7%, p = 0.96), or length of stay (8.4 vs 8.4 days, p = 0.72) between the RT and no RT groups, respectively. The mortality rate in the RT group was lower on univariate analysis (0.7% vs 1.4%, p = 0.008), but was not significantly different in the multivariable analyses. Multivariable and propensity score analyses were consistent with the lack of association between preoperative RT and postoperative wound complications. Neoadjuvant radiotherapy does not appear to be an independent risk factor for wound complications after radical surgery for rectal cancer. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance).

PubMed

Boughey, Judy C; Ballman, Karla V; Hunt, Kelly K; McCall, Linda M; Mittendorf, Elizabeth A; Ahrendt, Gretchen M; Wilke, Lee G; Le-Petross, Huong T

2015-10-20

The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery. Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed. Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery. AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy. © 2015 by American Society of Clinical Oncology.

Central pathology review with two-stage quality assurance for pathological response after neoadjuvant chemotherapy in the ARTemis Trial.

PubMed

Thomas, Jeremy St John; Provenzano, Elena; Hiller, Louise; Dunn, Janet; Blenkinsop, Clare; Grybowicz, Louise; Vallier, Anne-Laure; Gounaris, Ioannis; Abraham, Jean; Hughes-Davies, Luke; McAdam, Karen; Chan, Stephen; Ahmad, Rizvana; Hickish, Tamas; Houston, Stephen; Rea, Daniel; Caldas, Carlos; Bartlett, John Ms; Cameron, David Allan; Hayward, Richard Laurence; Earl, Helena Margaret

2017-08-01

The ARTemis Trial tested standard neoadjuvant chemotherapy±bevacizumab in the treatment of HER2-negative early breast cancer. We compare data from central pathology review with report review and also the reporting behavior of the two central pathologists. Eight hundred women with HER2-negative early invasive breast cancer were recruited. Response to chemotherapy was assessed from local pathology reports for pathological complete response in breast and axillary lymph nodes. Sections from the original core biopsy and surgical excision were centrally reviewed by one of two trial pathologists blinded to the local pathology reports. Pathologists recorded response to chemotherapy descriptively and also calculated residual cancer burden. 10% of cases were double-reported to compare the central pathologists' reporting behavior. Full sample retrieval was obtained for 681 of the 781 patients (87%) who underwent surgery within the trial and were evaluable for pathological complete response. Four hundred and eighty-three (71%) were assessed by JSJT, and 198 (29%) were assessed by EP. Residual cancer burden calculations were possible in 587/681 (86%) of the centrally reviewed patients, as 94/681 (14%) had positive sentinel nodes removed before neoadjuvant chemotherapy invalidating residual cancer burden scoring. Good concordance was found between the two pathologists for residual cancer burden classes within the 65-patient quality assurance exercise (kappa 0.63 (95% CI: 0.57-0.69)). Similar results were obtained for the between-treatment arm comparison both from the report review and the central pathology review. For pathological complete response, report review was as good as central pathology review but for minimal residual disease, report review overestimated the extent of residual disease. In the ARTemis Trial central pathology review added little in the determination of pathological complete response but had a role in evaluating low levels of residual disease. Calculation of residual cancer burden was a simple and reproducible method of quantifying response to neoadjuvant chemotherapy as demonstrated by performance comparison of the two pathologists.

Neoadjuvant Radiotherapy: Changing the Treatment Sequence to Allow Immediate Free Autologous Breast Reconstruction.

PubMed

Hughes, Kimberley; Neoh, Derek

2018-06-16

 Locally advanced breast cancer (LABC) is traditionally treated with a multimodal approach of chemotherapy, surgery, and postmastectomy radiotherapy (PMRT). The advantages of immediate breast reconstruction (IBR) are well described and include improved aesthetic outcomes, fewer surgical procedures, shorter treatment period, and a higher quality of life. However, this sequence makes immediate free autologous reconstruction more challenging as PMRT can have deleterious and unpredictable effects on the flap. We have reversed this treatment sequence with neoadjuvant chemotherapy and radiotherapy, followed by mastectomy and immediate free autologous reconstruction. To our knowledge, this is the first series to assess the outcomes of neoadjuvant radiotherapy on immediate free microvascular breast reconstruction.  A review of patients with LABC who underwent immediate free autologous breast reconstruction post neoadjuvant chemoradiotherapy between 2013 and 2017 was conducted. All reconstructions were performed by a single reconstructive team. The primary end points were flap failure and surgical complications. Secondary end points were pathological response rate and disease recurrence.  A total of 40 women with an average age of 48.1 (36-61) and average body mass index of 25.6 (18-37) were included. The most common choice of flap was immediate deep inferior epigastric perforator (DIEP, 31), followed by transverse or diagonal upper gracilis (5), muscle-sparing transversus abdominis (3), and stacked DIEP (1). Our major complication rate was 12.5% and minor complication 15%. There were no cases of local recurrence and only three cases (7.5%) of distant disease progression.  From our experience, this treatment sequence allows patients to have an immediate gold standard reconstruction without an increase in surgical morbidity. It affords the benefits of IBR without concern in delaying adjuvant therapy and appears to be safe from an oncological perspective. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Long-Term Follow-Up of a Prospective Trial of Trimodality Therapy of Weekly Paclitaxel, Radiation, and Androgen Deprivation in High-Risk Prostate Cancer With or Without Prior Prostatectomy

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

Hussain, Arif, E-mail: ahussain@som.umaryland.edu; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD; Baltimore VA Medical Center, Baltimore, MD

2012-01-01

Purpose: Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). Methods and Materials: Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) {>=}0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8-10; 3) GS 7 + PSA 10-20 ng/mL; or 4) PSA 20-150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m{sup 2}/wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). Results: Fifty-ninemore » patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45-86 years), PSA 5.9 (0.1-92.1 ng/mL), GS 8 (6-9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8-82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. Conclusions: In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m{sup 2}/week in RP patients and 60 mg/m{sup 2}/week in LAPC patients is feasible and well-tolerated.« less

Pressurized intraperitoneal aerosol chemotheprapy after misdiagnosed gastric cancer: Case report and review of the literature.

PubMed

Nowacki, Maciej; Grzanka, Dariusz; Zegarski, Wojciech

2018-05-21

We report the first application of pressurized intraperitoneal aerosol chemotherapy (PIPAC) as a rescue therapy before palliative D2 gastrectomy combined with liver metastasectomy performed in a 49-year-old woman with peritoneal carcinomatosis who was primarily diagnosed with and underwent surgery for a Krukenberg tumor. The PIPAC procedure was performed with the use of cisplatin at 7.5 mg/m 2 and doxorubicin at 1.5 mg/m 2 for 30 min at 37 °C. Eight weeks after the PIPAC procedure, the patient underwent open classic D2 gastrectomy with the creation of a Roux-en-Y anastomosis (RNY) combined with liver metastasectomy. The patient underwent the classic protocol for chemotherapy combined with Xeloda. The patient felt better and returned to her daily activities. Multicenter data should be gathered to confirm the usefulness of PIPAC as a rescue or neoadjuvant supportive therapy in a very select group of patients who have been recently qualified to undergo classic chemotherapy or standard oncologic surgical procedures.

Revisiting the ADT mass of the five-dimensional rotating black holes with squashed horizons

NASA Astrophysics Data System (ADS)

Peng, Jun-Jin

2017-10-01

We evaluate the Abbott-Deser-Tekin (ADT) mass of the five-dimensional rotating black holes with squashed horizons on two different on-shell reference backgrounds, which are the flat background and the boundary matched Kaluza-Klein (KK) monopole. The mass on the former, identified with the one on the background of the asymptotic geometry, differs from the mass on the latter by that of the KK monopole. However, each mass satisfies the first law of black hole thermodynamics. To test the results in five dimensions, we compute the mass in the context of the dimensionally reduced theory. Finally, in contrast with the original ADT formulation, its off-shell generalisation is applied to calculate the mass as well.

Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer.

PubMed

Artioli, Grazia; Grazia, Artioli; Mocellin, Simone; Simone, Mocellin; Borgato, Lucia; Lucia, Borgato; Cappetta, Alessandro; Alessandro, Cappetta; Bozza, Fernando; Fernando, Bozza; Zavagno, Giorgio; Giorgio, Zavagno; Zovato, Stefania; Stefania, Zovato; Marchet, Alberto; Alberto, Marchet; Pastorelli, Davide; Davide, Pastorelli

2010-09-01

This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer. Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery. Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response. The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.

Cognitive Impacts of Estrogen Treatment in Androgen-Deprived Males: What Needs to be Resolved.

PubMed

Wibowo, Erik

2017-01-01

Many prostate cancer (PCa) patients are on androgen deprivation therapy (ADT) as part of their cancer treatments but ADT may lead to cognitive impairments. ADT depletes men of both androgen and estrogen. Whether estradiol supplementation can improve cognitive impairments in patients on ADT is understudied. To summarize data on the effects of estradiol treatment on cognitive function of androgen-deprived genetic male populations (PCa patients and male-to-female transsexuals) and castrated male animals. Publications were identified by a literature search on PubMed and Google Scholar. While some studies showed that estradiol improves cognitive function (most notably, spatial ability) for castrated rats, what remains uninvestigated are: 1) whether estradiol can improve cognition after long-term androgen deprivation, 2) how estradiol affects memory retention, and 3) how early vs. delayed estradiol treatment after castration influences cognition. For androgendeprived genetic males, estradiol treatment may improve some cognitive functions (e.g., verbal and visual memory), but the findings are not consistent due to large variability in the study design between studies. Future studies are required to determine the best estradiol treatment protocol to maximize cognitive benefits for androgen-deprived genetic males. Tests that assess comparable cognitive domains in human and rodents are needed. What particularly under-investigated is how the effects of estradiol on cognitive ability intersect with other parameters; sleep, depression and physical fatigue. Such studies have clinical implications to improve the quality of life for both PCa patients on ADT as well as for male-to-female transsexuals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Technology and Career Preparation: Using Virtual Interview Recordings (VIRs) in an Apparel, Design, and Textiles (ADT) Professional Seminar Course

ERIC Educational Resources Information Center

Eike, Rachel J.; Rowell, Amy; Mihuta, Tiffani

2016-01-01

The purpose of this study was to identify key virtual-recorded interview (VIR) skills that are essential to Apparel, Design, and Textile (ADT) student performance. The virtual, computer-recording interview platform, InterviewStream, was used as the data collection instrument in this qualitative, exploratory case study. Virtual interviews have been…

GEMMs shine a light on resistance to androgen deprivation therapy for prostate cancer

PubMed Central

Karantanos, Theodoros; Thompson, Timothy C.

2013-01-01

Summary Androgen deprivation therapy (ADT) for advanced prostate cancer inexorably leads to resistance, and clinically useful biomarkers are lacking. The value of genetically engineered mice for co-clinical studies is clearly demonstrated in a recent publication that reveals XAF1, XIAP, and SRD5A1 as novel predictive biomarkers and therapeutic targets for ADT resistance. PMID:23845440

Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using direct homologous challenge

USDA-ARS?s Scientific Manuscript database

The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularl...

Assessment of Teaching Approaches in an Introductory Astronomy College Classroom

NASA Astrophysics Data System (ADS)

Alexander, William R.

In recent years, there have been calls from the astronomy education research community for the increased use of learner-centered approaches to teaching, and systematic assessments of various teaching approaches using such tools as the Astronomy Diagnostic Test 2.0 (ADT 2.0). The research presented is a response to both calls. The ADT 2.0 was used in a modified form to obtain baseline assessments of introductory college astronomy classes that were taught in a traditional, mostly didactic manner. The ADT 2.0 (modified) was administered both before and after the completion of the courses. The courses were then altered to make modest use of learner-centered lecture tutorials. The ADT 2.0 (modified) was again administered before and after completion of the modified courses. Overall, the modest learner-centered approach showed mixed statistical results, with an increase in effect size (from medium to large), but no change in normalized gain index (both were low). Additionally, a mathematically rigorous approach showed no statistically significant improvements in conceptual understanding compared with a mathematically nonrigorous approach. This study will interpret the results from a variety of perspectives. The overall implementation of the lecture tutorials and their implications for teaching will also be discussed.

'No power' (green) electrowetting display

NASA Astrophysics Data System (ADS)

Jentsch, Michael; Rawert, Juergen; Jerosch, Dieter; Blankenbach, Karlheinz

2011-05-01

Electrowetting displays were first reported in 1981, several approaches were examined. However, ADT's "Droplet- Driven-Displays" technology is the only bistable one which makes them very attractive for energy-saving systems. That means that the power supply can completely shut off after changing the content and it will keep its information for years. More features that make the ADT approach very unique are paper like white appearance (even in the powerless OFFstate) and the capability for backlighting (most of the other e-paper technologies like electrophoretics can not be backlighted). Further achievements are a white state reflectance of about 70% resulting in sunlight readability and a pixel size in the range from 0.3mm to 10mm. Summarizing, ADT's electrowetting technology is highly suitable for lowest power (means eco-friendly or "green") displays.

Neoadjuvant treatments for locally advanced, resectable esophageal cancer: A network meta-analysis.

PubMed

Chan, Kelvin K W; Saluja, Ronak; Delos Santos, Keemo; Lien, Kelly; Shah, Keya; Cramarossa, Gemma; Zhu, Xiaofu; Wong, Rebecca K S

2018-02-14

The relative survival benefits and postoperative mortality among the different types of neoadjuvant treatments (such as chemotherapy only, radiotherapy only or chemoradiotherapy) for esophageal cancer patients are not well established. To evaluate the relative efficacy and safety of neoadjuvant therapies in resectable esophageal cancer, a Bayesian network meta-analysis was performed. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for publications up to May 2016. ASCO and ASTRO annual meeting abstracts were also searched up to the 2015 conferences. Randomized controlled trials that compared at least two of the following treatments for resectable esophageal cancer were included: surgery alone, surgery preceded by neoadjuvant chemotherapy, neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy. The primary outcome assessed from the trials was overall survival. Thirty-one randomized controlled trials involving 5496 patients were included in the quantitative analysis. The network meta-analysis showed that neoadjuvant chemoradiotherapy improved overall survival when compared to all other treatments including surgery alone (HR 0.75, 95% CR 0.67-0.85), neoadjuvant chemotherapy (HR 0.83. 95% CR 0.70-0.96) and neoadjuvant radiotherapy (HR 0.82, 95% CR 0.67-0.99). However, the risk of postoperative mortality increased when comparing neoadjuvant chemoradiotherapy to either surgery alone (RR 1.46, 95% CR 1.00-2.14) or to neoadjuvant chemotherapy (RR 1.58, 95% CR 1.00-2.49). In conclusion, neoadjuvant chemoradiotherapy improves overall survival but may also increase the risk of postoperative mortality in patients locally advanced resectable esophageal carcinoma. © 2018 UICC.

Carcinoma of the ampulla of Vater: patterns of failure following resection and benefit of chemoradiotherapy.

PubMed

Palta, Manisha; Patel, Pretesh; Broadwater, Gloria; Willett, Christopher; Pepek, Joseph; Tyler, Douglas; Zafar, S Yousuf; Uronis, Hope; Hurwitz, Herbert; White, Rebekah; Czito, Brian

2012-05-01

Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single-institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery. A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier method. A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n = 43) or neoadjuvant (n = 18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P = .03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8 years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P = .001) with trend toward 3-year DFS (66% vs 48%, P = .09) and OS (62% vs 46%, P = .074) benefit in patients receiving CRT. Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered.

Accuracy of MDCT in the preoperative definition of Peritoneal Cancer Index (PCI) in patients with advanced ovarian cancer who underwent peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC).

PubMed

Mazzei, Maria Antonietta; Khader, Leila; Cirigliano, Alfredo; Cioffi Squitieri, Nevada; Guerrini, Susanna; Forzoni, Beatrice; Marrelli, Daniele; Roviello, Franco; Mazzei, Francesco Giuseppe; Volterrani, Luca

2013-12-01

To evaluate the accuracy of MDCT in the preoperative definition of Peritoneal Cancer Index (PCI) in patients with advanced ovarian cancer who underwent a peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant chemotherapy to obtain a pre-surgery prognostic evaluation and a prediction of optimal cytoreduction surgery. Pre-HIPEC CT examinations of 43 patients with advanced ovarian cancer after neoadjuvant chemotherapy were analyzed by two radiologists. The PCI was scored according to the Sugarbaker classification, based on lesion size and distribution. The results were compared with macroscopic and histologic data after peritonectomy and HIPEC. To evaluate the accuracy of MDCT to detect and localize peritoneal carcinomatosis, both patient-level and regional-level analyses were conducted. A correlation between PCI CT and histologic values for each patient was searched according to the PCI grading. Considering the patient-level analysis, CT shows a sensitivity, specificity, PPV, NPV, and an accuracy in detecting the peritoneal carcinomatosis of 100 %, 40 %, 93 % 100 %, and 93 %, respectively. Considering the regional level analysis, a sensitivity, specificity, PPV, NPV, and diagnostic accuracy of 72 %, 80 %, 66 %, 84 %, and 77 %, respectively were obtained for the correlation between CT and histology. Our results encourage the use of MDCT as the only technique sufficient to select patients with peritoneal carcinomatosis for cytoreductive surgery and HIPEC on the condition that a CT examination will be performed using a dedicated protocol optimized to detect minimal peritoneal disease and CT images will be analyzed by an experienced reader.

Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

PubMed

Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

1998-01-01

The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes were strongly correlated with disease-free survival and overall survival in univariate analyses. Additionally, in a proportional hazard regression model and in an accelerated failure time model, metastatic axillary lymph nodes significantly influenced both disease-free survival and overall survival, whereas pathological response of primary tumor did so on disease-free survival only. After neoadjuvant chemotherapy, pathological responses of both primary tumor and metastatic axillary lymph nodes had a marked prognostic significance and influenced outcome for patients with locally advanced breast carcinoma. Our results suggest that maximal tumor shrinkage and sterilization of potentially involved axillary nodes may represent a major goal of neoadjuvant chemotherapy. Further studies are warranted to clarify whether these results reflect the therapeutic effect or intrinsic biologic factors of the tumor.

Neoadjuvant sunitinib effectiveness in T4 renal clear cell carcinoma: a case report.

PubMed

Ricciardulli, Stefano; Del Biondo, Dario; Cicero, Calogero; Leo, Genesio; Zeccolini, Guglielmo; Celia, Antonio

2015-01-01

Sunitinib therapy showed an improvement in survival of patients with metastatic renal cell carcinoma. A 51-year-old man, with Eastern Cooperative Oncology Group Score (ECOG) of 0, presented at our Institute in March 2012 for macrohematuria and urinary retention. A computed tomography (CT) scan of the abdomen showed a right renal lesion. The lesion had a diameter of 15 cm and was developing towards the liver, in the absence of cleavage planes between the liver and kidney. A 12 mm finding, suspected as secondary lesion, was detected at the level of the VII hepatic segment. Neoadjuvant chemotherapy with Sunitinib was proposed. The patient underwent a ultrasound-guided biopsy, which confirmed the presence of Clear Cell Carcinoma. The patient began chemotherapy treatment in May 2012 according to the scheme SUNITINIB 50 mg daily for 4 weeks every 6 weeks. After four courses of treatment, according to RECIST criteria for solid tumors, 40% (9 cm vs 15 cm) regression of the primary tumor and 33% (8 mm vs 12 mm) regression of the secondary lesion were observed at a CT scan of the abdomen. In February 2013, Laparoscopic Adrenal-Sparing Radical Nephrectomy was performed. At a follow-up of 3 months, performed with a thorax and abdomen CT scans, there was a complete remission of hepatic secondary lesion and no areas of secondary localization of disease. This case report showed the effectiveness of neoadjuvant chemotherapy with Sunitinib. The use of this chemotherapy agent can change the approach to the management of cRCC.

Prediction of Chemoresistance in Women Undergoing Neo-Adjuvant Chemotherapy for Locally Advanced Breast Cancer: Volumetric Analysis of First-Order Textural Features Extracted from Multiparametric MRI

PubMed Central

Losio, C.; Della Corte, A.; Venturini, E.; Ambrosi, A.; Panizza, P.; De Cobelli, F.

2018-01-01

Purpose To assess correlations between volumetric first-order texture parameters on baseline MRI and pathological response after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (BC). Materials and Methods 69 patients with locally advanced BC candidate to neoadjuvant chemotherapy underwent MRI within 4 weeks from the start of therapeutic regimen. T2, DWI, and DCE sequences were analyzed and maps were generated for Apparent Diffusion Coefficient (ADC), T2 signal intensity, and the following dynamic parameters: k-trans, peak enhancement, area under curve (AUC), time to maximal enhancement (TME), wash-in rate, and washout rate. Volumetric analysis of these parameters was performed, yielding a histogram analysis including first-order texture kinetics (percentiles, maximum value, minimum value, range, standard deviation, mean, median, mode, skewness, and kurtosis). Finally, correlations between these values and response to NAC (evaluated on the surgical specimen according to RECIST 1.1 criteria) were assessed. Results Out of 69 tumors, 33 (47.8%) achieved complete pathological response, 26 (37.7%) partial response, and 10 (14.5%) no response. Higher levels of AUCmax (p value = 0.0338), AUCrange (p value = 0.0311), and TME75 (p value = 0.0452) and lower levels of washout10 (p value = 0.0417), washout20 (p value = 0.0138), washout25 (p value = 0.0114), and washout30 (p value = 0.05) were predictive of noncomplete response. Conclusion Histogram-derived texture analysis of MRI images allows finding quantitative parameters predictive of nonresponse to NAC in women affected by locally advanced BC. PMID:29853811

Prediction of Chemoresistance in Women Undergoing Neo-Adjuvant Chemotherapy for Locally Advanced Breast Cancer: Volumetric Analysis of First-Order Textural Features Extracted from Multiparametric MRI.

PubMed

Panzeri, M M; Losio, C; Della Corte, A; Venturini, E; Ambrosi, A; Panizza, P; De Cobelli, F

2018-01-01

To assess correlations between volumetric first-order texture parameters on baseline MRI and pathological response after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (BC). 69 patients with locally advanced BC candidate to neoadjuvant chemotherapy underwent MRI within 4 weeks from the start of therapeutic regimen. T2, DWI, and DCE sequences were analyzed and maps were generated for Apparent Diffusion Coefficient (ADC), T2 signal intensity, and the following dynamic parameters: k -trans, peak enhancement, area under curve (AUC), time to maximal enhancement (TME), wash-in rate, and washout rate. Volumetric analysis of these parameters was performed, yielding a histogram analysis including first-order texture kinetics (percentiles, maximum value, minimum value, range, standard deviation, mean, median, mode, skewness, and kurtosis). Finally, correlations between these values and response to NAC (evaluated on the surgical specimen according to RECIST 1.1 criteria) were assessed. Out of 69 tumors, 33 (47.8%) achieved complete pathological response, 26 (37.7%) partial response, and 10 (14.5%) no response. Higher levels of AUCmax ( p value = 0.0338), AUCrange ( p value = 0.0311), and TME 75 ( p value = 0.0452) and lower levels of washout 10 ( p value = 0.0417), washout 20 ( p value = 0.0138), washout 25 ( p value = 0.0114), and washout 30 ( p value = 0.05) were predictive of noncomplete response. Histogram-derived texture analysis of MRI images allows finding quantitative parameters predictive of nonresponse to NAC in women affected by locally advanced BC.

Immediate autologous breast reconstruction after neoadjuvant chemoradiotherapy for breast cancer: initial results of the first 29 patients.

PubMed

Grinsell, Damien; Pitcher, Meron; Wong, Shirley; Guerrieri, Mario; Nielsen, Hans H M

2018-03-01

Breast reconstruction after mastectomy in the treatment of locally advanced breast cancer is often done in stages and before radiotherapy. We have previously published an algorithm for immediate free autologous reconstruction after neoadjuvant chemotherapy and preoperative radiotherapy. This protocol was designed to provide a shorter and simpler reconstructive path whilst improving cosmesis and maintaining oncological efficiency. A total of 29 patients were included and underwent surgery for 30 cancers by the first author between 2010 and September 2015. Data were prospectively entered into a database and analysed for tumour size, chemotherapeutic response, lymph node involvement, surgical complications and tumour recurrence. The mean age was 55 ± 7 years. Eighty percent of patients had either a partial or complete chemotherapeutic response defined as >25% decrease in tumour size. Twenty-eight patients had free abdominal tissue transfer. One patient was excluded due to advanced disease. There were no take-backs due to microsurgical issues. One patient was reoperated on for a haematoma. Four patients had recurrent cancer during follow-up, three of whom are deceased. Many, but not all, breast reconstructive surgeons consider autologous reconstruction as the 'gold' standard in the presence of radiotherapy. Rearranging the order of radiotherapy and surgery means operating in a recently irradiated field. We believe the surgical challenges are outweighed by a shorter and simpler reconstructive journey that additionally results in a better cosmesis. It is possible to perform immediate free autologous reconstruction after neoadjuvant chemotherapy and preoperative radiotherapy with excellent results and at least equivalent oncological efficacy. © 2017 Royal Australasian College of Surgeons.

Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis–Free Survival and Prostate Cancer–Specific Mortality

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

Naik, Mihir, E-mail: naikm@ccf.org; Reddy, Chandana A.; Stephans, Kevin L.

Objectives/Background: To determine whether a 6-month posttreatment prostate-specific antigen (PSA) value in patients with prostate cancer (PCa) treated with concurrent androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) serves as an early predictor for biochemical relapse free survival (bRFS), distant metastasis–free survival (DMFS), and prostate cancer–specific mortality (PCSM). Methods: A retrospective review of intermediate-risk and high-risk PCa patients treated with EBRT and concurrent ADT at a single institution between 1996 and 2012. All patients received high-dose radiation with either 78 Gy in 39 fractions or 70 Gy in 28 fractions. Kaplan-Meier analysis was used to estimate bRFS and DMFS, andmore » cumulative incidence was used to estimate PCSM. Results: 532 patients were identified. The median follow-up time was 7.5 years (range, 1-16.25 years). The median initial PSA (iPSA) was 13.0 ng/mL (range, 0.37-255 ng/mL), and the median duration of ADT was 6 months (range, 1-78 months). The median PSA 6 months after EBRT was 0.1 ng/mL (range, 0-19 ng/mL), and 310 patients (58.3%) had a 6-month PSA ≤0.1 ng/mL. Multivariable analysis (MVA) demonstrated that a 6-month post-EBRT PSA of >0.1 ng/mL was an independent predictor of worse bRFS (hazard ratio [HR] = 2.518; P<.0001), DMFS (HR=3.743; P<.0001), and PCSM (HR=5.435; P<.0001). On MVA, a Gleason score of 8 to 10 also correlated with worse DMFS and PCSM (P<.05). The duration of ADT (1-6 vs >6 months) was not predictive of any clinical endpoint. Conclusions: A 6-month posttreatment PSA >0.1 ng/mL in intermediate-risk and high-risk PCa patients treated with concurrent high-dose EBRT and ADT is associated with worse bRFS, DMFS, and PCSM. The duration of ADT was not predictive of any clinical endpoint. A 6-month PSA after definitive EBRT and ADT helps identify patients at higher risk of disease progression and may serve as a predictive tool to select patients for early salvage therapy on future clinical trials.« less

77 FR 3325 - Emergency Temporary Closure of the I-64 Sherman-Minton Bridge Over the Ohio River Between Indiana...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-23

... closure of the I-64 Sherman-Minton Bridge has affected traffic throughout the Louisville and Southern Indiana region. The closed bridge carried an Average Daily Traffic (ADT) count of 80,000 vehicles. The I-65 Kennedy Bridge has an ADT of 130,000 vehicles. The additional traffic on I-65 due to the Sherman...

Laboratory pavement polishing device (wear machine) versus field friction test units and accumulative traffic (ADT). Phase 2. Correlation study

NASA Astrophysics Data System (ADS)

Godwin, H. F.; Loyed, D. B.; Miley, W. G.; Page, G. C.

1981-04-01

The degree to which pavement wear (vehicular traffic) could be predicted from testing samples of in-service pavements in the laboratory pavement polishing device was determined. This investigation was made on asphaltic concrete pavements, primarily friction courses used in Florida. These pavements were tested at different levels of accumulative traffic (ADT) for approximately 2 years.

Management Options for Biochemically Recurrent Prostate Cancer.

PubMed

Fakhrejahani, Farhad; Madan, Ravi A; Dahut, William L

2017-05-01

Prostate cancer is the most common solid tumor malignancy in men worldwide. Treatment with surgery and radiation can be curative in organ-confined disease. Unfortunately, about one third of men develop biochemically recurrent disease based only on rising prostate-specific antigen (PSA) in the absence of visible disease on conventional imaging. For these patients with biochemical recurrent prostate cancer, there is no uniform guideline for subsequent management. Based on available data, it seems prudent that biochemical recurrent prostate cancer should initially be evaluated for salvage radiation or prostatectomy, with curative intent. In selected cases, high-intensity focused ultrasound and cryotherapy may be considered in patients that meet very narrow criteria as defined by non-randomized trials. If salvage options are not practical or unsuccessful, androgen deprivation therapy (ADT) is a standard option for disease control. While some patients prefer ADT to manage the disease immediately, others defer treatment because of the associated toxicity. In the absence of definitive randomized data, patients may be followed using PSA doubling time as a trigger to initiate ADT. Based on retrospective data, a PSA doubling time of less than 3-6 months has been associated with near-term development of metastasis and thus could be used signal to initiate ADT. Once treatment is begun, patients and their providers can choose between an intermittent and continuous ADT strategy. The intermittent approach may limit side effects but in patients with metastatic disease studies could not exclude a 20% greater risk of death. In men with biochemical recurrence, large studies have shown that intermittent therapy is non-inferior to continuous therapy, thus making this a reasonable option. Since biochemically recurrent prostate cancer is defined by technological limitations of radiographic detection, as new imaging (i.e., PSMA) strategies are developed, it may alter how the disease is monitored and perhaps managed. Furthermore, patients have no symptoms related to their disease and thus many prefer options that minimize toxicity. For this reason, herbal agents and immunotherapy are under investigation as potential alternatives to ADT and its accompanying side effects. New therapeutic options combined with improved imaging to evaluate the disease may markedly change how biochemically recurrent prostate cancer is managed in the future.

Stability and imaging of the ASML EUV alpha demo tool

NASA Astrophysics Data System (ADS)

Hermans, Jan V.; Baudemprez, Bart; Lorusso, Gian; Hendrickx, Eric; van Dijk, Andre; Jonckheere, Rik; Goethals, Anne-Marie

2009-03-01

Extreme Ultra-Violet (EUV) lithography is the leading candidate for semiconductor manufacturing of the 22nm technology node and beyond, due to the very short wavelength of 13.5nm. However, reducing the wavelength adds complexity to the lithographic process. The impact of the EUV specific conditions on lithographic performance needs to be understood, before bringing EUV lithography into pre-production. To provide early learning on EUV, an EUV fullfield scanner, the Alpha Demo Tool (ADT) from ASML was installed at IMEC, using a Numerical Aperture (NA) of 0.25. In this paper we report on different aspects of the ADT: the imaging and overlay performance and both short and long-term stability. For 40nm dense Lines-Spaces (LS), the ADT shows an across field overlapping process window of 270nm Depth Of Focus (DOF) at 10% Exposure Latitude (EL) and a wafer CD Uniformity (CDU) of 3nm 3σ, without any corrections for process or reticle. The wafer CDU is correlated to different factors that are known to influence the CD fingerprint from traditional lithography: slit intensity uniformity, focus plane deviation and reticle CD error. Taking these contributions into account, the CD through slit fingerprint for 40nm LS is simulated with excellent agreement to experimental data. The ADT shows good CD stability over 9 months of operation, both intrafield and across wafer. The projection optics reflectivity has not degraded over 9 months. Measured overlay performance with respect to a dry tool shows |Mean|+3σ below 20nm with more correction potential by applying field-by-field corrections (|Mean|+3σ <=10nm). For 22nm SRAM application, both contact hole and metal layer were printed in EUV with 10% CD and 15nm overlay control. Below 40nm, the ADT shows good wafer CDU for 30nm dense and isolated lines (on the same wafer) and 38nm dense Contact Holes (CH). First 28nm dense line CDU data are achieved. The results indicate that the ADT can be used effectively for EUV process development before installation of the pre-production tool, the ASML NXE Gen. 1 at IMEC.

Efficacy of a multi-component exercise programme and nutritional supplementation on musculoskeletal health in men treated with androgen deprivation therapy for prostate cancer (IMPACT): study protocol of a randomised controlled trial.

PubMed

Owen, Patrick J; Daly, Robin M; Livingston, Patricia M; Mundell, Niamh L; Dalla Via, Jack; Millar, Jeremy L; Fraser, Steve F

2017-10-03

Prostate cancer is the most commonly diagnosed cancer in men in developed countries. Androgen deprivation therapy (ADT) is a systemic treatment shown to increase survival in selected patients with prostate cancer. The use of ADT continues to increase for all stages and grades of prostate cancer despite known treatment-induced adverse effects. The primary aim of this study is to examine the efficacy of a targeted, multi-component resistance and impact-loading exercise programme together with a daily protein-, calcium- and vitamin D-enriched supplement on bone health in men treated with ADT for prostate cancer. Secondary aims are to determine the effects of this intervention on measures of total body and regional body composition, cardiometabolic risk, inflammatory markers, health-related quality of life and cognitive function. This study is a two-arm randomised controlled trial. Men currently treated with ADT for prostate cancer will be randomised to either a 52-week, community-based, exercise training and nutritional supplementation intervention (n = 51) or usual care control (n = 51). Participants will be assessed at baseline, 26 weeks and 52 weeks for all measures. The primary outcome measures are proximal femur and lumbar spine areal bone mineral density (BMD). Secondary outcomes comprise: changes in tibial and radial bone structure and strength, total body and regional body composition, muscle strength and function, as well as cardiometabolic health, catabolic/inflammatory and anabolic/anti-inflammatory cytokines, health-related quality of life and cognitive function. This study investigates whether a multi-component intervention incorporating a targeted bone and muscle-loading programme in combination with a protein-, calcium- and vitamin D-enriched supplement can ameliorate multiple adverse effects of ADT when compared to usual care. The results will contribute to the development of exercise training and nutrition guidelines for optimising overall health in men treated with ADT for prostate cancer. Australia New Zealand Clinical Trial Registry (ANZCTR), ID: ACTRN12614000317695 . Registered on 25 march 2014.

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.

Physician practices of bone density testing and drug prescribing to prevent or treat osteoporosis during androgen deprivation therapy.

PubMed

Tanvetyanon, Tawee

2005-01-15

Androgen deprivation therapy (ADT) is a strong risk factor for osteoporosis. The current study identified physician practices in preventing or treating osteoporosis during ADT. The practices of interest are the uses of dual-energy X-ray absorptiometry (DXA) scans, bisphosphonates, calcium or vitamin D supplement, calcitonin, or estrogen. A retrospective medical record review was conducted. Patients were included if they had received ADT with goserelin injection for >/= 1 year. Multivariable logistic regression analysis was performed to identify independent predictors of receiving at least one intervention. Analyses included 184 patients. Most were the elderly with multiple risk factors for osteoporosis. Only 8.7% (95% confidence interval [CI], 4.6-13.0%) of patients received a DXA scan at least once during the past 3 years. Oral and intravenous bisphosphonates were prescribed in 4.9% (95%CI, 1.8-8.0%) and 0.5% (95%CI, 0-2.0%) of patients, respectively, during the past year. Overall, 14.7% of patients (95%CI, 9.5-20.0%) received at least one intervention. Concurrent risk factors for osteoporosis, including smoking, alcoholism, advanced age, low body mass index, long duration of ADT, multiple comorbidities, history of fractures, and steroid use, were not independent predictors of having received interventions. However, bone metastasis was, with a hazard ratio of 5.6 (95%CI, 1.99-15.6%). Primary care physicians provided the greatest number of interventions and cancer-related specialists provided the fewest. The majority of patients with prostate carcinoma undergoing ADT did not receive interventions to prevent or treat osteoporosis. Having other concurrent risk factors for osteoporosis was not predictive of receiving these few interventions. (c) 2004 American Cancer Society.

Efficacy and safety of flexibly dosed brexpiprazole for the adjunctive treatment of major depressive disorder: a randomized, active-referenced, placebo-controlled study.

PubMed

Hobart, Mary; Skuban, Aleksandar; Zhang, Peter; Josiassen, Mette Krog; Hefting, Nanco; Augustine, Carole; Brewer, Claudette; Sanchez, Raymond; McQuade, Robert D

2018-04-01

To assess the efficacy, safety, and tolerability of brexpiprazole as adjunctive treatment in adults with major depressive disorder (MDD) and an inadequate response to prior antidepressant treatment (ADT). Patients with a current major depressive episode after prior treatment with 1-3 ADTs entered an 8- or 10-week prospective treatment phase in which they received double-blind placebo adjunct to open-label ADT. Inadequate responders were randomized (2:2:1) to brexpiprazole 2-3 mg/day, placebo, or quetiapine extended-release (XR) 150-300 mg/day, adjunct to the same ADT, for 6 weeks. The primary efficacy endpoint was the change from baseline (randomization) to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The key secondary efficacy endpoint was the change in Sheehan Disability Scale (SDS) mean score. Adjunctive brexpiprazole showed a greater improvement in MADRS total score than adjunctive placebo (least squares mean difference [95% confidence interval] = -1.48 [-2.56, -0.39]; p = .0078), whereas adjunctive quetiapine XR did not separate from placebo (-0.30 [-1.63, 1.04]; p = .66). Adjunctive brexpiprazole failed to separate from placebo on the SDS mean score (-0.23 [-0.52, 0.07]; p = .13), but did improve functioning on two of the three SDS items (family life and social life). The most frequent treatment-emergent adverse events in patients receiving brexpiprazole were akathisia (6.1%), somnolence (5.6%), and headache (5.6%). Adjunctive brexpiprazole 2-3 mg/day improved symptoms of depression compared with adjunctive placebo in patients with MDD and an inadequate response to ADTs, and was well tolerated with no unexpected side effects.

Role of Microsomal Retinol/Sterol Dehydrogenase-Like Short-Chain Dehydrogenases/Reductases in the Oxidation and Epimerization of 3α-Hydroxysteroids in Human Tissues

PubMed Central

Belyaeva, Olga V.; Chetyrkin, Sergei V.; Clark, Amy L.; Kostereva, Natalia V.; SantaCruz, Karen S.; Chronwall, Bibie M.; Kedishvili, Natalia Y.

2008-01-01

Allopregnanolone (ALLO) and androsterone (ADT) are naturally occurring 3α-hydroxysteroids that act as positive allosteric regulators of γ-aminobutyric acid type A receptors. In addition, ADT activates nuclear farnesoid X receptor and ALLO activates pregnane X receptor. At least with respect to γ-aminobutyric acid type A receptors, the biological activity of ALLO and ADT depends on the 3α-hydroxyl group and is lost upon its conversion to either 3-ketosteroid or 3β-hydroxyl epimer. Such strict structure-activity relationships suggest that the oxidation or epimerization of 3α-hydroxysteroids may serve as physiologically relevant mechanisms for the control of the local concentrations of bioactive 3α-hydroxysteroids. The exact enzymes responsible for the oxidation and epimerization of 3α-hydroxysteroids in vivo have not yet been identified, but our previous studies showed that microsomal nicotinamide adenine dinucleotide-dependent short-chain dehydrogenases/reductases (SDRs) with dual retinol/sterol dehydrogenase substrate specificity (RoDH-like group of SDRs) can oxidize and epimerize 3α-hydroxysteroids in vitro. Here, we present the first evidence that microsomal nicotinamide adenine dinucleotide-dependent 3α-hydroxysteroid dehydrogenase/epimerase activities are widely distributed in human tissues with the highest activity levels found in liver and testis and lower levels in lung, spleen, brain, kidney, and ovary. We demonstrate that RoDH-like SDRs contribute to the oxidation and epimerization of ALLO and ADT in living cells, and show that RoDH enzymes are expressed in tissues that have microsomal 3α-hydroxysteroid dehydrogenase/epimerase activities. Together, these results provide further support for the role of RoDH-like SDRs in human metabolism of 3α-hydroxysteroids and offer a new insight into the enzymology of ALLO and ADT inactivation. PMID:17289849

Role of microsomal retinol/sterol dehydrogenase-like short-chain dehydrogenases/reductases in the oxidation and epimerization of 3alpha-hydroxysteroids in human tissues.

PubMed

Belyaeva, Olga V; Chetyrkin, Sergei V; Clark, Amy L; Kostereva, Natalia V; SantaCruz, Karen S; Chronwall, Bibie M; Kedishvili, Natalia Y

2007-05-01

Allopregnanolone (ALLO) and androsterone (ADT) are naturally occurring 3alpha-hydroxysteroids that act as positive allosteric regulators of gamma-aminobutyric acid type A receptors. In addition, ADT activates nuclear farnesoid X receptor and ALLO activates pregnane X receptor. At least with respect to gamma-aminobutyric acid type A receptors, the biological activity of ALLO and ADT depends on the 3alpha-hydroxyl group and is lost upon its conversion to either 3-ketosteroid or 3beta-hydroxyl epimer. Such strict structure-activity relationships suggest that the oxidation or epimerization of 3alpha-hydroxysteroids may serve as physiologically relevant mechanisms for the control of the local concentrations of bioactive 3alpha-hydroxysteroids. The exact enzymes responsible for the oxidation and epimerization of 3alpha-hydroxysteroids in vivo have not yet been identified, but our previous studies showed that microsomal nicotinamide adenine dinucleotide-dependent short-chain dehydrogenases/reductases (SDRs) with dual retinol/sterol dehydrogenase substrate specificity (RoDH-like group of SDRs) can oxidize and epimerize 3alpha-hydroxysteroids in vitro. Here, we present the first evidence that microsomal nicotinamide adenine dinucleotide-dependent 3alpha-hydroxysteroid dehydrogenase/epimerase activities are widely distributed in human tissues with the highest activity levels found in liver and testis and lower levels in lung, spleen, brain, kidney, and ovary. We demonstrate that RoDH-like SDRs contribute to the oxidation and epimerization of ALLO and ADT in living cells, and show that RoDH enzymes are expressed in tissues that have microsomal 3alpha-hydroxysteroid dehydrogenase/epimerase activities. Together, these results provide further support for the role of RoDH-like SDRs in human metabolism of 3alpha-hydroxysteroids and offer a new insight into the enzymology of ALLO and ADT inactivation.

Effect of daily fluctuations in ambient temperature on reproductive failure traits of Landrace and Yorkshire sows under Thai tropical environmental conditions.

PubMed

Jaichansukkit, Teerapong; Suwanasopee, Thanathip; Koonawootrittriron, Skorn; Tummaruk, Padet; Elzo, Mauricio A

2017-03-01

The aim of this study was to determine the effects of daily ranges and maximum ambient temperatures, and other risk factors on reproductive failure of Landrace (L) and Yorkshire (Y) sows under an open-house system in Thailand. Daily ambient temperatures were added to information on 35,579 litters from 5929 L sows and 1057 Y sows from three commercial herds. The average daily temperature ranges (ADT) and the average daily maximum temperatures (PEAK) in three gestation periods from the 35th day of gestation to parturition were classified. The considered reproductive failure traits were the occurrences of mummified fetuses (MM), stillborn piglets (STB), and piglet death losses (PDL) and an indicator trait for number of piglets born alive below the population mean (LBA). A multiple logistic regression model included farrowing herd-year-season (HYS), breed group of sow (BG), parity group (PAR), number of total piglets born (NTB), ADT1, ADT2, ADT3, PEAK1, PEAK2, and PEAK3 as fixed effects, while random effects were animal, repeated observations, and residual. Yorkshire sows had a higher occurrence of LBA than L sows (P = 0.01). The second to fifth parities sows had lower reproductive failures than other parities. The NTB regression coefficients of log-odds were positive (P < 0.01) for all traits. Narrower ranges of ADT3 increased the occurrence of MM, STB, and PDL (P < 0.01), while higher PEAK3 increased the occurrence of MM, STB, PDL, and LBA (P < 0.001). To reduce the risk of reproductive failures, particularly late in gestation, producers would need to closely monitor their temperature management strategies.

The Astronomy Diagnostic Test: Comparing Your Class to Others

NASA Astrophysics Data System (ADS)

Hufnagel, B.; Deming, G.

1999-05-01

A standard diagnostic test can be a powerful tool to assess the conceptual understanding of students, as has been proven for undergraduate physics instruction over the last ten years (e.g., E.F. Redish and R.N. Steinberg 1999, Physics Today, 52:1, 24). If you are now using, or are considering adopting, a more interactive teaching style such as that used by Eric Mazur (Peer Instruction: a User's Manual, [Prentice-Hall: 1997]) or Michael Zeilik and his collaborators (1997, AJP, 65:12, 987), you may want to use a standard diagnostic test designed for undergraduate astronomy classes. Details of the validation of the ADT are at Slater et al., also presented in this session. A comparative database of ADT scores, by class and by question, can help the instructor assess student preparedness and the effectiveness of alternative teaching methods. In the spring of 1999, 19 astronomy instructors at 7 state universities, 4 community colleges, 4 liberal arts schools, 1 woman's college and 1 technical university across the USA gave the ADT to their classes once at the beginning of the course, and again at the end of the course. The average pre-course ADT scores by class from these ~ 1000 students show two surprising results: the conceptual understanding of introductory classes is about the same (34%) regardless of type of school, geographic location, or average student age. However, there is a significant gender difference, with females scoring an average of 29% and males 39%, with the standard errors both less than 1%. The Astronomy Diagnostic Test (ADT) and its comparative by-class database will be available at the National Institute for Science Education (NISE) website after 1 June 1999. This research was supported by the National Science Foundation through Grant DGE-9714489, and by the generosity of the participating astronomy instructors.

Conserved charge of a gravity theory with p -form gauge fields and its property under Kaluza-Klein reduction

NASA Astrophysics Data System (ADS)

Peng, Jun-Jin

2017-05-01

In this paper, we investigate the conserved charges of generally diffeomorphism invariant gravity theories with a wide variety of matter fields, particularly of the theories with multiple scalar fields and p -form potentials, in the context of the off-shell generalized Abbott-Deser-Tekin (ADT) formalism. We first construct a new off-shell ADT current that consists of the terms for the variation of a Killing vector and expressions of the field equations as well as the Lie derivative of a surface term with respect to the Killing vector within the framework of generally diffeomorphism invariant gravity theories involving various matter fields. After deriving the off-shell ADT potential corresponding to this current, we propose a formula of conserved charges for these theories. Next, we derive the off-shell ADT potential associated with the generic Lagrangian that describes a large range of gravity theories with a number of scalar fields and p -form potentials. Finally, the properties of the off-shell generalized ADT charges for the theory of Einstein gravity and the gravity theories with a single p -form potential are investigated by performing Kaluza-Klein dimensional reduction along a compactified direction. The results indicate that the charge contributed by all the fields in the lower-dimensional theory is equal to that of the higher-dimensional one at mathematical level with the hypothesis that the higher-dimensional spacetime allows for the existence of the compactified dimension. In order to illustrate our calculations, the mass and angular momentum for the five-dimensional rotating Kaluza-Klein black holes are explicitly evaluated as an example.

Plumbagin improves the efficacy of androgen deprivation therapy in prostate cancer: A pre-clinical study.

PubMed

Abedinpour, Parisa; Baron, Véronique T; Chrastina, Adrian; Rondeau, Gaelle; Pelayo, Jennifer; Welsh, John; Borgström, Per

2017-12-01

Plumbagin is a candidate drug for the treatment of prostate cancer. Previous observations indicated that it may improve the efficacy of androgen deprivation therapy (ADT). This study evaluates the effectiveness of treatment with combinations of plumbagin and alternative strategies for ADT in mouse models of prostate cancer to support its clinical use. Plumbagin was administered per oral in a new sesame oil formulation. Standard toxicology studies were performed in rats. For tumor growth studies, mouse prostate cancer cell spheroids were placed on top of grafted prostate tissue in a dorsal chamber and allowed to form tumors. Mice were separated in various treatment groups and tumor size was measured over time by intra-vital microscopy. Survival studies were done in mice after injection of prostate cancer cells in the prostate of male animals. Androgen receptor (AR) levels were analyzed by Western blot from prostate cancer cells treated with plumbagin. Plumbagin caused a decrease in AR levels in vitro. In mice, plumbagin at 1 mg/kg in sesame oil displayed low toxicity and caused a 50% tumor regression when combined with castration. The combination of plumbagin with various forms of chemical ADT including treatment with a GnRH receptor agonist, a GnRH receptor antagonist, or CYP17A1 inhibitors, outperformed ADT alone, increasing mouse survival compared to the standard regimen of castration alone. In contrast, the combination of plumbagin with AR antagonists, such as bicalutamide and enzalutamide, showed no improvement over AR antagonists alone. Thus, plumbagin is effective in combination with drugs that prevent the synthesis of testosterone or its conversion to dihydrotestosterone, but not with drugs that bind to AR. Plumbagin significantly improves the effect of ADT drugs currently used in the clinic, with few side effects in mice. © 2017 Wiley Periodicals, Inc.

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial.

PubMed

Kyriakopoulos, Christos E; Chen, Yu-Hui; Carducci, Michael A; Liu, Glenn; Jarrard, David F; Hahn, Noah M; Shevrin, Daniel H; Dreicer, Robert; Hussain, Maha; Eisenberger, Mario; Kohli, Manish; Plimack, Elizabeth R; Vogelzang, Nicholas J; Picus, Joel; Cooney, Matthew M; Garcia, Jorge A; DiPaola, Robert S; Sweeney, Christopher J

2018-04-10

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m 2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P < .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

Mass and angular momentum of black holes in low-energy heterotic string theory

NASA Astrophysics Data System (ADS)

Peng, Jun-Jin

2016-04-01

We investigate conserved charges in the low-energy effective field theory describing heterotic string theory. Starting with a general Lagrangian that consists of a metric, a scalar field, a vector gauge field, together with a two-form potential, we derive off-shell Noether potentials of the Lagrangian and generalize the Abbott-Deser-Tekin (ADT) formalism to the off-shell level by establishing one-to-one correspondence between the ADT potential and the off-shell Noether potential. It is proved that the off-shell generalized ADT formalism is conformally invariant. Then, we apply the formulation to compute mass and angular momentum of the four-dimensional Kerr-Sen black hole and the five-dimensional rotating charged black string in the string frame without a necessity to transform the metrics into the Einstein frame.

[Neoadjuvant therapy for esophageal cancer - indication and efficacy].

PubMed

Kato, Ken; Hamaguchi, Tetsuya; Yamada, Yasuhide; Shirao, Kuniaki; Shimada, Yasuhiro

2007-10-01

Some approaches such as adjuvant chemotherapy, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been tried to improve the efficacy of treatment for resectable esophageal cancer patients. The usefullness of neoadjuvant chemotherapy, has remained a matter of controversy. However, there is a report from JCOG9907 in Japan that two courses of neoadjuvant 5-FU/CDDP improved the survival of esophageal squamous cell cancer patients. Neoadjuvant chemoradiotherapy has not had a consistent evaluation because of the varying results of each trial. But from the results of meta-analysis and CALGB9781, the neoadjuvant chemoradiotherapy called "trimodality therapy" has been a standard treatment in the United States. We should evaluate whether there would be similar effectiveness in Japan, where the histology and operative approach are different. Some approaches such as DNA microarray and proteomics, which can predict the treatment effect, are being tried.

Major surgery in an osteosarcoma patient refusing blood transfusion: case report.

PubMed

Dhanoa, Amreeta; Singh, Vivek A; Shanmugam, Rukmanikanthan; Rajendram, Raja

2010-11-08

We describe an unusual case of osteosarcoma in a Jehovah's Witness patient who underwent chemotherapy and major surgery without the need for blood transfusion. This 16-year-old girl presented with osteosarcoma of the right proximal tibia requiring proximal tibia resection, followed by endoprosthesis replacement. She was successfully treated with neoadjuvant chemotherapy and surgery with the support of haematinics, granulocyte colony-stimulating factor, recombinant erythropoietin and intraoperative normovolaemic haemodilution. This case illustrates the importance of maintaining effective, open communication and exploring acceptable therapeutic alternative in the management of these patients, whilst still respecting their beliefs.

C-reactive protein for the early prediction of anastomotic leak after esophagectomy in both neoadjuvant and non-neoadjuvant therapy case: a propensity score matching analysis.

PubMed

Park, Jae Kil; Kim, Jae Jun; Moon, Seok Whan

2017-10-01

Anastomotic leak is one of most significant causes of mortality after esophagectomy. Therefore, it is clinically valuable to detect anastomotic leak early after esophagectomy in esophageal cancer. The purpose of this study is to investigate the associations between routine postoperative laboratory findings and anastomotic leak and to analyze the laboratory findings to find out an independent predictive marker for anastomotic leak. In addition, this study compares cases treated with neoadjuvant therapy (NT) and those without (non-NT). We retrospectively assessed the medical records of 201 consecutive cases that met this study's criteria from January 2009 to December 2016. All patients underwent curative and complete esophagectomy for intra-thoracic esophageal cancer. We compiled and analyzed routine laboratory findings from the day before surgery to the eighth postoperative day on a daily basis. Routine laboratory tests consisted of 26 separate tests, including complete blood cell counts, blood chemistries, as well as erythrocyte sedimentation rate and C-reactive protein (CRP). Barium esophagogram with chest computed tomography (CT) was performed on the seventh postoperative day to evaluate the presence of an anastomotic leak. A total of 45 of 201 patients underwent NT. Anastomotic leaks were found in 23 (11.4%) of 201 patients (8 patients in NT and 15 patients in non-NT). White blood cell (WBC) from the second postoperative day (P=0.031, P=0.006, P=0.007, P=0.007, P=0.041, and P=0.003, respectively) and CRP from the third postoperative day (P=0.012, P<0.001, P=0.014, P<0.001, P=0.001, and P=0.006, respectively) were associated with anastomotic leak in non-NT; however, only CRP on the third, fifth, sixth, and seventh postoperative days (P=0.041, P=0.037, P=0.002, and P=0.003, respectively) was associated with anastomotic leak in NT. The CRP level on the third postoperative day was a significant independent predictive marker of anastomotic leak (P=0.041, odd ratio (OR) 1.056, 95% confidential interval (CI): 1.002-1.113) and had a significant diagnostic cutoff value for the development of anastomotic leak (non-NT: cutoff value 17.12 mg/dL, sensitivity 69.2%, specificity 78.1%, P<0.001, area 0.822; NT: cutoff value 16.42 mg/dL, sensitivity 80.0%, specificity 70.0%, P=0.042, area 0.7104). There were divergent laboratory findings reflective of anastomotic leak between patients who underwent NT and those who did not. The CRP level on the third postoperative day had a significant cutoff value for early detection of anastomotic leak after esophagectomy in both NT and non-NT groups.

GEMMs shine a light on resistance to androgen deprivation therapy for prostate cancer.

PubMed

Karantanos, Theodoros; Thompson, Timothy C

2013-07-08

Androgen deprivation therapy (ADT) for advanced prostate cancer inexorably leads to resistance, and clinically useful biomarkers are lacking. The value of genetically engineered mice for coclinical studies is clearly demonstrated in a recent publication that reveals XAF1, XIAP, and SRD5A1 as novel predictive biomarkers and therapeutic targets for ADT resistance. Copyright © 2013 Elsevier Inc. All rights reserved.

Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study.

PubMed

Doria, Carlo; Leali, Paolo Tranquilli; Solla, Federico; Maestretti, Gianluca; Balsano, Massimo; Scarpa, Robero Mario

2016-01-01

Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. The best defense against osteoporosis in prostate cancer is to identify patients with a high risk for fracture during the first clinical visit, select an effective anti-osteoporosis agent, and advise the patient to change his lifestyle and diet to prevent further bone loss. New agents include denosumab, a human monoclonal antibody that inhibits the RANK ligand (RANKL). RANKL promotes the formation, activity, and survival of osteoclasts and, thus, supports the breakdown of bone. This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT in prostate cancer patients in three European countries (Italy, France, Switzerland). In this 24-month observation study we enrolled 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer. All patients aged ≥55 years and had a dual-energy X-ray absorptiometry (DEXA) T-score <-1.0 (hip or spine, measured within last 2 years) and ≥ 1 fragility fracture. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg weekly) for 2 years. All patient received supplemental vitamin D (600 IU per day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), Bone Mineral Density (BMD), fracture incidence, Visual Analogue Scale (VAS) score for back pain, and Short Form-8 (SF-8TM) health survey score for health-related quality of life (HRQoL). Percent changes from baseline in BTMs and BMD were assessed using the paired t test; a P-value 0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24 months were 5.6% with denosumab vs -1.1% with alendronate (P<0.001). New vertebral fractures developed in fewer patients in the denosumab group than in the alendronate group during the 24-month period, although this difference was not significant (P=0.10). Back pain significantly (P<0.001) improved from baseline at all time points during the study in both study groups. SF-8 health survey scores significantly improved following treatment with both drugs. Incidence of adverse drug reactions were similar in both groups. In our study denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures.

Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study

PubMed Central

Doria, Carlo; Leali, Paolo Tranquilli; Solla, Federico; Maestretti, Gianluca; Balsano, Massimo; Scarpa, Robero Mario

2016-01-01

Summary Introduction Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. The best defense against osteoporosis in prostate cancer is to identify patients with a high risk for fracture during the first clinical visit, select an effective anti-osteoporosis agent, and advise the patient to change his lifestyle and diet to prevent further bone loss. New agents include denosumab, a human monoclonal antibody that inhibits the RANK ligand (RANKL). RANKL promotes the formation, activity, and survival of osteoclasts and, thus, supports the breakdown of bone. Purpose This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT in prostate cancer patients in three European countries (Italy, France, Switzerland). Patients and methods In this 24-month observation study we enrolled 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer. All patients aged ≥55 years and had a dual-energy X-ray absorptiometry (DEXA) T-score <−1.0 (hip or spine, measured within last 2 years) and ≥ 1 fragility fracture. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg weekly) for 2 years. All patient received supplemental vitamin D (600 IU per day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), Bone Mineral Density (BMD), fracture incidence, Visual Analogue Scale (VAS) score for back pain, and Short Form-8 (SF-8TM) health survey score for health-related quality of life (HRQoL). Percent changes from baseline in BTMs and BMD were assessed using the paired t test; a P-value 0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24 months were 5.6% with denosumab vs −1.1% with alendronate (P<0.001). New vertebral fractures developed in fewer patients in the denosumab group than in the alendronate group during the 24-month period, although this difference was not significant (P=0.10). Back pain significantly (P<0.001) improved from baseline at all time points during the study in both study groups. SF-8 health survey scores significantly improved following treatment with both drugs. Incidence of adverse drug reactions were similar in both groups. Conclusion In our study denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures. PMID:28228781

New players for advanced prostate cancer and the rationalisation of insulin-sensitising medication.

PubMed

Gunter, Jennifer H; Sarkar, Phoebe L; Lubik, Amy A; Nelson, Colleen C

2013-01-01

Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of "old players" for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer.

HIFU therapy for patients with high risk prostate cancer

NASA Astrophysics Data System (ADS)

Solovov, V. A.; Vozdvizhenskiy, M. O.; Matysh, Y. S.

2017-03-01

Objectives. Patients with high-risk prostate cancer undergoing radical prostatectomy, external beam radiation therapy (EBRT) combined with androgen deprivation therapy (ADT) or ADT alone. The widely accepted definition of high-risk prostate was first proposed by D'Amico based on a pretreatment Gleason score of ≥8, clinical stage T3, PSA level ≥20 ng/mL. There is no trial that compares traditional methods of treatment of such patients with HIFU therapy. Here we explored the effectiveness of the HIFU in multimodal treatment for patients with high risk prostate cancer. Materials & Methods. 701 patients with high risk prostate cancer were treated in our center between September 2007 and December 2013. Gleason score were 8-10, stage T3N0M0, age 69 (58-86) years, mean PSA before treatment 43.3 (22.1-92.9) ng/ml, mean prostate volume - 59.3 (38-123) cc. 248 patients were treated by HIFU. We compare this group of patients with patients who undertook EBRT: number 196, and ADT: number 257. Mean follow-up time 58 months (6-72). Results. The 5-year overall survival rates in patients after HIFU were 73.8 %, after EBRT - 63.0 % and after ADT - 18.1%. Conclusions. Our experience showed that HIFU therapy in combined treatment were successful for high risk prostate cancer.

Application of δ recycling to electron automated diffraction tomography data from inorganic crystalline nanovolumes.

PubMed

Rius, Jordi; Mugnaioli, Enrico; Vallcorba, Oriol; Kolb, Ute

2013-07-01

δ Recycling is a simple procedure for directly extracting phase information from Patterson-type functions [Rius (2012). Acta Cryst. A68, 399-400]. This new phasing method has a clear theoretical basis and was developed with ideal single-crystal X-ray diffraction data. On the other hand, introduction of the automated diffraction tomography (ADT) technique has represented a significant advance in electron diffraction data collection [Kolb et al. (2007). Ultramicroscopy, 107, 507-513]. When combined with precession electron diffraction, it delivers quasi-kinematical intensity data even for complex inorganic compounds, so that single-crystal diffraction data of nanometric volumes are now available for structure determination by direct methods. To check the tolerance of δ recycling to missing data-collection corrections and to deviations from kinematical behaviour of ADT intensities, δ recycling has been applied to differently shaped nanocrystals of various inorganic materials. The results confirm that it can phase ADT data very efficiently. In some cases even more complete structure models than those derived from conventional direct methods and least-squares refinement have been found. During this study it has been demonstrated that the Wilson-plot scaling procedure is largely insensitive to sample thickness variations and missing absorption corrections affecting electron ADT intensities.

Surgery for oesophageal cancer at Galway University Hospital 1993-2008.

PubMed

Chang, K H; McAnena, O J; Smith, M J; Salman, R R; Khan, M F; Lowe, D

2010-12-01

Surgical volume and outcome remain controversial in the management of oesophageal cancer. To assess the outcome of oesophagectomy for cancer at Galway University Hospital (GUH). Between 1994 and 2008, patients who underwent oesophagectomy were analysed. During the study period, 126 oesophagectomies were performed for cancer. The average surgeon volume was 9 cases per year. The 30-day and overall in-hospital mortality rates were 6.3 and 7.9%, respectively. Restructuring of our critical care services has led to a reduction in 30-day mortality from 8.2 to 5.1%. The use of neoadjuvant chemoradiotherapy has increased from 17 to 35% during the study period. In patients who underwent resection, the 3 and 5-year overall survival rates were 45 and 29%, respectively. Operative morbidity and mortality at GUH are comparable with worldwide outcomes. Improved resources and national restructuring of cancer services have significantly improved the quality of care and outcomes of patients.

Survival After Neoadjuvant and Adjuvant Treatments Compared to Surgery Alone for Resectable Esophageal Carcinoma: A Network Meta-analysis.

PubMed

Pasquali, Sandro; Yim, Guang; Vohra, Ravinder S; Mocellin, Simone; Nyanhongo, Donald; Marriott, Paul; Geh, Ju Ian; Griffiths, Ewen A

2017-03-01

This network meta-analysis compared overall survival after neoadjuvant or adjuvant chemotherapy (CT), radiotherapy (RT), or combinations of both (chemoradiotherapy, CRT) or surgery alone to identify the most effective approach. The optimal treatment for resectable esophageal cancer is unknown. A search for randomized controlled trials reporting on neoadjuvant and adjuvant therapies was conducted. Using a network meta-analysis, treatments were ranked based on their effectiveness for improving survival. In 33 eligible randomized controlled trials, 6072 patients were randomized to receive either surgery alone (N = 2459) or neoadjuvant CT (N = 1332), RT (N = 58), and CRT (N = 1196) followed by surgery or surgery followed by adjuvant CT (N = 542), RT (N = 383), and CRT (N = 102). Twenty-one comparisons were generated. Neoadjuvant CRT followed by surgery compared with surgery alone was the only treatment to significantly improve survival [hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.68-0.87]. When trials were grouped considering neoadjuvant and adjuvant therapies and surgery alone, neoadjuvant therapies combined with surgery compared with surgery alone showed a survival advantage (HR = 0.83, 95% CI 0.76-0.90), whereas surgery along with adjuvant therapies showed no significant survival advantage (HR = 0.87, 95% CI 0.67-1.14). A subgroup analysis of neoadjuvant therapies showed a superior effectiveness of neoadjuvant CRT and surgery compared with surgery alone (HR = 0.77, 95% CI 0.68-0.87). This network meta-analysis showed neoadjuvant CRT followed by surgery to be the most effective strategy in improving survival of resectable esophageal cancer. Resources should be focused on developing the most effective neoadjuvant CRT regimens for both adenocarcinomas and squamous cell carcinomas of the esophagus.

Oncological outcomes from trimodality therapy receiving definitive doses of neoadjuvant chemoradiation (≥60 Gy) and factors influencing consideration for surgery in stage III non-small cell lung cancer.

PubMed

Vyfhuis, Melissa A L; Bhooshan, Neha; Burrows, Whitney M; Turner, Michelle; Suntharalingam, Mohan; Donahue, James; Nichols, Elizabeth M; Feliciano, Josephine; Bentzen, Søren M; Badiyan, Shahed; Carr, Shamus R; Friedberg, Joseph; Simone, Charles B; Edelman, Martin J; Feigenberg, Steven J; Mohindra, Pranshu

2017-01-01

Guidelines for locally advanced non-small cell lung cancer (LA-NSCLC) recommend definitive chemoradiation therapy (CRT) for cN2-N3 disease, reserving surgery for patients with minimal nodal involvement at presentation. The current literature suggests that surgery after CRT for stage III NSCLC can improve freedom-from-recurrence (FFR) but has not consistently demonstrated an improvement in overall survival, perhaps partly due to the low (45-50.4 Gy) preoperative doses delivered that result in low rates of mediastinal nodal clearance. We therefore analyzed factors associated with trimodality therapy receipt and determined outcomes in patients with LA-NSCLC who were treated with definitive doses (≥60 Gy) of neoadjuvant CRT prior to surgery. We retrospectively analyzed 355 consecutive patients with LA-NSCLC who were treated with curative intent between January 2000 and December 2013. The Kaplan-Meier method was used to estimate the overall survival and FFR of patients who were initially planned to receive trimodality treatment but never underwent surgery (unplanned bimodality) compared with those who were never considered to be surgical candidates (planned bimodality) and those who underwent surgical resection after CRT (trimodality). Cox proportional hazards regression with forward selection was used for multivariate analyses, and the Fisher exact test was used to test contingency tables. Patients who received trimodality therapy had a longer median survival than those with unplanned or planned bimodality therapy at 59.9, 20.1, and 17.3 months, respectively ( P < .001). The survival benefit with surgery persisted in patients with stage IIIB ( P < .001) and N3 ( P = .010) nodal disease when mediastinal nodal clearance was achieved. FFR was also improved with surgical resection ( P = .001). Race ( P < .001), stage ( P < .001), performance status ( P < .001), age ( P < .001), and diagnosis of chronic obstructive pulmonary disease ( P = .009) were significant indicators that influenced both the decision to initially choose trimodality therapy at consultation and to actually perform surgical resection. Trimodality treatment significantly improves survival and FFR in patients with LA-NSCLC when definitive doses of radiation with neoadjuvant chemotherapy are employed. We identified important demographic features that predict the use of surgical intervention in patients with stage III NSCLC.

[Neoadjuvant chemotherapy for advanced gastric cancer using FLEP therapy].

PubMed

Mochizuki, F; Fujii, M; Kasakura, Y; Kochi, M; Imai, S; Eguchi, T; Tsuneda, Y; Kanamori, N; Kaiga, T; Kobayashi, M

2000-10-01

Combination chemotherapy with 5-FU, LV, ETP and CDDP (FLEP) for advanced gastric cancer uses a combination of regional and systemic delivery for the control of both local and disseminated disease in the intra- and extra-abdominal regions. We performed this regimen as neoadjuvant chemotherapy (NAC). Fifteen patients with unresectable primary advanced gastric cancer underwent FLEP. The treatment regimen was 5-FU at 370 mg/m2, LV at 30 mg/body (days 1 to 5, i.v. 24 h) and ETP and CDDP each at 70 mg/m2 (days 7 and 21, ia 2 h). This regimen was repeated every four weeks. The overall response rate was 46.7% (7/15), and the 50% and median survival times were 11.43 and 12.35 months, respectively. The adverse events were Grade 3 leukocytopenia, Grade 3 thrombocytopenia, and Grade 3 stomatitis in 20.0%, 13.3%, and 6.7% of the patients, respectively. The 50% and median survival time overall were 11.43 and 12.35 months, respectively. Of the 15 NAC patients, curability B patients showed a statistically higher survival rate than curability C and unresected patients. In conclusion, FLEP was effective for unresectable advanced gastric cancer.

Basal (18)F-FDG PET/CT as a predictive biomarker of tumor response for neoadjuvant therapy in breast cancer.

PubMed

García Vicente, A M; Soriano Castrejón, A; Pruneda-González, R E; Fernández Calvo, G; Muñoz Sánchez, M M; Álvarez Cabellos, R; Espinosa Aunión, R; Relea Calatayud, F

2016-01-01

To explore the relation between tumor kinetic assessed by (18)F-FDG PET and final neoadjuvant chemotherapy (NC) response within a molecular phenotype perspective. Prospective study included 144 women with breast cancer. All patients underwent a dual-time point (18)F-FDG PET/CT previous to NC. The retention index (RI), between SUV-1 and SUV-2 was calculated. Molecular subtypes were re-grouped in low, intermediate and high-risk biological phenotypes. After NC, all residual primary tumor specimens were histopathologically classified in tumor regression grades (TRG) and response groups. The relation between SUV-1, SUV-2 and RI with the TRG and response groups was evaluated in all molecular subtypes and in accordance with the risk categories. Responder's lesions showed significant greater SUVmax compared to non-responders. The RI value did not show any significant relation with response. Attending to molecular phenotypes, statistical differences were observed with greater SUV for responders having high-risk molecular subtypes. Glycolytic tumor characteristics showed a significant correlation with NC response and dependence of risk phenotype. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Efficacy and Safety of Neoadjuvant Treatment with Bevacizumab, Liposomal Doxorubicin, Cyclophosphamide and Paclitaxel Combination in Locally/Regionally Advanced, HER2-Negative, Grade III at Premenopausal Status Breast Cancer: A Phase II Study.

PubMed

Tampaki, Ekaterini C; Tampakis, Athanasios; Alifieris, Constantinos E; Krikelis, Dimitrios; Pazaiti, Anastasia; Kontos, Michalis; Trafalis, Dimitrios T

2018-05-09

In the era of personalized therapy, targeted treatment in specific patient populations is mandated. We evaluated the efficacy and safety of neoadjuvant treatment on locally advanced breast cancer (LABC) with a monoclonal agent against vascular endothelial growth factor (VEGF), bevacizumab plus chemotherapy combination of liposomal doxorubicin, cyclophosphamide and paclitaxel (PLAC-B). Patients enrolled were at premenopausal status and characterized by human epidermal growth factor receptor 2 (HER2)-negative, hormone-receptor positive (estrogen receptor/progesterone receptor-positive [ER/PR+]) or triple-negative (TNBC), LABC (T > 3 cm), with high-grade ductal carcinoma. Patients had to have a measurable disease and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, with adequate hematologic, renal, and hepatic function. Patients received intravenous liposomal doxorubicin 30 mg/m 2 , cyclophosphamide 600 mg/m 2 , paclitaxel 120 mg/m 2 , and bevacizumab 8 mg/kg on day 1 of 15-day cycles for four cycles (four administrations as neoadjuvant treatment). The primary endpoint was complete clinical (cCR) and pathologic (pCR) response rates, while secondary endpoints included safety, breast-conserving surgery (BCS) conversion rate, and disease-free survival (DFS). Sixty-two women were enrolled; 20 were ER/PR+ and 42 had TNBC. All underwent surgery, six received mastectomy, and 56 (90.3%) received BCS, with an equal conversion rate from initial indication for mastectomy. cCR was 25.8%. pCR in the breast and axilla occurred in 24 patients (38.7%). pCR was 42.9% for TNBC and 30% for ER/PR+. Hematologic adverse events (AEs) included neutropenia (74.2% total; 22.6% grade 3 [G3]) and febrile neutropenia (6.5% G3); non-hematologic G3 AEs included nausea (6.5%), mucositis (9.7%), and infection (3.2%), all of which were managed without negative sequelae. Over a 3-year follow-up, all patients were alive and DFS was 87.1%. PLAC-B as neoadjuvant treatment of this subpopulation with TNBC and ER/PR+ patients is effective and safe. Further studies are necessitated.

A Population-based Study on Lymph Node Retrieval in Patients with Esophageal Cancer: Results from the Dutch Upper Gastrointestinal Cancer Audit.

PubMed

van der Werf, L R; Dikken, J L; van Berge Henegouwen, M I; Lemmens, V E P P; Nieuwenhuijzen, G A P; Wijnhoven, B P L

2018-05-01

For esophageal cancer, the number of retrieved lymph nodes (LNs) is often used as a quality indicator. The aim of this study is to analyze the number of retrieved LNs in The Netherlands, assess factors associated with LN yield, and explore the association with short-term outcomes. This is a population-based study on lymph node retrieval in patients with esophageal cancer, presenting results from the Dutch Upper Gastrointestinal Cancer Audit. For this retrospective national cohort study, patients with esophageal carcinoma who underwent esophagectomy between 2011 and 2016 were included. The primary outcome was the number of retrieved LNs. Univariable and multivariable regression analyses were used to test for association with ≥ 15 LNs. 3970 patients were included. Between 2011 and 2016, the median number of LNs increased from 15 to 20. Factors independently associated with ≥ 15 LNs were: 0-10 kg preoperative weight loss (versus: unknown weight loss, odds ratio [95% confidence interval]: 0.71 [0.57-0.88]), Charlson score 0 (versus: Charlson score 2: 0.76 [0.63-0.92]), cN2 category (reference: cN0, 1.32 [1.05-1.65]), no neoadjuvant therapy and neoadjuvant chemotherapy (reference: neoadjuvant chemoradiotherapy, 1.73 [1.29-2.32] and 2.15 [1.54-3.01]), minimally invasive transthoracic (reference: open transthoracic, 1.46 [1.15-1.85]), open transthoracic (versus open and minimally invasive transhiatal, 0.29 [0.23-0.36] and 0.43 [0.32-0.59]), hospital volume of 26-50 or > 50 resections/year (reference: 0-25, 1.94 [1.55-2.42] and 3.01 [2.36-3.83]), and year of surgery [reference: 2011, odds ratios (ORs) 1.48, 1.53, 2.28, 2.44, 2.54]. There was no association of ≥ 15 LNs with short-term outcomes. The number of LNs retrieved increased between 2011 and 2016. Weight loss, Charlson score, cN category, neoadjuvant therapy, surgical approach, year of resection, and hospital volume were all associated with increased LN yield. Retrieval of ≥ 15 LNs was not associated with increased postoperative morbidity/mortality.

YKL-40/c-Met expression in rectal cancer biopsies predicts tumor regression following neoadjuvant chemoradiotherapy: a multi-institutional study.

PubMed

Senetta, Rebecca; Duregon, Eleonora; Sonetto, Cristina; Spadi, Rossella; Mistrangelo, Massimiliano; Racca, Patrizia; Chiusa, Luigi; Munoz, Fernando H; Ricardi, Umberto; Arezzo, Alberto; Cassenti, Adele; Castellano, Isabella; Papotti, Mauro; Morino, Mario; Risio, Mauro; Cassoni, Paola

2015-01-01

Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, p< 0.01 and p = 0.006, respectively). Thirty of the 32 biopsies co-expressing both markers had partial or absent tumor response (TRG 2-5), strengthening their positive predictive value (94%). The exclusive predictive role of YKL-40 and c-Met was confirmed using a multivariate analysis (p = 0.004 and p = 0.007 for YKL-40 and c-Met, respectively). TRG was the sole morphological parameter associated with poor outcome. c-Met and YKL-40 expression is a reliable predictor of partial/absent response to neoadjuvant CRT in rectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.

Anastomotic Complications After Ivor Lewis Esophagectomy in Patients Treated With Neoadjuvant Chemoradiation Are Related to Radiation Dose to the Gastric Fundus

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

Vande Walle, Caroline; Ceelen, Wim P., E-mail: wim.ceelen@ugent.be; Boterberg, Tom

2012-03-01

Purpose: Neoadjuvant chemoradiation (CRT) is increasingly used in locally advanced esophageal cancer. Some studies have suggested that CRT results in increased surgical morbidity. We assessed the influence of CRT on anastomotic complications in a cohort of patients who underwent CRT followed by Ivor Lewis esophagectomy. Patients and Methods: Clinical and pathologic data were collected from all patients treated with neoadjuvant CRT (36 Gy combined with 5-fluorouracil and cisplatin) followed by Ivor Lewis esophagectomy. On the radiotherapy (RT) planning computed tomography scans, normal tissue volumes were drawn encompassing the proximal esophageal region and the gastric fundus. Within these volumes, dose-volume histogramsmore » were analyzed to generate the total dose to 50% of the volume (D{sub 50}). We studied the ability of the D{sub 50} to predict anastomotic complications (leakage, ischemia, or stenosis). Dose limits were derived using receiver operating characteristics analysis. Results: Fifty-four patients were available for analysis. RT resulted in either T or N downstaging in 51% of patients; complete pathologic response was achieved in 11%. In-hospital mortality was 5.4%, and major morbidity occurred in 36% of patients. Anastomotic complications (AC) developed in 7 patients (13%). No significant influence of the D{sub 50} on the proximal esophagus was noted on the anastomotic complication rate. The median D{sub 50} on the gastric fundus, however, was 33 Gy in patients with AC and 18 Gy in patients without AC (p = 0.024). Using receiver operating characteristics analysis, the D{sub 50} limit on the gastric fundus was defined as 29 Gy. Conclusions: In patients undergoing neoadjuvant CRT followed by Ivor Lewis esophagectomy, the incidence of AC is related to the RT dose on the gastric fundus but not to the dose received by the proximal esophagus. When planning preoperative RT, efforts should be made to limit the median dose on the gastric fundus to 29 Gy with a V{sub 30} below 40%.« less

BioInt: an integrative biological object-oriented application framework and interpreter.

PubMed

Desai, Sanket; Burra, Prasad

2015-01-01

BioInt, a biological programming application framework and interpreter, is an attempt to equip the researchers with seamless integration, efficient extraction and effortless analysis of the data from various biological databases and algorithms. Based on the type of biological data, algorithms and related functionalities, a biology-specific framework was developed which has nine modules. The modules are a compilation of numerous reusable BioADTs. This software ecosystem containing more than 450 biological objects underneath the interpreter makes it flexible, integrative and comprehensive. Similar to Python, BioInt eliminates the compilation and linking steps cutting the time significantly. The researcher can write the scripts using available BioADTs (following C++ syntax) and execute them interactively or use as a command line application. It has features that enable automation, extension of the framework with new/external BioADTs/libraries and deployment of complex work flows.

Auditory discrimination therapy (ADT) for tinnitus management.

PubMed

Herraiz, C; Diges, I; Cobo, P

2007-01-01

Auditory discrimination training (ADT) designs a procedure to increase cortical areas responding to trained frequencies (damaged cochlear areas with cortical misrepresentation) and to shrink the neighboring over-represented ones (tinnitus pitch). In a prospective descriptive study of 27 patients with high frequency tinnitus, the severity of the tinnitus was measured using a visual analog scale (VAS) and the tinnitus handicap inventory (THI). Patients performed a 10-min auditory discrimination task twice a day during one month. Discontinuous 4 kHz pure tones were mixed randomly with short broadband noise sounds through an MP3 system. After the treatment mean VAS scores were reduced from 5.2 to 4.5 (p=0.000) and the THI decreased from 26.2% to 21.3% (p=0.000). Forty percent of the patients had improvement in tinnitus perception (RESP). Comparing the ADT group with a control group showed statistically significant improvement of their tinnitus as assessed by RESP, VAS, and THI.

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

Nelson, John W.; Ghafoori, A. Paiman; Willett, Christopher G.

Purpose: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical resection, survival remains poor, with high rates of local and distant failure. To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy. Methods and Materials: A total of 45 patients (13 with proximal and 32 with distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median follow-up was 30 months for all patients and 40 months for survivors. Results: Of the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treatedmore » neoadjuvantly. The 5-year actuarial overall survival, disease-free survival, metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and 78%, respectively. The median survival was 34 months. No patient died perioperatively. Patient age {<=}60 years and perineural involvement adversely affected survival on univariate analysis. Patients undergoing R0 resection had a significantly improved rate of local control but no survival advantage. Despite having more advanced disease at presentation, patients treated neoadjuvantly had a longer survival (5-year survival 53% vs. 23%, p = 0.16) and similar rates of Grade 2-3 surgical morbidity (16% vs. 33%, p = 0.24) compared with those treated in the postoperative setting. Conclusion: These study results suggest a possible local control benefit from chemoradiotherapy combined with surgery in patients with advanced, resected biliary cancer. Furthermore, our results suggest that a treatment strategy that includes preoperative chemoradiotherapy might result in improved tumor resectability with similar surgical morbidity compared with patients treated postoperatively, as well as potentially improved survival outcomes. Distant failure remains a significant failure pattern, suggesting the need for more effective systemic therapy.« less

Is the routine use of a water-soluble contrast enema prior to closure of a loop ileostomy necessary? A review of a single institution experience.

PubMed

Dimitriou, Nikoletta; Panteleimonitis, Sofoklis; Dhillon, Ajit; Boyle, Kirsten; Norwood, Mike; Hemingway, David; Yeung, Justin; Miller, Andrew

2015-12-04

The aims of the study were to determine the radiological leak rate in those patients who had undergone a resection for left-sided colorectal cancer and to see if the presence of a leak can be related with the postoperative clinical period. We also aimed to identify any common factors between patients with leak. A retrospective analysis of prospectively collected data of all patients who underwent a left-sided colorectal cancer resection with formation of a defunctioning ileostomy was undertaken. Between 2005 and 2010, 418 such patients were identified. A water-soluble contrast enema was performed in 339 patients (81.1 %). Of these, 24 (7.1 %) were reported to show an anastomotic leak. Data for these 24 patients is presented in this study. Twenty-three (95.8 %) of the leaks occurred in patients who had undergone an anterior resection; 95.8 % of the patients with a leak were male. Fifteen (62.5 %) patients underwent neo-adjuvant radiation. The mean length of stay in those patients shown to have a subsequent radiological leak was 18.8 days (median), compared with the overall unit figures of 12 days. Only 29.2 % of the patients who had a leak identified had an uncomplicated postoperative period. Overall 87.5 % of the patients had a reversal of the ileostomy. Radiological leakage is not uncommon. The majority of patients, who were shown to have a radiological leak in this study, were male, had undergone an anterior resection, had received neo-adjuvant radiation, had a longer initial length of stay and had postoperative complications. Water-soluble contrast enemas could be selectively used in patients with these characteristics.

The perioperative charge equivalence of interstitial brachytherapy and radical prostatectomy with 1-year followup.

PubMed

Kohan, A D; Armenakas, N A; Fracchia, J A

2000-02-01

We compare the comprehensive 1-year charges in a consecutive group of patients undergoing radical prostatectomy and transperineal interstitial brachytherapy for clinically localized prostate cancer at a single urban institution. A total of 60 consecutive men with clinically localized prostate cancer (T1-T2, N0, M0) were treated during a 15-month period with radical prostatectomy or interstitial brachytherapy. Hospital and outpatient records were analyzed for each patient in regard to preoperative, operative and postoperative charges. Parameters included number of encounters, diagnostic and therapeutic interventions, hospitalization and operative charges, and followup visits, diagnostic tests and interventions for 1 year. All charge calculations were based arbitrarily on the 1996 Medicare fee schedule, factoring in the mandated global charge reimbursement period of 90 days for both procedures. Of the patients 38 underwent radical prostatectomy (prostatectomy group) and 22 underwent interstitial brachytherapy (brachytherapy group). The brachytherapy group was older with higher pretreatment serum prostate specific antigen and clinical stage disease, and more frequently received neoadjuvant hormonal therapy compared to the prostatectomy group. The 2 groups were similar in Gleason score and, when applicable, duration of neoadjuvant hormonal therapy. Preoperative charges were 15.3% lower for prostatectomy than for brachytherapy (not statistically significant). Conversely, operative charges for prostatectomy were 13.5% higher (p = 0.04). The major difference among preoperative, operative and postoperative charges was for those incurred postoperatively by the brachytherapy group, which were 56.0% higher than those for the prostatectomy group ($2,285.20 versus $1,007.20, p = 0.0004). Transperineal interstitial seed implantation is perceived by many as more cost-effective than radical prostatectomy for patients with clinically localized prostate cancer. We demonstrated that when such patients were followed for 1 year, the comprehensive charges for radical prostatectomy and interstitial brachytherapy were equivalent.

Locoregional outcomes in clinical stage IIB breast cancer after neoadjuvant therapy and mastectomy with or without radiation.

PubMed

Diaz, Dayssy A; Hurley, Judith; Reis, Isildinha; Takita, Cristiane; Zhao, Wei; Wright, Jean

2014-12-01

Low rates of locoregional recurrence (LRR) in patients with clinical stage IIB breast cancer (cT2N1 or cT3N0) who undergo neoadjuvant therapy (NAT) and mastectomy have been reported. We aimed to quantify the risk of LRR and the relationship between LRR and potential risk factors in this subset of patients. We conducted a retrospective review of 116 patients with clinical IIB breast cancer who underwent NAT followed by mastectomy +/- postmastectomy radiotherapy (PMRT) between 2000 and 2009. We estimated the rate of LRR by cumulative incidence. The effect of prognostic factors was examined by Gray's test and Fine and Gray's test. Median follow-up: 63 months. Median age: 49. 28.4% cT2N1 and 71.6% cT3N0. 62.1% of tumors were ER+, 22.6% HER2+, 19% triple negative (TN). All patients underwent NAT and mastectomy. The majority of patients (87%) received PMRT; 32.3% were treated to chest wall (CW) only, and 67.7% to CW plus supraclavicular (SCV) field. Compared to cT2N1, patients with cT3N0 disease were more likely to be pN0 (60% vs 27%, P = 0.005). There was no significant relationship between risk of LRR and pathologic complete response (pCR), use of PMRT, RT to SCV field, or TN status, but there was higher risk of LRR in cT2N1 than cT3N0 (HR 6.03, P = 0.015). LRR was more common in cT2N1 than in cT3N0 disease, emphasizing the negative prognostic implication of clinically node-positive presentation.

Comparison of breast-conserving surgery with mastectomy in locally advanced breast cancer after good response to neoadjuvant chemotherapy: A PRISMA-compliant systematic review and meta-analysis.

PubMed

Sun, Yixuan; Liao, Mingjuan; He, Liu; Zhu, Chenfang

2017-10-01

The application of breast-conserving surgery (BCS) on patients with locally advanced breast cancer (LABC) with good response to neoadjuvant chemotherapy (NACT) still remains controversial. The objective in this study is to analyze the safety of BCS in the management of LABC in patients with good response to NACT. We searched the electronic databases of Medline (Pubmed) and Cochrane Library for reports on local recurrence (LR), regional recurrence (RR), distant recurrence (DR), 5-year disease-free survival (DFS) or 5-year overall survival (OS) in patients with LABC receiving BCS or mastectomy (MT) and with good response to NACT. Based on the research results, we conducted a meta-analysis using Review Manager 5.3. Our study showed that 16 studies with a combined total of 3531 patients, of whom 1465 patients underwent BCS, whereas 2066 patients underwent MT. There was no significant heterogeneity among these studies (Q statistic: P = .88; I = 0%). Patients with good response to NACT showed no significant difference in LR and RR [odd ratio (OR) = 0.83; 95% confidence interval (CI): 0.60-1.15; P = .26; OR = 0.56; 95% CI: 0.33-0.93; P = .03], while we figured out a lower DR (OR = 0.51; 95% CI: 0.42-0.63; P < .01), a higher DFS (OR = 2.35; 95% CI: 1.84 to 3.01, P < .01) and a higher OS (OR = 2.12; 95% CI: 1.51 to 2.98, P < .01) in BCS compared with MT. This meta-analysis concluded that BCS was a safe surgery for patients with LABC and had good response to NACT.

Comparing Coordinated Versus Sequential Salpingo-Oophorectomy for BRCA1 and BRCA2 Mutation Carriers With Breast Cancer.

PubMed

S Chapman, Jocelyn; Roddy, Erika; Panighetti, Anna; Hwang, Shelley; Crawford, Beth; Powell, Bethan; Chen, Lee-May

2016-12-01

Women with breast cancer who carry BRCA1 or BRCA2 mutations must also consider risk-reducing salpingo-oophorectomy (RRSO) and how to coordinate this procedure with their breast surgery. We report the factors associated with coordinated versus sequential surgery and compare the outcomes of each. Patients in our cancer risk database who had breast cancer and a known deleterious BRCA1/2 mutation before undergoing breast surgery were included. Women who chose concurrent RRSO at the time of breast surgery were compared to those who did not. Sixty-two patients knew their mutation carrier status before undergoing breast cancer surgery. Forty-three patients (69%) opted for coordinated surgeries, and 19 (31%) underwent sequential surgeries at a median follow-up of 4.4 years. Women who underwent coordinated surgery were significantly older than those who chose sequential surgery (median age of 45 vs. 39 years; P = .025). There were no differences in comorbidities between groups. Patients who received neoadjuvant chemotherapy were more likely to undergo coordinated surgery (65% vs. 37%; P = .038). Sequential surgery patients had longer hospital stays (4.79 vs. 3.44 days, P = .01) and longer operating times (8.25 vs. 6.38 hours, P = .006) than patients who elected combined surgery. Postoperative complications were minor and were no more likely in either group (odds ratio, 4.76; 95% confidence interval, 0.56-40.6). Coordinating RRSO with breast surgery is associated with receipt of neoadjuvant chemotherapy, longer operating times, and hospital stays without an observed increase in complications. In the absence of risk, surgical options can be personalized. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy cycles on survival of patients with advanced-stage ovarian cancer

PubMed Central

Chung, Young Shin; Kim, Yun-Ji; Lee, Inha; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae

2017-01-01

Background There is currently no consensus regarding the optimal number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced ovarian cancer. This study aimed to evaluate the impact of the number of neoadjuvant chemotherapy (NAC) and postoperative adjuvant chemotherapy (POAC) cycles on the survival of patients with advanced ovarian cancer undergoing NAC/IDS/POAC. Methods We retrospectively reviewed data from 203 patients who underwent NAC/IDS/POAC at Yonsei Cancer Hospital between 2006 and 2016. All patients underwent taxane plus carboplatin chemotherapy for NAC and POAC. The patient outcomes were analyzed according to the number of NAC, POAC, and total chemotherapy (NAC+POAC) cycles. Results Patients who received fewer than 6 cycles of total chemotherapy (n = 8) had poorer progression-free survival (PFS) and overall survival (OS) than those completing at least 6 cycles (p = 0.005 and p<0.001, respectively). Among patients who completed at least 6 cycles of total chemotherapy (n = 189), Kaplan-Meier analysis revealed no significant difference in either PFS or OS according to the number of NAC cycles (1–3 vs. ≥4; p = 0.136 and p = 0.267, respectively). Among patients who experienced complete remission after 3 cycles of POAC (n = 98), the addition of further POAC cycles did not improve the PFS or OS (3 vs. ≥4; p = 0.641 and p = 0.104, respectively). Conclusion IDS after 4 cycles of NAC may be a safe and effective option when completing 6 cycles of total chemotherapy. Furthermore, the addition of more than 3 cycles of POAC does not appear to influence the survival of patients achieving completion remission after 3 cycles of POAC. PMID:28873393

Impact of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy cycles on survival of patients with advanced-stage ovarian cancer.

PubMed

Chung, Young Shin; Kim, Yun-Ji; Lee, Inha; Lee, Jung-Yun; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae

2017-01-01

There is currently no consensus regarding the optimal number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced ovarian cancer. This study aimed to evaluate the impact of the number of neoadjuvant chemotherapy (NAC) and postoperative adjuvant chemotherapy (POAC) cycles on the survival of patients with advanced ovarian cancer undergoing NAC/IDS/POAC. We retrospectively reviewed data from 203 patients who underwent NAC/IDS/POAC at Yonsei Cancer Hospital between 2006 and 2016. All patients underwent taxane plus carboplatin chemotherapy for NAC and POAC. The patient outcomes were analyzed according to the number of NAC, POAC, and total chemotherapy (NAC+POAC) cycles. Patients who received fewer than 6 cycles of total chemotherapy (n = 8) had poorer progression-free survival (PFS) and overall survival (OS) than those completing at least 6 cycles (p = 0.005 and p<0.001, respectively). Among patients who completed at least 6 cycles of total chemotherapy (n = 189), Kaplan-Meier analysis revealed no significant difference in either PFS or OS according to the number of NAC cycles (1-3 vs. ≥4; p = 0.136 and p = 0.267, respectively). Among patients who experienced complete remission after 3 cycles of POAC (n = 98), the addition of further POAC cycles did not improve the PFS or OS (3 vs. ≥4; p = 0.641 and p = 0.104, respectively). IDS after 4 cycles of NAC may be a safe and effective option when completing 6 cycles of total chemotherapy. Furthermore, the addition of more than 3 cycles of POAC does not appear to influence the survival of patients achieving completion remission after 3 cycles of POAC.

MRI and PET/CT for evaluation of the pathological response to neoadjuvant chemotherapy in breast cancer: A systematic review and meta-analysis.

PubMed

Li, Huimin; Yao, Liang; Jin, Penghui; Hu, Lidong; Li, Xiaofei; Guo, Tiankang; Yang, Kehu

2018-05-11

Neoadjuvant chemotherapy (NAC) has become an essential treatment for breast cancer. However, there is still no consensus on the best tool to evaluate pathological response to NAC. Two reviewers systematically searched Cochrane, PubMed, EMBASE, Web of Science, and CBM (last updated in February 2017) for eligible articles. We independently screened and selected studies that conformed to the inclusion criteria and extracted the requisite data. Pooled sensitivity, specificity, and the area under the SROC curve were calculated to estimate the diagnostic accuracy of magnetic resonance imaging (MRI) and positron emission computed tomography (PET/CT). And the relative DOR (RDOR) was used to compare accuracy for levels of the covariable. Thirteen studies involving 575 patients who underwent MRI and 618 who underwent PET/CT were included in our analysis. The pooled sensitivity and specificity of MRI were 0.88 (95% CI: 0.78-0.94) and 0.69 (95% CI: 0.51-0.83), respectively. The corresponding values for PET/CT were 0.77 (95% CI: 0.58-0.90) and 0.78 (95% CI: 0.63-0.88), respectively. The area under the SROC curve for MRI and PET/CT were 0.88 and 0.84, respectively. And the RDOR = 1.44 (95% CI, 0.46-4.47 P = 0.83). MRI had a higher sensitivity and PET/CT had a higher specificity in predicting the pathologic response after NAC in patients with breast cancer. According to the area under the SROC curve and anatomic discriminative resolution, MRI is the more suitable recommendation for predicting the pathologic response after NAC. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Lung Resection after Definitive and Neo-Adjuvant Chemoradiation for Stage IIIA/B Locally Advanced Non-Small Cell Lung Cancer: a Retrospective Analysis].

PubMed

Schreiner, Waldemar; Gavrychenkova, Sofiia; Dudek, Wojciech; Lettmaier, Sebastian; Rieker, Ralf; Fietkau, Rainer; Sirbu, Horia

2018-06-01

The outcomes of so called "salvage" resections after definitive chemoradiation vs. curative resections after neoadjuvant chemoradiation therapy (IT-resection) in patients with stage IIIA/B locally advanced non-small cell lung cancer have rarely been compared. The aim of our study was to compare perioperative results, postoperative and recurrence-free survival and to identify relevant prognostic survival factors for both therapy strategies. Between June 2008 and May 2017, 43 patients underwent pulmonary resection following induction therapy (group 1) and 14 patients underwent salvage resection after definitive chemoradiation (group 2). Retrospective analysis was performed of demographic factors, tumour stage and location, initial therapy, preoperative regression status, perioperative morbidity and mortality, postoperative and recurrence-free survival. In group 2, significantly higher radiation dose was applied (p < 0.001) and the interval between chemoradiation and lung resection was significantly longer (p = 0.02). In addition, significantly higher perioperative blood loss and more frequent blood transfusions were noted (p = 0.003 and 0.005, respectively). Perioperative morbidity and mortality were statistically comparable in the two groups (p = 0.72 and 0.395, respectively). Postoperative 5 year survival in group 1 was 55%, in group 2 48% (log-rank p = 0.353). Five year recurrence-free survival in group 1 was 53%, in group 2 42% (log-rank p = 0.180). Diffuse metastasis occurred mostly in group 2, whereas in group 1 oligometastasis was more frequently noted. Postoperative outcome after salvage resection seems statistically comparable to results following curative resection after induction therapy. Diffuse distant metastasis is frequently noted. Careful patient selection is required. Georg Thieme Verlag KG Stuttgart · New York.

Neoadjuvant conformal chemoradiation with induction chemotherapy for rectal adenocarcinoma. A prospective observational study.

PubMed

Fekete, Zsolt; Muntean, Alina-Simona; Hica, Ştefan; Rancea, Alin; Resiga, Liliana; Csutak, Csaba; Todor, Nicolae; Nagy, Viorica Magdalena

2014-06-01

The purpose of this prospective observational study was to evaluate the rate and the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphincter-saving surgery. We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy. The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p<0.01), cN0 (p<0.01), distance from anal verge >5 cm (p<0.01), initial CEA <6.2 ng/ml (p<0.01), higher number of chemotherapy cycles with Oxaliplatin (pROC=0.05) and protraction of radiotherapy of >35 days (p<0.01). Nine patients from 81 (11.1%) presented complete response (7 pathological and 2 clinical); the independent prognostic factors were stage cT2 versus cT3-4 (p<0.01), initial tumor size ≤3.5 cm and distance from anal verge >5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.

Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy.

PubMed

Lo, Charlotte S; Sanii, Sanaz; Kroeger, David R; Milne, Katy; Talhouk, Aline; Chiu, Derek S; Rahimi, Kurosh; Shaw, Patricia A; Clarke, Blaise A; Nelson, Brad H

2017-02-15

Purpose: Some forms of chemotherapy can enhance antitumor immunity through immunogenic cell death, resulting in increased T-cell activation and tumor infiltration. Such effects could potentially sensitize tumors to immunotherapies, including checkpoint blockade. We investigated whether platinum- and taxane-based chemotherapy for ovarian cancer induces immunologic changes consistent with this possibility. Experimental Design: Matched pre- and post-neoadjuvant chemotherapy tumor samples from 26 high-grade serous carcinoma (HGSC) patients were analyzed by immunohistochemistry (IHC) for a large panel of immune cells and associated factors. The prognostic significance of post-chemotherapy TIL patterns was assessed in an expanded cohort ( n = 90). Results: Neoadjuvant chemotherapy was associated with increased densities of CD3 + , CD8 + , CD8 + TIA-1 + , PD-1 + and CD20 + TIL. Other immune subsets and factors were unchanged, including CD79a + CD138 + plasma cells, CD68 + macrophages, and MHC class I on tumor cells. Immunosuppressive cell types were also unchanged, including FoxP3 + PD-1 + cells (putative regulatory T cells), IDO-1 + cells, and PD-L1 + cells (both macrophages and tumor cells). Hierarchical clustering revealed three response patterns: (i) TIL high tumors showed increases in multiple immune markers after chemotherapy; (ii) TIL low tumors underwent similar increases, achieving patterns indistinguishable from the first group; and (iii) TIL negative cases generally remained negative. Despite the dramatic increases seen in the first two patterns, post-chemotherapy TIL showed limited prognostic significance. Conclusions: Chemotherapy augments pre-existing TIL responses but fails to relieve major immune-suppressive mechanisms or confer significant prognostic benefit. Our findings provide rationale for multipronged approaches to immunotherapy tailored to the baseline features of the tumor microenvironment. Clin Cancer Res; 23(4); 925-34. ©2016 AACR . ©2016 American Association for Cancer Research.

Tumor Metabolism and Blood Flow Changes by Positron Emission Tomography: Relation to Survival in Patients Treated With Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer

PubMed Central

Dunnwald, Lisa K.; Gralow, Julie R.; Ellis, Georgiana K.; Livingston, Robert B.; Linden, Hannah M.; Specht, Jennifer M.; Doot, Robert K.; Lawton, Thomas J.; Barlow, William E.; Kurland, Brenda F.; Schubert, Erin K.; Mankoff, David A.

2008-01-01

Purpose Patients with locally advanced breast carcinoma (LABC) receive preoperative chemotherapy to provide early systemic treatment and assess in vivo tumor response. Serial positron emission tomography (PET) has been shown to predict pathologic response in this setting. We evaluated serial quantitative PET tumor blood flow (BF) and metabolism as in vivo measurements to predict patient outcome. Patients and Methods Fifty-three women with primary LABC underwent dynamic [18F]fluorodeoxyglucose (FDG) and [15O]water PET scans before and at midpoint of neoadjuvant chemotherapy. The FDG metabolic rate (MRFDG) and transport (FDG K1) parameters were calculated; BF was estimated from the [15O]water study. Associations between BF, MRFDG, FDG K1, and standardized uptake value and disease-free survival (DFS) and overall survival (OS) were evaluated using the Cox proportional hazards model. Results Patients with persistent or elevated BF and FDG K1 from baseline to midtherapy had higher recurrence and mortality risks than patients with reductions. In multivariable analyses, BF and FDG K1 changes remained independent prognosticators of DFS and OS. For example, in the association between BF and mortality, a patient with a 5% increase in tumor BF had a 67% higher mortality risk compared with a patient with a 5% decrease in tumor BF (hazard ratio = 1.67; 95% CI, 1.24 to 2.24; P < .001). Conclusion LABC patients with limited or no decline in BF and FDG K1 experienced higher recurrence and mortality risks that were greater than the effects of clinical tumor characteristics. Tumor perfusion changes over the course of neoadjuvant chemotherapy measured directly by [15O]water or indirectly by dynamic FDG predict DFS and OS. PMID:18626006

Hospital variation and the impact of postoperative complications on the use of perioperative chemo(radio)therapy in resectable gastric cancer. Results from the Dutch Upper GI Cancer Audit.

PubMed

Schouwenburg, M G; Busweiler, L A D; Beck, N; Henneman, D; Amodio, S; van Berge Henegouwen, M I; Cats, A; van Hillegersberg, R; van Sandick, J W; Wijnhoven, B P L; Wouters, M W J; Nieuwenhuijzen, G A P

2018-04-01

Dutch national guidelines on the diagnosis and treatment of gastric cancer recommend the use of perioperative chemotherapy in patients with resectable gastric cancer. However, adjuvant chemotherapy is often not administered. The aim of this study was to evaluate hospital variation on the probability to receive adjuvant chemotherapy and to identify associated factors with special attention to postoperative complications. All patients who received neoadjuvant chemotherapy and underwent an elective surgical resection for stage IB-IVa (M0) gastric adenocarcinoma between 2011 and 2015 were identified from a national database (Dutch Upper GI Cancer Audit). A multivariable linear mixed model was used to evaluate case-mix adjusted hospital variation and to identify factors associated with adjuvant therapy. Of all surgically treated gastric cancer patients who received neoadjuvant chemotherapy (n = 882), 68% received adjuvant chemo(radio)therapy. After adjusting for case-mix and random variation, a large hospital variation in the administration rates for adjuvant was observed (OR range 0.31-7.1). In multivariable analysis, weight loss, a poor health status and failure of neoadjuvant chemotherapy completion were strongly associated with an increased likelihood of adjuvant therapy omission. Patients with severe postoperative complications had a threefold increased likelihood of adjuvant therapy omission (OR 3.07 95% CI 2.04-4.65). Despite national guidelines, considerable hospital variation was observed in the probability of receiving adjuvant chemo(radio)therapy. Postoperative complications were strongly associated with adjuvant chemo(radio)therapy omission, underlining the need to further reduce perioperative morbidity in gastric cancer surgery. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

The degree of circumferential tumour involvement as a prognostic factor in oesophageal cancer.

PubMed

Sillah, Karim; Pritchard, Susan A; Watkins, Gillian R; McShane, James; West, Catharine M; Page, Richard; Welch, Ian M

2009-08-01

Tumour length is an adverse prognostic factor in oesophageal cancer. However, the prognostic role of the degree of oesophageal circumference (DOC) involved by tumour with or without resection margin invasion is not clear. This work assessed the relationship between DOC involved by tumour, clinico-pathological variables and prognosis. The clinico-pathological details of 320 patients who underwent potentially curative oesophagogastrectomy for cancer between 1994 and 2007 were analysed. The DOC involved with tumour measured macroscopically on the resected specimen was classified as small (<2.5 cm, n = 115), large (> or = 2.5 cm, n = 144) or circumferential (i.e. involving the whole circumference, n = 61). Univariate and multivariate survival analyses were carried out. The DOC with tumour was higher in ulcerating tumours than stenosing or polypoidal types (p = 0.017). Tumour length, T-stage, neoadjuvant chemotherapy and vascular invasion were independently associated with DOC with tumour on multivariate analysis (p < 0.05 for all). DOC > or = 2.5 cm was an adverse prognostic factor in univariate analysis (p = 0.002) with a hazard ratio of 1.52 [95% CI 1.13-2.04] compared with those <2.5 cm. Circumferential tumours had a similar prognosis to tumours > or = 2.5 cm (p = 0.60). The prognostic significance of DOC with tumour was lost in multivariate analysis where the factors retaining independence were patient age, T-stage, lymph node metastasis, vascular invasion and positive resection margins. However, when patients were stratified by use of neoadjuvant chemotherapy (n = 121), the DOC with tumour retained prognostic significance on multivariate analysis in the 199 patients who did not undergo neoadjuvant chemotherapy (p = 0.04). The DOC with tumour appears to provide prognostic information in oesophageal cancer surgery, especially in patients who do not undergo preoperative chemotherapy.

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.

Wound complications in rectal cancer patients undergoing primary closure of the perineal wound after abdominoperineal resection.

PubMed

El-Gazzaz, Galal; Kiran, Ravi Pokala; Lavery, Ian

2009-12-01

Perineal wound complications have a significant impact on postoperative morbidity after excision of the rectum and anus. The aim of this study is to evaluate factors affecting perineal wound complications after primary closure of the wound following abdominoperineal resection. Data were reviewed from all patients who underwent abdominoperineal resection for rectal carcinoma between 1982 and 2007. Data pertaining to demographics, tumor characteristics, and use of preoperative neoadjuvant therapy were retrieved. Complications studied included delayed wound healing, wound infection, dehiscence, abscess or sinus, reoperation, and perineal hernias. Patients who developed perineal wound complications (Group A) were compared with the remaining patients (Group B) to evaluate factors associated with the development of perineal wound complications. Six hundred ninety-six patients (59% male) met the inclusion criteria. The mean age was 63 years (standard deviation, 13), and the mean body mass index was 28.9 kg/m2 (standard deviation, 7.8). Two hundred seventy-three patients (39.2%) received neoadjuvant chemoradiation. The overall rate of wound complications was 16.2%, and reoperation was required in 5.2% of patients. Group A and Group B patients were similar with respect to age (P = 0.1), gender (P = 0.7), grade (P = 0.4), and stage of disease (P = 0.5). A greater proportion of Group A patients had associated comorbidity (P = 0.001), obesity (0.04), neoadjuvant chemoradiation (0.02), and intraoperative bleeding (0.04). In multivariate analysis, comorbidity was the only independent factor associated with the development of perineal complications (odds ratio, 1.8 (1.09-2.96)). Most patients have perineal wound healing without complications after abdominoperineal resection. In multivariate analysis, comorbidity was the only significant factor that predicted perineal wound complications.

Severe myositis of the hip flexors after pre-operative chemoradiation therapy for locally advanced rectal cancer: case report.

PubMed

Florczynski, Matthew M; Sanatani, Michael S; Mai, Lauren; Fisher, Barbara; Moulin, Dwight E; Cao, Jeffrey; Louie, Alexander V; Pope, Janet E; Leung, Eric

2016-03-22

The use of neoadjuvant radiation therapy and chemotherapy in the treatment of locally advanced rectal adenocarcinoma has been shown to reduce disease recurrence when combined with surgery and adjuvant chemotherapy. We report a case of a patient who developed a debilitating bilateral myopathy of the hip flexors after successful treatment for rectal cancer. To the best of our knowledge, this is the first such complication from radiation therapy reported in a patient with colorectal cancer. The disproportionate severity of our patient's myopathy relative to the dose of radiation used also makes this case unique among reports of neuromuscular complications from radiation therapy. The patient is a 65-year-old male with node negative, high-grade adenocarcinoma of the rectum penetrating through the distal rectal wall. He underwent neoadjuvant concurrent pelvic radiation therapy and capecitabine-based chemotherapy, followed by abdominoperineal resection and post-operative FOLFOX chemotherapy. Five months post-completion of pelvic radiotherapy and 2 months after the completion of adjuvant chemotherapy, he presented with bilateral weakness of the iliopsoas muscles and severe pain radiating to the groin. The patient improved with 40 mg/d of prednisone, which was gradually tapered to 2 mg/d over 6 months, with substantial recovery of muscle strength and elimination of pain. The timing, presentation and response of our patient's symptoms to corticosteroids are most consistent with a radiation recall reaction. Radiation recall is a phenomenon whereby previously irradiated tissue becomes vulnerable to toxicity by subsequent systemic therapy and is rarely associated with myopathies. Radiation recall should be considered a potential complication of neoadjuvant radiation therapy for rectal cancer, and for ongoing research into the optimization of treatment for these patients. Severe myopathies caused by radiation recall may be fully reversible with corticosteroid treatment.

Effects of an immuno-enhanced diet containing antioxidants in esophageal cancer surgery following neoadjuvant therapy.

PubMed

Aiko, S; Kumano, I; Yamanaka, N; Tsujimoto, H; Takahata, R; Maehara, T

2012-02-01

Neoadjuvant therapy-induced immunological deterioration may be a key factor in postoperative morbidity in patients with esophageal cancer. This study aimed to determine the effects of perioperative feeding with an immuno-enhanced diet on immune competence in patients treated with neoadjuvant therapy followed by surgery. Because an immuno-enhanced diet that contained several antioxidants was used, perioperative oxidative stress and the effects of the immuno-enhanced diet on this stress were also investigated. Of 39 patients with esophageal cancer who underwent similar surgical procedures, 26 patients who received chemotherapy or chemoradiation therapy before surgery were randomly divided into two groups: group 1 (n= 14) was given an immuno-enhanced diet for 5 days before surgery, and group 2 (n= 12) received no enteral feeding products before surgery. Group 3 (n= 13) consisted of patients that did not receive neoadjuvant therapy and received no enteral feeding products before surgery. Several markers for coagulation and fibrinolysis were determined and immunological assessments were performed for each patient. To measure reactive oxygen metabolites and the total antioxidant capacity, diacron-reactive oxygen metabolites (d-ROMs) and OXY-adsorbent tests were performed using a free radical elective evaluator. Significant depression in lymphocyte numbers was observed in groups 1 and 2 before and early after surgery as compared to group 3. Numbers of B cells, CD4/CD8 ratio, and phytohemagglutinin-induced lymphocyte transformation tests were also significantly decreased in groups 1 and 2 on postoperative day 1. Fibrin and fibrinogen degradation products were significantly elevated in group 2 compared to group 1. d-ROMs and OXY-adsorbent test values were elevated before surgery and were decreased transiently early after surgery. Compared to groups 2 and 3, d-ROMs values were significantly lower in group 1 patients throughout the postoperative period, while OXY-adsorbent test values were significantly higher in group 2 patients. Oxidative index was significantly suppressed in group 1 compared to group 3. No significant intergroup differences were observed with regard to morbidity after surgery. Although the baseline levels of immunological function might have been different because of less-advanced cancer stages in group 3, neoadjuvant therapy significantly affected several immunological parameters. Preoperative administration of an immuno-enhanced diet did not significantly prevent neoadjuvant therapy-induced immunological deterioration prior to esophageal cancer surgery. Patients with esophageal cancer had elevated levels of oxidant and antioxidant activities before surgery, which were transiently decreased early after surgery. Although the underlying mechanisms for these perioperative changes are unclear, this study showed that an immuno-enhanced diet containing several antioxidants may reduce oxidative stress following esophageal cancer surgery. After these mechanisms are studied further, oxidative stress control may become another tool for perioperative management to reduce morbidity after esophageal cancer surgery. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Charge carrier dynamics in organic semiconductors and their donor-acceptor composites: Numerical modeling of time-resolved photocurrent

NASA Astrophysics Data System (ADS)

Johnson, Brian; Kendrick, Mark J.; Ostroverkhova, Oksana

2013-09-01

We present a model that describes nanosecond (ns) time-scale photocurrent dynamics in functionalized anthradithiophene (ADT) films and ADT-based donor-acceptor (D/A) composites. By fitting numerically simulated photocurrents to experimental data, we quantify contributions of multiple pathways of charge carrier photogeneration to the photocurrent, as well as extract parameters that characterize charge transport (CT) in organic films including charge carrier mobilities, trap densities, hole trap depth, and trapping and recombination rates. In pristine ADT films, simulations revealed two competing charge photogeneration pathways: fast, occurring on picosecond (ps) or sub-ps time scales with efficiencies below 10%, and slow, which proceeds at the time scale of tens of nanoseconds, with efficiencies of about 11%-12%, at the applied electric fields of 40-80 kV/cm. The relative contribution of these pathways to the photocurrent was electric field dependent, with the contribution of the fast process increasing with applied electric field. However, the total charge photogeneration efficiency was weakly electric field dependent exhibiting values of 14%-20% of the absorbed photons. The remaining 80%-86% of the photoexcitation did not contribute to charge carrier generation at these time scales. In ADT-based D/A composites with 2 wt.% acceptor concentration, an additional pathway of charge photogeneration that proceeds via CT exciton dissociation contributed to the total charge photogeneration. In the composite with the functionalized pentacene (Pn) acceptor, which exhibits strong exciplex emission from a tightly bound D/A CT exciton, the contribution of the CT state to charge generation was small, ˜8%-12% of the total number of photogenerated charge carriers, dependent on the electric field. In contrast, in the composite with PCBM acceptor, the CT state contributed about a half of all photogenerated charge carriers. In both D/A composites, the charge carrier mobilities were reduced and trap densities and average trap depths were increased, as compared to a pristine ADT donor film. A considerably slower recombination of free holes with trapped electrons was found in the composite with the PCBM acceptor, which led to slower decays of the transient photocurrent and considerably higher charge retention, as compared to a pristine ADT donor film and the composite with the functionalized Pn acceptor.

The Astronomy Diagnostic Test: Past, Present and Future

NASA Astrophysics Data System (ADS)

Deming, G. L.; Hufnagel, B. R.

2000-12-01

During 1998, the Collaboration for Astronomy Education Research (Adams, Adrian, Brick, Deming, Hufnagel, Slater, and Zeilik) developed a content-based diagnostic test for undergraduate non-science majors taking their first introductory level astronomy course. Student interviews and written feedback were used to construct a series of questions reflecting the students' natural language and with distractors (wrong answers) that mirror commonly held misconceptions. Version 1.9 of the Astronomy Diagnostic Test (ADT) was administered during Spring 1999 by volunteers teaching astronomy at 22 institutions across the United States. Minor modifications were made and Version 2.0 was released on June 21, 1999. The ADT 2.0 currently is available to the astronomical community through two websites and we continue to collect pretest/posttest results. Award of an NSF Small Grant for Exploratory Research has enabled us to work with a team of education researchers at the Ontario Institute for Studies in Education. Our database will be subjected to a statistical analysis in order to establish reliability of ADT 2.0. In addition, content, face, and construct validity are being examined. If you are teaching an introductory astronomy course aimed at non-science majors for Spring 2001, your class can be part of this project. We are looking for volunteers! We are also interested in hearing your ideas for a "next-generation" version of the ADT. Funding provided by NSF grant REC-0089239

A theoretical study on the characteristics of the intermolecular interactions in the active site of human androsterone sulphotransferase: DFT calculations of NQR and NMR parameters and QTAIM analysis.

PubMed

Astani, Elahe K; Heshmati, Emran; Chen, Chun-Jung; Hadipour, Nasser L

2016-07-01

A theoretical study at the level of density functional theory (DFT) was performed to characterize noncovalent intermolecular interactions, especially hydrogen bond interactions, in the active site of enzyme human androsterone sulphotransferase (SULT2A1/ADT). Geometry optimization, interaction energy, (2)H, (14)N, and (17)O electric field gradient (EFG) tensors, (1)H, (13)C, (17)O, and (15)N chemical shielding (CS) tensors, Natural Bonding Orbital (NBO) analysis, and quantum theory of atoms in molecules (QTAIM) analysis of this active site were investigated. It was found that androsterone (ADT) is able to form hydrogen bonds with residues Ser80, Ile82, and His99 of the active site. The interaction energy calculations and NBO analysis revealed that the ADT molecule forms the strongest hydrogen bond with Ser80. Results revealed that ADT interacts with the other residues through electrostatic and Van der Waals interactions. Results showed that these hydrogen bonds influence on the calculated (2)H, (14)N, and (17)O quadrupole coupling constants (QCCs), as well as (1)H, (13)C, (17)O, and (15)N CS tensors. The magnitude of the QCC and CS changes at each nucleus depends directly on its amount of contribution to the hydrogen bond interaction. Copyright © 2016 Elsevier Inc. All rights reserved.

New Players for Advanced Prostate Cancer and the Rationalisation of Insulin-Sensitising Medication

PubMed Central

Gunter, Jennifer H.; Sarkar, Phoebe L.; Lubik, Amy A.; Nelson, Colleen C.

2013-01-01

Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of “old players” for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer. PMID:23573093

Androgen-deprivation therapy plus chemotherapy in metastatic hormone-sensitive prostate cancer. A systematic review and meta-analysis of randomized clinical trials.

PubMed

Ramos-Esquivel, Allan; Fernández, Cristina; Zeledón, Zenén

2016-08-01

To assess the efficacy and toxicity of androgen-deprivation therapy (ADT) plus chemotherapy in patients with hormone-sensitive metastatic prostate cancer. Randomized clinical trials were identified after systematic searching of databases and conference proceedings. A random-effect model was used to determine the pooled hazard ratio (HR) for the efficacy outcomes-overall survival (OS), biochemical progression-free survival (PFS), and clinical PFS, according to the inverse-variance method. Heterogeneity was measured using the Q and I(2) statistics. A narrative review was done to explore the major adverse drug reactions reported for each trial. After systematic searching, we included 6 trials (n = 2,675) in this meta-analysis. Estramustine-based chemotherapy plus ADT was not associated with improved OS (HR = 0.64; 95% CI: 0.22-1.89; P = 0.42). In contrast, docetaxel plus ADT was associated with improved OS (HR = 0.75; 95% CI: 0.61-0.91; P = 0.004) and clinical PFS (HR = 0.64; 95% CI: 0.57-0.72; P<0.00001). There was no significant heterogeneity detected among trials. Regarding adverse drug reactions grade 3 or higher, neutropenia was the most frequent side effect reported in a range from 12% to 32%. The addition of docetaxel-based chemotherapy to ADT improves OS and clinical PFS in hormone-sensitive metastatic prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Optimal location of radiation therapy centers with respect to geographic access.

PubMed

Santibáñez, Pablo; Gaudet, Marc; French, John; Liu, Emma; Tyldesley, Scott

2014-07-15

To develop a framework with which to evaluate locations of radiation therapy (RT) centers in a region based on geographic access. Patient records were obtained for all external beam radiation therapy started in 2011 for the province of British Columbia, Canada. Two metrics of geographic access were defined. The primary analysis was percentage of patients (coverage) within a 90-minute drive from an RT center (C90), and the secondary analysis was the average drive time (ADT) to an RT center. An integer programming model was developed to determine optimal center locations, catchment areas, and capacity required under different scenarios. Records consisted of 11,096 courses of radiation corresponding to 161,616 fractions. Baseline geographic access was estimated at 102.5 minutes ADT (each way, per fraction) and 75.9% C90. Adding 2 and 3 new centers increased C90 to 88% and 92%, respectively, and decreased ADT by between 43% and 61%, respectively. A scenario in which RT was provided in every potential location that could support at least 1 fully utilized linear accelerator resulted in 35.3 minutes' ADT and 93.6% C90. The proposed framework and model provide a data-driven means to quantitatively evaluate alternative configurations of a regional RT system. Results suggest that the choice of location for future centers can significantly improve geographic access to RT. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Changes of the Oceanic Long-term and seasonal variation in a Global-warming Climate

NASA Astrophysics Data System (ADS)

Xia, Q.; He, Y.; Dong, C.

2015-12-01

Abstract: Gridded absolute dynamic topography (ADT) from AVISO and outputs of sea surface height above geoid from a series of climate models run for CMIP5 are used to analysis global sea level variation. Variance has been calculated to determine the magnitude of change in sea level variation over two decades. Increasing trend of variance of ADT suggests an enhanced fluctuation as well as geostrophic shear of global ocean. To further determine on what scale does the increasing fluctuation dominate, the global absolute dynamic topography (ADT) has been separated into two distinguished parts: the global five-year mean sea surface (MSS) and the residual absolute dynamic topography (RADT). Increased variance of MSS can be ascribed to the nonuniform rising of global sea level and an enhancement of ocean gyres in the Pacific Ocean. While trend in the variance of RADT is found to be close to zero which suggests an unchanged ocean mesoscale variability. The Gaussian-like distribution of global ADT are used to study the change in extreme sea levels. Information entropy has also been adapted in our study. Increasing trend of information entropy which measures the degree of dispersion of a probability distribution suggests more appearance of extreme sea levels. Extreme high sea levels are increasing with a higher growing rate than the mean sea level rise.

Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients.

PubMed

Samson, Pamela; Robinson, Clifford; Bradley, Jeffrey; Lockhart, A Craig; Puri, Varun; Broderick, Stephen; Kreisel, Daniel; Krupnick, A Sasha; Patterson, G Alexander; Meyers, Bryan; Crabtree, Traves

2016-12-01

The aim of this study was to evaluate differences in pathologic complete response (pCR) rates and overall survival among patients receiving either neoadjuvant chemotherapy or chemoradiation before esophagectomy for locally advanced esophageal cancer. Patients with esophageal cancer receiving either neoadjuvant chemotherapy or chemoradiation before esophagectomy were identified using the National Cancer Database. Univariate analysis compared patient, tumor, and postoperative outcome characteristics. Logistic regression was performed to identify variables associated with achieving pCR. Kaplan-Meier analysis was performed to compare overall median survival by neoadjuvant therapy type and pCR status. Finally, a Cox proportional hazards model was fitted to identify variables associated with increased mortality hazard. From 2006 to 2012, a total of 916 of 7338 of patients (12.5%) received neoadjuvant chemotherapy whereas 6422 (87.5%) received neoadjuvant chemoradiation. Patients who received neoadjuvant chemoradiation were more likely to achieve a pCR (17.2% versus 6.4%, p < 0.001) and less likely to have positive margins (5.6% versus 11.5%, p < 0.001) than were patients who received neoadjuvant chemotherapy, with no difference in 30- or 90-day mortality. Achieving a pCR was associated with improved overall median survival (59.5 ± 4.0 months versus 30.1 ± 0.76 months for those with persistent disease, p < 0.001). On logistic regression, neoadjuvant chemoradiation therapy was independently associated with achieving a pCR (OR = 2.75, 95% confidence interval: 2.01-3.77, p < 0.001). Despite improvement in the pCR rate with neoadjuvant chemoradiation, neoadjuvant therapy type was not independently associated with long-term survival (hazard ratio = 1.12; 95% confidence interval: 0.97-1.30, p = 0.12). Although neoadjuvant chemoradiation is more successful in downstaging esophageal cancer before esophagectomy, it was not independently prognostic for improved long-term survival. Other factors affecting long-term survival among pathologic complete responders and among patients with persistent disease should be investigated to clarify this association. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Variation in neoadjuvant chemotherapy utilization for epithelial ovarian cancer at high volume hospitals in the United States and associated survival.

PubMed

Barber, Emma L; Dusetzina, Stacie B; Stitzenberg, Karyn B; Rossi, Emma C; Gehrig, Paola A; Boggess, John F; Garrett, Joanne M

2017-06-01

To estimate variation in the use of neoadjuvant chemotherapy by high volume hospitals and to determine the association between hospital utilization of neoadjuvant chemotherapy and survival. We identified incident cases of stage IIIC or IV epithelial ovarian cancer in the National Cancer Database from 2006 to 2012. Inclusion criteria were treatment at a high volume hospital (>20 cases/year) and treatment with both chemotherapy and surgery. A logistic regression model was used to predict receipt of neoadjuvant chemotherapy based on case-mix predictors (age, comorbidities, stage etc). Hospitals were categorized by the observed-to-expected ratio for neoadjuvant chemotherapy use as low, average, or high utilization hospitals. Survival analysis was performed. We identified 11,574 patients treated at 55 high volume hospitals. Neoadjuvant chemotherapy was used for 21.6% (n=2494) of patients and use varied widely by hospital, from 5%-55%. High utilization hospitals (n=1910, 10 hospitals) had a median neoadjuvant chemotherapy rate of 39% (range 23-55%), while low utilization hospitals (n=2671, 14 hospitals) had a median rate of 10% (range 5-17%). For all ovarian cancer patients adjusting for clinical and socio-demographic factors, treatment at a hospital with average or high neoadjuvant chemotherapy utilization was associated with a decreased rate of death compared to treatment at a low utilization hospital (HR 0.90 95% CI 0.83-0.97 and HR 0.85 95% CI 0.75-0.95). Wide variation exists in the utilization of neoadjuvant chemotherapy to treat stage IIIC and IV epithelial ovarian cancer even among high volume hospitals. Patients treated at hospitals with low rates of neoadjuvant chemotherapy utilization experience decreased survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Variation in Neoadjuvant Chemotherapy Utilization for Epithelial Ovarian Cancer at High Volume Hospitals in the United States and Associated Survival

PubMed Central

Barber, Emma L; Dusetzina, Stacie B; Stitzenberg, Karyn B; Rossi, Emma C; Gehrig, Paola A; Boggess, John F; Garrett, Joanne M

2017-01-01

Objective To estimate variation in the use of neoadjuvant chemotherapy by high volume hospitals and to determine the association between hospital utilization of neoadjuvant chemotherapy and survival. Methods We identified incident cases of stage IIIC or IV epithelial ovarian cancer in the National Cancer Database from 2006–2012. Inclusion criteria were treatment at a high volume hospital (>20 cases/yr) and treatment with both chemotherapy and surgery. A logistic regression model was used to predict receipt of neoadjuvant chemotherapy based on case-mix predictors (age, comorbidities, stage etc). Hospitals were categorized by the observed-to-expected ratio for neoadjuvant chemotherapy use as low, average, or high utilization hospitals. Survival analysis was performed. Results We identified 11,574 patients treated at 55 high volume hospitals. Neoadjuvant chemotherapy was used for 21.6% (n=2494) of patients and use varied widely by hospital, from 5%–55%. High utilization hospitals (n=1910, 10 hospitals) had a median neoadjuvant chemotherapy rate of 39% (range 23–55%), while low utilization hospitals (n=2671, 14 hospitals) had a median rate of 10% (range 5–17%). For all ovarian cancer patients adjusting for clinical and socio-demographic factors, treatment at a hospital with average or high neoadjuvant chemotherapy utilization was associated with a decreased rate of death compared to treatment at a low utilization hospital (HR 0.90 95%CI 0.83–0.97 and HR 0.85 95%CI 0.75–0.95). Conclusions Wide variation exists in the utilization of neoadjuvant chemotherapy to treat stage IIIC and IV epithelial ovarian cancer even among high volume hospitals. Patients treated at hospitals with low rates of neoadjuvant chemotherapy utilization experience decreased survival. PMID:28366545

[11C]Choline PET/CT in therapy response assessment of a neoadjuvant therapy in locally advanced and high risk prostate cancer before radical prostatectomy.

PubMed

Schwarzenböck, Sarah M; Knieling, Anna; Souvatzoglou, Michael; Kurth, Jens; Steiger, Katja; Eiber, Matthias; Esposito, Irene; Retz, Margitta; Kübler, Hubert; Gschwend, Jürgen E; Schwaiger, Markus; Krause, Bernd J; Thalgott, Mark

2016-09-27

Recent studies have shown promising results of neoadjuvant therapy in prostate cancer (PC). The aim of this study was to evaluate the potential of [11C]Choline PET/CT in therapy response monitoring after combined neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high risk PC patients. In [11C]Choline PET/CT there was a significant decrease of SUVmax and SUVmean (p = 0.004, each), prostate volume (p = 0.005) and PSA value (p = 0.003) after combined neoadjuvant therapy. MRI showed a significant prostate and tumor volume reduction (p = 0.003 and 0.005, respectively). Number of apoptotic cells was significantly higher in prostatectomy specimens of the therapy group compared to pretherapeutic biopsies and the control group (p = 0.02 and 0.003, respectively). 11 patients received two [11C]Choline PET/CT and MRI scans before and after combined neoadjuvant therapy followed by radical prostatectomy and pelvic lymph node dissection. [11C]Choline uptake, prostate and tumor volume, PSA value (before/after neoadjuvant therapy) and apoptosis (of pretherapeutic biopsy/posttherapeutic prostatectomy specimens of the therapy group and prostatectomy specimens of a matched control group without neoadjuvant therapy) were assessed and tested for differences and correlation using SPSS. The results showing a decrease in choline uptake after combined neoadjuvant therapy (paralleled by regressive and apoptotic changes in histopathology) confirm the potential of [11C]Choline PET/CT to monitor effects of neoadjuvant therapy in locally advanced and high risk PC patients. Further studies are recommended to evaluate its use during the course of neoadjuvant therapy for early response assessment.

Imaging-guided preclinical trials of vascular targeting in prostate cancer

NASA Astrophysics Data System (ADS)

Kalmuk, James

Purpose: Prostate cancer is the most common non-cutaneous malignancy in American men and is characterized by dependence on androgens (Testosterone/Dihydrotestosterone) for growth and survival. Although reduction of serum testosterone levels by surgical or chemical castration transiently inhibits neoplastic growth, tumor adaptation to castrate levels of androgens results in the generation of castration-resistant prostate cancer (CRPC). Progression to CRPC following androgen deprivation therapy (ADT) has been associated with changes in vascular morphology and increased angiogenesis. Based on this knowledge, we hypothesized that targeting tumor vasculature in combination with ADT would result in enhanced therapeutic efficacy against prostate cancer. Methods: To test this hypothesis, we examined the therapeutic activity of a tumor-vascular disrupting agent (tumor-VDA), EPC2407 (Crolibulin(TM)), alone and in combination with ADT in a murine model of prostate cancer (Myc-CaP). A non-invasive multimodality imaging approach based on magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and ultrasound (US) was utilized to characterize tumor response to therapy and to guide preclinical trial design. Imaging results were correlated with histopathologic (H&E) and immunohistochemical (CD31) assessment as well as tumor growth inhibition and survival analyses. Results: Our imaging techniques were able to capture an acute reduction (within 24 hours) in tumor perfusion following castration and VDA monotherapy. BLI revealed onset of recurrent disease 5-7 days post castration prior to visible tumor regrowth suggestive of vascular recovery. Administration of VDA beginning 1 week post castration for 3 weeks resulted in sustained vascular suppression, inhibition of tumor regrowth, and conferred a more pronounced survival benefit compared to either monotherapy. Conclusion: The high mortality rate associated with CRPC underscores the need for investigating novel treatment strategies for this patient population. The results of our preclinical studies demonstrated the therapeutic potential of vascular targeting in combination with ADT against prostate cancer as well as highlight the capability of imaging to guide study design. Further investigation into the utility of VDAs in combination with ADT in prostate cancer is warranted.

Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

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

Feng, Felix Y., E-mail: ffeng@med.umich.edu; Department of Radiation Oncology, Veterans Affairs Medical Center, Ann Arbor, Michigan; Blas, Kevin

2013-05-01

Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64more » months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.« less

Distinctive Effect of Donepezil Treatment on P300 and N200 Subcomponents of Auditory Event-Related Evoked Potentials in Alzheimer Disease Patients.

PubMed

Vaitkevičius, Arūnas; Kaubrys, Gintaras; Audronytė, Eglė

2015-07-03

Latency of P300 subcomponent of event-related potentials (ERPs) increases in Alzheimer disease (AD) patients, which correlate well with cognitive impairment. Cholinesterase inhibitors (ChEIs) reduce P300 latency in AD patients with parallel improvement in cognition. It is not known whether N200 response to ChEIs is similar to that of P300. The aim of this study was to evaluate and compare characteristics of P300 and N200 in AD patients, treatment-naïve and on stable donepezil treatment, matched by age, education, sex, and cognitive function. We recruited 22 consecutive treatment-naïve AD patients (AD-N group), 22 AD patients treated with a stable donepezil dose of 10 mg/day for at least 3 months (AD-T group), and 50 healthy controls were recruited. Neuropsychological testing (MMSE, ADAS-Cog, and additional tests) and ERP recording was performed and analyzed. All groups did not differ according to age, duration of education, or sex (p>0.05). AD-N and AD-T groups did not differ according to cognitive function. The AD-T group had longer duration of disease than the AD-N group (p<0.001). The AD-T and AD-N groups did not differ in P300 latencies (p=0.49). N200 latency was longer in the AD-T group (p<0.001). The general linear model showed that significant predictors of P300 latency were age (p=0.019) and AD treatment status (p<0.001). Duration of AD was a significant predictor of N200 latency (p=0.004). The response of N200 latency to donepezil treatment differs from the response of P300. P300 is a better marker of ChEI treatment-dependent cognitive functions. N200 is more dependent on the duration of AD.

Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the ‘FC Prostate’ randomized controlled trial

PubMed Central

2013-01-01

Background Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The ‘Football Club (FC) Prostate’ study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition, cardiovascular function, physical function parameters, glucose tolerance, bone health, and patient-reported outcomes in men undergoing ADT for prostate cancer. Methods/Design Using a single-center randomized controlled design, 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6 months or more at The Copenhagen University Hospital will be enrolled on this trial. After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care. The soccer intervention will consist of 12 weeks of training 2–3 times/week for 45–60 min after which the assessment protocol will be repeated. Soccer training will then continue bi-weekly for an additional 20 weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects. The primary endpoint is changes in lean body mass from baseline to 12 weeks assessed by dual X-ray absorptiometry scan. Secondary endpoints include changes of cardiovascular, metabolic, and physical function parameters, as well as markers of bone metabolism and patient-reported outcomes. Discussion The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT. The results may pave the way for innovative, community-based interventions in the approach to treating prostate cancer. Trial registration ClinicalTrials.gov: NCT01711892 PMID:24330570

Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

PubMed

Matsuo, Koji; Johnson, Marian S; Im, Dwight D; Ross, Malcolm S; Bush, Stephen H; Yunokawa, Mayu; Blake, Erin A; Takano, Tadao; Klobocista, Merieme M; Hasegawa, Kosei; Ueda, Yutaka; Shida, Masako; Baba, Tsukasa; Satoh, Shinya; Yokoyama, Takuhei; Machida, Hiroko; Ikeda, Yuji; Adachi, Sosuke; Miyake, Takahito M; Iwasaki, Keita; Yanai, Shiori; Takeuchi, Satoshi; Nishimura, Masato; Nagano, Tadayoshi; Takekuma, Munetaka; Shahzad, Mian M K; Pejovic, Tanja; Omatsu, Kohei; Kelley, Joseph L; Ueland, Frederick R; Roman, Lynda D

2018-03-01

To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery. © 2017 Wiley Periodicals, Inc.

Molecular Simulations of The Formation of Gold-Molecule-Gold Junctions

NASA Astrophysics Data System (ADS)

Wang, Huachuan

2013-03-01

We perform classical molecular simulations by combining grand canonical Monte Carlo (GCMC) sampling with molecular dynamics (MD) simulation to explore the dynamic gold nanojunctions in a Alkenedithiol (ADT) solvent. With the aid of a simple driving-spring model, which can reasonably represent the long-range elasticity of the gold electrode, the spring forces are obtained during the dynamic stretching procedure. A specific multi-time-scale double reversible reference system propagator (double-RESPA) algorithm has been designed for the metal-organic complex in MD simulations to identify the detailed metal-molecule bonding geometry at metal-molecule-metal interface. We investigate the variations of bonding sites of ADT molecules on gold nanojunctions at Au (111) surface at a constant chemical potential. Simulation results show that an Au-ADT-Au interface is formed on Au nanojunctions, bond-breaking intersection is at 1-1 bond of the monatomic chain of the cross-section, instead of at the Au-S bond. Breaking force is around 1.5 nN. These are consistent with the experimental measurements.

Definitive treatment of androgen receptor-positive salivary duct carcinoma with androgen deprivation therapy and external beam radiotherapy.

PubMed

Soper, Margaret S; Iganej, Shawn; Thompson, Lester D R

2014-01-01

Salivary duct carcinoma (SDC) is an aggressive malignancy with high recurrence rates. Standard management includes surgical resection followed by adjuvant radiation. Androgen receptor positivity has been described to be present in 40% to 90% of SDCs, and a recent case series showed a benefit to androgen deprivation therapy (ADT) in recurrent or metastatic disease. We present the case of an 87-year-old woman with a locally advanced androgen receptor-positive parotid SDC treated definitively with ADT and external beam radiotherapy, a regimen modeled after the treatment of prostate cancer. She had a complete response on positron emission tomography (PET)/CT scan and had no evidence of disease 24 months after the completion of treatment. To our knowledge, this case report is the first to describe the use of ADT plus radiation to definitively treat SDC. This regimen could be considered in patients with androgen receptor-positive SDCs who are considered unresectable or who refuse surgery. Copyright © 2013 Wiley Periodicals, Inc.

What is the role of neoadjuvant chemotherapy, radiation, and adjuvant treatment in resectable esophageal cancer?

PubMed

Altorki, Nasser; Harrison, Sebron

2017-03-01

The majority of patients with operable esophageal cancers present with locally advanced disease, for which surgical resection as a sole treatment modality has been historically associated with poor survival. Even following radical resection, most of these patients will eventually succumb to their disease due to distant metastasis. For this reason, there has been intense interest in the role of neoadjuvant therapy. Neoadjuvant therapy primarily consists of either chemotherapy, radiation therapy, or a combination of the two. Multiple studies of variable scope, design, and patient characteristics have been conducted to determine whether neoadjuvant therapy is warranted, and-if so-what is the best modality of treatment. Despite nearly three decades of study, decisions regarding neoadjuvant therapy for esophageal cancer remain controversial. Regardless, the available evidence provided by large, prospective studies supports preoperative chemotherapy as opposed to surgery alone. Therefore, in our opinion, there is no longer any question as to whether induction therapy is appropriate for locally advanced esophageal cancer. Less clear, however, is the evidence that the addition of radiation to chemotherapy in the preoperative setting is superior to neoadjuvant chemotherapy alone. Our group generally advocates for neoadjuvant chemotherapy alone followed by radical esophageal resection. The data for adjuvant therapy are soft, and particularly troubling is the high rate of treatment drop out in trials studying adjuvant therapy. Therefore, we strongly prefer neoadjuvant chemotherapy and reserve adjuvant chemotherapy for those rare, highly selected patients-patients with T1 tumors, for example-who do not receive neoadjuvant treatment and are found to have occult nodal disease at the time of surgery.

C-reactive protein for the early prediction of anastomotic leak after esophagectomy in both neoadjuvant and non-neoadjuvant therapy case: a propensity score matching analysis

PubMed Central

Park, Jae Kil; Moon, Seok Whan

2017-01-01

Background Anastomotic leak is one of most significant causes of mortality after esophagectomy. Therefore, it is clinically valuable to detect anastomotic leak early after esophagectomy in esophageal cancer. The purpose of this study is to investigate the associations between routine postoperative laboratory findings and anastomotic leak and to analyze the laboratory findings to find out an independent predictive marker for anastomotic leak. In addition, this study compares cases treated with neoadjuvant therapy (NT) and those without (non-NT). Methods We retrospectively assessed the medical records of 201 consecutive cases that met this study’s criteria from January 2009 to December 2016. All patients underwent curative and complete esophagectomy for intra-thoracic esophageal cancer. We compiled and analyzed routine laboratory findings from the day before surgery to the eighth postoperative day on a daily basis. Routine laboratory tests consisted of 26 separate tests, including complete blood cell counts, blood chemistries, as well as erythrocyte sedimentation rate and C-reactive protein (CRP). Barium esophagogram with chest computed tomography (CT) was performed on the seventh postoperative day to evaluate the presence of an anastomotic leak. Results A total of 45 of 201 patients underwent NT. Anastomotic leaks were found in 23 (11.4%) of 201 patients (8 patients in NT and 15 patients in non-NT). White blood cell (WBC) from the second postoperative day (P=0.031, P=0.006, P=0.007, P=0.007, P=0.041, and P=0.003, respectively) and CRP from the third postoperative day (P=0.012, P<0.001, P=0.014, P<0.001, P=0.001, and P=0.006, respectively) were associated with anastomotic leak in non-NT; however, only CRP on the third, fifth, sixth, and seventh postoperative days (P=0.041, P=0.037, P=0.002, and P=0.003, respectively) was associated with anastomotic leak in NT. The CRP level on the third postoperative day was a significant independent predictive marker of anastomotic leak (P=0.041, odd ratio (OR) 1.056, 95% confidential interval (CI): 1.002–1.113) and had a significant diagnostic cutoff value for the development of anastomotic leak (non-NT: cutoff value 17.12 mg/dL, sensitivity 69.2%, specificity 78.1%, P<0.001, area 0.822; NT: cutoff value 16.42 mg/dL, sensitivity 80.0%, specificity 70.0%, P=0.042, area 0.7104). Conclusions There were divergent laboratory findings reflective of anastomotic leak between patients who underwent NT and those who did not. The CRP level on the third postoperative day had a significant cutoff value for early detection of anastomotic leak after esophagectomy in both NT and non-NT groups. PMID:29268376

Exercise and prostate cancer: From basic science to clinical applications.

PubMed

Campos, Christian; Sotomayor, Paula; Jerez, Daniel; González, Javier; Schmidt, Camila B; Schmidt, Katharina; Banzer, Winfried; Godoy, Alejandro S

2018-06-01

Prostate cancer (PCa) is a disease of increasing medical significance worldwide. In developed countries, PCa is the most common non-skin cancer in men, and one of the leading causes of cancer-related deaths. Exercise is one of the environmental factors that have been shown to influence cancer risk. Moreover, systemic reviews and meta-analysis have suggested that total physical activity is related to a decrease in the risk of developing PCa. In addition, epidemiological studies have shown that exercise, after diagnosis, has benefits regarding PCa development, and positive outcome in patients under treatment. The standard treatment for locally advanced or metastatic PCa is Androgen deprivation therapy (ADT). ADT produces diverse side effects, including loss of libido, changes in body composition (increase abdominal fat), and reduced muscle mass, and muscle tone. Analysis of numerous research publications showed that aerobic and/or resistance training improve patient's physical condition, such us, cardiorespiratory fitness, muscle strength, physical function, body composition, and fatigue. Therefore, exercise might counteract several ADT treatment-induced side effects. In addition of the aforementioned benefits, epidemiological, and in vitro studies have shown that exercise might decrease PCa development. Thus, physical activity might attenuate the risk of PCa and supervised exercise intervention might improve deleterious effects of cancer treatment, such as ADT side effects. This review article provides evidence indicating that exercise could complement, and potentiate, the current standard treatments for advanced PCa, probably by creating an unfavorable microenvironment that can negatively affect tumor development, and progression. © 2018 Wiley Periodicals, Inc.

Optimal Location of Radiation Therapy Centers With Respect to Geographic Access

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

Santibáñez, Pablo; Gaudet, Marc; French, John

2014-07-15

Purpose: To develop a framework with which to evaluate locations of radiation therapy (RT) centers in a region based on geographic access. Methods and Materials: Patient records were obtained for all external beam radiation therapy started in 2011 for the province of British Columbia, Canada. Two metrics of geographic access were defined. The primary analysis was percentage of patients (coverage) within a 90-minute drive from an RT center (C90), and the secondary analysis was the average drive time (ADT) to an RT center. An integer programming model was developed to determine optimal center locations, catchment areas, and capacity required undermore » different scenarios. Results: Records consisted of 11,096 courses of radiation corresponding to 161,616 fractions. Baseline geographic access was estimated at 102.5 minutes ADT (each way, per fraction) and 75.9% C90. Adding 2 and 3 new centers increased C90 to 88% and 92%, respectively, and decreased ADT by between 43% and 61%, respectively. A scenario in which RT was provided in every potential location that could support at least 1 fully utilized linear accelerator resulted in 35.3 minutes' ADT and 93.6% C90. Conclusions: The proposed framework and model provide a data-driven means to quantitatively evaluate alternative configurations of a regional RT system. Results suggest that the choice of location for future centers can significantly improve geographic access to RT.« less

Does Stereotype Threat Affect Post-Course Scores on the Astronomy Diagnostic Test?

NASA Astrophysics Data System (ADS)

Deming, G. L.; Hufnagel, B.; Landato, J. M.; Hodari, A. K.

2003-12-01

During the 1990s, Claude Steele and others demonstrated that women mathematics students under-performed while men over-performed on selected GRE questions when told that the exam could differentiate by gender. Stereotype threat is triggered for these women when they fear someone else may negatively stereotype them, and therefore, their performance is affected. In a limited study involving 229 students, we investigated the effect of stereotype threat on performance on the Astronomy Diagnostic Test (ADT). The ADT was administered as a pre-test in four introductory astronomy classes intended for non-science majors. The same professors taught pairs of classes at the University of Maryland, a large research institution, and W. R. Harper College, a small liberal arts school. The classes were treated the same until the final day before the post-course ADT was given. One "threatened" class at each campus was told that gender mattered so they should be sure to include it on the ADT. The "control" classes were told that gender does not matter. The results show no stereotype threat effect on the women in these introductory classes. The university men did slightly over-perform at low statistical significance. As Steele suggested, students must identify with a subject in order to strongly invoke a stereotype threat. This research was supported in part by the National Science Foundation through grants REC-0089239 to GLD, DGE-97014489 to BH, and DGE-9714452 for AKH.

Rectal Tumour Staging with Endorectal Ultrasound: Is There Any Difference between Western and Eastern European Countries?

PubMed

Fábián, Anna; Bor, Renáta; Farkas, Klaudia; Bálint, Anita; Milassin, Ágnes; Rutka, Mariann; Tiszlavicz, László; Wittmann, Tibor; Nagy, Ferenc; Molnár, Tamás; Szepes, Zoltán

2016-01-01

Background. Rectal tumour management depends highly on locoregional extension. Rectal endoscopic ultrasound (ERUS) is a good alternative to computed tomography and magnetic resonance imaging. However, in Hungary only a small amount of rectal tumours is examined with ERUS. Methods. Our retrospective study (2006-2012) evaluates the diagnostic accuracy of ERUS and compares the results, the first data from Central Europe, with those from Western Europe. The effect of neoadjuvant therapy, rectal probe type, and investigator's experience were also assessed. Results. 311 of the 647 ERUS assessed locoregional extension. Histological comparison was available in 177 cases: 67 patients underwent surgery alone; 110 received neoadjuvant chemoradiotherapy (CRT); ERUS preceded CRT in 77 and followed it in 33 patients. T-staging was accurate in 72% of primarily operated patients. N-staging was less accurate (62%). CRT impaired staging accuracy (64% and 59% for T- and N-staging). Rigid probes were more accurate (79%). At least 30 examinations are needed to master the technique. Conclusions. The sensitivity of ERUS complies with the literature. ERUS is easy to learn and more accurate in early stages but unnecessary for restaging after CRT. Staging accuracy is similar in Western and Central Europe, although the number of examinations should be increased.

COX-2 verexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy

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

Smith, Fraser M.; Reynolds, John V.; Kay, Elaine W.

2006-02-01

Purpose: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT). Methods and Materials: Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis. Results: Good response (TRG 1 + 2), moderate response (TRG 3), and poor response (TRG 4 + 5) were seen in 21 patients (42%), 11 patientsmore » (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3 + 4) to treatment than were those with normal COX-2 expression (p = 0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p = 0.0007, chi-square test). Conclusions: COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates.« less

Systemic Chemotherapy using FLOT - Regimen Combined with Cytoreductive Surgery plus HIPEC for Treatment of Peritoneal Metastasized Gastric Cancer. .

PubMed

Müller, H; Hotopp, Th; Tofeili, A; Wutke, K

2014-05-01

The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy using FLOT - protocol followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) followed by systemic chemotherapyand in patients with peritoneal carciriomatosis (PC) from gastric cancer. Twenty six (median age 53 years, range 39 - 71) were scheduled for three cycles of neoadjuvant systemic chemotherapy using bi-weekly FLOT - protocol followed by CRS + HIPEC. Thereafter 3 additional cycles of FLOT were given. During HIPEC in Colliseum technique Oxaliplatin was given in a dosage of 200 mg/m2 and Docetaxel in a dosage of 80 mg/m2. All patients underwent cytoreductive surgery plus HIPEC. Peritoneal Cancer index was > 15 in 3 cases only. Complete resection could be carried out in all cases (CC-O 18, CC-18). Postoperative complication rate was 23% with no mortality within 30 days. Anastomotic leakage rate was 3.2%. Overall survival was 19.0 months with a 2-year survival rate 38%. Regression analysis demonstrated a Peritoneal Cancer Index PCI > 12 as negative factor for survival. Neoadju- vant chemotherapy using FLOT - protocol followed by CRS + HIPEC seems to be associated with prolonged OS in patients with peritoneal carcinomatosis from gastric cancer. This treatment is not recommended for patients with extensive peritoneal involvement and PCI > 12.

Neoadjuvant Radiation Is Associated With Improved Survival in Patients With Resectable Pancreatic Cancer: An Analysis of Data From the Surveillance, Epidemiology, and End Results (SEER) Registry

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

Stessin, Alexander M.; Weill Medical College of Cornell University, New York, NY; Meyer, Joshua E.

2008-11-15

Purpose: Cancer of the exocrine pancreas is the fifth leading cause of cancer death in the United States. Neoadjuvant chemoradiation has been investigated in several trials as a strategy for downstaging locally advanced disease to resectability. The aim of the present study is to examine the effect of neoadjuvant radiation therapy (RT) vs. other treatments on long-term survival for patients with resectable pancreatic cancer in a large population-based sample group. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) registry database (1994-2003) was queried for cases of surgically resected pancreatic cancer. Retrospective analysis was performed. The endpoint of themore » study was overall survival. Results: Using Kaplan-Meier analysis we found that the median overall survival of patients receiving neoadjuvant RT was 23 months vs. 12 months with no RT and 17 months with adjuvant RT. Using Cox regression and controlling for independent covariates (age, sex, stage, grade, and year of diagnosis), we found that neoadjuvant RT results in significantly higher rates of survival than other treatments (hazard ratio [HR], 0.55; 95% confidence interval, 0.38-0.79; p = 0.001). Specifically comparing adjuvant with neoadjuvant RT, we found a significantly lower HR for death in patients receiving neoadjuvant RT rather than adjuvant RT (HR, 0.63; 95% confidence interval, 0.45-0.90; p = 0.03). Conclusions: This analysis of SEER data showed a survival benefit for the use of neoadjuvant RT over surgery alone or surgery with adjuvant RT in treating pancreatic cancer. Therapeutic strategies that use neoadjuvant RT should be further explored for patients with resectable pancreatic cancer.« less

Neoadjuvant luteinizing-hormone-releasing hormone agonist plus low-dose estramustine phosphate improves prostate-specific antigen-free survival in high-risk prostate cancer patients: a propensity score-matched analysis.

PubMed

Koie, Takuya; Mitsuzuka, Koji; Yoneyama, Takahiro; Narita, Shintaro; Kawamura, Sadafumi; Kaiho, Yasuhiro; Tsuchiya, Norihiko; Tochigi, Tatsuo; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara; Yoneyama, Tohru; Tobisawa, Yuki

2015-10-01

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with a neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). In the present study, we used a retrospective design via propensity score matching to elucidate the clinical benefit of neoadjuvant LHRH+EMP for high-risk Pca. The Michinoku Urological Cancer Study Group database contained data for 1,268 consecutive Pca patients treated with RP alone at 4 institutions between April 2000 and March 2011 (RP alone group). In the RP alone group, we identified 386 high-risk Pca patients. The neoadjuvant LHRH+EMP group included 274 patients with high-risk Pca treated between September 2005 and November 2013 at Hirosaki University. Neoadjuvant LHRH+EMP therapy included LHRH and EMP administration at a dose of 280 mg/day for 6 months before RP. The outcome measures were overall survival (OS) and BRFS. The propensity score-matched analysis indicated 210 matched pairs from both groups. The 5-year BRFS rates were 90.4 and 65.8 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P < 0.0001). The 5-year OS rates were 100 and 96.1 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P = 0.110). Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP appeared to reduce the risk of biochemical recurrence. A prospective randomized study is warranted to determine the clinical implications of the neoadjuvant therapy described here.

Chronic biloma after right hepatectomy for stage IV hepatoblastoma managed with roux-en-Y biliary cystenterostomy

PubMed Central

Murphy, Andrew J.; Rauth, Thomas P.; Lovvorn, Harold N.

2012-01-01

We report the complex case of a 12-month-old female with stage IV hepatoblastoma accompanied by thrombosis and cavernous transformation of the portal vein. Following neoadjuvant chemotherapy, she underwent right hepatectomy, which was complicated by iatrogenic injury of her left hepatic duct, and subsequently developed a postoperative biloma and chronic biliocutaneous fistula. Concomitant with multiple percutaneous interventions to manage the biloma nonoperatively while the child completed her adjuvant chemotherapy, she progressed to develop chronic malnutrition, jaundice, and failure to thrive. Once therapy was completed and the child was deemed free of disease she underwent exploratory laparotomy with roux-en-Y biliary cyst-enterostomy for definitive management, resulting in resolution of her biliary fistula, jaundice, and marked improvement in her nutritional status. Roux-en-Y biliary cyst-enterostomy is a unique and efficacious management option in the highly selected patient population with chronic biliary leak refractory to minimally invasive management. PMID:23164033

Primary peritoneal serous carcinoma presenting as inflammatory breast cancer.

PubMed

Khalifeh, Ibrahim; Deavers, Michael T; Cristofanilli, Massimo; Coleman, Robert L; Malpica, Anais; Gilcrease, Michael Z

2009-01-01

Metastasis to the breast from extramammary malignancies is rare. Nevertheless, its recognition is important because the prognosis and treatment differ from that of primary breast cancer. We report a unique case of primary peritoneal serous carcinoma that initially presented as inflammatory breast cancer. The patient received neoadjuvant chemotherapy for breast cancer and subsequently underwent bilateral total mastectomy and bilateral sentinel lymph node biopsy. She was found to have extensive intralymphatic carcinoma in both breasts, with only focal minimal breast parenchymal involvement, and residual metastatic carcinoma in bilateral sentinel lymph nodes. Further work-up revealed pelvic ascites and omental nodularities. The patient underwent laparoscopic bilateral salpingo-oophorectomy, which revealed high-grade serous carcinoma involving both ovaries and fallopian tubes. Molecular testing of tumor from the ovary and axillary lymph node showed an identical pattern of allelic loss, confirming a common origin for both tumors. To our knowledge, this is the first reported case of an extramammary primary malignancy that not only presented as inflammatory breast cancer but also was diagnosed and initially treated as such.

Neoadjuvant Anti-Angiogenesis Therapy for Prostate Cancer

DTIC Science & Technology

2004-08-01

O’Laughlin, R, Landini, C, Shalhav, AL, Stadler, WM, Zagaja , GP, Desai, A, Holroyd, K, Sokoloff, MH. Neoadjuvant combination anti- angiogenesis and androgen...CB, Zagaja , GP, Shalhav, AL. Neoadjuvant combination androgen ablation and anti-angiogenesis therapy in men with high grade and locally-advanced

Embodied masculinity and androgen deprivation therapy.

PubMed

Oliffe, John

2006-05-01

This paper describes the findings from an ethnographic study of 16 Anglo-Australian men treated with androgen deprivation therapy (ADT) for advanced prostate cancer. Utilising a social constructionist gendered analysis, participants' experiences, particularly in relation to embodied masculinity, are described in the context of reduced testosterone that accompany ADT. The findings indicated that participants reformulated many ideals of hegemonic masculinity in response to functional body changes. However, hegemonic masculinity strongly influenced participants' philosophical resolve to "fight" prostate cancer. The findings are considered in broader ongoing debates about essentialist sex and the social construction of gender.

Accuracy of Physical Examination, Ultrasonography, and Mammography in Predicting Residual Pathologic Tumor Size in Patients Treated With Neoadjuvant Chemotherapy

PubMed Central

Chagpar, Anees B.; Middleton, Lavinia P.; Sahin, Aysegul A.; Dempsey, Peter; Buzdar, Aman U.; Mirza, Attiqa N.; Ames, Fredrick C.; Babiera, Gildy V.; Feig, Barry W.; Hunt, Kelly K.; Kuerer, Henry M.; Meric-Bernstam, Funda; Ross, Merrick I.; Singletary, S Eva

2006-01-01

Objective: To assess the accuracy of physical examination, ultrasonography, and mammography in predicting residual size of breast tumors following neoadjuvant chemotherapy. Background: Neoadjuvant chemotherapy is an accepted part of the management of stage II and III breast cancer. Accurate prediction of residual pathologic tumor size after neoadjuvant chemotherapy is critical in guiding surgical therapy. Although physical examination, ultrasonography, and mammography have all been used to predict residual tumor size, there have been conflicting reports about the accuracy of these methods in the neoadjuvant setting. Methods: We reviewed the records of 189 patients who participated in 1 of 2 protocols using doxorubicin-containing neoadjuvant chemotherapy, and who had assessment by physical examination, ultrasonography, and/or mammography no more than 60 days before their surgical resection. Size correlations were performed using Spearman rho analysis. Clinical and pathologic measurements were also compared categorically using the weighted kappa statistic. Results: Size estimates by physical examination, ultrasonography, and mammography were only moderately correlated with residual pathologic tumor size after neoadjuvant chemotherapy (correlation coefficients: 0.42, 0.42, and 0.41, respectively), with an accuracy of ±1 cm in 66% of patients by physical examination, 75% by ultrasonography, and 70% by mammography. Kappa values (0.24–0.35) indicated poor agreement between clinical and pathologic measurements. Conclusion: Physical examination, ultrasonography, and mammography were only moderately useful for predicting residual pathologic tumor size after neoadjuvant chemotherapy. PMID:16432360

Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features

PubMed Central

Gangeh, Mehrdad; Tadayyon, Hadi; Sadeghi-Naini, Ali; Gandhi, Sonal; Wright, Frances C.; Slodkowska, Elzbieta; Curpen, Belinda; Tran, William; Czarnota, Gregory J.

2018-01-01

Background Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC) settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS), textural analysis and molecular features in patients with locally advanced breast cancer. Methods The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF) data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR), partial responders (PR), and non-responders (NR). Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times. Results Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the three response groups with accuracies less than 60% at all scan time points. Recurrence free survival (RFS) of response groups determined based on combined features followed similar trend as determined based on clinical and pathology. Conclusions This work demonstrates the potential of using QUS, texture and molecular features for predicting the response of primary breast tumors to chemotherapy early, and guiding the treatment planning of refractory patients. PMID:29298305

MRI assessment and outcomes in patients receiving neoadjuvant chemotherapy only for primary rectal cancer: long-term results from the GEMCAD 0801 trial.

PubMed

Patel, U B; Brown, G; Machado, I; Santos-Cores, J; Pericay, C; Ballesteros, E; Salud, A; Isabel-Gil, M; Montagut, C; Maurel, J; Ramón-Ayuso, J; Martin, N; Estevan, R; Fernandez-Martos, C

2017-02-01

Primary chemotherapy has been tested as a possible approach for patients with high risk features but predicted clear mesorectal margins on preoperative MRI assessment. This study investigates the prognostic relevance of baseline and post-treatment MRI and pathology staging in rectal cancer patients undergoing primary chemotherapy. Forty-six patients with T3 tumour > =2 mm from the mesorectal fascia were prospectively treated with Neoadjuvant Capecitabine, Oxaliplatin and Bevacizumab prior to surgery between 2009 and 2011. The baseline and post-treatment MRI: T, Nodal and Extra-mural venous invasion (EMVI) status were recorded as well as post-treatment MRI Tumour regression grade (TRG) and modified-RECIST assessment of tumour length. The post-treatment pathology (yp) assessments of T3 substage, N, EMVI and TRG status were also recorded. Three-year disease-free survival (DFS) and cumulative incidence of recurrence were estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging and response on MRI and pathology with survival outcomes. About 46 patients underwent neoadjuvant chemotherapy alone for high risk margin safe primary rectal cancer. The median follow-up was 41 months, 5 patients died and 11 patients experienced relapse (2 local, 8 distant and 1 both). In total 23/46 patients were identified with MRI features of EMVI at baseline. mrEMVI positive status carried independent prognostic significance for DFS (P = 0.0097) with a hazard ratio of 31.33 (95% CI: 2.3-425.4). The histopathologic factor that was of independent prognostic importance was a final ypT downstage of ypT3a or less, hazard ratio: 14.0 (95% CI: 1.5-132.5). mrEMVI is an independent prognostic factor at baseline for poor outcomes in rectal cancer treated with neoadjuvant chemotherapy while ≤ypT3a is associated with an improvement in DFS. Future preoperative therapy evaluation in rectal cancer patients will need to stratify treatment according to baseline EMVI status as a crucial risk factor for recurrence in patients with predicted CRM clear rectal cancer. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characterizing the Hypermutated Subtype of Advanced Prostate Cancer as a Predictive Biomarker for Precision Medicine

DTIC Science & Technology

2016-10-01

endometrial can- cer patients. Cancer Res 2006, 66:7810e7817jmd.amjpathol.org - The Journal of Molecular Diagnostics E U RO P E AN URO L OG Y 6 9 ( 2 0 1 6...PSA = prostate-specific antigen. E U RO P E AN URO L OGY 6 9 ( 2 0 1 6 ) 9 9 2 – 9 9 5 993adenocarcinoma and underwent neoadjuvant androgen deprivation...copies of genes. Selected genes are labeled. E U RO P E AN URO LOG Y 6 9 ( 2 0 1 6 ) 9 9 2 – 9 9 5994presence of biallelic BRCA2 copy loss in the primary

Clostridial abdominal gas gangrene masquerading as a bowel perforation in an advanced-stage ovarian cancer patient.

PubMed

Abaid, L N; Thomas, R H; Epstein, H D; Goldstein, B H

2013-08-01

The coexistence of clostridial gas gangrene and a gynecologic malignancy is extremely rare, with very few cases involving ovarian cancer. A patient originally presented to our gynecologic oncology service with stage IV ovarian cancer; she underwent a diagnostic laparoscopy and neoadjuvant chemotherapy. On postoperative day 6, the patient developed severe abdominal pain, nausea, and emesis, suggestive of a bowel perforation. Further evaluation confirmed that her symptoms were attributed to Clostridium perfringens-related gas gangrene. Despite immediate surgical intervention, the patient succumbed to her disease. Clostridial gas gangrene is associated with an extremely high mortality rate. Therefore, accurate detection and prompt management are indispensable to ensuring a favorable patient outcome.

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

Randomized, Double-Blinded, Placebo-Controlled, Trial of Risedronate for the Prevention of Bone Mineral Density Loss in Nonmetastatic Prostate Cancer Patients Receiving Radiation Therapy Plus Androgen Deprivation Therapy

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

Choo, Richard; Lukka, Himu; Cheung, Patrick

Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5more » on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT.« less

MicroRNA expressions associated with progression of prostate cancer cells to antiandrogen therapy resistance

PubMed Central

2014-01-01

Background Development of resistance to androgen deprivation therapy (ADT) is a major obstacle for the management of advanced prostate cancer. Therapies with androgen receptor (AR) antagonists and androgen withdrawal initially regress tumors but development of compensatory mechanisms including AR bypass signaling leads to re-growth of tumors. MicroRNAs (miRNAs) are small regulatory RNAs that are involved in maintenance of cell homeostasis but are often altered in tumor cells. Results In this study, we determined the association of genome wide miRNA expression (1113 unique miRNAs) with development of resistance to ADT. We used androgen sensitive prostate cancer cells that progressed to ADT and AR antagonist Casodex (CDX) resistance upon androgen withdrawal and treatment with CDX. Validation of expression of a subset of 100 miRNAs led to identification of 43 miRNAs that are significantly altered during progression of cells to treatment resistance. We also show a correlation of altered expression of 10 proteins targeted by some of these miRNAs in these cells. Conclusions We conclude that dynamic alterations in miRNA expression occur early on during androgen deprivation therapy, and androgen receptor blockade. The cumulative effect of these altered miRNA expression profiles is the temporal modulation of multiple signaling pathways promoting survival and acquisition of resistance. These early events are driving the transition to castration resistance and cannot be studied in already developed CRPC cell lines or tissues. Furthermore our results can be used a prognostic marker of cancers with a potential to be resistant to ADT. PMID:24387052

A description of heterosexual couples' sexual adjustment to androgen deprivation therapy for prostate cancer.

PubMed

Walker, Lauren M; Robinson, John W

2011-08-01

It is estimated that 600,000 men are currently living in North America with castrate levels of testosterone as a result of androgen deprivation therapy for prostate cancer. The goal of this study was to explore how patients and their partners adjust to changes associated with androgen deprivation therapy (ADT). Eighteen couples were interviewed regarding their adjustment to ADT side effects. Three distinct patterns of adjustment were observed. One group of couples had assumed sex to be impossible after commencing ADT, and quickly accepted the loss of sex in exchange for a life extending treatment (four couples). Another group was found to be struggling to either maintain satisfying sex or adapt to the loss of their sexual relationship (five couples). The third group had struggled, but found that they were satisfied with their sexual outcome (nine couples). A subset of these couples successfully adjusted to changes in the man's sexual function and found satisfying ways to be sexually active (five couples). The finding that some couples are able to enjoy satisfying sex, despite castrate levels of testosterone, raised questions about how patients are prepared to undergo ADT and how they are managed. It is possible that both the couples who gave up on sex because they believed that satisfying sex was impossible, and the couples who continued to struggle to adjust, may have faired better if they had known how other couples are able to maintain satisfying sex while the man is androgen-deprived. Copyright © 2010 John Wiley & Sons, Ltd.

Hypoxic Tumor Kinase Signaling Mediated by STAT5A in Development of Castration-Resistant Prostate Cancer

PubMed Central

Røe, Kathrine; Bratland, Åse; Vlatkovic, Ljiljana; Ragnum, Harald Bull; Saelen, Marie Grøn; Olsen, Dag Rune; Marignol, Laure; Ree, Anne Hansen

2013-01-01

In this study, we hypothesized that androgen-deprivation therapy (ADT) in prostate cancer, although initially efficient, induces changes in the tumor kinome, which subsequently promote development of castration-resistant (CR) disease. Recognizing the correlation between tumor hypoxia and poor prognosis in prostate cancer, we further hypothesized that such changes might be influenced by hypoxia. Microarrays with 144 kinase peptide substrates were applied to analyze CWR22 prostate carcinoma xenograft samples from ADT-naïve, androgen-deprived (AD), long-term AD (ADL), and CR disease stages. The impact of hypoxia was assessed by matching the xenograft kinase activity profiles with those acquired from hypoxic and normoxic prostate carcinoma cell cultures, whereas the clinical relevance was evaluated by analyzing prostatectomy tumor samples from patients with locally advanced disease, either in ADT-naïve or early CR disease stages. By using this novel peptide substrate microarray method we revealed high kinase activity mediated by signal transducer and activator of transcription 5A (STAT5A) in CR prostate cancer. Additionally, we uncovered high STAT5A kinase activity already in regressing ADL xenografts, before renewed CR growth was evidenced. Finally, since increased STAT5A kinase activity also was detected after exposing prostate carcinoma cells to hypoxia, we propose long-term ADT to induce tumor hypoxia and stimulate STAT5A kinase activity, subsequently leading to renewed CR tumor growth. Hence, the study detected STAT5A as a candidate to be further investigated for its potential as marker of advanced prostate cancer and as possible therapeutic target protein. PMID:23675504

Concept and viability of androgen annihilation for advanced prostate cancer.

PubMed

Mohler, James L

2014-09-01

There remains no standard of care for patients with a rising prostate-specific antigen level after radical prostatectomy or radiotherapy but who have no radiographic metastases, even though this is the second largest group of patients with prostate cancer (CaP) in the United States. Androgen deprivation therapy (ADT) may cure some men with advanced CaP based on single-institution series and a randomized clinical trial of immediate versus delayed ADT for men found to have pelvic lymph node metastasis at the time of radical prostatectomy. ADT may be more effective when initiated for minimal disease burden, which can be detected using PSA after radical prostatectomy or radiotherapy, and if more complete disruption of the androgen axis using newer agents decreases the chance that androgen-sensitive cells survive to adapt to a low-androgen environment. Androgens may be "annihilated" simultaneously using a luteinizing hormone-releasing hormone antagonist or agonist to inhibit testicular production of testosterone, a P45017A1 (CYP17A1) inhibitor to diminish metabolism of testosterone via the adrenal pathway and dihydrotestosterone (DHT) via the backdoor pathway, a 5α-reductase (SRD5A) inhibitor to diminish testosterone reduction to DHT and backdoor metabolism of progesterone substrates to DHT, and a newer antiandrogen to compete better with DHT for the androgen receptor ligand-binding domain. Early initiation of androgen annihilation for induction as part of planned intermittent ADT should be safe, may reduce tumor burden below a threshold that allows eradication by the immune system, and may cure many men who have failed definitive local therapy. © 2014 American Cancer Society.

Analysis and comparison of safety models using average daily, average hourly, and microscopic traffic.

PubMed

Wang, Ling; Abdel-Aty, Mohamed; Wang, Xuesong; Yu, Rongjie

2018-02-01

There have been plenty of traffic safety studies based on average daily traffic (ADT), average hourly traffic (AHT), or microscopic traffic at 5 min intervals. Nevertheless, not enough research has compared the performance of these three types of safety studies, and seldom of previous studies have intended to find whether the results of one type of study is transferable to the other two studies. First, this study built three models: a Bayesian Poisson-lognormal model to estimate the daily crash frequency using ADT, a Bayesian Poisson-lognormal model to estimate the hourly crash frequency using AHT, and a Bayesian logistic regression model for the real-time safety analysis using microscopic traffic. The model results showed that the crash contributing factors found by different models were comparable but not the same. Four variables, i.e., the logarithm of volume, the standard deviation of speed, the logarithm of segment length, and the existence of diverge segment, were positively significant in the three models. Additionally, weaving segments experienced higher daily and hourly crash frequencies than merge and basic segments. Then, each of the ADT-based, AHT-based, and real-time models was used to estimate safety conditions at different levels: daily and hourly, meanwhile, the real-time model was also used in 5 min intervals. The results uncovered that the ADT- and AHT-based safety models performed similar in predicting daily and hourly crash frequencies, and the real-time safety model was able to provide hourly crash frequency. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrating diet and exercise into care of prostate cancer patients on androgen deprivation therapy

PubMed Central

Moyad, Mark A; Newton, Robert U; Tunn, Ulf W; Gruca, Damian

2016-01-01

Improved diagnosis and treatment regimens have resulted in greater longevity for men with prostate cancer. This has led to an increase in both androgen deprivation therapy (ADT) use and duration of exposure, and therefore to its associated adverse effects, such as sexual dysfunction, osteoporosis, reduced muscle mass, increased fat mass, and increased incidence of cardiovascular disease and type 2 diabetes. Given that the adverse effects of ADT are systemic, often debilitating, and difficult to treat, efforts continue in the development of new strategies for long-term management of prostate cancer. The PubMed database was searched to select trials, reviews, and meta-analyses in English using such search terms as “prostate cancer” and “androgen deprivation therapy”, “cardiovascular risk”, “lean body mass”, “exercise”, and “diet”. The initial searches produced 379 articles with dates 2005 or more recent. Articles published after 2004 were favored. This review utilizes the latest data to provide a status update on the effects of exercise and diet on patients with prostate cancer, focusing on ADT-associated side effects, and it discusses the evidence for such interventions. Since the evidence of large-scale trials in patients with prostate cancer is missing, and an extrapolation of supporting data to all patient subgroups cannot be provided, individualized risk assessments remain necessary before the initiation of exercise and diet programs. Exercise, diet, and nutritional supplementation interventions have the potential to provide effective, accessible, and relatively inexpensive strategies for mitigating ADT-associated toxicities without introducing additional adverse effects. PMID:27574584

Treatment strategy for metastatic prostate cancer with extremely high PSA level: reconsidering the value of vintage therapy.

PubMed

Yamada, Yasutaka; Sakamoto, Shinichi; Amiya, Yoshiyasu; Sasaki, Makoto; Shima, Takayuki; Komiya, Akira; Suzuki, Noriyuki; Akakura, Koichiro; Ichikawa, Tomohiko; Nakatsu, Hiroomi

2018-05-04

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml -1 ), intermediate (100-999 ng ml -1 ), and high (≥1000 ng ml -1 ). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

Patient-centered outcomes to decide treatment strategy for patients with low rectal cancer.

PubMed

Honda, Michitaka; Akiyoshi, Takashi; Noma, Hisashi; Ogura, Atsushi; Nagasaki, Toshiya; Konishi, Tsuyoshi; Fujimoto, Yoshiya; Nagayama, Satoshi; Fukunaga, Yosuke; Ueno, Masashi

2016-10-01

For patients with low-lying rectal cancer, the feasibility of anus-preserving surgery in combination with neoadjuvant chemoradiotherapy (NACRT) has been not well established from the perspective of patient-centered outcomes. We investigated 278 patients with low-lying rectal adenocarcinoma from 2005 to 2012. We compared their symptoms and QOL scores of patients who underwent anus-preserving surgery with (n = 88) and without (n = 143) NACRT according to the Wexner scale, EORTC QLQ C-30, CR29, and the modified fecal incontinence quality life scale (mFIQL). Furthermore, to assess the rationale for intersphincteric resection (ISR) with NACRT, we also compared QOL of patients who underwent ISR with NACRT (n = 31) and abdominoperineal resection (APR, n = 47). The adjusted mean differences of the Wexner score estimates of the patients who underwent ISR and very low anterior resection (VLAR) with or without NACRT were 5.29 (P = 0.004) and 2.67 (P = 0.009), respectively. No significant difference was observed in the QOL scores of two treatment groups. Furthermore, there were no significant differences in the QOL or function scores of patients who underwent ISR with NACRT and APR. The incontinence was significantly worse in patients who receive NACRT. However, there were no significant differences in their QOL or function scores. J. Surg. Oncol. 2016;114:630-636. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Dual-targeted tRNA-dependent amidotransferase ensures both mitochondrial and chloroplastic Gln-tRNAGln synthesis in plants

PubMed Central

Pujol, Claire; Bailly, Marc; Kern, Daniel; Maréchal-Drouard, Laurence; Becker, Hubert; Duchêne, Anne-Marie

2008-01-01

Aminoacyl-tRNAs are generally formed by direct attachment of an amino acid to tRNAs by aminoacyl-tRNA synthetases, but Gln-tRNA is an exception to this rule. Gln-tRNAGln is formed by this direct pathway in the eukaryotic cytosol and in protists or fungi mitochondria but is formed by an indirect transamidation pathway in most of bacteria, archaea, and chloroplasts. We show here that the formation of Gln-tRNAGln is also achieved by the indirect pathway in plant mitochondria. The mitochondrial-encoded tRNAGln, which is the only tRNAGln present in mitochondria, is first charged with glutamate by a nondiscriminating GluRS, then is converted into Gln-tRNAGln by a tRNA-dependent amidotransferase (AdT). The three subunits GatA, GatB, and GatC are imported into mitochondria and assemble into a functional GatCAB AdT. Moreover, the mitochondrial pathway of Gln-tRNAGln formation is shared with chloroplasts as both the GluRS, and the three AdT subunits are dual-imported into mitochondria and chloroplasts. PMID:18441100

Multidisciplinary design optimisation of a recurve bow based on applications of the autogenetic design theory and distributed computing

NASA Astrophysics Data System (ADS)

Fritzsche, Matthias; Kittel, Konstantin; Blankenburg, Alexander; Vajna, Sándor

2012-08-01

The focus of this paper is to present a method of multidisciplinary design optimisation based on the autogenetic design theory (ADT) that provides methods, which are partially implemented in the optimisation software described here. The main thesis of the ADT is that biological evolution and the process of developing products are mainly similar, i.e. procedures from biological evolution can be transferred into product development. In order to fulfil requirements and boundary conditions of any kind (that may change at any time), both biological evolution and product development look for appropriate solution possibilities in a certain area, and try to optimise those that are actually promising by varying parameters and combinations of these solutions. As the time necessary for multidisciplinary design optimisations is a critical aspect in product development, ways to distribute the optimisation process with the effective use of unused calculating capacity, can reduce the optimisation time drastically. Finally, a practical example shows how ADT methods and distributed optimising are applied to improve a product.

Predictors of overall and recurrence-free survival after neoadjuvant chemotherapy for gastroesophageal adenocarcinoma: Pooled analysis of individual patient data (IPD) from randomized controlled trials (RCTs).

PubMed

Ronellenfitsch, U; Schwarzbach, M; Hofheinz, R; Kienle, P; Nowak, K; Kieser, M; Slanger, T E; Burmeister, B; Kelsen, D; Niedzwiecki, D; Schuhmacher, C; Urba, S; van de Velde, C; Walsh, T N; Ychou, M; Jensen, K

2017-08-01

Neoadjuvant chemotherapy improves prognosis of patients with locally advanced gastroesophageal adenocarcinoma. The aim of this study was to identify predictors for postoperative survival following neoadjuvant therapy. These could be useful in deciding about postoperative continuation of chemotherapy. This meta-analysis used IPD from RCTs comparing neoadjuvant chemotherapy with surgery alone for gastroesophageal adenocarcinoma. Trials providing IPD on age, sex, performance status, pT/N stage, resection status, overall and recurrence-free survival were included. Survival was calculated in the entire study population and subgroups stratified by supposed predictors and compared using the log-rank test. Multivariable Cox models were used to identify independent survival predictors. Four RCTs providing IPD from 553 patients fulfilled the inclusion criteria. (y)pT and (y)pN stage and resection status strongly predicted postoperative survival both after neoadjuvant therapy and surgery alone. Patients with R1 resection after neoadjuvant therapy survived longer than those with R1 resection after surgery alone. Patients with stage pN0 after surgery alone had better prognosis than those with ypN0 after neoadjuvant therapy. Patients with stage ypT3/4 after neoadjuvant therapy survived longer than those with stage pT3/4 after surgery alone. Multivariable regression identified resection status and (y)pN stage as predictors of survival in both groups. (y)pT stage predicted survival only after surgery alone. After neoadjuvant therapy for gastroesophageal adenocarcinoma, survival is determined by the same factors as after surgery alone. However, ypT stage is not an independent predictor. These results can facilitate the decision about postoperative continuation of chemotherapy in pretreated patients. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Application value of biplane transrectal ultrasonography plus ultrasonic elastosonography and contrast-enhanced ultrasonography in preoperative T staging after neoadjuvant chemoradiotherapy for rectal cancer.

PubMed

Xiao, Ying; Xu, Dong; Ju, Haixing; Yang, Chen; Wang, Liping; Wang, Jinming; Hazle, John D; Wang, Dongguo

2018-07-01

To determine the accuracy of biplane transrectal ultrasonography (TRUS) plus ultrasonic elastosonography (UE) and contrast-enhanced ultrasonography (CEUS) in preoperative T staging after neoadjuvant chemoradiotherapy for rectal cancer. Fifty-three patients with advanced lower rectal cancer were examined before and after neoadjuvant chemoradiotherapy with use of TRUS plus UE and CEUS and were diagnosed as having T stage disease. We compared ultrasonic T stages before and after neoadjuvant chemoradiotherapy and analyzed any changes. Also, with postoperative pathological stages as the gold standard, we compared ultrasonic and pathological T stages and determined their consistency by the kappa statistic. For patients with rectal cancer, ultrasonic T stages were lower after neoadjuvant chemoradiotherapy than before, with a statistically significant difference (P < 0.05). The posttreatment downstaging rate was 39.6% (21/53). A total of 84.9% received correct staging with use of biplane TRUS plus UE and CEUS in the evaluation of preoperative T staging after neoadjuvant chemoradiotherapy for rectal cancer, which was highly consistent with that of pathological staging (κ = 0.768, P < 0.05). Its sensitivities were 80.0%, 50.0%, 75.0%, 96.3%, and 100% in the diagnoses of stages T0 to T4 rectal cancers, respectively; the specificities were 95.4%, 97.9%, 95.1%, 88.5%, and 100% at stages T0 to T4, respectively. Biplane TRUS plus UE and CEUS can be used to accurately perform preoperative T staging in rectal cancer after neoadjuvant chemoradiotherapy; in addition, this procedure well reflects changes in depth of rectal cancer invasion into the intestinal wall before and after neoadjuvant chemoradiotherapy. It is of great value in clinically evaluating the efficacy of neoadjuvant chemoradiotherapy, in selecting therapeutic regimens, and in avoiding overtreatment. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of obesity on pathological complete response and survival in breast cancer patients receiving uncapped doses of neoadjuvant anthracycline-taxane-based chemotherapy.

PubMed

Farr, Alex; Stolz, Myriam; Baumann, Lukas; Bago-Horvath, Zsuzsanna; Oppolzer, Elisabeth; Pfeiler, Georg; Seifert, Michael; Singer, Christian F

2017-06-01

The effect of obesity in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to determine the obesity-related effect on pathological complete response (pCR) and survival in women receiving full uncapped doses of NAC. We retrospectively analyzed the data of all consecutive women who underwent anthracycline-taxane-based NAC for primary breast cancer between 2005 and 2015 at the Department of Obstetrics and Gynecology, Medical University of Vienna. Following the WHO criteria, women with a body mass index (BMI) ≥30 kg/m 2 at baseline were considered obese, whereas those with a BMI <30 kg/m 2 were considered non-obese. Those with dose reductions or dose capping were not eligible for study inclusion. Cox regression and logistic regression were performed. The Kaplan-Meier method was used to analyze disease-free, progression-free, and overall survival. The pCR served as the main outcome measure. Among 120 women who received neoadjuvant epirubicin plus cyclophosphamide and docetaxel, 28 (23.3%) were obese and 92 (76.7%) were non-obese. In the multivariate logistic regression model that adjusted for potentially confounding variables, obesity had an independent positive predictive effect on pCR (OR 4.29, 95% CI, 1.42-13.91; p = 0.011), which was significant in the postmenopausal subgroup (OR 4.72, 95% CI, 1.47-15.84; p = 0.01). When comparing non-obese with obese women, we found that obese women experienced longer progression-free survival (HR 0.10, 95% CI, 8.448 × 10 -4 -0.81; p = 0.025). Obese women receiving full uncapped doses of anthracycline-taxane-based NAC have increased pCR and favorable progression-free survival. This could result from increased dose intensity with increased efficacy and toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Impact of Skin-Sparing Mastectomy With Immediate Reconstruction in Patients With Stage III Breast Cancer Treated With Neoadjuvant Chemotherapy and Postmastectomy Radiation

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

Prabhu, Roshan; Godette, Karen; Winship Cancer Institute, Emory University, Atlanta, GA

2012-03-15

Purpose: The safety and efficacy of skin-sparing mastectomy (SSM) with immediate reconstruction (IR) in patients with locally advanced breast cancer are unclear. The purpose of this study is to compare the outcomes of women with noninflammatory Stage III SSM with IR vs. non-SSM-treated women who underwent neoadjuvant chemotherapy and adjuvant radiation therapy (XRT). Methods and Materials: Between October 1997 and March 2010, 100 consecutive patients (40 SSM with IR vs. 60 non-SSM) with Stage III breast cancer received anthracycline- and/or taxane-based neoadjuvant chemotherapy, mastectomy, and adjuvant XRT. Clinical stage (SSM with IR vs. for non-SSM) was IIIA (75% vs. 67%),more » IIIB (8% vs. 18%), and IIIC (8% vs. 8%). Tumors greater than 5 cm were found in 74% vs. 69%; 97% of patients in both groups were clinically node positive; and 8% vs. 18% had T4b disease. Results: The time from initial biopsy to XRT was prolonged for SSM-IR patients (274 vs. 254 days, p = 0.04), and there was a trend toward XRT delay of more than 8 weeks (52% vs. 31%, p = 0.07) after surgery. The rate of complications requiring surgical intervention was higher in the SSM-IR group (37.5% vs. 5%, p < 0.001). The 2-year actuarial locoregional control, breast cancer-specific survival, and overall survival rates for SSM with IR vs. non-SSM were 94.7% vs. 97.4%, 91.5% vs. 86.3%, and 87.4% vs. 84.8%, respectively (p = not significant). Conclusions: In our small study with limited follow-up, SSM with IR prolonged overall cancer treatment time and trended toward delaying XRT but did not impair oncologic outcomes. Complication rates were significantly higher in this group. Longer follow-up is needed.« less

The impact of skin-sparing mastectomy with immediate reconstruction in patients with Stage III breast cancer treated with neoadjuvant chemotherapy and postmastectomy radiation.

PubMed

Prabhu, Roshan; Godette, Karen; Carlson, Grant; Losken, Albert; Gabram, Sheryl; Fasola, Carolina; O'Regan, Ruth; Zelnak, Amelia; Torres, Mylin

2012-03-15

The safety and efficacy of skin-sparing mastectomy (SSM) with immediate reconstruction (IR) in patients with locally advanced breast cancer are unclear. The purpose of this study is to compare the outcomes of women with noninflammatory Stage III SSM with IR vs. non-SSM-treated women who underwent neoadjuvant chemotherapy and adjuvant radiation therapy (XRT). Between October 1997 and March 2010, 100 consecutive patients (40 SSM with IR vs. 60 non-SSM) with Stage III breast cancer received anthracycline- and/or taxane-based neoadjuvant chemotherapy, mastectomy, and adjuvant XRT. Clinical stage (SSM with IR vs. for non-SSM) was IIIA (75% vs. 67%), IIIB (8% vs. 18%), and IIIC (8% vs. 8%). Tumors greater than 5 cm were found in 74% vs. 69%; 97% of patients in both groups were clinically node positive; and 8% vs. 18% had T4b disease. The time from initial biopsy to XRT was prolonged for SSM-IR patients (274 vs. 254 days, p = 0.04), and there was a trend toward XRT delay of more than 8 weeks (52% vs. 31%, p = 0.07) after surgery. The rate of complications requiring surgical intervention was higher in the SSM-IR group (37.5% vs. 5%, p < 0.001). The 2-year actuarial locoregional control, breast cancer-specific survival, and overall survival rates for SSM with IR vs. non-SSM were 94.7% vs. 97.4%, 91.5% vs. 86.3%, and 87.4% vs. 84.8%, respectively (p = not significant). In our small study with limited follow-up, SSM with IR prolonged overall cancer treatment time and trended toward delaying XRT but did not impair oncologic outcomes. Complication rates were significantly higher in this group. Longer follow-up is needed. Copyright © 2012 Elsevier Inc. All rights reserved.

A preoperative low cancer antigen 125 level (≤25.8 mg/dl) is a useful criterion to determine the optimal timing of interval debulking surgery following neoadjuvant chemotherapy in epithelial ovarian cancer.

PubMed

Morimoto, Akemi; Nagao, Shoji; Kogiku, Ai; Yamamoto, Kasumi; Miwa, Maiko; Wakahashi, Senn; Ichida, Kotaro; Sudo, Tamotsu; Yamaguchi, Satoshi; Fujiwara, Kiyoshi

2016-06-01

The purpose of this study is to investigate the clinical characteristics to determine the optimal timing of interval debulking surgery following neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer. We reviewed the charts of women with advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer who underwent interval debulking surgery following neoadjuvant chemotherapy at our cancer center from April 2006 to April 2014. There were 139 patients, including 91 with ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) Stage IIIc in 56 and IV in 35], two with fallopian tube cancers (FIGO Stage IV, both) and 46 with primary peritoneal cancer (FIGO Stage IIIc in 27 and IV in 19). After 3-6 cycles (median, 4 cycles) of platinum-based chemotherapy, interval debulking surgery was performed. Sixty-seven patients (48.2%) achieved complete resection of all macroscopic disease, while 72 did not. More patients with cancer antigen 125 levels ≤25.8 mg/dl at pre-interval debulking surgery achieved complete resection than those with higher cancer antigen 125 levels (84.7 vs. 21.3%; P< 0.0001). Patients with no ascites at pre-interval debulking surgery also achieved a higher complete resection rate (63.5 vs. 34.1%; P< 0.0001). Moreover, most patients (86.7%) with cancer antigen 125 levels ≤25.8 mg/dl and no ascites at pre-interval debulking surgery achieved complete resection. A low cancer antigen 125 level of ≤25.8 mg/dl and the absence of ascites at pre-interval debulking surgery are major predictive factors for complete resection during interval debulking surgery and present useful criteria to determine the optimal timing of interval debulking surgery. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

Pucci, Sabina, E-mail: sabina.pucci@uniroma2.it; Polidoro, Chiara; Joubert, Alessandro

Purpose: The identification of predictive biomarkers for neoadjuvant chemoradiation therapy (CRT) is a current clinical need. The heterodimer Ku70/80 plays a critical role in DNA repair and cell death induction after damage. The aberrant expression and localization of these proteins fail to control DNA repair and apoptosis. sClusterin is the Ku70 partner that sterically inhibits Bax-dependent cell death after damage in some pathologic conditions. This study sought to evaluate the molecular relevance of Ku70-Ku80-Clu as a molecular cluster predicting the response to neoadjuvant CRT in patients with locally advanced rectal cancer (LARC). Methods and Materials: Patients enrolled in this studymore » underwent preoperative CRT followed by surgical excision. A retrospective study based on individual response, evaluated by computed tomography and diffusion-weighted magnetic resonance imaging, identified responder (56%) and no-responder patients (44%). Ku70/80 and Clu expression were observed in biopsy specimens obtained before and after treatment with neoadjuvant CRT from the same LARC patients. In vitro studies before and after irradiation were also performed on radioresistant (SW480) and radiosensitive (SW620) colorectal cancer cell lines, mimicking sensitive or resistant tumor behavior. Results: We found a conventional nuclear localization of Ku70/80 in pretherapeutic tumor biopsies of responder patients, in agreement with their role in DNA repair and regulating apoptosis. By contrast, in the no-responder population we observed an unconventional overexpression of Ku70 in the cytoplasm (P<.001). In this context we also overexpression of sClu in the cytoplasm, which accorded with its role in stabilizing of Bax-Ku70 complex, inhibiting Bax-dependent apoptosis. Strikingly, Ku80 in these tumor tissues was lost (P<.005). In vitro testing of colon cancer cells finally confirmed the results observed in tumor biopsy specimens, proving that Ku70/80-Clu deregulation is extensively involved in the resistance mechanism. Conclusion: These results strongly suggest a potential role of these proteins as a new prognostic tool to predict the response to chemoradiation in LARC.« less

Spatial-Temporal [{sup 18}F]FDG-PET Features for Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiation Therapy

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

Tan, Shan; Department of Control Science and Engineering, Huazhong University of Science and Technology, Wuhan; Kligerman, Seth

2013-04-01

Purpose: To extract and study comprehensive spatial-temporal {sup 18}F-labeled fluorodeoxyglucose ([{sup 18}F]FDG) positron emission tomography (PET) features for the prediction of pathologic tumor response to neoadjuvant chemoradiation therapy (CRT) in esophageal cancer. Methods and Materials: Twenty patients with esophageal cancer were treated with trimodal therapy (CRT plus surgery) and underwent [{sup 18}F]FDG-PET/CT scans both before (pre-CRT) and after (post-CRT) CRT. The 2 scans were rigidly registered. A tumor volume was semiautomatically delineated using a threshold standardized uptake value (SUV) of ≥2.5, followed by manual editing. Comprehensive features were extracted to characterize SUV intensity distribution, spatial patterns (texture), tumor geometry, andmore » associated changes resulting from CRT. The usefulness of each feature in predicting pathologic tumor response to CRT was evaluated using the area under the receiver operating characteristic curve (AUC) value. Results: The best traditional response measure was decline in maximum SUV (SUV{sub max}; AUC, 0.76). Two new intensity features, decline in mean SUV (SUV{sub mean}) and skewness, and 3 texture features (inertia, correlation, and cluster prominence) were found to be significant predictors with AUC values ≥0.76. According to these features, a tumor was more likely to be a responder when the SUV{sub mean} decline was larger, when there were relatively fewer voxels with higher SUV values pre-CRT, or when [{sup 18}F]FDG uptake post-CRT was relatively homogeneous. All of the most accurate predictive features were extracted from the entire tumor rather than from the most active part of the tumor. For SUV intensity features and tumor size features, changes were more predictive than pre- or post-CRT assessment alone. Conclusion: Spatial-temporal [{sup 18}F]FDG-PET features were found to be useful predictors of pathologic tumor response to neoadjuvant CRT in esophageal cancer.« less

Next-generation sequencing of circulating tumor DNA to predict recurrence in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy.

PubMed

Chen, Yu-Hsiang; Hancock, Bradley A; Solzak, Jeffrey P; Brinza, Dumitru; Scafe, Charles; Miller, Kathy D; Radovich, Milan

2017-01-01

Next-generation sequencing to detect circulating tumor DNA is a minimally invasive method for tumor genotyping and monitoring therapeutic response. The majority of studies have focused on detecting circulating tumor DNA from patients with metastatic disease. Herein, we tested whether circulating tumor DNA could be used as a biomarker to predict relapse in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy. In this study, we analyzed samples from 38 early-stage triple-negative breast cancer patients with matched tumor, blood, and plasma. Extracted DNA underwent library preparation and amplification using the Oncomine Research Panel consisting of 134 cancer genes, followed by high-coverage sequencing and bioinformatics. We detected high-quality somatic mutations from primary tumors in 33 of 38 patients. TP53 mutations were the most prevalent (82%) followed by PIK3CA (16%). Of the 33 patients who had a mutation identified in their primary tumor, we were able to detect circulating tumor DNA mutations in the plasma of four patients (three TP53 mutations, one AKT1 mutation, one CDKN2A mutation). All four patients had recurrence of their disease (100% specificity), but sensitivity was limited to detecting only 4 of 13 patients who clinically relapsed (31% sensitivity). Notably, all four patients had a rapid recurrence (0.3, 4.0, 5.3, and 8.9 months). Patients with detectable circulating tumor DNA had an inferior disease free survival ( p  < 0.0001; median disease-free survival: 4.6 mos. vs. not reached; hazard ratio = 12.6, 95% confidence interval: 3.06-52.2). Our study shows that next-generation circulating tumor DNA sequencing of triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy can predict recurrence with high specificity, but moderate sensitivity. For those patients where circulating tumor DNA is detected, recurrence is rapid.

Pretreatment Dysphagia in Esophageal Cancer Patients May Eliminate the Need for Staging by Endoscopic Ultrasonography.

PubMed

Ripley, R Taylor; Sarkaria, Inderpal S; Grosser, Rachel; Sima, Camelia S; Bains, Manjit S; Jones, David R; Adusumilli, Prasad S; Huang, James; Finley, David J; Rusch, Valerie W; Rizk, Nabil P

2016-01-01

Neoadjuvant therapy is commonly administered to patients with localized disease who have T3-4 esophageal disease as staged by endoscopic ultrasound (EUS). Previously, we noted that patients who present with dysphagia have a higher EUS T stage. We hypothesized that the presence of dysphagia is predictive of EUS T3-4 disease and that staging EUS could be forgone for esophageal cancer patients with dysphagia. We performed a prospective, intent-to-treat, single-cohort study in which patients with potentially resectable esophageal cancer completed a standardized four-tier dysphagia score survey. EUS was performed as part of our standard evaluation. To determine whether the presence of dysphagia predicted EUS T3-4 disease, the dysphagia score was compared with EUS T stage. The study enrolled 114 consecutive patients between August 2012 and February 2014: 77% (88 of 114) received neoadjuvant therapy, 18% (20 of 114) did not, and 5% (6 of 114) pursued treatment elsewhere. In total, 70% (80 of 114) underwent esophagectomy; of these, 54% (61 of 114) had dysphagia and 46% (53 of 114) did not. Dysphagia scores were 66% (40 of 61) grade 1, 25% (15 of 61) grade 2, and 10% (6 of 61) grade 3 to 4. Among patients with dysphagia, 89% (54 of 61) had T3-4 disease by EUS; among those without dysphagia, only 53% (28 of 53) had T3-4 disease by EUS (p < 0.001). The presence of dysphagia in patients with esophageal cancer was highly predictive of T3-4 disease by EUS. On the basis of this finding, approximately 50% of patients currently undergoing staging EUS at our institution could potentially forgo EUS before neoadjuvant therapy. Patients without dysphagia, however, should still undergo EUS. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics

PubMed Central

de Rosa, Nicole; Rodriguez-Bigas, Miguel A.; Chang, George J.; Veerapong, Jula; Borras, Ester; Krishnan, Sunil; Bednarski, Brian; Messick, Craig A.; Skibber, John M.; Feig, Barry W.; Lynch, Patrick M.; Vilar, Eduardo

2016-01-01

Purpose DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. Methods Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer–specific survival were calculated by the Kaplan-Meier method. Results The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer–specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. Conclusion dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions. PMID:27432916

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

PubMed

Alsina, Maria; Rivera, Fernando; Ramos, Francisco Javier; Galán, Maica; López, Rafael; García-Alfonso, Pilar; Alés-Martinez, José Enrique; Queralt, Bernardo; Antón, Antonio; Carrato, Alfredo; Grávalos, Cristina; Méndez-Vidal, Maria José; López, Carlos; de Mena, Inmaculada Ruiz; Tabernero, Josep; Giralt, Jordi; Aranda, Enrique

2018-02-01

Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles. Six weeks later, patients with response or stabilisation initiated 6 weeks of cisplatin/cetuximab/radiotherapy, followed by surgery. The primary objective was the clinical complete response (cCR) rate after induction therapy plus chemoradiotherapy in intent-to-treat patients. Thirty-eight patients were evaluable after chemoradiotherapy, 84% of whom showed disease control. Six patients (12%) achieved a cCR, with a 54% overall response rate. Twenty-seven patients underwent surgery, 11 of whom (22%; nine SCC, two adenocarcinoma) had a pathological CR (41%). Fifteen patients were alive after a median follow-up of 23.2 months. Median progression-free survival was 12.2 months (95% confidence interval [CI] 1.7-22.8). Median overall survival was 23.4 months (95% CI 12.2-36.6) and was significantly longer among the 22 patients with complete resection than in the five patients without (42.1 vs. 24.9 months; p = 0.02, hazard ratio: 3.6, 95% CI 1.1-11.6). The toxicity profile was acceptable. Neoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature. Registration: The study is registered at ClinicalTrials.gov (NCT00733889).

Sarcomatoid Carcinoma of the Lung: The Mayo Clinic Experience in 127 Patients.

PubMed

Maneenil, Kunlatida; Xue, Zhiqiang; Liu, Ming; Boland, Jennifer; Wu, Fengying; Stoddard, Shawn M; Molina, Julian; Yang, Ping

2018-05-01

Pulmonary sarcomatoid carcinoma (PSC) is an unusual form of non-small-cell lung cancer (NSCLC). Because of its rarity and heterogeneity, the treatment and prognosis of PSC have not been clearly described. We retrospectively evaluated all patients with a diagnosis of PSC from 1997 to 2015 at the Mayo Clinic (Rochester, MN). The clinical characteristics, treatment details, and outcomes were collected. The survival rates of the PSC patients were compared with those for other subtypes of NSCLC. We used propensity score matching to minimize the bias resulting from to imbalanced comparison groups. The study included 127 PSC patients. The median age at diagnosis was 68 years (range, 32-89 years), most of whom were men (61%) and smokers (82%). The clinical stage was I, II, III, and IV in 15.9%, 20.6%, 22.2%, and 41.3%, respectively. The median survival time was 9.9 months (95% confidence interval [CI], 7.6-12.6 months). The 1-, 2-, and 5-year survival rates were 42%, 23%, and 15%, respectively. Most patients received multimodality treatment. Of the 3 patients who received neoadjuvant chemotherapy, a partial response was demonstrated in 2. Twenty-five patients who underwent palliative chemotherapy were evaluated for tumor response: 52% experienced progression, 40% stable disease, 8.0% a partial response, and 0% a complete response. Multivariate analysis showed T stage, M stage, and treatment with surgery plus neoadjuvant chemotherapy or surgery plus adjuvant therapy were independent prognostic factors (P < .05). In matched analysis, multivariate models revealed worse overall survival for PSC compared with adenocarcinoma (hazard ratio, 2.38; 95% CI, 1.61-2.53) and squamous cell carcinoma (hazard ratio, 2.20; 95% CI, 1.44-2.34). We found the outcome of PSC to be significantly worse than that of adenocarcinoma and squamous cell carcinoma. Neoadjuvant or adjuvant chemotherapy, in addition to surgical resection, should be considered. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence and Predictors of Neoadjuvant Therapy for Stage IIIA Non-Small Cell Lung Cancer in the National Cancer Database: Importance of Socioeconomic Status and Treating Institution

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

Sher, David J., E-mail: david_sher@rush.edu; Liptay, Michael J.; Fidler, Mary Jo

Purpose: The optimal locoregional therapy for stage IIIA non-small cell lung cancer (NSCLC) is controversial, with definitive chemoradiation therapy (CRT) and neoadjuvant therapy followed by surgery (NT-S) serving as competing strategies. In this study, we used the National Cancer Database to determine the prevalence and predictors of NT in a large, modern cohort of patients. Methods and Materials: Patients with stage IIIA NSCLC treated with CRT or NT-S between 2003 and 2010 at programs accredited by the Commission on Cancer were included. Predictors were categorized as clinical, time/geographic, socioeconomic, and institutional. In accord with the National Cancer Database, institutions were classifiedmore » as academic/research program and as comprehensive and noncomprehensive community cancer centers. Logistic regression and random effects multilevel logistic regression were performed for univariable and multivariable analyses, respectively. Results: The cohort consisted of 18,581 patients, 3,087 (16.6%) of whom underwent NT-S (10.6% induction CRT, 6% induction chemotherapy). The prevalence of NT-S was constant over time, but there were significant relative 31% and 30% decreases in pneumonectomy and right-sided pneumonectomy, respectively, over time (P trend <.02). In addition to younger age, lower T stage, and favorable comorbidity score, indicators of higher socioeconomic status were strong independent predictors of NT-S, including white race, higher income, and private/managed insurance. The type of institution (academic/research program vs comprehensive or noncomprehensive community cancer centers, odds ratio 1.54 and 2.08, respectively) strongly predicted NT-S, but treatment volume did not. Conclusions: Neoadjuvant therapy followed by surgery was an uncommon treatment approach in Commission on Cancer programs, and the prevalence of postinduction pneumonectomy decreased over time. Higher socioeconomic status and treatment at academic institutions were significant predictors of NT-S. Further research should be performed to enable a better understanding of these disparities.« less

Impact of Surgical Approach on Long-term Survival in Esophageal Adenocarcinoma Patients With or Without Neoadjuvant Chemoradiotherapy.

PubMed

Noordman, Bo Jan; van Klaveren, David; van Berge Henegouwen, Mark I; Wijnhoven, Bas P L; Gisbertz, Suzanne S; Lagarde, Sjoerd M; van der Gaast, Ate; Hulshof, Maarten C C M; Biermann, Katharina; Steyerberg, Ewout W; van Lanschot, J Jan B

2018-05-01

To compare overall survival in patients with esophageal adenocarcinoma who underwent transhiatal esophagectomy (THE) with limited lymphadenectomy or transthoracic esophagectomy (TTE) with extended lymphadenectomy with or without neoadjuvant chemoradiotherapy (nCRT). The application of neoadjuvant therapy might change the association between the extent of lymphadenectomy and survival in patients with esophageal adenocarcinoma. This may influence the choice of surgical approach in patients treated with nCRT. Patients with potentially curable subcarinal esophageal adenocarcinoma treated with surgery alone or nCRT followed by surgery in 7 centers were included. The effect of surgical approach on overall survival, differentiated by the addition or omission of nCRT, was analyzed using a multivariable Cox regression model that included well-known prognostic factors and factors that might have influenced the choice of surgical approach. In total, 701 patients were included, of whom 318 had TTE with extended lymphadenectomy and 383 had THE with limited lymphadenectomy. TTE had differential effects on survival (P for interaction = 0.02), with a more favorable prognostic effect in patients who were treated with surgery alone [hazard ratio (HR) = 0.77, 95% confidence interval (CI) 0.58-1.03]. This association was statistically significant in a subgroup of patients with 1 to 8 positive lymph nodes in the resection specimen (HR = 0.62, 95% CI 0.43-0.90). The favorable prognostic effect of TTE over THE was absent in the nCRT and surgery group (HR = 1.16, 95% CI 0.80-1.66) and in the subgroup of nCRT patients with 1 to 8 positive lymph nodes in the resection specimen (HR = 1.00, 95% CI 0.61-1.68). Compared to surgery alone, the addition of nCRT may reduce the need for TTE with extended lymphadenectomy to improve long-term survival in patients with esophageal adenocarcinoma.

DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics.

PubMed

de Rosa, Nicole; Rodriguez-Bigas, Miguel A; Chang, George J; Veerapong, Jula; Borras, Ester; Krishnan, Sunil; Bednarski, Brian; Messick, Craig A; Skibber, John M; Feig, Barry W; Lynch, Patrick M; Vilar, Eduardo; You, Y Nancy

2016-09-01

DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer-specific survival were calculated by the Kaplan-Meier method. The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer-specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions. © 2016 by American Society of Clinical Oncology.

The use of self-expanding silicone stents in esophageal cancer care: optimal pre-, peri-, and postoperative care.

PubMed

Martin, Robert; Duvall, Ryan; Ellis, Susan; Scoggins, Charles R

2009-03-01

Preoperative nutritional supplementation, management of esophageal leaks, and postoperative anastomotic strictures still remain common problems in the management of esophageal cancer. Jejunal feeding tubes, total parenteral nutrition (TPN) with nasogastric suction, and repeated esophageal dilations remain the most common treatments, respectively. The aim of this study was to evaluate the use of removable silicone stents in (1) the preoperative nutritional optimization during neoadjuvant therapy, (2) the management of perioperative anastomotic leak, and (3) the management of postoperative anastomotic strictures. Review of our prospectively maintained esophageal database identified 15 patients who had removable self-expanding silicone stents placed in the management of one of these three management problems from July 2004 to August 2006. Preoperative therapy: Five patients underwent initial stent placement in preparation for neoadjuvant therapy. Dysphagia relief was seen in 100% of patients, with optimal caloric needs taken within 24 h of placement. All patients tolerated neoadjuvant therapy without delay from dehydration or malnutrition. One stent migration was found at the time of operation, which was removed without sequelae. Perioperative therapy: Five patients developed delayed (>10 days) esophageal leaks that were managed with removable esophageal stent and percutaneous drainage (in three patients). All patients had successful exclusion of the leak on the day of the procedure with resumption of oral intake on the evening of procedure. All five healed leaks without sequelae. Postoperative therapy: Five patients developed postoperative anastomotic strictures that required dilation and placement of removable esophageal stent. The median number of dilations was 1 (range 1-2), with all stents placed for approximate 3 months duration. All patients had immediate dysphagia relief after stent placement. Removable esophageal stents are novel treatment option to optimize relief of symptoms and return the patients back to a more normal oral intake. Continued evaluation is needed to consider stent use as first-line therapy.

Do differences in age specific androgenic steroid hormone levels account for differing prostate cancer rates between Arabs and Caucasians?

PubMed

Kehinde, Elijah O; Akanji, Abayomi O; Al-Hunayan, Adel; Memon, Anjum; Luqmani, Yunus; Al-Awadi, Khaleel A; Varghese, Ramani; Bashir, Abdul Aziz; Daar, Abdallah S

2006-04-01

Factors responsible for the low incidence of clinical prostate cancer in the Arab population remain unclear, but may be related to differences in androgenic steroid hormone metabolism between Arabs and other populations, especially as prostate cancer is believed to be androgen dependent. We therefore measured the levels of serum androgenic steroids and their binding proteins in Arab men and compared results obtained with values reported for Caucasian populations to determine if any differences could at least partially account for differences in incidence of prostate cancer rates between the two populations. Venous blood samples were obtained from 327 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-79 years. Samples were also obtained from 30 Arab men with newly diagnosed prostate cancer. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), derived free androgen index (FAI); adrenal C19 -steroids, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (ADT) were determined by chemiluminescent immunoassay. Age specific reference intervals, mean and median for each analyte were determined. Frequency distribution pattern for each hormone was plotted. The reference range for hormones with normal distribution was mean +/- 2SD and 2.5-97.5% for those with non-normal distribution. The mean serum levels of the hormones in Arab men with prostate cancer were compared with values in healthy age-matched Arab men. There was a significant decrease between the 21-29 years age group and the 70-79 years age group for TT (-38.77%), DHEAS (-70%), ADT (-36%) and FAI (-63.25%), and an increase for SHBG (+64%). The calculated reference ranges are TT (2.73-30.45 nmol/L), SHBG (6.45-65.67 nmol/L), FAI (14.51-180.34), DHEAS (0.9-11.0 micromol/L) and ADT (0.54-4.26 ng/mL). The mean TT, SHBG, DHEAS and ADT in Arab men were significantly lower than those reported for Caucasians especially in the 21-29 years age group. Arab men with newly diagnosed prostate cancer had higher serum TT (P < 0.7), ADT (P < 0.2), SHBG (P < 0.2) and lower DHEAS (P < 0.008) compared to aged matched controls. Serum TT, SHBG, DHEAS and ADT levels are significantly lower in Arab men compared to those reported for Caucasian men, especially in early adulthood. Arab men with newly diagnosed prostate cancer have higher circulating androgens compared to healthy controls. We suggest that low circulating androgens and their adrenal precursors in Arab men when compared to Caucasians may partially account for the relatively lower risk for prostate cancer among Arab men.

Neoadjuvant therapy versus upfront surgical strategies in resectable pancreatic cancer: A Markov decision analysis.

PubMed

de Geus, S W L; Evans, D B; Bliss, L A; Eskander, M F; Smith, J K; Wolff, R A; Miksad, R A; Weinstein, M C; Tseng, J F

2016-10-01

Neoadjuvant therapy is gaining acceptance as a valid treatment option for borderline resectable pancreatic cancer; however, its value for clearly resectable pancreatic cancer remains controversial. The aim of this study was to use a Markov decision analysis model, in the absence of adequately powered randomized trials, to compare the life expectancy (LE) and quality-adjusted life expectancy (QALE) of neoadjuvant therapy to conventional upfront surgical strategies in resectable pancreatic cancer patients. A Markov decision model was created to compare two strategies: attempted pancreatic resection followed by adjuvant chemoradiotherapy and neoadjuvant chemoradiotherapy followed by restaging with, if appropriate, attempted pancreatic resection. Data obtained through a comprehensive systematic search in PUBMED of the literature from 2000 to 2015 were used to estimate the probabilities used in the model. Deterministic and probabilistic sensitivity analyses were performed. Of the 786 potentially eligible studies identified, 22 studies met the inclusion criteria and were used to extract the probabilities used in the model. Base case analyses of the model showed a higher LE (32.2 vs. 26.7 months) and QALE (25.5 vs. 20.8 quality-adjusted life months) for patients in the neoadjuvant therapy arm compared to upfront surgery. Probabilistic sensitivity analyses for LE and QALE revealed that neoadjuvant therapy is favorable in 59% and 60% of the cases respectively. Although conceptual, these data suggest that neoadjuvant therapy offers substantial benefit in LE and QALE for resectable pancreatic cancer patients. These findings highlight the value of further prospective randomized trials comparing neoadjuvant therapy to conventional upfront surgical strategies. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Efficacy of aripiprazole augmentation in Japanese patients with major depressive disorder: a subgroup analysis and Montgomery-Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression item analyses of the Aripiprazole Depression Multicenter Efficacy study.

PubMed

Ozaki, Norio; Otsubo, Tempei; Kato, Masaki; Higuchi, Teruhiko; Ono, Hiroaki; Kamijima, Kunitoshi

2015-01-01

Results from this randomized, placebo-controlled study of aripiprazole augmentation to antidepressant therapy (ADT) in Japanese patients with major depressive disorder (MDD) (the Aripiprazole Depression Multicenter Efficacy [ADMIRE] study) revealed that aripiprazole augmentation was superior to ADT alone and was well tolerated. In subgroup analyses, we investigated the influence of demographic- and disease-related factors on the observed responses. We also examined how individual symptom improvement was related to overall improvement in MDD. Data from the ADMIRE study were analyzed. Subgroup analyses were performed on the primary outcome measures: the mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from the end of selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI) treatment to the end of the randomized treatment. Changes in the MADRS total scores were consistently greater with aripiprazole than placebo in each of the subgroups. Efficacy was not related to sex, age, number of adequate ADT trials in the current episode, MDD diagnosis, number of depressive episodes, duration of the current episode, age at first depressive episode, time since the first depressive episode, type of SSRI/SNRI, or severity at the end of SSRI/SNRI treatment phase. Compared to placebo, aripiprazole resulted in significant and rapid improvement on seven of the 10 MADRS items, including sadness. These post-hoc analyses indicated that aripiprazole was effective for a variety of Japanese patients with MDD who had exhibited inadequate responses to ADT. Additionally, we suggest that aripiprazole significantly and rapidly improved the core depressive symptoms. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Hormone therapy for radiorecurrent prostate cancer.

PubMed

Payne, H; Khan, A; Chowdhury, S; Davda, R

2013-12-01

The management of patients who relapse after radical radiotherapy is a challenging problem for the multidisciplinary team. This group of men may have been considered ineligible or chosen not to be treated with an initial surgical approach as a result of high-risk features or significant comorbid conditions. It is important not to miss the opportunity for definitive local salvage therapies at this stage, and eligible patients should undergo careful restaging to determine their suitability for these approaches. For those men not suitable for local treatment, androgen deprivation therapy (ADT) remains an option. Literature review of the evidence relating to the management of hormone therapy for radiorecurrent prostate cancer. Results from retrospective studies have shown that not all men with biochemical relapse will experience distant metastasis or a reduction in survival due to prostate cancer progression. Therefore, the timing of ADT commencement remains controversial. However, it would seem appropriate to offer immediate therapy to men with advanced disease or unfavourable prostate-specific antigen (PSA) kinetics at relapse. Patients with more favourable risk factors and PSA kinetics may be considered for watchful waiting and deferred ADT to avoid or delay the associated toxicities. Patients with non-metastatic disease can be given the option of castration-based therapy or an antiandrogen such as bicalutamide which may have potential advantages in maintenance of sexual function, physical capacity and bone mineral density but at the expense of an increase in gynaecomastia and mastalgia. Recent data suggest the burden of toxicity from ADT may be reduced by the use of intermittent hormone therapy without compromising survival in this group of patients with radiorecurrence. Hormone therapy remains an option for men with radiorecurrent prostate cancer.

Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles

PubMed Central

Hoang, David T; Iczkowski, Kenneth A; Kilari, Deepak; See, William; Nevalainen, Marja T

2017-01-01

Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways. The exact mechanisms underlying the transition from androgen-dependent PC to CRPC remain incompletely understood. Reactivation of AR has been shown to occur in CRPC despite depletion of circulating androgens by ADT. At the same time, the presence of AR-negative cell populations in CRPC has also been identified. While AR signaling has been proposed as the primary driver of CRPC, AR-independent signaling pathways may represent additional mechanisms underlying CRPC progression. Identification of new therapeutic strategies to target both AR-positive and AR-negative PC cell populations and, thereby, AR-driven as well as non-AR-driven PC cell growth and survival mechanisms would provide a two-pronged approach to eliminate CRPC cells with potential for synthetic lethality. In this review, we provide an overview of AR-dependent and AR-independent molecular mechanisms which drive CRPC, with special emphasis on the role of the Jak2-Stat5a/b signaling pathway in promoting castrate-resistant growth of PC through both AR-dependent and AR-independent mechanisms. PMID:27741508

Radium-223 IN metastatic hormone-sensitive high-grade prostate cancer: initial experience.

PubMed

Osvaldo, García-Pérez Francisco; Salvador, Medina-Ornelas Sevastián; Zael, Santana-Ríos; Nora, Sobrevilla-Moreno

2017-01-01

Our study evaluates the feasibility of compassionate exemption of Radium-223 ( 223 Ra) treatment in metastatic hormone-sensitive high-grade prostate cancer (mHSHGPC) patients with concomitant androgen deprivation-therapy (ADT). Seven patients with mHSHGPC, were treated with six cycles of 223 Ra plus ADT. All patients had undergone to 18 F-NaF-PET/CT. A qualitative analyses of the 18 F-NaF-PET/CT was performed in conjunction with Alkaline Phosphatase (ALP), Lactate-dehydrogenase (LDH) and Prostatic-Specific Antigen (PSA) values. The mean of SUVmax values were used as a quantitative measure of tumoral burden. Changes in PSA, ALP, LDH from baseline were evaluated, and were defined as increase or decrease of at least 30%. Clinical response was achieved if there was pain reduction using visual analogic scale. Four patients showed a significant reduction in mean SUVmax after 3 cycles of 223 Ra, and one after 6 cycles. Patients who showed reductions in mean SUVmax after Ra-223 also showed reductions in PSA, ALP and LDH. Four weeks after the last cycle of 223 Ra all patients had decreased total PSA, ALP and LDH values ≥ 30% also significant improvement on pain. No progress disease was documented after 14 ± 4 weeks. We found slight to moderate decreases in neutrophils and hemoglobin in two patients. We concluded that 223 Ra plus ADT can be useful in mHSHGPC; the semi-quantitative 18 F-NaF-PET/CT as a method effective to monitor the treatment response. Due to concomitant administration of ADT, 18 F-NaF-PET/CT cannot differentiate whether the findings were due to androgen blockade or the 223 Ra; nevertheless, data supporting the efficacy of 223 Ra is the significant improvement on pain.

SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy.

PubMed

Shiota, Masaki; Fujimoto, Naohiro; Yokomizo, Akira; Takeuchi, Ario; Itsumi, Momoe; Inokuchi, Junichi; Tatsugami, Katsunori; Uchiumi, Takeshi; Naito, Seiji

2015-09-01

De novo androgen synthesis is thought to be involved in the progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT). During androgen synthesis, 5α-reductase encoded by SRD5A catalyses testosterone into more active dihydrotestosterone and may be involved in the progression to CRPC. Then, this study aimed to reveal the association between genetic variations in SRD5A and the prognosis in metastatic prostate cancer. We studied the polymorphisms rs518673 and rs166050 in SRD5A1, and rs12470143, rs523349, rs676033 and rs2208532 in SRD5A2 as well as the time to CRPC progression and overall survival in 104 patients with metastatic prostate cancer that had undergone primary ADT. The association between the polymorphisms and the progression to CRPC as well as overall survival was examined. Patients carrying the more active GG genotype in SRD5A2 rs523349 exhibited a higher risk of the progression (hazard ration [95% confidence interval], 1.93 [1.14-3.14], p=0.016) and death (hazard ration [95% confidence interval], 2.14 [1.16-3.76], p=0.016), compared with less active GC/CC genotypes in SRD5A2 rs523349. High 5α-reductase activity due to the polymorphism in SRD5A2 may contribute to resistance to ADT. Furthermore, SRD5A2 rs523349 polymorphism may be a promising biomarker for metastatic prostate cancer patients treated with primary ADT and a molecular target for advanced prostate cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Skeletal Health After Continuation, Withdrawal, or Delay of Alendronate in Men With Prostate Cancer Undergoing Androgen-Deprivation Therapy

PubMed Central

Greenspan, Susan L.; Nelson, Joel B.; Trump, Donald L.; Wagner, Julie M.; Miller, Megan E.; Perera, Subashan; Resnick, Neil M.

2008-01-01

Purpose Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT. Patients and Methods A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers. Results Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% ± 0.7) and hip (mean, 1.3% ± 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, −1.9% ± 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (± 1.2%) increase at the spine and a 3.2% (± 1.5%) at the hip (both P < .05). Bone turnover remained suppressed. Conclusion Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health. PMID:18802155

Optimized breast MRI functional tumor volume as a biomarker of recurrence-free survival following neoadjuvant chemotherapy.

PubMed

Jafri, Nazia F; Newitt, David C; Kornak, John; Esserman, Laura J; Joe, Bonnie N; Hylton, Nola M

2014-08-01

To evaluate optimal contrast kinetics thresholds for measuring functional tumor volume (FTV) by breast magnetic resonance imaging (MRI) for assessment of recurrence-free survival (RFS). In this Institutional Review Board (IRB)-approved retrospective study of 64 patients (ages 29-72, median age of 48.6) undergoing neoadjuvant chemotherapy (NACT) for breast cancer, all patients underwent pre-MRI1 and postchemotherapy MRI4 of the breast. Tumor was defined as voxels meeting thresholds for early percent enhancement (PEthresh) and early-to-late signal enhancement ratio (SERthresh); and FTV (PEthresh, SERthresh) by summing all voxels meeting threshold criteria and minimum connectivity requirements. Ranges of PEthresh from 50% to 220% and SERthresh from 0.0 to 2.0 were evaluated. A Cox proportional hazard model determined associations between change in FTV over treatment and RFS at different PE and SER thresholds. The plot of hazard ratios for change in FTV from MRI1 to MRI4 showed a broad peak with the maximum hazard ratio and highest significance occurring at PE threshold of 70% and SER threshold of 1.0 (hazard ratio = 8.71, 95% confidence interval 2.86-25.5, P < 0.00015), indicating optimal model fit. Enhancement thresholds affect the ability of MRI tumor volume to predict RFS. The value is robust over a wide range of thresholds, supporting the use of FTV as a biomarker. © 2013 Wiley Periodicals, Inc.

Hypofractionated Volumetric Modulated Arc Radiotherapy with simultaneous Elective Nodal Irradiation is feasible in prostate cancer patients: A single institution experience.

PubMed

Hegazy, Mohamed W; Mahmood, Rana I; Al Otaibi, Mohammed F; Khalil, Ehab M

2016-06-01

To assess feasibility, toxicity and biochemical relapse-free survival (b-RFS) for a group of organ confined (OC) Saudi prostate cancer patients treated by hypo-fractionated Volumetric Modulated Arc Radiation Therapy (VMAT) Simultaneous Integrated Boost (SIB) Elective Nodal Irradiation (ENI) whole pelvic radiotherapy (WPRT). Between March 2009 and January 2014, 29 OC prostate cancer patients; median age 64years, PS 0-1 were treated in King Faisal Specialist Hospital - Riyadh, Kingdom of Saudi Arabia using VMAT-SIB-ENI-WPRT, to a total dose of 70Gy in 28 fractions. Twenty Four patients (83%) were treated with neo-adjuvant; concurrent androgen deprivation therapy (ADT). Median follow-up (FU) was 42months (range: 18-72months). The 3-year actuarial b-RFS for low/intermediate and high risk groups were 100%, and 48%, respectively (p=0.09) with a median FU period of 34months (range: 14-53months). Gleason Score (p=0.02), and pretreatment PSA (p=0.01) were predictive for biochemical failure on univariate analysis; with no observed prostate cancer-related deaths. Grade 2 acute/late GI and GU toxicities were 28%/0% and 17%/10% respectively with no reported grade 3/4 toxicities. Four (50%) out of the 8 patients with baseline partial potency, retained sexual function on long term follow-up. Hypo-fractionation dose escalation VMAT-SIB-ENI-WPRT using 2 arcs is a feasible technique for intermediate/high risk OC prostate cancer patients, with acceptable rates of acute/late toxicities, much favorable planning target volume (PTV) coverage, and shorter overall treatment time. Prospective randomized controlled trials are encouraged to confirm its equivalence to other fractionation schemes. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Progression following neoadjuvant systemic chemotherapy may not be a contraindication to a curative approach for colorectal carcinomatosis.

PubMed

Passot, Guillaume; Vaudoyer, Delphine; Cotte, Eddy; You, Benoit; Isaac, Sylvie; Noël Gilly, François; Mohamed, Faheez; Glehen, Olivier

2012-07-01

The objective of this retrospective study was to evaluate the influence of neoadjuvant systemic chemotherapy on patients with colorectal carcinomatosis before a curative procedure. Peritoneal carcinomatosis (PC) from colorectal cancer may be treated with a curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The role of perioperative systemic chemotherapy for this particular metastatic disease remains unclear. One hundred twenty patients with PC from colorectal cancer were consecutively treated by 131 procedures combining CRS with HIPEC. The response to neoadjuvant systemic chemotherapy was assessed on data from previous explorative surgery and/or radiological imaging. Ninety patients (75%) were treated with neoadjuvant systemic chemotherapy in whom 32 (36%) were considered to have responded, 19 (21%) had stable disease, and 19 (21%) developed diseases progression. Response could not be evaluated in 20 patients (22%). On univariate analysis, the use of neoadjuvant systemic chemotherapy had a significant positive prognostic influence (P = 0.042). On multivariate analysis, the completeness of CRS and the use of adjuvant systemic chemotherapy were the only significant prognostic factors (P < 0.001 and P = 0.049, respectively). Response to neoadjuvant systemic chemotherapy had no significant prognostic impact with median survival of 31.4 months in patients showing disease progression. In patients with PC from colorectal cancer without extraperitoneal metastases, failure of neoadjuvant systemic chemotherapy should not constitute an absolute contraindication to a curative procedure combining CRS and HIPEC.

Primitive neuroectodermal tumor of the cervix: a case report

PubMed Central

2011-01-01

Introduction Peripheral primitive neuroectodermal tumor of the cervix uteri is extremely rare. Between 1987 and 2010, there were only nine cases reported in the English literature, with considerably different management policies. Case presentation A 45-year-old Iranian woman presented to our facility with a primitive neuroectodermal tumor of the cervix uteri. Her clinical stage IB2 tumor was treated successfully with chemotherapy. Our patient underwent radical hysterectomy. There was no trace of the tumor after four years of follow-up. Conclusions According to current knowledge, primitive neuroectodermal tumors belong to the Ewing's sarcoma family, and the improvement of treatment outcome in our patient was due to dose-intensive neoadjuvant chemotherapy, surgery and consolidation chemotherapy in accordance with the protocol for bony Ewing's sarcoma. PMID:21962148

Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology.

PubMed

Vetterlein, Malte W; Wankowicz, Stephanie A M; Seisen, Thomas; Lander, Richard; Löppenberg, Björn; Chun, Felix K-H; Menon, Mani; Sun, Maxine; Barletta, Justine A; Choueiri, Toni K; Bellmunt, Joaquim; Trinh, Quoc-Dien; Preston, Mark A

2017-11-15

Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, to the authors' knowledge, it is unknown whether this benefit persists in histological variants. The objective of the current study was to assess the effect of neoadjuvant chemotherapy on the probability of non-organ-confined disease and overall survival after radical cystectomy (RC) in patients with histological variants. Querying the National Cancer Data Base, the authors identified 2018 patients with histological variants who were undergoing RC for bladder cancer between 2003 and 2012. Variants were categorized as micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other histology. Logistic regression models estimated the odds of non-organ-confined disease at the time of RC for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup. Patients with neuroendocrine tumors (odds ratio [OR], 0.16; 95% confidence interval [95% CI], 0.08-0.32 [P<.001]), micropapillary differentiation (OR, 0.30; 95% CI, 0.10-0.95 [P=.041]), sarcomatoid urothelial carcinoma (OR, 0.40; 95% CI, 0.17-0.94 [P=.035]), and adenocarcinoma (OR, 0.24; 95% CI, 0.06-0.91 [P=.035]) were less likely to harbor non-organ-confined disease at the time of RC when treated with neoadjuvant chemotherapy. An overall survival benefit for neoadjuvant chemotherapy was only found in patients with neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]). Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better overall survival and lower rates of non-organ-confined disease at the time of RC. For tumors with micropapillary differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant chemotherapy decreased the frequency of non-organ-confined disease at the time of RC. However, this favorable effect did not translate into a statistically significant overall survival benefit for these patients, potentially due to the aggressive tumor biology. Cancer 2017;123:4346-55. © 2017 American Cancer Society. © 2017 American Cancer Society.

Comparative Toxicity and Dosimetric Profile of Whole-Pelvis Versus Prostate Bed-Only Intensity-Modulated Radiation Therapy After Prostatectomy

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

Deville, Curtiland, E-mail: deville@uphs.upenn.edu; Vapiwala, Neha; Hwang, Wei-Ting

2012-03-15

Purpose: To assess whether whole-pelvis (WP) intensity modulated radiation therapy (IMRT) for prostate cancer (PCa) after prostatectomy is associated with increased toxicity compared to prostate-bed only (PB) IMRT. Methods and Materials: All patients (n = 67) undergoing postprostatectomy IMRT to 70.2 Gy at our institution from January 2006 to January 2009 with minimum 12-month follow-up were divided into WP (n = 36) and PB (n = 31) comparison groups. WP patients received initial pelvic nodal IMRT to 45 Gy. Pretreatment demographics, bladder and rectal dose-volume histograms, and maximum genitourinary (GU) and gastrointestinal (GI) toxicities were compared. Logistic regression models evaluatedmore » uni- and multivariate associations between pretreatment demographics and toxicities. Results: Pretreatment demographics including age and comorbidities were similar between groups. WP patients had higher Gleason scores, T stages, and preoperative prostate-specific antigen (PSA) levels, and more WP patients underwent androgen deprivation therapy (ADT). WP minimum (Dmin) and mean bladder doses, bladder volumes receiving more than 5 Gy (V5) and V20, rectal Dmin, and PB bladder and rectal V65 were significantly increased. Maximum acute GI toxicity was Grade 2 and was increased for WP (61%) vs. PB (29%) patients (p = 0.001); there was no significant difference in acute Grade {>=}2 GU toxicity (22% WP vs. 10% PB; p = 0.193), late Grade {>=}2 GI toxicity (3% WP vs. 0% PB; p = 0.678), or late Grade {>=}2 GU toxicity (28% WP vs. 19% PB; p = 0.274) with 25-month median follow-up (range, 12-44 months). On multivariate analysis, long-term ADT use was associated with Grade {>=}2 late GU toxicity (p = 0.02). Conclusion: Despite dosimetric differences in irradiated bowel, bladder, and rectum, WP IMRT resulted only in clinically significant increased acute GI toxicity in comparison to that with PB IMRT, with no differences in GU or late GI toxicity.« less

Critical factors to achieve low voltage- and capacitance-based organic field-effect transistors.

PubMed

Jang, Mi; Park, Ji Hoon; Im, Seongil; Kim, Se Hyun; Yang, Hoichang

2014-01-15

Hydrophobic organo-compatible but low-capacitance dielectrics (10.5 nFcm(-2) ), polystyrene-grafted SiO2 could induce surface-mediated large crystal grains of face-to-face stacked triethylsilylethynyl anthradithiophene (TES-ADT), producing more efficient charge-carrier transport, in comparison to μm-sized pentacene crystals containing a face-to-edge packing. Low-voltage operating TES-ADT OFETs showed good device performance (μFET ≈ 1.3 cm(2) V(-1) s(-1) , Vth ≈ 0.5 V, SS ≈ 0.2 V), as well as excellent device reliability. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Construction of diabatic energy surfaces for LiFH with artificial neural networks

NASA Astrophysics Data System (ADS)

Guan, Yafu; Fu, Bina; Zhang, Dong H.

2017-12-01

A new set of diabatic potential energy surfaces (PESs) for LiFH is constructed with artificial neural networks (NNs). The adiabatic PESs of the ground state and the first excited state are directly fitted with NNs. Meanwhile, the adiabatic-to-diabatic transformation (ADT) angles (mixing angles) are obtained by simultaneously fitting energy difference and interstate coupling gradients. No prior assumptions of the functional form of ADT angles are used before fitting, and the ab initio data including energy difference and interstate coupling gradients are well reproduced. Converged dynamical results show remarkable differences between adiabatic and diabatic PESs, which suggests the significance of non-adiabatic processes.

Human touch to detect hypothermia in neonates in Indian slum dwellings.

PubMed

Agarwal, Siddharth; Sethi, Vani; Srivastava, Karishma; Jha, Prabhat; Baqui, Abdullah H

2010-07-01

To assess the validity of human touch (HT) method to measure hypothermia compared against axillary digital thermometry (ADT) and study association of hypothermia with poor suckle and underweight status in newborns and environmental temperature in 11 slums of Indore city, India. Field supervisors of slum-based health volunteers measured body temperature of 152 newborns by HT and ADT, observed suckling and weighed newborns. Underweight status was determined using WHO growth standards. Hypothermia prevalence (axillary temperature <36.5 degrees C) was 30.9%. Prevalence varied by season but insignificantly. Hypothermia was insignificantly associated with poor suckle (31% vs 19.7%, p=0.21) and undernutrition (33.3% vs 25.3%, p=0.4). HT had moderate diagnostic accuracy when compared with ADT (kappa: 0.38, sensitivity: 74.5%, specificity: 68.5%). HT emerged simpler and programmatically feasible. There is a need to examine whether trained and supervised community-based health workers and mothers can use HT accurately to identify and manage hypothermia and other simple signs of newborn illness using minimal algorithm at home and more confidently refer such newborns to proximal facilities linked to the program to ensure prompt management of illness.

Inhibition of FOXC2 restores epithelial phenotype and drug sensitivity in prostate cancer cells with stem-cell properties

PubMed Central

Paranjape, A N; Soundararajan, R; Werden, S J; Joseph, R; Taube, J H; Liu, H; Rodriguez-Canales, J; Sphyris, N; Wistuba, I; Miura, N; Dhillon, J; Mahajan, N; Mahajan, K; Chang, J T; Ittmann, M; Maity, S N; Logothetis, C; Tang, D G; Mani, S A

2016-01-01

Advanced prostate adenocarcinomas enriched in stem-cell features, as well as variant androgen receptor (AR)-negative neuroendocrine (NE)/small-cell prostate cancers are difficult to treat, and account for up to 30% of prostate cancer-related deaths every year. While existing therapies for prostate cancer such as androgen deprivation therapy (ADT), destroy the bulk of the AR-positive cells within the tumor, eradicating this population eventually leads to castration-resistance, owing to the continued survival of AR-/lo stem-like cells. In this study, we identified a critical nexus between p38MAPK signaling, and the transcription factor Forkhead Box Protein C2 (FOXC2) known to promote cancer stem-cells and metastasis. We demonstrate that prostate cancer cells that are insensitive to ADT, as well as high-grade/NE prostate tumors, are characterized by elevated FOXC2, and that targeting FOXC2 using a well-tolerated p38 inhibitor restores epithelial attributes and ADT-sensitivity, and reduces the shedding of circulating tumor cells in vivo with significant shrinkage in the tumor mass. This study thus specifies a tangible mechanism to target the AR-/lo population of prostate cancer cells with stem-cell properties. PMID:26804168

Switched-Observer-Based Adaptive Neural Control of MIMO Switched Nonlinear Systems With Unknown Control Gains.

PubMed

Long, Lijun; Zhao, Jun

2017-07-01

In this paper, the problem of adaptive neural output-feedback control is addressed for a class of multi-input multioutput (MIMO) switched uncertain nonlinear systems with unknown control gains. Neural networks (NNs) are used to approximate unknown nonlinear functions. In order to avoid the conservativeness caused by adoption of a common observer for all subsystems, an MIMO NN switched observer is designed to estimate unmeasurable states. A new switched observer-based adaptive neural control technique for the problem studied is then provided by exploiting the classical average dwell time (ADT) method and the backstepping method and the Nussbaum gain technique. It effectively handles the obstacle about the coexistence of multiple Nussbaum-type function terms, and improves the classical ADT method, since the exponential decline property of Lyapunov functions for individual subsystems is no longer satisfied. It is shown that the technique proposed is able to guarantee semiglobal uniformly ultimately boundedness of all the signals in the closed-loop system under a class of switching signals with ADT, and the tracking errors converge to a small neighborhood of the origin. The effectiveness of the approach proposed is illustrated by its application to a two inverted pendulum system.

The Relationship between Hot Flashes and Testosterone Recovery after 12 Months of Androgen Suppression for Men with Localised Prostate Cancer in the ASCENDE-RT Trial.

PubMed

Dosani, M; Morris, W J; Tyldesley, S; Pickles, T

2017-10-01

This study describes the proportion of men who experienced hot flashes (flashes), and the testosterone level at onset, peak frequency and cessation of flashes after 12 months of androgen deprivation therapy (ADT) in men undergoing curative-intent external beam radiation therapy (± brachytherapy boost). We also aimed to characterise testosterone recovery in this population. This was a pre-specified secondary analysis of the ASCENDE-RT clinical trial. Three hundred and ninety-eight men were randomised. All received 12 months of ADT. The presence and frequency of flashes were patient reported. Cessation of flashes was defined as the first date a patient reported resolution of this symptom. Testosterone recovery was defined as any single serum testosterone above the threshold of 5, 7.5 or 10 nmol/l. The median age and follow-up were 68 years and 6.1 years. Flashes were reported in 93% of men. Flashes began and reached peak frequency at a median time of 4.0 months from the first luteinizing hormone-releasing hormone injection when testosterone levels had fallen to castrate. The median time to cessation of flashes was 7.6 months after the cessation of ADT (last injection + 3 months), when the median testosterone had risen to 5.7 nmol/l. A resolution of flashes was reported in 99% of patients. Baseline testosterone was available in 338 patients (85%). The median baseline testosterone was 13.2 nmol/l. The median (95% confidence interval) time of testosterone recovery to thresholds of 5 nmol/l, 7.5 nmol/l and 10 nmol/l were 9 (9-10) months, 13 (10-15) months and 18 (17-19) months from the cessation of ADT. At the time of censor, 96, 94 and 91% of patients had recovered testosterone to thresholds of 5, 7.5 and 10 nmol/l. Flashes occur at castrate levels of testosterone, with cessation of hot flashes antedating full recovery of testosterone in most patients. Rates of testosterone recovery after 12 months of ADT exceed 90%, although it can be delayed. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer.

PubMed

Shilkrut, Mark; Merrick, Gregory S; McLaughlin, P William; Stenmark, Matthew H; Abu-Isa, Eyad; Vance, Sean M; Sandler, Howard M; Feng, Felix Y; Hamstra, Daniel A

2013-02-01

The objective of this study was to determine whether the addition of low-dose-rate brachytherapy or androgen-deprivation therapy (ADT) improves clinical outcome in patients with high-risk prostate cancer (HiRPCa) who received dose-escalated radiotherapy (RT). Between 1995 and 2010, 958 patients with HiRPCa were treated at Schiffler Cancer Center (n = 484) or at the University of Michigan (n = 474) by receiving either dose-escalated external-beam RT (EBRT) (n = 510; minimum prescription dose, 75 grays [Gy]; median dose, 78 Gy) or combined-modality RT (CMRT) consisting of (103) Pd implants (n = 369) or (125) I implants (n = 79) both with pelvic irradiation (median prescription dose, 45 Gy). The cumulative incidences of biochemical failure (BF) and prostate cancer-specific mortality (PCSM) were estimated by using the Kaplan-Meier method and Fine and Gray regression analysis. The median follow-up was 63.2 months (interquartile range, 35.4-99.0 months), and 250 patients were followed for >8 years. Compared with CMRT, patients who received EBRT had higher prostate-specific antigen levels, higher tumor classification, lower Gleason sum, and more frequent receipt of ADT for a longer duration. The 8-year incidence BF and PCSM among patients who received EBRT was 40% (standard error, 38%-44%) and 13% (standard error, 11%-15%) compared with 14% (standard error, 12%-16%; P < .0001) and 7% (standard error 6%-9%; P = .003) among patients who received CMRT. On multivariate analysis, the hazard ratios (HRs) for BF and PCSM were 0.35 (95% confidence interval [CI], 0.23-0.52; P < .0001) and 0.41 (95% CI, 0.23-0.75; P < .003), favoring CMRT. Increasing duration of ADT predicted decreased BF (P = .04) and PCSM (P = .001), which was greatest with long-term ADT (BF: HR, 0.33; P < .0001; 95% CI, 0.21-0.52; PCSM: HR, 0.30; P = .001; 95% CI, 0.15-0.6) even in the subgroup that received CMRT. In this retrospective comparison, both low-dose-rate brachytherapy boost and ADT were associated with decreased risks of BF and PCSM compared with EBRT. Copyright © 2012 American Cancer Society.

Decision analytic cost-effectiveness model to compare prostate cryotherapy to androgen deprivation therapy for treatment of radiation recurrent prostate cancer

PubMed Central

Boyd, Kathleen A; Jones, Rob J; Paul, Jim; Birrell, Fiona; Briggs, Andrew H; Leung, Hing Y

2015-01-01

Objective To determine the cost-effectiveness of salvage cryotherapy (SC) in men with radiation recurrent prostate cancer (RRPC). Design Cost-utility analysis using decision analytic modelling by a Markov model. Setting and methods Compared SC and androgen deprivation therapy (ADT) in a cohort of patients with RRPC (biopsy proven local recurrence, no evidence of metastatic disease). A literature review captured published data to inform the decision model, and resource use data were from the Scottish Prostate Cryotherapy Service. The model was run in monthly cycles for RRPC men, mean age of 70 years. The model was run over the patient lifetime, to assess changes in patient health states and the associated quality of life, survival and cost impacts. Results are reported in terms of the discounted incremental costs and discounted incremental quality-adjusted life years (QALYs) gained between the 2 alternative interventions. Probabilistic sensitivity analysis used a 10 000 iteration Monte Carlo simulation. Results SC has a high upfront treatment cost, but delays the ongoing monthly cost of ADT. SC is the dominant strategy over the patient lifetime; it is more effective with an incremental 0.56 QALY gain (95% CI 0.28 to 0.87), and less costly with a reduced lifetime cost of £29 719 (€37 619) (95% CI −51 985 to −9243). For a ceiling ratio of £30 000, SC has a 100% probability to be cost-effective. The cost neutral point was at 3.5 years, when the upfront cost of SC (plus any subsequent cumulative cost of side effects and ADT) equates the cumulative cost in the ADT arm. Limitations of our model may arise from its insensitivity to parameter or structural uncertainty. Conclusions The platform for SC versus ADT cost-effective analysis can be employed to evaluate other treatment modalities or strategies in RRPC. SC is the dominant strategy, costing less over a patient's lifetime with improvements in QALYs. Trial registration number This economic analysis was undertaken as part of the CROP RCT study ISRCTN:72677390; it was a pre-trial economic model developed and analysed during the pre-results stage of the RCT. PMID:26482768

[Practical neoadjuvant and adjuvant therapies for rectal cancer. How many patients are actually recruited in multimodality therapy concepts? An analysis of the Tumour Centre Schwerin].

PubMed

Sauer, J; Sobolewski, K; Dommisch, K

2009-09-01

For rectal cancer in UICC stage II or III, a neoadjuvant chemoradiotherapy or short-course radiotherapy is established to reduce the incidence of local relapses. It has been documented that the neoadjuvant therapy is superior to the adjuvant therapy. In spite of the formulation of therapeutic principles in guidelines, they are not consistently applied. The actual rate of application and the reasons for a change from the recommended treatment strategy have been investigated. The data of the tumour centre West Mecklenburg were analysed. Data concerning the type and stage of rectal cancer, multimodal treatment (surgery with or without neoadjuvant therapy or adjuvant therapy) and treatment according to the level of medical care of hospitals were recorded from 2000 to 2008. In addition, in our clinic prospectively collected data of patients with rectal cancer (September 2006 until December 2008) were used to find out the reasons for the denial of neoadjuvant therapy. During the observation period we detected 348 patients with rectal cancer in UICC stage II or III in the area of the tumour centre West Mecklenburg. 16 % of these patients were treated pre-operatively. An increase in the preoperative multimodal treatment from 3 % to 39 % was observed. Hospitals with higher provisions of medical care applied the multimodal treatment 4-fold more frequently during this period of time. 55 patients of our own clinic were found to be of UICC stage II or III. 6 patients were emergency cases. The carcinoma was found in the lower or middle third of the rectum in 38 of our patients. The endosonographical examination could not adequately show the tumour or was falsely negative in 16 of these patients. A neoadjuvant treatment was started for 58 % of the patients. Overall, 76 of patients with rectal carcinoma were treated adjuvant or neoadjuvant, 62 of them with a complete treatment scheme. The application of neoadjuvant treatment for rectal carcinoma in UICC stage II or III in West Mecklenburg was unexpectedly low during the observation period. However, an increase in treatment frequency was detected. During the same period of time the number of patients treated in hospitals of basic and standard medical care decreased by half. This is the reason for the regional increase of neoadjuvant treatment. 47 % of the patients of our clinic received neoadjuvant chemoradiotherapy or a short-course radiotherapy. Including the adjuvant treatment, 76 % of all patients were treated multimodally. An increase in neoadjuvant treatment can only be achieved by shifting patients to centres with an appropriate diagnostic facility and a regular tumour board for rectal cancer. (c) Georg Thieme Verlag Stuttgart-New York.

Telangiectatic osteosarcoma.

PubMed

Colomina, Jordi; Peiro, Ana; Trullols, Laura; Garcia, Isidre

2013-04-01

To review records of 8 patients with telangiectatic osteosarcoma (TOS) and determine whether pathologic fractures correlate with recurrence and survival. Records of 4 men and 4 women aged 17 to 44 (mean, 28) years treated for TOS were reviewed. RESULTS; Of the 8 patients, 4 developed a pathologic fracture and 4 did not. In each group, 2 patients underwent limb salvage surgery and 2 underwent amputation. All patients received neoadjuvant and adjuvant chemotherapy with a combination of at least 2 of the following drugs: doxorubicin, methotrexate, cisplatin, and vincristin. After a mean follow-up of 5.6 (range, 2-16) years, all 4 patients with a pathologic fracture and 2 of the 4 patients without a pathologic fracture were still alive and disease-free. For the remaining patients, one died after 31 months from progression of a lung metastasis, and the other was alive with the disease and had had 2 recurrences, a lung metastasis, and an infection with Klebsiella oxytoca that eventually led to an amputation. The presence of a pathologic fracture in patients with TOS was not associated with worse outcome in terms of recurrence and survival.

Uniportal thoracoscopy combined with laparoscopy as minimally invasive treatment of esophageal cancer

PubMed Central

Caronia, Francesco Paolo; Arrigo, Ettore; Failla, Andrea Valentino; Sgalambro, Francesco; Giannone, Giorgio; Lo Monte, Attilio Ignazio; Cajozzo, Massimo; Santini, Mario

2018-01-01

A 67-year-old man was referred to our attention for management of esophageal adenocarcinoma, localized at the level of the esophagogastric junction and obstructed the 1/3 of the esophageal lumen. Due to the extension of the disease (T3N1M0-Stage IIIA), the patient underwent neo-adjuvant chemo-radiation therapy and he was then scheduled for a minimally invasive surgical procedure including laparoscopic gastroplasty, uniportal thoracoscopic esophageal dissection and intrathoracic end-to-end esophago-gastric anastomosis. No intraoperative and post-operative complications were seen. The patient was discharged in post-operative day 9. Pathological study confirmed the diagnosis of adenocarcinoma (T2N1M0-Stage IIB) and he underwent adjuvant chemotherapy. At the time of present paper, patient is alive and well without signs of recurrence or metastasis. Our minimally approach compared to standard open procedure would help reduce post-operative pain and favours early return to normal activity. However, future experiences with a control group are required before our strategy can be widely used. PMID:29850166

Uniportal thoracoscopy combined with laparoscopy as minimally invasive treatment of esophageal cancer.

PubMed

Caronia, Francesco Paolo; Arrigo, Ettore; Failla, Andrea Valentino; Sgalambro, Francesco; Giannone, Giorgio; Lo Monte, Attilio Ignazio; Cajozzo, Massimo; Santini, Mario; Fiorelli, Alfonso

2018-04-01

A 67-year-old man was referred to our attention for management of esophageal adenocarcinoma, localized at the level of the esophagogastric junction and obstructed the 1/3 of the esophageal lumen. Due to the extension of the disease (T3N1M0-Stage IIIA), the patient underwent neo-adjuvant chemo-radiation therapy and he was then scheduled for a minimally invasive surgical procedure including laparoscopic gastroplasty, uniportal thoracoscopic esophageal dissection and intrathoracic end-to-end esophago-gastric anastomosis. No intraoperative and post-operative complications were seen. The patient was discharged in post-operative day 9. Pathological study confirmed the diagnosis of adenocarcinoma (T2N1M0-Stage IIB) and he underwent adjuvant chemotherapy. At the time of present paper, patient is alive and well without signs of recurrence or metastasis. Our minimally approach compared to standard open procedure would help reduce post-operative pain and favours early return to normal activity. However, future experiences with a control group are required before our strategy can be widely used.

Esophageal stenosis: a differential diagnosis between esophageal cancer and metastasis from other neoplasia.

PubMed

Paris, Ida; Prelaj, Arsela; Onesti, Concetta Elisa; Baldoni, Alessandra; Giovagnoli, Maria Rosaria; Bassanelli, Maria; Lauro, Salvatore; Marchetti, Paolo

2014-01-01

The occurrence of radiological mediastinal lymphadenopathy as the only evidence of tumor recurrence of cervical carcinoma is very rare. We report on such a case with stenosis of the esophagus. A 36-year-old Caucasian woman, without any relevant history of gynecological cancer, underwent a trans-vaginal ultrasound with evidence of any cervical lesion locally extended. After histologically-proven diagnosis of squamous cell carcinoma of the cervix uterine, the patient was treated by neoadjuvant chemoradiation, followed by total abdominal hysterectomy with bilateral salpingoophorectomy. A subsequent close follow-up was negative for recurrence of disease until December 2008, two years after diagnosis. At that period, the patient experienced cough and severe dysphagia and for this reason she underwent several examinations including esophagogastroduodenoscopy, whole-body computed tomographic scan and bronchoscopy with transbronchial needle aspiration. Histology led to diagnosis of recurrence of cervical cancer, HPV31-positive, in multiple mediastinal lymphnodes, with infiltration of the esophageal mucosa. Mediastinal lymphade-nopathy in patients with a history of cervical carcinoma should be suspicious of metastatic disease, even if there is no radiological evidence of distant metastases.

Neoadjuvant radiotherapeutic strategies in pancreatic cancer

PubMed Central

Roeder, Falk

2016-01-01

This review summarizes the current status of neoadjuvant radiation approaches in the treatment of pancreatic cancer, including a description of modern radiation techniques, and an overview on the literature regarding neoadjuvant radio- or radiochemotherapeutic strategies both for resectable and irresectable pancreatic cancer. Neoadjuvant chemoradiation for locally-advanced, primarily non- or borderline resectable pancreas cancer results in secondary resectability in a substantial proportion of patients with consecutively markedly improved overall prognosis and should be considered as possible alternative in pretreatment multidisciplinary evaluations. In resectable pancreatic cancer, outstanding results in terms of response, local control and overall survival have been observed with neoadjuvant radio- or radiochemotherapy in several phase I/II trials, which justify further evaluation of this strategy. Further investigation of neoadjuvant chemoradiation strategies should be performed preferentially in randomized trials in order to improve comparability of the current results with other treatment modalities. This should include the evaluation of optimal sequencing with newer and more potent systemic induction therapy approaches. Advances in patient selection based on new molecular markers might be of crucial interest in this context. Finally modern external beam radiation techniques (intensity-modulated radiation therapy, image-guided radiation therapy and stereotactic body radiation therapy), new radiation qualities (protons, heavy ions) or combinations with alternative boosting techniques widen the therapeutic window and contribute to the reduction of toxicity. PMID:26909133

Loss of skeletal muscle mass during neoadjuvant treatments correlates with worse prognosis in esophageal cancer: a retrospective cohort study.

PubMed

Järvinen, Tommi; Ilonen, Ilkka; Kauppi, Juha; Salo, Jarmo; Räsänen, Jari

2018-02-12

Nutritional deficits, cachexia, and sarcopenia are extremely common in esophageal cancer. The aim of this article was to assess the effect of loss of skeletal muscle mass during neoadjuvant treatment on the prognosis of esophageal cancer patients. Esophageal cancer patients (N = 115) undergoing neoadjuvant therapy and surgery between 2010 and 2014 were identified from our surgery database and retrospectively analyzed. Computed tomography imaging of the total cross-sectional muscle tissue measured at the third lumbar level defined the skeletal muscle index, which defined sarcopenia (SMI < 52.4 cm2/m2 for men and < 38.5 cm2/m2 for women). Images were collected before and after neoadjuvant treatments. Sarcopenia in preoperative imaging was prevalent in 92 patients (80%). Median overall survival was 900 days (interquartile range 334-1447) with no difference between sarcopenic (median = 900) and non-sarcopenic (median = 914) groups (p = 0.872). Complication rates did not differ (26.1% vs 32.6%, p = 0.725). A 2.98% decrease in skeletal muscle index during neoadjuvant treatment correlated with poor 2-year survival (log-rank p = 0.04). Loss of skeletal muscle tissue during neoadjuvant treatment correlates with worse overall survival.

Neoadjuvant chemotherapy for atypical teratoid rhabdoid tumors: case report.

PubMed

Thatikunta, Meena; Mutchnick, Ian; Elster, Jennifer; Thompson, Matthew P; Huang, Michael A; Spalding, Aaron C; Moriarty, Thomas

2017-05-01

Atypical teratoid rhabdoid tumors (ATRTs) are a rare pediatric brain tumor with high mortality rate. Several large series have reported achieving gross-total resection (GTR) in less than 50% of patients due to the lesions' large size, vascularity, and limited blood volume in young patients. While neoadjuvant chemotherapy for choroid plexus carcinomas in pediatric patients has become widely accepted, it has not been used as widely for other pediatric brain tumors. To the best of the authors' knowledge, there are only 3 published cases of neoadjuvant chemotherapy for ATRTs. In the present report, the authors present a fourth case of neoadjuvant chemotherapy for ATRT and review the available literature on this strategy. A 17-month-old child presented with a left ventricular ATRT for which imaging raised concern for a highly vascularized tumor. The authors undertook neoadjuvant chemotherapy with 2 cycles of Head Start II therapy, which reduced the size of the ventricular tumor by 35% and decreased the vascularity of the lesion on imaging. The estimated blood loss during resection was 425 ml and GTR was achieved. The patient continued with postoperative chemotherapy but suffered an on-therapy recurrence. While higher-quality data are necessary, available evidence suggests that neoadjuvant chemotherapy can reduce the size and vascularity of ATRTs and facilitate a surgical avenue for large or "inoperable" tumors.

Patient and tumor characteristics associated with breast cancer recurrence after complete pathological response to neoadjuvant chemotherapy.

PubMed

Ju, Na Rae; Jeffe, Donna B; Keune, Jason; Aft, Rebecca

2013-01-01

Breast cancer patients whose tumors achieve a pathological complete response (pCR) with neoadjuvant chemotherapy have a prognosis which is better than that predicted for the stage of their disease. However, within this subgroup of patients, recurrences have been observed. We sought to examine factors associated with recurrence in a population of breast cancer patients who achieved a pCR with neoadjuvant chemotherapy. A retrospective chart review was conducted of all patients with unilateral breast cancer treated with neoadjuvant chemotherapy from January 1, 2000 to December 31, 2010 at one comprehensive cancer center. A pCR was defined as no residual invasive cancer in the breast in the surgical specimen following neoadjuvant therapy. Recurrence was defined as visceral or bony reappearance of cancer after completion of all therapy. Of 818 patients who completed neoadjuvant chemotherapy, 144 (17.6 %) had pCR; six with bilateral breast cancer were excluded from further analysis. The mean time to follow-up was 47.2 months. Among the 138 patients with unilateral breast cancer, there were 14 recurrences (10.1 %). Using a binary multiple logistic regression model, examining types of chemotherapy and surgery, race, lymph node assessment, and lymph node status, breast cancer side, triple-negative status, and radiation receipt, only African-American patients (OR: 5.827, 95 % CI: 1.280-26.525; p = 0.023) were more likely to develop distant recurrence. The mean time to recurrence was 31.9 months. In our study, race was the only independent predictor of recurrence after achieving pCR with neoadjuvant chemotherapy. The reasons for this observation require further study.

Exploring patient experiences of neo-adjuvant chemotherapy for breast cancer.

PubMed

Beaver, Kinta; Williamson, Susan; Briggs, Jean

2016-02-01

Neo-adjuvant chemotherapy is recommended for 'inoperable' locally advanced and inflammatory breast cancers. For operable breast cancers, trials indicate no survival differences between chemotherapy given pre or post-surgery. Communicating evidence based information to patients is complex and studies examining patient experiences of neo-adjuvant chemotherapy are lacking. This study aims to explore the experiences of women who received neo-adjuvant chemotherapy for breast cancer. A qualitative approach using in-depth interviews with 20 women who had completed neo-adjuvant chemotherapy for breast cancer. Interview data were analysed using thematic analysis. The sample included a relatively young group of women, with caring responsibilities. Five main themes emerged: coping with the rapid transition from 'well' to 'ill', information needs and decision making, needing support and empathy, impact on family, and creating a new 'normal'. More support was needed towards the end of chemotherapy, when side effects were at their most toxic, and decisions about forthcoming surgery were being made. Some women were referred to psychological services, but usually when a crisis point had been reached. Information and support would have been beneficial at key time points. This information is vital in developing services and interventions to meet the complex needs of these patients and potentially prevent late referral to psychological services. Specialist oncology nurses are able to develop empathetic relationships with patients and have the experience, knowledge and skills to inform and support women experiencing neo-adjuvant chemotherapy. Targeting key time points and maintaining relationship throughout neo-adjuvant chemotherapy would be highly beneficial. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

PubMed

Sabanathan, Dhanusha; Eslick, Guy D; Shannon, Jenny

2016-12-01

Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs. A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design. The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I 2  = 89.35; P < .001). Of the 11 studies, 4 used a combination that included oxaliplatin, 2 included irinotecan, and 5 included a combination of both. Also, 7 studies used cetuximab and 4 bevacizumab. The overall progression-free survival was estimated at 14.4 months. Current evidence suggests that neoadjuvant chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

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.

Genetic polymorphisms in 5-Fluorouracil-related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer.

PubMed

Nelson, Bailey; Carter, Jane V; Eichenberger, Maurice R; Netz, Uri; Galandiuk, Susan

2016-11-01

Many patients with rectal cancer undergo preoperative neoadjuvant chemoradiation, with approximately 70% exhibiting pathologic downstaging in response to treatment. Currently, there is no accurate test to predict patients who are likely to be complete responders to therapy. 5-Fluorouracil is used regularly in the neoadjuvant treatment of rectal cancer. Genetic polymorphisms affect the activity of thymidylate synthase, an enzyme involved in 5-Fluorouracil metabolism, which may account for observed differences in response to neoadjuvant treatment between patients. Detection of genetic polymorphisms might identify patients who are likely to have a complete response to neoadjuvant therapy and perhaps allow them to avoid operation. DNA was isolated from whole blood taken from patients with newly diagnosed rectal cancer who received neoadjuvant therapy (n = 50). Response to therapy was calculated with a tumor regression score based on histology from the time of operation. Polymerase chain reaction was performed targeting the promoter region of thymidylate synthase. Polymerase chain reaction products were separated using electrophoresis to determine whether patients were homozygous for a double-tandem repeat (2R), a triple-tandem repeat (3R), or were heterozygous (2R/3R). A single nucleotide polymorphism, 3G or 3C, also may be present in the second repeat unit of the triple-tandem repeat allele. Restriction fragment length polymorphism assays were performed in patients with at least one 3R allele using HaeIII. Patients with at least 1 thymidylate synthase 3G allele were more likely to have a complete or partial pathologic response to 5-Fluorouracil neoadjuvant therapy (odds ratio 10.4; 95% confidence interval, 1.3-81.6; P = .01) than those without at least one 3G allele. Identification of rectal cancer patients with specific genetic polymorphisms in enzymes involved in 5-Fluorouracil metabolism seems to predict the likelihood of complete or partial pathologic response to preoperative neoadjuvant therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Nipple skin-sparing mastectomy is feasible for advanced disease.

PubMed

Burdge, Eric C; Yuen, James; Hardee, Matthew; Gadgil, Pranjali V; Das, Chandan; Henry-Tillman, Ronda; Ochoa, Daniela; Korourian, Soheila; Suzanne Klimberg, V

2013-10-01

Skin-sparing mastectomy (SSM) or nipple skin-sparing mastectomy (NSSM) are procedures commonly offered as part of the surgical treatment for breast cancer. Each involves a mastectomy with preservation of the skin overlying the breast (in SSM) and often also the skin overlying the nipple-areolar complex (NSSM). At the time of mastectomy, immediate reconstruction with a tissue expander or implant is performed for a more favorable cosmetic outcome. Until now, these procedures have been reserved for low-risk patients and are rarely offered to patients with advanced disease where neoadjuvant chemotherapy and postmastectomy radiation are a planned part of the treatment. We report our experience of SSM and NSSM in such high-risk patients. This retrospective study from 2001 to 2012 evaluates the outcomes of 527 patients who underwent SSM or NSSM. Sixty patients with advanced disease who underwent neoadjuvant chemotherapy followed by SSM or NSSM with immediate reconstruction and subsequent radiotherapy (RT) were identified. The cosmetic and oncologic outcomes of this patient group were noted. A total of 527 patients in our study group had a total of 1,035 skin-sparing mastectomies (558 NSSM and 477 SSM; 444 patients with bilateral and 83 with unilateral procedures). Of the 60 patients with locally advanced disease, 39 underwent NSSM and 21 underwent SSM. All patients received RT to the diseased side. Mean age of the group was 50.2 ± 10.8 years, with a range of 27-75 years for NSSM and 29-73 years for SSM. The lymph node status was positive in 71.8 % with an average tumor size of 3.8 ± 2.5 cm. The overall radiation-induced complication rate was 38.1 % (8 of 21) in the SSM group and 30.8 % (12 of 39) in the NSSM group. Wound infections and tissue necrosis occurred at a rate of 16.7 %. The implant was removed in 5 % of these cases. Capsular contracture occurred at a rate of 10.2 %. Radiation-related nonbreast complications occurred in 6.7 % of the cases. Examples of these radiation-related nonbreast complications included radiation pneumonitis, stenosis of the superior vena cava requiring venoplasty and severe atypical chest pain thought to be consistent with osteochondritis. The locoregional recurrence rate (median follow-up of 18 months) was 14.3 % (3 of 21) in the SSM group and 10.3 % (4 of 39) in the NSSM group. SSM and NSSM have been offered to patients with relatively low-risk breast cancer as oncologically safe while affording superior cosmesis with one-step immediate reconstruction. Our series demonstrates that either procedure can be offered to patients with more advanced cancers requiring postoperative RT. The complication rates are comparable to those reported for patients undergoing RT after traditional mastectomies.

Relief of dysphagia during neoadjuvant treatment for cancer of the esophagus or gastroesophageal junction.

PubMed

Sunde, B; Ericson, J; Kumagai, K; Lundell, L; Tsai, J A; Lindblad, M; Rouvelas, I; Friesland, S; Wang, N; Nilsson, M

2016-07-01

Dysphagia is the main symptom of cancer of the esophagus and gastroesophageal junction and causing nutritional problems and weight loss, often counteracted by insertion of self-expandable metal stents or nutrition via an enteral route. Clinical observations indicate that neoadjuvant therapy may effectively and promptly alleviate dysphagia, making such nutrition supportive interventions redundant before surgical resection. The objective of the current study was to carefully study the effects of induction neoadjuvant therapy on dysphagia and its subsequent course and thereby investigate the actual need for alimentary gateways for nutritional support. Thirty-five consecutive patients scheduled for neoadjuvant therapy were recruited and assessed regarding dysphagia and appetite at baseline, after the first cycle of preoperative treatment with either chemotherapy alone or with chemoradiotherapy and before surgery. Platinum-based therapy in combination with 5-fluorouracil was administered intravenously days 1-5 every 3 weeks and consisted of three treatments. Patients receiving combined chemoradiotherapy started radiotherapy on day one of second chemotherapy cycle. They received fractions of 2 Gy/day each up to a total dose of 40 Gy. Watson and Ogilvie dysphagia scores were used to assess dysphagia, while appetite was assessed by the Edmonton Assessment System Visual analogue scale-appetite questionnaire. Patients were evaluated at regular outpatient clinic visits or by telephone. The histological tumor response in the surgical specimen was assessed using the Chirieac scale. Ten patients scheduled for neoadjuvant chemotherapy and 25 patients scheduled for chemoradiotherapy were included in the analysis. There was a significant improvement in dysphagia in both treatment groups, according to both scales, already from baseline to the completion of the first chemotherapy cycle which remained to the end of the neoadjuvant treatment (P < 0.001). Appetite also improved after the first chemotherapy cycle (P = 0.03). Body weight did not change during any type of neoadjuvant therapy. We were unable to demonstrate any association between relief of dysphagia and the degree of histological response to neoadjuvant therapy in the surgical specimen. The present study shows that a platin - 5FU-based neoadjuvant chemotherapy, with or without concomitant radiotherapy, effectively and promptly relieves dysphagia in patients presenting with cancers of the esophagus or gastroesophageal junction already after the first cycle. © 2015 International Society for Diseases of the Esophagus.

Intrinsic Charge Trapping Observed as Surface Potential Variations in diF-TES-ADT Films.

PubMed

Hoffman, Benjamin C; McAfee, Terry; Conrad, Brad R; Loth, Marsha A; Anthony, John E; Ade, Harald W; Dougherty, Daniel B

2016-08-24

Spatial variations in surface potential are measured with Kelvin probe force microscopy for thin films of 2,8-difluoro-5,11-bis(triethylsilylethynyl)anthradithiophenes (diF-TES-ADT) grown on SiO2 and silane-treated SiO2 substrates by organic molecular beam deposition. The variations are observed both between and within grains of the polycrystalline organic film and are quantitatively different than electrostatic variations on the substrate surfaces. The skewness of surface potential distributions is larger on SiO2 than on HMDS-treated substrates. This observation is attributed to the impact of substrate functionalization on minimizing intrinsic crystallographic defects in the organic film that can trap charge.

Use of trastuzumab as an adjuvant/neoadjuvant therapy in patients with HER2-positive breast cancer in China: The Nvwa study.

PubMed

Li, Junjie; Shao, Zhimin; Xu, Binghe; Jiang, Zefei; Cui, Shude; Zhang, Jin; Liao, Ning; Jiang, Jun; Wang, Yongsheng; Ouyang, Quchang; Ying, Ziwei

2018-05-01

The aim of this study was to understand current trends in trastuzumab use in China as a neoadjuvant/adjuvant therapy for human epidermal growth factor receptor-2 positive (HER2+) breast cancer and identify factors influencing trastuzumab use.This was a retrospective, multicenter, cross-sectional study of patients diagnosed with HER2+ breast cancer (stage I-III), between July 2013 and June 2014, at 155 hospitals in 29 provinces/cities in China. Demographic and clinical data, including tumor characteristics and details of adjuvant/neoadjuvant therapies used, were collected. Data analysis included univariate analysis, multivariate logistic regression, and subgroup analyses.Of 4994 HER2+ patients (mean age 51.1 ± 9.9 years) included, only 29.8% received trastuzumab, with 30.5% in adjuvant therapy and 18.3% in neoadjuvant therapy. The highest rates of adjuvant trastuzumab were in Beijing (59.3%), Jiangsu (57.1%), and Ningxia (50.0%), while those of neoadjuvant trastuzumab were in Guangdong (24.8%), Beijing (14.1%), and Zhejiang (10.7%). Multivariate regression results revealed that factors associated with trastuzumab use were medical insurance cover for trastuzumab, residing locally to the hospital, more lymph node involvement, and more advanced tumor stage. Subgroup analysis revealed that patients receiving neoadjuvant therapy were likely to be younger, premenopausal and non-local, and had lymph node metastases, more advanced tumor, and progesterone receptor positive tumor.Trastuzumab use in patients with HER2+ breast cancer is relatively low in China, especially for neoadjuvant therapy. Insurance coverage seems to be the most correlated factor that influences the use of trastuzumab in Chinese patients with HER2+ breast cancer.

Utility of Adjuvant Chemotherapy After Neoadjuvant Chemoradiation and Esophagectomy for Esophageal Cancer.

PubMed

Burt, Bryan M; Groth, Shawn S; Sada, Yvonne H; Farjah, Farhood; Cornwell, Lorraine; Sugarbaker, David J; Massarweh, Nader N

2017-08-01

To determine whether adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and esophagectomy is associated with improved overall survival for patients with locally advanced esophageal cancer, and to evaluate how pathologic disease response to neoadjuvant treatment impacts this effect. Neoadjuvant chemoradiation is currently the preferred management approach for locoregional esophageal cancer. Although there is interest in the use of AC, the benefit of systemic therapy after neoadjuvant chemoradiation and esophagectomy is unclear. Retrospective cohort study of patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy in the National Cancer Data Base (2006-2012). Among 3592 patients with esophageal cancer (84.7% adenocarcinoma, 15.2% squamous cell carcinoma), 335 (9.3%) were treated with AC. AC was not associated with a significantly lower risk of death among patients with no residual disease (ypT0N0) or residual non-nodal disease (ypT+N0). Among patients with residual nodal disease (ypTanyN+), AC was associated with a 30% lower risk of death in the overall cohort [hazard ratio (HR) 0.70, (0.57-0.85)] and among those with adenocarcinoma [HR 0.69 (0.57-0.85)]. Using a 90-day postoperative landmark, findings were similar. Among patients with postoperative length of stay ≤10 days and no unplanned readmission, AC was associated with approximately 40% lower risk of death among patients with residual nodal disease [overall cohort, HR 0.63 (0.48-0.84); adenocarcinoma, HR 0.66 (0.49-0.88)]. AC after neoadjuvant chemoradiation and esophagectomy is associated with improved survival in patients with residual nodal disease. Our findings suggest AC may provide additional benefit for esophageal cancer patients, and merits further investigation.

Imaging Analysis of Hepatoblastoma Resectability Across Neoadjuvant Chemotherapy

PubMed Central

Murphy, Andrew J.; Ayers, Gregory D.; Hilmes, Melissa A.; Mukherjee, Kaushik; Wilson, Kevin J.; Allen, Wade M.; Fernandez-Pineda, Israel; Shinall, Myrick C.; Zhao, Zhiguo; Furman, Wayne L.; McCarville, Mary Beth; Davidoff, Andrew M.; Lovvorn, Harold N.

2013-01-01

Purpose Hepatoblastomas often require neoadjuvant chemotherapy to facilitate partial hepatectomy, which necessitates freedom of tumor borders from the confluence of hepatic veins (COHV), portal vein bifurcation (PVB), and retrohepatic inferior vena cava (IVC). This study aimed to clarify the effect of incremental neoadjuvant cycles on the AHEP0731 protocol criteria of hepatoblastoma resectability. Methods Hepatoblastoma responses to neoadjuvant chemotherapy were analyzed among patients (n=23) treated at two children’s hospitals between 1996 and 2010. Using digital imaging data, ellipsoid and point-based models were created to measure tumor volume regression and respective distances from tumor borders nearest to the COHV, PVB, and IVC. Results Hepatoblastoma volumes regressed with incremental neoadjuvant chemotherapy cycles (p<0.001). Although tumor borders regressed away from the COHV (p=0.008), on average only 1.1mm was gained. No change from tumor borders to the PVB was detected (p=0.102). Distances from tumor borders to the IVC remained stable at one hospital (p=0.612), but increased only 0.15mm every 10 days of therapy at the other (p=0.002). Neoadjuvant chemotherapy induced slightly more tumors to meet the threshold vascular margin of 1cm (baseline to completion): COHV, 11 (47.8%) to 17 (73.9%; p=0.058); PVB, 11 (47.8%) to 15 (65.2%; p=0.157); IVC, 4 (17.4%) to 10 (43.5%; p=0.034). No differences were detected in demographic or disease-specific characteristics between patients who did or did not achieve this 1cm margin after conclusion of chemotherapy. Conclusion Hepatoblastoma volumes regress significantly with increasing neoadjuvant chemotherapy cycles. However, tumors often remain anchored to the major hepatic vasculature, showing marginal improvement in resectability criteria. PMID:23845613

Factors associated with reduction in use of neoadjuvant androgen suppression therapy before radical prostatectomy.

PubMed

O'Shaughnessy, Matthew J; Jarosek, Stephanie L; Virnig, Beth A; Konety, Badrinath R; Elliott, Sean P

2013-04-01

To determine whether the prescribing patterns for nonindicated androgen suppression therapy (AST), using neoadjuvant AST as the model, changed according to the prevailing clinical evidence, changes in reimbursement, or evidence of increased harm from treatment. We identified 34,976 men with prostate cancer who had undergone radical prostatectomy within 12 months of diagnosis from the Surveillance, Epidemiology, and End Results-Medicare data set (1992-2007), and their clinical and demographic parameters were assessed. We measured the Medicare claims for receipt of AST before radical prostatectomy and calculated the annual rates of neoadjuvant AST, which were adjusted for confounding variables using multivariate logistic regression analysis, and compared them with the prevailing published clinical data on the outcomes of neoadjuvant AST, changes in reimbursement, or published data on clinical harm from treatment. The use of neoadjuvant AST increased from 7.8% in 1992 to a peak of 17.6% in 1996 and then decreased steadily to 4.6% in 2007. This rate change was significant on multivariate regression analysis, with a single join point in 1996 (P <.001), and corresponded to published data showing improved surgical margin rates and pathologic downstaging in the early 1990s and data showing no improvement in disease recurrence or overall survival beginning in 1997. Changes in reimbursement and evidence of harm from AST were not associated with the decreased use of neoadjuvant AST. Using neoadjuvant AST as the model for the nonindicated use of AST, physicians reduced AST use in response to high-level evidence showing a lack of benefit, despite the high reimbursement. This suggests that physicians adapt to emerging evidence and use evidence-based practice. Copyright © 2013 Elsevier Inc. All rights reserved.

Blood neutrophil-lymphocyte ratio predicts survival in locally advanced cancer stomach treated with neoadjuvant chemotherapy FOLFOX 4.

PubMed

el Aziz, Lamiss Mohamed Abd

2014-12-01

Accurate predictors of survival for patients with advanced gastric cancer treated with neoadjuvant chemotherapy are currently lacking. In this study, we aimed to evaluate the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with stage III-IV gastric cancer who received neoadjuvant chemotherapy FOLFOX 4 as neoadjuvant chemotherapy. We enrolled 70 patients with stage III-IV cancer stomach in this study. Patients received FOLFOX 4 as neoadjuvant chemotherapy. Blood sample was collected before chemotherapy. The NLR was divided into two groups: high (>3) and low (≤ 3). Univariate analysis on progression-free survival (PFS) and overall survival (OS) was performed using the Kaplan-Meier and log-rank tests, and multivariate analysis was conducted using the Cox proportional hazards regression model. The toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria. The univariate analysis showed that PFS and OS were both worse for patients with high NLR than for those with low NLR before chemotherapy (median PFS 28 and 44 months, respectively, P = 0.001; median OS 30 and 48 months, P = 0.001). Multivariate analysis showed that NLRs before chemotherapy were independent prognostic factors of OS but not for progression-free survival. NLR may serve as a potential biomarker for survival prognosis in patients with stage III-IV gastric cancer receiving neoadjuvant chemotherapy. The FOLFOX 4 demonstrated an acceptable toxicity.

Preoperative neo-adjuvant therapy for curable rectal cancer--reaching a consensus 2008.

PubMed

Scott, N A; Susnerwala, S; Gollins, S; Myint, A Sun; Levine, E

2009-03-01

Our aim was to determine the range of neo-adjuvant therapy the multidisciplinary team (MDT) currently offers patients with curable (M(0)) rectal cancer. A senior oncologist from each of the four oncology centres in north Wales and the north-west of England (approximate target population 8 million - Glan Clwyd, Clatterbridge, Christie and Preston) reviewed his/her understanding of the current evidence of neo-adjuvant therapy in rectal cancer. Then a representative from each centre was asked to identify which of three neo-adjuvant options (no neo-adjuvant therapy, short-course radiotherapy 25 Gy over five fractions and long-course chemoradiotherapy) he/she would use for a rectal cancer in the upper, middle or lower third of the rectum staged by magnetic resonance imaging as being T(2)-T(4) and/or N(0)-N(2). In all cases of locally advanced rectal cancer (T(3a) N(1)-T(4)), oncologists from the four oncology centres recommended long-course chemoradiotherapy before rectal resection. This consensus was maintained for cases of lower third T(3a) N(0) cancers. Thereafter, the majority of patients with rectal cancer are offered adjuvant short-course radiotherapy. Neo-adjuvant therapy is less likely to be offered if the tumour is early (T(2), N(0)) and/or situated in the upper third of the rectum.

Risk factors for positive margins in conservative surgery for breast cancer after neoadjuvant chemotherapy.

PubMed

Bouzón, Alberto; Acea, Benigno; García, Alejandra; Iglesias, Ángela; Mosquera, Joaquín; Santiago, Paz; Seoane, Teresa

2016-01-01

Breast conservative surgery after neoadjuvant chemotherapy intends to remove any residual tumor with negative margins. The purpose of this study was to analyze the preoperative clinical-pathological factors influencing the margin status after conservative surgery in breast cancer patients receiving neoadjuvant chemotherapy. A retrospective study of 91 breast cancer patients undergoing neoadjuvant chemotherapy (92 breast lesions) during the period 2006 to 2013. A Cox regression analysis to identify baseline tumor characteristics associated with positive margins after breast conservative surgery was performed. Of all cases, 71 tumors were initially treated with conservative surgery after neoadjuvant chemotherapy. Pathologic exam revealed positive margins in 16 of the 71 cases (22.5%). The incidence of positive margins was significantly higher in cancers with initial size >5cm (P=.021), in cancers with low tumor grade (P=.031), and in patients with hormone receptor-positive cancer (P=.006). After a median follow-up of 45.2 months, 7 patients of the 71 treated with conservative surgery had disease recurrence (9.8%). There was no significant difference in terms of disease-free survival according to the margin status (P=.596). A baseline tumor size >5cm, low tumor grade and hormone receptor-positive status increase the risk for surgical margin involvement in breast conservative surgery after neoadjuvant chemotherapy. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

The Role of Neoadjuvant Trials in Drug Development for Solid Tumors.

PubMed

Funt, Samuel A; Chapman, Paul B

2016-05-15

The relatively low success rate of phase II oncology trials in predicting success of novel drugs in phase III trials and in gaining regulatory approval may be due to reliance on the endpoint of response rate defined by the RECIST. The neoadjuvant treatment paradigm allows the antitumor activity of a novel therapy to be determined on a pathologic basis at the time of surgery instead of by RECIST, which was not developed to guide clinical decision making or correlate with long-term outcomes. Indeed, the FDA endorsed pathologic complete response (pCR) as a surrogate for overall survival (OS) in early-stage breast cancer and granted accelerated approval to pertuzumab based on this endpoint. We propose that pCR is a biologically rational method of determining treatment effect that may be more likely to predict OS. We discuss some advantages of the neoadjuvant trial design, review the use of neoadjuvant therapy as standards of care, and consider the neoadjuvant platform as a method for drug development. Clin Cancer Res; 22(10); 2323-8. ©2016 AACR. ©2016 American Association for Cancer Research.

[A case of neoadjuvant chemotherapy for locally advanced rectal cancer, which had a invasion into the vagina followed by curative resection].

PubMed

Kimura, Kei; Kagawa, Yoshinori; Kato, Takeshi; Ishida, Tomo; Morimoto, Yoshihiro; Matusita, Katsunori; Kusama, Hiroki; Hashimoto, Tadayoshi; Katura, Yoshiteru; Nitta, Kanae; Takeno, Atushi; Nakahira, Shin; Okishiro, Masatsugu; Sakisaka, Hideki; Taniguchi, Hirokazu; Egawa, Chiyomi; Takeda, Yutaka; Tamura, Shigeyuki

2014-11-01

A-64-years-old woman with locally advanced rectal cancer, which had invaded the vagina, was referred to our hospital. She was administered neoadjuvant chemotherapy to reduce the tumor size. After 4 courses of chemotherapy consisting of folinic acid, fluorouracil, and oxaliplatin (mFOLFOX6), an enhanced computed tomography (CT) scan and magnetic resonance imaging (MRI) indicated marked tumor shrinkage. We performed a laparoscopically assisted low anterior resection, which included total mesorectal resection, resection of the vaginal posterior wall, and right lateral lymph node resection. The chemotherapy prevented us from having to create a permanent colostomy. The efficacy of the neoadjuvant chemotherapy was Grade 1b. We experienced a case of neoadjuvant chemotherapy followed by curative resection.

Mutation of a Rice Gene Encoding a Phenylalanine Biosynthetic Enzyme Results in Accumulation of Phenylalanine and Tryptophan[W

PubMed Central

Yamada, Tetsuya; Matsuda, Fumio; Kasai, Koji; Fukuoka, Shuichi; Kitamura, Keisuke; Tozawa, Yuzuru; Miyagawa, Hisashi; Wakasa, Kyo

2008-01-01

Two distinct biosynthetic pathways for Phe in plants have been proposed: conversion of prephenate to Phe via phenylpyruvate or arogenate. The reactions catalyzed by prephenate dehydratase (PDT) and arogenate dehydratase (ADT) contribute to these respective pathways. The Mtr1 mutant of rice (Oryza sativa) manifests accumulation of Phe, Trp, and several phenylpropanoids, suggesting a link between the synthesis of Phe and Trp. Here, we show that the Mtr1 mutant gene (mtr1-D) encodes a form of rice PDT with a point mutation in the putative allosteric regulatory region of the protein. Transformed callus lines expressing mtr1-D exhibited all the characteristics of Mtr1 callus tissue. Biochemical analysis revealed that rice PDT possesses both PDT and ADT activities, with a preference for arogenate as substrate, suggesting that it functions primarily as an ADT. The wild-type enzyme is feedback regulated by Phe, whereas the mutant enzyme showed a reduced feedback sensitivity, resulting in Phe accumulation. In addition, these observations indicate that rice PDT is critical for regulating the size of the Phe pool in plant cells. Feeding external Phe to wild-type callus tissue and seedlings resulted in Trp accumulation, demonstrating a connection between Phe accumulation and Trp pool size. PMID:18487352

Somatostatin analogs and disease control in castration-resistant prostate cancer: different biological behavior? Case series and review of the literature.

PubMed

D'Angelillo, Rolando Maria; Greco, Carlo; Fiore, Michele; Ippolito, Edy; Eolo Trodella, Luca; Iurato, Aurelia; Molfese, Elisabetta; Ramella, Sara; Trodella, Lucio

2014-01-01

Castration-resistant prostate cancer is a recent biological behavior where disease can elude androgen deprivation therapy (ADT). Several pathways have been described, including neuroendocrine dedifferentiation. Patients with neuroendocrine dedifferentiation show an increase in chromogranin A (CgA) along with a PSA increase. Our aim was to evaluate the response of patients with castration-resistant prostate cancer and high CgA serum levels after treatment with inhibitors of neuroendocrine cells (somatostatin analogs) in combination with ADT. From January 2009 to April 2011, 10 patients with castration-resistant prostate cancer and rising PSA levels along with a CgA increase were evaluated. The therapy was based on somatostatin analogs and LHRH anologs. Total PSA and CgA were measured every 2 months. In 9 of the 10 patients, a reduction of the values of pre-treatment CgA was detected, while a reduction of PSA was found in 8 patients. No grade 2 or higher toxicity was recorded. Only 3 patients had grade 1 gastrointestinal toxicity. Time to progression was 13 months. Therapy with somatostatin analogs could increase the therapeutic window of ADT with a low toxicity profile in a subpopulation of patients with castration-resistant prostate cancer who experience a rise in CgA due to neuroendocrine regulation.

[Utilization of multimodal therapy concepts in stomach carcinoma in Germany].

PubMed

Bösing, N M; Heise, J W; Röher, H D

2000-01-01

In view of disappointing results after surgery alone multimodal therapeutic regimes are used to improve long-term prognosis in locally advanced gastric carcinomas. In presence of many reports about encouraging results ("down staging", improved R0-resection rates) but simultaneously missing evidence of efficiency of neoadjuvant therapies in respect to long-term survival (large randomized multicenter trials do not exist until today) and the herewith related uncertainties, we started an inquiry among many surgical units with the intention to evaluate the clinical practice of multimodal treatment for gastric cancer patients in Germany today. In a questionnaire (3/99) we asked among 97 surgical units (41 university hospitals, 56 big community hospitals) in Germany for the management of gastric cancer patients with special interest to practice and state of adjuvant and neoadjuvant therapeutic strategies. Further we analyzed all resected gastric cancer patients (1986-1995) without neoadjuvant treatment in advanced stage of disease (pT3/4NxMx; stage III/IV (UICC'92) in respect to R0-resection rate and long-term prognosis (Kaplan-Meier). Overall feedback amounted to 78% (76/97) and was higher in university hospitals (90%) than in big community hospitals (70%). Today, neoadjuvant therapies are of more interest than adjuvant therapeutic regimes. But also neoadjuvant therapy is only used in 32% as a rule (in 16% with, in 16% without study conditions). 25% of all surgical units do not employ any neoadjuvant therapy in locally advanced gastric cancer until today. In all other surgical units neoadjuvant treatment is performed more individually and sporadically (43%) only in some patients. Neoadjuvant therapies are practiced by haematooncologists in 50%, gastroenterologists in 32% and surgeons in 27%. The predominant neoadjuvant therapeutic strategy is chemotherapy alone (84%). Many surgical units in Germany are interested to participate in a multicenter trial with more interest in neoadjuvant than adjuvant therapy. 185 of 309 resected gastric cancer patients (60%) were classified as stage IIIa, stage IIIb or stage IV patients. R0-resection rate of these advanced gastric cancer patients amounted to 37%; only 24% of them survived 5 years or more. Considering the missing evidence that multimodal therapies are able to prolong long-term survival in advanced gastric cancer patients, its use without study conditions is questionable. Conclusions, taken from data of clinical trials regarding carcinomas of the esophagus and esophagealgastric junction, are inconsistent in respect to long-term prognosis and results are not transferable to gastric carcinomas. A prospective randomized multicenter trial in advanced gastric cancer patients is of great importance. Following our data, in Germany a high readiness to participate in the forthcoming EORTC-study is present.

Morbidity and mortality according to age following gastrectomy for gastric cancer.

PubMed

Nelen, S D; Bosscha, K; Lemmens, V E P P; Hartgrink, H H; Verhoeven, R H A; de Wilt, J H W

2018-04-23

This study investigated age-related differences in surgically treated patients with gastric cancer, and aimed to identify factors associated with outcome. Data from the Dutch Upper Gastrointestinal Cancer Audit were used. All patients with non-cardia gastric cancer registered between 2011 and 2015 who underwent surgery were selected. Patients were analysed by age group (less than 70 years versus 70 years or more). Multivariable logistic regression was used to assess the influence of clinicopathological factors on morbidity and mortality. A total of 1109 patients younger than 70 years and 1206 aged 70 years or more were included. Patients aged at least 70 years had more perioperative or postoperative complications (41·2 versus 32·5 per cent; P < 0·001) and a higher 30-day mortality rate (7·9 versus 3·2 per cent; P < 0·001) than those younger than 70 years. In multivariable analysis, age 70 years or more was associated with a higher risk of complications (odds ratio 1·29, 95 per cent c.i. 1·05 to 1·59). Postoperative mortality was not significantly associated with age. In the entire cohort, morbidity and mortality were influenced most by ASA grade, neoadjuvant chemotherapy and type of resection. ASA grade, neoadjuvant chemotherapy and type of resection are independent predictors of morbidity and death in patients with gastric cancer, irrespective of age. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

PubMed Central

García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf Dieter; Fernández-Esparrach, Gloria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Miriam; Delgado, Salvadora; Ginés, Angels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Oscar; Victoria, Iván; Feliz, Luis; María de Lacy, Antonio; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

2014-01-01

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team. PMID:25400468

Tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric adenocarcinoma: a prospective, multi-center cohort study

PubMed Central

De Martini, Paolo; Ceresoli, Marco; Mari, Giulio M.; Costanzi, Andrea; Maggioni, Dario; Pugliese, Raffaele; Ferrari, Giovanni

2017-01-01

Background To verify the prognostic value of the pathologic and radiological tumor response after neoadjuvant chemotherapy in the treatment of locally advanced gastric adenocarcinoma. Methods A total of 67 patients with locally advanced gastric cancer (clinical ≥ T2 or nodal disease and without evidence of distant metastases) underwent perioperative chemotherapy (ECF or ECX regimen) from December 2009 through June 2015 in two surgical units. Histopathological and radiological response to chemotherapy were evaluated by using tumor regression grade (TRG) (Becker’s criteria) and volume change assessed by CT. Results Fifty-one (86%) patients completed all chemotherapy scheduled cycles successfully and surgery was curative (R0) in 64 (97%) subjects. The histopathological analysis showed 19 (29%) specimens with TRG1 (less than 10% of vital tumor left) and 25 (37%) patients had partial or complete response (CR) assessed by CT scan. Median disease free survival (DFS) and overall survival (OS) were 25.70 months (range, 14.52–36.80 months) and 36.60 months (range, 24.3–52.9 months), respectively. The median follow up was 27 months (range, 5.00–68.00 months). Radiological response and TRG were found to be a prognostic factor for OS and DFS, while tumor histology was not significantly related to survival. Conclusions Both radiological response and TRG have been shown as promising survival markers in patients treated with perioperative chemotherapy for locally advanced gastric cancer. Other predictive markers of response to chemotherapy are strongly required. PMID:29299362

Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study.

PubMed

Barra, Filipe Ramos; de Souza, Fernanda Freire; Camelo, Rosimara Eva Ferreira Almeida; Ribeiro, Andrea Campos de Oliveira; Farage, Luciano

2017-01-01

To assess the feasibility of contrast-enhanced spectral mammography (CESM) of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC). In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM). We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively). The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886). The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598). Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88). CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent.

Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis.

PubMed

Bajpai, Jyoti; Gamnagatti, Shivanand; Kumar, Rakesh; Sreenivas, Vishnubhatla; Sharma, Mehar Chand; Khan, Shah Alam; Rastogi, Shishir; Malhotra, Arun; Safaya, Rajni; Bakhshi, Sameer

2011-04-01

Histological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy. To establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease. Thirty-one treatment-naïve osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006-2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response ≥90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out. Both pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume. In osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma.

Phase II study of neoadjuvant treatment with doxorubicin, docetaxel, and capecitabine (ATX) in locally advanced or inflammatory breast cancer.

PubMed

Manga, Gumersindo Pérez; Shahi, Parham Khosravi; Ureña, Miguel Méndez; Pereira, Rosa Quiben; Plaza, María Isabel Palomero; Peron, Yann Izarzugaza; Val, Ricardo González Del; Carrión, Joaquín Belón; Cañón, Esperanza Pérez; Alfonso, Pilar García

2010-07-01

Pathologic complete response (pCR) after preoperative systemic chemotherapy (PSCh) is associated with better outcome in locally advanced breast cancer (LABC). PSCh included: doxorubicin (A) 50 mg/m(2) i.v. on day 1; docetaxel (T) 30 mg/m(2) i.v. on days 1, 8 and 15; and capecitabine (X) 1,500 mg/m(2)/day p.o. on days 1-14, in a 4-week course repeated for up to four cycles (ATX), followed by surgery. The primary end point of this study was to evaluate the pCR rate. Secondary endpoints included clinical response rate, disease-free survival (DFS), overall survival (OS), and the toxicity profile. A total of 60 patients were included in the analysis. Median age was 49 years, and 63.3% of patients were hormone receptor positive. The median number of cycles of PSCh was four (95% CI: 3-4). Five patients (8.3%) achieved pCR in both breast and nodes, and 16.7% reached pCR only in nodes. The clinical response rate was 77% (27% complete response), but only 18% of the patients underwent conservative surgery. With a median follow-up of 20 months, 3-year DFS and OS were 76 and 90%, respectively. Grade III/IV toxicity included neutropenia (74%), febrile neutropenia (9%), mucositis (12%), and diarrhea (12%). ATX every 28 days for four cycles is associated with a modest activity (low pCR rate) in the neoadjuvant setting of LABC.

Diffuse Optical Monitoring of the Neoadjuvant Breast Cancer Therapy

PubMed Central

Choe, Regine; Durduran, Turgut

2012-01-01

Recent advances in the use of diffuse optical techniques for monitoring the hemodynamic, metabolic and physiological signatures of the neoadjuvant breast cancer therapy effectiveness is critically reviewed. An extensive discussion of the state-of-theart diffuse optical mammography is presented alongside a discussion of the current approaches to breast cancer therapies. Overall, the diffuse optics field is growing rapidly with a great deal of promise to fill an important niche in the current approaches to monitor, predict and personalize neoadjuvant breast cancer therapies. PMID:23243386

Evaluation of Adherence to Quality Measures for Prostate Cancer Radiotherapy in the United States: Results from the Quality Research in Radiation Oncology (QRRO) Survey

PubMed Central

Zelefsky, Michael J.; Lee, W. Robert; Zietman, Anthony; Khalid, Najma; Crozier, Cheryl; Owen, Jean; Wilson, J. Frank

2012-01-01

Purpose To test the feasibility of using proposed quality indicators to assess radiotherapy quality in prostate cancer management based on a 2007 stratified random survey of treating academic and non-academic US institutions. Methods and Materials 414 patients with clinically localized prostate cancer treated with external beam radiotherapy (EBRT) or brachytherapy were selected from 45 institutions. Indicators used as specific measurable clinical performance measures to represent surrogates for quality of radiotherapy delivery included established measures, such as the use of prescription doses ≥75 Gy for intermediate- and high-risk EBRT patients and androgen-deprivation therapy (ADT) in conjunction with EBRT for patients with high-risk disease, and emerging measures, including daily target localization (image-guidance) to correct for organ motion for EBRT patients. Results 167 patients (47%) were treated with 6 MV photons, 31 (9%) were treated with 10 MV, 65 (18%) received 15 MV, and the remaining 90 (26%) 16–23 MV. For intermediate- plus high-risk patients (n=181), 78% were treated to ≥75 Gy. Among favorable-risk patients, 72% were treated to ≥75 Gy. Among high-risk EBRT patients, 60 (87%) were treated with ADT in conjunction with EBRT and 13% (n=9) with radiotherapy alone. Among low- and intermediate-risk patients, 10% and 42%, respectively, were treated with ADT plus EBRT. For 24% of EBRT patients (85/354), weekly electronic portal imaging was obtained as verification films without daily target localization and the remaining 76% were treated with daily localization of the target using various methods. Conclusions Adherence to defined quality indicators was observed in a majority of patients. ≈90% of high-risk patients are treated with ADT plus EBRT and ≈80% of intermediate- and high-risk patients receive prescription doses >=75 Gy, consistent with the published results of randomized trials. PMID:23471563

Evaluation of Adherence to Quality Measures for Prostate Cancer Radiotherapy in the United States: Results from the Quality Research in Radiation Oncology (QRRO) Survey.

PubMed

Zelefsky, Michael J; Lee, W Robert; Zietman, Anthony; Khalid, Najma; Crozier, Cheryl; Owen, Jean; Wilson, J Frank

2013-01-01

To test the feasibility of using proposed quality indicators to assess radiotherapy quality in prostate cancer management based on a 2007 stratified random survey of treating academic and non-academic US institutions. 414 patients with clinically localized prostate cancer treated with external beam radiotherapy (EBRT) or brachytherapy were selected from 45 institutions. Indicators used as specific measurable clinical performance measures to represent surrogates for quality of radiotherapy delivery included established measures, such as the use of prescription doses ≥75 Gy for intermediate- and high-risk EBRT patients and androgen-deprivation therapy (ADT) in conjunction with EBRT for patients with high-risk disease, and emerging measures, including daily target localization (image-guidance) to correct for organ motion for EBRT patients. 167 patients (47%) were treated with 6 MV photons, 31 (9%) were treated with 10 MV, 65 (18%) received 15 MV, and the remaining 90 (26%) 16-23 MV. For intermediate- plus high-risk patients (n=181), 78% were treated to ≥75 Gy. Among favorable-risk patients, 72% were treated to ≥75 Gy. Among high-risk EBRT patients, 60 (87%) were treated with ADT in conjunction with EBRT and 13% (n=9) with radiotherapy alone. Among low- and intermediate-risk patients, 10% and 42%, respectively, were treated with ADT plus EBRT. For 24% of EBRT patients (85/354), weekly electronic portal imaging was obtained as verification films without daily target localization and the remaining 76% were treated with daily localization of the target using various methods. Adherence to defined quality indicators was observed in a majority of patients. ≈90% of high-risk patients are treated with ADT plus EBRT and ≈80% of intermediate- and high-risk patients receive prescription doses >=75 Gy, consistent with the published results of randomized trials.

Effect of Whole Pelvic Radiotherapy for Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy and Long-Term Androgen Deprivation Therapy

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

Mantini, Giovanna; Tagliaferri, Luca, E-mail: luca.tagliaferri@rm.unicatt.it; Mattiucci, Gian Carlo

2011-12-01

Purpose: To evaluate the effect of whole pelvic radiotherapy (WPRT) in prostate cancer patients treated with RT and long-term (>1 year) androgen deprivation therapy (ADT). Methods and materials: Prostate cancer patients with high-risk features (Stage T3-T4 and/or Gleason score {>=}7 and/or prostate-specific antigen level {>=}20 ng/mL) who had undergone RT and long-term ADT were included in the present analysis. Patients with bowel inflammatory disease, colon diverticula, and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy (PORT). Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels (15%, 20%, 25%,more » and 30%). Biochemical disease-free survival (bDFS) was analyzed in each group according to the RT type (WPRT or PORT). Results: A total of 358 patients treated between 1994 and 2007 were included in the analysis (46.9% with WPRT and 53.1% with PORT). The median duration of ADT was 24 months (range, 12-38). With a median follow-up of 52 months (range, 20-150), the overall 4-year bDFS rate was 90.5%. The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT (90.4% vs. 90.5%; p = NS). However, in the group of patients with the greatest nodal risk (>30%), a significant bDFS improvement was recorded for the patients who had undergone WPRT (p = .03). No differences were seen in acute toxicity among the patients treated with WPRT or PORT. The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT (p = NS). Conclusions: Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement (>30%), although a definitive recommendation should be confirmed by a randomized trial.« less

Dramatically Polarized Opinion on the Role of Brachytherapy Boost in Management of High-risk Prostate Cancer: A Survey of North American Genitourinary Expert Radiation Oncologists.

PubMed

McClelland, Shearwood; Sandler, Kiri A; Degnin, Catherine; Chen, Yiyi; Mitin, Timur

2018-06-01

Three randomized clinical trials have established brachytherapy (BT) boost in combination with external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT) as superior to definitive EBRT and ADT alone in terms of biochemical control (but not overall survival) at the expense of increased toxicity in men with high-risk (HR) prostate cancer (PCa). The current view regarding these 2 treatment algorithms among North American genitourinary (GU) experts is not known. A survey was distributed to 88 practicing North American GU physicians serving on decision-making committees of cooperative group research organizations. Questions pertained to opinions regarding BT as monotherapy for low-risk PCa and BT boost for HR PCa. Responders were asked to self-identify as BT experts versus non-experts. Treatment recommendations were correlated with practice patterns using the Fisher exact test. Forty-two radiation oncologists completed the survey, of whom 23 (55%) recommend EBRT and ADT alone and 19 (45%) recommend addition of BT boost. Twenty-five participants (60%) identified themselves as BT experts. Nearly 90% of those recommending BT boost were BT experts versus approximately 10% of non-BT experts (P < .001). Responders who recommended BT monotherapy as first-choice treatment for low-risk PCa were more likely to recommend BT boost for HR PCa (P < .0001). There is a dramatic polarization in opinions regarding incorporation of BT boost into EBRT + ADT therapy for patients with HR PCa among North American GU radiation oncology experts, who serve on decision-making committees and influence the national treatment guidelines and future clinical trials. Those who identify themselves as BT experts are significantly more likely to recommend BT boost. These findings are likely to influence the national guidelines and implementation of BT boost in current and future North American PCa clinical studies. Copyright © 2018 Elsevier Inc. All rights reserved.

High-Dose Conformal Radiotherapy Reduces Prostate Cancer-Specific Mortality: Results of a Meta-analysis

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

Viani, Gustavo Arruda, E-mail: gusviani@gmail.com; Godoi Bernardes da Silva, Lucas; Stefano, Eduardo Jose

2012-08-01

Purpose: To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). Methods and Materials: The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. Results: Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trialsmore » showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. Conclusions: This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.« less

Effects of strength training on body composition, physical functioning, and quality of life in prostate cancer patients during androgen deprivation therapy.

PubMed

Nilsen, Tormod S; Raastad, Truls; Skovlund, Eva; Courneya, Kerry S; Langberg, Carl W; Lilleby, Wolfgang; Fosså, Sophie D; Thorsen, Lene

2015-11-01

Androgen deprivation therapy (ADT) increases survival rates in prostate cancer (PCa) patients with locally advanced disease, but is associated with side effects that may impair daily function. Strength training may counteract several side effects of ADT, such as changes in body composition and physical functioning, which in turn may affect health-related quality of life (HRQOL). However, additional randomised controlled trials are needed to expand this knowledge. Fifty-eight PCa patients on ADT were randomised to either 16 weeks of high-load strength training (n = 28) or usual care (n = 30). The primary outcome was change in total lean body mass (LBM) assessed by dual x-ray absorptiometry (DXA). Secondary outcomes were changes in regional LBM, fat mass, and areal bone mineral density (aBMD) measured by DXA; physical functioning assessed by 1-repetition maximum (1RM) tests, sit-to-stand test, stair climbing test and Shuttle walk test; and HRQOL as measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30. No statistically significant effect of high-load strength training was demonstrated on total LBM (p = 0.16), but significant effects were found on LBM in the lower and upper extremities (0.49 kg, p < 0.01 and 0.15 kg, p < 0.05, respectively). Compared to usual care, high-load strength training showed no effect on fat mass, aBMD or HRQOL, but beneficial effects were observed in all 1RM tests, sit-to-stand test and stair climbing tests. Adherence to the training program was 88% for lower body exercises and 84% for upper body exercises. In summary, high-load strength training improved LBM in extremities and physical functioning, but had no effect on fat mass, aBMD, or HRQOL in PCa patients on ADT.

No increased risk of coronary heart disease for patients receiving androgen deprivation therapy for prostate cancer in Chinese/Taiwanese men.

PubMed

Wang, L H; Liu, C K; Chen, C H; Kao, L T; Lin, H C; Huang, C Y

2016-01-01

The relationship between androgen deprivation therapy (ADT) and coronary heart disease (CHD) remains controversial. Furthermore, the majority of such studies focused on Caucasian populations, and there is still a paucity of studies among Asian populations. This population-based study aimed to investigate the relationship between ADT and CHD in an ethnic Chinese (i.e., Taiwanese) population. We used data sourced from the Taiwan 'Longitudinal Health Insurance Database'. This study included 1278 patients with prostate cancer in the study group and 1278 subjects without prostate cancer in the comparison group. Each patient was individually tracked for a 3-year period to identify those who had subsequently received a diagnosis of CHD. The results showed that the incidence rate of CHD during the 3-year follow-up period was 4.69 (95% CI: 2.99-5.48) per 100 person-years and 2.67 (95% CI: 2.15-3.27) per 100 person-years for the study and comparison cohort, respectively. The Cox proportional hazard regression showed that the hazard ratio for CHD during the 3-year follow-up period for prostate cancer patients was 1.65 (95% confidence interval (CI) = 1.25-2.16) compared with comparison subjects after adjusting for patients' geographic location, monthly income, urbanization level, hypertension, diabetes, hyperlipidemia, and stroke. However, we failed to find a significant difference in the adjusted hazard of CHD during the 3-year follow-up period between prostate cancer patients who did and those who did not receive ADT (hazard ratio = 1.12, 95% CI = 0.79-1.59). We concluded that prostate cancer but not ADT was significantly associated with CHD. In addition, a common cause of prostate cancer and coronary heart disease could exist. © 2015 American Society of Andrology and European Academy of Andrology.

Effect of Prostate Magnetic Resonance Imaging/Ultrasound Fusion-guided Biopsy on Radiation Treatment Recommendations

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

Reed, Aaron; Valle, Luca F.; Shankavaram, Uma

Purpose: Targeted magnetic resonance imaging (MRI)/ultrasound fusion prostate biopsy (MRI-Bx) has recently been compared with the standard of care extended sextant ultrasound-guided prostate biopsy (SOC-Bx), with the former associated with an increased rate of detection of clinically significant prostate cancer. The present study sought to determine the influence of MRI-Bx on radiation therapy and androgen deprivation therapy (ADT) recommendations. Methods and Materials: All patients who had received radiation treatment and had undergone SOC-Bx and MRI-Bx at our institution were included. Using the clinical T stage, pretreatment prostate-specific antigen, and Gleason score, patients were categorized into National Comprehensive Cancer Network riskmore » groups and radiation treatment or ADT recommendations assigned. Intensification of the recommended treatment after multiparametric MRI, SOC-Bx, and MRI-Bx was evaluated. Results: From January 2008 to January 2016, 73 patients received radiation therapy at our institution after undergoing a simultaneous SOC-Bx and MRI-Bx (n=47 with previous SOC-Bx). Repeat SOC-Bx and MRI-Bx resulted in frequent upgrading compared with previous SOC-Bx (Gleason score 7, 6.7% vs 44.6%; P<.001; Gleason score 8-10, 2.1% vs 38%; P<.001). MRI-Bx increased the proportion of patients classified as very high risk from 24.7% to 41.1% (P=.027). Compared with SOC-Bx alone, including the MRI-Bx findings resulted in a greater percentage of pathologically positive cores (mean 37% vs 44%). Incorporation of multiparametric MRI and MRI-Bx results increased the recommended use and duration of ADT (duration increased in 28 of 73 patients and ADT was added for 8 of 73 patients). Conclusions: In patients referred for radiation treatment, MRI-Bx resulted in an increase in the percentage of positive cores, Gleason score, and risk grouping. The benefit of treatment intensification in accordance with the MRI-Bx findings is unknown.« less

Multidisciplinary management of hepatoblastoma in children: Experience from a developing country.

PubMed

Shanmugam, Naresh; Scott, Julius Xavier; Kumar, Vimal; Vij, Mukul; Ramachandran, Priya; Narasimhan, Gomathy; Reddy, Mettu Srinivas; Kota, Venugopal; Munirathnam, Deenadayalan; Kelgeri, Chayarani; Sundaram, Karthick; Rela, Mohamed

2017-03-01

Advances in chemotherapy, liver resection techniques, and pediatric liver transplantation have vastly improved survival in children with hepatoblastoma (HB). These are best managed by a multidisciplinary team (MDT) in a setting where all treatment options are available. Until recently, this was difficult to achieve in India. All children (<16 years) with HB treated in a pediatric liver surgery and transplantation unit between January 2011 and July 2016 were reviewed. Data regarding the clinical presentation, preoperative management, surgical treatment, postoperative course, and outcomes were extracted from a prospectively managed database. Thirty children were treated for HB during the study period. Nine children were PRETEXT 4, 7 were PRETEXT 3, 13 were PRETEXT 2, and 1 was PRETEXT 1 (where PRETEXT is pretreatment extension). All children received a neoadjuvant chemotherapy before surgery followed by an adjuvant chemotherapy. Nineteen children had complete resection, while six underwent primary living donor liver transplantation. There were six mortalities including five children who poorly responded to chemotherapy with progressive tumor extension. At a median follow-up of 30 months, two children who underwent resection and one child who underwent liver transplant had disease recurrence. Improved outcomes can be achieved in children with HB even in countries with limited resources when they are managed by MDTs with expertise in pediatric oncology, liver resection, and liver transplantation. © 2016 Wiley Periodicals, Inc.

Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial.

PubMed

Gupta, Sudeep; Maheshwari, Amita; Parab, Pallavi; Mahantshetty, Umesh; Hawaldar, Rohini; Sastri Chopra, Supriya; Kerkar, Rajendra; Engineer, Reena; Tongaonkar, Hemant; Ghosh, Jaya; Gulia, Seema; Kumar, Neha; Shylasree, T Surappa; Gawade, Renuka; Kembhavi, Yogesh; Gaikar, Madhuri; Menon, Santosh; Thakur, Meenakshi; Shrivastava, Shyam; Badwe, Rajendra

2018-06-01

Purpose We compared the efficacy and toxicity of neoadjuvant chemotherapy followed by radical surgery versus standard cisplatin-based chemoradiation in patients with locally advanced squamous cervical cancer. Patients and Methods This was a single-center, phase III, randomized controlled trial ( ClinicalTrials.gov identifier: NCT00193739). Eligible patients were between 18 and 65 years old and had stage IB2, IIA, or IIB squamous cervical cancer. They were randomly assigned, after stratification by stage, to receive either three cycles of neoadjuvant chemotherapy using paclitaxel and carboplatin once every 3 weeks followed by radical hysterectomy or standard radiotherapy with concomitant cisplatin once every week for 5 weeks. Patients in the neoadjuvant group received postoperative adjuvant radiation or concomitant chemotherapy and radiotherapy, if indicated. The primary end point was disease-free survival (DFS), defined as survival without relapse or death related to cancer, and secondary end points included overall survival and toxicity. Results Between September 2003 and February 2015, 635 patients were randomly assigned, of whom 633 (316 patients in the neoadjuvant chemotherapy plus surgery group and 317 patients in the concomitant chemoradiation group) were included in the final analysis, with a median follow-up time of 58.5 months. The 5-year DFS in the neoadjuvant chemotherapy plus surgery group was 69.3% compared with 76.7% in the concomitant chemoradiation group (hazard ratio, 1.38; 95% CI, 1.02 to 1.87; P = .038), whereas the corresponding 5-year OS rates were 75.4% and 74.7%, respectively (hazard ratio, 1.025; 95% CI, 0.752 to 1.398; P = .87). The delayed toxicities at 24 months or later after treatment completion in the neoadjuvant chemotherapy plus surgery group versus the concomitant chemoradiation group were rectal (2.2% v 3.5%, respectively), bladder (1.6% v 3.5%, respectively), and vaginal (12.0% v 25.6%, respectively). Conclusion Cisplatin-based concomitant chemoradiation resulted in superior DFS compared with neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer.

Ligand versus metal protonation of an iron hydrogenase active site mimic.

PubMed

Eilers, Gerriet; Schwartz, Lennart; Stein, Matthias; Zampella, Giuseppe; de Gioia, Luca; Ott, Sascha; Lomoth, Reiner

2007-01-01

The protonation behavior of the iron hydrogenase active-site mimic [Fe2(mu-adt)(CO)4(PMe3)2] (1; adt=N-benzyl-azadithiolate) has been investigated by spectroscopic, electrochemical, and computational methods. The combination of an adt bridge and electron-donating phosphine ligands allows protonation of either the adt nitrogen to give [Fe2(mu-Hadt)(CO)4(PMe3)2]+ ([1 H]+), the Fe-Fe bond to give [Fe2(mu-adt)(mu-H)(CO)4(PMe3)2]+ ([1 Hy]+), or both sites simultaneously to give [Fe2(mu-Hadt)(mu-H)(CO)4(PMe3)2]2+ ([1 HHy]2 +). Complex 1 and its protonation products have been characterized in acetonitrile solution by IR, (1)H, and (31)P NMR spectroscopy. The solution structures of all protonation states feature a basal/basal orientation of the phosphine ligands, which contrasts with the basal/apical structure of 1 in the solid state. Density functional calculations have been performed on all protonation states and a comparison between calculated and experimental spectra confirms the structural assignments. The ligand protonated complex [1 H]+ (pKa=12) is the initial, metastable protonation product while the hydride [1 Hy]+ (pKa=15) is the thermodynamically stable singly protonated form. Tautomerization of cation [1 H]+ to [1 Hy]+ does not occur spontaneously. However, it can be catalyzed by HCl (k=2.2 m(-1) s(-1)), which results in the selective formation of cation [1 Hy]+. The protonations of the two basic sites have strong mutual effects on their basicities such that the hydride (pK(a)=8) and the ammonium proton (pK(a)=5) of the doubly protonated cationic complex [1 HHy]2+ are considerably more acidic than in the singly protonated analogues. The formation of dication [1 HHy]2+ from cation [1 H]+ is exceptionally slow with perchloric or trifluoromethanesulfonic acid (k=0.15 m(-1) s(-1)), while the dication is formed substantially faster (k>10(2) m(-1) s(-1)) with hydrobromic acid. Electrochemically, 1 undergoes irreversible reduction at -2.2 V versus ferrocene, and this potential shifts to -1.6, -1.1, and -1.0 V for the cationic complexes [1 H]+, [1 Hy]+, and [1 HHy]2+, respectively, upon protonation. The doubly protonated form [1 HHy]2+ is reduced at less negative potential than all previously reported hydrogenase models, although catalytic proton reduction at this potential is characterized by slow turnover.

Refining Preoperative Therapy for Locally Advanced Rectal Cancer

Cancer.gov

In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

Practice Patterns and Outcomes for Pemetrexed Plus Platinum Doublet as Neoadjuvant Chemotherapy in Adenocarcinomas of Lung: Looking Beyond the Usual Paradigm.

PubMed

Noronha, V; Zanwar, S; Joshi, A; Patil, V M; Mahajan, A; Janu, A; Agarwal, J P; Bhargava, P; Kapoor, A; Prabhash, K

2018-01-01

Neoadjuvant chemotherapy (NACT) is the standard of care in non-small cell lung cancers (NSCLC) with locally advanced N2 disease. There is a scarcity of data for the pemetrexed-platinum regimen as NACT. Also, apart from N2 disease, the role of NACT in locally advanced NSCLCs for tumour downstaging is unclear. Non-metastatic adenocarcinomas of lung treated with pemetrexed-platinum-based NACT were analysed. The patients with locoregionally advanced N2 disease and those who were borderline candidates for upfront definitive treatment were planned for NACT after discussion in a multidisciplinary clinic. In total, four cycles of 3-weekly pemetrexed and platinum were delivered in the combined neoadjuvant and adjuvant setting. A response assessment was carried out using RECIST criteria. Progression-free (PFS) and overall survival were calculated using the Kaplan-Meier method. Of 114 patients, 96 evaluable patients received NACT with pemetrexed-platinum. The most common indication for NACT was N2 disease at baseline (46.8%). The objective response rate was 36.4% (95% confidence interval 22-52%), including two complete and 32 partial responses, whereas 12.5% of patients had progressive disease on NACT. The median PFS was 14 months (95% confidence interval 10.7-17.3) and the median overall survival was 22 months (95% confidence interval 15.6-28.4) at a median follow-up of 16 months. There was a significant improvement in the overall survival of patients undergoing definitive therapy versus no definitive therapy (median overall survival 25 months [95% confidence interval 19.6-30.4] versus 12 months [95% confidence interval 3.2-20.7], respectively; P = 0.015, hazard ratio 0.56 [95% confidence interval 0.3-0.9]). Among patients who could not undergo definitive chemoradiation upfront due to dosimetric constraints (n = 34), 24 (70.6%) patients finally underwent definitive therapy after NACT. Pemetrexed-platinum-based NACT seems to be an effective option and many borderline cases, where upfront definitive therapy is not feasible, may become amenable to the same after incorporation of NACT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Results of Neoadjuvant Short-Course Radiation Therapy Followed by Transanal Endoscopic Microsurgery for T1-T2 N0 Extraperitoneal Rectal Cancer

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

Arezzo, Alberto, E-mail: alberto.arezzo@unito.it; Arolfo, Simone; Allaix, Marco Ettore

Purpose: This study was undertaken to assess the short-term outcomes of neoadjuvant short-course radiation therapy (SCRT) followed by transanal endoscopic microsurgery (TEM) for T1-T2 N0 extraperitoneal rectal cancer. Recent studies suggest that neoadjuvant radiation therapy followed by TEM is safe and has results similar to those with abdominal rectal resection for the treatment of extraperitoneal early rectal cancer. Methods and Materials: We planned a prospective pilot study including 25 consecutive patients with extraperitoneal T1-T2 N0 M0 rectal adenocarcinoma undergoing SCRT followed by TEM 4 to 10 weeks later (SCRT-TEM). Safety, efficacy, and acceptability of this treatment modality were compared with historicalmore » groups of patients with similar rectal cancer stage and treated with long-course radiation therapy (LCRT) followed by TEM (LCRT-TEM), TEM alone, or laparoscopic rectal resection with total mesorectal excision (TME) at our institution. Results: The study was interrupted after 14 patients underwent SCRT of 25 Gy in 5 fractions followed by TEM. Median time between SCRT and TEM was 7 weeks (range: 4-10 weeks). Although no preoperative complications occurred, rectal suture dehiscence was observed in 7 patients (50%) at 4 weeks follow-up, associated with an enterocutaneous fistula in the sacral area in 2 cases. One patient required a colostomy. Quality of life at 1-month follow-up, according to European Organization for Research and Treatment of Cancer QLQ-C30 survey score, was significantly worse in SCRT-TEM patients than in LCRT-TEM patients (P=.0277) or TEM patients (P=.0004), whereas no differences were observed with TME patients (P=.604). At a median follow-up of 10 months (range: 6-26 months), we observed 1 (7%) local recurrence at 6 months that was treated with abdominoperineal resection. Conclusions: SCRT followed by TEM for T1-T2 N0 rectal cancer is burdened by a high rate of painful dehiscence of the suture line and enterocutaneous fistula, compared to TEM alone and TEM following LCRT, which forced us to stop the study.« less

Can Angiotensin-Converting Enzyme Inhibitors Reduce the Incidence, Severity, and Duration of Radiation Proctitis?

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

Alashkham, Abduelmenem, E-mail: alashkham@yahoo.com; Paterson, Catherine; Rauchhaus, Petra

2016-01-01

Purpose: To determine whether participants taking angiotensin-converting enzyme inhibitors (ACEIs) and treated with radical radiation therapy with neoadjuvant/adjuvant hormone therapy have less incidence, severity, and duration of radiation proctitis. Methods and Materials: A propensity score analysis of 817 patients who underwent radical radiation therapy with neoadjuvant or adjuvant hormone therapy as primary line management in a cohort study during 2009 to 2013 was conducted. Patients were stratified as follows: group 1, hypertensive patients taking ACEIs (as a study group); group 2, nonhypertensive patients not taking ACEIs; and group 3, hypertensive patients not taking ACEIs (both as control groups). The incidence,more » severity, and duration of proctitis were the main outcome. χ{sup 2} tests, Mann-Whitney U tests, analysis of variance, risk ratio (RR), confidence interval (CI), Kaplan-Meier plots, and log-rank tests were used. Results: The mean age of the participants was 68.91 years, with a follow-up time of 3.38 years. Based on disease and age-matched comparison, there was a statistically significant difference of proctitis grading between the 3 groups: χ{sup 2} (8, n=308) = 72.52, P<.001. The Mann-Whitney U test indicated that grades of proctitis were significantly lower in hypertensive patients taking ACEIs than in nonhypertensive patients not taking ACEIs and hypertensive patients not taking ACEIs (P<.001). The risk ratio (RR) of proctitis in hypertensive patients taking ACEIs was significantly lower than in hypertensive patients not taking ACEIs (RR 0.40, 95% CI 0.30-0.53, P<.001) and in nonhypertensive patients not taking ACEIs (RR 0.58, 95% CI 0.44-0.77, P<.001). Time to event analysis revealed that hypertensive patients taking ACEIs were significantly different from the control groups (P<.0001). Furthermore, hypertensive patients taking ACEIs had significantly faster resolution of proctitis (P<.0001). Conclusion: Patients who were taking ACEIs were significantly less likely to have high-grade proctitis after radical radiation therapy with neoadjuvant or adjuvant hormone therapy (P<.001). The intake of ACEIs was significantly associated with a reduced risk of radiation-induced proctitis and also with acceleration of its resolution.« less

Neo-adjuvant chemotherapy with cisplatin induces low expression of NMDA receptors and postoperative cognitive impairment.

PubMed

Cheng, Jing; Liu, Xiaoqing; Cao, Longhui; Zhang, Tianhua; Li, Huiting; Lin, Wenqian

2017-01-10

Whether Neo-adjuvant chemotherapy can affect patients' postoperative brain function is not clear. In this study, we investigated the effect of preoperative cisplatin treatment on postoperative cognitive function and its possible mechanism in rats. Moreover, we also tested whether the NMDAR inhibitor memantine could attenuate cisplatin-induced alterations. 12-month-oldSprague-Dawley rats randomly received an intraperitoneal injection of either cisplatin once a week at a dose of 3mg/kg for three consecutive weeks or an equivalent volume of normal saline. After the injections, the normal saline injection group was divided into 3 groups (n=5 each): a normal saline group (group S), normal saline+pentobarbital group (group SP), and normal saline+pentobarbital+operation group (group SPO).The cisplatin injection group was divided into 3 groups: a cisplatin group (group C), cisplatin+pentobarbital group (group CP), and cisplatin+pentobarbital+operation group (group CPO).Rats in the group SP, SPO,CP and CPO were anaesthetized with sodium pentobarbital and then the SPO and CPO groups underwent a simple laparotomy operation. The effects of memantine were tested through two additional groups of rats (cisplatin+memantine group (group CM) and cisplatin+pentobarbital+operation+memantine group (group CPOM)). A Morris water maze test was performed to evaluate the spatial learning and memory ability five days after anesthesia or operation. After the test, the hippocampi were removed for detection of the expression of NMDAR by western bloting. The relevant protein expression levels of PSD95 and ERK1/2 were detected by western blot analysis. Rats treated with cisplatin had a longer mean escape latency and spent a shorter amount of time in the target quadrant than did the normal saline injection rats. Furthermore, the protein expression levels of NMDA receptors, PSD95 and ERK1/2 were decreased in cisplatin group and memantine could up-regulate their expression. These results suggest that neo-adjuvant chemotherapy with cisplatin exacerbate the postoperative cognitive dysfunction in rats, and this may be caused by a lower expression of NMDA receptors in the hippocampus. Memantine could attenuate these alterations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report

NASA Astrophysics Data System (ADS)

Shia, Wei-Chung; Chen, Dar-Ren; Huang, Yu-Len; Wu, Hwa-Koon; Kuo, Shou-Jen

2015-10-01

The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer. Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes. The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%. Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making.

Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection.

PubMed

van Rijk, Maartje C; Nieweg, Omgo E; Rutgers, Emiel J T; Oldenburg, Hester S A; Olmos, Renato Valdés; Hoefnagel, Cornelis A; Kroon, Bin B R

2006-04-01

Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.

Neoadjuvant chemotherapy modifies serum angiotensinase activities in women with breast cancer.

PubMed

Ramírez-Expósito, María Jesús; Carrera-González, María del Pilar; Mayas, María Dolores; Dueñas, Basilio; Martínez-Ferrol, Julia; Martínez-Martos, José Manuel

2012-05-01

The aim of this study was to investigate the putative changes in serum angiotensinase activities (aminopeptidase N, APN; aminopeptidase B, APB; aminopeptidase A, APA; aspartyl aminopeptidase, ASAP) involved in the renin-angiotensin system (RAS) in women with breast cancer treated or not with a neoadjuvant therapy of paclitaxel and anthracycline and in healthy women volunteers. We fluorometrically analysed serum APN, APB, APA and ASAP activities using their corresponding aminoacyl-β-naphthylamides as substrates in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline. When compared with healthy controls, women with breast cancer not treated with neoadjuvant chemotherapy, showed a decrease in angiotensinase activity, which support the putative increase of angiotensin II (Ang II) levels, indicating that the tumour process would favour the development of the disease. Also, an increase in APN and APB activities was observed, which support a role for angiotensin IV (Ang IV). In women treated with a neoadjuvant therapy, we described an increase in ASAP and APA activities, supporting the idea that this treatment increases Ang II catabolism. The resulting decrease in Ang II level could lead to an inhibition of the tumour growth. Present results show changes in serum angiotensinase activities in women with breast cancer and in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline. Therefore, considerable attention should be focused on the development of RAS blockade therapy as a new strategy for breast cancer treatment. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Neoadjuvant chemotherapy in soft tissue sarcomas: latest evidence and clinical implications

PubMed Central

Pasquali, Sandro; Gronchi, Alessandro

2017-01-01

Soft tissue sarcomas are a rare and multifaceted group of solid tumours. Neoadjuvant chemotherapy is increasingly used to limit loss of function after wide surgical excision with the ultimate aim of improving patient survival. Recently, advances in the identification of effective treatment strategies and improvements in patient risk stratification have been reached. A randomized trial demonstrated that neoadjuvant epirubicin and ifosfamide improves survival of patients affected by five high-risk soft tissue sarcoma histologies of trunk and extremities, including undifferentiated pleomorphic sarcoma, myxoid liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumours, and leiomyosarcoma. Selection of patients for these treatments is expected to be improved by the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system, as it tailors T-stage categories on primary tumour site and considers a prognostic nomogram for retroperitoneal sarcoma, which also includes soft tissue sarcoma histology and other patient and tumour features not directly included in the TNM staging. Within this framework, this article will present neoadjuvant treatment strategies for high-risk soft tissue sarcoma, emphasizing the most recent advances and discussing the need for further research to improve the effectiveness of neoadjuvant treatments. PMID:28607580

Neoadjuvant therapy in pancreatic cancer: an emerging strategy.

PubMed

Bittoni, Alessandro; Santoni, Matteo; Lanese, Andrea; Pellei, Chiara; Andrikou, Kalliopi; Stefano, Cascinu

2014-01-01

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths among men and women, being responsible for 6% of all cancer-related deaths. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. In recent years, increasing evidences support the use of neoadjuvant strategies in pancreatic cancer in patients with resectable pancreatic cancer as well as in patients with borderline resectable or locally advanced PDAC in order to allow early treatment of micrometastatic disease, tumour regression, and reduced risk of peritoneal tumour implantation during surgery. Furthermore, neoadjuvant treatment allows evaluation of tumour response and increases patient's compliance. However, most evidences in this setting come from retrospective analysis or small case series and in many studies chemotherapy or chemoradiation therapies used were suboptimal. Currently, prospective randomized trials using the most active chemotherapy regimens available are trying to define the real benefit of neoadjuvant strategies compared to conventional adjuvant strategies. In this review, the authors examined available data on neoadjuvant treatment in patients with resectable pancreatic cancer as well as in patients with borderline resectable or locally advanced PDAC and the future directions in this peculiar setting.

The Comparison of the Advantages of Neoadjuvant Chemoradiotherapy versus Postoperative Chemoradiotherapy: Outcomes in Esophageal Cancer Patients.

PubMed

Sadrizadeh, Ali; Bagheri, Reza; Soltani, Ehsan; Anvari, Kazem; Toussi, Mehdi Seilanian; Moadikhah, Soheila

2018-03-01

Esophageal cancer is the eighth most common type of cancer worldwide. For the treatment of which, surgical intervention alone or with neoadjuvant chemoradiotherapy or chemotherapy is recommended. In this study, we aimed to compare the benefits of neoadjuvant chemoradiotherapy versus postoperative chemoradiotherapy. We collected data regarding 325 patients admitted for esophageal cancer to Qaem Hospital, Mashhad, Iran, during 2006-2016. The participants were divided into two groups of neoadjuvant and postoperative adjuvant therapies. Chi-square, McNemar, Kaplan-Mayer, and multivariate regression tests were performed using SPSS. Gender, age, stage of the disease, tumor grade and location, disease histopathology, and the recurrence showed no significant differences between the two groups (P ˃ 0.05), but there was a significant association between the two types of treatment in terms of postoperative complications (P = 0.03). We followed up 147 patients postoperatively and found no significant differences between the groups (P ˃ 0.05). No conclusion can be drawn on whether there are any advantages in adjuvant chemoradiotherapy over neoadjuvant approaches. Further confirmatory trials, particularly randomized trials, are necessary before any recommendations can be made.

Induction gemcitabine and oxaliplatin therapy followed by a twice-weekly infusion of gemcitabine and concurrent external-beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer: a single institutional experience.

PubMed

Leone, Francesco; Gatti, Marco; Massucco, Paolo; Colombi, Federica; Sperti, Elisa; Campanella, Delia; Regge, Daniele; Gabriele, Pietro; Capussotti, Lorenzo; Aglietta, Massimo

2013-01-15

Chemoradiotherapy (CRT) may render curative resection feasible in patients with locally advanced pancreatic carcinoma (LAPC). The authors previously demonstrated the achievement of significant disease control and a median survival of 14 months by CRT in patients with LAPC. In this study, they evaluated the use of induction chemotherapy followed by a CRT neoadjuvant protocol. Patients first received induction gemcitabine and oxaliplatin (GEMOX) (gemcitabine 1000 mg/m(2), oxaliplatin 100 mg/m(2)). Patients without disease progression then received gemcitabine twice weekly (50 mg/m(2) daily) concurrent with radiotherapy (50.4 grays) and were re-evaluated for resectability. Thirty-nine patients (15 with borderline resectable disease and 24 with unresectable disease) entered the study. The treatment was well tolerated. Disease control was obtained in 29 of 39 patients. Two patients progressed after GEMOX, and 7 progressed after CRT. After a median follow-up of 13 months, the median progression-free survival (PFS) was 10.2 months. The median PFS of patients with borderline resectable and unresectable disease was 16.6 and 9.1 months, respectively (P = .056). For the whole group, the median overall survival (OS) was 16.7 months (27.8 months for patients with borderline resectable disease, 13.3 for patients with unresectable disease; P = .045). Eleven patients (9 with borderline resectable disease and 2 with unresectable disease at diagnosis) underwent successful resection. Patients who underwent resection had a significantly longer median PFS compared with nonresected patients (19.7 months vs 7.6 months, respectively). The median OS among resected and nonresected patients was 31.5 months and 12.3 months, respectively (P < .001). The current results indicated that induction GEMOX followed by CRT is feasible in patients with LAPC. Both those with borderline resectable disease and those with unresectable disease received clinical benefit, a chance to obtain resectability, and improved survival. The authors concluded that this protocol warrants further evaluation. Copyright © 2012 American Cancer Society.

Is neoadjuvant chemoradiation with dose-escalation and consolidation chemotherapy sufficient to increase surgery-free and distant metastases-free survival in baseline cT3 rectal cancer?

PubMed

São Julião, Guilherme Pagin; Habr-Gama, Angelita; Vailati, Bruna Borba; Aguilar, Patricia Bailão; Sabbaga, Jorge; Araújo, Sérgio Eduardo Alonso; Mattacheo, Adrian; Alexandre, Flavia Andrea; Fernandez, Laura Melina; Gomes, Diogo Bugano; Gama-Rodrigues, Joaquim; Perez, Rodrigo Oliva

2018-01-01

Patients with cT3 rectal cancer are less likely to develop complete response to neoadjuvant chemoradiation (nCRT) and still face significant risk for systemic relapse. In this setting, radiation (RT) dose-escalation and consolidation chemotherapy in "extended" nCRT regimens have been suggested to improve primary tumor response and decrease the risks of systemic recurrences. For these reasons we compared surgery-free and distant-metastases free survival among cT3 patients undergoing standard or extended nCRT. Patients with distal and non-metastatic T3 rectal cancer managed by nCRT were retrospectively reviewed. Patients undergoing standard CRT (50.4 Gy and 2 cycles of 5FU-based chemotherapy) were compared to those undergoing extended CRT (54 Gy and 6 cycles of 5FU-based chemotherapy). Patients were assessed for tumor response at 8-10 weeks. Patients with complete clinical response (cCR) underwent organ-preservation strategy (Watch & Wait). Patients were referred to salvage surgery in the event of local recurrence during follow-up. Cox's logistic regression was performed to identify independent features associated with improved surgery-free survival after cCR and distant-metastases-free survival. 155 patients underwent standard and 66 patients extended CRT. Patients undergoing extended CRT were more likely to harbor larger initial tumor size (p = 0.04), baseline nodal metastases (cN+; p < 0.001) and higher tumor location (p = 0.02). Cox-regression analysis revealed that the type of nCRT regimen was not independently associated with distinct surgery-free survival after cCR or distant-metastases-free survival (p > 0.05). Dose-escalation and consolidation chemotherapy are insufficient to increase long-term surgery-free survival among cT3 rectal cancer patients and provides no advantage in distant metastases-free survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Neoadjuvant Systemic Therapy Use for Younger Patients with Breast Cancer Treated in Different Types of Cancer Centers Across the United States.

PubMed

Mohiuddin, Jahan J; Deal, Allison M; Carey, Lisa A; Lund, Jennifer L; Baker, Brock R; Zagar, Timothy M; Jones, Ellen L; Marks, Lawrence B; Chen, Ronald C

2016-11-01

Multiple clinical trials have shown that neoadjuvant systemic therapy has a benefit in women who are borderline lumpectomy candidates and in those with locally advanced breast cancers by reducing the mastectomy rate and making inoperable tumors operable. The study aim was to examine the patterns of neoadjuvant chemotherapy and endocrine therapy use among younger women in the United States treated at different types of cancer centers. Data from the National Cancer Data Base for 118,086 women younger than 65 years with clinical stage IIA (T2N0 only) to IIIC breast cancer. Following the National Comprehensive Cancer Network guideline categorization, patients were grouped into those who were borderline lumpectomy candidates (clinical stage IIA [T2N0 only], IIB, or IIIA [T3N1 only]) or those with locally advanced disease (clinical stage IIIA [T0-3N2 only], IIIB, or IIIC). The main outcome was the proportion of women who received neoadjuvant systemic therapy. Use of neoadjuvant chemotherapy ranged from 17% (stage IIA) to 79% (stage IIIB). Across almost all stage and receptor subtypes, the use was lower in community vs academic centers. On multivariable analysis, use of neoadjuvant chemotherapy was decreased in community vs academic centers (borderline lumpectomy candidates: adjusted risk ratio = 0.73; 95% CI, 0.69-0.77; locally advanced disease: adjusted risk ratio = 0.78; 95% CI, 0.74-0.83). Use of guideline-concordant neoadjuvant chemotherapy is significantly higher among women treated at academic vs community centers in young and healthy women who do not commonly have contraindications to this treatment. Our study identified a potential disparity in cancer care by type of center where patients receive treatment. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group.

PubMed

Provenzano, Elena; Bossuyt, Veerle; Viale, Giuseppe; Cameron, David; Badve, Sunil; Denkert, Carsten; MacGrogan, Gaëtan; Penault-Llorca, Frédérique; Boughey, Judy; Curigliano, Giuseppe; Dixon, J Michael; Esserman, Laura; Fastner, Gerd; Kuehn, Thorsten; Peintinger, Florentia; von Minckwitz, Gunter; White, Julia; Yang, Wei; Symmans, W Fraser

2015-09-01

Neoadjuvant systemic therapy is being used increasingly in the treatment of early-stage breast cancer. Response, in the form of pathological complete response, is a validated and evaluable surrogate end point of survival after neoadjuvant therapy. Thus, pathological complete response has become a primary end point for clinical trials. However, there is a current lack of uniformity in the definition of pathological complete response. A review of standard operating procedures used by 28 major neoadjuvant breast cancer trials and/or 25 sites involved in such trials identified marked variability in specimen handling and histologic reporting. An international working group was convened to develop practical recommendations for the pathologic assessment of residual disease in neoadjuvant clinical trials of breast cancer and information expected from pathology reports. Systematic sampling of areas identified by informed mapping of the specimen and close correlation with radiological findings is preferable to overly exhaustive sampling, and permits taking tissue samples for translational research. Controversial areas are discussed, including measurement of lesion size, reporting of lymphovascular space invasion and the presence of isolated tumor cells in lymph nodes after neoadjuvant therapy, and retesting of markers after treatment. If there has been a pathological complete response, this must be clearly stated, and the presence/absence of residual ductal carcinoma in situ must be described. When there is residual invasive carcinoma, a comment must be made as to the presence/absence of chemotherapy effect in the breast and lymph nodes. The Residual Cancer Burden is the preferred method for quantifying residual disease in neoadjuvant clinical trials in breast cancer; other methods can be included per trial protocols and regional preference. Posttreatment tumor staging using the Tumor-Node-Metastasis system should be included. These recommendations for standardized pathological evaluation and reporting of neoadjuvant breast cancer specimens should improve prognostication for individual patients and allow comparison of treatment outcomes within and across clinical trials.

Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer

PubMed Central

Aldakkak, Mohammed; Christians, Kathleen K; Krepline, Ashley N; George, Ben; Ritch, Paul S; Erickson, Beth A; Johnston, Fabian M; Evans, Douglas B; Tsai, Susan

2015-01-01

Background The prognostic value of CA19-9 in patients with pancreatic cancer (PC) treated with neoadjuvant therapy has not been well described. Methods Pre-treatment CA19-9 levels (with concomitant normal bilirubin level) in patients with localized PC were categorized as normal (≤35), low (36–200), moderate (201–1000), or high (>1000). Post-treatment CA19-9 was measured after neoadjuvant therapy, prior to surgery. Results Pre-treatment CA19-9 levels were evaluable in 235 patients, levels were normal in 60 (25%) patients, low in 78 (33%) patients, moderate in 69 (29%) and high in 28 (12%). After neoadjuvant therapy, post-treatment CA19-9 normalized (≤ 35) in 40 (51%) of the patients in the low group, 14 (21%) of the moderate and 5 (19%) of the high group (P < 0.001). Of the 235 patients, 168 (71%) completed all intended therapy including a pancreatectomy; 44 (73%), 62 (79%), 46 (67%) and 16 (57%) of the normal, low, moderate and high groups (P = 0.10). Among these 168 patients, the median overall survival was 38.4, 43.6, 44.7, 27.2 and 26.4 months for normal, low, moderate and high CA19-9 groups (log rank P = 0.72). Among resected patients, an elevated pre-treatment CA19-9 was of little prognostic value; instead, it was the CA19-9 response to neoadjuvant therapy that was prognostic [hazard ratio (HR): 1.80, P = 0.02]. Conclusions Among patients who completed neoadjuvant therapy and surgery, pre-treatment CA19-9 obtained at the time of diagnosis was not predictive of overall survival, but normalization of post-treatment CA19-9 in response to neoadjuvant therapy was highly prognostic. PMID:26255895

Duodenal Bulb Adenocarcinoma Benefitted from Neoadjuvant Chemotherapy: A Case Report.

PubMed

Zhang, Geng-Yuan; Mao, Jie; Zhao, Bin; Long, Bo; Zhan, Hao; Zhang, Jun-Qiang; Zhou, Hui-Nian; Guo, Ling-Yun; Jiao, Zuo-Yi

2017-01-01

Duodenal bulb adenocarcinoma is an extremely rare malignancy in the alimentary tract which has a low incidence rate and nonspecific symptoms. It is difficult to diagnose early, and the misdiagnosis rate is high. CT, MRI, upper gastrointestinal endoscopy, and other advanced imaging modalities should be combined to make a comprehensive evaluation. The diagnostic confirmation of this tumor type mainly depends on the pathological examination. The combination of surgery with other treatment modalities is effective. A review of reports on duodenal bulb adenocarcinoma with chemotherapy revealed 6 cases since 1990. However, there are few reports on neoadjuvant chemotherapy for the disease. In this report, preoperative S-1 in combination with oxaliplatin neoadjuvant chemotherapy achieved a complete pathological response in the treatment of duodenal bulb adenocarcinoma. Neoadjuvant chemotherapy shows a better clinical efficacy in the treatment of duodenal bulb adenocarcinoma, but its value needs to be further verified. © 2017 S. Karger AG, Basel.

68Ga-PSMA-11 PET Imaging of Response to Androgen Receptor Inhibition: First Human Experience.

PubMed

Hope, Thomas A; Truillet, Charles; Ehman, Eric C; Afshar-Oromieh, Ali; Aggarwal, Rahul; Ryan, Charles J; Carroll, Peter R; Small, Eric J; Evans, Michael J

2017-01-01

The purpose of this work was to evaluate the effect of androgen receptor (AR) inhibition on prostate-specific membrane antigen (PSMA) uptake imaged using 68 Ga-PSMA-11 PET in a mouse xenograft model and in a patient with castration-sensitive prostate cancer. We imaged 3 groups of 4 mice bearing LNCaP-AR xenografts before and 7 d after treatment with ARN-509, orchiectomy, or control vehicle. Additionally, we imaged one patient with castration-sensitive prostate cancer before and 4 wk after treatment with androgen deprivation therapy (ADT). Uptake on pre- and posttreatment imaging was measured and compared. PSMA uptake increased 1.5- to 2.0-fold in the xenograft mouse model after treatment with both orchiectomy and ARN-509 but not with vehicle. Patient imaging demonstrated a 7-fold increase in PSMA uptake after the initiation of ADT. Thirteen of 22 lesions in the imaged patient were visualized on PSMA PET only after treatment with ADT. Inhibition of the AR can increase PSMA expression in prostate cancer metastases and increase the number of lesions visualized using PSMA PET. The effect seen in cell and animal models can be recapitulated in humans. A better understanding of the temporal changes in PSMA expression is needed to leverage this effect for both improved diagnosis and improved therapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Human touch vs. axillary digital thermometry for detection of neonatal hypothermia at community level.

PubMed

Agarwal, Siddharth; Sethi, Vani; Pandey, Ravindra Mohan; Kondal, Dimple

2008-06-01

We examined the diagnostic accuracy of human touch (HT) method in assessing hypothermia against axillary digital thermometry (ADT) by a trained non-medical field investigator (who supervised activities of community health volunteers) in seven villages of Agra district, Uttar Pradesh, India. Body temperature of 148 newborns born between March and August 2005 was measured at four points in time for each enrolled newborn (within 48 h and on days 7, 30 and 60) by the field investigator under the axilla using a digital thermometer and by HT method using standard methodology. Total observations were 533. Hypothermia assessed by HT was in agreement with that assessed by ADT (<36.5 degrees C) in 498 observations. Hypothermia assessed by HT showed a high diagnostic accuracy when compared against ADT (kappa 0.65-0.81; sensitivity 74%; specificity 96.7%; positive predictive value 22; negative predictive value 0.26). HT is a simple, quick, inexpensive and programmatically important method. However, being a subjective assessment, its reliability depends on the investigator being adequately trained and competent in making consistently accurate assessments. There is also a need to assess whether with training and supervision even the less literate mothers, traditional birth attendants and community health volunteers can accurately assess mild and moderate hypothermia before promoting HT for early identification of neonatal risk in community-based programs.

Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

PubMed

Rice, Thomas W; Ishwaran, Hemant; Kelsen, David P; Hofstetter, Wayne L; Apperson-Hansen, Carolyn; Blackstone, Eugene H

2016-11-01

We report analytic and consensus processes that produced recommendations for neoadjuvant pathologic stage groups (ypTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 7,773 had pathologic assessment after neoadjuvant therapy. Risk-adjusted survival for each patient was developed. Random forest analysis identified data-driven neoadjuvant pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. An additional analysis produced data-driven anatomic neoadjuvant pathologic stage groups based only on ypT, ypN, and ypM categories. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus neoadjuvant pathologic stage groups. Grade and location were much less discriminating for stage grouping ypTNM than pTNM. Data-driven stage grouping without grade and location produced nearly identical groups for squamous cell carcinoma and adenocarcinoma. However, ypTNM groups and their associated survival differed from pTNM. The need for consensus process was minimal. The consensus groups, identical for both cell types were as follows: ypStage I comprised ypT0-2N0M0; ypStage II ypT3N0M0; ypStage IIIA ypT0-2N1M0; ypStage IIIB ypT3N1M0, ypT0-3N2, and ypT4aN0M0; ypStage IVA ypT4aN1-2, ypT4bN0-2, and ypTanyN3M0; and ypStage IVB ypTanyNanyM1. Absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories ypTisN0-3M0 and ypT0N0-3M0, dissimilar stage group compositions, and markedly different early- and intermediate-stage survival necessitated a unified, unique set of stage grouping for patients of either cell type who receive neoadjuvant therapy. © 2016 International Society for Diseases of the Esophagus.

Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer.

PubMed

Tanaka, Satoru; Iwamoto, Mitsuhiko; Kimura, Kosei; Matsunami, Nobuki; Morishima, Hirotaka; Yoshidome, Katsuhide; Nomura, Takashi; Morimoto, Takashi; Yamamoto, Daigo; Tsubota, Yu; Kobayashi, Toshihiro; Uchiyama, Kazuhisa

2015-06-01

We treated patients with operable human epidermal growth factor receptor 2-positive breast cancer with neoadjuvant anthracycline regimens followed by nanoparticle albumin-bound paclitaxel plus trastuzumab. Of the 44 patients, 49% achieved a pathologic complete response (pCR). The pCR rate was 36% and 71% in the patients with estrogen receptor-positive and -negative cancer, respectively. Neoadjuvant therapy using this combination appears to be effective and safe. Introduction: Neoadjuvant chemotherapy plus trastuzumab. Neoadjuvant chemotherapy plus trastuzumab results in a 30% to 50% pathologic complete response (pCR) rate in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been associated with improved therapeutic outcomes. Thus, the pCR rate can be useful in evaluating novel agents in this patient population. Nanoparticle albumin-bound (nab)-paclitaxel (PTX) can reduce the toxicity of PTX while maintaining its efficacy. The present study evaluated the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+) breast cancer. We treated patients with stage I to IIIA breast cancer using neoadjuvant epirubicin/cyclophosphamide (EC) or 5-fluorouracil/epirubicin/cyclophosphamide every 3 weeks (q3w) for 4 cycles, followed by nab-PTX (260 mg/m(2)) plus trastuzumab q3w for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery rate, and safety. Forty-six patients were enrolled. One patient met the exclusion criteria because of the coexistence of another malignant disease; therefore, we evaluated 45 patients in the entire study. One patient experienced rapid disease progression during EC therapy, leaving 44 patients evaluable for nab-PTX treatment. Of the 45 patients, 49% achieved a pCR. The pCR rate was 36% and 71% in those with estrogen receptor-positive and -negative cancer, respectively. Of all the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; only 1 patient required a dose reduction for nab-PTX because of peripheral neuropathy. Neoadjuvant therapy using this combination appears to be effective and safe. Copyright © 2015 Elsevier Inc. All rights reserved.

Intraductal location of the sclerosing adenosis of the breast.

PubMed

Unal, Bulent; Gur, A Serhat; Bhargava, Rohit; Edington, Howard; Ahrendt, Gretchen; Soran, Atilla

2009-01-01

Sclerosing adenosis is a benign breast disease with non-specific images on ultrasound or mammogram. It can mimic infiltrating carcinoma when the above mentioned imaging techniques are used. Herein we present a patient with breast cancer who received neoadjuvant chemotherapy and subsequently underwent mastectomy. Ductoscopy was performed to the mastectomised breast specimen as per the ductoscopy research protocol. Ductoscopy revealed several nodular lesions in the duct with no additional demonstrable intraductal pathology. The lesions were reported as sclerosing adenosis by pathologist. As to our knowledge, this is the first case in literature that demonstrates the use of ductoscopy in diagnosing the sclerosing adenosis in the breast tissue. Ductoscopy and development of ductoscopy guided biopsy techniques may be used as an early diagnostic method for the ductal breast lesions (Fig. 2, Ref. 10). Full Text (Free, PDF) www.bmj.sk.