Clinical correlates and prognostic value of different metastatic sites in patients with malignant melanoma of the skin: a SEER database analysis.

PubMed

Abdel-Rahman, Omar

2018-03-01

Population-based data on the clinical correlates and prognostic value of the pattern of metastases among patients with cutaneous melanoma are needed. Surveillance, Epidemiology and End Results (SEER) database (2010-2013) has been explored through SEER*Stat program. For each of six distant metastatic sites (bone, brain, liver, lung, distant lymph nodes, and skin/subcutaneous), relevant correlation with baseline characteristics were reported. Survival analysis has been conducted through Kaplan-Meier analysis, and multivariate analysis has been conducted through a Cox proportional hazard model. A total of 2691 patients with metastatic cutaneous melanoma were identified in the period from 2010 to 2013. Patients with isolated skin/subcutaneous metastases have the best overall and melanoma-specific survival (MSS) followed by patients with isolated distant lymph node metastases followed by patients with isolated lung metastases. Patients with isolated liver, bone, or brain metastases have the worst overall and MSS (p < .0001 for both end points). Multivariate analysis revealed that age more than 70 at diagnosis (p = .012); multiple sites of metastases (p <.0001), no surgery to the primary tumor (p <.0001), and no surgery to the metastatic disease (p < .0001) were associated with worse overall survival (OS). For MSS, nodal positivity (p = .038), multiple sites of metastases (p < .0001), no surgery to the primary tumor (p < .0001), and no surgery to the metastatic disease (p < .0001) were associated with worse survival. The prognosis of metastatic cutaneous melanoma patients differs considerably according to the site of distant metastases. Further prospective studies are required to evaluate the role of local treatment in the management of metastatic disease.

A nomogram for predicting distant brain failure in patients treated with gamma knife stereotactic radiosurgery without whole brain radiotherapy

PubMed Central

Ayala-Peacock, Diandra N.; Peiffer, Ann M.; Lucas, John T.; Isom, Scott; Kuremsky, J. Griff; Urbanic, James J.; Bourland, J. Daniel; Laxton, Adrian W.; Tatter, Stephen B.; Shaw, Edward G.; Chan, Michael D.

2014-01-01

Background We review our single institution experience to determine predictive factors for early and delayed distant brain failure (DBF) after radiosurgery without whole brain radiotherapy (WBRT) for brain metastases. Materials and methods Between January 2000 and December 2010, a total of 464 patients were treated with Gamma Knife stereotactic radiosurgery (SRS) without WBRT for primary management of newly diagnosed brain metastases. Histology, systemic disease, RPA class, and number of metastases were evaluated as possible predictors of DBF rate. DBF rates were determined by serial MRI. Kaplan–Meier method was used to estimate rate of DBF. Multivariate analysis was performed using Cox Proportional Hazard regression. Results Median number of lesions treated was 1 (range 1–13). Median time to DBF was 4.9 months. Twenty-seven percent of patients ultimately required WBRT with median time to WBRT of 5.6 months. Progressive systemic disease (χ2= 16.748, P < .001), number of metastases at SRS (χ2 = 27.216, P < .001), discovery of new metastases at time of SRS (χ2 = 9.197, P < .01), and histology (χ2 = 12.819, P < .07) were factors that predicted for earlier time to distant failure. High risk histologic subtypes (melanoma, her2 negative breast, χ2 = 11.020, P < .001) and low risk subtypes (her2 + breast, χ2 = 11.343, P < .001) were identified. Progressive systemic disease (χ2 = 9.549, P < .01), number of brain metastases (χ2 = 16.953, P < .001), minimum SRS dose (χ2 = 21.609, P < .001), and widespread metastatic disease (χ2 = 29.396, P < .001) were predictive of shorter time to WBRT. Conclusion Systemic disease, number of metastases, and histology are factors that predict distant failure rate after primary radiosurgical management of brain metastases. PMID:24558022

Outcomes of surgery for gastric cancer with distant metastases: a retrospective study from the SEER database

PubMed Central

Weng, Shanshan; Dong, Caixia; Zhu, Lizhen; Yang, Ziru; Zhong, Jing; Yuan, Ying

2017-01-01

Background The role of surgical therapy in gastric cancer patients with distant metastases remains controversial. This retrospective analysis was performed to identify whether gastric cancer patients with distant metastases might benefit from surgery. Patients and methods A total of 5185 patients from the SEER database who were initially diagnosed with histologically confirmed gastric cancer with distant metastases from 2004 to 2009 were included. Patients were divided into the following three groups: patients who underwent resection of both the primary tumor and distant metastatic tumors (‘PMTR’ group), patients who only underwent resection of the primary tumor (‘PTR’ group) and patients who did not undergo any surgery (‘No surgery’ group). We employed the Kaplan-Meier analysis, the log-rank test and multivariate Cox proportional hazards regression models to estimate the survival time of the different groups. Results A total of 5185 patients had a median survival time (MST) of 9.0 months. The improvement in survival of the ‘PMTR’ and ‘PTR’ groups was significantly different compared with that of the ‘No surgery’ group (MST, 12.0 vs 12.0 vs 9.0 months, respectively, P<0.001; 1-year survival rate, 49.6% vs 49.1% vs 30.1%, respectively, P<0.001; 3-year survival rate, 12.5% vs 15.1% vs 5.8%, respectively, P<0.001), whereas no significant difference was found between the ‘PMTR’ group and ‘PTR’ group (P=0.642). Multivariate Cox proportional analysis showed that surgery was an independent prognostic factor (‘PMTR’, hazard ratio (HR) =0.648, 95% confidence interval (CI) 0.574-0.733, P<0.001; ‘PTR’, HR=0.631, 95% CI 0.583-0.684, P<0.001). Conclusions This retrospective analysis demonstrated that combined PTR and metastasectomy or PTR alone were independent prognostic factors for survival improvement in gastric cancer patients with distant metastases. Because no statistically significant difference in survival was observed between the ‘PMTR’ group and ‘PTR’ group, PTR, which is a more minor surgery, might be more appropriate than PMTR in clinical practice for gastric cancer patients with distant metastases. PMID:28008147

Metastases from distant primary tumours on the head and neck: clinical manifestation and diagnostics of 91 cases.

PubMed

Baum, Sven Holger; Mohr, Christopher

2018-06-01

The aim of this study was to evaluate which primary tumours metastasize on the head and neck region, identify the kind of clinical manifestation, the types of diagnostics that should be performed, and prove that the therapy appears possible and useful. As many as 91 patients with a distant metastasis on the head and neck were enrolled in this retrospective clinical study from January 2004 to September 2016. All the patients were evaluated for clinical symptoms, primary tumour, localization, diagnostics, and surgical procedure. A total of 31 patients had asymptomatic swelling, 27 patients had symptomatic swelling, and nine experienced isolated pain without swelling. Most other symptoms were organ-specific. The most frequent localizations were the orbit (44 metastases), mandible (19), neck region (9), and skin (7). The most common primary tumours were breast carcinoma (44), bronchial carcinoma (12), and renal carcinoma (9). A biopsy was performed on 38 patients, a partial resection was done on 28 patients, extirpation on six patients, and a radical resection on 19 patients. Distant metastases on the head and neck are rare and, therefore, pose a challenge for the oncologist and other involved disciplines. Most distant metastases occur within the first five years. Late metastases, especially in breast carcinoma, are still possible after 20 years. A surgical examination should be carried out if the findings are not clear due to multiple differential diagnoses. In particular, surgical options under palliative aspects should be examined.

Upper aerodigestive tract cancer and the lung: a tale of two aspirations.

PubMed

Vaideeswar, P; Ghodke, R

2012-01-01

Patients with upper aerodigestive epithelial cancers frequently develop second primary cancers due to common risk factors or develop distant metastases depending on the locoregional status of the primary tumor. In most instances, the organ affected is the lung. Pulmonary spread usually occurs due to hematogenous or lymphatic dissemination. The following is a report of two patients with upper aerodigestive tract squamous cell carcinomas who developed lung metastases due to aspiration, a route not well documented in recent literature.

Human melanoma metastasis in NSG mice correlates with clinical outcome in patients

PubMed Central

Quintana, Elsa; Piskounova, Elena; Shackleton, Mark; Weinberg, Daniel; Eskiocak, Ugur; Fullen, Douglas R.; Johnson, Timothy M.; Morrison, Sean J.

2015-01-01

Studies of human cancer metastasis have been limited by a lack of experimental assays in which cancer cells from patients metastasize in vivo in a way that correlates with clinical outcome. This makes it impossible to study intrinsic differences in the metastatic properties of cancers from different patients. We recently developed an assay in which human melanomas readily engraft in NOD/SCID IL2Rγnull (NSG) mice (1, 2). Here we show that melanomas from 25 patients exhibited reproducible differences in the rate of spontaneous metastasis after transplantation into NSG mice and that these differences correlated with clinical outcome in the patients. Stage IIIB/C melanomas that formed distant metastases within 22 months in patients also formed tumors that metastasized widely in NSG mice, while stage IIIB/C melanomas that did not form distant metastases within 22–50 months in patients metastasized more slowly in NSG mice. These differences in the efficiency of metastasis correlated with the frequency of circulating melanoma cells in the blood of NSG mice, suggesting that the rate of entry into the blood is one factor that limits the rate of metastasis. NSG mice can therefore be used to study the metastasis of human melanomas in vivo, revealing intrinsic differences among stage III melanomas in their ability to circulate/survive in the blood and metastasize. PMID:23136044

Muscle metastasis from non-small cell lung cancer: two cases and literature review.

PubMed

Tezcan, Y; Koc, M

2014-08-01

Non-small cell lung cancers (NSCLC) is the most commonly observed group among lung cancers. Adenocancers are histopathologically more common. Males are more affected than females, an effect which is directly related to smoking. They generally cause distant haematogenous and lymphatic metastasis. Distant haematogenous metastases are often seen in contralateral lung, brain, bone, adrenals, and liver. Muscle metastases from NSCLC are quite rare and male cases are more frequently affected compared to female cases. NSCLC cases with muscle metastasis are at the same time accompanied by distant organ metastases such as bone, brain, and liver. All treatment approaches are considered to be palliative in these cases, which are symptomatologically quite severe. In the present study, we presented the rarely observed cases of two male patients with muscle metastasis from NSCLC together with the related literature.

Increased expression of EZH2 in Merkel cell carcinoma is associated with disease progression and poorer prognosis.

PubMed

Harms, Kelly L; Chubb, Heather; Zhao, Lili; Fullen, Douglas R; Bichakjian, Christopher K; Johnson, Timothy M; Carskadon, Shannon; Palanisamy, Nallasivam; Harms, Paul W

2017-09-01

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing. Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that has a high risk of disease progression with nodal and distant metastases. Here, we evaluated EZH2 expression by immunohistochemistry in a cohort of 85 MCC tumors (29 primary tumors, 41 lymph node metastases, 13 in-transit metastases, and 2 distant metastases) with clinical follow-up. We show strong/moderate EZH2 expression in 54% of tumors. Importantly, weak expression of EZH2 in the primary tumor, but not nodal metastases, correlated with improved prognosis compared to moderate/strong EZH2 expression (5-year MCC-specific survival of 68% versus 22%, respectively, P=.024). In addition, EZH2 was expressed at higher levels in nodal metastases compared to primary tumors (P=.005). Our data demonstrate that EZH2 has prognostic value and may play an oncogenic role in MCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Conventional Risk Stratification Fails to Predict Progression of Succinate Dehydrogenase-deficient Gastrointestinal Stromal Tumors: A Clinicopathologic Study of 76 Cases.

PubMed

Mason, Emily F; Hornick, Jason L

2016-12-01

Gastrointestinal stromal tumors (GISTs) that lack kinase mutations often show loss of function of the succinate dehydrogenase (SDH) complex, due to germline mutation or promoter hypermethylation. SDH-deficient GISTs are exclusive to the stomach and have a multinodular architecture. It has been suggested that conventional risk stratification criteria may not predict outcome for this group of tumors, although data are limited. Here, we report the clinical, histologic, and genetic findings from a large cohort of 76 SDH-deficient GISTs diagnosed from 2005 to 2015, identified on the basis of histologic features or family history (45 female/31 male; mean age at diagnosis 32 y; range 11 to 71 y; 10 patients 50 y of age or above). Immunohistochemistry for SDHB and SDHA showed loss of SDHB in all cases and loss of SDHA in 28 (37%) tumors. Tumor size ranged from 1.9 to 22.5 cm; the primary tumor was multifocal in 29%. Mitotic rate ranged from 1 to 80 per 5 mm (median 5.5). Lymph node metastases were found at primary resection in 14 (18%) patients. Twenty-four patients (32%) had distant metastases at presentation, and 52 of 70 patients (74%) with follow-up developed distant metastases, most often to the liver, but also bone, lungs, breast, and brain. Applying conventional criteria (size and mitotic rate), 60% to 82% of patients with tumors ranging from very low risk to high risk for progressive disease developed distant metastases, regardless of the category. Carney-Stratakis syndrome and Carney triad were diagnosed in 6 and 8 patients, respectively. Of 35 patients tested, 26 harbored SDH mutations (11 SDHA, 8 SDHB, 6 SDHC, 1 SDHD). Follow-up data available for 70 patients ranged from 1 month to 39.3 years: 20 patients had no evidence of disease (mean 6.1 y), 32 were alive with metastases (mean 10.9 y), and 18 died of disease (mean 7.0 y after diagnosis). In summary, SDH-deficient GISTs account for approximately 8% of gastric GISTs and are associated with a high rate of distant metastasis, regardless of conventional risk category. Many affected patients have germline SDH mutations (most often SDHA). Identification of SDH-deficient GISTs is critical for prognostication and genetic counseling.

Effects of Radiation on Metastasis and Tumor Cell Migration

PubMed Central

Vilalta, Marta; Rafat, Marjan; Graves, Edward E.

2016-01-01

It is well known that tumor cells migrate from the primary lesion to distant sites to form metastases and that these lesions limit patient outcome in a majority of cases. However the extent to which radiation influences this process and to which migration in turn alters radiation response remains controversial. There are preclinical and clinical reports showing that focal radiotherapy can both increase the development of distant metastasis, as well as that it can induce the regression of established metastases through the abscopal effect. More recently, preclinical studies have suggested that radiation can attract migrating tumor cells and may thereby facilitate tumor recurrence. In this review, we summarize these phenomena and their potential mechanisms of action, and evaluate their significance for modern radiation therapy strategies. PMID:27022944

Differentiated thyroid cancer in children and adolescents.

PubMed

Farahati, J; Parlowsky, T; Mäder, U; Reiners, C; Bucsky, P

1998-08-01

There have been only a few studies on differentiated childhood thyroid cancer (DTC) in children and adolescents. We analyzed the characteristics of DTC with respect to age, gender and histology in 114 patients under 18 years of age. In a questionnaire-based survey, data of 114 patients, aged between 3 years and 18 years, was collected from 65 clinical institutions in Germany. Characteristics of 80 females and 34 males were evaluated, and the prognostic effect of age, gender, histology, multicentric growth, tumor stage and N-status on distant metastases was tested using multivariate discriminant analysis. Between-group comparison was performed using student t-test and chi-squared test. The incidence of DTC in females was higher than in males with a peak of female:male ratio at puberty, which was more pronounced in children with papillary thyroid cancer, but not with follicular thyroid cancer. Papillary thyroid cancer was associated with more advanced disease (P=0.009), more lymph-node involvement (P=0.007) and more distant metastases (P=0.02) compared with follicular thyroid cancer. Multivariate analysis showed advanced tumor stage as the only significant factor (P=0.02) associating with distant metastasis. It can be concluded that in children and adolescents: 1. The incidence of papillary thyroid cancer is higher in females than males, with a peak at puberty. 2. The only significant factor associated with distant metastases is the advanced tumor stage. 3. Childhood thyroid cancer is frequently associated with lymph-node involvement, distant metastases and advanced tumor stage. 4. Papillary childhood thyroid cancer is more aggressive than follicular type.

18F-FDG PET/CT as a staging procedure in primary stage II and III breast cancer: comparison with conventional imaging techniques.

PubMed

Koolen, Bas B; Vrancken Peeters, Marie-Jeanne T F D; Aukema, Tjeerd S; Vogel, Wouter V; Oldenburg, Hester S A; van der Hage, Jos A; Hoefnagel, Cornelis A; Stokkel, Marcel P M; Loo, Claudette E; Rodenhuis, Sjoerd; Rutgers, Emiel J Th; Valdés Olmos, Renato A

2012-01-01

The aim of the present study was to investigate if 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) outperforms conventional imaging techniques for excluding distant metastases prior to neoadjuvant chemotherapy (NAC) treatment in patients with stage II and III breast cancer. Second, we assessed the clinical importance of false positive findings. One hundred and fifty four patients with stage II or III breast cancer, scheduled to receive NAC, underwent an 18F-FDG PET/CT scan and conventional imaging, consisting of bone scintigraphy, ultrasound of the liver, and chest radiography. Suspect additional lesions at staging examination were confirmed by biopsy and histopathology and/or additional imaging. Metastases that were detected within 6 months after the PET/CT scan were considered evidence of occult metastasis, missed by staging examination. Forty-two additional distant lesions were seen in 25 patients with PET/CT and could be confirmed in 20 (13%) of 154 patients. PET/CT was false positive for 8 additional lesions (19%) and misclassified the presence of metastatic disease in 5 (3%) of 154 patients. In 16 (80%) of 20 patients, additional lesions were exclusively seen with PET/CT, leading to a change in treatment in 13 (8%) of 154 patients. In 129 patients with a negative staging PET/CT, no metastases developed during the follow-up of 9.0 months. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT in the detection of additional distant lesions in patients with stage II or III breast cancer are 100, 96, 80, 100, and 97%, respectively. FDG PET/CT is superior to conventional imaging techniques in the detection of distant metastases in patients with untreated stage II or III breast cancer and is associated with a low false positive rate. PET/CT may be of additional value in the staging of breast cancer prior to NAC.

Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS

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

Shultz, David B.; Modlin, Leslie A.; Jayachandran, Priya

Purpose: To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS). Patients and Methods: We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS. Results: Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the timemore » of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites. Conclusion: Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.« less

Thyroxine to triiodothyronine hyperconversion thyrotoxicosis in patients with large metastases of follicular thyroid carcinoma.

PubMed

Takano, Toru; Miyauchi, Akira; Ito, Yasuhiro; Amino, Nobuyuki

2006-06-01

We experienced two cases of follicular thyroid carcinoma with distant metastases, which showed high levels of free triiodothyronine (T(3)) while free thyroxine (T(4)) levels remained in the low or normal range. In this report, we described the detail of these cases and examined the cause of T(3) thyrotoxicosis. In one of the cases, quantitative measurement of types I and II iodothyronine deiodinase mRNAs was performed using a surgically dissected tissue from the primary tumor and a distant metastasis. In the both tissues, types I and II iodothyronine deiodinase mRNAs were expressed in the same level as in the normal thyroid tissues. These results suggest that T(3) thyrotoxicosis in our patients was caused by hyperconversion of administered levothyroxine to T(3). In the follow-up of patients with distant metastases of follicular carcinoma, not only free T(4), but also free T(3) should be tested to avoid the excessive administration of levothyroxine.

Anti-thyroid peroxidase antibodies are associated with the absence of distant metastases in patients with newly diagnosed breast cancer.

PubMed

Farahati, Jamshid; Roggenbuck, Dirk; Gilman, Elena; Schütte, Martin; Jagminaite, Elena; Seyed Zakavi, Rasoul; Löning, Thomas; Heissen, Eberhard

2012-04-01

The presence of thyroid peroxidase antibodies (TPOab) are reported to be associated with improved outcome among breast cancer patients. We evaluated the correlation between TPOab and diagnostic parameters among newly diagnosed breast cancer patients. Three hundred and fourteen newly diagnosed patients with breast cancer, diagnosed and treated in Bethesda Essen between January 2002 and June 2006, were included in this study; 258 (82.2%) without TPOab (≤100 IU/mL) and 56 (17.8%) with TPOab (>100 IU/mL). Blood analysis was performed to measure serum levels of carcinoembryonic antigen (CEA), cancer antigen 15-3 (CA-15-3), free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH) and TPOab by radioimmunoassay. Data regarding age, tumor size, grading, TNM classification, receptor status, lymph node, and distant metastases were collected and analyzed from patient reports. Statistics were performed using Pearson’s χ2-test and logistic regression analysis. There were no incidences of distant metastasis among 56 patients with TPOab, whereas 17 (6.6%) of 258 cases without TPOab displayed distant metastases (p=0.04). Logistic regression showed an inverse association of TPOab with CA-15-3 and CEA levels (p<0.001, respectively). Both groups, with and without TPOab, revealed no significant differences with respect to age, tumor size, grading, TNM classification, fT3, fT4, and receptor status. TPOab positive patients had higher TSH levels (2.55±3.58), compared to TPOab negative cases (1.20±1.15) (p<0.001). TPOab occurrence is associated with significantly lower frequency of distant metastases in breast cancer. TPOab level inversely correlates with the conventional tumor markers CA-15-3 and CEA.

Three or More Courses of Stereotactic Radiosurgery for Patients with Multiply Recurrent Brain Metastases.

PubMed

Kotecha, Rupesh; Damico, Nicholas; Miller, Jacob A; Suh, John H; Murphy, Erin S; Reddy, Chandana A; Barnett, Gene H; Vogelbaum, Michael A; Angelov, Lilyana; Mohammadi, Alireza M; Chao, Samuel T

2017-06-01

Although patients with brain metastasis are treated with primary stereotactic radiosurgery (SRS), the use of salvage therapies and their consequence remains understudied. To study the intracranial recurrence patterns and salvage therapies for patients who underwent multiple SRS courses. A retrospective review was performed of 59 patients with brain metastases who underwent ≥3 SRS courses for new lesions. Cox regression analyzed factors predictive for overall survival. The median age at diagnosis was 52 years. Over time, patients underwent a median of 3 courses of SRS (range: 3-8) to a total of 765 different brain metastases. The 6-month risk of distant intracranial recurrence after the first SRS treatment was 64% (95% confidence interval: 52%-77%). Overall survival was 40% (95% confidence interval: 28%-53%) at 24 months. Only 24 patients (41%) had a decline in their Karnofsky Performance Status ≤70 at last office visit. Quality of life was preserved among 77% of patients at 12 months, with 45% experiencing clinically significant improvement during clinical follow-up. Radiation necrosis developed in 10 patients (17%). On multivariate analysis, gender (males, Hazard Ratio [HR]: 2.0, P < .05), Karnofsky Performance Status ≤80 (HR 3.2, P < .001), extracranial metastases (HR: 3.6, P < .001), and a distant intracranial recurrence ≤3 months from initial to repeat SRS (HR: 3.8, P < .001) were associated with a poorer survival. In selected patients, performing ≥3 SRS courses controls intracranial disease. Patients may need salvage SRS for distant intracranial relapse, but focal retreatments are associated with modest toxicity, do not appear to negatively affect a patient's performance status, and help preserve quality of life. Copyright © 2017 by the Congress of Neurological Surgeons

Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis.

PubMed

McDonald, Oliver G; Li, Xin; Saunders, Tyler; Tryggvadottir, Rakel; Mentch, Samantha J; Warmoes, Marc O; Word, Anna E; Carrer, Alessandro; Salz, Tal H; Natsume, Sonoko; Stauffer, Kimberly M; Makohon-Moore, Alvin; Zhong, Yi; Wu, Hao; Wellen, Kathryn E; Locasale, Jason W; Iacobuzio-Donahue, Christine A; Feinberg, Andrew P

2017-03-01

During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis. Changes were targeted to thousands of large chromatin domains across the genome that collectively specified malignant traits, including euchromatin and large organized chromatin histone H3 lysine 9 (H3K9)-modified (LOCK) heterochromatin. Remarkably, distant metastases co-evolved a dependence on the oxidative branch of the pentose phosphate pathway (oxPPP), and oxPPP inhibition selectively reversed reprogrammed chromatin, malignant gene expression programs, and tumorigenesis. These findings suggest a model whereby linked metabolic-epigenetic programs are selected for enhanced tumorigenic fitness during the evolution of distant metastasis.

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.

Breast Carcinoma with Oncotype DX Recurrence Score Lower Than 18: Rate of Distant Metastases in a Large Series with Clinical Follow-Up

PubMed Central

Wen, Hannah Y; Krystel-Whittemore, Melissa; Patil, Sujata; Pareja, Fresia; Bowser, Zenica L; Dickler, Maura N.; Norton, Larry; Morrow, Monica; Hudis, Clifford A.; Brogi, Edi

2016-01-01

Backgrounds A 21-gene expression assay (Oncotype DX™ Recurrence Score (“RS”)) that utilizes RT-PCR is used clinically in early-stage estrogen receptor-positive, HER2-negative breast carcinoma (ER+/HER2− BC) to determine both prognosis with tamoxifen therapy and the utility of adding adjuvant chemotherapy. Use of the assay is associated with reductions in overall chemotherapy usage. This study examined the treatments and outcomes in patients with low recurrence scores. Methods We reviewed the institutional database to identify patients with node-negative, ER+/HER2− BC and the 21-gene recurrence score results treated at our center between September 2008 and August 2013. Results We identified 1406 consecutive patients with node-negative ER+/HER2− BC and low RS [RS 0–10: n=510; RS 11–17: n=896]. The median age at BC diagnosis was 56 years; 63 (4%) patients were younger than 40 years. Overall, 1361 (97%) of patients received endocrine therapy and 170 (12%) received chemotherapy. The median follow-up time was 46 months. Six patients (0.4%) developed distant metastases (one patient with RS = 5, and five with RS of 11–17). In the RS 11–17 cohort, the absolute rate of distant metastasis among patients <40 years old was 7.1% (3/42), versus 0.2% (2/854) among patients ≥40 years. Conclusions Our data document a 0.4% rate of distant metastasis within 5 years of BC diagnosis among patients with node-negative ER+/HER2− BC of RS<18. Patients younger than 40 years at BC diagnosis were observed to have a higher rate of distant metastases. Analysis of data from other studies is necessary to further validate this observation. PMID:27526056

Dysphagia: An Unusual Presentation of Metastatic Uterine Cervical Carcinoma.

PubMed

Hameed, Anam; Dekovich, Alexander A; Lum, Phillip J; Shafi, Mehnaz A

2017-03-01

Worldwide, cervical cancer is the third most common cancer among women and the fourth leading cause of death from cancer. The most common sites of metastasis are the pelvic lymph nodes, vagina, and the pelvic sidewalls. Distant metastases are uncommon but can involve the bone, lung, and liver. Characteristics associated with increased rate of distant metastasis include bulky tumor, endometrial extension, lymph node involvement, and advanced disease. We report the case of a woman with stage II cervical carcinoma, who presented with dysphagia due to cervical cancer metastases to the mediastinum.

Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer

PubMed Central

Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun

2016-01-01

As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype. PMID:27340922

Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer.

PubMed

Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun

2016-08-02

As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype.

[Therapeutic outcomes in patients with cervical cancer FIGO stage IB1].

PubMed

Kornovski, Y; Ismail, E; Kaneva, M

2012-01-01

To establish overall and disease-free survival (OS and DFS) for patients with FIGO IB1 stage cervical cancer for median period of follow-up of 41 months. Between 11.2002-11.2011 110 women with histologically confirmed cervical cancer IB1 stage were operated on by the author. Surgery was radical hysterectomy class III (Piver) and pelvic lymphonodulectomy (ovariectomy was optionally). 76 patients were submitted to adjuvant RT (TGT- 52 - 54 Gy). The period of follow-up ranges from 2 to 104 monts, median 41 monts. The acturial OS and DFS in patients with cervical cancer IB1 stage were estimated as 90% and 90.9%, respectively. Eleven patients had died for the period of follow-up and in 10 occurred local or distant recurrences. The time to develop recurrences was estimated as 16.81 months. Four patients developed local recurrences and six--distant metastases. Surgical and combined therapy of cervical cancer patients IB1 stage leads to high rate OS and DFS--90% and 90.9%, respectively. The incidence rate of distant metastases (5.5%)--in six patients in this stage makes pelvic lymph node dissection crucial and the presence of LM in gluteal and presacral lymph nodes requires paraaortic lymph node dissection.

PET imaging in adaptive radiotherapy of prostate tumors.

PubMed

Beuthien-Baumann, Bettina; Koerber, Stefan A

2018-06-04

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

Racial disparities in the development of breast cancer metastases among older women: a multilevel study.

PubMed

Schootman, Mario; Jeffe, Donna B; Gillanders, William E; Aft, Rebecca

2009-02-15

Distant metastases are the most common and lethal type of breast cancer relapse. The authors examined whether older African American breast cancer survivors were more likely to develop metastases compared with older white women. They also examined the extent to which 6 pathways explained racial disparities in the development of metastases. The authors used 1992-1999 Surveillance, Epidemiology, and End Results (SEER) data with 1991-1999 Medicare data. They used Medicare's International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify metastases of respiratory and digestive systems, brain, bone, or other unspecified sites. The 6 pathways consisted of patient characteristics, tumor characteristics, type of treatment received, access to medical care, surveillance mammography use, and area-level characteristics (poverty rate and percentage African American) and were obtained from the SEER or Medicare data. Of the 35,937 women, 10.5% developed metastases. In univariate analysis, African American women were 1.61 times (95% confidence interval [CI], 1.54-1.83) more likely to develop metastasis than white women. In multivariate analysis, tumor grade, stage at diagnosis, and census-tract percentage African American explained why African American women were more likely to develop metastases than white women (hazard ratio, 0.84; 95% CI, 0.68-1.03). Interventions to reduce late-stage breast cancer among African Americans also may reduce racial disparities in subsequent increased risk of developing metastasis. African Americans diagnosed with high-grade breast cancer could be targeted to reduce their risk of metastasis. Future studies should identify specific reasons why the racial distribution in census tracts was associated with racial disparities in the risk of breast cancer metastases. (c) 2009 American Cancer Society.

Characteristics of differentiated thyroid carcinoma in children and adolescents with respect to age, gender, and histology.

PubMed

Farahati, J; Bucsky, P; Parlowsky, T; Mäder, U; Reiners, C

1997-12-01

Because of its rarity there have been only a few detailed studies on differentiated thyroid carcinoma (DTC) in children. The current investigation was undertaken to assess the characteristics of DTC with respect to age, gender, and histology in children and adolescents. In a questionnaire-based survey, data from 114 children and adolescents with DTC (age range, 3-18 years) was collected from 65 clinical institutions in Germany. Characteristics of 80 females and 34 males were evaluated and the influence of age, gender, histology, multicentric growth, tumor stage, and lymph node involvement on distant metastases was tested using multivariate discriminant analysis. Comparison between groups was performed using the Student's t test and chi-square test. Correlation between incidence and age was assessed by linear regression analysis. The overall incidence of thyroid carcinoma in females was higher than in males, with a peak of female/male ratio occurring at puberty. The incidence of DTC correlated with age in females < 16 years (correlation coefficient [r] = 0.84; P = 0.0006), which was more pronounced in children with papillary thyroid carcinoma (PTC) (r = 0.83; P = 0.006) but not in those with follicular thyroid carcinoma (FTC) (r = 0.20; P = 0.16). FTC was associated with less advanced disease (P = 0.009), fewer lymph nodes involved (P = 0.007), and fewer metastases (P = 0.02) compared with PTC. Males tended to have a higher risk for distant metastases. However, statistical analysis failed to reach a level of significance (P = 0.08). Multivariate analysis revealed tumor stage as the only powerful factor (P = 0.02) correlated with distant metastasis. The incidence of PTC shows a marked increase in females with the highest female/male ratio occurring at puberty. Childhood thyroid carcinoma frequently is associated with lymph node involvement, distant metastases, and extrathyroidal tumor infiltration. In children FTC appears to be less aggressive than PTC. Advanced local-regional extension stage appears to be the most powerful factor influencing the risk for distant metastases in children.

Overt Skeletal Metastases in a Patient of Occult (Microscopic) Follicular Thyroid Carcinoma: a Rare Case.

PubMed

Jha, Chandan Kumar; Agrawal, Vinita; Mishra, Anjali; Pradhan, P K

2018-03-01

Occult follicular thyroid carcinoma (FTC) presenting as distant metastases is a rare occurrence. However, despite being occult in majority of these cases, primary tumor can be detected on thyroid imaging or during surgery. Here, we present an extremely rare case of an occult FTC with overt skeletal metastases in which primary tumor was discernible only on microscopic examination.

Role of pelvic radiotherapy for locally advanced rectal cancer and synchronous unresectable distant metastases.

PubMed

Liu, K T; Wan, J F; Zhu, J; Li, G C; Sun, W J; Shen, L J; Cai, S J; Gu, W L; Lian, P; Zhang, Z

2016-12-01

To evaluate the efficacy and safety of pelvic irradiation combined systematic chemotherapy in patients with locally advanced (cT3-T4 and/or cN+) rectal cancer and synchronous unresectable distant metastases. A total of 76 eligible patients who received pelvic radiotherapy and concurrent capecitabine-based chemotherapy were retrospectively reviewed. Patients survival curves were constructed using the Kaplan-Meier method, and a multivariate analysis was performed to identify independent prognostic factors. Most of the adverse events were mild during the period of combined chemoradiotherapy. Twenty-two patients experienced resection of primary tumour and 16 patients underwent radical surgery of all lesions. Only five patients had pelvic progression during the follow-up period. The median progression-free survival and median overall survival were 13 and 30 months, respectively. Radical surgery of all lesions following chemoradiotherapy was found to be an independent prognostic factor according to multivariate analysis. Pelvic irradiation combined with systematic chemotherapy in patients with locally advanced rectal cancer and synchronous unresectable distant metastases is effective and tolerable, both for pelvic and distant control. A curative resection following chemoradiotherapy was associated with prolonged survival. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer.

PubMed

Neskey, David M; Osman, Abdullah A; Ow, Thomas J; Katsonis, Panagiotis; McDonald, Thomas; Hicks, Stephanie C; Hsu, Teng-Kuei; Pickering, Curtis R; Ward, Alexandra; Patel, Ameeta; Yordy, John S; Skinner, Heath D; Giri, Uma; Sano, Daisuke; Story, Michael D; Beadle, Beth M; El-Naggar, Adel K; Kies, Merrill S; William, William N; Caulin, Carlos; Frederick, Mitchell; Kimmel, Marek; Myers, Jeffrey N; Lichtarge, Olivier

2015-04-01

TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high-risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high-risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high-risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations that confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations. ©2015 American Association for Cancer Research.

Evolutionary Action score of TP53 (EAp53) identifies high risk mutations associated with decreased survival and increased distant metastases in head and neck cancer

PubMed Central

Neskey, David M.; Osman, Abdullah A.; Ow, Thomas J.; Katsonis, Panagiotis; McDonald, Thomas; Hicks, Stephanie C.; Hsu, Teng-Kuei; Pickering, Curtis R.; Ward, Alexandra; Patel, Ameeta; Yordy, John S.; Skinner, Heath D.; Giri, Uma; Sano, Daisuke; Story, Michael D.; Beadle, Beth M.; El-Naggar, Adel K.; Kies, Merrill S.; William, William N.; Caulin, Carlos; Frederick, Mitchell; Kimmel, Marek; Myers, Jeffrey N.; Lichtarge, Olivier

2015-01-01

TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC) with mutations occurring in over two third of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed Evolutionary Action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations which confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations. PMID:25634208

Upregulation of c-mesenchymal epithelial transition expression and RAS mutations are associated with late lung metastasis and poor prognosis in colorectal carcinoma.

PubMed

Liu, Jianhua; Zeng, Weiqiang; Huang, Chengzhi; Wang, Junjiang; Xu, Lishu; Ma, Dong

2018-05-01

The present study aimed to investigate whether c-mesenchymal epithelial transition factor (C-MET) overexpression combined with RAS (including KRAS, NRAS and HRAS ) or BRAF mutations were associated with late distant metastases and the prognosis of patients with colorectal cancer (CRC). A total of 374 patients with stage III CRC were classified into 4 groups based on RAS/BRAF and C-MET status for comprehensive analysis. Mutations in RAS / BRAF were determined using Sanger sequencing and C-MET expression was examined using immunohistochemistry. The associations between RAS/BRAF mutations in combination with C-MET overexpression and clinicopathological variables including survival were evaluated. In addition, their predictive value for late distant metastases were statistically analyzed via logistic regression and receiver operating characteristic analysis. Among 374 patients, mutations in KRAS, NRAS, HRAS, BRAF and C-MET overexpression were observed in 43.9, 2.4, 0.3, 5.9 and 71.9% of cases, respectively. Considering RAS/BRAF mutations and C-MET overexpression, vascular invasion (P=0.001), high carcino-embryonic antigen level (P=0.031) and late distant metastases (P<0.001) were more likely to occur in patients of group 4. Furthermore, survival analyses revealed RAS/BRAF mutations may have a more powerful impact on survival than C-MET overexpression, although they were both predictive factors for adverse prognosis. Further logistic regression suggested that RAS/BRAF mutations and C-MET overexpression may predict late distant metastases. In conclusion, RAS/BRAF mutations and C-MET overexpression may serve as predictive indicators for metastatic behavior and poor prognosis of CRC.

Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations

PubMed Central

Brown, David; Smeets, Dominiek; Székely, Borbála; Larsimont, Denis; Szász, A. Marcell; Adnet, Pierre-Yves; Rothé, Françoise; Rouas, Ghizlane; Nagy, Zsófia I.; Faragó, Zsófia; Tőkés, Anna-Mária; Dank, Magdolna; Szentmártoni, Gyöngyvér; Udvarhelyi, Nóra; Zoppoli, Gabriele; Pusztai, Lajos; Piccart, Martine; Kulka, Janina; Lambrechts, Diether; Sotiriou, Christos; Desmedt, Christine

2017-01-01

Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression. We observed two modes of disease progression. In some patients, all distant metastases cluster on a branch separate from their primary lesion. Clonal frequency analyses of somatic mutations show that the metastases have a monoclonal origin and descend from a common ‘metastatic precursor’. Alternatively, multiple metastatic lesions are seeded from different clones present within the primary tumour. We further show that a metastasis can be horizontally cross-seeded. These findings provide insights into breast cancer dissemination. PMID:28429735

Imaging and Management of Intrathoracic Renal Cell Carcinoma Metastases.

PubMed

Price, Melissa; Wu, Carol C; Genshaft, Scott; Sadow, Peter M; Xie, Ling; Shepard, Jo-Anne O; McDermott, Shaunagh

2018-06-01

Renal cell carcinoma (RCC) has a propensity to metastasize to the chest, with the lungs being the most common distant metastatic site. The histologic subtype of RCC has implications for prognosis. Significant advances have been made in the management of metastatic RCC, both in systemic and locoregional therapies. The aim of this article is to review appearances of intrathoracic metastases from RCC and to discuss treatment considerations.

The role of whole brain radiation therapy in the management of melanoma brain metastases

PubMed Central

2014-01-01

Background Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as “radioresistant,” the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). Methods We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). Conclusions Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease control may be especially important in the subset of patients with absent or stable extracranial disease, where the competing risk of death from extracranial disease is low. These results are hypothesis generating and require confirmation from ongoing randomized trials. PMID:24954062

Review: circulating tumor cells in the practice of breast cancer oncology.

PubMed

Ramos-Medina, R; Moreno, F; Lopez-Tarruella, S; Del Monte-Millán, M; Márquez-Rodas, I; Durán, E; Jerez, Y; Garcia-Saenz, J A; Ocaña, I; Andrés, S; Massarrah, T; González-Rivera, M; Martin, M

2016-08-01

The primary cause of tumor-related death in breast cancer is still represented by distant metastasization. The dissemination of tumor cells from the primary tumor to distant sites through bloodstream cannot be early detected by standard imaging methods. Circulating tumor cells (CTCs) play a major role in the metastatic spread of breast cancer. Different analytical systems for CTCs isolation and detection have been developed and novel areas of research are directed towards developing assays for CTCs molecular characterization. This review describes the current state of art on CTCs detection techniques and the present and future clinical implications of CTCs enumeration and characterization.

The Influence of Diabetes Mellitus and Metformin on Distant Metastases in Oropharyngeal Cancer: A Multicenter Study

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

Spratt, Daniel E.; Beadle, Beth M.; Zumsteg, Zachary S., E-mail: zachary.zumsteg@cshs.org

Purpose: Local control in oropharyngeal cancer has improved to unprecedented rates with combined modality therapy; as a result, distant metastases are becoming a principal challenge. We aimed to determine the impact of diabetes mellitus and metformin use on clinical outcomes in a large population of oropharyngeal cancer patients treated in the modern era. Methods and Materials: We identified 1745 consecutive patients with oropharyngeal cancer treated at 2 large cancer centers with external beam radiation therapy from 1998 to 2011. A total of 184 patients had diabetes mellitus at the time of diagnosis, of whom 102 were taking metformin. The outcomesmore » assessed included local failure-free survival (LFFS), regional failure-free survival (RFFS), distant metastasis-free survival (DMFS), and overall survival (OS). Results: The median follow-up time was 4.3 years. The 5-year actuarial rates of DMFS were 89.6% for nondiabetic patients and 78.7% for diabetic nonmetformin users (P=.011) and of OS were 83.0% for nondiabetic patients and 70.7% for diabetic nonmetformin users (P=.048). Diabetic metformin users had 5-year DMFS (90.1%) and OS (89.6%) similar to those of nondiabetic patients. Multivariate analysis (diabetic nonmetformin users as reference) demonstrated improved DMFS for nondiabetic patients (adjusted hazard ratio 0.54; 95% confidence interval 0.32-0.93; P=.03) and a trend toward improved DMFS with metformin use (adjusted hazard ratio 0.46; 95% confidence interval 0.20-1.04; P=.06). LFFS and RFFS were high in all groups and were not significantly different by diabetic status or metformin use. Conclusions: Diabetic patients not using metformin independently have significantly higher rates of distant metastases than do nondiabetic patients, whereas metformin users have rates of distant metastases similar to those of nondiabetic patients. Further prospective investigation is warranted to validate the benefit of metformin in oropharyngeal cancer.« less

Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia.

PubMed

Maklad, Ahmed Marzouk; Bayoumi, Yasser; Senosy Hassan, Mohamed Abdalazez; Elawadi, AbuSaleh A; AlHussain, Hussain; Elyamany, Ashraf; Aldhahri, Saleh F; Al-Qahtani, Khalid Hussain; AlQahtani, Mubarak; Tunio, Mutahir A

2016-01-01

We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66-70 Gy, 63 Gy to clinical target volume, and 50.4-56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. The median follow-up time was 52.2 months (range: 11-87 months). Epstein-Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16-50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein-Barr virus were independent predictors for disease-free survival. Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein-Barr virus status before IMRT were important independent prognostic factors.

Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

NASA Astrophysics Data System (ADS)

Li, Xiaosong; Hode, Tomas; Guerra, Maria C.; Ferrel, Gabriela L.; Nordquist, Robert E.; Chen, Wei R.

2011-02-01

Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

The natural history and patterns of metastases from mucosal melanoma: an analysis of 706 prospectively-followed patients.

PubMed

Lian, B; Cui, C L; Zhou, L; Song, X; Zhang, X S; Wu, D; Si, L; Chi, Z H; Sheng, X N; Mao, L L; Wang, X; Tang, B X; Yan, X Q; Kong, Y; Dai, J; Li, S M; Bai, X; Zheng, N; Balch, C M; Guo, J

2017-04-01

We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would differ from primary mucosal melanomas at different anatomical sites. Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites. The anatomic sites of the primary mucosal melanomas were from the lower GI tract (26.5%), nasal cavity and paranasal sinuses (23%), gynecological sites (22.5%), oral cavity (15%), urological sites (5%), upper GI tract (5%), and other sites (3.0%). At initial diagnosis, 14.5% were stage I disease, 41% Stage II, 21.5% Stage III, and 23.0% stage IV. Predominant metastatic sites were regional lymph nodes (21.5%), lung (21%), liver (18.5%), and distant nodes (9%). Oral cavity mucosal melanoma had a higher incidence of regional nodal metastases (31.7% versus 19.8%, P = 0.009), and a higher incidence of lung metastases (32.5% versus 18.5%, P = 0.007) compared to other primary mucosal melanomas. There was a 10% incidence of CKIT mutation and 12% BRAF mutation. Mucosal melanomas from nasal pharyngeal and oral, gastrointestinal, gynecological, and urological had a similar survival with a 1-year survival rate (88%, 83%, 86%), 2-year survival rate (66%, 57%, 61%), 5-year survival rate (27%, 16%, 20%), respectively. The largest sample size allows, for the first time, a comparison of primary melanoma stage and patterns of metastases across anatomical sites. With few exceptions, the presenting stages, incidence of nodal and distant metastases, the site of predilection of distant metastases, or overall survival were similar despite different primary anatomic sites. These findings suggest that clinical trials involving mucosal melanomas and the administration of systemic therapy can be applied equally to mucosal melanomas regardless of their primary anatomic site. © The Author 2016. 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.

Nasopharyngeal cancer: a review of 1605 patients treated radically with cobalt 60. [5- and 10-year survival rates and complications of radiotherapy

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

Huang, S.C.

A retrospective study was performed on 1605 patients with histologically proven and radically treated nasopharyngeal carcinoma. All were followed for a minimum of five years; 833 patients had a minimum follow-up period of ten years. Treatment results were reviewed according to: (1) size of primary tumor; (2) base of skull invasion; (3) cranial nerve involvement; (4) cervical node metastases; and (5) distant spread. An appropriate staging system was developed that reflected these prognostic factors. The evidence presented indicates that in this series of patients, base of skull involvement was less ominous than cranial nerve involvement. Unilteral lymph node involvement carriedmore » a better prognosis than bilateral neck nodes, this was the poorest sign of all since it predicted distant metastases. The average 5-year survival rate for 1605 patients in all stages, was 529/1605(32.1%); the 10-year survival rate for 833 patients in all stages was 20.2%.« less

Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases.

PubMed

Le Pennec, Soazig; Konopka, Tomasz; Gacquer, David; Fimereli, Danai; Tarabichi, Maxime; Tomás, Gil; Savagner, Frédérique; Decaussin-Petrucci, Myriam; Trésallet, Christophe; Andry, Guy; Larsimont, Denis; Detours, Vincent; Maenhaut, Carine

2015-04-01

The contribution of intratumor heterogeneity to thyroid metastatic cancers is still unknown. The clonal relationships between the primary thyroid tumors and lymph nodes (LN) or distant metastases are also poorly understood. The objective of this study was to determine the phylogenetic relationships between matched primary thyroid tumors and metastases. We searched for non-synonymous single-nucleotide variants (nsSNVs), gene fusions, alternative transcripts, and loss of heterozygosity (LOH) by paired-end massively parallel sequencing of cDNA (RNA-Seq) in a patient diagnosed with an aggressive papillary thyroid cancer (PTC). Seven tumor samples from a stage IVc PTC patient were analyzed by RNA-Seq: two areas from the primary tumor, four areas from two LN metastases, and one area from a pleural metastasis (PLM). A large panel of other thyroid tumors was used for Sanger sequencing screening. We identified seven new nsSNVs. Some of these were early events clonally present in both the primary PTC and the three matched metastases. Other nsSNVs were private to the primary tumor, the LN metastases and/or the PLM. Three new gene fusions were identified. A novel cancer-specific KAZN alternative transcript was detected in this aggressive PTC and in dozens of additional thyroid tumors. The PLM harbored an exclusive whole-chromosome 19 LOH. We have presented the first, to our knowledge, deep sequencing study comparing the mutational spectra in a PTC and both LN and distant metastases. This study has yielded novel findings concerning intra-tumor heterogeneity, clonal evolution and metastases dissemination in thyroid cancer. © 2015 Society for Endocrinology.

PANCREAS METASTASES FROM PAPILLARY THYROID CARCINOMA: A REVIEW OF THE LITERATURE.

PubMed

Davidson, Maja; Olsen, Randall J; Ewton, April A; Robbins, Richard J

2017-12-01

Although locoregional metastases occur in 5 to 10% of patients with papillary thyroid cancer (PTC), distant metastases are rare, especially to the pancreas. Here we review the literature regarding metastases to the pancreas from PTC and present an illustrative patient. The literature search was performed through using the PubMed database. The information regarding our illustrative case was obtained from the medical records of our institution. Since 1991, 11 cases of pancreas metastases of PTC have been reported. The average age at diagnosis was 55.3 years. There were 8 males and 3 females. Three had classic PTC histology, 2 had tall cell variant, and 2 had follicular variant. Four had T4 tumors, and 2 had T3 tumors. Seven had thyroid cancer spread to regional lymph nodes. One had distant metastasis. Pancreas metastases were diagnosed from 1 month to 13 years after primary PTC was detected; the average was 7 years. Our patient was an 84-year-old female diagnosed with PTC with a BRAFV600E mutation following total thyroidectomy. A whole-body scan after radioactive iodine (RAI) remnant ablation was negative for metastases. A pancreatic tumor was identified 2 years later on a fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan. A biopsy of the tumor was histologically similar to PTC and positive for thyroglobulin, thyroid transcription factor-1, and the BRAFV600E mutation. The biological reasons why PTCs metastasize to the pancreas remain to be elucidated. Older patients with non-RAI avid, FDG-PET-positive metastases, and symptoms of pancreatitis are at increased risk of this rare entity. FDG = fluorodeoxyglucose FNA = fine-need aspiration PTC = papillary thyroid cancer RAI = radioactive iodine Tg = thyroglobulin TgAb = antithyroglobulin antibodies TNM = tumor-node-metastasis.

Total half-body systemic irradiation for occult metastases in non-small cell lung cancer: an Eastern Cooperative Oncology group pilot report

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

Salazar, O.M.; Scarantino, C.W.; Rubin, P.

1980-11-01

There is a high probability for patients with locally advanced, unresectable, nonmetastatic, nonsmall-cell bronchogenic carcinoma (NSCBC) to harbor subclinical distant metastases at diagnosis. Approximately 30% will disseminate in the first three months and an additional 50% will disseminate before a year has elapsed. Twenty advanced nonmetastatic patients wtith NSCBC were treated with localized split-course chest irradiation (LCI) plus total body (upper and lower half-body) irradiation for occult metastases. Thirty equally advanced, nonmetastatic patients, who were treated with only localized split-course chest irradiation, were matched and served as a retrospective control group. Apparently, the median recurrence free survival, metastatic free interval,more » and median survival were significantly prolonged, and there was a decrease in the incidence of liver metastases in patients receiving HBI for occult metastases over the patients of the control group. Although elective HBI seems to delay the appearance of distant metastases, it did not prevent their occurrence, alter patterns of first relapse, or significantly improve the overall survival. Nevertheless, a therapeutic gain may have been achieved and is discussed. The incidence of radiation pneumonitis with 800 rad of UHBI corrected for lung transmission was 9%. A hypothesis and a rationale for a more effective combined modality therapy in these patients is given.« less

Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis.

PubMed

St Romain, Paul; Madan, Rashna; Tawfik, Ossama W; Damjanov, Ivan; Fan, Fang

2012-03-01

Prior studies have suggested that the type of breast cancer influences the location of distant metastases ("organotropism") and that there may be discordance of estrogen receptor and human epidermal growth factor receptor 2 (Her2) expression between primaries and metastases. Our aims were to investigate the relationship between tumor type and metastatic site and to compare biomarker expression between primary and metastatic tumors. We retrospectively reviewed 102 biopsy-proven cases of breast cancer metastatic to distant sites from 2000 to 2010 and 34 corresponding primaries for histologic subtype, grade, lymphovascular invasion, lymph node metastasis, and expression of estrogen receptor and Her2. Most metastases were of ductal (88) and lobular (11) histologic types. Available data on primaries indicated that the majority were grade III with positive lymph node metastasis and lymphovascular invasion. Biomarkers on 73 metastases showed 37 estrogen receptor positive/Her2-, 6 estrogen receptor positive/Her2+, 8 estrogen receptor negative/Her2+, and 22 estrogen receptor negative/Her2-. The most common metastatic sites were the lung (26%), bone (32%), and liver (21%). We found no association between estrogen receptor/Her2 profile and metastatic site (P = .16). When compared with ductal carcinoma, lobular carcinoma showed a unique metastatic pattern to gastrointestinal tract/gynecologic sites (P = .014). Of 34 cases with paired prognostic markers for primary and metastatic sites, 7 (20%) demonstrated discordance in estrogen receptor-positive/Her2 profile between the primary and the metastasis. Because the estrogen receptor-positive/Her2 profile of metastatic breast cancer did not always match that of the primary tumor, it is important to repeat the prognostic markers of metastasis. Copyright © 2012 Elsevier Inc. All rights reserved.

Photodynamic therapy stimulates anti-tumor immune response in mouse models: the role of regulatory Tcells, anti-tumor antibodies, and immune attacks on brain metastases

NASA Astrophysics Data System (ADS)

Vatansever, Fatma; Kawakubo, Masayoshi; Chung, Hoon; Hamblin, Michael R.

2013-02-01

We have previously shown that photodynamic therapy mediated by a vascular regimen of benzoporphyrin derivative and 690nm light is capable of inducing a robust immune response in the mouse CT26.CL25 tumor model that contains a tumor-rejection antigen, beta-galactosidase (β-gal). For the first time we show that PDT can stimulate the production of serum IgG antibodies against the β-gal antigen. It is known that a common cause of death from cancer, particularly lung cancer, is brain metastases; especially the inoperable ones that do not respond to traditional cytotoxic therapies either. We asked whether PDT of a primary tumor could stimulate immune response that could attack the distant brain metastases. We have developed a mouse model of generating brain metastases by injecting CT26.CL25 tumor cells into the brain as well as injecting the same cancer cells under the skin at the same time. When the subcutaneous tumor was treated with PDT, we observed a survival advantage compared to mice that had untreated brain metastases alone.

Ultrasound-based follow-up does not increase survival in early-stage melanoma patients: A comparative cohort study.

PubMed

Ribero, S; Podlipnik, S; Osella-Abate, S; Sportoletti-Baduel, E; Manubens, E; Barreiro, A; Caliendo, V; Chavez-Bourgeois, M; Carrera, C; Cassoni, P; Malvehy, J; Fierro, M T; Puig, S

2017-11-01

Different protocols have been used to follow up melanoma patients in stage I-II. However, there is no consensus on the complementary tests that should be requested or the appropriate intervals between visits. Our aim is to compare an ultrasound-based follow-up with a clinical follow-up. Analysis of two prospectively collected cohorts of melanoma patients in stage IB-IIA from two tertiary referral centres in Barcelona (clinical-based follow-up [C-FU]) and Turin (ultrasound-based follow-up [US-FU]). Kaplan-Meier curves were used to evaluate distant metastases-free survival (DMFS), disease-free interval (DFI), nodal metastases-free survival (NMFS) and melanoma-specific survival (MSS). A total of 1149 patients in the American Joint Committee on Cancer stage IB and IIA were included in this study, of which 554 subjects (48%) were enrolled for a C-FU, and 595 patients (52%) received a protocolised US-FU. The median age was 53.8 years (interquartile range [IQR] 41.5-65.2) with a median follow-up time of 4.14 years (IQR 1.2-7.6). During follow-up, 69 patients (12.5%) in C-FU and 72 patients (12.1%) in US-FU developed disease progression. Median time to relapse for the first metastatic site was 2.11 years (IQR 1.14-4.04) for skin metastases, 1.32 (IQR 0.57-3.29) for lymph node metastases and 2.84 (IQR 1.32-4.60) for distant metastases. The pattern of progression and the total proportion of metastases were not significantly different (P = .44) in the two centres. No difference in DFI, DMFS, NMFS and MSS was found between the two cohorts. Ultrasound-based follow-up does not increase the survival of melanoma patients in stage IB-IIA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Futility of fluorodeoxyglucose F 18 positron emission tomography in initial evaluation of patients with T2 to T4 melanoma.

PubMed

Clark, Paige B; Soo, Victoria; Kraas, Jonathan; Shen, Perry; Levine, Edward A

2006-03-01

Evaluation of newly diagnosed patients with melanoma for metastasis is requisite to treatment planning. The reported diagnostic yield of whole-body conventional radiological imaging in initial staging of patients with melanoma is low. However, the diagnostic yield of positron emission tomography (PET) for distant metastases is unclear. There is no utility of PET as part of a routine metastatic survey in patients with T2 to T4 melanoma. Retrospective review of a cohort study between December 1998 and July 2004. University hospital tertiary care center. There were 64 patients with T2 to T4 melanomas who underwent PET for detection of occult metastases at our institution. All patients underwent surgical excision of the primary lesion and sentinel lymph node dissection. Data included were pathologic findings of the primary lesion and sentinel lymph nodes, laboratory data, and radiological reports. None of the patients had clinically suspected regional or distant metastases prior to PET. The diagnostic yield of PET was evaluated through retrospective analysis. Positive scans were then correlated for accuracy with follow-up imaging, biopsy, and clinical information when available. Positron emission tomography did not reveal occult distant metastases in any of the patients. Positron emission tomographic scans showed no abnormalities in 94% of these patients. In 2 patients (3%), false-positive findings were reported on PET (muscular activity and intranodal melanocytic nevocellular inclusion). Further, PET was not useful in predicting regional lymph node metastases. Nineteen of 64 patients had positive sentinel lymph nodes, and only 2 (11%) were identified on PET. Overall, PET did not change clinical management in any of the patients. This study suggests no utility for PET in the detection of occult metastases in patients at initial diagnosis of melanoma. Omission of PET imaging from preoperative evaluations for patients with melanoma is recommended.

Surgical Management of Metastatic Disease.

PubMed

Keung, Emily Z; Fairweather, Mark; Raut, Chandrajit P

2016-10-01

Sarcomas are rare cancers of mesenchymal cell origin that include many histologic subtypes and molecularly distinct entities. For primary resectable sarcoma, surgery is the mainstay of treatment. Despite treatment, approximately 50% of patients with soft tissue sarcoma are diagnosed with or develop distant metastases, significantly affecting their survival. Although systemic therapy with conventional chemotherapy remains the primary treatment modality for those with metastatic sarcoma, increased survival has been achieved in select patients who receive multimodality therapy, including surgery, for their metastatic disease. This article provides an overview of the literature on surgical management of pulmonary and hepatic sarcoma metastases. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases.

PubMed

Qian, Yun; Sang, Yiwen; Wang, Frederick X C; Hong, Bo; Wang, Qi; Zhou, Xinhui; Weng, Tianhao; Wu, Zhigang; Zheng, Min; Zhang, Hong; Yao, Hangping

2016-11-01

Liver metastasis development in pancreatic cancer patients is common and confers a poor prognosis. Clinical relevance of biomarker analysis in metastatic tissue is necessary. B7-H4 has an inhibitory effect on T cell mediated response and may be involved in tumor development. Although B7-H4 expression has been detected in pancreatic cancer, its expression in liver metastases from pancreatic cancer is still unknown. In this study, overall 43 pancreatic cancer liver metastases (with matched primaries in 15/43 cases) and 57 pancreatic cancer cases without liver metastases or other distant metastases were analyzed for their expression of B7-H4 by immunohistochemistry. Survival curves and log-rank tests were used to test the association of B7-H4 expression with survival. B7-H4 was highly expressed in 28 (65.1%) of the 43 liver metastases and 9 (60.0%) of the 15 matched primary tumors. The expression of B7-H4 in liver metastases was significantly higher than in the matched primary tumors (p < 0.05). Patients with high B7-H4 expression in their primary pancreatic cancer had higher risk of developing liver metastases (p < 0.05). In univariate analysis, B7-H4 expression was significantly associated with the risk of death (p < 0.05). And the multivariate analysis identified that B7-H4 was an independent prognostic indicator (p < 0.05). Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis. B7-H4 may promote pancreatic cancer metastasis and was promising to be a potential prognostic indicator of pancreatic cancer.

Phase 3 Trials of Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis

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

Sahgal, Arjun, E-mail: arjun.sahgal@sunnybrook.ca; Aoyama, Hidefumi; Kocher, Martin

Purpose: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRSmore » alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group.« less

Pancreatic Cancer Genomics 2.0: Profiling Metastases.

PubMed

Collisson, Eric A; Maitra, Anirban

2017-03-13

Pancreatic ductal adenocarcinoma, even when diagnosed early, nearly always metastasizes. Recurrent mutations and genomic instability are early events in the disease. Two recent papers advance our understanding of how the cancer genome evolves as the primary tumor migrates from its origin in the pancreas to colonize distant metastatic sites. Copyright © 2017 Elsevier Inc. All rights reserved.

Neck dissection after chemoradiotherapy for oropharyngeal and hypopharyngeal cancer: the correlation between cervical lymph node metastasis and prognosis.

PubMed

Hanai, Nobuhiro; Kawakita, Daisuke; Ozawa, Taijiro; Hirakawa, Hitoshi; Kodaira, Takeshi; Hasegawa, Yasuhisa

2014-02-01

Recently, the role of chemoradiotherapy (CRT) for preserving organs in the treatment of head and neck cancer has been increasing. However, the indication for post-CRT neck dissection (ND) and its surgical extent is still controversial. The purpose of this study was to discuss the indications for post-CRT ND and the proper extent of the surgical procedure. We performed a retrospective analysis on N2-3 oropharyngeal and hypopharyngeal squamous cell carcinoma (OHSCC) patients treated with CRT in our institute from 1995 to 2008, and determined the prognostic impact of post-CRT ND and the distribution of cervical lymph node (CLN) metastasis based on the pathological results of ND. The patients without pathological CLN metastases had good prognoses, whereas patients with pathological CLN metastases exhibited a significantly high recurrence rate (P = 0.033). Based on the pathological results of ND, performing selective ND at levels II-IV can contain 88 and 85 % of CLN metastasis of the oropharynx and hypopharynx, respectively. In all cases, when pathological CLN metastases were found at level V in ND following CRT, distant metastases developed. The presence of pathological CLN metastasis affects prognosis, but also a diffuse distribution of CLN metastasis worsens prognosis; that is, the presence of CLN metastasis at level V after CRT appears to be an indicator of distant metastasis. Post-CRT ND may not make sense as a salvage intervention for improving the prognosis in such situations. We concluded that the proper extent of post-CRT ND of OHSCC is selective ND including levels II-IV.

The Role of TPS and TPA in the Diagnostics of Distant Metastases.

PubMed

Kucera, Radek; Topolcan, Ondrej; Fiala, Ondrej; Kinkorova, Judita; Treska, Vladislav; Zedníková, Ilona; Slouka, David; Simanek, Vaclav; Safanda, Martin; Babuska, Vaclav

2016-02-01

The aim of the study was to assess the degree to which tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS), as well as carcinoembryonic antigen (CEA), can assist in the detection of distant metastases. We assessed 157 patients with colorectal and breast cancer divided into two groups. The first was a group of patients with cancer at stages 1, 2 and 3; the second was a group of patients with cancer at stage 4 with metastasis. We found significantly higher levels of all biomarkers in the metastatic group compared to the group with cancer at stages 1-3 (p<0.0001). The calculated area under the receiver operating characteristic (ROC) curve was 0.9929 for TPS, 0.9337 for TPA and 0.7234 for CEA. The cut-off was calculated for each biomarker at 95% specificity, TPS cut-off=255 IU/l (sensitivity 95%), TPA cut-off=200 IU/l (sensitivity 70%) and CEA cut-off=18 μg/l (sensitivity 37%). We suggest combining CEA with TPS or TPA in the detection of distant metastases or using only cytokeratins. This approach can significantly increase the quality of detection of the metastatic process. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia

PubMed Central

Maklad, Ahmed Marzouk; Bayoumi, Yasser; Senosy Hassan, Mohamed Abdalazez; Elawadi, AbuSaleh A; AlHussain, Hussain; Elyamany, Ashraf; Aldhahri, Saleh F; Al-Qahtani, Khalid Hussain; AlQahtani, Mubarak; Tunio, Mutahir A

2016-01-01

Background We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. Patients and methods From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume, and 50.4–56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. Results The median follow-up time was 52.2 months (range: 11–87 months). Epstein–Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16–50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein–Barr virus were independent predictors for disease-free survival. Conclusion Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein–Barr virus status before IMRT were important independent prognostic factors. PMID:27822060

Patterns of breast cancer relapse in accordance to biological subtype.

PubMed

Ignatov, Atanas; Eggemann, Holm; Burger, Elke; Ignatov, Tanja

2018-04-19

To evaluate the pattern of recurrence of breast cancer according to its biological subtype in a large cohort of patients treated with therapy representative of current practice. Patients treated between 2000 and 2016 with known biological subtype were eligible. Data were prospectively collected. Primary endpoint was the subtype-dependent pattern and time of recurrence. Loco-regional and distant site and time of recurrence were assessed. Median follow-up time was 80.8 months. For 12,053 (82.5%) of 14,595 patients with primary non-metastatic invasive breast cancer a subtype classification was possible. The luminal A subtype had the highest 10-year survival followed by luminal B and luminal/HER2. The worst survival demonstrated HER2 enriched and TNBC. HER2 and TNBC had the highest rate of recurrence in the first 5 years, whereas the rate of recurrence for luminal A and luminal B tumors was initially low, but remained continuously even after 10 years of follow-up. Luminal A tumors demonstrated the lowest rate of distant metastases predominantly in bone. So did luminal B tumors. HER2 enriched subtype was characterized with increased rate of loco-regional recurrence and distant metastases in bone, liver and brain. Luminal/HER2 had pattern of relapse similar to HER2 enriched tumors, with exception of loco-regional relapse and brain metastases. TNBC had higher rate of lung, bone and brain metastases as well as loco-regional relapse. Breast cancer subtypes are associated with different time and pattern of recurrence and it should be considered during treatment decision.

GBM skin metastasis: a case report and review of the literature

PubMed Central

Lewis, Gary D; Rivera, Andreana L; Tremont-Lukats, Ivo W; Ballester-Fuentes, Leomar Y; Zhang, Yi Jonathan; Teh, Bin S

2017-01-01

Glioblastoma (GBM) is the most common type of malignant tumor found in the brain, and acts very aggressively by quickly and diffusely infiltrating the surrounding brain parenchyma. Despite its aggressive nature, GBM is rarely found to spread extracranially and develop distant metastases. The most common sites of these rare metastases are the lungs, pleura and cervical lymph nodes. There are also a few case reports of skin metastasis. We present the clinical, imaging and pathologic features of a case of a GBM with metastasis to the soft tissue scar and skin near the original craniotomy site. In addition, we discuss the details of this case in the context of the previously reported literature. PMID:28718312

A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model.

PubMed

Oh, Keunhee; Lee, Ok-Young; Shon, Suh Youn; Nam, Onyou; Ryu, Po Mee; Seo, Myung Won; Lee, Dong-Sup

2013-01-01

Tumor cell interactions with the microenvironment, especially those of bone-marrow-derived myeloid cells, are important in various aspects of tumor metastasis. Myeloid-derived suppressor cells (MDSCs) have been suggested to constitute tumor-favoring microenvironments. In this study, we elucidated a novel mechanism by which the MDSCs can mediate spontaneous distant metastasis of breast cancer cells. Murine breast cancer cells, 4T1 and EMT6, were orthotopically grafted into the mammary fat pads of syngeneic BALB/c mice. CD11b(+)Gr-1(+) MDSCs in the spleen, liver, lung and primary tumor mass were analyzed. To evaluate the role of MDSCs in the distant metastasis, MDSCs were depleted or reconstituted in tumor-bearing mice. To evaluate whether MDSCs in the metastasizing tumor microenvironment affect breast cancer cell behavior, MDSCs and cancer cells were co-cultivated. To investigate the role of MDSCs in in vivo metastasis, we blocked the interactions between MDSCs and cancer cells. Using a murine breast cancer cell model, we showed that murine breast cancer cells with high IL-6 expression recruited more MDSCs and that the metastasizing capacity of cancer cells paralleled MDSC recruitment in tumor-bearing mice. Metastasizing, but not non-metastasizing, tumor-derived factors induced MDSCs to increase IL-6 production and full activation of recruited MDSCs occurred in the primary tumor site and metastatic organ in the vicinity of metastasizing cancer cells, but not in lymphoid organs. In addition, tumor-expanded MDSCs expressed Adam-family proteases, which facilitated shedding of IL-6 receptor, thereby contributing to breast cancer cell invasiveness and distant metastasis through IL-6 trans-signaling. The critical role of IL-6 trans-signaling was confirmed in both the afferent and efferent pathways of metastasis. In this study, we showed that metastasizing cancer cells induced higher MDSCs infiltration and prompted them to secret exaggerated IL-6 as well as soluble IL-6Ra, which, in turn, triggered a persistent increase of pSTAT3 in tumor cells. This potential tumor-MDSC axis involving IL-6 trans-signaling directly affected breast cancer cell aggressiveness, leading to spontaneous metastasis.

Characterisation of the triple negative breast cancer phenotype associated with the development of central nervous system metastases.

PubMed

Laimito, Katerin Rojas; Gámez-Pozo, Angelo; Sepúlveda, Juan; Manso, Luis; López-Vacas, Rocío; Pascual, Tomás; Fresno Vara, Juan A; Ciruelos, Eva

2016-01-01

Breast cancer (BC) is the most frequent tumour in women, representing 20-30% of all malignancies, and continues to be the leading cause of cancer deaths among European women. Triple-negative (TN) BC biological aggressiveness is associated with a higher dissemination rate, with central nervous system (CNS) metastases common. This study aims to elucidate the association between gene expression profiles of PTGS2, HBEGF and ST6GALNAC5 and the development of CNS metastases in TNBC. This is a case-controlled retrospective study comparing patients (pts) with CNS metastases versus patients without them after adjuvant treatment. The selection of the samples was performed including 30 samples in both case and control groups. Formalin-fixed, paraffin-embedded samples were retrieved from the Hospital 12 de Octubre Biobank. Five 10 µm sections from each FFPE sample were deparaffinised with xylene and washed with ethanol, and the RNA was then extracted with the RecoverAll Kit (Ambion). Gene expression was assessed using TaqMan assays. A total of 53 patients were included in the study. The average age was 55 years (range 25-85). About 47 patients (88.67%) had ductal histology and presented high grade (III) tumours (40 patients; 75.47%). Eight women in the case group presented first distant recurrence in the CNS (34.80%), local recurrence (three patients, 13.04%), lungs (two patients; 8.7%), bone (one patient; 4.34%) and other locations (seven patients; 30.38%). In the control group, first distant recurrence occurred locally (six patients; 46.1%), in bone (two patients; 15.4%), lungs (one patient; 7.7%) and other sites (four patients; 23.1%). RNA was successfully obtained from 53 out of 60 samples. PTGS2, HBEGF, and ST6GALNAC5 expression values were not related to metastasis location. TN tumours frequently metastasise to the visceral organs, particularly lungs and brain, and are less common in bone. The literature suggests that expression of the three genes of interest (PTGS2, HBEGF, and ST6GALNAC5) could be different in TNBC patients with CNS metastasis when compared to patients without it. We did not find a differential expression pattern in PTGS2, HBEGF, and ST6GALNAC5 genes in primary TNBC showing CNS metastases. Further studies are needed to clarify the role of these genes in CNS metastases in TNBC patients.

Impact of breast cancer subtypes and patterns of metastasis on outcome.

PubMed

Kast, Karin; Link, Theresa; Friedrich, Katrin; Petzold, Andrea; Niedostatek, Antje; Schoffer, Olaf; Werner, Carmen; Klug, Stefanie J; Werner, Andreas; Gatzweiler, Axel; Richter, Barbara; Baretton, Gustavo; Wimberger, Pauline

2015-04-01

Clinical outcome of patients with stage IV breast cancer is dependent on tumor biology, extent, and localization of metastases. Routine imaging diagnostics for distant metastasis is not recommended by the national guidelines for breast cancer follow-up. In this study, we evaluated different patterns of metastases of cancer subtypes in order to generate hypotheses on individualization of follow-up after breast cancer in the adjuvant setting. Patients of the Regional Breast Cancer Center Dresden diagnosed within the years 2006-2011 were classified into the five intrinsic subtypes luminal A (ER+, Her2-, G1/2), luminal B/Her2 negative (ER+, Her2-, G3), triple positive (ER+, PR+, Her2+), Her2-enriched (ER-, Her2+), and triple negative (ER-, PR-, Her2-) and with a median follow-up of 45 months. Tumor stage at time of first diagnosis of breast cancer as well as time and site of metastasis at first diagnosis of distant metastatic disease was analyzed. Tumor specimen of 2284 female patients with primary breast cancer was classified into five subtypes. Distant recurrence-free survival at 3 years was most unfavorable in Her2-enriched (66.8 %), triple negative (75.9 %), and triple-positive breast cancer (81.7 %). The same subtypes most frequently presented with visceral metastases only at first presentation: Her2-enriched 46.9 %, triple negative 45.5 %, and triple-positive breast cancer 37.5 %. Longest median survival of 2.3 years was seen in luminal A and in Her2-enriched metastatic disease, respectively. Median survival was significantly better in the luminal A, Her2-enriched, and triple-positive subtype compared to triple-negative breast cancer (p < 0.005). Differences in time to metastatic disease, first localization of metastases, and overall survival after diagnosis of metastatic disease were shown. Considering new targeted therapies and the option of surgery of oligometastases, screening for visceral metastases might be reasonable after diagnosis of Her2-positive subtypes.

Global-scale profiling of differential expressed lysine acetylated proteins in colorectal cancer tumors and paired liver metastases.

PubMed

Shen, Zhanlong; Wang, Bo; Luo, Jianyuan; Jiang, Kewei; Zhang, Hui; Mustonen, Harri; Puolakkainen, Pauli; Zhu, Jun; Ye, Yingjiang; Wang, Shan

2016-06-16

Lysine acetylated modification was indicated to impact colorectal cancer (CRC)'s distant metastasis. However, the global acetylated proteins in CRC and the differential expressed acetylated proteins and acetylated sites between CRC primary and distant metastatic tumor remains unclear. Our aim was to construct a complete atlas of acetylome in CRC and paired liver metastases. Combining high affinity enrichment of acetylated peptides with high sensitive mass spectrometry, we identified 603 acetylation sites from 316 proteins, among which 462 acetylation sites corresponding to 243 proteins were quantified. We further classified them into groups according to cell component, molecular function and biological process and analyzed the metabolic pathways, domain structures and protein interaction networks. Finally, we evaluated the differentially expressed lysine acetylation sites and revealed that 31 acetylated sites of 22 proteins were downregulated in CRC liver metastases compared to that in primary CRC while 40 acetylated sites of 32 proteins were upregulated, of which HIST2H3AK19Ac and H2BLK121Ac were the acetylated histones most changed, while TPM2 K152Ac and ADH1B K331Ac were the acetylated non-histones most altered. These results provide an expanded understanding of acetylome in CRC and its distant metastasis, and might prove applicable in the molecular targeted therapy of metastatic CRC. This study described provides, for the first time, that full-scale profiling of lysine acetylated proteins were identified and quantified in colorectal cancer (CRC) and paired liver metastases. The novelty of the study is that we constructed a complete atlas of acetylome in CRC and paired liver metastases. Moreover, we analyzed these differentially expressed acetylated proteins in cell component, molecular function and biological process. In addition, metabolic pathways, domain structures and protein interaction networks of acetylated proteins were also investigated. Our approaches shows that of the differentially expressed proteins, HIST2H3AK19Ac and H2BLK121Ac were the acetylated histones most changed, while TPM2 K152Ac and ADH1B K331Ac were the acetylated non-histones most altered. Our findings provide an expanded understanding of acetylome in CRC and its distant metastasis, and might prove applicable in the molecular targeted therapy of metastatic CRC. Copyright © 2016 Elsevier B.V. All rights reserved.

The advantages of subtotal thyroidectomy and suppression of TSH in the primary treatment of papillary carcinoma of the thyroid

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

Crile, G. Jr.; Antunez, A.R.; Esselstyn, C.B. Jr.

1985-06-01

Patients between the ages of 6 and 45 years with distant metastases from papillary carcinoma of the thyroid can be treated as effectively by subtotal thyroidectomy and suppressive doses of thyroid hormone as by total thyroidectomy followed by treatment with iodine 131 (/sup 131/I). Moreover, distant metastases can be treated by either /sup 131/I or suppression as effectively after they are apparent on x-ray as they can be when treated in a subclinical stage. Therefore, in patients younger than 45 years old it is rarely necessary to perform a total thyroidectomy or to do frequent postoperative scans. In patients oldermore » than 44 or younger than 7 who have distant metastases or extensive involvement of both lobes, total or almost total thyroidectomy is justified if it can be done with minimal morbidity. In patients of this age group whose tumors fail to respond to suppressive doses of thyroid, /sup 131/I should be used. In view of the importance of diagnostic related groups (DRG) to the economy of hospitals, we note that the cost of total thyroidectomy, ablation by /sup 131/I, and intermittent body scans is at least three times that of less radical procedures which, in conjunction with suppression by thyroid feeding, give the same survival with less morbidity.« less

Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma From the Time of First Metastasis.

PubMed

Kuk, Deborah; Shoushtari, Alexander N; Barker, Christopher A; Panageas, Katherine S; Munhoz, Rodrigo R; Momtaz, Parisa; Ariyan, Charlotte E; Brady, Mary Sue; Coit, Daniel G; Bogatch, Kita; Callahan, Margaret K; Wolchok, Jedd D; Carvajal, Richard D; Postow, Michael A

2016-07-01

Subtypes of melanoma, such as mucosal, uveal, and acral, are believed to result in worse prognoses than nonacral cutaneous melanoma. After a diagnosis of distant metastatic disease, however, the overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma has not been directly compared. We conducted a single-center, retrospective analysis of 3,454 patients with melanoma diagnosed with distant metastases from 2000 to 2013, identified from a prospectively maintained database. We examined melanoma subtype, date of diagnosis of distant metastases, age at diagnosis of metastasis, gender, and site of melanoma metastases. Of the 3,454 patients (237 with mucosal, 286 with uveal, 2,292 with nonacral cutaneous, 105 with acral cutaneous, and 534 with unknown primary melanoma), 2,594 died. The median follow-up was 46.1 months. The median overall survival for those with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma was 9.1, 13.4, 11.4, 11.7, and 10.4 months, respectively. Patients with uveal melanoma, cutaneous melanoma (acral and nonacral), and unknown primary melanoma had similar survival, but patients with mucosal melanoma had worse survival. Patients diagnosed with metastatic melanoma in 2006-2010 and 2011-2013 had better overall survival than patients diagnosed in 2000-2005. In a multivariate model, patients with mucosal melanoma had inferior overall survival compared with patients with the other four subtypes. Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting. Despite distinct tumor biology, the survival was similar for those with metastatic uveal melanoma, acral, nonacral cutaneous, and unknown primary melanoma. Uveal, acral, and mucosal melanoma are assumed to result in a worse prognosis than nonacral cutaneous melanoma or unknown primary melanoma. No studies, however, have been conducted assessing the overall survival of patients with these melanoma subtypes starting at the time of distant metastatic disease. The present study found that patients with uveal, acral, nonacral cutaneous, and unknown primary melanoma have similar overall survival after distant metastases have been diagnosed. These findings provide information for oncologists to reconsider previously held assumptions and appropriately counsel patients. Patients with mucosal melanoma have worse overall survival and are thus a group in need of specific research and advocacy. ©AlphaMed Press.

Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma From the Time of First Metastasis

PubMed Central

Kuk, Deborah; Shoushtari, Alexander N.; Barker, Christopher A.; Panageas, Katherine S.; Munhoz, Rodrigo R.; Momtaz, Parisa; Ariyan, Charlotte E.; Brady, Mary Sue; Coit, Daniel G.; Bogatch, Kita; Callahan, Margaret K.; Wolchok, Jedd D.; Carvajal, Richard D.

2016-01-01

Background. Subtypes of melanoma, such as mucosal, uveal, and acral, are believed to result in worse prognoses than nonacral cutaneous melanoma. After a diagnosis of distant metastatic disease, however, the overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma has not been directly compared. Materials and Methods. We conducted a single-center, retrospective analysis of 3,454 patients with melanoma diagnosed with distant metastases from 2000 to 2013, identified from a prospectively maintained database. We examined melanoma subtype, date of diagnosis of distant metastases, age at diagnosis of metastasis, gender, and site of melanoma metastases. Results. Of the 3,454 patients (237 with mucosal, 286 with uveal, 2,292 with nonacral cutaneous, 105 with acral cutaneous, and 534 with unknown primary melanoma), 2,594 died. The median follow-up was 46.1 months. The median overall survival for those with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma was 9.1, 13.4, 11.4, 11.7, and 10.4 months, respectively. Patients with uveal melanoma, cutaneous melanoma (acral and nonacral), and unknown primary melanoma had similar survival, but patients with mucosal melanoma had worse survival. Patients diagnosed with metastatic melanoma in 2006–2010 and 2011–2013 had better overall survival than patients diagnosed in 2000–2005. In a multivariate model, patients with mucosal melanoma had inferior overall survival compared with patients with the other four subtypes. Conclusion. Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting. Despite distinct tumor biology, the survival was similar for those with metastatic uveal melanoma, acral, nonacral cutaneous, and unknown primary melanoma. Implications for Practice: Uveal, acral, and mucosal melanoma are assumed to result in a worse prognosis than nonacral cutaneous melanoma or unknown primary melanoma. No studies, however, have been conducted assessing the overall survival of patients with these melanoma subtypes starting at the time of distant metastatic disease. The present study found that patients with uveal, acral, nonacral cutaneous, and unknown primary melanoma have similar overall survival after distant metastases have been diagnosed. These findings provide information for oncologists to reconsider previously held assumptions and appropriately counsel patients. Patients with mucosal melanoma have worse overall survival and are thus a group in need of specific research and advocacy. PMID:27286787

Cardiac metastases of Ewing sarcoma detected by 18F-FDG PET/CT.

PubMed

Coccia, Paola; Ruggiero, Antonio; Rufini, Vittoria; Maurizi, Palma; Attinà, Giorgio; Marano, Riccardo; Natale, Luigi; Leccisotti, Lucia; Calcagni, Maria L; Riccardi, Riccardo

2012-04-01

Positron emission tomography (PET) is widely used in the diagnostic evaluation and staging of different malignant tumors. The role of PET/computed tomographic scan in detecting distant metastases in the workup of Ewing sarcoma in children or young adults is less well defined. We report a case of a boy affected by a metastatic Ewing sarcoma with cardiac asymptomatic metastasis detected by F-FDG PET/computed tomography.

Metastatic hidradenocarcinoma: Surgery and chemotherapy.

PubMed

Amel, Trabelsi; Olfa, Gharbi; Faten, Hammedi; Makrem, Hochlef; Slim, Ben Ahmed; Moncef, Mokni

2009-12-01

Hidradenocarcinoma is a rare carcinoma of high malignant potential. It most metastasizes to regional lymph nodes and distant viscera. We report a case of 52-year-old woman who presented with an invasive hidradenocarcinoma of the finger, treated with surgical excision. The patient presented with skin and lymph node metastases four years after, treated by chemotherapy. Hidradenocarcinoma is an aggressive tumor. It seems important to use adjuvant therapies particularly for recurrent and metastatic forms.

Infrequent Loss of Luminal Differentiation in Ductal Breast Cancer Metastasis

PubMed Central

Calvo, Julia; Sánchez-Cid, Lourdes; Muñoz, Montserrat; Lozano, Juan José; Thomson, Timothy M.; Fernández, Pedro L.

2013-01-01

Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and –positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes. PMID:24205108

Clear cell hidradenocarcinoma of the ear helix: report of primary ear helix adnexal carcinoma with regional lymph node metastasis.

PubMed

Bae, Tae Hui; Kang, Shin Hyuk; Kim, Han Koo; Kim, Woo Seob; Kim, Mi Kyung

2014-07-01

Clear cell hidradenocarcinoma is a rare tumor of eccrine sweat gland origin that has a predilection for the head and neck. It has an indolent growth pattern and a higher incidence of regional and distant metastases. Metastasizing adnexal carcinomas are rare; thus, currently there is no uniform treatment guideline. We report a case of an 89-year-old female patient with clear cell hidradenocarcinoma manifesting in the right ear helix that metastasized to the right parotid gland who was treated by wide local excision and radiation therapy.

Unexpected metastatic pheochromocytoma - an unusual presentation.

PubMed

Birrenbach, Tanja; Stanga, Zeno; Cottagnoud, Philippe; Stucki, Armin

2008-01-01

The classic triad of pheochromocytoma consists of episodic headache, sweating, and tachycardia. General clinicians should be aware, however, that this rare entity might present with a wide spectrum of clinical symptoms. We recently observed a noteworthy case of malignant pheochromocytoma where there was a lack of specific symptoms despite an advanced tumor stage. Malignancy is an important cause of mortality. Reliable diagnosis of malignancy depends upon evidence of local invasion, distant metastases, or recurrence. As in our case, new scintigraphic methods, such as 111-In-pentetreotide scintigraphy (Octreoscan), may occasionally reveal 123-I-metaiodobenzylguanidine-negative distant metastases and help to establish an early diagnosis of malignancy. Tumor size, and perhaps even biochemical profile, may be factors increasing the likelihood of a malignant process and may contribute to early identification of patients at risk.

Efficacy, safety and outcome of frameless image-guided robotic radiosurgery for brain metastases after whole brain radiotherapy.

PubMed

Lohkamp, Laura-Nanna; Vajkoczy, Peter; Budach, Volker; Kufeld, Markus

2018-05-01

Estimating efficacy, safety and outcome of frameless image-guided robotic radiosurgery for the treatment of recurrent brain metastases after whole brain radiotherapy (WBRT). We performed a retrospective single-center analysis including patients with recurrent brain metastases after WBRT, who have been treated with single session radiosurgery, using the CyberKnife® Radiosurgery System (CKRS) (Accuray Inc., CA) between 2011 and 2016. The primary end point was local tumor control, whereas secondary end points were distant tumor control, treatment-related toxicity and overall survival. 36 patients with 140 recurrent brain metastases underwent 46 single session CKRS treatments. Twenty one patients had multiple brain metastases (58%). The mean interval between WBRT and CKRS accounted for 2 years (range 0.2-7 years). The median number of treated metastases per treatment session was five (range 1-12) with a tumor volume of 1.26 ccm (mean) and a median tumor dose of 18 Gy prescribed to the 70% isodose line. Two patients experienced local tumor recurrence within the 1st year after treatment and 13 patients (36%) developed novel brain metastases. Nine of these patients underwent additional one to three CKRS treatments. Eight patients (22.2%) showed treatment-related radiation reactions on MRI, three with clinical symptoms. Median overall survival was 19 months after CKRS. The actuarial 1-year local control rate was 94.2%. CKRS has proven to be locally effective and safe due to high local tumor control rates and low toxicity. Thus CKRS offers a reliable salvage treatment option for recurrent brain metastases after WBRT.

Outcome Analysis of Patients With Oral Cavity Cancer and Extracapsular Spread in Neck Lymph Nodes

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

Liao, Chun-Ta, E-mail: liaoct@adm.cgmh.org.tw; Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Lee, Li-Yu

Purpose: Extracapsular spread (ECS) in neck lymph nodes is a major adverse prognostic factor in patients with oral cavity squamous cell carcinoma (OSCC). We conducted a retrospective analysis of prognostic factors in this patient group and tried to identify a subset of patients with a worse prognosis suitable for more aggressive therapeutic interventions. Methods and Materials: Enrolled in the study were 255 OSCC patients with ECS in neck nodes and without evidence of distant metastasis. All participants were followed-up for at least 2 years or censored at last follow-up. The 5-year rates of control, distant metastasis, and survival were themore » main outcome measures. Results: Level IV/V lymph node metastases and tumor depth {>=}12 mm were independent predictors of 5-year survival and identified three prognostic groups. In the low-risk group (no level IV/V metastases and tumor depth <12 mm), the 5-year disease-free, disease-specific, and overall survival rates were 60%, 66%, and 50%, respectively. In the intermediate-risk group (no level IV/V metastases and tumor depth {>=}12 mm), the 5-year disease-free, disease-specific, and overall survival rates were 39%, 41%, and 28%, respectively. In the high-risk group (evidence of level IV/V metastases), the 5-year disease-free, disease-specific, and overall survival rates were 14%, 12%, and 10%, respectively. Conclusions: Among OSCC patients with ECS, those with level IV/V metastases appear to have the worst prognosis followed by without level IV/V metastases and tumor depth {>=}12 mm. An aggressive therapeutic approach may be suitable for intermediate- and high-risk patients.« less

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

Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes.

PubMed

Furet, Elise; El Bouchtaoui, Morad; Feugeas, Jean-Paul; Miquel, Catherine; Leboeuf, Christophe; Beytout, Clémentine; Bertheau, Philippe; Le Rhun, Emilie; Bonneterre, Jacques; Janin, Anne; Bousquet, Guilhem

2017-06-06

Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases. Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases. Fifty-two patients with HER2-overexpressing or triple-negative breast carcinoma with lymph nodes and distant metastases were included in this study. Transcriptomic analyses were performed on laser-microdissected tumor cells from 28 metastatic lymph-nodes. Supervised analyses compared the transcriptomic profiles of women who developed brain metastases and those who did not. As a validation series, we studied metastatic lymph-nodes from 24 other patients.Immunohistochemistry investigations showed that p16 mean scores were significantly higher in patients with brain metastases than in patients without (7.4 vs. 1.7 respectively, p < 0.01). This result was confirmed on the validation series. Multivariate analyses showed that the p16 score was the only variable positively associated with the risk of brain metastases (p = 0.01).With the same threshold of 5 for p16 scores using a Cox model, overall survival was shorter in women with a p16 score over 5 in both series. The risk of brain metastases in women with HER2-overexpressing or triple-negative breast cancer could be better assessed by studying p16 protein expression on surgically removed axillary lymph-nodes.

Esophageal Cancer.

PubMed

Short, Matthew W; Burgers, Kristina G; Fry, Vincent T

2017-01-01

Esophageal cancer has a poor prognosis and high mortality rate, with an estimated 16,910 new cases and 15,910 deaths projected in 2016 in the United States. Squamous cell carcinoma and adenocarcinoma account for more than 95% of esophageal cancers. Squamous cell carcinoma is more common in nonindustrialized countries, and important risk factors include smoking, alcohol use, and achalasia. Adenocarcinoma is the predominant esophageal cancer in developed nations, and important risk factors include chronic gastroesophageal reflux disease, obesity, and smoking. Dysphagia alone or with unintentional weight loss is the most common presenting symptom, although esophageal cancer is often asymptomatic in early stages. Physicians should have a low threshold for evaluation with endoscopy if any symptoms are present. If cancer is confirmed, integrated positron emission tomography and computed tomography should be used for initial staging. If no distant metastases are found, endoscopic ultrasonography should be performed to determine tumor depth and evaluate for nodal involvement. Localized tumors can be treated with endoscopic mucosal resection, whereas regional tumors are treated with esophagectomy, neoadjuvant chemotherapy, chemoradiotherapy, or a combination of modalities. Nonresectable tumors or tumors with distant metastases are treated with palliative interventions. Specific prevention strategies have not been proven, and there are no recommendations for esophageal cancer screening.

Post-operative radiation therapy for advanced-stage oropharyngeal cancer.

PubMed

Hansen, Eric; Panwala, Kathryn; Holland, John

2002-11-01

Between 1985 and 1999, 43 patients with locally-advanced, resectable oropharyngeal cancer were treated with combined surgery and post-operative radiation therapy (RT) at Oregon Health and Science University. Five patients (12 per cent) had Stage III disease and 38 patients (88 per cent) had Stage IV disease. All patients had gross total resections of the primary tumour. Thirty-seven patients had neck dissections for regional disease. RT consisted of a mean tumour-bed dose of 63.0 Gy delivered in 1.8-2.0 Gy fractions over a mean of 49 days. At three- and five-years, the actuarial local control was 96 per cent and the actuarial local/regional control was 80 per cent. The three- and five-year actuarial rates of distant metastases were 41 per cent and 46 per cent, respectively. The actuarial overall survival at three- and five-years was 41 per cent and 34 per cent, respectively. The actuarial rates of progression-free survival were 49 per cent at three-years and 45 per cent at five years. Combined surgery and post-operative RT for advanced-stage oropharyngeal cancer results in excellent local/regional control. This particular group of patients experienced a high-rate of developing distant metastases.

Effect of Occult Metastases on Survival in Node-Negative Breast Cancer

PubMed Central

Weaver, Donald L.; Ashikaga, Takamaru; Krag, David N.; Skelly, Joan M.; Anderson, Stewart J.; Harlow, Seth P.; Julian, Thomas B.; Mamounas, Eleftherios P.; Wolmark, Norman

2011-01-01

BACKGROUND Retrospective and observational analyses suggest that occult lymph-node metastases are an important prognostic factor for disease recurrence or survival among patients with breast cancer. Prospective data on clinical outcomes from randomized trials according to sentinel-node involvement have been lacking. METHODS We randomly assigned women with breast cancer to sentinel-lymph-node biopsy plus axillary dissection or sentinel-lymph-node biopsy alone. Paraffin-embedded tissue blocks of sentinel lymph nodes obtained from patients with pathologically negative sentinel lymph nodes were centrally evaluated for occult metastases deeper in the blocks. Both routine staining and immunohistochemical staining for cytokeratin were used at two widely spaced additional tissue levels. Treating physicians were unaware of the findings, which were not used for clinical treatment decisions. The initial evaluation at participating sites was designed to detect all macrometastases larger than 2 mm in the greatest dimension. RESULTS Occult metastases were detected in 15.9% (95% confidence interval [CI], 14.7 to 17.1) of 3887 patients. Log-rank tests indicated a significant difference between patients in whom occult metastases were detected and those in whom no occult metastases were detected with respect to overall survival (P = 0.03), disease-free survival (P = 0.02), and distant-disease–free interval (P = 0.04). The corresponding adjusted hazard ratios for death, any outcome event, and distant disease were 1.40 (95% CI, 1.05 to 1.86), 1.31 (95% CI, 1.07 to 1.60), and 1.30 (95% CI, 1.02 to 1.66), respectively. Five-year Kaplan-Meier estimates of overall survival among patients in whom occult metastases were detected and those without detectable metastases were 94.6% and 95.8%, respectively. CONCLUSIONS Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination; however, the magnitude of the difference in outcome at 5 years was small (1.2 percentage points). These data do not indicate a clinical benefit of additional evaluation, including immunohistochemical analysis, of initially negative sentinel nodes in patients with breast cancer. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003830.) PMID:21247310

Excellent Local Control Rates and Distinctive Patterns of Failure in Myxoid Liposarcoma Treated With Conservation Surgery and Radiotherapy

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

Guadagnolo, B. Ashleigh; Zagars, Gunar K.; Ballo, Matthew T.

2008-03-01

Purpose: To evaluate the local control rates and patterns of metastatic relapse in patients with localized myxoid liposarcoma treated with conservation surgery and radiotherapy (RT). Patients and Methods: Between 1960 and 2003, 127 patients with non-metastatic myxoid liposarcoma were treated with conservation surgery and RT at our institution. The median patient age was 39 years (range, 14-79 years). Of the 127 patients, 46% underwent preoperative RT (median dose, 50 Gy) and 54% underwent postoperative RT (median dose, 60 Gy). Also, 28% received doxorubicin-based chemotherapy as a part of their treatment. Results: The median follow-up was 9.1 years. The overall survivalmore » rate at 5 and 10 years was 87% and 79%, respectively. The corresponding disease-free survival rates were 81% and 73%. The local control rate at {>=}5 years was 97%. The actuarial rate of distant metastases at 5 and 10 years was 15% and 24%, respectively. Of the 27 patients who developed distant metastases, 48% did so in the retroperitoneum, 22% in other extrapulmonary soft tissues, 22% in the lung, 15% in bone, and 4% in the liver. Conclusion: The results of our study have shown that RT and conservation surgery for localized myxoid liposarcoma provide excellent local control. Distant metastatic relapse tended to occur in the retroperitoneum and other nonpulmonary soft tissues. Therefore, staging and surveillance imaging should include the abdomen and pelvis, as well as the thorax, for patients with localized myxoid liposarcoma.« less

Outcomes of uterine cervical cancer patients with pelvic lymph node metastases after radiotherapy without boost irradiation of metastases.

PubMed

Yoshizawa, Eriko; Koiwai, Keiichiro; Ina, Hironobu; Fukazawa, Ayumu; Sakai, Katsuya; Ozawa, Takesumi; Matsushita, Hirohide; Kadoya, Masumi

2017-04-01

The aim of this study was to evaluate the outcomes of uterine cervical cancer patients with pelvic lymph node (PLN) metastases after radiotherapy without boost irradiation of the metastases and to clarify the necessity of the boost irradiation of metastatic lesions. Thirty-two patients with uterine cervical cancer metastasizing only to the PLN were treated with definitive radiotherapy without boost irradiation of the metastases between 2008 and 2012 at our institution and were selected for this study. The pattern of progression, overall survival, and progression-free survival were analyzed. Ninety percent of the PLN metastases were controlled by radiotherapy. Twenty-two of 32 patients (69%) experienced progression. Distant metastases as initial progression were observed in 21 of these 22 patients (95%). Only two patients experienced failures in pre-treatment metastatic PLN as initial progression, along with other failures. Severe late lower gastrointestinal toxicities were not observed in any patients. Two-year cumulative overall survival and progression-free survival were 74% and 31%, respectively. Boost irradiation of PLN metastases is not necessarily indispensable. Further studies to examine the necessity of boost irradiation of PLN metastases in radiotherapy for uterine cervical cancer patients with metastases are required. © 2017 Japan Society of Obstetrics and Gynecology.

Seven fractions to deliver partial breast irradiation: the toxicity is Low.

PubMed

Trovo, Marco; Avanzo, Michele; Vinante, Lorenzo; Furlan, Carlo; Fiorica, Francesco; Perin, Tiziana; Militello, Loredana; Spazzapan, Simon; Berretta, Massimiliano; Jena, Rajesh; Stancanello, Joseph; Piccoli, Erica; Mileto, Mario; Micheli, Elvia; Roncadin, Mario; Massarut, Samuele

2017-05-23

To assess toxicity and clinical outcome, in breast cancer patients treated with external beam partial breast irradiation (PBI) consisting of 35 Gy in 7 daily fractions (5 Gy/fraction). Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old or over and treated with breast conservative surgery for early stage invasive carcinoma. Seventy-three patients were analyzed. Median follow-up was 40 months. The proposed schedule was well tolerated. No Grade 3 toxicity was documented. Late toxicity was assessable for all the treated patients. Two patients (2.7%) developed Grade 2 pain 6 months after PBI. Four patients (5%) developed asymptomatic fat necrosis. Grade 2 fibrosis was observed in 5 patients (6.7%). No correlation was found between early and late toxicity and the type of adjuvant systemic therapy (no therapy vs. hormonal therapy vs. chemotherapy). No statistical correlation between dosimetric parameters and toxicity was found. Patients who developed Grade 2 radiation fibrosis had not higher radiation volumes to the untreated normal breast than those without fibrosis. Cosmesis was judged good/excellent in the majority of the cases (93%). One patient relapsed locally, and one developed distant metastases, corresponding to a 5-year local control and distant metastases-free survival of 98% and 96.7%, respectively. 35 Gy in 7 daily fractions is an effective and well-tolerated regimen to deliver PBI.

Treatment of Vascular Soft Tissue Sarcomas With Razoxane, Vindesine, and Radiation

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

Rhomberg, Walter; Wink, Anna; Pokrajac, Boris

2009-05-01

Purpose: In previous studies, razoxane and vindesine together with radiotherapy was proved to be effective in soft tissue sarcomas (STS). Because razoxane leads to a redifferentiation of pathological tumor blood vessels, it was of particular interest to study the influence of this drug combination in vascular soft tissue sarcomas. Methods and Materials: This open multicenter Phase II study was performed by the Austrian Society of Radiooncology. Among 13 evaluable patients (10 angiosarcomas and 3 hemangio-pericytomas), 9 had unresectable measurable disease, 3 showed microscopic residuals, and 1 had a resection with clear margins. They received a basic treatment with razoxane andmore » vindesine supported by radiation therapy. Outcome measures were objective response rates, survival time, and the incidence of distant metastases. Results: In nine patients with measurable vascular soft tissue sarcomas (eight angiosarcomas and one hemangiopericytoma), 6 complete remissions, 2 partial remissions, and 1 minor remission were achieved, corresponding to a major response rate of 89%. A maintenance therapy with razoxane and vindesine of 1 year or longer led to a suppression of distant metastases. The median survival time from the start of the treatment is 23+ months (range, 3-120+) for 12 patients with macroscopic and microscopic residual disease. The progression-free survival at 6 months was 75%. The combined treatment was associated with a low general toxicity, but attention must be given to increased normal tissue reactions. Conclusions: This trimodal treatment leads to excellent response rates, and it suppresses distant metastases when given as maintenance therapy.« less

Low rates of loco-regional recurrence following extended lymph node dissection for gastric cancer.

PubMed

Muratore, A; Zimmitti, G; Lo Tesoriere, R; Mellano, A; Massucco, P; Capussotti, L

2009-06-01

The study by MacDonald et al. [Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725-30] has reported low loco-regional recurrence rates (19%) after gastric cancer resection and adjuvant radiotherapy. However, the lymph node dissection was often "inadequate". The aim of this retrospective study is to analyse if an extended lymph node dissection (D2) without adjuvant radiotherapy may achieve comparable loco-regional recurrence rates. A prospective database of 200 patients who underwent a curative resection for gastric carcinoma from January 2000 to December 2006 was analysed. D2 lymph node dissection was standard. Recurrences were categorized as loco-regional, peritoneal, or distant. No patients received neoadjuvant or adjuvant radiotherapy. The in-hospital mortality rate was 1% (2 patients). The mean number of dissected lymph nodes was 25.9. Overall and disease-free survival at 5years were 60.7% and 61.2% respectively. During the follow-up, 60 patients (30%) have recurred at 76 sites: 38 (50%) distant metastases, 25 (32.9%) peritoneal metastases, and 13 (17.1%) loco-regional recurrences. The loco-regional recurrence was isolated in 6 patients and associated with peritoneal or distant metastases in 7 patients. The mean time to the first recurrence was 18.9 (95% confidence interval: 15.0-21.9) months. Extended lymph node dissection is safe and warrants low loco-regional recurrence rates.

Surgical treatment of lung metastases in patients with embryonal pediatric solid tumors: an update.

PubMed

Fuchs, Joerg; Seitz, Guido; Handgretinger, Rupert; Schäfer, Juergen; Warmann, Steven W

2012-02-01

Distant metastases regularly occur in children with solid tumors. The most affected organ is the lung. Nearly in all extracranial pediatric solid tumors, the presence of lung metastases is associated with an adverse prognosis for the children. Therefore, the correct treatment of lung metastases is essential and influences the outcome. Despite different national and international trials for pediatric tumor entities, specific surgical aspects or guidelines for lung metastases are usually not addressed thoroughly in these protocols. The aim of this article is to present the diagnostic challenges and principles of surgical treatment by focusing on the influence of surgery on the outcome of children. Special points of interest are discussed that emphasize sarcomas, nephroblastomas, hepatoblastomas, and other tumors. Surgery of lung metastases is safe, has a positive impact on the patients' prognosis, and should be aggressive depending on the tumor entity. An interdisciplinary approach, including pediatric oncology and radiology, is mandatory in any case. Copyright © 2012 Elsevier Inc. All rights reserved.

PREDICTORS OF INFLAMMATORY LOCAL RECURRENCE AFTER BREAST-CONSERVING THERAPY FOR BREAST CANCER: MATCHED CASE-CONTROL STUDY.

PubMed

Akoum, Riad; Abdalla, Eddie K; Saade, Michel; Awdeh, Adnan; Abi-Aad, Fouad; Bejjani, Noha; Ghossain, Antoine; Brihi, Emile; Audi, Akram

2015-01-01

Inflammatory local recurrence (ILR) after breast-conserving surgery for noninflammatory breast cancer (BC) is associated with dismal prognosis. Risk factors for ILR are not well defined. Between 2001 and 2010, twelve patients at our hospital developed ILR after breast-conserving surgery, adjuvant chemotherapy, and radiotherapy for BC. We compared their clinico-pathological characteristics to those of 24 patients with noninflammatory local recurrence (non-ILR), 24 patients with distant metastases, and 48 disease-free controls, matched for age and observation period. The median time to ILR was 10 months. In univariate analysis, extent of lymph node involvement (p < 0.05), multifocality (p < 0.05), c-erbB2 overexpression (p < 0.05), and lymphovascular invasion (LVI) (p < 0.001) affected the risk of ILR. Conditional logistic regression analysis showed a significant association between ILR and combined LVI and high histopathological grade. The odds ratio (OR) for ILR versus non-ILR was 6.14 (95% confidence interval [CI] 1.48-25.38) and for ILR versus distant metastases it was 3.05 (95% CI 0.09-97.83) when both LVI and high histopathological grade were present. Patients with family history of BC were more likely to present with ILR than non-ILR (OR 5.47; 95% CI 1.55-19.31) or distant relapse (OR 5.62; 95% CI 0.26-119.95). Pre- and postmenopausal women with high-grade BC and LVI are at increased risk to develop ILR, especially in the presence of family history of BC. Identification of risk factors for this lethal form of recurrent BC may lead to more effective preventive treatment strategies in properly selected patients.

Merkel Cell Carcinoma: 27-Year Experience at the Peter MacCallum Cancer Centre

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

Hui, Andrew C., E-mail: achui@bigpond.net.au; Stillie, Alison L.; Seel, Matthew

2011-08-01

Purpose: To retrospectively evaluate the treatment outcome of patients with Merkel cell carcinoma after local and/or regional treatment. Methods and Materials: Patients presenting to our center between January 1980 and July 2006 with Merkel cell carcinoma and without distant metastases were reviewed. The primary endpoint was locoregional control. Secondary endpoints were distant recurrence, survival and treatment toxicity. Results: A total of 176 patients were identified. The median age was 79 years. The median follow-up was 2.2 years for all patients and 3.9 years for those alive at the last follow-up visit. The most common primary site was the head andmore » neck (56%), and 62 patients(35%) had regional disease at presentation. The initial surgery to the primary tumor involved (wide) local excision in 140 patients and biopsy only in 28 patients (8 patients had no identifiable primary tumor); 33 patients underwent nodal surgery. Of the 176 patients, 165 (94%) underwent radiotherapy (RT) and 29 of them also underwent concurrent chemotherapy. The median radiation dose was 50 Gy (range, 18-60). Locoregional recurrence developed in 33 patients(19%), with a median interval to recurrence of 8 months. Distant metastases developed in 43 patients(24%). Age, primary tumor size, and RT (no RT vs. <45 Gy vs. {>=}45 Gy) were predictive of locoregional control on univariate analysis. However, only RT remained significant on multivariate analysis. The estimated 5-year actuarial rate for locoregional control, progression-free survival, and overall survival was 76%, 60%, and 45%, respectively. Conclusion: The locoregional control rate for Merkel cell carcinoma in our study was comparable to those from other series using combined modality treatment with RT an integral part of treatment.« less

Tumor attributes predicting cutaneous metastatic destiny: a report of two interesting cases.

PubMed

Gurumurthi, Ravichandran; Thirumalai, Raja; Easow, Jose M; Mohan, Subhashini

2014-07-01

Cutaneous metastases are the result of complex interaction between the tumor cells ("seed") and the host environment ("soil"). Metastases to the skin can be an early sign of internal malignancy or represent recurrence of the primary tumor and portends a poorer prognosis. Invasion and metastasis are the hallmarks of on cogenesis. Skin is the largest organ in the body, but the incidence of metastases is low. With advances in molecular biology, factors responsible for the initiation and perpetuation of metastatic tumor cells at distant sites are being elucidated. The concept of "pre-metastatic niche" and interaction between various chemokines has given a new outlook in understanding the organ specificity of metastatic tumor cells. We present two cases of cutaneous metastases with interesting clinical findings correlating with its biologic subtypes.

Characterisation of the triple negative breast cancer phenotype associated with the development of central nervous system metastases

PubMed Central

Laimito, Katerin Rojas; Gámez-Pozo, Angelo; Sepúlveda, Juan; Manso, Luis; López-Vacas, Rocío; Pascual, Tomás; Fresno Vara, Juan A; Ciruelos, Eva

2016-01-01

Aims Breast cancer (BC) is the most frequent tumour in women, representing 20–30% of all malignancies, and continues to be the leading cause of cancer deaths among European women. Triple-negative (TN) BC biological aggressiveness is associated with a higher dissemination rate, with central nervous system (CNS) metastases common. This study aims to elucidate the association between gene expression profiles of PTGS2, HBEGF and ST6GALNAC5 and the development of CNS metastases in TNBC. Methods This is a case-controlled retrospective study comparing patients (pts) with CNS metastases versus patients without them after adjuvant treatment. The selection of the samples was performed including 30 samples in both case and control groups. Formalin-fixed, paraffin-embedded samples were retrieved from the Hospital 12 de Octubre Biobank. Five 10 µm sections from each FFPE sample were deparaffinised with xylene and washed with ethanol, and the RNA was then extracted with the RecoverAll Kit (Ambion). Gene expression was assessed using TaqMan assays. Results A total of 53 patients were included in the study. The average age was 55 years (range 25–85). About 47 patients (88.67%) had ductal histology and presented high grade (III) tumours (40 patients; 75.47%). Eight women in the case group presented first distant recurrence in the CNS (34.80%), local recurrence (three patients, 13.04%), lungs (two patients; 8.7%), bone (one patient; 4.34%) and other locations (seven patients; 30.38%). In the control group, first distant recurrence occurred locally (six patients; 46.1%), in bone (two patients; 15.4%), lungs (one patient; 7.7%) and other sites (four patients; 23.1%). RNA was successfully obtained from 53 out of 60 samples. PTGS2, HBEGF, and ST6GALNAC5 expression values were not related to metastasis location. Conclusion TN tumours frequently metastasise to the visceral organs, particularly lungs and brain, and are less common in bone. The literature suggests that expression of the three genes of interest (PTGS2, HBEGF, and ST6GALNAC5) could be different in TNBC patients with CNS metastasis when compared to patients without it. We did not find a differential expression pattern in PTGS2, HBEGF, and ST6GALNAC5 genes in primary TNBC showing CNS metastases. Further studies are needed to clarify the role of these genes in CNS metastases in TNBC patients. PMID:27170832

Metastatic hidradenocarcinoma: Surgery and chemotherapy

PubMed Central

Amel, Trabelsi; Olfa, Gharbi; Faten, Hammedi; Makrem, Hochlef; Slim, Ben Ahmed; Moncef, Mokni

2009-01-01

Context: Hidradenocarcinoma is a rare carcinoma of high malignant potential. It most metastasizes to regional lymph nodes and distant viscera. Case report: We report a case of 52-year-old woman who presented with an invasive hidradenocarcinoma of the finger, treated with surgical excision. The patient presented with skin and lymph node metastases four years after, treated by chemotherapy. Conclusion: Hidradenocarcinoma is an aggressive tumor. It seems important to use adjuvant therapies particularly for recurrent and metastatic forms. PMID:22666726

Primary clear cell carcinoma of parotid gland: Case report and review of literature.

PubMed

Rodríguez, Marta Saldaña; Reija, Maria Fe García; Rodilla, Irene González

2013-01-01

Clear cell carcinoma (CCC) is a rare low-grade carcinoma that represents only 1% to 2% of all salivary glands tumors. The finding of a clear cell tumor in a parotid gland involves the necessity of differential diagnosis between primary clear cell parotid tumors and metastases, mainly from kidney. The biological behavior is not very aggressive and development, which is very slow, is usually asymptomatic and indeed, the tumor often reaches considerable dimensions before being diagnosed. The treatment of choice is the surgical excision. There are rare cases of local recurrence and distant metastases. The aim of this article is to report a primary CCC in the parotid gland that microscopically closely resembled a metastatic CCC of renal origin, making microscopic differentiation difficult.

Primary clear cell carcinoma of parotid gland: Case report and review of literature

PubMed Central

Rodríguez, Marta Saldaña; Reija, Maria Fe García; Rodilla, Irene González

2013-01-01

Clear cell carcinoma (CCC) is a rare low-grade carcinoma that represents only 1% to 2% of all salivary glands tumors. The finding of a clear cell tumor in a parotid gland involves the necessity of differential diagnosis between primary clear cell parotid tumors and metastases, mainly from kidney. The biological behavior is not very aggressive and development, which is very slow, is usually asymptomatic and indeed, the tumor often reaches considerable dimensions before being diagnosed. The treatment of choice is the surgical excision. There are rare cases of local recurrence and distant metastases. The aim of this article is to report a primary CCC in the parotid gland that microscopically closely resembled a metastatic CCC of renal origin, making microscopic differentiation difficult. PMID:23798840

Intracranial Epidural Metastases of Adrenal Pheochromocytoma: A Rare Entity.

PubMed

Boettcher, Lillian B; Abou-Al-Shaar, Hussam; Ravindra, Vijay M; Horn, Jeffrey; Palmer, Cheryl Ann; Menacho, Sarah T

2018-06-01

Pheochromocytomas are uncommon neuroendocrine tumors of the adrenal medulla. Malignant behavior is seen in approximately 10% of these lesions, evidenced by distant metastasis to sites without chromaffin tissue. Here we report a rare case of intracranial epidural metastases of an adrenal pheochromocytoma in a 24-year-old man. The patient originally presented at age 10 years with adrenal pheochromocytoma and subsequently developed extensive metastatic bone and lung disease. He was monitored in the intervening years until recent imaging demonstrated an enlarging right parietal mass. On surgical resection of the parietal lesion, the tumor was highly vascularized and confined to the epidural space. To the best of our knowledge, this is the first reported case of metastatic epidural spread of pheochromocytoma without concomitant subdural or intraparenchymal extension. Copyright © 2018 Elsevier Inc. All rights reserved.

[Surgical treatment of metastases and its impact on prognosis in patients with metastatic colorectal carcinoma].

PubMed

Sevčíková, K; Ušáková, V; Bartošová, Z; Sabol, M; Ondrušová, M; Ondruš, D; Spánik, S

2014-01-01

Approximately one quarter of patients with colorectal carcinoma (CRC) have distant metastases at initial dia-gnosis and almost 50% will develop them during the disease course. Only radical surgical resection of metastases improves clinical outcome and offers a chance of longterm survival. Initially unresectable metastases can become resectable after downsizing with systemic therapy. Retrospective analysis included 21 patients with metastatic colorectal carcinoma (mCRC) who were treated from 2006 to 2012 and underwent resection/ ablation of metastases. Fourteen patients had resection at initial dia-gnosis of metastatic disease and seven patients achieved operability of metastases after systemic treatment. The aim of the analysis was to evaluate surgical treatment of metastases and its impact on prognosis in patients with mCRC in correlation with clinical pathological  genetic factors. The median age of patients was 59 years. Fourteen patients had metastases in the liver, one patient had metastases in the lungs, two patients had combination of hepatic and extrahepatic metastases and four patients had metastases in other regions. During median followup of 47 months, 17 patients experienced disease progression and 13 patients died. Median progression free survival (PFS) after surgical resection/ ablation of metastases was 17 months (95% CI 13.8820.12), and median overall survival (OS) was 48 months (95% CI 38.7757.23). KRAS mutation was detected in 47.6% of patients and BRAF mutation in 9.5% of patients. Patients with BRAF mutation had worse PFS (median = 10 months vs 17 months; p = 0.523) and OS (median = 22 months vs 51 months; p = 0.05) compared to patients with BRAF wildtype. No difference was observed in PFS and OS between the patients with one or more metastatic lesions and between the patients who underwent resection/ ablation of metastases initially or after systemic treatment. These data suggest that resection/ ablation of metastases significantly improves prognosis of patients with mCRC and support the notion that mutated BRAF has a strong negative prognostic significance also in the group of patients, who undergo surgical resection/ ablation of metastatic lesions.

US surveillance of regional lymph node recurrence after breast cancer surgery.

PubMed

Moon, Hee Jung; Kim, Min Jung; Kim, Eun-Kyung; Park, Byeong-Woo; Youk, Ji Hyun; Kwak, Jin Young; Sohn, Joohyuk; Kim, Seung-Il

2009-09-01

To determine the diagnostic indexes of lymph node ultrasonography (US) of the axillary and supraclavicular regions for detecting lymph node recurrence (LNR) after breast cancer surgery and assess the effect of lymph node evaluation on prognosis during bilateral breast US. Institutional review board approved this retrospective study and waived informed consent. Between January 2003 and December 2004, 3982 lymph node US examinations, including bilateral axillary and supraclavicular areas, were performed in 1817 women (mean age, 49.9 years; range, 22-86 years) after breast cancer surgery, nine of whom had palpable lesions. Final diagnosis was based on cytopathologic results, clinical follow-up, and imaging studies for at least 12 months after breast US. Diagnostic indexes of US for detecting LNR were assessed. The frequency of distant metastases between patients with ipsilateral LNR and those without was compared. Three-year mortality rates of patients with ipsilateral LNR only and those with distant metastases were evaluated. Of 1817 patients, 54 had suspicious LNR at US (28 at first, 20 at second, five at third, and one at fourth US examination). Thirty-nine of 1817 patients (2.1%), including nine with palpable lesions, had LNR, 11 of whom had ipsilateral LNR only. At first lymph node US, LNR was detected in 17 patients; at second, in 10; at third, in two; and at fourth, in one. Nine had false-negative results. The respective sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of lymph node US for detecting LNR per woman was 76.9% (30 of 39), 98.7% (1754 of 1778), 98.2% (1784 of 1817), 55.6% (30 of 54), and 99.5% (1754 of 1763); those of first lymph node US were 85.0% (17 of 20), 99.4% (1786 of 1797), 99.2% (1803 of 1817), 60.7% (17 of 28), and 99.8% (1786 of 1789); and those of total US examinations were 78.0% (32 of 41), 99.4% (3917 of 3941), 99.2% (3949 of 3982), 57.1% (32 of 56), and 99.8% (3917 of 3926). Distant metastases were found more frequently in patients with ipsilateral LNR (62%) than in those without (2.3%) (P < .0001). The 3-year mortality rate of patients with ipsilateral LNR only was significantly lower than that in patients with distant metastases (P = .03). Ipsilateral LNR is a predictor of distant metastasis, and lymph node evaluation during breast US is useful for early detection of LNR in asymptomatic patients.

Regional lymph node metastases are a strong risk factor for venous thromboembolism: results from the Vienna Cancer and Thrombosis Study

PubMed Central

Dickmann, Boris; Ahlbrecht, Jonas; Ay, Cihan; Dunkler, Daniela; Thaler, Johannes; Scheithauer, Werner; Quehenberger, Peter; Zielinski, Christoph; Pabinger, Ingrid

2013-01-01

Advanced cancer is a risk factor for venous thromboembolism. However, lymph node metastases are usually not considered an established risk factor. In the framework of the prospective, observational Vienna Cancer and Thrombosis Study we investigated the association between local (N0), regional (N1–3), and distant (M1) cancer stages and the occurrence of venous thromboembolism. Furthermore, we were specifically interested in the relationship between stage and biomarkers that have been reported to be associated with venous thromboembolism. We followed 832 patients with solid tumors for a median of 527 days. The study end-point was symptomatic venous thromboembolism. At study inclusion, 241 patients had local, 138 regional, and 453 distant stage cancer. The cumulative probability of venous thromboembolism after 6 months in patients with local, regional and distant stage cancer was 2.1%, 6.5% and 6.0%, respectively (P=0.002). Compared to patients with local stage disease, patients with regional and distant stage disease had a significantly higher risk of venous thromboembolism in multivariable Cox-regression analysis including age, newly diagnosed cancer (versus progression of disease), surgery, radiotherapy, and chemotherapy (regional: HR=3.7, 95% CI: 1.5–9.6; distant: HR=5.4, 95% CI: 2.3–12.9). Furthermore, patients with regional or distant stage disease had significantly higher levels of D-dimer, factor VIII, and platelets, and lower hemoglobin levels than those with local stage disease. These results demonstrate an increased risk of venous thromboembolism in patients with regional disease. Elevated levels of predictive biomarkers in patients with regional disease underpin the results and are in line with the activation of the hemostatic system in the early phase of metastatic dissemination. PMID:23585523

Aberrant Cx43 Expression and Mislocalization in Metastatic Human Melanomas.

PubMed

Alaga, Katanya C; Crawford, Melissa; Dagnino, Lina; Laird, Dale W

2017-01-01

At present, it is unclear if melanocytes contain Cx43 gap junctions and whether Cx43 expression is regulated in melanoma onset and progression. To this end, we cultured pure populations of mouse melanocytes and found that they had no detectable Cx43 and exhibited an inability for dye transfer indicating they were devoid of functional gap junctions. Given the evidence that melanomas acquire the expression of other connexin isoforms during tumor progression, we assessed if Cx43 was also expressed and assembled into gap junctions at any stage of human melanoma onset and progression to distant metastases. Nearly all primary melanomas within the epidermis lacked Cx43. In contrast, nodal metastases expressed low levels of Cx43 which was markedly higher in distant metastases that had invaded vital organs. Importantly, in all stages of melanoma progression, Cx43 could be detected in intracellular compartments but was rarely assembled into gap junctions indicative of functional gap junction channels. Overall, these studies suggest that melanocytes do not form Cx43 homocellular gap junctions and even though Cx43 levels increase during melanoma progression, this connexin rarely assembles into gap junction structures.

Aberrant Cx43 Expression and Mislocalization in Metastatic Human Melanomas

PubMed Central

Alaga, Katanya C.; Crawford, Melissa; Dagnino, Lina; Laird, Dale W.

2017-01-01

At present, it is unclear if melanocytes contain Cx43 gap junctions and whether Cx43 expression is regulated in melanoma onset and progression. To this end, we cultured pure populations of mouse melanocytes and found that they had no detectable Cx43 and exhibited an inability for dye transfer indicating they were devoid of functional gap junctions. Given the evidence that melanomas acquire the expression of other connexin isoforms during tumor progression, we assessed if Cx43 was also expressed and assembled into gap junctions at any stage of human melanoma onset and progression to distant metastases. Nearly all primary melanomas within the epidermis lacked Cx43. In contrast, nodal metastases expressed low levels of Cx43 which was markedly higher in distant metastases that had invaded vital organs. Importantly, in all stages of melanoma progression, Cx43 could be detected in intracellular compartments but was rarely assembled into gap junctions indicative of functional gap junction channels. Overall, these studies suggest that melanocytes do not form Cx43 homocellular gap junctions and even though Cx43 levels increase during melanoma progression, this connexin rarely assembles into gap junction structures. PMID:28607585

Recurrent dermatofibrosarcoma protuberans with pulmonary metastases presenting twelve years after initial diagnosis: 18F-FDG PET/CT imaging findings.

PubMed

Suman, Sudhir; Sharma, Punit; Jain, Tarun Kumar; Sahoo, Manas Kumar; Bal, Chandrasekhar; Kumar, Rakesh

2014-01-01

Dermatofibrosarcoma protuberans is a rare cutaneous tumor that is locally aggressive and has a high rate of recurrence after surgical excision. The tumor grows slowly, typically over years. On rare occasions, metastasis to distant sites (especially the lung) or regional lymph nodes may occur. Here, we present F-FDG PET/CT imaging findings of a 52-year-old man with a local recurrence of dermatofibrosarcoma protuberans in the anterior abdominal wall with metastases to bilateral lungs.

Sentinel lymph node biopsy in thick malignant melanoma: A 16-year single unit experience.

PubMed

Hunger, Robert E; Michel, Aude; Seyed Jafari, S Morteza; Shafighi, Maziar

2015-01-01

The role of sentinel lymph node biopsy (SLNB) and its benefits in patients with thick melanoma is still controversial. We evaluated the clinical effect of SLNB in patients with thick melanoma. We performed a retrospective cohort review (1996-2012) of thick melanomas. Collected data included the patient and tumour characteristics. Locoregional recurrence, distant metastases, disease free and overall survival were compared between the patients with positive and negative SLNB. 126 thick melanomas with a mean age of 64.09 years were included in the study. Positive SLNB were found in 47 (37.3%) patients. Significantly more locoregional recurrence (P = 0.002) and distant metastases (P = 0.030) were detected in the patients with positive SLNB. Furthermore, the patients with negative SLNB showed significantly better disease free survival (P = 0.021). Positive SLNB might be prognostic factor in thick melanoma and aggravates the outcome of thick melanomas.

Colonic metastasis from carcinoma of the breast that mimics a primary intestinal cancer.

PubMed

Uygun, Kazim; Kocak, Zafer; Altaner, Semsi; Cicin, Irfan; Tokatli, Fusun; Uzal, Cem

2006-08-31

Although the lung, liver, or bones are the most common location for distant metastases in breast cancer patients, metastases to the intestinal tract are very rarely recognized in the clinic. We will present an unusual case of colonic metastasis from a carcinoma of the breast that mimics a primary intestinal cancer, along with a through review of English language medical literature. Despite the fact that isolated gastrointestinal (GI) metastases are very rare and much less common than benign disease processes or second primaries of the intestinal tract in patients with a history of breast cancer, metastatic disease should be given consideration whenever a patient experiences GI symptoms.

A unique case of ovarian psammocarcinoma with mediastinal, pulmonary, subcutaneous, and omental metastases.

PubMed

Chase, Daniel M; Sparks, Dorothy A; Gener, Melissa; Smith, James

2009-08-01

Psammocarcinoma is a rare form of serous ovarian and peritoneal carcinoma, characterized by abundant psammoma bodies, invasiveness, and low-grade cytological features. Many of the cases which have been reported had extraovarian spread and peritoneal seeding at the time of presentation. We present a case of 45-year-old woman with ovarian psammocarcinoma who initially presented with a metastatic subcutaneous nodule, and was found to have pulmonary and mediastinal metastases. We believe this to be the first report of a psammocarcinoma with these metastases. Ovarian and peritoneal psammocarcinomas are quite rare, and because of this, knowledge of their behavior is limited. Although most seem to follow an indolent course similar to that of borderline lesions of the ovary, this case demonstrates that some of these tumors may be clinically aggressive with distant metastases.

Brain Metastases in Newly Diagnosed Breast Cancer: A Population-Based Study.

PubMed

Martin, Allison M; Cagney, Daniel N; Catalano, Paul J; Warren, Laura E; Bellon, Jennifer R; Punglia, Rinaa S; Claus, Elizabeth B; Lee, Eudocia Q; Wen, Patrick Y; Haas-Kogan, Daphne A; Alexander, Brian M; Lin, Nancy U; Aizer, Ayal A

2017-08-01

Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking. To characterize the incidence proportions and median survivals of patients with breast cancer and brain metastases at the time of cancer diagnosis. Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Data were stratified by subtype, age, sex, and race. Multivariable logistic and Cox regression were performed to identify predictors of the presence of brain metastases at diagnosis and factors associated with all-cause mortality, respectively. For incidence, we identified a population-based sample of 238 726 adult patients diagnosed as having invasive breast cancer between 2010 and 2013 for whom the presence or absence of brain metastases at diagnosis was known. Patients diagnosed at autopsy or with an unknown follow-up were excluded from the survival analysis, leaving 231 684 patients in this cohort. Incidence proportion and median survival of patients with brain metastases and newly diagnosed breast cancer. We identified 968 patients with brain metastases at the time of diagnosis of breast cancer, representing 0.41% of the entire cohort and 7.56% of the subset with metastatic disease to any site. A total of 57 were 18 to 40 years old, 423 were 41 to 60 years old, 425 were 61-80 years old, and 63 were older than 80 years. Ten were male and 958 were female. Incidence proportions were highest among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive (1.1% among entire cohort, 11.5% among patients with metastatic disease to any distant site) and triple-negative (0.7% among entire cohort, 11.4% among patients with metastatic disease to any distant site) subtypes. Median survival among the entire cohort with brain metastases was 10.0 months. Patients with HR-positive HER2-positive subtype displayed the longest median survival (21.0 months); patients with triple-negative subtype had the shortest median survival (6.0 months). The findings of this study provides population-based estimates of the incidence and prognosis for patients with brain metastases at time of diagnosis of breast cancer. The findings lend support to consideration of screening imaging of the brain for patients with HER2-positive or triple-negative subtypes and extracranial metastases.

A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors.

PubMed

Santagata, Sara; Portella, Luigi; Napolitano, Maria; Greco, Adelaide; D'Alterio, Crescenzo; Barone, Maria Vittoria; Luciano, Antonio; Gramanzini, Matteo; Auletta, Luigi; Arra, Claudio; Zannetti, Antonella; Scala, Stefania

2017-05-31

C-X-C chemokine receptor 4 (CXCR4) is over-expressed in multiple human cancers and correlates with tumor aggressiveness, poor prognosis and increased risk for distant metastases. Imaging agents for CXCR4 are thus highly desirable. We developed a novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) conjugating the new developed CXCR4 peptidic antagonist Peptide R with the NIR fluorescent dye VivoTag-S750. Specific CXCR4 binding was obtained in cells overexpressing human CXCR4 (B16-hCXCR4 and human melanoma cells PES43), but not in CXCR4 low expressing cells (FB-1). Ex vivo evaluation demonstrated that PepR-NIR750 specifically detects B16-hCXCR4-derived subcutaneous tumors and lung metastases. Fluorescence Molecular Tomography (FMT) in vivo imaging was performed on mice carrying subcutaneous CHO and CHO-CXCR4 tumors. PepR-NIR750 accumulates only in CXCR4-positive expressing subcutaneous tumors. Additionally, an intense NIR fluorescence signal was detected in PES43-derived lung metastases of nude mice injected with PepR-NIR750 versus mice injected with VivoTag-S750. With a therapeutic intent, mice bearing PES43-derived lung metastases were treated with Peptide R. A the dramatic reduction in PES43-derived lung metastases was detected through a decrease of the PepR-NIR750 signal. PepR-NIR750 is a specific probe for non-invasive detection of human high CXCR4-expressing tumors and metastatic lesion and thus a valuable tool for cancer molecular imaging.

Intratumoral Heterogeneity of SMAD4 Immunohistochemical Expression and Its Role in Prediction of Recurrence Pattern in Patients with Resectable Pancreatic Cancer.

PubMed

Pokataev, Ilya; Kudaibergenova, Asel; Artemyeva, Anna; Popova, Anna; Rumyantsev, Alexey; Podluzhny, Danil; Kudashkin, Nikolay; Fedyanin, Mikhail; Tryakin, Alexey; Tjulandin, Sergey

2018-04-20

The aim of our study was to evaluate consistency of SMAD4 expression in different tumor areas and its correlation with recurrence pattern in patients after resection for pancreatic cancer (PC). Records of patients who underwent resection for nonmetastatic PC between 2001 and 2015 were analyzed. Formalin-fixed, paraffin-embedded tissue sections from different areas of primary tumor and lymph node metastases were analyzed immunohistochemically (IHC) for SMAD4 expression using TMA technology. SMAD4 expression was assessed in 356 tissue sections obtained from 91 patients. SMAD4 expression was positive in all assessed tumor slides only in 7 of 26 patients (26.9%). There were 54 recurrences (9 locoregional, 41 distant, and 4 both local and distant) with median follow-up of 21.7 months. There was no correlation between SMAD4 expression and locoregional recurrence pattern (p = 0.30). SMAD4 status influenced neither distant recurrence-free survival (p = 0.99) nor overall survival (p = 0.13). Different areas inside primary tumor and lymph node metastases express SMAD4 heterogeneously. SMAD4 IHC expression is not a biomarker of the recurrence pattern after surgical resection for PC.

Metastasis in dedifferentiated liposarcoma: Predictors and outcome in 148 patients.

PubMed

Tirumani, S H; Tirumani, H; Jagannathan, J P; Shinagare, A B; Hornick, J L; Ramaiya, N H; Wagner, A J

2015-07-01

To describe the pattern of dedifferentiated liposarcoma (DDLPS) metastases and to analyze their predictors and outcome. In this retrospective study, we reviewed the imaging and clinical records of all consenting patients with histopathology-confirmed DDLPS seen from 2000 through 2012. The predictive value of clinical and histopathologic parameters for metastasis later in the disease course was analyzed using univariate and multivariate analyses. Survival of patients with and without metastasis was compared using Log-rank test. Records of 148 patients (57 women, 91 men; mean age 59 years, range 30-87 years) were reviewed. Distant metastases were observed in 44/148 patients (29.7%), 9/44 (20.5%) at presentation and 35/44 (79.5%) developing them later at a median interval of 8 months (IQR = 0.80-26 months). Median duration of follow-up was 38 months (IQR = 18-74 months) with 77/148 patients (31 with metastases) deceased at the time of analysis. Median survival was 28 months (IQR = 10-56 months) for patients with metastases and 38 months (IQR, 17-65 months) for patients without metastases (p = 0.0123, Log-Rank test; Hazard ratio 1.79 [95% confidence interval 1.11-2.84]). Lung was the most common site of metastases (33 patients, 22.3%). On univariate analysis, grade and local recurrence were associated with subsequent risk of metastasis where as age, tumor size, site, de novo dedifferentiation, number of previous surgical resections, margin positivity and chemoradiation were not. On multivariate analysis, high tumor grade (p-value = 0.0005, OR 5.05; 95% CI 2.01-13.48) and local recurrence (p-value = 0.0025, OR 4.46; 95% CI 1.67-13.40) predicted metastasis. Lung was most frequent site of DDLPS metastases. Risk of developing metastatic disease was statistically associated with tumor grade and local recurrence. Metastatic disease was associated with decreased survival. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel Risk Stratification Score for Predicting Early Distant Brain Failure and Salvage Whole Brain Radiotherapy after Stereotactic Radiosurgery for Brain Metastases

PubMed Central

Press, Robert H.; Prabhu, Roshan S.; Nickleach, Dana C.; Liu, Yuan; Shu, Hui-Kuo G.; Kandula, Shravan; Patel, Kirtesh R.; Curran, Walter J.; Crocker, Ian

2015-01-01

Background The purpose of this study was to evaluate predictors of early distant brain failure (DBF) and salvage whole brain radiotherapy (WBRT) after treatment with stereotactic radiosurgery (SRS) for brain metastases and create a clinically relevant risk score in order to stratify patients’ risk of these events. Methods We reviewed records of 270 patients with brain metastases treated with SRS between 2003-2012. Pre-treatment patient and tumor characteristics were analyzed by univariate and multivariable analyses. Cumulative incidence (CI) of first DBF and salvage WBRT were calculated. Significant factors were used to create a score for stratifying early (6-month) DBF risk. Results No prior WBRT, total lesion volume <1.3 cm3, primary breast cancer or malignant melanoma histology, and multiple metastases (≥2) were found to be significant predictors for early DBF. Each factor was ascribed one point due to similar hazard ratios. Scores of 0-1, 2, and 3-4 were considered low, intermediate, and high risk, respectively. This correlated with 6-month CI of DBF of 16.6%, 28.8%, and 54.4%, respectively (p<0.001). For patients without prior WBRT, the 6-month CI of salvage WBRT by 6-months was 2%, 17.7%, and 25.7%, respectively (p<0.001). Conclusion Early DBF after SRS requiring salvage WBRT remains a significant clinical problem. Patient stratification for early DBF can better inform the decision for initial treatment strategy for brain metastases. The provided risk score may help predict for early DBF and subsequent salvage WBRT if initial SRS is used. External validation is needed prior to clinical implementation. PMID:26242475

Curative Chemoradiotherapy in Patients With Stage IVB Cervical Cancer Presenting With Paraortic and Left Supraclavicular Lymph Node Metastases

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

Kim, Ji-Yoon; Kim, Joo-Young; Kim, Jin Hee

2012-11-01

Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with curative intent in patients with stage IVB cervical cancer initially presenting with paraortic and left supraclavicular lymph node metastases. Methods and Materials: The medical records of 25 patients with both paraortic and left supraclavicular lymph nodal metastases (group I) were reviewed and compared with those of 101 women with paraortic lymph node metastases alone (group II). Group I received a mean 59.4 Gy to the paraortic and left supraclavicular areas and 50.4 Gy to the pelvis, followed by 30 Gy of high-dose-rate brachytherapy in 6 fractions. Group IImore » received the same dose to the paraortic area and pelvis followed by intracavitary brachytherapy. All patients received platinum-based chemotherapy simultaneously. Results: Of the 25 patients in group I, 16 (64%) experienced acute grade 3-4 hematologic toxicities, and 1 had a late grade 3 genitourinary toxicity. Complete responses, including the primary mass and pelvic, paraortic, and left supraclavicular lymph nodes, were observed in 13 patients (52%). At a median follow-up of 32 months for surviving patients, 3 experienced in-field failure, 6 showed distant failure, and 9 showed both. The 3-year overall and disease-free survival rates were 49% and 33%, respectively. In comparison, of the 101 patients in group II, 16 showed in-field failure, 14 experienced distant failure, and 11 showed both. The 3-year overall and disease-free survival rates were 69% and 57%, respectively. Conclusions: Curative CCRT is feasible in patients with stage IVB cervical cancer presenting with paraortic and left supraclavicular lymph nodal metastases, with acceptable late toxicity and high response rates, despite high rates of acute hematologic toxicity.« less

Multidose Stereotactic Radiosurgery (9 Gy × 3) of the Postoperative Resection Cavity for Treatment of Large Brain Metastases

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

Minniti, Giuseppe, E-mail: gminniti@ospedalesantandrea.it; Department of Neurological Sciences, Scientific Institute IRCCS Neuromed, Pozzilli; Esposito, Vincenzo

2013-07-15

Purpose: To evaluate the clinical outcomes with linear accelerator-based multidose stereotactic radiosurgery (SRS) to large postoperative resection cavities in patients with large brain metastases. Methods and Materials: Between March 2005 to May 2012, 101 patients with a single brain metastasis were treated with surgery and multidose SRS (9 Gy × 3) for large resection cavities (>3 cm). The target volume was the resection cavity with the inclusion of a 2-mm margin. The median cavity volume was 17.5 cm{sup 3} (range, 12.6-35.7 cm{sup 3}). The primary endpoint was local control. Secondary endpoints were survival and distant failure rates, cause of death,more » performance measurements, and toxicity of treatment. Results: With a median follow-up of 16 months (range, 6-44 months), the 1-year and 2-year actuarial survival rates were 69% and 34%, respectively. The 1-year and 2-year local control rates were 93% and 84%, with respective incidences of new distant brain metastases of 50% and 66%. Local control was similar for radiosensitive (non-small cell lung cancer and breast cancer) and radioresistant (melanoma and renal cell cancer) brain metastases. On multivariate Cox analysis stable extracranial disease, breast cancer histology, and Karnofsky performance status >70 were associated with significant survival benefit. Brain radionecrosis occurred in 9 patients (9%), being symptomatic in 5 patients (5%). Conclusions: Adjuvant multidose SRS to resection cavity represents an effective treatment option that achieves excellent local control and defers the use of whole-brain radiation therapy in selected patients with large brain metastases.« less

Survival was Significantly Better with Surgical/Medical/Radiation Co-interventions in a Single-Institution Practice Audit of Frameless Stereotactic Radiosurgery.

PubMed

Taggar, Amandeep; MacKenzie, Joanna; Li, Haocheng; Lau, Harold; Lim, Gerald; Nordal, Robert; Hudson, Alana; Khan, Rao; Spencer, David; Voroney, Jon-Paul

2016-05-17

To audit outcomes after introducing frameless stereotactic radiosurgery (SRS) for brain metastases, including co-interventions: neurosurgery, systemic therapy, and whole brain radiotherapy (WBRT). We report median overall survival (MS), local failure, and distant brain failure. We hypothesized patients treated with SRS would have clinically meaningful improved MS compared with historic institutional values. We further hypothesized that patients treated with co-interventions would have clinically meaningful improved MS compared with patients treated with SRS alone. One hundred twenty patients (N = 120) with limited intracranial disease underwent 130 frameless SRS sessions from April 2010 to May 2013. Median follow-up was 11 months. MS was measured from brain metastases diagnosis, local failure, and distant brain failure from the time of first SRS. Practice pattern during the first year of the study favored upfront WBRT (79%) over SRS (21%) while upfront SRS (45%) was almost as common as upfront WBRT (55%) in the last year of the study. MS was 18 months; 37% received SRS alone as initial radiotherapy (MS 12 months); 63% received WBRT prior to SRS (MS 19 months); 50% received systemic therapy post-SRS (MS 21 months); and 26% had tumor resection then SRS to the surgical cavity (MS 42 months). Local failure occurred in 10% of lesions and radio-necrosis occurred in 4%. Differences in distant brain failure among patients treated with upfront SRS (40% rate), WBRT followed by SRS (33% rate) or systemic therapy post-SRS (37% rate) were not statistically significant. Frameless SRS effectively treats surgical cavities, persistent tumors post-WBRT, and can be used as an upfront treatment of brain metastases. Surgery, systemic therapy, and WBRT are associated with longer MS. Patients can live for years while receiving multiple therapies. Systemic therapy for patients with brain metastases is increasingly common, palliative care occurs earlier and improves survival, and WBRT use is not routine. Modern series sometimes produce unexpectedly good results. Classification and treatment protocols are evolving. This practice audit is note-worthy for (i) high median overall survival, (ii) systemic therapy after radiosurgery for patients with tumors treated by radiosurgery, (iii) distant brain failure not significantly related to WBRT, and (iv) neurosurgery, systemic therapy, and WBRT are independently associated with improved MS.

Immunohistochemical expression of metallothionein in normal human colorectal mucosa, in adenomas and in adenocarcinomas and their associated metastases.

PubMed

Giuffrè, G; Barresi, G; Sturniolo, G C; Sarnelli, R; D'Incà, R; Tuccari, G

1996-10-01

The immunohistochemical distribution pattern of metallothionein, a low molecular weight protein with strong affinity for divalent heavy metal ions, has been investigated in normal and neoplastic conditions of the large bowel. Utilizing a monoclonal mouse antibody the following formalin-fixed paraffin-embedded surgical or biopsy samples were studied: tubulo-villous adenomas (8 cases); adenocarcinomas with various degree of differentiation (85), nine of which were mucinous-type; synchronous tubular or tubulo-villous adenomas separate from carcinomas (30); transitional mucosa (45); metastases in lymph nodes (43); and distant metastases (45). Twenty biopsies from the right and left colon of 10 patients affected by irritable bowel syndrome were also analyzed. Normal colonic mucosa as well as transitional mucosa showed metallothionein immunopositivity in enterocytes at the luminal surface and crypts. Evident nuclear and cytoplasmic staining was encountered in tubulo-villous adenomas; the same reactivity was noted in the basal glandular component of colorectal carcinomas-synchronous adenomas, while less intense staining was noted in the apical villous portions. A variable metallothionein immunostaining was observed in adenocarcinomas (62.3%), in lymph node (55.8%) and distant hepatic (17.2%) and omental (43.8%) metastases, although it was not always concordant with that reported in the corresponding primary tumour. Whether the metallothionein positivity observed in normal and neoplastic cells is the result of expression of a stable form of the protein or an accumulation in the nucleus and cytoplasm remains to be clarified.

Dataset on FAP-induced emergence of spontaneous metastases and on the preparation of activatable FAP-targeting immunoliposomes to detect the metastases.

PubMed

Tansi, Felista L; Rüger, Ronny; Böhm, Claudia; Kontermann, Roland E; Teichgraeber, Ulf K; Fahr, Alfred; Hilger, Ingrid

2016-12-01

The underlying data demonstrates that fibroblast activation protein (FAP) paves the way for fibrosarcoma cells, which require the proteolysis of the extracellular matrix (ECM) and basement membranes to intravasate from implanted subcutaneous primary tumors into blood vessels, be transported to distant organs where they extravasate from the blood vessels, reattach and proliferate to metastases. The data additionally shows that FAP, when overexpressed on fibrosarcoma cells induces their invasion and formation of spontaneous metastases in multiple organs, particularly after subcutaneous co-implantation of the FAP-expressing and wildtype fibrosarcoma. The raw and processed data presented herein is related to a research article entitled "Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases" (F.L. Tansi, R. Rüger, C. Böhm, R.E. Kontermann, U.K. Teichgraeber, A. Fahr, I. Hilger, 2016) [1]. Furthermore, evidence for the detection of FAP-expressing tumor cells and cells of the tumor stroma by activatable FAP-targeting liposomes is presented in this dataset.

Loss of steroid hormone receptors is common in malignant pleural and peritoneal effusions of breast cancer patients treated with endocrine therapy

PubMed Central

Schrijver, Willemijne A.M.E.; Schuurman, Karianne; van Rossum, Annelot; Peeters, Ton; Ter Hoeve, Natalie

2017-01-01

Discordance in estrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancers and solid distant metastases (“conversion”) has been reported previously. Even though metastatic spread to the peritoneal and pleural cavities occurs frequently and is associated with high mortality, the rate of receptor conversion and the prognostic implications thereof remain elusive. We therefore determined receptor conversion in 91 effusion metastases (78 pleural, 13 peritoneal effusions) of 69 patients by immunohistochemistry (IHC) and in situ hybridization. Data were coupled to clinical variables and treatment history. ERα, PR and AR receptor status converted from positive in the primary tumor to negative in the effusion metastases or vice versa in 25-30%, 30-35% and 46-51% of cases for the 1% and 10% thresholds for positivity, respectively. 19-25% of patients converted clinically relevant from “ERα+ or PR+” to ERα-/PR- and 3-4% from ERα-/PR- to “ERα+ or PR+”. For HER2, conversion was observed in 6% of cases. Importantly, receptor conversion for ERα (p = 0.058) and AR (p < 0.001) was more often seen in patients adjuvantly treated with endocrine therapy. Analogous to this observation, HER2-loss was more frequent in patients adjuvantly treated with trastuzumab (p < 0.001). Alike solid distant metastases, receptor conversion for ERα, PR, AR and HER2 is a frequent phenomenon in peritoneal and pleural effusion metastases. Adjuvant endocrine and trastuzumab therapy imposes an evolutionary selection pressure on the tumor, leading to receptor loss in effusion metastases. Determination of receptor status in malignant effusion specimens will facilitate endocrine treatment decision-making at this lethal state of the disease, and is hence recommended whenever possible. PMID:28903441

Prediction of new brain metastases after radiosurgery: validation and analysis of performance of a multi-institutional nomogram.

PubMed

Ayala-Peacock, Diandra N; Attia, Albert; Braunstein, Steve E; Ahluwalia, Manmeet S; Hepel, Jaroslaw; Chung, Caroline; Contessa, Joseph; McTyre, Emory; Peiffer, Ann M; Lucas, John T; Isom, Scott; Pajewski, Nicholas M; Kotecha, Rupesh; Stavas, Mark J; Page, Brandi R; Kleinberg, Lawrence; Shen, Colette; Taylor, Robert B; Onyeuku, Nasarachi E; Hyde, Andrew T; Gorovets, Daniel; Chao, Samuel T; Corso, Christopher; Ruiz, Jimmy; Watabe, Kounosuke; Tatter, Stephen B; Zadeh, Gelareh; Chiang, Veronica L S; Fiveash, John B; Chan, Michael D

2017-11-01

Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) and Heller's explained relative risk (HERR) = 0.173 (SE = 0.048). Absolute number of metastases was evaluated for its ability to predict DBF in the derivation and validation datasets, and was inferior to the nomogram. A nomogram high-risk threshold yielding a 2.1-fold increased need for early WBRT was identified. Nomogram values also correlated to number of brain metastases at time of failure (r = 0.38, p < 0.0001). We present a multi-institutionally validated prognostic model and nomogram to predict risk of DBF and guide risk-stratification of patients who are appropriate candidates for radiosurgery versus upfront WBRT.

Metastatic Organotropism: An Intrinsic Property of Breast Cancer Molecular Subtypes.

PubMed

Wei, Shi; Siegal, Gene P

2017-03-01

It has long been known that some cancers have the propensity to metastasize to certain organs thus creating a nonrandom distribution of sites for distant relapse, a phenomenon known as "metastatic organotropism." Some of these examples include ovary primary to abdominal cavity, prostate primary to bone, and pancreas primary to liver. In contrast, other tumor types, such as mammary and renal cell carcinoma, can relapse in multiple organs although approximately half of advanced breast cancers metastasize to bone. On the other hand gene expression profiling studies have identified various breast cancer classes with prognostic significance. Recent studies have revealed that breast cancer subtypes differ not only in primary tumor characteristics but also in their metastatic behavior. In particular, the luminal tumors are remarkable for their significant bone-seeking phenotype; the HER2 subtype demonstrates a significant liver-homing characteristic; whereas so-called triple-negative breast cancers predispose to lung metastases. These findings suggest that this knowledge could potentially be utilized in the development of effective disease surveillance strategies in the pursuit of precision medicine, thus necessitating further investigation.

Management of Bone Metastases From Breast Cancer in Upper and Lower Body at the Same Time: A Case Report.

PubMed

Ciaglia, Gian Franco; Martino, Antonia; Sayad, Khadija; Scoglio, Claudio; Pezzulla, Donato; Cappabianca, Salvatore

2016-06-01

Breast cancer is by far the most common cancer in women, and it has the highest incidence rates in western Europe. At breast cancer diagnosis, approximately 5-6% of women present with distant spread with bone, representing the most common site of metastatic lesions. More than half of the women, who present with metastatic breast cancer at the primary diagnosis, will develop bone metastases. We report a clinical case of a 75-year-old woman, with a history of breast cancer who undergone surgery 7 years ago, presenting bone metastases in different areas. We tried to determinate the major areas of pain and then to quantify it with a one-dimensional scale. After that, we analyzed the images of the previous instrumental exams and the centering CT in order to compare them with what the patient reported and then to decide what we should have targeted first. The aim of our work was to try finding a methodology in order to determinate the priority in the selecting of the area to treat to apply in this kind of patients.

Impact of Blood-Brain Barrier Integrity on Tumor Growth and Therapy Response in Brain Metastases.

PubMed

Osswald, Matthias; Blaes, Jonas; Liao, Yunxiang; Solecki, Gergely; Gömmel, Miriam; Berghoff, Anna S; Salphati, Laurent; Wallin, Jeffrey J; Phillips, Heidi S; Wick, Wolfgang; Winkler, Frank

2016-12-15

The role of blood-brain barrier (BBB) integrity for brain tumor biology and therapy is a matter of debate. We developed a new experimental approach using in vivo two-photon imaging of mouse brain metastases originating from a melanoma cell line to investigate the growth kinetics of individual tumor cells in response to systemic delivery of two PI3K/mTOR inhibitors over time, and to study the impact of microregional vascular permeability. The two drugs are closely related but differ regarding a minor chemical modification that greatly increases brain penetration of one drug. Both inhibitors demonstrated a comparable inhibition of downstream targets and melanoma growth in vitro In vivo, increased BBB permeability to sodium fluorescein was associated with accelerated growth of individual brain metastases. Melanoma metastases with permeable microvessels responded similarly to equivalent doses of both inhibitors. In contrast, metastases with an intact BBB showed an exclusive response to the brain-penetrating inhibitor. The latter was true for macro- and micrometastases, and even single dormant melanoma cells. Nuclear morphology changes and single-cell regression patterns implied that both inhibitors, if extravasated, target not only perivascular melanoma cells but also those distant to blood vessels. Our study provides the first direct evidence that nonpermeable brain micro- and macrometastases can effectively be targeted by a drug designed to cross the BBB. Small-molecule inhibitors with these optimized properties are promising agents in preventing or treating brain metastases in patients. Clin Cancer Res; 22(24); 6078-87. ©2016 AACRSee related commentary by Steeg et al., p. 5953. ©2016 American Association for Cancer Research.

Latero-cervical lymph node metastases (N1b) represent an additional risk factor for papillary thyroid cancer outcome.

PubMed

Sapuppo, G; Palermo, F; Russo, M; Tavarelli, M; Masucci, R; Squatrito, S; Vigneri, R; Pellegriti, G

2017-12-01

Papillary thyroid carcinoma (PTC), the most common thyroid cancer histotype, has a good prognosis even when spread to the neck lymph node (LN). The prognostic role of LN metastases' location is still controversial. The aim of the present study was to evaluate the clinical relevance of the number and location of LN metastases at presentation in PTCs. This retrospective study included a consecutive series of 1653 PTC patients followed for a mean period of 5.9 years in a referral thyroid cancer clinic. All patients have undergone thyroidectomy with the dissection of at least six LNs. According to the LN status, patients were subdivided into 569 N0 (34.4%), 644 N1a (39.0%, central compartment) and 440 N1b (26.6%, latero-cervical compartment). Age at diagnosis was significantly lower in N1b (39.8, IQR 30.7-51.6) and N1a (40.1, IQR 31.3-50.1) than in N0 (44.7, IQR 36.6-55.0 yrs). The male gender was more prevalent in N1b than in N1a and N0 (F/M = 1.9/1, 4.0/1 and 5.5/1, respectively). Persistent/recurrent disease at last control was significantly more frequent in N1b (29.8%) than in N1a (14.3%), and in N1a than in N0 (4.2%) (p < 0.01 for all). Also, distant metastases were significantly (p < 0.001) more frequent in N1b (14.1%) than in N1a (4.3%) and N0 (1.6%). LN metastases' number (>5) was a significant risk factor for persistent/recurrent disease only for N1a patients. These data indicate that persistent/recurrent disease and distant metastases are significantly more frequent in patients with latero-cervical LN (N1b) metastases and that the LN location should be used for a better postsurgical risk stratification.

Histopathological Parameters predicting Occult Nodal Metastases in Tongue Carcinoma Cases: An Indian Perspective.

PubMed

Jacob, Tina Elizabeth; Malathi, N; Rajan, Sharada T; Augustine, Dominic; Manish, N; Patil, Shankargouda

2016-01-01

It is a well-established fact that in squamous cell carcinoma cases, the presence of lymph node metastases decreased the 5-year survival rate by 50% and also caused the recurrence of the primary tumor with development of distant metastases. Till date, the predictive factors for occult cervical lymph nodes metastases in cases of tongue squamous cell carcinoma remain inconclusive. Therefore, it is imperative to identify patients who are at the greatest risk for occult cervical metastases. This study was thus performed with the aim to identify various histopathologic parameters of the primary tumor that predict occult nodal metastases. The clinicopathologic features of 56 cases of lateral tongue squamous cell carcinoma with cT1NoMo/cT2NoMo as the stage and without prior radiotherapy or chemotherapy were considered. The surgical excision of primary tumor was followed by elective neck dissection. The glossectomy specimen along with the neck nodes were fixed in formalin and 5 urn thick sections were obtained. The hematoxylin & eosin stained sections were then subjected to microscopic examination. The primary tumor characteristics that were analyzed include tumor grade, invading front, depth of tumor, lymphovascular invasion, perineural invasion and inflammatory response. The nodes were examined for possible metastases using hematoxylin & eosin followed by cytokeratin immunohistochemistry. A total of 12 cases were found with positive occult nodal metastases. On performing univariate analysis, the histopathologic parameters that were found to be statistically significant were lymphovascular invasion (p = 0.004) and perineural invasion (p = 0.003) along with a cut-off depth of infiltration more than 5 mm (p = 0.01). Histopathologic assessment of the primary tumor specimen therefore continues to provide information that is central to guide clinical management, particularly in cases of occult nodal metastases. Clinical significance The study highlights the importance of extensive histopathological screening, which holds the key for establishing occult metastases. Pathological upgrading of tumors is possible following histopathological studies similar to the present one. Presence of occult metastases justify neck dissection in these clinically N0 cases. In an Indian setting, histopathological evaluation assumes a bigger role than other expensive and advanced techniques.

Emerging role of brain metastases in the prognosis of breast cancer patients.

PubMed

Hambrecht, Amanda; Jandial, Rahul; Neman, Josh

2011-08-10

Cancer starts with one rogue cell. Through mutations and genomic alterations, the cell acquires specific and stem cell-like characteristics necessary for invasion of a distant organ and ultimately metastasis. Metastatic brain cancer is a particularly formidable disease because of its poor prognosis and the highly resistant nature of the tumor to chemotherapy. Although several types of primary tumors have a tendency to metastasize to the brain, the incidence of brain metastases has increased dramatically in some subsets of breast cancer patients. Several conventional treatments are available, but success is limited and often short-lived. Given that no standard treatment options exist, there is a significant need to investigate the biology of these clinically recalcitrant tumors.

Emerging role of brain metastases in the prognosis of breast cancer patients

PubMed Central

Hambrecht, Amanda; Jandial, Rahul; Neman, Josh

2011-01-01

Cancer starts with one rogue cell. Through mutations and genomic alterations, the cell acquires specific and stem cell-like characteristics necessary for invasion of a distant organ and ultimately metastasis. Metastatic brain cancer is a particularly formidable disease because of its poor prognosis and the highly resistant nature of the tumor to chemotherapy. Although several types of primary tumors have a tendency to metastasize to the brain, the incidence of brain metastases has increased dramatically in some subsets of breast cancer patients. Several conventional treatments are available, but success is limited and often short-lived. Given that no standard treatment options exist, there is a significant need to investigate the biology of these clinically recalcitrant tumors. PMID:24367178

Dual Chemodrug-Loaded Single-Walled Carbon Nanohorns for Multimodal Imaging-Guided Chemo-Photothermal Therapy of Tumors and Lung Metastases

PubMed Central

Yang, Jingxing; Su, Huilan; Sun, Wenshe; Cai, Jiali; Liu, Shiyuan; Chai, Yimin; Zhang, Chunfu

2018-01-01

Tumor combination therapy using nano formulations with multimodal synergistic therapeutic effects shows great potential for complete ablation of tumors. However, targeting tumor metastases with nano structures is a major obstacle for therapy. Therefore, developing a combination therapy system able to target both primary tumors and their metastases at distant sites with synergistic therapy is desirable for the complete eradication of tumors. To this end, a dual chemodrug-loaded theranostic system based on single walled carbon nanohorns (SWNHs) is developed for targeting both primary breast tumors and their lung metastases. Methods: SWNHs were first modified simultaneously with poly (maleic anhydride-alt-1-octadecene) (C18PMH) and methoxypolyethyleneglycol-b-poly-D, L-lactide (mPEG-PLA) via hydrophobic-hydrophobic interactions and π-π stacking. Then cisplatin and doxorubicin (DOX) (2.9:1 molar ratio) were sequentially loaded onto the modified nanohorns in a noninterfering way. After careful examinations of the release profiles of the loaded drugs and the photothermal performance of the dual chemodrug-loaded SWNHs, termed SWNHs/C18PMH/mPEG-PLA-DOX-Pt, the dual drug chemotherapeutic and chemo-photothermal synergetic therapeutic effects on tumor cells were evaluated. Subsequently, the in vivo behavior and tumor accumulation of the drug-loaded SWNHs were studied by photoacoustic imaging (PAI). For chemo-photothermal therapy of tumors, 4T1 tumor bearing mice were intravenously injected with SWNHs/C18PMH/mPEG-PLA-DOX-Pt at a dose of 10 mg/kg b.w. (in SWNHs) and tumors were illuminated by an 808 nm laser (1W/cm2 for 5 min) 24 h post-injection. Results: DOX and cisplatin were loaded onto the modified SWNHs with high efficiency (44 wt% and 66 wt%, respectively) and released in a pH-sensitive, tandem and sustainable manner. The SWNHs/C18PMH/mPEG-PLA-DOX-Pt had a hydrodynamic diameter of 182 ± 3.2 nm, were highly stable in physiological environment, and had both dual drug chemotherapeutic (CI = 0.439) and chemo-photothermal synergistic antitumor effects (CI = 0.396) in vitro. Moreover, the dual drug-loaded SWNHs had a long blood half-life (10.9 h) and could address both the primary breast tumors and their lung metastases after intravenous administration. Consequently, chemo-photothermal combination therapy ablated the primary tumors and simultaneously eradicated the metastatic lung nodules. Conclusion: Our study demonstrates that SWNHs/C18PMH/mPEG-PLA-DOX-Pt is highly potent for chemo-photothermal combination therapy of primary tumors and cocktail chemotherapy of their metastases at a distant site. PMID:29556368

Clinical characteristics of XP11.2 translocation/TFE3 gene fusion renal cell carcinoma: a systematic review and meta-analysis of observational studies.

PubMed

Cheng, Xiangming; Gan, Weidong; Zhang, Gutian; Li, Xiaogong; Guo, Hongqian

2016-07-11

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) is a rare subtype of RCC which is firstly described as a distinct entity in 2004 so that clinical characteristics of Xp11.2 RCC in different gender and age are unknown. The purpose of systematic review and meta-analysis is to provide a comprehensive assessment on them. MEDLINE, EMBASE and Cochrane databases were searched for studies which evaluate the clinical characteristics of Xp11.2 RCC. The literature published between July 2004 and May 2014 was searched. A total of 15 studies with 147 participants were included. The meta-analysis demonstrated that number of patients of all age in female was higher than in male with pooled OR of 3.93(95 % CI = 1.66-9.34). However, incidence of distant metastases (OR = 0.34, 95 % CI = 0.12-1.57) and lymphatic metastases (OR = 0.51, 95 % CI = 0.14-1.91), tumor stage (OR = 0.85, 95 % CI = 0.34-2.15) and overall survival (OS) (OR = 0.46, 95 % CI = 0.05-4.34) between male and female were comparable. Incidence in female was higher than in male with pooled OR of 5.13(95 % CI = 1.67-15.72) in adults, while in children no gender-related predominance (OR = 1.19, 95 % CI = 0.38-3.72) was observed. In addition, incidence of distant metastases (OR = 1.00, 95 % CI = 0.13-7.84) and lymphatic metastases (OR = 1.00, 95 % CI = 0.07-13.67) and tumor stage (OR = 1.94, 95 % CI = 0.20-19.03) between children and adults were comparable. Survival curves presented comparable outcomes between male and female (P = 0.707) as well as between children and adults (P = 0.383). Female patients with Xp11.2 RCC in adults exhibit a high incidence compared to male, but not in children. Comparable clinical characteristics including incidence of distant and lymphatic metastases, tumor stage and prognosis is presented between male and female as well as between children and adults.

Comprehensive Clinical Assessment of 740 Cases of Surgically Treated Thyroid Cancer in Children of Belarus

PubMed Central

Demidchik, Yuri E.; Demidchik, Eugene P.; Reiners, Christoph; Biko, Johannes; Mine, Mariko; Saenko, Vladimir A.; Yamashita, Shunichi

2006-01-01

Objective: A retrospective study was designed to evaluate the results of surgical treatment and follow-up data in thyroid cancer patients less than 15 years old at the time of surgery. Summary Background Data: Pediatric thyroid carcinomas have a high rate of lymph nodal and distant metastases. Risk factors for recurrences and postoperative morbidity have not been assessed yet in a representative series. Methods: The group included 740 pediatric patients with thyroid cancer. Total thyroidectomy was performed in 426 (57.6%), lobectomy in 248 (33.5%), subtotal thyroidectomy in 58 (7.8%) cases, and 8 patients (1.1%) underwent partial lobectomy. Results: The mean follow-up period was 115.8 months (range, 1.5–236.4 months). Recurrence was diagnosed in 204 cases (27.6%), including 73 local relapses (9.9%), 90 distant metastases (12.2%), and a combination of local and distant recurrences in 41 (5.5%) patients. Multivariate statistical assessment revealed the following independent parameters significantly associated with the risk of recurrent nodal disease: a young age at diagnosis, multifocal carcinomas, N1 status, and lack of neck lymph node dissection. For lung metastases, the significant risk factors were female gender, young age at diagnosis, and presence of symptoms. The observed 5- and 10-year survival for the entire group was 99.5% and 98.8%, respectively. Postoperative hypoparathyroidism was significantly associated with multifocal tumors, central compartment removal, and ipsilateral dissection. Conclusions: Total thyroidectomy followed by radioiodine therapy is an optimal treatment strategy that makes it possible to achieve a cure in a vast majority of pediatric patients with differentiated thyroid carcinomas. Risk of recurrence is strongly associated with tumor stage, extent of surgery, the young patient's age, and presence of symptoms at diagnosis. PMID:16552205

Clonal evolution and heterogeneity in metastatic head and neck cancer-An analysis of the Austrian Study Group of Medical Tumour Therapy study group.

PubMed

Melchardt, Thomas; Magnes, Teresa; Hufnagl, Clemens; Thorner, Aaron R; Ducar, Matthew; Neureiter, Daniel; Tränkenschuh, Wolfgang; Klieser, Eckhard; Gaggl, Alexander; Rösch, Sebastian; Rasp, Gerd; Hartmann, Tanja N; Pleyer, Lisa; Rinnerthaler, Gabriel; Weiss, Lukas; Greil, Richard; Egle, Alexander

2018-04-01

Tumour heterogeneity and clonal evolution within a cancer patient are deemed responsible for relapse in malignancies and present challenges to the principles of targeted therapy, for which treatment modality is often decided based on the molecular pathology of the primary tumour. Nevertheless, the clonal architecture in distant relapse of head and neck cancer is fairly unknown. For this project, we analysed a cohort of 386 patients within the Austrian Registry of head and neck cancer. We identified 26 patients with material from the primary tumour, the distant metastasis after curative first-line treatment and a germline sample for analysis of clonal evolution. After pathological analyses, these samples were analysed using a targeted massively parallel sequencing (MPS) panel of 257 genes known to be recurrently mutated in head and neck cancer plus a genome-wide SNP-set. Despite histological diagnosis of distant metastasis, no corresponding mutation in the supposed metastases was found in two of 23 (8.6%) evaluable patients suggesting a primary tumour of the lung instead of a distant metastasis of head and neck cancer. We observed a branched pattern of evolution in 31.6% of the analysed patients. This pattern was associated with a shorter time to distant metastasis, compared with a pattern of punctuated evolution. Structural genomic changes over time were also present in 7 of 12 (60%) evaluable patients with metachronous metastases. Targeted MPS demonstrated substantial heterogeneity at the time of diagnosis and a complex pattern of evolution during disease progression in head and neck cancer. Copy number analyses revealed additional changes that were not detected by mutational analyses. Mutational and structural changes contribute to tumour heterogeneity at diagnosis and progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Core-needle biopsy of breast cancer is associated with a higher rate of distant metastases 5 to 15 years after diagnosis than FNA biopsy.

PubMed

Sennerstam, Roland B; Franzén, Bo S H; Wiksell, Hans O T; Auer, Gert U

2017-10-01

The literature offers discordant results regarding whether diagnostic biopsy is associated with the dissemination of cancer cells, resulting in local and/or distant metastasis. The long-term outcomes of patients with breast cancer were compared between those who were diagnosed using either fine-needle aspiration biopsy (FNAB) or core-needle biopsy (CNB) during 2 decades: the 1970s and 1990s. In the 1970s, the only diagnostic needle biopsy method used for breast cancer in Sweden was FNAB. CNB was introduced 1989 and became established in Stockholm Gotland County in the early 1990s. The authors compared the clinical outcomes of patients diagnosed using FNAB from 1971 to 1976 (n = 354) versus those of patients diagnosed using CNB from 1991 to 1995 (n = 1729). Adjusting for differences in various treatment modalities, mammography screening, tumor size, DNA ploidy, and patient age between the 2 decades, 2 strictly matched samples representing FNAB (n = 181) and CNB (n = 203) were selected for a 15-year follow-up study. In a comparison of the rates of distant metastasis in the strictly matched patient groups from the FNAB and CNB cohorts, significantly higher rates of late-appearing (5-15 years after diagnosis) distant metastasis were observed among the patients who were diagnosed on CNB compared with those who were diagnosed on FNAB. No significant difference in local metastasis was observed between the 2 groups. At 5 to 15 years after diagnosis of the primary tumor, CNB-diagnosed patients had significantly higher rates of distant metastases than FNAB-diagnosed patients. Cancer Cytopathol 2017;125:748-56. © 2017 American Cancer Society. © 2017 American Cancer Society.

Omitting elective nodal irradiation during thoracic irradiation in limited-stage small cell lung cancer--evidence from a phase II trial.

PubMed

Colaco, Rovel; Sheikh, Hamid; Lorigan, Paul; Blackhall, Fiona; Hulse, Paul; Califano, Raffaele; Ashcroft, Linda; Taylor, Paul; Thatcher, Nicholas; Faivre-Finn, Corinne

2012-04-01

Omitting elective nodal irradiation (ENI) in limited-stage disease small cell lung cancer (LD-SCLC) is expected to result in smaller radiation fields. We report on data from a randomised phase II trial that omitted ENI in patients receiving concurrent chemo-radiotherapy for LD-SCLC. 38 patients with LD-SCLC were randomised to receive once-daily (66 Gy in 33 fractions) or twice-daily (45 Gy in 30 fractions) radiotherapy (RT). 3D-conformal RT was given concurrently with cisplatin and etoposide starting with the second cycle of a total of four cycles. The gross tumour volume was defined as primary tumour with involved lymph nodes (nodes ≥1 cm in short axis) identifiable with CT imaging. ENI was not used. Six recurrence patterns were identified: recurrence within planning target volume (PTV) only, recurrence within PTV+regional nodal recurrence and/or distant recurrence, isolated nodal recurrence outside PTV, nodal recurrence outside PTV+distant recurrence, distant metastases only and no recurrence. At median follow-up 16.9 months, 31/38 patients were evaluable and 14/31 patients had relapsed. There were no isolated nodal recurrences. Eight patients relapsed with intra-thoracic disease: 2 within PTV only, 4 within PTV and distantly and 2 with nodal recurrence outside PTV plus distant metastases. Rates of grade 3+ acute oesophagitis and pneumonitis in the 31 evaluable patients were 23 and 3% respectively. In our study of LD-SCLC, omitting ENI based on CT imaging was not associated with a high risk of isolated nodal recurrence, although further prospective studies are needed to confirm this. Routine ENI omission will be further evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Identifying metastatic breast tumors using textural kinetic features of a contrast based habitat in DCE-MRI

NASA Astrophysics Data System (ADS)

Chaudhury, Baishali; Zhou, Mu; Goldgof, Dmitry B.; Hall, Lawrence O.; Gatenby, Robert A.; Gillies, Robert J.; Drukteinis, Jennifer S.

2015-03-01

The ability to identify aggressive tumors from indolent tumors using quantitative analysis on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) would dramatically change the breast cancer treatment paradigm. With this prognostic information, patients with aggressive tumors that have the ability to spread to distant sites outside of the breast could be selected for more aggressive treatment and surveillance regimens. Conversely, patients with tumors that do not have the propensity to metastasize could be treated less aggressively, avoiding some of the morbidity associated with surgery, radiation and chemotherapy. We propose a computer aided detection framework to determine which breast cancers will metastasize to the loco-regional lymph nodes as well as which tumors will eventually go on to develop distant metastses using quantitative image analysis and radiomics. We defined a new contrast based tumor habitat and analyzed textural kinetic features from this habitat for classification purposes. The proposed tumor habitat, which we call combined-habitat, is derived from the intersection of two individual tumor sub-regions: one that exhibits rapid initial contrast uptake and the other that exhibits rapid delayed contrast washout. Hence the combined-habitat represents the tumor sub-region within which the pixels undergo both rapid initial uptake and rapid delayed washout. We analyzed a dataset of twenty-seven representative two dimensional (2D) images from volumetric DCE-MRI of breast tumors, for classification of tumors with no lymph nodes from tumors with positive number of axillary lymph nodes. For this classification an accuracy of 88.9% was achieved. Twenty of the twenty-seven patients were analyzed for classification of distant metastatic tumors from indolent cancers (tumors with no lymph nodes), for which the accuracy was 84.3%.

Three-dimensional conformal radiation therapy for esophageal squamous cell carcinoma: is elective nodal irradiation necessary?

PubMed

Zhao, Kuai-le; Ma, Jin-bo; Liu, Guang; Wu, Kai-liang; Shi, Xue-hui; Jiang, Guo-liang

2010-02-01

To evaluate the local control, survival, and toxicity associated with three-dimensional conformal radiotherapy (3D-CRT) for squamous cell carcinoma (SCC) of the esophagus, to determine the appropriate target volumes, and to determine whether elective nodal irradiation is necessary in these patients. A prospective study of 3D-CRT was undertaken in patients with esophageal SCC without distant metastases. Patients received 68.4 Gy in 41 fractions over 44 days using late-course accelerated hyperfractionated 3D-CRT. Only the primary tumor and positive lymph nodes were irradiated. Isolated out-of-field regional nodal recurrence was defined as a recurrence in an initially uninvolved regional lymph node. All 53 patients who made up the study population tolerated the irradiation well. No acute or late Grade 4 or 5 toxicity was observed. The median survival time was 30 months (95% confidence interval, 17.7-41.8). The overall survival rate at 1, 2, and 3 years was 77%, 56%, and 41%, respectively. The local control rate at 1, 2, and 3 years was 83%, 74%, and 62%, respectively. Thirty-nine of the 53 patients (74%) showed treatment failure. Seventeen of the 39 (44%) developed an in-field recurrence, 18 (46%) distant metastasis with or without regional failure, and 3 (8%) an isolated out-of-field nodal recurrence only. One patient died of disease in an unknown location. In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems. Copyright 2010 Elsevier Inc. All rights reserved.

Primary leiomyosarcoma of the seminal vesicle: case report and review of the literature.

PubMed

Cauvin, Cécile; Moureau-Zabotto, Laurence; Chetaille, Bruno; Hilgers, Werner; Denoux, Yves; Jacquemier, Jocelyne; Guiramand, Jérôme; Sarran, Anthony; Bertucci, François

2011-07-29

Primary leiomyosarcoma of the seminal vesicle is exceedingly rare. We report a case of a 59-year-old man with tumour detected by rectal symptoms and ultrasonography. Computed tomography and magnetic resonance imaging suggested an origin in the right seminal vesicle. Transperineal biopsy of the tumour revealed leiomyosarcoma. A radical vesiculo-prostactectomy with bilateral pelvic lymphadenectomy was performed. Pathological examination showed a grade 2 leiomyosarcoma of the seminal vesicle. The patient received adjuvant radiotherapy. He developed distant metastases 29 months after diagnosis, and received chemotherapy. Metastatic disease was controlled by second-line gemcitabine-docetaxel combination. Fifty-one months after diagnosis of the primary tumour, and 22 months after the first metastases, the patient is alive with excellent performance status, and multiple asymptomatic stable lung and liver lesions. We report the eighth case of primary leiomyosarcoma of the seminal vesicle and the first one with a so long follow-up.

Adenoid cystic salivary gland carcinoma: treatment with irradiation and surgery

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

Simpson, J.R.; Thawley, S.E.; Matsuba, H.M.

1984-05-01

The recrods of 71 patients with adenoid cystic carcinoma of the salivary glands were reviewed to determine the dose response relationships for this aggressive tumor. Local control after treament was determined for all patients and analyzed with respect to extent of surgery and dose of radiation. Of 70 patients who were available for evaluation of local control, 28 (40%) had a local recurrence and 42 (60%) did not. The highest control rates were found in patients who underwent both radiation therapy and surgery. Patients who received a dose equal to or greater than 6,000 rad (60 Gy) in addition tomore » surgery had significantly higher local control rates than those who received less than 6,000 rad (60 Gy). Distant metastases developed in 50% of patients regardless of local control, with the following distribution: 39% lung, 19% bone, and 10% disseminated soft-tissue metastases.« less

Sentinel Node Biopsy in Melanoma: A Short Update

PubMed Central

Ferrara, Gerardo; Partenzi, Antonietta; Filosa, Alessandra

2018-01-01

Several controversies are still ongoing about sentinel node biopsy in melanoma. It is basically a staging procedure for melanoma > 0.75 mm in thickness or for thinner melanoma in the presence of ulceration, high mitotic rate, and/or lymphovascular invasion. Complete lymph node dissection after a positive sentinel node can also allow a better locoregional disease control but seems not to prevent the development of distant metastases. The use of sentinel node biopsy in atypical Spitz tumors should be discouraged because of their peculiar biological properties. PMID:29719827

Urothelial bladder cancer with cavitary lung metastases

PubMed Central

Kurian, Anil; Lee, Jason; Born, Abraham

2011-01-01

Transitional cell carcinoma (TCC) of the bladder tends to remain superficial; however, in 5% to 20% of cases, it progresses to muscle invasion and, more rarely, can metastasize. TCC of the bladder primarily spreads via regional lymphatics. The most common sites of distant metastases of TCC are the liver, lung, mediastinum and bone. Long-term survival of patients with metastatic bladder cancer is rare. Patterns of pulmonary metastasis include multiple nodules, a solitary mass or interstitial micronodule. When multiple nodules are present, they are round and well-circumscribed, without calcification or cavitation. An unusual case of rapidly metastatic TCC to the lung causing large cavitary masses and nodules is presented. Imaging performed after the patient began chemotherapy revealed widespread necrosis of the metastatic cavitary masses causing moderate volume hemoptysis. PMID:21766082

Stereotactic Radiosurgery in the Management of Limited (1-4) Brain Metasteses: Systematic Review and International Stereotactic Radiosurgery Society Practice Guideline.

PubMed

Chao, Samuel T; De Salles, Antonio; Hayashi, Motohiro; Levivier, Marc; Ma, Lijun; Martinez, Roberto; Paddick, Ian; Régis, Jean; Ryu, Samuel; Slotman, Ben J; Sahgal, Arjun

2017-11-03

Guidelines regarding stereotactic radiosurgery (SRS) for brain metastases are missing recently published evidence. To conduct a systematic review and provide an objective summary of publications regarding SRS in managing patients with 1 to 4 brain metastases. Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted using PubMed and Medline up to November 2016. A separate search was conducted for SRS for larger brain metastases. Twenty-seven prospective studies, critical reviews, meta-analyses, and published consensus guidelines were reviewed. Four key points came from these studies. First, there is no detriment to survival by withholding whole brain radiation (WBRT) in the upfront management of brain metastases with SRS. Second, while SRS on its own provides a high rate of local control (LC), WBRT may provide further increase in LC. Next, WBRT does provide distant brain control with less need for salvage therapy. Finally, the addition of WBRT does affect neurocognitive function and quality of life more than SRS alone. For larger brain metastases, surgical resection should be considered, especially when factoring lower LC with single-session radiosurgery. There is emerging data showing good LC and/or decreased toxicity with multisession radiosurgery. A number of well-conducted prospective and meta-analyses studies demonstrate good LC, without compromising survival, using SRS alone for patients with a limited number of brain metastases. Some also demonstrated less impact on neurocognitive function with SRS alone. Practice guidelines were developed using these data with International Stereotactic Radiosurgery Society consensus. Copyright © 2017 by the Congress of Neurological Surgeons

TNM-O: ontology support for staging of malignant tumours.

PubMed

Boeker, Martin; França, Fábio; Bronsert, Peter; Schulz, Stefan

2016-11-14

Objectives of this work are to (1) present an ontological framework for the TNM classification system, (2) exemplify this framework by an ontology for colon and rectum tumours, and (3) evaluate this ontology by assigning TNM classes to real world pathology data. The TNM ontology uses the Foundational Model of Anatomy for anatomical entities and BioTopLite 2 as a domain top-level ontology. General rules for the TNM classification system and the specific TNM classification for colorectal tumours were axiomatised in description logic. Case-based information was collected from tumour documentation practice in the Comprehensive Cancer Centre of a large university hospital. Based on the ontology, a module was developed that classifies pathology data. TNM was represented as an information artefact, which consists of single representational units. Corresponding to every representational unit, tumours and tumour aggregates were defined. Tumour aggregates consist of the primary tumour and, if existing, of infiltrated regional lymph nodes and distant metastases. TNM codes depend on the location and certain qualities of the primary tumour (T), the infiltrated regional lymph nodes (N) and the existence of distant metastases (M). Tumour data from clinical and pathological documentation were successfully classified with the ontology. A first version of the TNM Ontology represents the TNM system for the description of the anatomical extent of malignant tumours. The present work demonstrates its representational power and completeness as well as its applicability for classification of instance data.

Incidence of isolated nodal failure in non-small cell lung cancer patients included in a prospective study of the value of PET-CT.

PubMed

Kolodziejczyk, Milena; Bujko, Krzysztof; Michalski, Wojciech; Kepka, Lucyna

2012-07-01

Elective nodal irradiation (ENI) is not recommended in PET-CT-based radiotherapy for NSCLC despite a low level of evidence to support such guidelines. The aim of this investigation is to find out whether omitting ENI is safe. Sixty-seven patients treated within a frame of a previously published prospective trial of the value of PET-CT were included in the analysis. Seventeen (25%) patients received ENI due to higher initial nodal involvement and in the remaining 50 patients (75%) with N0-N1 or single N2 disease ENI was omitted. Isolated nodal failure (INF) was recorded if relapse occurred in the initially uninvolved regional lymph node without previous or simultaneous local recurrence regardless of the status of distant metastases. With a median follow-up of 32 months, the estimated 3-year overall survival was 42%, local progression-free interval was 55%, and distant metastases-free interval was 62%. Three patients developed INF; all had ENI omitted from treatment, giving a final result of three INFs in 50 (6%) patients treated without ENI. In this group of patients, the 3-year cause-specific cumulative incidence of INF was 6.4% (95% confidence interval: 0-17%). The omission of ENI appears to be not as safe as suggested by current recommendations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Targeting Breast Cancer Micrometastases: To Eliminate the Seeds of Evil

DTIC Science & Technology

2017-04-01

incurable and responsible for over 90% of breast cancer-related death . Thus, the prevention of metastasis is an imperative clinical need. We seek to...overcome the challenge of eliminating microscopic metastases of breast cancer, so that distant recurrences and related deaths can be significantly reduced

Lymph-vascular space involvement and outer one-third myometrial invasion are strong predictors of distant haematogeneous failures in patients with stage I-II endometrioid-type endometrial cancer.

PubMed

Gadducci, Angiolo; Cavazzana, Andrea; Cosio, Stefania; DI Cristofano, Claudio; Tana, Roberta; Fanucchi, Antonio; Teti, Giancarlo; Cristofani, Renza; Genazzani, Andrea Riccardo

2009-05-01

The aim of this retrospective study was to assess the predictive value of different clinicopathological variables (patient age, tumour size, FIGO grade, myometrial invasion, lymph-vascular space involvement [LVSI], invasion margins, peri-tumour phlogistic infiltrate and mitotic activity) for the risk of distant haematogenous recurrences in patients with endometrioid-type stage Ib-II endometrial cancer. Between August 1990 and April 2005, 259 patients had undergone laparotomy, peritoneal washing, total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without pelvic +/- para-aortic lymphadenectomy for endometrioid-type endometrial cancer. Thirty-six (13.9%) patients had developed recurrent disease after a median time of 17 months (range, 2-128 months). The relapse had been locoregional in 9, distant in 21 and both locoregional plus distant in 6 cases. This study assessed 12 patients with FIGO stage Ib-II disease who had developed distant haematogenous recurrences and 20 randomly chosen control patients with FIGO stage Ib-II disease who had remained recurrence-free after a median follow-up of 52 months (range, 37-66 months). Adjuvant therapy had been: no further treatment in 15 patients, external pelvic irradiation in 14 patients, adjuvant external pelvic irradiation plus brachytherapy in 2 patients and platinum-based chemotherapy followed by external pelvic irradiation in 1 patient. The site of distant failure had been the lung in 9 patients, liver in 2 patients and lung plus liver in 1 patient. A concomitant locoregional relapse (vagina or lymph nodes) had occurred in 3 patients. The median interval between surgery and the development of distant failure had been 16.5 months (range, 5-113 months). On univariate analysis, a higher incidence of FIGO grade 3 (50% versus 10%, p=0.0114), outer one-third myometrial invasion (91.7% versus 35.0%, p=0.0051) and LVSI (75.0.% versus 20.0%, p=0.0022) was found in the patients who had developed distant haematogeneous metastases compared to the recurrence-free women. Multivariate analysis showed that LVSI (p=0.0264) and deep myometrial invasion (p=0.0345) were independent predictive variables for the risk of distant haematogeneous failure. Patients with these pathological findings should be enrolled in randomised trials designed to assess the role of adjuvant chemotherapy alone or combined with sequential and/or concomitant external pelvic irradiation.

A primer of bone metastases management in breast cancer patients.

PubMed

Petrut, B; Trinkaus, M; Simmons, C; Clemons, M

2008-01-01

Bone is the most common site for distant spread of breast cancer. Following a diagnosis of metastatic bone disease, patients can suffer from significant morbidity because of pain and skeletal related events (SRES). Bisphosphonates are potent inhibitors of osteoclastic function and the mainstay of bone-directed therapy for bone metastases. The aims of bisphosphonates are to prevent and delay SRES, to reduce bone pain, and to improve quality of life. Bisphosphonate therapy appears to have revolutionized treatment of bone metastases, but bisphosphonate use has several limitations. Those limitations include the high cost of the agents and the need for return trips to the clinic for intravenous treatment. Moreover, many uncertainties surround bisphosphonate use-for example, the timing of bisphosphonate initiation, the choice of bisphosphonate to use, the optimal duration of treatment, and the appropriate means to identify patients who will and will not benefit. In addition, potentially serious adverse effects have been associated with bisphosphonate use-for example, renal toxicity, gastrointestinal side effects, and osteonecrosis of the jaw. The present review is intended as a primer for oncology specialists who treat patients with bone metastases secondary to breast cancer. It focuses on bisphosphonate treatment guidelines, the evidence for those guidelines, and a discussion of new therapeutic agents. It also discusses the use of biochemical markers of bone metabolism, which show promise for predicting the risk of a patient's developing a SRE and of benefiting from bisphosphonate treatment.

Brain Metastasis Velocity: A Novel Prognostic Metric Predictive of Overall Survival and Freedom From Whole-Brain Radiation Therapy After Distant Brain Failure Following Upfront Radiosurgery Alone

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

Farris, Michael, E-mail: mfarris@wakehealth.edu; McTyre, Emory R.; Cramer, Christina K.

Purpose: Prior statistical models attempted to identify risk factors for time to distant brain failure (DBF) or time to salvage whole-brain radiation therapy (WBRT) to predict the benefit of early WBRT versus stereotactic radiosurgery (SRS) alone. We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone. Methods and Materials: BMV was defined as the cumulative number of new brain metastases that developed over time since first SRS in years. Patients were classified by BMV into low-, intermediate-, and high-risk groups, consisting of <4, 4 to 13, and >13 newmore » metastases per year, respectively. Histology, number of metastases at the time of first SRS, and systemic disease status were assessed for effect on BMV. Results: Of 737 patients treated at our institution with upfront SRS without WBRT, 286 had ≥1 DBF event. A lower BMV predicted for improved overall survival (OS) following initial DBF (log-rank P<.0001). Median OS for the low, intermediate, and high BMV groups was 12.4 months (95% confidence interval [CI], 10.4-16.9 months), 8.2 months (95% CI, 5.0-9.7 months), and 4.3 months (95% CI, 2.6-6.7 months), respectively. Multivariate analysis showed that BMV remained the dominant predictor of OS, with a hazard ratio of 2.75 for the high BMV group (95% CI, 1.94-3.89; P<.0001) and a hazard ratio of 1.65 for the intermediate BMV group (95% CI, 1.18-2.30; P<.004). A lower BMV was associated with decreased rates of salvage WBRT (P=.02) and neurologic death (P=.008). Factors predictive for a higher BMV included ≥2 initial brain metastases (P=.004) and melanoma histology (P=.008). Conclusions: BMV is a novel metric associated with OS, neurologic death, and need for salvage WBRT after initial DBF following upfront SRS alone.« less

Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

PubMed

Saâda-Bouzid, E; Defaucheux, C; Karabajakian, A; Coloma, V P; Servois, V; Paoletti, X; Even, C; Fayette, J; Guigay, J; Loirat, D; Peyrade, F; Alt, M; Gal, J; Le Tourneau, C

2017-07-01

Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1 that have recently been approved in pretreated recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK). We retrospectively compared TGK on immunotherapy and TGK on last treatment in patients with R/M HNSCC treated with PD-1/PD-L1 inhibitors in four French centers. The TGK ratio (TGKR, ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. Hyperprogression was defined as a TGKR ≥ 2. From September 2012 to September 2015, 34 patients were identified. Patterns of recurrence included exclusive loco-regional recurrence in 14 patients, exclusive distant metastases in 11 patients, and both in 9 patients. No pseudo-progression was observed. Hyperprogression was observed in 10 patients (29%), including 9 patients with at least a locoregional recurrence, and only 1 patient with exclusively distant metastases. Hyperprogression significantly correlated with a regional recurrence (TGKR ≥ 2: 90% versus TGKR < 2: 37%, P = 0.008), but not with local or distant recurrence. Hyperprogression was associated with a shorter progression-free survival (PFS) according to RECIST (P = 0.003) and irRECIST (P = 0.02), but not with overall survival (P = 0.77). Hyperprogression was observed in 29% of patients with R/M HNSCC treated with anti-PD-L1/PD-1 agents and correlated with a shorter PFS. It occurred in 39% of patients with at least a locoregional recurrence and 9% of patients with exclusively distant metastases. No pseudo-progressions were reported. Mechanisms and causality of hyperprogression should further be assessed through prospective controlled studies. © 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.

Discovery of prognostic biomarkers for predicting lung cancer metastasis using microarray and survival data.

PubMed

Huang, Hui-Ling; Wu, Yu-Chung; Su, Li-Jen; Huang, Yun-Ju; Charoenkwan, Phasit; Chen, Wen-Liang; Lee, Hua-Chin; Chu, William Cheng-Chung; Ho, Shinn-Ying

2015-02-21

Few studies have investigated prognostic biomarkers of distant metastases of lung cancer. One of the central difficulties in identifying biomarkers from microarray data is the availability of only a small number of samples, which results overtraining. Recently obtained evidence reveals that epithelial-mesenchymal transition (EMT) of tumor cells causes metastasis, which is detrimental to patients' survival. This work proposes a novel optimization approach to discovering EMT-related prognostic biomarkers to predict the distant metastasis of lung cancer using both microarray and survival data. This weighted objective function maximizes both the accuracy of prediction of distant metastasis and the area between the disease-free survival curves of the non-distant and distant metastases. Seventy-eight patients with lung cancer and a follow-up time of 120 months are used to identify a set of gene markers and an independent cohort of 26 patients is used to evaluate the identified biomarkers. The medical records of the 78 patients show a significant difference between the disease-free survival times of the 37 non-distant- and the 41 distant-metastasis patients. The experimental results thus obtained are as follows. 1) The use of disease-free survival curves can compensate for the shortcoming of insufficient samples and greatly increase the test accuracy by 11.10%; and 2) the support vector machine with a set of 17 transcripts, such as CCL16 and CDKN2AIP, can yield a leave-one-out cross-validation accuracy of 93.59%, a test accuracy of 76.92%, a large disease-free survival area of 74.81%, and a mean survival prediction error of 3.99 months. The identified putative biomarkers are examined using related studies and signaling pathways to reveal the potential effectiveness of the biomarkers in prospective confirmatory studies. The proposed new optimization approach to identifying prognostic biomarkers by combining multiple sources of data (microarray and survival) can facilitate the accurate selection of biomarkers that are most relevant to the disease while solving the problem of insufficient samples.

Sentinel lymph node biopsy does not change melanoma-specific survival among patients with Breslow thickness greater than four millimeters.

PubMed

Caracò, Corrado; Celentano, Egidio; Lastoria, Secondo; Botti, Gerardo; Ascierto, Paolo Antonio; Mozzillo, Nicola

2004-03-01

Management of patients with cutaneous melanoma in the absence of lymph node metastases is still controversial. The experience at the National Cancer Institute in Naples was analyzed to evaluate 3-year disease-free survival and overall survival for all patients who underwent sentinel lymph node biopsy (SLB) with Breslow thickness greater than 4 mm. Data from 359 sentinel biopsies performed in the past 5 years were reviewed to determine the effect of the treatment on disease-free survival and overall survival after stratifying patients for node status, tumor ulceration, and Breslow thickness. Statistical analysis showed a better 3-year survival for sentinel node-negative patients than for sentinel node-positive cases (88.4% and 72.9%, respectively; P <.05). Tumor ulceration retained its prognostic significance despite lymph node status, indicating a higher risk for development of distant metastases. Survival curves associated with thicker melanomas did not show significant differences between negative- and positive-SLB patients. SLB provides accurate staging of nodal status in melanoma patients who have no clinical evidence of metastases. Longer follow-up and final results from ongoing trials are necessary to definitively clarify the role of this procedure.

Management of Bone Metastases From Breast Cancer in Upper and Lower Body at the Same Time: A Case Report

PubMed Central

Ciaglia, Gian Franco; Martino, Antonia; Sayad, Khadija; Scoglio, Claudio; Pezzulla, Donato; Cappabianca, Salvatore

2016-01-01

Breast cancer is by far the most common cancer in women, and it has the highest incidence rates in western Europe. At breast cancer diagnosis, approximately 5-6% of women present with distant spread with bone, representing the most common site of metastatic lesions. More than half of the women, who present with metastatic breast cancer at the primary diagnosis, will develop bone metastases. We report a clinical case of a 75-year-old woman, with a history of breast cancer who undergone surgery 7 years ago, presenting bone metastases in different areas. We tried to determinate the major areas of pain and then to quantify it with a one-dimensional scale. After that, we analyzed the images of the previous instrumental exams and the centering CT in order to compare them with what the patient reported and then to decide what we should have targeted first. The aim of our work was to try finding a methodology in order to determinate the priority in the selecting of the area to treat to apply in this kind of patients. PMID:28983365

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

PubMed

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

2017-01-01

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

Oral metastasis from primary transitional cell carcinoma of the renal pelvis: report of a case.

PubMed

Zhang, Y; Gu, Z-Y; Tian, Z; Yang, C; Cai, X-Y

2010-07-01

Transitional cell carcinoma of the renal pelvis is initially a slow growing tumor arising from the transitional epithelium of the mucous membrane of the renal pelvis. Recurrences occur in two forms: superficial bladder cancer and distant metastases. The common metastasis is in the lung, liver, brain and bone. Oral metastasis is seldom reported. The authors report an unusual case of transitional cell carcinoma of the renal pelvis metastasized to the oral cavity and lung simultaneously in a 74-year-old man, which occurred 1 year after a left nephroureterectomy. The patient underwent six courses of chemotherapy (gemcitabine, oxaliplatin, fluorouracil and nedaplatin), and received radiotherapy for the oral lesion. The symptoms were alleviated, but the tumor recurred in the oral cavity 2 years later. Brain and liver metastases were confirmed by CT. Repeated radiotherapy for oral metastasis was performed, but the patient died 4 years after the initial nephroureterectomy due to multiple metastases. Copyright 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Treatment and outcome of patients with chest wall recurrence after mastectomy and breast reconstruction.

PubMed

Chagpar, Anees; Langstein, Howard N; Kronowitz, Steven J; Singletary, S Eva; Ross, Merrick I; Buchholz, Thomas A; Hunt, Kelly K; Kuerer, Henry M

2004-02-01

Chest wall recurrence (CWR) in the setting of previous mastectomy and breast reconstruction can pose complex management dilemmas for clinicians. We examined the impact of breast reconstruction on the treatment and outcomes of patients who subsequently developed a CWR. Between 1988 and 1998, 155 breast cancer patients with CWR after mastectomy were evaluated at our center. Of these patients, 27 had previously undergone breast reconstruction (immediate in 20; delayed in 7). Clinicopathologic features, treatment decisions, and outcomes were compared between the patients with and without previous breast reconstruction. Nonparametric statistics were used to analyse the data. There were no significant differences between the reconstruction and no-reconstruction groups in time to CWR, size of the CWR, number of nodules, ulceration, erythema, and association of CWR with nodal metastases. In patients with previous breast reconstruction, surgical resection of the CWR and repair of the resulting defect tended to be more complex and was more likely to require chest wall reconstruction by the plastic surgery team rather than simple excision or resection with primary closure (26% [7 of 27] versus 8% [10 of 128], P = 0.013). Risk of a second CWR, risk of distant metastases, median overall survival after CWR, and distant-metastasis-free survival after CWR did not differ significantly between patients with and without previous breast reconstruction. Breast reconstruction after mastectomy does not influence the clinical presentation or prognosis of women who subsequently develop a CWR. Collaboration with a plastic surgery team may be beneficial in the surgical management of these patients.

Successful radioimmunotherapy for micro and occult metastases in a SCID mouse model

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

Yokoyama, K.; Koshida, K.; Kinuya, S.

1996-05-01

It is often addressed that the most appropriate candidate, theoretically, for radioimmunotherapy (RIT) is not bulky tumor burden but for micro or occult metastatic foci, The major obstacles in the verification for veracious efficacy of RIT had been clinically and preclinically the difficulty in obtaining such a model. We have developed the model of testicular tumor (primary site) with visible small metastases to the lymph nodes (LNs) and non-visible (occult) lesions to distant organs in severe combined immunodeficient (SCID) mice. And thus, the suppression of minute tumor depositions after RIT was evaluated. One week after hemilateral intratesticular injection of 2more » million of HELA Hep 2 cells that expressed placental alkaline phosphatase (PLAP), the group of the mice were treated with a single dose of I-131 labeled HPMS-1, anti-PLAP MoAb or with saline control. The I-131 labeled HPMS-1 (5.6 MBq / 150 {mu}g) was intravenously administered and at 2 weeks after, the testis, retroperitoneal and intraperitoneal LNs and other gans were removed. For the control group, the testicular tumor and LNs metastases were found in 100% and 86% of the mice. The metastases in the liver and lung were not observed by histological examination but in all mouse samples, the PCR (polymerase chain reaction) assay could identify the human {beta}-globin gene derived from HeLa cells, indicating the presence of definitive metastases. For the treated group, the average testicular tumor weight was significantly reduced by the factor of 2.4 (132 mg vs 311 mg, p<0.01). The LNs metastases were even more distinctively suppressed by the factor of 45.7 (13 mg vs 599 mg, p,0.05). Remarkably, the PCR products from the occult metastases were almost completely controlled; 97% suppression found for the liver and 81% for the lung. Thus, we conclude that using I-131 as a label, RIT is justified to used for targeting and killing minute tumor foci.« less

Analysis of results of radiation therapy for stage IB carcinoma of the cervix.

PubMed

Montana, G S; Fowler, W C; Varia, M A; Walton, L A; Mack, Y

1987-11-01

From April of 1969 through December of 1980, 197 patients with Stage IB, invasive, epidermoid carcinoma of the cervix received radical radiation therapy. The treatment consisted of external beam and intracavitary therapy designed to deliver 7000 to 8000 rad to Point A and 5000 to 5500 rad to the pelvic lymph nodes. The 2-, 5-, and 10-year, disease-free survival rates were 87%, 83%, and 81%, respectively. Thirty-six patients developed recurrent and/or metastatic disease. The sites that failed to remain disease-free were: locoregional in five patients (3%), locoregional with distant metastases in 15 patients (8%), and distant metastases only in 14 patients (7%). In addition, there were two patients (1%) who are considered to have died of disease but the site or sites of recurrence could not be determined. Thirty-nine patients developed complications. The complications were mild and self-limiting--Grade I--in 24 patients (12%) and of moderate severity--Grade II--in eight patients (4%). Seven patients (4%) developed severe--Grade III--complications. A correlation was found between the dose to Point A, the bladder, and the rectum and the complications. The mean dose to Point A for patients without and with complications were 7453 rad (SE +/- 91) and 7737 (SE +/- 124), respectively, with a P value of .05. The mean dose to the bladder for patients without and with urinary complications was 5590 rad (SE +/- 103) and 6335 rad (SE +/- 411), respectively, with a P value of 0.14. The mean dose to the rectum for patients without and with intestinal complications was 5837 rad (SE +/- 103) and 6810 rad (SE +/- 236), respectively, with a P value of 0.001. No correlation was found between the dose to Point A and locoregional recurrences.

A Prospective Outcomes Study of Proton Therapy for Chordomas and Chondrosarcomas of the Spine

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

Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org; Rotondo, Ronny L.; Begosh-Mayne, Dustin

Purpose: To evaluate the effectiveness of definitive or adjuvant external beam proton therapy on survival in patients with chordomas and chondrosarcomas of the spine. Methods and Materials: Between March 2007 and May 2013, 51 patients with a median age of 58 years (range, 22-83 years) with chordoma (n=34) or chondrosarcomas (n=17) of the sacrum (n=21), the cervical spine (n=20), and the thoracolumbar spine (n=10) were treated with external beam proton therapy to a median dose of 70.2 Gy(RBE) [range, 64.2-75.6 Gy(RBE)] at our institution. Distant metastases, overall survival, cause-specific survival, local control, and disease-free survival were calculated. Results: The mean follow-up time was 3.7 yearsmore » (range, 0.3-7.7 years). Across all time points, 25 patients experienced disease recurrence: 18 local recurrences, 6 local and distant recurrences, and 1 distant metastasis. The 4-year rates of overall survival and cause-specific survival were 72%; disease-free survival was 57%, local control was 58%, and freedom from distant metastases was 86%. The median time to local progression was 1.7 years (range, 0.2-6.0 years), and the median time to distant progression was 1.6 years (range, 0.2-6.0 years). The risk factors for local recurrence were age ≤58 years (62% vs 26%; P=.04) and recurrence after prior surgery (29% vs 81%; P=.01). Secondary cancers developed in 2 patients: B-cell lymphoma 5.5 years after treatment and bladder cancer 2 years after treatment. We observed the following toxicities: sacral soft tissue necrosis requiring surgery (n=2), T1 vertebral fracture requiring fusion surgery (n=1), chronic urinary tract infections (n=1), surgery for necrotic bone cyst (n=1), and grade 2 bilateral radiation nephritis (n=1). Conclusion: High-dose proton therapy controls more than half of spinal chordomas and chondrosarcomas and compares favorably with historic photon data. Local progression is the dominant mode of treatment failure and may be reduced by treating patients at the time of initial diagnosis. The impact of age is a novel finding of this study.« less

Pathological characteristics and clinical specifications in gastroenteropancreatic neuroendocrine tumors: a study of 68 cases.

PubMed

Stoica-Mustafa, Elena; Pechianu, C; Iorgescu, Andreea; Hortopan, Monica; Dima, Simona Olimpia; Tomulescu, V; Dumitraşcu, T; Ungureanu, C; Andronesi, D; Popescu, I; Herlea, V

2012-01-01

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a group of tumors, having their origin in cells of diffuse endocrine system, with particular clinical course, diagnosis and treatment. In our study, were included 68 patients with neuroendocrine digestive tumors admitted, diagnosed and treated in Fundeni Clinical Institute, Bucharest, in the last ten years--2000-2010 (retrospective study). Thirty-three (49%) patients were males, 35 (51%) females, and the main age was 58.9 years. In 62 (90.3%) cases was possible to find the primary tumor. The examined tumors had different localizations: pancreas--32 (47.04%) cases (head--17 (24.99%) cases, and body and tail--15 (22.05%) cases), stomach--7 (10.29%) cases, small intestine--7 (10.29%) cases, 6 (8.82%) cases--unknown primary site (diagnosis was established on metastases), right colon--6 (8.82%) cases, liver--6 (8.82%) cases, rectum--2 (2.94%) cases, and retroperitoneum--2 (2.94%) cases. Microscopic examination revealed 59 (86.8%) malignant tumors and 9 (13.2%) benign tumors. Using WHO 2000 Classification, 28 cases of malignant tumors were well-differentiated neuroendocrine carcinomas, and 31 cases were poor differentiated neuroendocrine carcinomas. From malignant cases, 25 (42.3%) have distant metastases and 15 (25.9%) lymph node metastases. Cases of gastroenteropancreatic neuroendocrine tumors included in our study had clinical and histopathological features in correspondence with data from literature--slight predominance in women, predominance in 5th and 6th decades of life, the most frequent localizations were at pancreatic level--both head and body and tail, but the rarest were in colon and retroperitoneum. Most of the cases studied, were malignant tumors, from these more than a half were poor differentiated, and a quarter of them having lymph node or distant metastases.

Concurrent three-dimensional conformal radiotherapy and chemotherapy for postoperative recurrence of mediastinal lymph node metastases in patients with esophageal squamous cell carcinoma: a phase 2 single-institution study

PubMed Central

2014-01-01

Aim The aim of this study was to evaluate the effects of radiotherapy plus concurrent weekly cisplatin chemotherapy on the postoperative recurrence of mediastinal lymph node metastases in esophageal cancer patients. Methods Ninety-eight patients were randomly enrolled to receive either three-dimensional conformal radiotherapy alone (group A) or concurrent chemoradiotherapy (group B). A radiation dose of 62–70 Gy/31–35 fractions was delivered to the recurrent tumor. Furthermore, the patients in group B simultaneously received weekly doses of cisplatin (30 mg/m2), and the survival outcomes and toxic effects were compared. Results The response rate of group B (91.8%) was significantly greater than that of group A (73.5%) (χ2 = 5.765, P = 0.016). The 1- and 3-year survival rates of group B (85.7% and 46.9%, respectively) were also greater than those of group A (69.4% and 28.6%, respectively). However, there were no significant differences in the 5-year survival rates. The numbers of patients who died of distant metastases in groups A and B were 13 (26.5%) and 5 (10.2%), respectively (χ2 = 4.356, P = 0.036). Acute radiation-related esophagitis and granulocytopenia in group B was frequent. However, intergroup differences in terms of late toxicity were not significant. Conclusions Three-dimensional conformal radiotherapy (3DCRT) is a practical and feasible technique to treat the recurrence of mediastinal lymph node metastases of postoperative esophageal cancer. In addition, concurrent chemotherapy can increase local tumor control, decrease the distant metastasis rate, and increase the long-term survival rate. PMID:24438695

Concurrent three-dimensional conformal radiotherapy and chemotherapy for postoperative recurrence of mediastinal lymph node metastases in patients with esophageal squamous cell carcinoma: a phase 2 single-institution study.

PubMed

Ma, Dai-yuan; Tan, Bang-xian; Liu, Mi; Li, Xian-fu; Zhou, Ye-qin; Lu, You

2014-01-19

The aim of this study was to evaluate the effects of radiotherapy plus concurrent weekly cisplatin chemotherapy on the postoperative recurrence of mediastinal lymph node metastases in esophageal cancer patients. Ninety-eight patients were randomly enrolled to receive either three-dimensional conformal radiotherapy alone (group A) or concurrent chemoradiotherapy (group B). A radiation dose of 62-70 Gy/31-35 fractions was delivered to the recurrent tumor. Furthermore, the patients in group B simultaneously received weekly doses of cisplatin (30 mg/m(2)), and the survival outcomes and toxic effects were compared. The response rate of group B (91.8%) was significantly greater than that of group A (73.5%) (χ(2) = 5.765, P = 0.016). The 1- and 3-year survival rates of group B (85.7% and 46.9%, respectively) were also greater than those of group A (69.4% and 28.6%, respectively). However, there were no significant differences in the 5-year survival rates. The numbers of patients who died of distant metastases in groups A and B were 13 (26.5%) and 5 (10.2%), respectively (χ(2) = 4.356, P = 0.036). Acute radiation-related esophagitis and granulocytopenia in group B was frequent. However, intergroup differences in terms of late toxicity were not significant. Three-dimensional conformal radiotherapy (3DCRT) is a practical and feasible technique to treat the recurrence of mediastinal lymph node metastases of postoperative esophageal cancer. In addition, concurrent chemotherapy can increase local tumor control, decrease the distant metastasis rate, and increase the long-term survival rate.

Stereotactic radiosurgery alone for multiple brain metastases? A review of clinical and technical issues

PubMed Central

Ruschin, Mark; Ma, Lijun; Verbakel, Wilko; Larson, David; Brown, Paul D.

2017-01-01

Abstract Over the past three decades several randomized trials have enabled evidence-based practice for patients presenting with limited brain metastases. These trials have focused on the role of surgery or stereotactic radiosurgery (SRS) with or without whole brain radiation therapy (WBRT). As a result, it is clear that local control should be optimized with surgery or SRS in patients with optimal prognostic factors presenting with up to 4 brain metastases. The routine use of adjuvant WBRT remains debatable, as although greater distant brain control rates are observed, there is no impact on survival, and modern outcomes suggest adverse effects from WBRT on patient cognition and quality of life. With dramatic technologic advances in radiation oncology facilitating the adoption of SRS into mainstream practice, the optimal management of patients with multiple brain metastases is now being put forward. Practice is evolving to SRS alone in these patients despite a lack of level 1 evidence to support a clinical departure from WBRT. The purpose of this review is to summarize the current state of the evidence for patients presenting with limited and multiple metastases, and to present an in-depth analysis of the technology and dosimetric issues specific to the treatment of multiple metastases. PMID:28380635

Esophageal Cancer Metastases to Unexpected Sites: A Systematic Review

PubMed Central

2017-01-01

The most common pattern of esophageal cancer metastases (ECM) is to the lymph nodes, lung, liver, bones, adrenal glands, and brain. On the other hand, unexpected metastasis (UM) spread to uncommon sites has increasingly reported and consequently affected the pathway of diagnosis, staging, and management. Using the PubMed database, a systematic search of the following headings “Esophageal” and “Metastasis” or “Metastases” was performed, 10049 articles were identified, and the articles were included if they demonstrated unexpected ECM. 84% of cases were men with an average age of 60.7 years. EC was located in the lower third in 65%. Two-thirds of the UM originated from the lower esophagus, and the two major histological types were adenocarcinoma 40% and squamous cell carcinoma 60%. Metastases were disseminated toward five main anatomical sites: the head and neck (42%), thoracic (17%), abdomen and pelvis (25%), extremities (9%), and multiple skin and muscle metastases (7%). The EC metastases were found to be synchronous 42% and metachronous 58%, isolated in 53.5% and multiple in 46.5%. The overall survival rate was 10.2 months. Since distant metastases are responsible for most EC-related deaths, understanding of ECM dissemination patterns needs more extensive studies. These critical data are the cornerstone of optimal cancer approach and treatment. PMID:28659974

Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis.

PubMed

Asik, Mehmet; Binnetoglu, Emine; Sen, Hacer; Gunes, Fahri; Muratli, Asli; Kankaya, Duygu; Uysal, Fatma; Sahin, Mustafa; Ukinc, Kubilay

2015-01-01

Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). We reviewed reports of primary SCC of the thyroid gland published in the English literature. We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p < 0.05). Patients with primary SCC of the thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases.

Study of matrix metalloproteinases and their inhibitors in breast cancer

PubMed Central

Vizoso, F J; González, L O; Corte, M D; Rodríguez, J C; Vázquez, J; Lamelas, M L; Junquera, S; Merino, A M; García-Muñiz, J L

2007-01-01

An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases. PMID:17342087

Secondary signet-ring cell adenocarcinoma of urinary bladder from a gastric primary.

PubMed

Sharma, Pramod K; Vijay, Mukesh K; Das, Ranjit K; Chatterjee, Uttara

2011-05-01

Primary bladder tumor is a frequent urological malignancy, whereas the incidence of secondary bladder tumor from a distant organ is quite rare. Secondary bladder neoplasms represent 1% of all malignant bladder tumors, of which distant metastases from stomach account for about 4% of cases. We present the case of a 30-year-old male who underwent partial gastrectomy for Signet-ring cell carcinoma of the stomach and presented 2 years later with hematuria. On computerized tomography scan, a bladder tumor was found which was resected cystoscopically. The histopathological examination revealed secondary Signet-ring cell adenocarcinoma of the urinary bladder.

[The Role of Supraclavicular lymph node dissection in Breast Cancer Patients with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis].

PubMed

Zhang, W; Qi, X M; Chen, A X; Zhang, P; Cao, X C; Xiao, C H

2017-05-23

Objective: In this study, we evaluated the effect of supraclavicular lymph node dissection in breast cancer patients who presented with ipsilateral supraclavicular lymph node metastasis (ISLM) without distant metastasis. Methods: A total of 90 patients with synchronous ISLM without distant metastasis between 2000 and 2009 were retrospectively analyzed. Patients were retrospectively divided into two groups, namely supraclavicular lymph node dissection group(34 patients) and non-dissection group(56 patients), according to whether they underwentsupraclavicular lymph node dissection or not.The Kaplan-Meier method was applied to analyze the locoregional relapse free survival (LRFS) and overall survival(OS). Results: Median follow-upwas 85 months(range, 6 to 11 months). Local recurrence in 32 cases, 47 cases of distant metastasis, of which 25 patients were accompanied by both locoregional relapse and distant metastasis. Of the 32 patients with locoregional relapse, 11 patients were in the lymph node dissection group and 21 patients in the control group. Of the 47 patients with distant metastases, 17 were treated with lymph node dissection, 30 in the control group. Thirty-two patients died in the whole group and 16 patients underwentlymph node dissection and 16 patients didn't. There was no significant difference between the rate of 5-year LRFS and 5-year OS ( P =0.359, P =0.246). For patients of ER negative, the 5-year loco-regional relapse free survival rates were 63.7% and 43.3% in supraclavicular lymph node dissection group and control group, respectively. The 5-year overall survival rates were 52.1% and 52.3%, respectively, and there were no statistically significant differences ( P =0.118, P =0.951). For patients of PR negative, the 5-yearloco-regional relapse free rates were 59.8% and 46.2%, respectively, and the 5-year overall survival rates were 50.6% and 43.2%, respectively, and there was no significant difference between the two groups ( P =0.317, P =0.973). The 5-year recurrence-free survival rates of human epidermal growth factor receptor 2 (HER2)-positive patients were 61.2% and 48.0%( P =0.634), respectively, and the 5-year overall survival rates were 37.2% and 65.4%( P =0.032). Forty-seven patients suffered distant metastases and the 5-year metastases free survival rates were 37.3% and 38.5% in supraclavicular lymph node dissection group and control group, respectively. Conclusion: Supraclavicular lymph node dissection maybe an effective approach to improve the loco-regional control for the patients with ISLM, especially for ER negative and PR negative subtypes, but it might has adverseeffects for the patients with negative HER2 status.

Patient with Gorlin syndrome and metastatic basal cell carcinoma refractory to smoothened inhibitors.

PubMed

Zhu, Gefei A; Li, Angela S; Chang, Anne Lynn S

2014-08-01

Basal cell carcinomas (BCCs) in patients with Gorlin syndrome have been reported to be extremely sensitive to Smoothened (SMO) inhibitors, a novel targeted therapy against the Hedgehog pathway, because of characteristic mutations in these patients. A few cases of disease refractory to oral therapy with SMO inhibitors have been reported in patients with Gorlin syndrome and nonmetastatic BCCs, but refractory disease in distantly metastatic tumors has not been documented in this high-risk group. A man with Gorlin syndrome and innumerable cutaneous BCCs presented with biopsy-proven BCC in his lungs. After SMO inhibitor therapy, almost all of his cutaneous tumors shrank, but his lung metastases did not. These lung metastases remained refractory to treatment despite institution of a second SMO inhibitor. We report a case of Gorlin syndrome in a patient with metastatic BCC refractory to SMO inhibitors. Furthermore, clinical responses in this patient's cutaneous tumors did not parallel the responses in the distant site. However, serial imaging after diagnosis of metastatic disease can be critical to monitor for response to therapy.

Antithyroid peroxidase antibody positivity is associated with lower incidence of metastasis in breast cancer.

PubMed

Kemal, Yasemin; Demirag, Guzin; Ekiz, Kubilay; Yucel, Idris

2015-05-01

Thyroid extracts were first used to treat patients with metastatic breast cancer over a century ago. Since then, a number of studies have investigated the association between thyroid disorders and breast cancer. The presence of antibodies to thyroid peroxidase (TPOab) was recently reported to be associated with improved outcome in these patients. The aim of the present study was to evaluate the association between TPOab positivity and clinicopathological characteristics in breast cancer patients. The study included 318 newly diagnosed cases of breast cancer treated at Ondokuz Mayis University Hospital, Samsun, Turkey, between 2008 and 2012. Serum thyroid-stimulating hormone, free triiodothyronine and free thyroxine levels were measured at the time of diagnosis. Of the 318 patients, 253 were considered to be TPOab-negative (TPOab ≤34 IU/ml) and 65 TPOab-positive (TPOab >34 IU/ml). No cases with distant metastases were found in the TPOab-positive group. However, 20 (7.9%) of the 253 patients displayed distant metastases in the TPOab-negative group (P=0.01). Therefore, TPOab positivity was found to be associated with a lower incidence of metastasis in breast cancer patients.

Tumor vascularity and hematogenous metastasis in experimental murine intraocular melanoma.

PubMed Central

Grossniklaus, H E

1998-01-01

PURPOSE: The purpose of this study is to test the hypothesis that primary tumor vascularity in a murine model of intraocular melanoma positively correlates with the development and hematogenous spread of metastasis. METHODS: Forty 12-week-old C57BL6 mice were inoculated in either the anterior chamber (AC) or posterior compartment (PC) of 1 eye with 5 x 10(5) cells/microL of Queens tissue culture melanoma cells. The inoculated eye was enucleated at 2 weeks; the mice were sacrificed at 4 weeks postinoculation, and necropsies were performed. The enucleated eyes were examined for histologic and ultrastructural features, including relationship of tumor cells to tumor vascular channels, vascular pattern, and mean vascular density. RESULTS: Melanoma grew and was confined to the eye in 12 of 20 AC eyes and 10 of 20 PC eyes. Histologic and electron microscopic examination showed tumor invasion into vascular channels. Five of 12 AC tumors (42%) and 8 of 10 PC tumors (80%) metastasized. All of the AC tumors, but none of the PC tumors, that distantly metastasized also metastasized to ipsilateral cervical lymph nodes (P = .00535). There was no statistically significant difference of vascular pattern between the melanomas that did and did not metastasize to lungs in the PC group (P = .24), although there was a significant difference in the AC group (P = .02). Tumors with high-grade vascular patterns were more likely to metastasize than tumors with low-grade vascular patterns in the AC group. The mean vascular density positively correlated with the presence and number of metastases in both groups (P = .0000 and P < .001, respectively). There was no statistically significant difference of vascular pattern and mean vascular density for AC versus PC melanoma (P = .97). CONCLUSIONS: The rate of metastasis in this murine intraocular melanoma model positively correlates with primary tumor vascularity. The melanoma metastasizes via invasion of tumor vascular channels. AC melanoma also metastasizes through regional lymphatics. Images FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 PMID:10360307

Can insulin-like growth factor 1 (IGF-1), IGF-1 receptor connective tissue growth factor and Ki-67 labelling index have a prognostic role in pulmonary carcinoids?

PubMed

Kanakis, Georgios A; Grimelius, Lars; Papaioannou, Dimitrios; Kaltsas, Gregory; Tsolakis, Apostolos V

2018-04-27

Altered expression of Insulin-like Growth Factor-1 (IGF-1), its receptor (IGF-1R), Connective Tissue Growth Factor (CTGF) and Hypoxia Inducible Factor-1 (HIF-1), has been implicated in tumorigenesis. So far, these factors have not been studied systematically in Pulmonary Carcinoids (PCs). To examine IGF-1, IGF-1R, CTGF and HIF-1 expression in PCs, and assess their prognostic value over established factors. Retrospective study of 121 PCs (104 Typical and 17 Atypical). The expression of growth factors was studied immunohistochemically and tumors were considered positive if immunoreactivity appeared in >50% of cells. All studied parameters were expressed in the majority of tumors (IGF-1, IGF-1R, CTGF and HIF-1, in 78.5%, 67%, 72% and 78%, respectively). Their expression tended to be more frequent in TCs and in tumors with Ki-67≤2% (significant only for HIF-1; 82 vs. 53%; p=0.023 and 83 vs. 63%; p=0.025 respectively). CTGF was the only factor correlated with more extensive disease (larger size; presence of lymph node and distant metastases). According to logistic regression analysis, only advanced age, Ki-67≥3.4% and lymph node involvement could predict the development of distant metastases. IGF-1, IGF-1R, CTGF and HIF-1 are avidly expressed in PCs; however, their presence did not appear to be of statistically significant value over established prognostic factors.

Biochemical Response to Androgen Deprivation Therapy Before External Beam Radiation Therapy Predicts Long-term Prostate Cancer Survival Outcomes

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

Zelefsky, Michael J., E-mail: zelefskm@mskcc.org; Gomez, Daniel R.; Polkinghorn, William R.

2013-07-01

Purpose: To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5more » years. Results: The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Conclusions: Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes.« less

A primer of bone metastases management in breast cancer patients

PubMed Central

Petrut, B.; Trinkaus, M.; Simmons, C.; Clemons, M.

2008-01-01

Bone is the most common site for distant spread of breast cancer. Following a diagnosis of metastatic bone disease, patients can suffer from significant morbidity because of pain and skeletal related events (sres). Bisphosphonates are potent inhibitors of osteoclastic function and the mainstay of bone-directed therapy for bone metastases. The aims of bisphosphonates are to prevent and delay sres, to reduce bone pain, and to improve quality of life. Bisphosphonate therapy appears to have revolutionized treatment of bone metastases, but bisphosphonate use has several limitations. Those limitations include the high cost of the agents and the need for return trips to the clinic for intravenous treatment. Moreover, many uncertainties surround bisphosphonate use—for example, the timing of bisphosphonate initiation, the choice of bisphosphonate to use, the optimal duration of treatment, and the appropriate means to identify patients who will and will not benefit. In addition, potentially serious adverse effects have been associated with bisphosphonate use—for example, renal toxicity, gastrointestinal side effects, and osteonecrosis of the jaw. The present review is intended as a primer for oncology specialists who treat patients with bone metastases secondary to breast cancer. It focuses on bisphosphonate treatment guidelines, the evidence for those guidelines, and a discussion of new therapeutic agents. It also discusses the use of biochemical markers of bone metabolism, which show promise for predicting the risk of a patient’s developing a sre and of benefiting from bisphosphonate treatment. PMID:18231649

Unusual Asymptomatic Fluorodeoxyglucose Avid Pheochromocytoma in a Case of Myxoid Liposarcoma of the Extremity on 18-F Fluorodeoxyglucose Positron Emission Tomography-computed Tomography.

PubMed

Shivdasani, Divya; Singh, Natasha; Pereira, Melvika; Zade, Anand

2017-01-01

Sarcomas are a heterogeneous group of rare tumors and arise either from soft tissue or from bone. Soft-tissue sarcomas (STSs) initially metastasize to the lungs. Metastases to extrapulmonary sites such as liver, brain, and soft tissue distant from primary tumor usually develop later. However, cases with isolated adrenal metastasis without disseminated disease have been reported in literature. We present a case of primary myxoid liposarcoma of the lower limb, in which staging 18 -F fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan detected a suspicious FDG avid adrenal lesion which eventually on resection was diagnosed as asymptomatic pheochromocytoma. Pheochromocytomas have been reported to demonstrate FDG uptake mimicking metastasis. Hence, while interpreting FDG PET-CT scans in the context of STSs, both the extrapulmonary metastatic potential of aggressive histological subtypes of sarcoma and rare possibility of FDG avid coexistent benign tumor should be taken into consideration.

Malignant pilomatricoma in a dog with local and distant metastases treated with chemotherapy and bisphosphonates

PubMed Central

Treggiari, Elisabetta; Elliott, James W.

2017-01-01

A ten-year-old male neutered cross breed dog presented for evaluation of a mass associated with the left scapular bone, identified as a carcinoma. The dog had a malignant pilomatricoma removed from the left lateral thigh 6 months earlier. Histopathology review of the cutaneous and scapular mass identified the same tumour type, confirming metastatic disease; additional metastases to the inguinal lymph node, liver and lungs were identified. Chemotherapy resulted in partial responses/stable disease of very short duration. Bisphosphonates were administered due to lack of a measurable response and worsening of the associated lameness. The patient ultimately developed a symptomatic vertebral metastasis and was euthanased. The dog survived 255 days since medical treatment was started and 455 days since surgical removal of the primary tumour. This case report suggests that medical treatment with the addition of analgesia may be able to palliate clinical signs and possibly extend survival in dogs with metastatic epithelial cancer. PMID:28795016

Uveal Melanoma Treated With Iodine-125 Episcleral Plaque: An Analysis of Dose on Disease Control and Visual Outcomes

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

Perez, Bradford A.; Mettu, Pradeep; Vajzovic, Lejla

2014-05-01

Purpose: To investigate, in the treatment of uveal melanomas, how tumor control, radiation toxicity, and visual outcomes are affected by the radiation dose at the tumor apex. Methods and Materials: A retrospective review was performed to evaluate patients treated for uveal melanoma with {sup 125}I plaques between 1988 and 2010. Radiation dose is reported as dose to tumor apex and dose to 5 mm. Primary endpoints included time to local failure, distant failure, and death. Secondary endpoints included eye preservation, visual acuity, and radiation-related complications. Univariate and multivariate analyses were performed to determine associations between radiation dose and the endpointmore » variables. Results: One hundred ninety patients with sufficient data to evaluate the endpoints were included. The 5-year local control rate was 91%. The 5-year distant metastases rate was 10%. The 5-year overall survival rate was 84%. There were no differences in outcome (local control, distant metastases, overall survival) when dose was stratified by apex dose quartile (<69 Gy, 69-81 Gy, 81-89 Gy, >89 Gy). However, increasing apex dose and dose to 5-mm depth were correlated with greater visual acuity loss (P=.02, P=.0006), worse final visual acuity (P=.02, P<.0001), and radiation complications (P<.0001, P=.0009). In addition, enucleation rates were worse with increasing quartiles of dose to 5 mm (P=.0001). Conclusions: Doses at least as low as 69 Gy prescribed to the tumor apex achieve rates of local control, distant metastasis–free survival, and overall survival that are similar to radiation doses of 85 Gy to the tumor apex, but with improved visual outcomes.« less

Metastasizing Esthesioneuroblastoma in a Dog.

PubMed

Siudak, K; Klingler, M; Schmidt, M J; Herden, C

2015-07-01

A 7-year-old Afghan hound presented with a history of disorientation, loss of vision, and seizures. Magnetic resonance imaging helped identify a mass at the level of the main olfactory bulb that compressed and displaced adjacent tissues in the cribriform plate into the nasal cavity and nasopharynx. Bony structures were osteolytic. After removing almost 80% of the mass, the tumor recurred a few months later. Due to severe respiratory distress and subsequent to an ultrasound diagnosis of a liver tumor, the dog was euthanized. In addition to the nasal mass, a single nodule in the liver and multiple nodules in the lung were present. All masses had similar cell morphology and were diagnosed as metastasizing esthesioneuroblastoma. The neoplastic cells expressed neuron-specific enolase and chromogranin A, and a few cells within the nasal mass were positive for cytokeratin. This is the first description of a canine esthesioneuroblastoma with distant metastases. © The Author(s) 2014.

[Primary pulmonary hemangiopericytoma: 2 new cases].

PubMed

Essola, B; Remmelink, M; Kessler, R; Scillia, P; Rocmans, P

2003-10-01

We describe two new resected cases of primary pulmonary hemangiopericytoma and the review of cases published in the period 1954-2002. The first patient has a large pulmonary mass of the right apex revealed by scapular pain. The right upper lobectomy with free margins reveals hemangiopericytoma. Pelvic and pulmonary metastases appear two years after surgery, treated by two series of chemotherapy without clinical response. After acute nephrotoxicity controlled by hemodialysis, the patient dies with distant metastases three years and an half after thoracotomy. The second patient develops dry cough and thoracic pain with discovery of a cavitary mass in the right pulmonary field. Fine needle aspiration cytology suggests a mesenchymatous lesion. Three months after extended pneumonectomy, the intrathoracic tumour relapses and regresses partially under chemotherapy. Femoral and brain metastases are irradiated. The patient dies 22 months after thoracotomy. Histology and immunohistochemistry of both tumours closely related to solitary fibrous tumour confirm malignant hemangiopericytoma. Primary pulmonary hemangiopericytoma is rare and may be benign or malignant. Radical resection is the best treatment. Chemotherapy and radiotherapy may improve the prognosis. Compared with lung cancer, the tumour is a slow growing mass, often voluminous, with delayed symptoms, very few lymph node dissemination, rare brain metastasis, more frequent cutaneous or retroperitoneal dissemination, often after long-term and requiring indeed a 10 to 20 years follow-up.

[A case report of anorectal malignant melanoma showing a complete response after DTIC/ACNU/VCR therapy].

PubMed

Sasaki, Shin; Kojima, Tetsu; Hidemura, Akio; Hatanaka, Kazuhito; Uekusa, Toshimasa; Ishimaru, Masahiro

2010-10-01

We report herein the case of a 64-year-old male who presented with hematochezia. The patient was diagnosed with malignant melanoma of the anorectum using colonoscopy. Preoperative studies revealed no distant metastases, and he underwent Miles operation. Pathological exams revealed that the tumor had invaded the submucosa with lymphatic and venous invasion. Cancer cells were found in regional lymph nodes. Post-operative CT scan demonstrated multiple metastases in the liver, and he received two courses of combined chemotherapy, DAV regimen (dacarbazine: DTIC 100 mg iv days 1-5, nimustine hydrochloride: ACNU 100 mg iv day 1, vincristine sulfate: VCR 1 mg iv day 1), leading to a complete response. However, malignant melanoma cells were found in hernia contents at the operation for left inguinal hernia, which led to a diagnosis of recurrent malignant melanoma. The patient has subsequently been well without any sign of recurrence including liver metastases. To our knowledge, this is the first report of a complete response in a patient with multiple liver metastases of anorectal malignant melanoma after DAV regimen.

Dynamics of the hazard for distant metastases after ipsilateral breast tumor recurrence according to estrogen receptor status: An analysis of 2851 patients.

PubMed

Gennaro, Massimiliano; Di Cosimo, Serena; Ardoino, Ilaria; Veneroni, Silvia; Mariani, Luigi; Agresti, Roberto; Daidone, Maria Grazia; de Braud, Filippo; Apolone, Giovanni; Biganzoli, Elia; Demicheli, Romano

2018-05-14

Breast cancer (BC) patients with ipsilateral breast tumor recurrence (IBTR) are at high risk of developing distant metastases (DM). We aimed to evaluate the risk pattern of developing DM, with respect to the occurrence of IBTR, in a large series of patients homogeneously treated by conservative surgery (QUART) with a considerably long follow-up. Piecewise exponential model was used to investigate DM dynamics conditioning on known prognostic factors and IBTR occurrence as time dependent covariate. The model was extended to account for the timescale induced by IBTR, namely the time elapsed since IBTR to the endpoint. Among 2851 BCE patients receiving QUART, 209 were assessable for IBTR. After a median follow-up of 129 months, 588 patients presented DM (CCI = 27.3%) as first event and 92 (CCI = 48.8%) following IBTR. Primary tumor size and nodal status confirmed their prognostic value. The hazard for DM was early and high in Estrogen Receptor (ER) negative BC patients; while it was initially low but increases during follow-up in ER positive cases. Patients experiencing IBTR showed DM dynamic similar to that following primary tumor, with a sudden increased risk within 24 months from surgery, regardless the time elapsed since QUART. BC patients experiencing IBTR showed a sudden and sustained risk of DM following surgery. Our findings are consistent with the hypothesis that IBTR occurrence might act as a "time resector" for risk of DM, and provide a rationale for proper surveillance guidelines and systemic therapy for optimizing BC recurrence and appropriate choice of treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Locoregional Failure Rate After Preoperative Chemoradiation of Esophageal Adenocarcinoma and the Outcomes of Salvage Strategies

PubMed Central

Sudo, Kazuki; Taketa, Takashi; Correa, Arlene M.; Campagna, Maria-Claudia; Wadhwa, Roopma; Blum, Mariela A.; Komaki, Ritsuko; Lee, Jeffrey H.; Bhutani, Manoop S.; Weston, Brian; Skinner, Heath D.; Maru, Dipen M.; Rice, David C.; Swisher, Stephen G.; Hofstetter, Wayne L.; Ajani, Jaffer A.

2013-01-01

Purpose The primary purpose of surveillance of patients with esophageal adenocarcinoma (EAC) and/or esophagogastric junction adenocarcinoma after local therapy (eg, chemoradiotherapy followed by surgery or trimodality therapy [TMT]) is to implement a potentially beneficial salvage therapy to overcome possible morbidity/mortality caused by locoregional failure (LRF). However, the benefits of surveillance are not well understood. We report on LRFs and salvage strategies in a large cohort. Patients and Methods Between 2000 and 2010, 518 patients with EAC who completed TMT were analyzed for the frequency of LRF over time and salvage therapy outcomes. Standard statistical techniques were used. Results For 518 patients, the median follow-up time was 29.3 months (range, 1 to 149 months). Distant metastases (with or without LRF) occurred in 188 patients (36%), and LRF only occurred in 27 patients (5%). Eleven of 27 patients had lumen-only LRF. Most LRFs (89%) occurred within 36 months of surgery. Twelve patients had salvage chemoradiotherapy, but only five survived more than 2 years. Four patients needed salvage surgery, and three who survived more than 2 years developed distant metastases. The median overall survival of 27 patients with LRF was 17 months, and 10 patients (37%) survived more than 2 years. Thus, only 2% of all 518 patients benefited from surveillance/salvage strategies. Conclusion Our surveillance strategy, which is representative of many others currently being used, raises doubts about its effectiveness and benefits (along with concerns regarding types and times of studies and costs implications) to patients with EAC who have LRF only after TMT. Fortunately, LRFs are rare after TMT, but the salvage strategies are not highly beneficial. Our data can help develop an evidence-based surveillance strategy. PMID:24145339

Cutaneous metastases of a mammary carcinoma in a llama.

PubMed Central

Leichner, T L; Turner, O; Mason, G L; Barrington, G M

2001-01-01

An 8-year-old, female llama was evaluated for nonhealing, ulcerative, cutaneous lesions, which also involved the mammary gland. Biopsies of the lesions distant from and within the mammary gland area revealed an aggressive carcinoma. The tumor was confirmed at necropsy to be a mammary gland adenocarcinoma with cutaneous metastasis. Images Figure 1. PMID:11265189

Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.

PubMed

Abugharib, Ahmed; Jackson, William C; Tumati, Vasu; Dess, Robert T; Lee, Jae Y; Zhao, Shuang G; Soliman, Moaaz; Zumsteg, Zachary S; Mehra, Rohit; Feng, Felix Y; Morgan, Todd M; Desai, Neil; Spratt, Daniel E

2017-03-01

Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy. We performed a multi-institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made to determine the optimal definition of early salvage radiotherapy, including 1) the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to 21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen deprivation therapy, and biochemical relapse-free, distant metastases-free and prostate cancer specific survival. Median followup was 9.8 years. Time from radical prostatectomy to salvage radiotherapy did not correlate with 10-year biochemical relapse-free survival rates (R 2 = 0.18). Increasing pre-salvage radiotherapy prostate specific antigen strongly correlated with biochemical relapse-free survival (R 2 = 0.91). Increasing detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than 0.5 ng/ml) predicted worse 10-year biochemical relapse-free survival (62%, 44% and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%), distant metastases-free survival (86%, 79% and 66%, each p <0.001) and prostate cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On multivariable analysis early salvage radiotherapy (prostate specific antigen greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in biochemical failure, use of salvage androgen deprivation therapy and distant metastases compared to very early salvage radiotherapy (prostate specific antigen 0.01 to 0.2 ng/ml). The duration from radical prostatectomy to salvage radiotherapy is not independently prognostic for outcomes after salvage radiotherapy and it should not be used to define early salvage radiotherapy. Grouping all patients with pre-salvage radiotherapy prostate specific antigen 0.5 ng/ml or less may be inadequate to define early salvage radiotherapy and it has a relevant impact on ongoing and future clinical trials. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Increased expression of a set of genes enriched in oxygen binding function discloses a predisposition of breast cancer bone metastases to generate metastasis spread in multiple organs.

PubMed

Capulli, Mattia; Angelucci, Adriano; Driouch, Keltouma; Garcia, Teresa; Clement-Lacroix, Philippe; Martella, Francesco; Ventura, Luca; Bologna, Mauro; Flamini, Stefano; Moreschini, Oreste; Lidereau, Rosette; Ricevuto, Enrico; Muraca, Maurizio; Teti, Anna; Rucci, Nadia

2012-11-01

Bone is the preferential site of distant metastasis in breast carcinoma (BrCa). Patients with metastasis restricted to bone (BO) usually show a longer overall survival compared to patients who rapidly develop multiple metastases also involving liver and lung. Hence, molecular predisposition to generate bone and visceral metastases (BV) represents a clear indication of poor clinical outcome. We performed microarray analysis with two different chip platforms, Affymetrix and Agilent, on bone metastasis samples from BO and BV patients. The unsupervised hierarchical clustering of the resulting transcriptomes correlated with the clinical progression, segregating the BO from the BV profiles. Matching the twofold significantly regulated genes from Affymetrix and Agilent chips resulted in a 15-gene signature with 13 upregulated and two downregulated genes in BV versus BO bone metastasis samples. In order to validate the resulting signature, we isolated different MDA-MB-231 clonal subpopulations that metastasize only in the bone (MDA-BO) or in bone and visceral tissues (MDA-BV). Six of the signature genes were also significantly upregulated in MDA-BV compared to MDA-BO clones. A group of upregulated genes, including Hemoglobin B (HBB), were involved in oxygen metabolism, and in vitro functional analysis of HBB revealed that its expression in the MDA subpopulations was associated with a reduced production of hydrogen peroxide. Expression of HBB was detected in primary BrCa tissue but not in normal breast epithelial cells. Metastatic lymph nodes were frequently more positive for HBB compared to the corresponding primary tumors, whereas BO metastases had a lower expression than BV metastases, suggesting a positive correlation between HBB and ability of bone metastasis to rapidly spread to other organs. We propose that HBB, along with other genes involved in oxygen metabolism, confers a more aggressive metastatic phenotype in BrCa cells disseminated to bone. Copyright © 2012 American Society for Bone and Mineral Research.

Secondary signet-ring cell adenocarcinoma of urinary bladder from a gastric primary

PubMed Central

Sharma, Pramod K.; Vijay, Mukesh K.; Das, Ranjit K.; Chatterjee, Uttara

2011-01-01

Primary bladder tumor is a frequent urological malignancy, whereas the incidence of secondary bladder tumor from a distant organ is quite rare. Secondary bladder neoplasms represent 1% of all malignant bladder tumors, of which distant metastases from stomach account for about 4% of cases. We present the case of a 30-year-old male who underwent partial gastrectomy for Signet-ring cell carcinoma of the stomach and presented 2 years later with hematuria. On computerized tomography scan, a bladder tumor was found which was resected cystoscopically. The histopathological examination revealed secondary Signet-ring cell adenocarcinoma of the urinary bladder. PMID:21747602

The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer.

PubMed

Brockton, Nigel T; Gill, Stephanie J; Laborge, Stephanie L; Paterson, Alexander H G; Cook, Linda S; Vogel, Hans J; Shemanko, Carrie S; Hanley, David A; Magliocco, Anthony M; Friedenreich, Christine M

2015-07-10

Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the potential of metabolomic profiles for risk assessment and early detection and the signalling pathways controlling the metastatic tumour microenvironment. There is substantial synergy between the four projects and it is hoped that this integrated program of research will advance our understanding of key aspects of bone metastases from breast cancer to improve the prevention, prediction, detection, and treatment of these lesions.

Intensity-Modulated Radiation Therapy for the Treatment of Squamous Cell Anal Cancer With Para-aortic Nodal Involvement

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

Hodges, Joseph C.; Das, Prajnan, E-mail: PrajDas@mdanderson.or; Eng, Cathy

2009-11-01

Purpose: To determine the rates of toxicity, locoregional control, distant control, and survival in anal cancer patients with para-aortic nodal involvement, treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy at a single institution. Methods and Materials: Between 2001 and 2007, 6 patients with squamous cell anal cancer and para-aortic nodal involvement were treated with IMRT and concurrent infusional 5-fluorouracil and cisplatin. The primary tumor was treated with a median dose of 57.5 Gy (range, 54-60 Gy), involved para-aortic, pelvic, and inguinal lymph nodes were treated with a median dose of 55 Gy (range, 50.5-55 Gy), and noninvolved nodal regions weremore » treated with a median dose of 45 Gy (range, 43.5-45 Gy). Results: After a median follow-up of 25 months, none of the patients had a recurrence at the primary tumor, pelvic/inguinal nodes, or para-aortic nodes, whereas 2 patients developed distant metastases to the liver. Four of the 6 patients are alive. The 3-year actuarial locoregional control, distant control, and overall survival rates were 100%, 56%, and 63%, respectively. Four of the 6 patients developed Grade 3 acute gastrointestinal toxicity during chemoradiation. Conclusions: Intensity-modulated radiotherapy and concurrent chemotherapy could potentially serve as definitive therapy in anal cancer patients with para-aortic nodal involvement. Adjuvant chemotherapy may be indicated in these patients, as demonstrated by the distant failure rates. These patients need to be followed carefully because of the potential for treatment-related toxicities.« less

External Validity of a Risk Stratification Score Predicting Early Distant Brain Failure and Salvage Whole Brain Radiation Therapy After Stereotactic Radiosurgery for Brain Metastases.

PubMed

Press, Robert H; Boselli, Danielle M; Symanowski, James T; Lankford, Scott P; McCammon, Robert J; Moeller, Benjamin J; Heinzerling, John H; Fasola, Carolina E; Burri, Stuart H; Patel, Kirtesh R; Asher, Anthony L; Sumrall, Ashley L; Curran, Walter J; Shu, Hui-Kuo G; Crocker, Ian R; Prabhu, Roshan S

2017-07-01

A scoring system using pretreatment factors was recently published for predicting the risk of early (≤6 months) distant brain failure (DBF) and salvage whole brain radiation therapy (WBRT) after stereotactic radiosurgery (SRS) alone. Four risk factors were identified: (1) lack of prior WBRT; (2) melanoma or breast histologic features; (3) multiple brain metastases; and (4) total volume of brain metastases <1.3 cm 3 , with each factor assigned 1 point. The purpose of this study was to assess the validity of this scoring system and its appropriateness for clinical use in an independent external patient population. We reviewed the records of 247 patients with 388 brain metastases treated with SRS between 2010 at 2013 at Levine Cancer Institute. The Press (Emory) risk score was calculated and applied to the validation cohort population, and subsequent risk groups were analyzed using cumulative incidence. The low-risk (LR) group had a significantly lower risk of early DBF than did the high-risk (HR) group (22.6% vs 44%, P=.004), but there was no difference between the HR and intermediate-risk (IR) groups (41.2% vs 44%, P=.79). Total lesion volume <1.3 cm 3  (P=.004), malignant melanoma (P=.007), and multiple metastases (P<.001) were validated as predictors for early DBF. Prior WBRT and breast cancer histologic features did not retain prognostic significance. Risk stratification for risk of early salvage WBRT were similar, with a trend toward an increased risk for HR compared with LR (P=.09) but no difference between IR and HR (P=.53). The 3-level Emory risk score was shown to not be externally valid, but the model was able to stratify between 2 levels (LR and not-LR [combined IR and HR]) for early (≤6 months) DBF. These results reinforce the importance of validating predictive models in independent cohorts. Further refinement of this scoring system with molecular information and in additional contemporary patient populations is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

Early Postoperative FDG-PET-CT Imaging Results in a Relevant Upstaging in the pN2 Subgroup of Stage III Colorectal Cancer Patients.

PubMed

Fehr, Martin; Müller, Joachim; Knitel, Meinhard; Fornaro, Jürgen; Horber, Daniel; Koeberle, Dieter; Cerny, Thomas; Güller, Ulrich

2017-12-01

Clinical practice guidelines regarding follow-up in patients after curative resection of colorectal cancer (CRC) vary widely. Current follow-up recommendations do not include additional postoperative imaging before starting adjuvant treatment in any patients. We evaluated the potential benefit of our institutional approach, recommending 18 fluor-deoxy-glucose (FDG)-positron emission tomography (PET)-computed tomography (CT) imaging in CRC stage III patients with ≥4 locoregional lymph node metastases (pN2). Our study included all patients from a single center with complete resection of a pT1-4, pN2, cM0 CRC. All patients were considered free of distant metastases on the basis of preoperative CT imaging of the chest, abdomen, and pelvis. The main objective of the present study was to assess the proportion of patients with changes of therapeutic management (defined as any other treatment than the preplanned adjuvant chemotherapy) because of the results of additional postoperative FDG-PET-CT imaging. Fifty patients (22 female/28 male) were included; the median age was 64 years (range, 37-78 years). Previously undiagnosed metastatic disease resulting in a change of the therapeutic management was detected using postoperative FDG-PET-CT imaging in 7 patients (14.0%; 95% confidence interval, 5.8%-26.7%). The number needed to screen to detect new or previously occult metastases was 7 (7 of 50). To our knowledge, this is the first study to evaluate the role of an additional postoperative FDG-PET-CT scan before adjuvant treatment in patients with completely resected CRC with ≥4 lymph node metastases (pT1-4, pN2) and without distant metastases on preoperative CT imaging (cM0). Postoperative FDG-PET-CT imaging represents a valuable tool for the detection of new macrometastases in the subgroup of pN2 cM0 CRC patients. The low number needed to screen for consequent therapeutic changes is clinically relevant and should be further evaluated. Copyright © 2017 Elsevier Inc. All rights reserved.

Whole-body scintigraphy with radioiodine-131. A comprehensive list of false-positives with some examples.

PubMed

McDougall, I R

1995-10-01

Whole-body scintigraphy with radioiodine-131 is an important diagnostic test in the management of patients with differentiated thyroid cancer who have undergone surgical treatment. The scan can demonstrate the presence of residual thyroid or functioning metastases in lymph nodes or distant sites. However, there are a number of potential pitfalls in the interpretation of this scan that could lead to a false-positive diagnosis of cancer. The scintiscans are presented for five patients in whom uptake outside of the thyroid was not due to functioning metastases. Some of these abnormalities are physiologic, such as uptake of iodine in the gastrointestinal tract. A comprehensive list of false-positive results are tabulated.

Lung cancer progression and metastasis from the prognostic point of view.

PubMed

Inamura, Kentaro; Ishikawa, Yuichi

2010-08-01

Lung cancer is the leading cause of cancer death in men and women worldwide. Since the occurrence of metastases in distant organs is the major reason for mortality of cancer patients, we need to elucidate the underlying mechanisms. Many studies featuring analysis of gene expression, comparative genomic hybridization and loss of heterozygosity analysis have been performed and generated support for the hypothesis that metastatic potential is acquired early in tumorigenesis. Furthermore, it is now clear that the majority of tumor cells have the potential to metastasize. Although many changes in gene expression profiles have been established retrospectively, translational research is now a high priority to enable clinical application and treatment based on laboratory findings.

Prognostic value of site-specific extra-hepatic disease in hepatocellular carcinoma: a SEER database analysis.

PubMed

Oweira, Hani; Petrausch, Ulf; Helbling, Daniel; Schmidt, Jan; Mehrabi, Arianeb; Schöb, Othmar; Giryes, Anwar; Abdel-Rahman, Omar

2017-07-01

We the prognostic value of site-specific extra-hepatic disease in hepatocellular carcinoma (HCC) patients registered within the surveillance, epidemiology and end results (SEER) database. SEER database (2010-2013) has been queried through SEER*Stat program to determine the prognosis of advanced HCC patients according to the site of extra-hepatic disease. Survival analysis has been conducted through Kaplan Meier analysis. A total of 4396 patients with stage IV HCC were identified in the period from 2010-2013 and they were included into this analysis. Patients with isolated regional lymph node involvement have better outcomes compared to patients with any other site of extra-hepatic disease (P < 0.0001 for both endpoints). Among patients with distant metastases, patients with bone metastases have better outcomes compared to patients with lung metastases (P < 0.0001 for both endpoints). Multivariate analysis revealed that younger age, normal alpha fetoprotein, single site of extra-hepatic disease, local treatment to the primary tumor and surgery to the metastatic disease were associated with better overall survival and liver cancer-specific survival. Within the limits of the current SEER analysis, HCC patients with isolated lung metastases seem to have worse outcomes compared to patients with isolated bone or regional nodal metastases.​.

Chemokine Receptor CXCR4 Expression in Patients With Melanoma and Colorectal Cancer Liver Metastases and the Association With Disease Outcome

PubMed Central

Kim, Joseph; Mori, Takuji; Chen, Steven L.; Amersi, Farin F.; Martinez, Steve R.; Kuo, Christine; Turner, Roderick R.; Ye, Xing; Bilchik, Anton J.; Morton, Donald L.; Hoon, Dave S. B.

2006-01-01

Objective: To determine the role of chemokine receptor (CR) expression in patients with melanoma and colorectal cancer (CRC) liver metastases. Summary Background Data: Murine and in vitro models have identified CR as potential factors in organ-specific metastasis of multiple cancers. Chemokines via their respective receptors have been shown to promote cell migration to distant organs. Methods: Patients who underwent hepatic surgery for melanoma or CRC liver metastases were assessed. Screening cDNA microarrays of melanoma/CRC cell lines and tumor specimens were analyzed to identify CR. Microarray data were validated by quantitative real-time RT-PCR (qRT) in paraffin-embedded liver metastases. Migration assays and immunohistochemistry were performed to verify CR function and confirm CR expression, respectively. Results: Microarray analysis identified CXCR4 as the most common CR expressed by both cancers. qRT demonstrated CXCR4 expression in 24 of 27 (89%) melanoma and 28 of 29 (97%) CRC liver metastases. In vitro treatment of melanoma or CRC cells with CXCL12, the ligand for CXCR4, significantly increased cell migration (P < 0.001). Low versus high CXCR4 expression in CRC liver metastases correlated with a significant difference in overall survival (median 27 months vs. 10 months, respectively; P = 0.036). In melanoma, low versus high CXCR4 expression in liver metastases demonstrated no difference in overall survival (median 11 months vs. 8 months, respectively; P = not significant). Conclusions: CXCR4 is expressed and functional on melanoma and CRC cells. The ligand for CXCR4 is highly expressed in liver and may specifically attract melanoma and CRC CXCR4 (+) cells. Quantitative analysis of CXCR4 gene expression in patients with liver metastases has prognostic significance for disease outcome. PMID:16794396

EGFR-targeted nonviral NIS gene transfer for bioimaging and therapy of disseminated colon cancer metastases

PubMed Central

Urnauer, Sarah; Müller, Andrea M.; Schug, Christina; Schmohl, Kathrin A.; Tutter, Mariella; Schwenk, Nathalie; Rödl, Wolfgang; Morys, Stephan; Ingrisch, Michael; Bertram, Jens; Bartenstein, Peter; Clevert, Dirk-André; Wagner, Ernst; Spitzweg, Christine

2017-01-01

Liver metastases present a serious problem in the therapy of advanced colorectal cancer (CRC), as more than 20% of patients have distant metastases at the time of diagnosis with less than 5% being cured. Consequently, new therapeutic approaches are of major need together with high-resolution imaging methods that allow highly specific detection of small metastases. The unique combination of reporter and therapy gene function of the sodium iodide symporter (NIS) may represent a promising theranostic strategy for CRC liver metastases allowing non-invasive imaging of functional NIS expression and therapeutic application of 131I. For targeted NIS gene transfer polymers containing linear polyethylenimine (LPEI), polyethylene glycol (PEG) and the epidermal growth factor receptor (EGFR)-specific ligand GE11 were complexed with human NIS DNA (LPEI-PEG-GE11/NIS). Tumor specificity and transduction efficiency were examined in high EGFR-expressing LS174T metastases by non-invasive imaging using 18F-tetrafluoroborate (18F-TFB) as novel NIS PET tracer. Mice that were injected with LPEI-PEG-GE11/NIS 48 h before 18F-TFB application showed high tumoral levels (4.8±0.6% of injected dose) of NIS-mediated radionuclide uptake in comparison to low levels detected in mice that received untargeted control polyplexes. Three cycles of intravenous injection of EGFR-targeted NIS polyplexes followed by therapeutic application of 55.5 MBq 131I resulted in marked delay in metastases spread, which was associated with improved animal survival. In conclusion, these preclinical data confirm the enormous potential of EGFR-targeted synthetic polymers for systemic NIS gene delivery in an advanced multifocal CRC liver metastases model and open the exciting prospect of NIS-mediated radionuclide therapy in metastatic disease. PMID:29190908

MALIGNANT PLEURAL MESOTHELIOMA WITHOUT ASBESTOS EXPOSURE WITH DISTANT METASTASIS IN A PERIPHERAL LYMPH NODE: A CASE REPORT

PubMed Central

Kant, Surya; Verma, Sanjay Kumar; Sanjay

2008-01-01

SUMMARY Malignant mesothelioma is an uncommon pleural neoplasm and usually associated with inhalation exposure to asbestos. About 20% of the patients have no demonstrable exposure to asbestos. It rarely metastasizes in peripheral lymph nodes. Here is a case report of malignant pleural mesothelioma without asbestos exposure with cervical lymph node metastasis PMID:20396658

Orbital Metastasis: Rare Initial Presentation of an Occult Gall Bladder Carcinoma.

PubMed

Jain, Tarun Kumar; Parihar, Ashwin Singh; Sood, Ashwani; Basher, Rajender Kumar; Bollampally, Neeraja; Shekhawat, Amit Singh; Mittal, Bhagwant Rai

2018-03-01

Orbital metastases are known to arise from primary breast carcinoma followed by prostate, malignant melanoma, and lung carcinoma. We report a case of orbital metastasis as the initial presentation of an occult primary gall bladder carcinoma. The FDG PET/CT helped in localizing the occult distant primary site, which previously escaped detection, and also enabled the evaluation of orbital metastasis.

Massively parallel sequencing and genome-wide copy number analysis revealed a clonal relationship in benign metastasizing leiomyoma

PubMed Central

Lee, Li-Yu; Lin, Gigin; Chen, Shu-Jen; Lu, Yen-Jung; Huang, Huei-Jean; Yen, Chi-Feng; Han, Chien Min; Lee, Yun-Shien; Wang, Tzu-Hao; Chao, Angel

2017-01-01

Benign metastasizing leiomyoma (BML) is a rare disease entity typically presenting as multiple extrauterine leiomyomas associated with a uterine leiomyoma. It has been hypothesized that the extrauterine leiomyomata represent distant metastasis of the uterine leiomyoma. To date, the only molecular evidence supporting this hypothesis was derived from clonality analyses based on X-chromosome inactivation assays. Here, we sought to address this issue by examining paired specimens of synchronous pulmonary and uterine leiomyomata from three patients using targeted massively parallel sequencing and molecular inversion probe array analysis for detecting somatic mutations and copy number aberrations. We detected identical non-hot-spot somatic mutations and similar patterns of copy number aberrations (CNAs) in paired pulmonary and uterine leiomyomata from two patients, indicating the clonal relationship between pulmonary and uterine leiomyomata. In addition to loss of chromosome 22q found in the literature, we identified additional recurrent CNAs including losses of chromosome 3q and 11q. In conclusion, our findings of the clonal relationship between synchronous pulmonary and uterine leiomyomas support the hypothesis that BML represents a condition wherein a uterine leiomyoma disseminates to distant extrauterine locations. PMID:28533481

Massively parallel sequencing and genome-wide copy number analysis revealed a clonal relationship in benign metastasizing leiomyoma.

PubMed

Wu, Ren-Chin; Chao, An-Shine; Lee, Li-Yu; Lin, Gigin; Chen, Shu-Jen; Lu, Yen-Jung; Huang, Huei-Jean; Yen, Chi-Feng; Han, Chien Min; Lee, Yun-Shien; Wang, Tzu-Hao; Chao, Angel

2017-07-18

Benign metastasizing leiomyoma (BML) is a rare disease entity typically presenting as multiple extrauterine leiomyomas associated with a uterine leiomyoma. It has been hypothesized that the extrauterine leiomyomata represent distant metastasis of the uterine leiomyoma. To date, the only molecular evidence supporting this hypothesis was derived from clonality analyses based on X-chromosome inactivation assays. Here, we sought to address this issue by examining paired specimens of synchronous pulmonary and uterine leiomyomata from three patients using targeted massively parallel sequencing and molecular inversion probe array analysis for detecting somatic mutations and copy number aberrations. We detected identical non-hot-spot somatic mutations and similar patterns of copy number aberrations (CNAs) in paired pulmonary and uterine leiomyomata from two patients, indicating the clonal relationship between pulmonary and uterine leiomyomata. In addition to loss of chromosome 22q found in the literature, we identified additional recurrent CNAs including losses of chromosome 3q and 11q. In conclusion, our findings of the clonal relationship between synchronous pulmonary and uterine leiomyomas support the hypothesis that BML represents a condition wherein a uterine leiomyoma disseminates to distant extrauterine locations.

Intracranial meningeal hemangiopericytoma: Recurrences at the initial and distant intracranial sites and extraneural metastases to multiple organs

PubMed Central

WEI, GUANGQUAN; KANG, XIAOWEI; LIU, XIANPING; TANG, XING; LI, QINLONG; HAN, JUNTAO; YIN, HONG

2015-01-01

Regardless of the controversial pathogenesis, intracranial meningeal hemangiopericytoma (M-HPC) is a rare, highly cellular and vascularized mesenchymal tumor that is characterized by a high tendency for recurrence and extraneural metastasis, despite radical excision and postoperative radiotherapy. M-HPC shares similar clinical manifestations and radiological findings with meningioma, which causes difficulty in differentiation of this entity from those prognostically favorable mimics prior to surgery. Treatment of M-HPC, particularly in metastatic settings, remains a challenge. A case is described of primary M-HPC with recurrence at the initial and distant intracranial sites and extraneural multiple-organ metastases in a 36-year-old female. The metastasis of M-HPC was extremely extensive, and to the best of our knowledge this is the first case of M-HPC with delayed metastasis to the bilateral kidneys. The data suggests that preoperative computed tomography and magnetic resonance imaging could provide certain diagnostic clues and useful information for more optimal treatment planning. The results may imply that novel drugs, such as temozolomide and bevacizumab, as a component of multimodality therapy of M-HPC may deserve further investigation. PMID:26171177

Antithyroid peroxidase antibody positivity is associated with lower incidence of metastasis in breast cancer

PubMed Central

KEMAL, YASEMIN; DEMIRAG, GUZIN; EKIZ, KUBILAY; YUCEL, IDRIS

2015-01-01

Thyroid extracts were first used to treat patients with metastatic breast cancer over a century ago. Since then, a number of studies have investigated the association between thyroid disorders and breast cancer. The presence of antibodies to thyroid peroxidase (TPOab) was recently reported to be associated with improved outcome in these patients. The aim of the present study was to evaluate the association between TPOab positivity and clinicopathological characteristics in breast cancer patients. The study included 318 newly diagnosed cases of breast cancer treated at Ondokuz Mayis University Hospital, Samsun, Turkey, between 2008 and 2012. Serum thyroid-stimulating hormone, free triiodothyronine and free thyroxine levels were measured at the time of diagnosis. Of the 318 patients, 253 were considered to be TPOab-negative (TPOab ≤34 IU/ml) and 65 TPOab-positive (TPOab >34 IU/ml). No cases with distant metastases were found in the TPOab-positive group. However, 20 (7.9%) of the 253 patients displayed distant metastases in the TPOab-negative group (P=0.01). Therefore, TPOab positivity was found to be associated with a lower incidence of metastasis in breast cancer patients. PMID:26137279

Detection of CTCs in portal vein was associated with intrahepatic metastases and prognosis in patients with advanced pancreatic cancer

PubMed Central

Liu, Xiaoyu; Li, Changyu; Li, Junhao; Yu, Tianzhu; Zhou, Guofeng; Cheng, Jiemin; Li, Guoping; Zhou, Yang; Lou, Wenhui; Wang, Xiaolin; Gong, Gaoquan; Liu, Lingxiao; Chen, Yi

2018-01-01

Pancreatic cancer is amongst the most lethal malignancies with increasing incidence and mortality worldwide. Distant metastases, especially intrahepatic metastases, is the leading cause of death for pancreatic cancer. Circulating tumor cells (CTCs) are neoplastic cells released from the primary tumor into circulation, and play critical roles in metastases of various types of cancers. Though clinical studies showed that detection of CTCs in peripheral circulation was associated with worse prognosis in patients with breast cancer and hepatocellular carcinoma, detection CTCs in peripheral blood of pancreatic cancer was still challenging due to hepatic filtration and technical limitations. Previous studies have demonstrated that CTCs could be detected in portal vein circulation in patients with pancreaticobiliary carcinoma. In the present study, taking advantage of ultrasonography-guided transhepatic puncture, we analysis CTCs in portal vein blood obtained from patients with advanced pancreatic cancer. CTCs were detected in all 29-portal vein blood of samples, and absolute numbers of circulating pancreatic cancer cells in portal vein was significantly higher than that in peripheral circulation. Furthermore, we found that CTC counts in portal vein was highly associated with intrahepatic metastases and indicated poorer prognosis in patients with advanced pancreatic cancer. Short-term expansion and in vitro drug sensitivity assay showed that CTCs derived from portal vein blood were highly resistant to several chemotherapy regimens. In summary, detection of CTCs in portal vein could be a powerful tool to stratify the risk of intrahepatic metastases of pancreatic cancer, and provided new insight into the biological feature of pancreatic cancer metastases and drug resistance. PMID:29896289

Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy

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

De Crevoisier, Renaud; Baudin, Eric; Bachelot, Anne

Purpose: To analyze a prospective protocol combining surgery, chemotherapy (CT), and hyperfractionated accelerated radiotherapy (RT) in anaplastic thyroid carcinoma. Methods and materials: Thirty anaplastic thyroid carcinoma patients (mean age, 59 years) were treated during 1990-2000. Tumor extended beyond the capsule gland in 26 patients, with tracheal extension in 8. Lymph node metastases were present in 18 patients and lung metastases in 6. Surgery was performed before RT-CT in 20 patients and afterwards in 4. Two cycles of doxorubicin (60 mg/m{sup 2}) and cisplatin (120 mg/m{sup 2}) were delivered before RT and four cycles after RT. RT consisted of two dailymore » fractions of 1.25 Gy, 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum. Results: Acute toxicity (World Health Organization criteria) was Grade 3 or 4 pharyngoesophagitis in 10 patients; Grade 4 neutropenia in 21, with infection in 13; and Grade 3 or 4 anemia and thrombopenia in 8 and 4, respectively. At the end of the treatment, a complete local response was observed in 19 patients. With a median follow-up of 45 months (range, 12-78 months), 7 patients were alive in complete remission, of whom 6 had initially received a complete tumor resection. Overall survival rate at 3 years was 27% (95% confidence interval 10-44%) and median survival 10 months. In multivariate analysis, tracheal extension and macroscopic complete tumor resection were significant factors in overall survival. Death was related to local progression in 5% of patients, to distant metastases in 68%, and to both in 27%. Conclusions: Main toxicity was hematologic. High long-term survival was obtained when RT-CT was given after complete surgery. This protocol avoided local tumor progression, and death was mainly caused by distant metastases.« less

Orthotopic Patient-Derived Pancreatic Cancer Xenografts Engraft Into the Pancreatic Parenchyma, Metastasize, and Induce Muscle Wasting to Recapitulate the Human Disease.

PubMed

Go, Kristina L; Delitto, Daniel; Judge, Sarah M; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Judge, Andrew R; Trevino, Jose G

2017-07-01

Limitations associated with current animal models serve as a major obstacle to reliable preclinical evaluation of therapies in pancreatic cancer (PC). In an effort to develop more reliable preclinical models, we have recently established a subcutaneous patient-derived xenograft (PDX) model. However, critical aspects of PC responsible for its highly lethal nature, such as the development of distant metastasis and cancer cachexia, remain underrepresented in the flank PDX model. The purpose of this study was to evaluate the degree to which an orthotopic PDX model of PC recapitulates these aspects of the human disease. Human PDX-derived PC tumors were implanted directly into the pancreas of NOD.Cg-Prkdc Il2rg/SzJ mice. Tumor growth, metastasis, and muscle wasting were then evaluated. Orthotopically implanted PDX-derived tumors consistently incorporated into the murine pancreatic parenchyma, metastasized to both the liver and lungs and induced muscle wasting directly proportional to the size of the tumor, consistent of the cancer cachexia syndrome. Through the orthotopic implantation technique described, we demonstrate a highly reproducible model that recapitulates both local and systemic aspects of human PC.

Epidemiology, management and survival outcomes of primary cutaneous melanoma: a ten-year overview.

PubMed

Aubuchon, M M F; Bolt, L J J; Janssen-Heijnen, M L G; Verleisdonk-Bolhaar, S T H P; van Marion, A; van Berlo, C L H

2017-02-01

Malignant melanoma (MM) is the most aggressive type of skin cancer, accounting for 90% of all the skin cancer mortality. The objective of this study was providing an overview of current patient- and tumour characteristics, treatment strategies, complications and survival in patients with MM over the past ten years. Hereby, an up-to-date view of every day clinical practice is obtained. Files of patients treated for primary cutaneous melanoma (n = 686) in the VieCuri Medical Centre in the Netherlands between January 2002 and December 2013 were retrospectively reviewed. Relevant patient features, tumour characteristics, and (surgical) outcomes were evaluated. The majority of all the patients presented thin tumours (59.1% stage 1A/in situ melanoma). Men showed more ulceration (17.7% vs. 8.4%, p < .01) and a significantly higher Breslow thickness than women (1.2 mm vs. 0.9 mm, p < .01). 14.6% (40/273) underwent sentinel lymph node biopsy (SLNB); 10/40 (25%) showed nodal metastasis, 50 patients (7.3%) developed distant metastases (M: 10.6%, F: 5%, p < .01). One-, 5- and 10- year disease specific survival rates were 96%, 86% and 84%, respectively. Median survival for stage 4 MM was 3 months. Extensive surgery was uncommon (n = 3). Patients generally presented with thin melanomas. Lymph node disease and distant metastases remained infrequently observed during following years, and general 1- and 5-year overall disease-specific survival rates exceeded 85%. Small numbers of rescue surgery and palliative medical treatment warrant further centralisation and investigation.

Prognostic effect of liver metastasis in lung cancer patients with distant metastasis.

PubMed

Ren, Yijiu; Dai, Chenyang; Zheng, Hui; Zhou, Fangyu; She, Yunlang; Jiang, Gening; Fei, Ke; Yang, Ping; Xie, Dong; Chen, Chang

2016-08-16

Because the need of clinical prognostic evaluation by specific metastatic organ, we aim to analyze the prognostic factors in lung cancer patients with M1b disease with Surveillance Epidemiology and End-Results database (SEER). This retrospective study evaluated lung cancer patients of adenocarcinoma (AD), squamous cell carcinoma (SQCC), and small cell lung cancer (SCLC) selected from SEER. We provided the prognostic correlates of overall survival (OS) and lung cancer-specific survival (LCSS) in this population. 23,679 eligible patients were included. Bone was the most common metastatic site in AD (63.1%) and SQCC (61.1%), while liver was the most prevalent site (61.9%) in SCLC. Single site metastasis was significantly associated with better outcome compared to multiple sites metastases in all patients. Among patients with single site metastasis, OS and LCSS were longer for AD and SCLC if involving brain or bone, with median survival time of 5 to 7 months, comparing to 3 months if invloving liver (all p-values < 0.001). Similarly, among patients with multiple metastases, better outcomes were observed in AD patients (4 vs 3 months; OS and LCSS, p < 0.001) and SCLC patients (6 vs 4 months; OS, p = 0.017; LCSS, p = 0.023) without liver metastasis compared to those with liver metastasis. In conclusion, we estimated multiple survival outcomes by histology of primary tumor and sites of metastasis. Liver metastasis is found to be the worst prognostic factor for AD and SCLC patients with distant metastasis. More in-depth research is warranted to identify patients who are prone to develop distance metastasis, especially to liver.

Distant metastasis of intraosseous dentinogenic ghost cell tumour to the donor site of a bone graft

PubMed Central

Park, H-R; Min, J-H; Huh, K-H; Yi, W-J; Heo, M-S; Lee, S-S; Cho, Y-A

2013-01-01

A dentinogenic ghost cell tumour (DGCT) is an extremely rare odontogenic tumour which is considered as a solid, neoplastic variant of calcifying odontogenic cyst. Intraosseous DGCTs are more aggressive than extraosseous DGCTs and have a high propensity for local recurrence. This report describes a case of a diagnosis of recurrent DGCT at the primary site and a distant donor site. A 25-year-old female patient visited a dental hospital for a complaint of facial swelling for the previous month. Incisional biopsy was performed and the specimen was diagnosed as DGCT. Partial mandibulectomy for tumour resection and iliac bone graft was performed. 2 years later, the tumour recurred on the mandible and iliac bone. The recurrent lesion on the donor site was diagnosed as metastasized DGCT. This report highlights the possibility of distant metastasis occurring at a graft donor site. PMID:23420853

Renaissance in tumor immunotherapy: possible combination with phototherapy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hamblin, Michael R.

2016-03-01

Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce highly toxic reactive oxygen species that destroy tumors. The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity. This is best accomplished by educating the body's immune system to recognize the tumor as foreign so that after the primary tumor is destroyed, distant metastases will also be eradicated. PDT may accomplish this feat and stimulate long-term, specific anti-tumor immunity. PDT causes an acute inflammatory response, the rapid induction of large amounts of necrotic and apoptotic tumor cells, induction of damage-associated molecular patterns (DAMPS) including heat-shock proteins, stimulates tumor antigen presentation to naïve T-cells, and generation of cytotoxic T-cells that can destroy distant tumor metastases. By using various syngeneic mouse tumors in immunocompetent mice, we have studied specific PDT regimens related to tumor type as well as mouse genotype and phenotype. We have investigated the role of tumor-associated antigens in PDT-induced immune response by choosing mouse tumors that express: model defined antigen, naturally-occurring cancer testis antigen, and oncogenic virus-derived antigen. We studied the synergistic combination of low-dose cyclophosphamide and PDT that unmasks the PDT-induced immune response by depleting the immunosuppressive T-regulatory cells. PDT combined with immunostimulants (toll-like receptor ligands) can synergistically maximize the generation of anti-tumor immunity by activating dendritic cells and switching immunosuppressive macrophages to a tumor rejection phenotype. Tumors expressing defined tumor-associated antigens with known MHC class I peptides allows anti-tumor immunity to be quantitatively compared.

PET/CT with (11)C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data.

PubMed

Fanti, Stefano; Minozzi, Silvia; Castellucci, Paolo; Balduzzi, Sara; Herrmann, Ken; Krause, Bernd Joachim; Oyen, Wim; Chiti, Arturo

2016-01-01

For the last decade PET and PET/CT with (11)C-choline have been proposed for the evaluation of prostate cancer (PC), but the diagnostic performance of (11)C-choline PET/CT is still a matter of debate. We performed a comprehensive review of the most important clinical application of (11)C-choline PET, restaging of patients with biochemical relapse, following a rigorous methodological approach and including assessment of the risk of bias. We conducted a systematic review and meta-analysis of the literature assessing (11)C-choline PET/CT for its accuracy in the diagnosis and ability to detect the site of recurrence of PC in the restaging of patients with biochemical recurrence after initial treatment with curative intent. We performed a comprehensive literature search of PubMed and the Cochrane Library to determine the accuracy for the detection of the site of recurrence (prostate bed recurrences, metastatic spread to locoregional pelvic lymph nodes or distant metastases). Only studies with a reference standard (for prostatic bed histopathology, for histopathology or biopsy of distant metastases or a composite reference standard with clinical follow-up of at least 12 months, correlative imaging and clinical data) were included. Overall 425 studies were retrieved, of which 43 were judged as potentially relevant and 29 with 2,686 participants were finally included. Of these 29 studies, 18 reported results for any relapse, All 18 studies, with a total of 2,126 participants, reported detection rates. The pooled rate was 62 % (95 % CI 53 - 71 %). Of the 18 studies, 12 with 1,270 participants reported useful data to derive sensitivity and specificity. The pooled sensitivity was 89 % (95 % CI 83 - 93 %) and the pooled specificity was 89 % (95 % CI 73 - 96 %). Of 11 studies reporting results for local relapse, 9 with 993 participants reported detection rates. The pooled rate was 27 % (95 % CI 16 - 38 %). Six studies with 491 participants reported sensitivity and specificity. The pooled sensitivity was 61 % (95 % CI 40 - 80 %) and the pooled specificity was 97 % (95 % CI 87 - 99 %). Ten studies reported results for lymph nodes and distant metastases. For nodal disease, 7 studies with 752 participants reported detection rates. The pooled rate was 36 % (95 % CI 22 - 50 %). For bone metastases, 8 studies with 775 participants reported detection rates. The pooled rate was 25 % (95 % CI 16 - 34 %). There is a significant amount of (11)C-choline PET data published showing a high degree of consistency in inclusion criteria, acquisition protocols and scan interpretation criteria. Furthermore, the quality of the data derived limited to the same standard of reference was acceptable. Despite a high variability in the observed prevalence of any relapse, the diagnostic performance of (11)C-choline PET was in line with previous meta-analyses. Our data confirm the very good accuracy of (11)C-choline PET for detection of lymph node metastases and/or distant lesions in a single examination in patients with biochemical relapse.

Men and women show similar survival outcome in stage IV breast cancer.

PubMed

Wu, San-Gang; Zhang, Wen-Wen; Liao, Xu-Lin; Sun, Jia-Yuan; Li, Feng-Yan; Su, Jing-Jun; He, Zhen-Yu

2017-08-01

To evaluate the clinicopathological features, patterns of distant metastases, and survival outcome between stage IV male breast cancer (MBC) and female breast cancer (FBC). Patients diagnosed with stage IV MBC and FBC between 2010 and 2013 were included using the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were used to analyze risk factors for overall survival (OS). A total of 4997 patients were identified, including 60 MBC and 4937 FBC. Compared with FBC, patients with MBC were associated with a significantly higher rate of estrogen receptor-positive, progesterone receptor-positive, unmarried, lung metastases, and a lower frequency of liver metastases. Univariate and multivariate analyses showed no significant difference in OS between MBC and FBC. In the propensity score-matched population, there was also no difference in survival between MBC and FBC. Multivariate analysis of MBC showed that OS was longer for patients aged 50-69 years and with estrogen receptor-positive disease. There was no significant difference in survival outcome between stage IV MBC and FBC, but significant differences in clinicopathological features and patterns of metastases between the genders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Photodynamic therapy and fluorescence diagnostics of breast cancer metastases with photosense and alasense

NASA Astrophysics Data System (ADS)

Vakoulovskaya, Elena G.; Shental, Victor V.; Letyagin, Victor P.; Brjezovsky, Vitaly J.; Oumnova, L. V.; Vorozhtsov, Georgy N.; Philinov, V.; Stranadko, Eugeny P.

2002-06-01

Photodynamic Therapy (PDT) and fluorescent diagnostics (FD) using photosensitizers Photosense (Aluminium Phtalocyanine, (NIOPIC, Russia)(PS) and Alasense have been provided in 101 patients with breast cancer as a multicenter study. All patients had recurrences of breast cancer (skin metastases) after combined treatment, chemotherapy and radiotherapy. FD of tumor with detecting of subclinical sites, accumulation of PS in tumor, adjacent tissue, skin before and during PDT was fulfilled. Multiple surface irradiations were carried on with interval 24-72 hours (semiconductive laser - (lambda) =672+2nm) in light does 100J/cm2 and total light does 300-900 J/cm2. 2 months after PDT we had overall response rate of 86,87% with complete response (CR) in 51,48% and partial response in 35,39%. During year after PDT in 52 patients with CR we had CR in 36,6% local recurrences in 23,1%, progression (distant (lung or bone) metastasis) in 40,4% of cases. Our experience show pronounced efficacy of PDT for skin metastases of breast cancer.

[In-transit metastasis in melanoma: Efficacy of topical imiquimod combined with carbon dioxide laser or with electrocautery].

PubMed

Elfatoiki, F-Z; Longvert, C; Clerici, T; Bourgault-Villada, I; Roudier-Pujol, C; Vasseur, E; Saiag, P

2014-02-01

In-transit metastases in cutaneous melanoma are common and difficult to manage. Therapy is mainly palliative. Use of topical imiquimod has been assessed for surface metastases. We report on four patients with cutaneous melanoma metastases treated with topical imiquimod associated with carbon dioxide laser in the first two patients and with electrocoagulation in the two others. For two patients, we noted complete regression of the lesions after 15 and 18 months. For the two others, treatment was stopped after 9 to 10 months because of progression of subcutaneous metastasis and distant metastasis. Topical imiquimod is an alternative treatment used in superficial in-transit metastasis of melanoma. Its use as a monotherapy is sometimes ineffective. We elected to use combined pre-treatment with carbon dioxide laser or electrocoagulation in order to potentiate the action of imiquimod. This simple and inexpensive therapeutic strategy constitutes a palliative treatment that can allow prolonged local control of cutaneous metastasis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Role of the neural niche in brain metastatic cancer

PubMed Central

Termini, John; Neman, Josh; Jandial, Rahul

2014-01-01

Metastasis is the relenteless pursuit of cancer to escape its primary site and colonize distant organs. This malignant evolutionary process is biologically heterogeneous, yet one unifying element is the critical role of the microenvironment for arriving metastatic cells. Historically brain metastases were rarely investigated since patients with advanced cancer were considered terminal. Fortunately, advances in molecular therapies have led to patients living longer with metastatic cancer. However, one site remains recalcitrant to our treatment efforts – the brain. The central nervous system is the most complex biological system, which poses unique obstacles but also harbors opportunities for discovery. Much of what we know about the brain microenvironment comes from neuroscience. We suggest that the interrelated cellular responses in traumatic brain injury may guide us towards new perspectives in understanding brain metastases. In this view, brain metastases may be conceptualized as progressive oncologic injury to the nervous system. This review discusses our evolving understanding of the bidirectional interactions between the brain milieu and metastatic cancer. PMID:25035392

Role of the neural niche in brain metastatic cancer.

PubMed

Termini, John; Neman, Josh; Jandial, Rahul

2014-08-01

Metastasis is the relentless pursuit of cancer to escape its primary site and colonize distant organs. This malignant evolutionary process is biologically heterogeneous, yet one unifying element is the critical role of the microenvironment for arriving metastatic cells. Historically, brain metastases were rarely investigated because patients with advanced cancer were considered terminal. Fortunately, advances in molecular therapies have led to patients living longer with metastatic cancer. However, one site remains recalcitrant to our treatment efforts, the brain. The central nervous system is the most complex biologic system, which poses unique obstacles but also harbors opportunities for discovery. Much of what we know about the brain microenvironment comes from neuroscience. We suggest that the interrelated cellular responses in traumatic brain injury may guide us toward new perspectives in understanding brain metastases. In this view, brain metastases may be conceptualized as progressive oncologic injury to the nervous system. This review discusses our evolving understanding of bidirectional interactions between the brain milieu and metastatic cancer. ©2014 American Association for Cancer Research.

Metastatic eccrine porocarcinoma: report of a case and review of the literature

PubMed Central

2011-01-01

Eccrine porocarcinoma (EPC) is a rare type of skin cancer arising from the intraepidermal portion of eccrine sweat glands or acrosyringium, representing 0.005-0.01% of all cutaneous tumors. About 20% of EPC will recur and about 20% will metastasize to regional lymph nodes. There is a mortality rate of 67% in patients with lymph node metastases. Although rare, the occurrence of distant metastases has been reported. We report a case of patient with EPC of the left arm, with axillary nodal involvement and subsequent local relapse, treated by complete lymph node dissection and electrochemotherapy (ECT). EPC is an unusual tumor to diagnose. Neither chemotherapy nor radiation therapy has been proven to be of clinical benefit in treating metastatic disease. Although in the current case the short follow-up period is a limitation, we consider in the management of EPC a therapeutic approach involving surgery and ECT, because of its aggressive potential for loregional metastatic spread. PMID:21410982

Metastatic eccrine porocarcinoma: report of a case and review of the literature.

PubMed

Marone, Ugo; Caracò, Corrado; Anniciello, Anna Maria; Di Monta, Gianluca; Chiofalo, Maria Grazia; Di Cecilia, Maria Luisa; Mozzillo, Nicola

2011-03-16

Eccrine porocarcinoma (EPC) is a rare type of skin cancer arising from the intraepidermal portion of eccrine sweat glands or acrosyringium, representing 0.005-0.01% of all cutaneous tumors. About 20% of EPC will recur and about 20% will metastasize to regional lymph nodes. There is a mortality rate of 67% in patients with lymph node metastases. Although rare, the occurrence of distant metastases has been reported.We report a case of patient with EPC of the left arm, with axillary nodal involvement and subsequent local relapse, treated by complete lymph node dissection and electrochemotherapy (ECT).EPC is an unusual tumor to diagnose. Neither chemotherapy nor radiation therapy has been proven to be of clinical benefit in treating metastatic disease. Although in the current case the short follow-up period is a limitation, we consider in the management of EPC a therapeutic approach involving surgery and ECT, because of its aggressive potential for loregional metastatic spread.

Poor Prognosis after Second Locoregional Recurrences in the CALOR Trial

PubMed Central

Wapnir, Irene L.; Gelber, Shari; Anderson, Stewart J.; Mamounas, Eleftherios P.; Robidoux, André; Martín, Miguel; Nortier, Johan W.R.; Geyer, Charles E.; Paterson, Alexander H.G.; Láng, István; Price, Karen N.; Coates, Alan S.; Gelber, Richard D.; Rastogi, Priya; Regan, Meredith M.; Wolmark, Norman; Aebi, Stefan

2016-01-01

Purpose Isolated locoregional recurrences (ILRR) of breast cancer confer a significant risk of developing distant metastasis. Management practices and second-ILRR events in the CALOR trial are investigated. Methods 162 patients with ILRR were randomly assigned to receive post-operative chemotherapy, or no chemotherapy. Descriptive statistics characterize outcomes according to local therapy and the influence of hormone receptor status on subsequent recurrences. Competing risk regression models, Kaplan-Meier estimates, and Cox proportional hazards models evaluate associations between treatment, site of second recurrence and outcome. Results The median follow-up was 4.9 years. Of the 98 patients who received breast-conserving primary surgery (BCS), 89 had an ipsilateral-breast tumor recurrence (IBTR); salvage mastectomy was performed in 73 and repeat lumpectomy in 16. Another 8 had nodal-ILRR and 1 chest wall-ILRR. Among 64 whose primary surgery was mastectomy, 52 had chest wall/skin-ILRR and 12 nodal-ILRR. Fifteen patients developed a second-ILRR at a median time from ILRR of 1.6 years (range: 0.08–4.8). All second-ILRR occurred in patients with PR-negative ILRR. Seven (47%) of 15 patients with second-ILRR, and 19 (51%) of 37 with a distant recurrence have died. On multivariable analysis, chemotherapy for the primary cancer (HR 3.55, 95% CI 1.15–10.9, p=0.03) and time interval (continuous) from primary surgery (HR 0.87 95% CI 0.75–1.00, p=0.05) were significant predictors of survival following either a second-ILRR or distant recurrence. Conclusions Second-ILRRs represented about one-third of all recurrence events after ILRR and all were PR negative. These second-ILRRs, as well as distant metastases, portend an unfavorable outcome. PMID:27663567

Cytokine-enhanced vaccine and interferon-β plus suicide gene as combined therapy for spontaneous canine sarcomas.

PubMed

Finocchiaro, Liliana M E; Villaverde, Marcela S; Gil-Cardeza, María L; Riveros, María D; Glikin, Gerardo C

2011-10-01

Eleven soft tissue- and five osteosarcoma canine patients were subjected to: (i) periodic subcutaneous injection of irradiated xenogeneic cells secreting hGM-CSF and hIL-2 mixed with allogeneic or autologous tumor homogenates; and (ii) injections of cIFN-β and HSVtk-carrying lipoplexes and ganciclovir, marginal (after surgery) and/or intratumoral (in the case of partial tumor resection, local relapse or small surface tumors). This treatment alone (4 patients) or as surgery adjuvant (12 patients), was safe and well tolerated. In those patients presenting local disease (6/11), the suicide gene plus cIFN-β treatment induced local antitumor activity evidenced by the objective responses (3 complete, 2 partial) and stable diseases (2). In addition, the treatment prevented or delayed local relapse, regional metastases (lymph nodes developed only in 3/16) and distant metastases (0/16), suggesting a strong systemic antitumor immunity. The most encouraging result was the long survival times of 10 patients (>1 year, with good quality of life). Copyright © 2011 Elsevier Ltd. All rights reserved.

Correlation between severe infection and breast cancer metastases in the EORTC 10994/BIG 1-00 trial: Investigating innate immunity as a tumour suppressor in breast cancer.

PubMed

Touati, Nathan; Tryfonidis, Konstantinos; Caramia, Franco; Bonnefoi, Hervé; Cameron, David; Slaets, Leen; Parker, Belinda S; Loi, Sherene

2017-02-01

Breast cancer cells which express an innate immune signature regulated by interferon regulatory factor 7 (IRF7) have reduced metastatic potential. Infections can induce interferon signalling and may activate an anti-tumour immune response. We investigated whether 'severe infection' can be a clinical surrogate of this phenomenon and/or the presence of high levels of the IRF7 signature at diagnosis before neo-adjuvant chemotherapy (NACT) is associated with a reduced distant relapse risk, specifically in bones. Clinical data of the European Organisation for Research and Treatment of Cancer 10994/BIG 1-00 phase III trial which randomised 1856 patients treated with NACT between 2001 and 2006, were used. Severe infection was febrile neutropenia or any other grade III-IV infective adverse event during NACT. The IRF7 signature was calculated from gene expression data available for 160 patients on a pre-NACT biopsy. Cox models for distant relapse-free interval (DRFI) investigated the effect of the severe infection and IRF7. Fine and Gray models studied the occurrence of bone metastases as first distant relapse. Median follow-up was 4.8 years. No association between severe infection and DFRI was observed in the entire population (n = 1615 eligible patients) hazard ratio [(HR] = 0.99, 90% CI, confidence interval [CI] = 0.81-1.20). For IRF7 (N = 160), a trend towards an association with DRFI was observed (HR = 0.89 for a 50 unit increase, 90% CI = 0.78-1.02, p = 0.081). Higher levels of the IRF7 signature were significantly associated with a decreased bone metastases risk: (HR = 0.76 for a 50 unit increase, 95% CI, 0.62-0.94, p = 0.012). In this study it was shown that severe infection during NACT was not associated with decreased DRFI while high expression of the IRF7 gene signature was significantly associated with reduced bone relapse. This result may be useful for future adjuvant bisphosphonate/denosumab use. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Multifactorial Analysis of Melanoma: Prognostic Histopathological Features Comparing Clark's and Breslow's Staging Methods

PubMed Central

Balch, Charles M.; Murad, Tariq M.; Soong, Seng-Jaw; Ingalls, Anna Lee; Halpern, Norman B.; Maddox, William A.

1978-01-01

A multifactorial analysis was used to identify the dominant prognostic variables affecting survival from a computerized data base of 339 melanoma patients treated at this institution during the past 17 years. Five of the 13 parameters examined simultaneously were found to independently influence five year survival rates: 1) pathological stage (I vs II, p = 0.0014), 2) lesion ulceration (present vs absent, p = 0.006), 3) surgical treatment (wide excision vs wide excision plus lymphadenectomy, p = 0.024), 4) melanoma thickness (p = 0.032), and 5) location (upper extremity vs lower extremity vs trunk vs head and neck, p = 0.038). Additional factors considered that had either indirect or no influence on survival rates were clinical stage of disease, age, sex, level of invasion, pigmentation, lymphocyte infiltration, growth pattern, and regression. Most of these latter variables derived their prognostic value from correlation with melanoma thickness, except sex which correlated with location (extremity lesions were more frequent on females, trunk lesions on males). This statistical analysis enabled us to derive a mathematical equation for predicting an individual patient's probability of five year survival. Three categories of risk were delineated by measuring tumor thickness (Breslow microstaging) in Stage I patients: 1) thin melanomas (<0.76 mm) were associated with localized disease and a 100% cure rate: 2) intermediate thickness melanomas (0.76-4.00 mm) had an increasing risk (up to 80%) of harboring regional and/or distant metastases and 3) thick melanomas (≥4.00 mm) had a 80% risk of occult distant metastases at the time of initial presentation. The level of invasion (Clark's microstaging) correlated with survival, but was less predictive than measuring tumor thickness. Within each of Clark's Level II, III and IV groups, there were gradations of thickness with statistically different survival rates. Both microstaging methods (Breslow and Clark) were less predictive factors in patients with lymph node or distant metastases. Clinical trials evaluating alternative surgical treatments or adjunctive therapy modalities for melanoma patients should incorporate these parameters into their assessment, especially in Stage I (localized) disease where tumor thickness and the anatomical site of the primary melanoma are dominant prognostic factors. PMID:736651

The Number of Pathologically Positive Lymph Nodes and Pathological Tumor Depth Predicts Prognosis in Patients With Poorly Differentiated Squamous Cell Carcinoma of the Oral Cavity

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

Kang, Chung-Jan; Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Lin, Chien-Yu

2011-11-15

Purpose: The objective of this retrospective study was twofold: (1) to investigate prognostic factors for clinical outcomes in patients with poorly differentiated oral cavity squamous cell carcinoma and (2) to identify specific prognostic subgroups that may help to guide treatment decisions. Methods and Materials: We examined 102 patients with poorly differentiated oral cavity squamous cell carcinoma. All patients were followed for at least 24 months after surgery or until death. The 5-year rates of local control, neck control, distant metastasis, disease-free, disease-specific, and overall survival served as main outcome measures. Results: The 5-year rates were as follows: local control (79%),more » neck control (64%), distant metastases (27%), disease-free survival (48%), disease-specific survival (52%), and overall survival (42%). Multivariable analysis showed that the number of pathologically positive nodes ({>=}4 vs. {<=}3) was a significant predictor of neck control, distant metastasis, and disease-free, disease-specific, and overall survival rates. In addition, the presence of tumor depth of {>=}11 mm (vs. <11 mm) was a significant predictor of distant metastasis, disease-specific survival, and overall survival rates. The combination of the two predictors (26.5%, 27/102) was independently associated with poorer neck control (p = 0.0319), distant metastasis (p < 0.0001), and disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p < 0.0001) rates. Conclusions: In patients with poorly differentiated oral cavity squamous cell carcinoma, the presence of at least 4 pathologically positive lymph nodes and of a pathological tumor depth {>=}11 mm identifies a subset of subjects with poor clinical outcomes. Patients carrying both risk factors are suitable candidates for the development of novel therapeutic approaches.« less

Nuclear grade and DNA ploidy in stage IV breast cancer with only visceral metastases at initial diagnosis.

PubMed

De Lena, M; Barletta, A; Marzullo, F; Rabinovich, M; Leone, B; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriguez, R; Schittulli, F; Paradisco, A

1996-01-01

The presence of early metastases to distant sites in breast cancer patients is an infrequent event whose mechanisms are still not clear. The aim of this study was to evaluate the biologic and clinical role of DNA ploidy and cell nuclear grade of primary tumors in the metastatic process of a series of stage IV previously untreated breast cancer patients with only visceral metastases. DNA flow cytometry analysis on paraffin-embedded material and cell nuclear grading of primary tumors was performed on a series of 50 breast cancer patients with only visceral metastases at the time of initial diagnosis. Aneuploidy was found in 28/46 (61%) of evaluable cases and was independent of site of involvement, clinical response, time of progression and overall survival of patients. Of the 46 cases evaluable for nuclear grade, 5 (11%), 16 (35%) and 25 (54%) were classified as G1 (well-differentiated) G2 and G3, respectively. Nuclear grade also was unrelated to response to therapy and overall survival, whereas time to progression was significantly longer in G1-2 than G3 tumors with the logrank test (P < 0.03) and multivariate analysis. Our results seem to stress the difficulty to individualize different prognostic subsets from a series of breast cancer patients with only visceral metastases at initial diagnosis according to DNA flow cytometry and nuclear grade.

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

PubMed

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

2018-05-01

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

Clear cell hidradenocarcinoma of the breast: a very rare breast skin tumor.

PubMed

Mezzabotta, Maurizio; Declich, Paolo; Cardarelli, Mery; Bellone, Stefano; Pacilli, Paolo; Riggio, Eliana; Pallino, Antonio

2012-01-01

Hidradenocarcinoma is an uncommon malignant intradermal tumor of sweat gland origin with a predilection for the face and extremities. It is encountered equally in males and females, usually in the second half of life. These tumors tend to be locally aggressive. In our case, the tumor was located relatively superficially but without any apparent connection to the overlying skin. The typical disease course includes local and sometimes multiple recurrences, and some patients develop regional lymph node and distant metastases. These type of tumors in the parenchyma of the breast are extremely rare. We report a case of hidradenocarcinoma in a 77-year-old woman who presented with a palpable inflammatory nodule in the right breast.

The CpG island methylator phenotype is concordant between primary colorectal carcinoma and matched distant metastases.

PubMed

Cohen, Stacey A; Yu, Ming; Baker, Kelsey; Redman, Mary; Wu, Chen; Heinzerling, Tai J; Wirtz, Ralph M; Charalambous, Elpida; Pentheroudakis, George; Kotoula, Vassiliki; Kalogeras, Konstantine T; Fountzilas, George; Grady, William M

2017-01-01

The CpG island methylator phenotype (CIMP) in stage III colon cancer (CRC) has been associated with improved survival after treatment with adjuvant irinotecan-based chemotherapy. In this analysis, we determine whether CIMP status in the primary CRC is concordant with the CIMP status of matched metastases in order to determine if assessment of CIMP status in the primary tumor can be used to predict CIMP status of metastatic disease, which is relevant for patient management as well as for understanding the biology of CIMP CRCs. We assessed the CIMP status of 70 pairs of primary CRC and matched metastases using a CRC-specific panel of five markers ( CACNA1G , IGF2 , NEUROG1 , RUNX3 , and SOCS1 ) where CIMP positive was defined as 3/5 positive markers at a percent methylated reference threshold of ≥10%. Concordance was compared using the Fisher's exact test and P  < 0.05 was considered significant. Sixty-nine of the pairs (98.6%) showed concordant CIMP status in the primary tumor and matched metastasis; five (7.0%) of the pairs were concordantly CIMP positive. Only one pair (1.4%) had divergent CIMP status, demonstrating CIMP positivity (4/5 markers positive) in the primary tumor, while the matched metastasis was CIMP negative (0 markers positive). CIMP status is generally concordant between primary CRCs and matched metastases. Thus, CIMP status in the primary tumor is maintained in matched metastases and can be used to inform CIMP-based therapy options for the metastases.

Relationship between endobronchial ultrasound‐guided (EBUS)‐transbronchial needle aspiration utility and computed tomography staging, node size at EBUS, and positron emission tomography scan node standard uptake values: A retrospective analysis

PubMed Central

Marchand, Clare

2017-01-01

Background Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) diagnoses and stages mediastinal lymph node pathology. This retrospective study determined the relationship between EBUS‐TBNA utility and non‐small cell lung cancer (NSCLC) stage, lymph node size, and positron emission tomography (PET) standard uptake values (SUV), and the utility of neck ultrasound in bulky mediastinal disease. Methods Data of 284 consecutive patients who had undergone EBUS‐TBNA was collected. Two hundred patients had suspected NSCLC, with 148 confirmed NSCLC cases. The diagnostic utility of EBUS‐TBNA was determined according to NSCLC stage, EBUS lymph node size, PET SUV, use in distal metastases, and mutation testing. The utility of neck ultrasound for N3 disease was calculated in patients with bulky mediastinal disease. Results EBUS‐TBNA was well tolerated with 97% sensitivity in distant metastatic disease, avoiding the need for distal metastases biopsy in 81% of cases. It had equivalent diagnostic accuracy in all NSCLC stages and in lymph nodes <10 mm, <20 mm or >20 mm (sensitivity >92% in all cases), with no mutation testing failures. EBUS‐TBNA had 33% sensitivity in PET indolent (SUV < 4) nodes and 79% sensitivity in PET active nodes (SUV > 4). EBUS‐TBNA diagnosed 12 cases of lymphoma without flow cytometry. Conclusions The use of EBUS‐TBNA meant that distant metastatic biopsy was avoided in 81% of cases, performing well irrespective of cancer stage, node size, and facilitating mutation testing. Neck ultrasound failed to detect N3 disease in patients with bulky mediastinal disease. EBUS‐TBNA had a sensitivity of 33% for metastases in PET negative nodes, highlighting PET limitations. PMID:28436173

Combining Carbon Ion Radiotherapy and Local Injection of {alpha}-Galactosylceramide-Pulsed Dendritic Cells Inhibits Lung Metastases in an In Vivo Murine Model

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

Ohkubo, Yu; Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi; Iwakawa, Mayumi, E-mail: mayumii@nirs.go.j

2010-12-01

Purpose: Our previous report indicated that carbon ion beam irradiation upregulated membrane-associated immunogenic molecules, underlining the potential clinical application of radioimmunotherapy. The antimetastatic efficacy of local combination therapy of carbon ion radiotherapy and immunotherapy was examined by use of an in vivo murine model. Methods and Materials: Tumors of mouse squamous cell carcinoma (NR-S1) cells inoculated in the legs of C3H/HeSlc mice were locally irradiated with a single 6-Gy dose of carbon ions (290 MeV/nucleon, 6-cm spread-out Bragg peak). Thirty-six hours after irradiation, {alpha}-galactosylceramide-pulsed dendritic cells (DCs) were injected into the leg tumor. We investigated the effects on distant lungmore » metastases by counting the numbers of lung tumor colonies, making pathologic observations, and assessing immunohistochemistry. Results: The mice with no treatment (control) presented with 168 {+-} 53.8 metastatic nodules in the lungs, whereas the mice that received the combination therapy of carbon ion irradiation and DCs presented with 2.6 {+-} 1.9 (P = 0.009) at 2 weeks after irradiation. Immunohistochemistry showed that intracellular adhesion molecule 1, which activates DCs, increased from 6 h to 36 h after irradiation in the local tumors of the carbon ion-irradiated group. The expression of S100A8 in lung tissue, a marker of the lung pre-metastatic phase, was decreased only in the group with a combination of carbon ions and DCs. Conclusions: The combination of carbon ion radiotherapy with the injection of {alpha}-galactosylceramide-pulsed DCs into the primary tumor effectively inhibited distant lung metastases.« less

Intracranial control and radiographic changes with adjuvant radiation therapy for resected brain metastases: whole brain radiotherapy versus stereotactic radiosurgery alone.

PubMed

Patel, Kirtesh R; Prabhu, Roshan S; Kandula, Shravan; Oliver, Daniel E; Kim, Sungjin; Hadjipanayis, Constantinos; Olson, Jeffery J; Oyesiku, Nelson; Curran, Walter J; Khan, Mohammad K; Shu, Hui-Kuo; Crocker, Ian

2014-12-01

The aim of this study was to compare outcomes of postoperative whole brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) alone in patients with resected brain metastases (BM). We reviewed records of patients who underwent surgical resection of BM followed by WBRT or SRS alone between 2003 and 2013. Local control (LC) of the treated resected cavity, distant brain control (DBC), leptomeningeal disease (LMD), overall survival (OS), and radiographic leukoencephalopathy rates were estimated by the Kaplan-Meier method. One-hundred thirty-two patients underwent surgical resection for 141 intracranial metastases: 36 (27 %) patients received adjuvant WBRT and 96 (73 %) received SRS alone to the resection cavity. One-year OS (56 vs. 55 %, p = 0.64) and LC (83 vs. 74 %, p = 0.31) were similar between patients receiving WBRT and SRS. After controlling for number of BM, WBRT was associated with higher 1-year DBC compared with SRS (70 vs. 48 %, p = 0.03); single metastasis and WBRT were the only significant predictors for reduced distant brain recurrence in multi-variate analysis. Freedom from LMD was higher with WBRT at 18 months (87 vs. 69 %, p = 0.045), while incidence of radiographic leukoencephalopathy was higher with WBRT at 12 months (47 vs. 7 %, p = 0.001). One-year freedom from WBRT in the SRS alone group was 86 %. Compared with WBRT for patients with resected BM, SRS alone demonstrated similar LC, higher rates of LMD and inferior DBC, after controlling for the number of BM. However, OS was similar between groups. The results of ongoing clinical trials are needed to confirm these findings.

Intensity-Modulated Radiotherapy for Cervical Lymph Node Metastases From Unknown Primary Cancer

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

Madani, Indira; Vakaet, Luc; Bonte, Katrien

2008-07-15

Purpose: To compare the effectiveness of intensity-modulated radiotherapy (IMRT) and conventional (two-dimensional) radiotherapy in the treatment of cervical lymph node metastases from unknown primary cancer (UPC). Methods and Materials: Between February 2003 and September 2006, 23 patients with UPC of squamous cell carcinoma were treated with IMRT. Extended putative mucosal and bilateral nodal sites were irradiated to a median dose of 66 Gy. In 19 patients, IMRT was performed after lymph node dissection, and in 4 patients primary radiotherapy was given. The conventional radiotherapy group (historical control group) comprised 18 patients treated to a median dose of 66 Gy betweenmore » August 1994 and October 2003. Results: Twenty patients completed treatment. As compared with conventional radiotherapy, the incidence of Grade 3 acute dysphagia was significantly lower in the IMRT group (4.5% vs. 50%, p = 0.003). By 6 months, Grade 3 xerostomia was detected in 11.8% patients in the IMRT group vs. 53.4% in the historical control group (p = 0.03). No Grade 3 dysphagia or skin fibrosis was observed after IMRT but these were noted after conventional radiotherapy (26.7%, p = 0.01) and 26.7%, p = 0.03) respectively). With median follow-up of living patients of 17 months, there was no emergence of primary cancer. One patient had persistent nodal disease and another had nodal relapse at 5 months. Distant metastases were detected in 4 patients. The 2-year overall survival and distant disease-free probability after IMRT did not differ significantly from those for conventional radiotherapy (74.8% vs. 61.1% and 76.3% vs. 68.4%, respectively). Conclusions: Use of IMRT for UPC resulted in lower toxicity than conventional radiotherapy, and was similar in efficacy.« less

Cutaneous metastasis of cholangiocarcinoma.

PubMed

Liu, Min; Liu, Bai-Long; Liu, Bin; Guo, Liang; Wang, Qiang; Song, Yan-Qiu; Dong, Li-Hua

2015-03-14

To investigate the clinical characteristics and prognostic factors of cutaneous metastasis of cholangiocarcinoma by a retrospective analysis of published cases. An extensive search was conducted in the English literature within the PubMed database using the following keywords: cutaneous metastasis or skin metastasis and cholangiocarcinoma or bile duct. The data of 30 patients from 21 articles from 1978 to 2014 were analyzed. Patient data retrieved from the articles included the following: age, gender, time cutaneous metastasis occurred, number of cutaneous metastases throughout life, sites of initial cutaneous metastasis, anatomic site, pathology and differentiation of cholangiocarcinoma, and immunohistochemical results of the cutaneous metastasis. The assessment of overall survival after cutaneous metastasis (OSCM) was the primary endpoint. The median age at diagnosis of cutaneous metastasis of cholangiocarcinoma was 60.0 years (range: 35-77). This metastasis showed a predilection towards males, with a male to female ratio of 3.29. In 8 cases (27.6%), skin metastasis was the first sign of cholangiocarcinoma. Additionally, 18 cases (60.0%) manifested single cutaneous metastasis, while 12 cases (40.0%) demonstrated multiple skin metastases. In 50.0% of patients, the metastasis occurred in the drainage region, while 50.0% of patients had distant cutaneous metastases. The scalp was the most frequently involved region of distant skin metastasis, occurring in 36.7% of patients. The median OSCM of cholangiocarcinoma was 4.0 mo. Patient age and cutaneous metastatic sites showed no significant relation with OSCM, while male gender and single metastasis of the skin were associated with a poorer OSCM (hazard ratio: 0.168; P = 0.005, and hazard ratio: 0.296; P = 0.011, respectively). The prognosis of cutaneous metastasis of cholangiocarcinoma is dismal. Both male gender and single skin metastasis are associated with a poorer OSCM.

Indocyanine green detects sentinel lymph nodes in early breast cancer.

PubMed

Liu, Jun; Huang, Linping; Wang, Ning; Chen, Ping

2017-04-01

Objective To explore the clinical value of indocyanine green (ICG) for the fluorescence-guided detection of sentinel lymph nodes (SLNs) during sentinel lymph node biopsy (SLNB) in patients with early breast cancer. Methods This retrospective study included female patients with breast cancer. Patients were administered methylene blue and ICG using standard techniques. All SLNs that were collected during surgery were submitted for pathological examination. SLNs were defined as those that were either fluorescent, blue, fluorescent and blue or palpably suspicious. Surgical complications, axillary recurrence, distant metastasis and overall survival rates were observed postoperatively. Results A total of 60 patients were enrolled in the study. The fluorescence detection rate of SLNs was 100% ( n = 177), with a mean of 2.95 SLNs per patient. The methylene blue staining rate was 88.3% ( n = 106), with a mean of 1.77 SLNs per patient. Pathological assessment of intraoperative frozen specimens revealed SLN metastases in 10 patients, who immediately underwent axillary lymph node dissection. No patient had axillary recurrence or distant metastases, with a survival rate of 100%. Patients who underwent SLNB showed good appearance in the axillary wound, with no limited shoulder joint abduction and upper limb oedema. Conclusion Fluorescence-guided SLNB has several advantages and is suitable for clinical application.

Differences in clinical presentation of non-small cell lung cancer in never-smokers versus smokers.

PubMed

Lee, Joo Young; Na, Im Ii; Jang, Seung-Hun; Hwang, Yong Il; Choe, Du Hwan; Kim, Cheol Hyeon; Baek, Heejong

2013-12-01

This study was conducted to evaluate whether or not tumor spread and the diagnostic process in non-small cell lung cancer (NSCLC) is different based on smoking history. Associations between smoking status and clinical presentation were evaluated controlling for the effect of histology. Lung cancer with delayed diagnosis (LCDD) and incidental detection (LCID) were determined based on medical records. Of 914 patients, frequency of distant metastases was more common in never-smokers than in smokers (59% and 36%, respectively; P<0.001). Although never-smokers were more likely to have LCDD than smokers (18% and 11%, respectively; P=0.038), LCDD were not significantly associated with frequency of distant metastases [49% (LCDD) vs. 42% (non-LCDD); P=0.189] as well as tumor [29% (T3-4) vs. 24% (T1-2); P=0.134] and node [43% (N2-3) vs. 44% (N0-1); P=0.838] stage. Interestingly, never-smokers are more likely to have LCID than smokers (31% and 19%, respectively; P=0.010). In survival analysis, LCID (P=0.001; HR, 0.63) remained a prognostic factor, while LCDD did not. This study suggests distinct metastatic pattern and diagnostic processes of never-smokers. The link between survival and incidental detection was also indicated.

Identification and treatment of aggressive thyroid cancers. Part 2: risk assessment and treatment.

PubMed

Sturgeon, Cord; Angelos, Peter

2006-04-01

Most thyroid cancers are slow-growing, easily treatable tumors with an excellent prognosis after surgical resection and targeted medical therapy. Unfortunately, 10% to 15% of thyroid cancers exhibit aggressive behavior and do not follow an indolent course. Approximately one-third of patients with differentiated thyroid cancers will have tumor recurrences. Distant metastases are present in about 20% of patients with recurrent cancer. Approximately half of patients with distant metastases die within 5 years. The loss of the ability to concentrate radio-iodine and produce thyroglobulin is a sign of dedifferentiation, which occurs in about 30% of patients with persistent or recurrent thyroid cancer. Dedifferentiation is associated with poorer responses to conventional therapy and difficulty monitoring tumor burden. Clinicians must identify tumors with more aggressive biology and treat them accordingly with more aggressive regimens. Part 1 of this two-part article, which appeared in March, described in detail the distinct types of thyroid cancer, as well as risk factors, outcomes, treatment, and prognostic factors, with a focus on thyroid cancers of follicular cell origin. Part 2 covers risk assessment and staging, findings that suggest the presence of aggressive tumors, recurrent/metastatic disease, and treatment with chemotherapy and external-beam radiotherapy. Experimental treatments utilizing molecular targets, redifferentiation agents, and gene therapy are covered briefly as well.

Identification and treatment of aggressive thyroid cancers. Part 1: subtypes.

PubMed

Sturgeon, Cord; Angelos, Peter

2006-03-01

Most thyroid cancers are slow-growing, easily treatable tumors with an excellent prognosis after surgical resection and targeted medical therapy. Unfortunately, 10% to 15% of thyroid cancers exhibit aggressive behavior and do not follow an indolent course. Approximately one-third of patients with differentiated thyroid cancers will have tumor recurrences. Distant metastases are present in about 20% of patients with recurrent cancer. Approximately half of patients with distant metastases die within 5 years. The loss of the ability to concentrate radioiodine and produce thyroglobulin is a sign of dedifferentiation, which occurs in about 30% of patients with persistent or recurrent thyroid cancer. Dedifferentiation is associated with poorer responses to conventional therapy and difficulty monitoring tumor burden. Clinicians must identify tumors with more aggressive biology and treat them accordingly with more aggressive regimens. Part 1 of this two-part article describes in detail the distinct types of thyroid cancer, as well as risk factors, outcomes, and prognostic factors, with a focus on thyroid cancers of follicular cell origin. Part 2, which will appear in next month's issue, covers risk assessment and staging, findings that suggest the presence of aggressive tumors, recurrent/metastatic disease, and the value of treatment with chemotherapy and external-beam radiotherapy. Experimental treatments utilizing molecular targets, redifferentiation agents, and gene therapy are covered briefly as well.

Metastases of malignant neoplasms: Historical, biological, & clinical considerations.

PubMed

Wick, Mark R

2018-03-01

The metastasis of neoplastic cells from their site of origin to distant anatomic locations continues to be the principal cause of death from malignant tumors, and that fact has been recognized by physicians for over a century. After the work done by Halsted in the treatment of breast cancer in the 1880s, accepted surgical canon held that metastasis occurred in a linear fashion, with centrifugal "growth in continuity" from the primary neoplasm that first involved regional lymph nodes. Those structures were considered to then be the sources of more distant, visceral metastases. With that premise in mind, radical and "ultra-radical" surgical procedures were devised to remove as many lymph nodes as possible in the treatment of carcinomas and melanomas. However, such interventions were ineffective in altering tumor-related mortality. This review considers the details of the historical material just mentioned. It also reviews currently-held concepts on biological mechanisms of metastasis, the "sentinel" lymph node biopsy technique, and the important topic of metastatic tumor "dormancy" as the cause of surgical treatment failure. Finally, predictive models of tumor behavior are discussed, which are based on gene signatures. These will likely be the key to identifying malignant lesions of low surgical stage that ultimately prove fatal through later manifestation of metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Protocols for Migration and Invasion Studies in Prostate Cancer.

PubMed

van de Merbel, Arjanneke F; van der Horst, Geertje; Buijs, Jeroen T; van der Pluijm, Gabri

2018-01-01

Prostate cancer is the most common malignancy diagnosed in men in the western world. The development of distant metastases and therapy resistance are major clinical problems in the management of prostate cancer patients. In order for prostate cancer to metastasize to distant sites in the human body, prostate cancer cells have to migrate and invade neighboring tissue. Cancer cells can acquire a migratory and invasive phenotype in several ways, including single cell and collective migration. As a requisite for migration, epithelial prostate cancer cells often need to acquire a motile, mesenchymal-like phenotype. This way prostate cancer cells often lose polarity and epithelial characteristics (e.g., expression of E-cadherin homotypic adhesion receptor), and acquire mesenchymal phenotype (for example, cytoskeletal rearrangements, enhanced expression of proteolytic enzymes and other repertory of integrins). This process is referred to as epithelial-to-mesenchymal transition (EMT). Cellular invasion, one of the hallmarks of cancer, is characterized by the movement of cells through a three-dimensional matrix, resulting in remodeling of the cellular environment. Cellular invasion requires adhesion, proteolysis of the extracellular matrix, and migration of cells. Studying the migratory and invasive ability of cells in vitro represents a useful tool to assess the aggressiveness of solid cancers, including those of the prostate.This chapter provides a comprehensive description of the Transwell migration assay, a commonly used technique to investigate the migratory behavior of prostate cancer cells in vitro. Furthermore, we will provide an overview of the adaptations to the Transwell migration protocol to study the invasive capacity of prostate cancer cells, i.e., the Transwell invasion assay. Finally, we will present a detailed description of the procedures required to stain the Transwell filter inserts and quantify the migration and/or invasion.

Non-toxic approach for treatment of breast cancer and its cutaneous metastasis: Capecitabine (Xeloda) enhanced photodynamic therapy in a murine tumor model

NASA Astrophysics Data System (ADS)

Anand, Sanjay; Denisyuk, Anton; Bullock, Taylor; Govande, Mukul; Maytin, Edward V.

2018-02-01

Breast cancer (BCA) is the most frequently diagnosed cancer in women, with distant metastases to lung, liver, bone and skin occurring in approximately 40% of cases. Radiation therapy (RT) has been successfully employed for the treatment of BCA; however, multiple rounds of RT are associated with undesirable cutaneous side effects. This study explores PDT as a therapeutic alternative, to be given alone or in combination with RT and chemotherapy. Earlier, we had developed differentiation-enhanced combination photodynamic therapy (cPDT) using a neoadjuvant (5-fluorouracil; 5FU) prior to PDT. The neoadjuvant increases the levels of PpIX, leading to better efficacy following aminolevulinate (ALA)- based PDT. Here, to avoid the toxicity of systemic 5FU, we used a nontoxic 5FU precursor (Capecitabine; CPBN) in a new cPDT regimen. CBPN, a standard chemotherapeutic for BCA, is metabolized to 5FU specifically within tumor tissue. Murine (4T1) BCA cells were injected into breast fat pads of nude mice. CPBN was administered by oral gavage followed by intraperitoneal ALA and red light for PDT. CPBN pretreatment of 4T1 tumors led to increased tumor cell differentiation (3.5 fold), homogenous elevation of intratumoral PpIX levels (4.5 fold), and enhanced tumor cell death post-PDT (5 fold), relative to vehicle control. Using an in vivo imaging system (IVIS), a decline in tumor growth following CPBN-PDT was observed. Results showing the effect of CPBN-PDT on distant metastases of BCA to lung, lymph nodes and skin will be presented. In summary, CPBN-PDT, a novel combination approach, has a significant potential for translation into the clinic.

Oncofetal Protein IMP3: A Novel Molecular Marker That Predicts Metastasis of Papillary and Chromophobe Renal Cell Carcinomas

PubMed Central

Jiang, Zhong; Lohse, Christine M.; Chu, Peigou G.; Wu, Chin-Lee; Woda, Bruce A.; Rock, Kenneth L.; Kwon, Eugene D.

2009-01-01

BACKGROUND Whether an oncofetal protein, IMP3, can serve as a prognostic biomarker to predict metastasis for patients with localized papillary and chromophobe subtypes of renal cell carcinomas (RCCs) was investigated. METHODS The expression of IMP3 in 334 patients with primary papillary and chromophobe RCC from multiple medical centers was evaluated by immunohistochemistry. The 317 patients with localized papillary and chromophobe RCCs were further evaluated for outcome analyses. RESULTS IMP3 was significantly increased in a subset of localized papillary and chromophobe RCCs that subsequently metastasized. Patients with localized IMP3-positive tumors (n = 33; 10%) were over 10 times more likely to metastasize (risk ratio [RR], 11.38; 95% confidence interval [CI], 5.40–23.96; P <.001) and were nearly twice as likely to die (RR, 1.91; 95% CI, 1.13–3.22; P =.016) compared with patients with localized IMP3 negative tumors. The 5-year metastasis-free and overall survival rates were 64% and 58% for patients with IMP3-positive localized papillary and chromophobe RCCs compared with 98% and 85% for patients with IMP3 negative tumors, respectively. In multivariable analysis adjusting for the TNM stage and nuclear grade, patients with IMP3-positive tumors were still over 10 times more likely to progress to distant metastasis (RR, 13.45; 95% CI, 6.00–30.14; P <.001) and were still nearly twice as likely die (RR, 1.95; 95% CI, 1.15–3.31; P =.013) compared with patients with IMP3-negative tumors. CONCLUSIONS IMP3 is an independent prognostic biomarker that can be used to identify a subgroup of patients with localized papillary and chromophobe RCC who are at high risk for developing distant metastasis. PMID:18412154

Improvement in survival of patients with oral cavity squamous cell carcinoma: An international collaborative study.

PubMed

Amit, Moran; Yen, Tzu-Chen; Liao, Chun-Ta; Chaturvedi, Pankaj; Agarwal, Jai Prakash; Kowalski, Luiz P; Ebrahimi, Ardalan; Clark, Jonathan R; Kreppel, Matthias; Zöller, Joachim; Fridman, Eran; Bolzoni, Villaret A; Shah, Jatin P; Binenbaum, Yoav; Patel, Snehal G; Gil, Ziv

2013-12-15

An association between the survival of patients with oral cavity squamous cell carcinoma (OCSCC) and advancements in diagnosis and therapy has not been established. This was a retrospective, longitudinal, international, population-based study of 2738 patients who underwent resection of OCSCC during 2 different decades. Characteristics of patients from 7 international cancer centers who received treatment between 1990 and 2000 (group A; n = 735) were compared with patients who received treatment between 2001 and 2011 (group B; n = 2003). Patients in group B had more advanced tumors and tended to develop distant metastases more frequently than patients in group A (P = .005). More group B patients underwent selective neck dissection and received adjuvant radiotherapy (P < .001). Outcome analysis revealed a significant improvement in 5-year overall survival, from 59% for group A to 70% for group B (P < .001). There was also a significant improvement in disease-specific survival associated with operations performed before and after 2000 (from 69% to 81%, respectively; P < .001). Surgery after 2000, negative margins, adjuvant treatment, and early stage disease were independent predictors of a better outcome in multivariate analysis. The decade of treatment was an independent prognostic factor for cancer-specific mortality (hazard ratio, 0.42; 95% confidence interval, 0.3-0.6). The survival rate of patients with OCSCC improved significantly during the past 2 decades despite older age, more advanced disease stage, and a higher rate of distant metastases. The current results suggest that the prognosis for patients with OCSCC has improved over time, presumably because of advances in imaging and therapy. © 2013 American Cancer Society.

Hypofractionated Dose-Painting Intensity Modulated Radiation Therapy With Chemotherapy for Nasopharyngeal Carcinoma: A Prospective Trial

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

Bakst, Richard L.; Lee, Nancy; Pfister, David G.

2011-05-01

Purpose: To evaluate the feasibility of dose-painting intensity-modulated radiation therapy (DP-IMRT) with a hypofractionated regimen to treat nasopharyngeal carcinoma (NPC) with concomitant toxicity reduction. Methods and Materials: From October 2002 through April 2007, 25 newly diagnosed NPC patients were enrolled in a prospective trial. DP-IMRT was prescribed to deliver 70.2 Gy using 2.34-Gy fractions to the gross tumor volume for the primary and nodal sites while simultaneously delivering 54 Gy in 1.8-Gy fractions to regions at risk of microscopic disease. Patients received concurrent and adjuvant platin-based chemotherapy similar to the Intergroup 0099 trial. Results: Patient and disease characteristics are asmore » follows: median age, 46; 44% Asian; 68% male; 76% World Health Organization III; 20% T1, 52% T2, 16% T3, 12% T4; 20% N0, 36% N1, 36% N2, 8% N3. With median follow-up of 33 months, 3-year local control was 91%, regional control was 91%, freedom from distant metastases was 91%, and overall survival was 89%. The average mean dose to each cochlea was 43 Gy. With median audiogram follow-up of 14 months, only one patient had clinically significant (Grade 3) hearing loss. Twelve percent of patients developed temporal lobe necrosis; one patient required surgical resection. Conclusions: Preliminary findings using a hypofractionated DP-IMRT regimen demonstrated that local control, freedom from distant metastases, and overall survival compared favorably with other series of IMRT and chemotherapy. The highly conformal boost to the tumor bed resulted low rates of severe ototoxicity (Grade 3-4). However, the incidence of in-field brain radiation necrosis indicates that 2.34 Gy per fraction is not safe in this setting.« less

Management of penoscrotal extramammary Paget disease: case series and review of the literature

PubMed Central

Moretto, P.; Nair, V.J.; Hallani, S. El; Malone, S.; Belanger, E.; Morash, C.; Canil, C.M.

2013-01-01

Extramammary Paget disease (empd) is a rare, slow-growing neoplasm, considered to be an adenocarcinoma of the apocrine glands. In men, the penoscrotal region is the most commonly affected area. The disease can present as carcinoma in situ or as invasive disease that can subsequently metastasize to lymph nodes and distant sites. Because of the rarity of empd, the medical literature available to guide management of the disease is limited, particularly in patients with metastases. In addition, metastatic disease may pose a diagnostic challenge, because invasive cancer of the genitourinary or gastrointestinal tract can occur in association with empd. In the present case series, we describe our experience in treating penoscrotal empd with multimodality therapy, and we review the existing literature concerning its diagnosis and management. PMID:23904770

Inflammatory breast metastases of ovarian cancer: a case report.

PubMed

Kayikçioğlu, F; Boran, N; Ayhan, A; Güler, N

2001-12-01

Metastasis to the breast from extramammary malignancies is rare. A 35-year-old woman presented with bilaterally inflammatory breast involvement, 2 years after the diagnosis of stage IIIC epithelial ovarian cancer. Neoplastic tissue was immunohistochemically positive using antibodies against OC125 and negative for gross cystic disease fluid protein-15 (BRST-2) and estrogen receptor in biopsy material in the breast. Combination chemotherapy consisting of paclitaxel, cisplatin, and anthracycline was started. She died 18 months after the breast metastasis. Ovarian carcinoma usually presents with signs and symptoms related to the tumor burden within the abdominal cavity. The finding of isolated, distant metastases such as breast involvement without intraabdominal disease is extremely rare. Determining the origin of the primary tumor is important in directing the actual therapy. (c)2001 Elsevier Science.

The effect of surgery and grade on outcome of gastrointestinal stromal tumors.

PubMed

Pierie, J P; Choudry, U; Muzikansky, A; Yeap, B Y; Souba, W W; Ott, M J

2001-04-01

Gastrointestinal stromal tumors (GIST) are aggressive, rare, and difficult-to-cure gastrointestinal tumors. We believe that the clinical behavior of these tumors can be predicted by reproducible prognostic factors. A retrospective review of all patients (N = 70) with GIST treated at a tertiary care center from 1973 to 1998. Adequate data for evaluation were available for 69 patients. Male-female distribution was 40:29. Median age was 60 years. Median follow-up duration was 38 months. Tumor grade, stage, and histologic subtype at presentation; effect of grade, surgery and adjuvant therapy on recurrence, salvage, and survival. Tumor distribution included 61% in the upper, 23% in the middle, and 16% in the lower digestive tract, with a median tumor size of 7.9 cm (range, 1.8-25 cm). Tumors with more than 1 mitosis per 10 high-power fields constituted 57% of neoplasia in the series. Distant disease at initial visit occurred in 49% of patients. Complete gross resection occurred in 59% of patients. After complete resection, the 5-year survival rate was 42%, compared with 9% after incomplete resection (hazard ratio = 0.27, P<.001). Neither radiation nor chemotherapy demonstrated any significant benefit. Among 39 patients who were disease free after complete resection, 2% developed lymph node recurrence, 25% developed local recurrence, and 33% developed distant recurrences (54% liver, 20% peritoneum). By multivariate analysis the risk of local and/or distant metastases was significantly increased for tumors with more than 1 mitosis and size larger than 5 cm (P<.05). Multivariate analysis in all 69 patients revealed that incomplete resection, age greater than 50 years, non-smooth muscle histological feature, tumor with more than 1 mitosis, and tumor size larger than 5 cm significantly decreased survival. Complete gross surgical resection is presently the only means of cure for GIST. Tumors with more than 1 mitosis and a size larger than 5 cm have an especially poor prognosis, with decreased survival, and increased local and/or distant recurrence.

Recurrent subcutaneous trunk leiomyosarcoma: Management and review of the literature.

PubMed

Salemis, Nikolaos S

2013-01-01

Superficial leiomyosarcomas are rare malignant smooth-muscle tumors accounting for 4-6.5% of all soft-tissue sarcomas, less than 2-3% of cutaneous soft-tissue neoplasms and 0.04% of all cancers. They are divided into cutaneous or dermal and subcutaneous leiomyosarcomas. Subcutaneous tumors have been reported to be associated with an increased risk of local recurrences and distant metastases, compared to their cutaneous counterparts. In this study, we describe a rare case of a recurrent subcutaneous trunk leiomyosarcoma in a 68-year-old male patient. Local recurrence developed two years after the complete surgical resection with wide margins and adjuvant postoperative radiotherapy. The management of the patient is discussed along with a review of the literature. We conclude that subcutaneous leiomyosarcoma is a rare clinical entity which may be associated with an atypical clinical presentation. Physicians should be aware of the misleading features of this tumor in order to avoid delay in diagnosis and treatment. Early complete surgical resection with wide margins of at least 2 cm is the cornerstone of treatment and has been reported to mostly influence the prognosis. However, the tumor has a high tendency to recur locally and metastasize. Recurrence may develop despite wide resection and radiotherapy. Long-term follow-up is mandatory.

Recurrent subcutaneous trunk leiomyosarcoma: Management and review of the literature

PubMed Central

Salemis, Nikolaos S.

2013-01-01

Superficial leiomyosarcomas are rare malignant smooth-muscle tumors accounting for 4-6.5% of all soft-tissue sarcomas, less than 2-3% of cutaneous soft-tissue neoplasms and 0.04% of all cancers. They are divided into cutaneous or dermal and subcutaneous leiomyosarcomas. Subcutaneous tumors have been reported to be associated with an increased risk of local recurrences and distant metastases, compared to their cutaneous counterparts. In this study, we describe a rare case of a recurrent subcutaneous trunk leiomyosarcoma in a 68-year-old male patient. Local recurrence developed two years after the complete surgical resection with wide margins and adjuvant postoperative radiotherapy. The management of the patient is discussed along with a review of the literature. We conclude that subcutaneous leiomyosarcoma is a rare clinical entity which may be associated with an atypical clinical presentation. Physicians should be aware of the misleading features of this tumor in order to avoid delay in diagnosis and treatment. Early complete surgical resection with wide margins of at least 2 cm is the cornerstone of treatment and has been reported to mostly influence the prognosis. However, the tumor has a high tendency to recur locally and metastasize. Recurrence may develop despite wide resection and radiotherapy. Long-term follow-up is mandatory. PMID:23633873

Cetuximab in the treatment of metastatic mucoepidermoid carcinoma of the salivary glands: A case report and review of literature

PubMed Central

Grisanti, Salvatore; Amoroso, Vito; Buglione, Michela; Rosati, Anna; Gatta, Roberto; Pizzocaro, Claudio; Ferrari, Vittorio D; Marini, Giovanni

2008-01-01

Introduction Patients with metastatic mucoepidermoid carcinoma of salivary glands have a poor outcome. The epidermal growth factor receptor protein is overexpressed in approximately 70% of mucoepidermoid carcinoma patients and may represent a therapeutic target. However, whether treatment with anti-epidermal growth factor receptor agents is effective is unclear and clinical trials are difficult due to the rarity of the disease. Here we assessed the activity of cetuximab in mucoepidermoid carcinoma on a molecular basis. Case presentation We present the case of a 40-year old Caucasian man with a mucoepidermoid carcinoma of the major salivary glands who developed distant bone and visceral metastases despite platinum-based chemotherapy. Epidermal growth factor receptor was overexpressed and fluorescence in situ hybridization analysis demonstrated a chromosome 7 polysomy. The patient was treated with the monoclonal antibody cetuximab in combination with cisplatin. After 11 doses of cetuximab, the patient developed brain metastases but evidence of response was documented at all extracranial metastatic sites. Conclusion This case report indicates that cetuximab can be active in mucoepidermoid carcinoma and may restore sensitivity to cisplatin in platinum-treated patients. Cetuximab does not cross the blood brain barrier and may select a metastatic clone to home the central nervous system while responding at other sites. PMID:18826647

Metastatic craniopharyngioma: case report and literature review.

PubMed

Frangou, Evan Mark; Tynan, Jennifer Ruth; Robinson, Christopher Adam; Ogieglo, Lissa Marie; Vitali, Aleksander Michal

2009-09-01

Distant spread of craniopharyngioma is a rare but important complication. Most cases are a result of spread along the surgical path. We describe a rare case of metastatic leptomeningeal craniopharyngioma as a result of dissemination along CSF pathways in a child. A review of previously described cases is provided. A 14-year-old male was diagnosed with metastatic craniopharyngioma on routine follow-up imaging after multiple surgeries and radiation for locally recurrent craniopharyngioma. The lesion was erosive through the right parietal bone, but had remained clinically silent. The lesion was distant from previous surgical paths. The patient underwent right parietal craniotomy and resection of the lesion. Duraplasty and cranioplasty were necessary for closure. Histopathology confirmed adamantinomatous craniopharyngioma. One-year follow-up demonstrated no recurrence. A review of reported cases suggests that leptomeningeal implantation may be an important step in metastases of craniopharyngioma, although the mechanism is poorly understood. Attention to tumor spillage at the time of surgery may be important in preventing distant recurrences.

Atypical Distant Metastasis of Breast Malignant Phyllodes Tumors: A Case Report and Literature Review.

PubMed

de Foucher, Tiphaine; Roussel, Hélène; Hivelin, Mikael; Rossi, Léa; Cornou, Caroline; Bats, Anne-Sophie; Deloménie, Myriam; Lécuru, Fabrice; Ngô, Charlotte

2017-01-01

Malignant phyllodes tumors (MPT) are rare breast neoplasms. Preoperative diagnosis is often challenging due to the unspecific clinical, radiological, and histological characteristics of the tumor. Dissemination pathways are local with chest wall invasion, regional with lymph nodes metastasis, and distant, hematogenous, mostly to the lungs, bones, and brain. Distant metastasis (DM) can be synchronous or appear months to years after the diagnosis and initial management. The current report describes the case of a 57-year-old woman presenting with a giant/neglected MPT of the breast, with no DM at initial staging, treated by radical modified mastectomy. Motor disorders due to medullar compression by a paravertebral mass appeared at short follow-up, also treated surgically. The patient died from several DM of rapid evolution. To our knowledge, this is the only case described of MPT with metastases to soft tissue causing medullar compression. We present a literature review on unusual metastatic localizations of MPT.

Features and prognostic impact of distant metastases in 45 dogs with de novo stage IV cutaneous mast cell tumours: A prospective study.

PubMed

Pizzoni, S; Sabattini, S; Stefanello, D; Dentini, A; Ferrari, R; Dacasto, M; Giantin, M; Laganga, P; Amati, M; Tortorella, G; Marconato, L

2018-03-01

Distant metastases in dogs with cutaneous mast cell tumors (cMCT) are rare and incurable. The aims of this prospective study were to clarify the clinico-pathological features of stage IV cMCTs and to identify possible prognostic factors for progression-free interval (PFI) and survival time (ST). Dogs were eligible for recruitment if they had a previously untreated, histologically confirmed cMCT and if they underwent complete staging demonstrating stage IV disease. Dogs were uniformly followed-up, whereas treatment was not standardized and included no therapy, surgery, radiation therapy, chemotherapy, tyrosine-kinase inhibitors or a combination of these. 45 dogs with stage IV cMCT were enrolled. All dogs had distant metastatic disease, and 41 (91.1%) dogs had also metastasis in the regional lymph node. Histopathological grade and mutational status greatly varied among dogs. Median ST was 110 days. Notably, PFI and ST were independent of well-known prognostic factors, including anatomic site, histological grade, and mutational status. Conversely, tumor diameter >3 cm, more than 2 metastatic sites, bone marrow infiltration, and lack of tumor control at the primary site were confirmed to be negative prognostic factors by multivariate analysis. Currently, there is no satisfactory treatment for stage IV cMCT. Asymptomatic dogs with tumor diameter <3 cm and a low tumor burden, without bone marrow infiltration may be candidates for multimodal treatment. Stage IV dogs without lymph node metastasis may enjoy a surprisingly prolonged survival. The achievement of local tumor control seems to predict a better outcome in dogs with stage IV cMCT. © 2017 John Wiley & Sons Ltd.

Human breast cancer metastases to the brain display GABAergic properties in the neural niche.

PubMed

Neman, Josh; Termini, John; Wilczynski, Sharon; Vaidehi, Nagarajan; Choy, Cecilia; Kowolik, Claudia M; Li, Hubert; Hambrecht, Amanda C; Roberts, Eugene; Jandial, Rahul

2014-01-21

Dispersion of tumors throughout the body is a neoplastic process responsible for the vast majority of deaths from cancer. Despite disseminating to distant organs as malignant scouts, most tumor cells fail to remain viable after their arrival. The physiologic microenvironment of the brain must become a tumor-favorable microenvironment for successful metastatic colonization by circulating breast cancer cells. Bidirectional interplay of breast cancer cells and native brain cells in metastasis is poorly understood and rarely studied. We had the rare opportunity to investigate uncommonly available specimens of matched fresh breast-to-brain metastases tissue and derived cells from patients undergoing neurosurgical resection. We hypothesized that, to metastasize, breast cancers may escape their normative genetic constraints by accommodating and coinhabiting the neural niche. This acquisition or expression of brain-like properties by breast cancer cells could be a malignant adaptation required for brain colonization. Indeed, we found breast-to-brain metastatic tissue and cells displayed a GABAergic phenotype similar to that of neuronal cells. The GABAA receptor, GABA transporter, GABA transaminase, parvalbumin, and reelin were all highly expressed in breast cancer metastases to the brain. Proliferative advantage was conferred by the ability of breast-to-brain metastases to take up and catabolize GABA into succinate with the resultant formation of NADH as a biosynthetic source through the GABA shunt. The results suggest that breast cancers exhibit neural characteristics when occupying the brain microenvironment and co-opt GABA as an oncometabolite.

Human breast cancer metastases to the brain display GABAergic properties in the neural niche

PubMed Central

Neman, Josh; Termini, John; Wilczynski, Sharon; Vaidehi, Nagarajan; Choy, Cecilia; Kowolik, Claudia M.; Li, Hubert; Hambrecht, Amanda C.; Roberts, Eugene; Jandial, Rahul

2014-01-01

Dispersion of tumors throughout the body is a neoplastic process responsible for the vast majority of deaths from cancer. Despite disseminating to distant organs as malignant scouts, most tumor cells fail to remain viable after their arrival. The physiologic microenvironment of the brain must become a tumor-favorable microenvironment for successful metastatic colonization by circulating breast cancer cells. Bidirectional interplay of breast cancer cells and native brain cells in metastasis is poorly understood and rarely studied. We had the rare opportunity to investigate uncommonly available specimens of matched fresh breast-to-brain metastases tissue and derived cells from patients undergoing neurosurgical resection. We hypothesized that, to metastasize, breast cancers may escape their normative genetic constraints by accommodating and coinhabiting the neural niche. This acquisition or expression of brain-like properties by breast cancer cells could be a malignant adaptation required for brain colonization. Indeed, we found breast-to-brain metastatic tissue and cells displayed a GABAergic phenotype similar to that of neuronal cells. The GABAA receptor, GABA transporter, GABA transaminase, parvalbumin, and reelin were all highly expressed in breast cancer metastases to the brain. Proliferative advantage was conferred by the ability of breast-to-brain metastases to take up and catabolize GABA into succinate with the resultant formation of NADH as a biosynthetic source through the GABA shunt. The results suggest that breast cancers exhibit neural characteristics when occupying the brain microenvironment and co-opt GABA as an oncometabolite. PMID:24395782

The relationship between the site of metastases and outcome in children with stage IV Wilms Tumor: data from 3 European Pediatric Cancer Institutions.

PubMed

Berger, Michael; Fernandez-Pineda, Israel; Cabello, Rosa; Ramírez-Villar, Gema Lucía; Márquez-Vega, Catalina; Nustede, Rainer; Linderkamp, Christin; Schmid, Irene; Neth, Olaf; Graf, Norbert; de Agustin, Juan Carlos; von Schweinitz, Dietrich; Lacher, Martin; Hubertus, Jochen

2013-10-01

The aim of this study was to analyze in detail the site of metastasis of stage 4 Wilms tumor (WT) and its correlation with outcome. The databases from 3 major European pediatric cancer institutions were screened for children with WT between 1994 and 2011. Of 208 children identified, 31 (14.9%) had metastases at diagnosis. The lung was affected in 29 children (93.5%) and the liver in 6 children (19.4%). Twenty-seven children (87.1%) had metastases isolated to 1 organ, with the lung being the most common site (80.7%). Five-year overall survival was significantly better in those children with distant disease in either lung or liver (95.8%) compared with those affected in both lung and liver (57.1%, P=0.028). Further, prognostic markers were the response of metastases to preoperative chemotherapy (P=0.0138), high-risk histology (P=0.024), and local stage (P=0.026). Five-year overall survival was 82.1% and 5-year event-free survival was 67.9%. The overall follow-up time was 74.1 and 87.2 (2 to 151) months among survivors, and the treatment-related complication rate was 16.7%. In conclusion, in our series of stage 4 WT, prognosis was excellent if histology was favorable, metastatic disease was isolated to either lungs or liver, and if metastases responded to preoperative chemotherapy.

Management of primary and metastasized melanoma in Germany in the time period 1976-2005: an analysis of the Central Malignant Melanoma Registry of the German Dermatological Society.

PubMed

Schwager, Silke S; Leiter, Ulrike; Buettner, Petra G; Voit, Christiane; Marsch, Wolfgang; Gutzmer, Ralf; Näher, Helmut; Gollnick, Harald; Bröcker, Eva Bettina; Garbe, Claus

2008-04-01

This study analysed the changes of excision margins in correlation with tumour thickness as recorded over the last three decades in Germany. The study also evaluated surgical management in different geographical regions and treatment options for metastasized melanoma. A total of 42 625 patients with invasive primary cutaneous melanoma, recorded by the German Central Malignant Melanoma Registry between 1976 and 2005 were included. Multiple linear regression analysis was used to investigate time trends of excision margins adjusted for tumour thickness. Excision margins of 5.0 cm were widely used in the late 1970s but since then have been replaced by smaller margins that are dependent on tumour thickness. In the case of primary melanoma, one-step surgery dominated until 1985 and was mostly replaced by two-step excisions since the early 1990s. In eastern Germany, one-step management remained common until the late 1990s. During the last three decades loco-regional metastases were predominantly treated by surgery (up to 80%), whereas systemic therapy decreased. The primary treatment of distant metastases has consistently been systemic chemotherapy. This descriptive retrospective study revealed a significant decrease in excision margins to a maximum of 2.00 cm. A significant trend towards two-step excisions in primary cutaneous melanoma was observed throughout Germany. Management of metastasized melanoma showed a tendency towards surgical procedures in limited disease and an ongoing trend to systemic treatment in advanced disease.

Radiation Therapy Field Extent for Adjuvant Treatment of Axillary Metastases From Malignant Melanoma

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

Beadle, Beth M.; Guadagnolo, B. Ashleigh; Ballo, Matthew T.

2009-04-01

Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]). Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF. Results: At a median follow-up of 59 months, 111 patients (56%) hadmore » sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications. Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.« less

The diagnostic utility of Merkel cell polyomavirus immunohistochemistry in a fine needle aspirate of metastatic Merkel cell carcinoma of unknown primary to the pancreas.

PubMed

Li, Long; Molberg, Kyle; Cheedella, Naga; Thibodeaux, Joel; Hinson, Stacy; Lucas, Elena

2018-01-01

Merkel cell carcinoma (MCC) is an aggressive skin tumor with a high tendency for metastases. We report a case of MCC initially presenting as axillary and pancreatic metastases. A 33-year-old HIV-positive Hispanic male presented with a history of a rapidly growing axillary mass. A needle core biopsy demonstrated an epithelioid neoplasm composed of small to medium-sized cells with high nuclear-cytoplasmic ratio, nuclear molding, and frequent mitotic figures. A subsequent PET scan revealed a 1.5 cm FDG avid mass in the pancreas. Endoscopic ultrasound-guided FNA of the pancreatic mass showed neoplastic cells with similar morphology to those of the axillary mass. The tumor cells were positive with pancytokeratin AE1/AE3, CK20, CD56, synatophysin, chromogranin, and Merkel cell polyomavirus (MCPyV). This case of MCC most likely originated from a resolved primary skin lesion drained by the involved axillary lymph node with subsequent metastases to the pancreas and distant lymph nodes. © 2017 Wiley Periodicals, Inc.

Advances in diagnosis and treatment of metastatic cervical cancer

PubMed Central

2016-01-01

Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases. PMID:27171673

Management of non metastatic phyllodes tumors of the breast: review of the literature.

PubMed

Khosravi-Shahi, Parham

2011-12-01

Phyllodes tumors of the breast are rare tumors, accounting for less than 0.5% of all breast tumors. These tumors are comprised of both stromal and epithelial elements; and traditionally they are graded by the use of a set of histologic features into benign, borderline, and malignant subtypes. Unfortunately, the histologic classification of phyllodes tumors does not reliably predict clinical behavior. The mainstay of treatment of non metastatic phyllodes tumors of the breast is complete surgical resection with wide resection margins. Lumpectomy or partial mastectomy is the preferred surgical therapy. However, despite the complete surgical resection, local failure rate may be high; and 22% of malignant tumors may give rise to haematogenous metastases. The most frequent site of distant metastases is the lungs. Several predictive factors of recurrence and metastases have been described in the literature, such as positive surgical margins, increased stromal cellularity, stromal overgrowth, stromal atypia and increased mitotic activity. Nevertheless, the role of adjuvant therapies (radiotherapy and chemotherapy) is presently undefined and should be tested in multicenter, prospective, randomized trials. Copyright © 2011 Elsevier Ltd. All rights reserved.

Extracranial metastasizing solitary fibrous tumors (SFT) of meninges: histopathological features of a case with long-term follow-up.

PubMed

Gessi, Marco; Gielen, Gerrit H; Roeder-Geyer, Eva-Dorette; Sommer, Clemens; Vieth, Michael; Braun, Veit; Kuchelmeister, Klaus; Pietsch, Torsten

2013-02-01

Extrapleural solitary fibrous tumors are uncommon mesenchymal neoplasms frequently observed in middle-aged adults and are classified, according to the WHO classification of soft tissue tumors, as part of the hemangiopericytoma tumor group. However, these two entities remain separated in the WHO classification of tumors of the central nervous system. In fact, meningeal solitary fibrous tumors are believed to be benign lesion and only in a minority of cases local relapses have been described, although detailed survival clinical studies on solitary fibrous tumors of meninges are rare. In contrast to hemangiopericytoma, which frequently shows distant extracranial metastases, such an event is exceptional in patients with meningeal solitary fibrous tumors and has been clinically reported in a handful of cases only and their histopathological features have not been investigated in detail. In this report, we describe the detailed clinico-pathological features of a meningeal solitary fibrous tumor presenting during a 17-year follow-up period, multiple intra-, extracranial relapses and lung metastases. © 2012 Japanese Society of Neuropathology.

Advances in diagnosis and treatment of metastatic cervical cancer.

PubMed

Li, Haoran; Wu, Xiaohua; Cheng, Xi

2016-07-01

Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases.

Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies.

PubMed

Miller, Jacob A; Kotecha, Rupesh; Ahluwalia, Manmeet S; Mohammadi, Alireza M; Chao, Samuel T; Barnett, Gene H; Murphy, Erin S; Vogelbaum, Michael A; Angelov, Lilyana; Peereboom, David M; Suh, John H

2017-06-15

The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 months), HER2-positive (15.4 months), and luminal B (18.8 months) cohorts (P<.001). Among patients with HER2-amplified disease, the median survival was extended with the use of both HER2 antibodies (17.9 months vs 15.1 months; P = .04) and TKIs (21.1 months vs 15.4 months; P = .03). The 12-month cumulative incidences of local failure among molecular subtypes were 6.0% in the luminal A cohort, 10.3% in the luminal B cohort, 15.4% in the HER2-positive cohort, and 9.9% in the basal cohort (P = .01). Concurrent HER2/epidermal growth factor receptor TKIs with stereotactic radiosurgery significantly decreased the 12-month cumulative incidence of local failure from 15.1% to 5.7% (P<.001). Molecular subtypes appear to be prognostic for survival and predictive of the response to radiotherapy. TKIs were found to improve survival and local control, and may decrease the rate of distant failure. To preserve neurocognition, these results support a paradigm of upfront radiosurgery and HER2-directed therapy in the HER2-amplified population, reserving whole-brain radiotherapy for salvage. Cancer 2017;123:2283-2293. © 2017 American Cancer Society. © 2017 American Cancer Society.

Thermochemoradiation Therapy Using Superselective Intra-arterial Infusion via Superficial Temporal and Occipital Arteries for Oral Cancer With N3 Cervical Lymph Node Metastases

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

Mitsudo, Kenji, E-mail: mitsudo@yokohama-cu.ac.jp; Koizumi, Toshiyuki; Iida, Masaki

2012-08-01

Purpose: To evaluate the therapeutic results and histopathological effects of treatment with thermochemoradiation therapy using superselective intra-arterial infusion via the superficial temporal and occipital arteries for N3 cervical lymph node metastases of advanced oral cancer. Methods and Materials: Between April 2005 and September 2010, 9 patients with N3 cervical lymph node metastases of oral squamous cell carcinoma underwent thermochemoradiation therapy using superselective intra-arterial infusion with docetaxel (DOC) and cisplatin (CDDP). Treatment consisted of hyperthermia (2-8 sessions), superselective intra-arterial infusions (DOC, total 40-60 mg/m{sup 2}; CDDP, total 100-150 mg/m{sup 2}) and daily concurrent radiation therapy (total, 40-60 Gy) for 4-6 weeks.more » Results: Six of 9 patients underwent neck dissection 5-8 weeks after treatment. In four of these 6 patients, all metastatic lymph nodes, including those at N3, were grade 3 (non-viable tumor cells present) or grade 4 (no tumor cells present) tumors, as classified by the system by Shimosato et al (Shimosato et al Jpn J Clin Oncol 1971;1:19-35). In 2 of these 6 patients, the metastatic lymph nodes were grade 2b (destruction of tumor structures with a small amount of residual viable tumor cells). The other 3 patients did not undergo neck dissection due to distant metastasis after completion of thermochemoradiation therapy (n=2) and refusal (n=1). The patient who refused neck dissection underwent biopsy of the N3 lymph node and primary sites and showed grade 3 cancer. During follow-up, 5 patients were alive without disease, and 4 patients died due to pulmonary metastasis (n=3) and noncancer-related causes (n=1). Five-year survival and locoregional control rates were 51% and 88%, respectively. Conclusions: Thermochemoradiation therapy using intra-arterial infusion provided good histopathologic effects and locoregional control rates in patients with N3 metastatic lymph nodes. However, patients with N3 metastatic lymph nodes experienced a high rate of distant metastases.« less

Total venous inflow occlusion and pericardial auto-graft reconstruction for right atrial hemangiosarcoma resection in a dog.

PubMed

Verbeke, Fei; Binst, Dominique; Stegen, Ludo; Waelbers, Tim; de Rooster, Hilde; Van Goethem, Bart

2012-10-01

A sizeable right atrial hemangiosarcoma in a 6-year-old Bordeaux dog, World Health Organization (WHO) stage 2, was excised using total venous inflow occlusion. The defect was restored with a non-vascularized pericardial auto-graft. The dog had a disease-free interval of 7 mo. The dog was euthanized 9 months later, at which time there were distant metastases but no indication of local recurrence.

Cryotherapy for conjunctival primary acquired melanosis and malignant melanoma. Experience with 62 cases.

PubMed

Jakobiec, F A; Rini, F J; Fraunfelder, F T; Brownstein, S

1988-08-01

Sixty-two patients were treated by some combination of cryotherapy and surgery with an average follow-up of 3.3 years for one of the following diseases: focal or diffuse flat conjunctival primary acquired melanosis (PAM) with atypia but without a nodule of melanoma (10 cases); unifocal malignant melanoma with or without focal or diffuse PAM (30 cases); and multinodular/multicentric melanoma with and without PAM (22 cases). Of the ten patients who had PAM with atypia, invasive nodules of malignant melanoma did not develop. A second treatment was required to control the disease in four of the ten patients with extensive or diffuse lesions, and one has mild persistent disease. Of the 30 patients with unifocal nodules of malignant melanoma, 27 remained free of recurrence after one treatment, and 2 are asymptomatic after two treatments. One patient with a thick nodule at presentation required a parotidectomy and radical neck dissection for cervical metastases after recurrence in the conjunctival sac. In the group of 22 patients with multinodular malignant melanoma, only two did not have recurrent disease after one treatment. Of those who received multiple therapies, seven remained free of recurrence for at least 2 years after the last treatment; regional or distant metastases developed in nine; four required exenteration; and eight died. Conjunctival adjunctive cryotherapy avoids exenteration in extensive lesions of pure PAM and in unifocal melanoma, but even after multiple therapies, multinodular malignant melanoma had a 45% rate of metastasis. Metastasis was related to the presence of PAM sine pigmento in four patients (microscopically but not clinically detectable PAM); to the location of the nodules (9 of 10 patients who experienced metastases had forniceal, palpebral, and/or caruncular nodules); to the thickness or depth of invasion of the nodules (greater than 2 mm); and to the development of intralymphatic spread ("in-transit" local metastasis) within the conjunctival sac in six patients. No metastases were encountered among patients with strictly limbal nodules and among five patients with invasive nodules composed of spindle cells in part or in toto. Therapeutic success in this spectrum of melanocytic proliferations is closely correlated with the clinical extent of the disease when initiating definitive therapy.

[Recurrences after surgical treatment of early (pT1) cancer of the stomach: laws of development, extended lymphadenectomy in prophylaxis of recurrences].

PubMed

Skoropad, V Iu; Berdov, B A

2007-01-01

Long-term results of treatment of 175 patients with early cancer of the stomach are analyzed. Recurrences of the disease (local, regional recurrences and distant metastases) were diagnosed in 14 (8.2% of all operated) patients. Duration of recurrence-free period ranged from 2-3 months to 9.5 years; median was 12 months. Tumor spread, regional nodes affection, tumor morphological structure, age of patients were the main prognostic factors for recurrences. Extent of surgery and lymphodissection did not correlate with recurrences rate. It is concluded that extended lymphodissection in patients with early cancer of the stomach should not be regarded as a real method for an increase of treatment efficacy.

AURKA promotes cancer metastasis by regulating epithelial-mesenchymal transition and cancer stem cell properties in hepatocellular carcinoma

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

Chen, Chenlin; Song, Guangyuan; Xiang, Jue

AURKA (aurora kinase A) has been confirmed as an oncogene in cancer development; however, its role and underlying mechanisms in the metastasis of hepatocellular carcinoma (HCC) remain unknown. In this study, We found that AURKA was up-regulated in HCC tissues and correlated with pathological stage and distant metastasis. Further found that AURKA was involved in the cancer metastases after radiation in HCC. While overexpression of AURKA induced epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) behaviors though PI3K/AKT pathway, silencing AURKA suppressed radiation-enhanced cell invasiveness of HCC. Taken together, our results suggested that AURKA contributed in metastasis of irradiated residulmore » HCC though facilitating EMT and CSC properties, suggesting the potential clinical application of AURKA inhibitors in radiotherapy for patients with HCC. - Highlights: • First reported overexpression of AURKA in HCC and correlation with poor OS. • AURKA was involved in the cancer metastases after radiation in HCC. • Further found AURKA promoted EMT and CSC behaviors though PI3K/AKT pathway. • Silencing AURKA suppressed radiation-enhanced cell invasiveness of HCC. • AURKA may be potential therapeutic target of HCC.« less

Inflammatory metastatic breast cancer with gallbladder metastasis: an incidental finding.

PubMed

Ebrahim, Hassan; Graham, David; Rice, David; Ribadeneyra, Michael; Thorner, Kim; Shipley, William; Wehmueller, Michael

2015-07-01

Breast cancer is the most frequently diagnosed cancer in women, with an estimated 231,840 new cases representing 14.0% of all new cancer cases in the United States in 2015. Early screening and modern techniques of imaging and diagnosis have led to a significant improvement in detecting early-stage breast cancers and to a decrease in the incidence of metastatic breast cancer (MBC). About 20%-30% of patients who are initially diagnosed with an early-stage, nonmetastatic breast cancer will subsequently develop a distant metastatic disease. Between 6%-10% of the new breast cancer cases present initially as stage IV, referred to as de novo MBC. The most common sites of breast cancer metastases are lymph nodes, chest wall, skeleton, lung, skin, and the central nervous system (CNS). Lobular carcinoma, in particular, may metastasize to the gastrointestinal tract, peritoneum, and retroperitoneum. Gallbladder metastasis from breast cancer is very rare, and only 15-20 cases have been reported in the literature. Most of those cases have been associated particularly with a lobular histology. We report an additional rare case of MBC to the gallbladder, but with a ductal histology. ©2015 Frontline Medical Communications.

Thyroid neoplasms after radiation therapy for adolescent acne vulgaris. [X radiation

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

Paloyan, E.; Lawrence, A.M.

There is a potential hazard of thyroid cancer after exposure to external irradiation for the treatment of adolescent acne vulgaris. We noted a 60% incidence of thyroid carcinoma among 20 patients with such a history, who were operated on for thyroid nodules during a five-year period. Eighty-three percent of the patients with carcinoma had either a follicular or a mixed papillary-follicular carcinoma; 17% had a papillary carcinoma; 33% had regional node metastases; none had evidence of distant metastases. The interval between radiation exposure and thyroidectomy ranged from nine to 41 years. This association of thyroid neoplasms and a prior historymore » of radiation for acne vulgaris may be coincidental and therefore remains to be proved by retrospective surveys of large numbers of treated patients with appropriate controls.« less

Lung microenvironment promotes the metastasis of human hepatocellular carcinoma cells to the lungs.

PubMed

Jin, Yun; Ai, Junhua; Shi, Jun

2015-01-01

Cancer metastasis is a highly tissue-specific and organ-selective process. It has been shown that the affected tissues and/or organs play a major role in this complex process. The lung is the most common target organ of extrahepatic hepatocellular carcinoma (HCC) metastasis, but the precise molecular mechanism underlying this organ-specific metastasis remains unclear. We hypothesized that lung microenvironment was able to promote the metastasis of HCC cells to the lungs leading to distant metastases. In support of our hypothesis, we provided evidence from targeted metastasis in various types of cancer and contributing factors in the microenvironment of targeted tissues/organs. A better understanding of the steps involved in the interplay between HCC cells and lung microenvironment may offer new perspectives for the medical management of lung metastases of HCC.

TU-D-207B-02: Delta-Radiomics: The Prognostic Value of Therapy-Induced Changes in Radiomics Features for Stage III Non-Small Cell Lung Cancer Patients

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

Fave, X; Court, L; UT Health Science Center, Graduate School of Biomedical Sciences, Houston, TX

Purpose: To determine how radiomics features change during radiation therapy and whether those changes (delta-radiomics features) can improve prognostic models built with clinical factors. Methods: 62 radiomics features, including histogram, co-occurrence, run-length, gray-tone difference, and shape features, were calculated from pretreatment and weekly intra-treatment CTs for 107 stage III NSCLC patients (5–9 images per patient). Image preprocessing for each feature was determined using the set of pretreatment images: bit-depth resample and/or a smoothing filter were tested for their impact on volume-correlation and significance of each feature in univariate cox regression models to maximize their information content. Next, the optimized featuresmore » were calculated from the intratreatment images and tested in linear mixed-effects models to determine which features changed significantly with dose-fraction. The slopes in these significant features were defined as delta-radiomics features. To test their prognostic potential multivariate cox regression models were fitted, first using only clinical features and then clinical+delta-radiomics features for overall-survival, local-recurrence, and distant-metastases. Leave-one-out cross validation was used for model-fitting and patient predictions. Concordance indices(c-index) and p-values for the log-rank test with patients stratified at the median were calculated. Results: Approximately one-half of the 62 optimized features required no preprocessing, one-fourth required smoothing, and one-fourth required smoothing and resampling. From these, 54 changed significantly during treatment. For overall-survival, the c-index improved from 0.52 for clinical factors alone to 0.62 for clinical+delta-radiomics features. For distant-metastases, the c-index improved from 0.53 to 0.58, while for local-recurrence it did not improve. Patient stratification significantly improved (p-value<0.05) for overallsurvival and distant-metastases when delta-radiomics features were included. The delta-radiomics versions of autocorrelation, kurtosis, and compactness were selected most frequently in leave-one-out iterations. Conclusion: Weekly changes in radiomics features can potentially be used to evaluate treatment response and predict patient outcomes. High-risk patients could be recommended for dose escalation or consolidation chemotherapy. This project was funded in part by grants from the National Cancer Institute (NCI) and the Cancer Prevention Research Institute of Texas (CPRIT).« less

Total venous inflow occlusion and pericardial auto-graft reconstruction for right atrial hemangiosarcoma resection in a dog

PubMed Central

Verbeke, Fei; Binst, Dominique; Stegen, Ludo; Waelbers, Tim; de Rooster, Hilde; Van Goethem, Bart

2012-01-01

A sizeable right atrial hemangiosarcoma in a 6-year-old Bordeaux dog, World Health Organization (WHO) stage 2, was excised using total venous inflow occlusion. The defect was restored with a non-vascularized pericardial auto-graft. The dog had a disease-free interval of 7 mo. The dog was euthanized 9 months later, at which time there were distant metastases but no indication of local recurrence. PMID:23543933

SLP-2 overexpression could serve as a prognostic factor in node positive and HER2 negative breast cancer.

PubMed

Cao, Wenfeng; Zhang, Bin; Li, Jin; Liu, Yanxue; Liu, Zhihua; Sun, Baocun

2011-12-01

This study aimed to evaluate the utility as a prognostic factor of SLP-2 on the outcome of breast cancer patients. We performed immunohistochemical analysis to examine the SLP-2 expression in a large panel of invasive breast cancer samples. Of the 496 samples, 261 showed overexpression of SLP-2. Importantly, there were significant associations between SLP-2 overexpression and tumour size (p = 0.002), lymph node/distant metastases, clinical stage (p < 0.001), HER2/neu expression (p = 0.003). In addition, there were obvious differences in levels of SLP-2 expression within four molecular subtypes of breast cancer (p = 0.011). High level SLP-2 expression was shown in tumour samples of HER2 and luminal B subtypes, and low level SLP-2 expression was shown in luminal A and triple negative subtypes, suggesting that overexpression of SLP-2 was closely correlated with HER2/neu expression, and that both SLP-2 and HER2/neu can play a role in lymph node/distant metastases of breast cancers. Thus lymph node status, HER2/neu and SLP-2 high-level expression can act as independent prognostic factors. There is an obvious link between SLP-2 and HER2/neu expression. Overexpression of SLP-2 is associated with poorer total survival, especially in lymph node positive coupled with HER2/neu negative patients.

Meningeal hemangiopericytoma with delayed multiple distant metastases.

PubMed

Chang, Chiung-Chih; Chang, Yung-Yee; Lui, Chun-Chung; Huang, Chao-Cheng; Liu, Jia-Shou

2004-10-01

A 43-year-old housewife suffered from an occipital headache, and brain computed tomography (CT) showed an occipital meningeal tumor. She received a complete tumor excision and the tumor pathology was interpreted as atypical meningioma. Five years later, a subacute left neck pain with radiation to the left arm occurred. A tumor invading the second and third cervical vertebrae with compression on the dural sac was found. Angiography revealed hypervascular tumor staining supplied from the left vertebral artery. CT-guided biopsy was performed and nests of atypical spindle cells accompanied by staghorn vascular pattern were revealed histologically. Immunohistochemical studies showed positive vimentin staining but negative reactions to epithelial membrane antigen, cytokeratin low molecular weight, cytokeratin high molecular weight, CD34 and S-100 protein. Estimation of the Ki-67 proliferative (mitotic) index by using MIB-1 monoclonal antibody was 12%. Later on, a systemic survey revealed lesions in the left lung, liver and kidney. The diagnosis was revised to hemangiopericytoma. Distant metastasis is common in this tumor. However, the delayed multiple metastases without local recurrence were relatively rare. The clinical course in this patient also supported that a high mitotic activity may correlate with a poor prognosis even if the pathology is taken from the metastatic tissue, and that long-term follow-up is mandatory. Detailed immunohistochemical staining is helpful in avoiding misdiagnosis of meningioma.

Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer.

PubMed

Huang, Shao Hui; Perez-Ordonez, Bayardo; Weinreb, Ilan; Hope, Andrew; Massey, Christine; Waldron, John N; Kim, John; Bayley, Andrew J; Cummings, Bernard; Cho, B C John; Ringash, Jolie; Dawson, Laura A; Siu, Lillian L; Chen, Eric; Irish, Jonathan; Gullane, Patrick; Hui, Angela; Liu, Fei-Fei; Shen, Xiaowei; Xu, Wei; O'Sullivan, Brian

2013-01-01

To describe the natural course of distant metastases (DMs) following radiotherapy (RT) or chemoradiotherapy (CRT) in HPV(+) oropharyngeal carcinoma (OPC). OPC treated with RT/CRT from 1/1/2000 to 5/31/2010 were reviewed. The natural course of DM were compared between HPV(+) and HPV(-) cohorts. Median follow-up was 3.9 years. The DM rate were similar (11% vs. 15% at 3-years, p=0.25) between the HPV(+) (n=457) vs. the HPV(-) (n=167) cases. While almost all (24/25) HPV(-) DM occurred within 2-years following RT (1 was at 2.1 years), 7/54 (13%) of HPV(+) DM were detected beyond 3 years (up to 5.3 years). Disseminating to >2 organs occurred in 18 (33%) HPV(+) vs. none in HPV(-). Post-DM survival rates were 11% vs. 4% at 2-years (p=0.02) for the HPV(+) vs. HPV(-) cases respectively. 5/6 HPV(+) with lung oligo-metastasis were still alive with stable disease beyond 2-years after salvage procedures for DM (chemotherapy: 3; surgical resection: 2; radiotherapy: 1). Although DM rates are similar, the natural course of HPV(+) DM differs from that of HPV(-) patients: it may occur after a longer interval, often with a "disseminating" phenotype, and a small number may have prolonged survival after salvage for DM. Copyright © 2012 Elsevier Ltd. All rights reserved.

131I therapy of thyroid cancer patients.

PubMed

Reiners, C; Farahati, J

1999-12-01

Thyroid cancer is a rare malignancy with wide interethnic and geographic variations. In Germany thyroid carcinoma is the 13th most frequent malignancy (2.7 new cases yearly per 100,000 inhabitants). The overall temporal incidence is increasing slightly in recent years. The most common types of cancer are papillary (60-80%) and follicular cancers (10-20%). The relevant prognostic indicators are tumor stage and distant metastases. The mean survival rates in papillary thyroid cancer usually exceed 90%, whereas in follicular thyroid cancer they amount to approximately 80%. The standard treatment procedure in differentiated papillary and follicular thyroid cancer consists of total thyroidectomy followed by adjuvant ablative therapy with radioiodine. Only in papillary thyroid cancer stage pT1N0M0 lobectomy alone is considered to be appropriate. In patients with locally invasive differentiated thyroid cancers stage pT4 adjuvant percutaneous radiation therapy is a treatment option. Radioiodine therapy has to be performed under the stimulative influence of TSH. Usually TSH suppressive medication with Levothyroxine has to be withdrawn approximately 4 weeks prior to radioiodine therapy. In the future, exogenous stimulation by recombinant TSH may be used instead of thyroid hormone withdrawal. It has been proven by different studies that ablative radioiodine therapy reduces the frequency of recurrences and tumor spread in patients with thyroid cancer significantly. In patients with distant metastases, up to 50% of complete responses may be achieved with radioiodine treatment.

[Breast lesions of a metastatic melanoma on a radiotherapy territory: Treatment by vemurafenib and carcinologic surgery].

PubMed

Fernandez, J; Montaudié, H; Courdi, A; Georgiou, C; Camuzard, O; Chignon-Sicard, B

2016-02-01

This article describes the unique case of a female patient who presented distant melanoma metastasis on the breast while having irradiation therapy for breast cancer. This happened eight months after the initial treatment for a melanoma of the back (under the right scapula). Furthermore, this case report demonstrates the efficiency of Vemurafenib® as a treatment for late stage melanomas. The patient was a 47-year-old female that had a superficial spreading melanoma under the right scapula (Breslow 1.02mm) that was treated with 2cm skin excision and sentinel lymph node sampling that was negative. The melanoma was positive for the BRAF600E mutation. One month after this incident, the patient developed breast cancer that was treated with conservative surgery and radiotherapy. Three months after the end of the irradiation treatment, she developed multiple melanoma metastasis on the skin of the breast. Our multidisciplinary team decided to initiate a treatment with vemurafenib. The patient showed an excellent response, so the surgical team completed the treatment with a radical mastectomy and immediate reconstruction with a pedicled latissimus dorsi flap. The histologic report of the mastectomy specimen showed no sign of melanocytic proliferation, that demonstrates the efficacy of vemurafenib. The patient showed no relapse after two years of follow-up. The speed of development and location of cutaneous metastases in this case brought us to think about the effects of radiation therapy on the skin. Radiation therapy causes acute complications (radiodermatitis) by cellular and molecular mechanisms. Moreover, depressed immunity is found after irradiation. Association of these mecanisms could explain the appearance of these metastases in irradiation field. The efficiency of vemurafenib found in our case is consistent with what is described in literature, especially with the improvement in median overall survival. This case demonstrates a unique case of distant melanoma metastasis on the irradiation field of a breast cancer. It also demonstrates the efficacy of vemurafenib as well as the efficacy of a radical complementary surgical treatment in these patients. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Inverse association between age at the time of radiation exposure and extent of disease in cases of radiation-induced childhood thyroid carcinoma in Belarus.

PubMed

Farahati, J; Demidchik, E P; Biko, J; Reiners, C

2000-03-15

Increased incidence of childhood thyroid carcinoma, particularly in the youngest children, has been reported from Belarus since the nuclear reactor accident at Chernobyl in 1986. The relation between disease severity and age at the time of the accident, not previously established in this cohort, was analyzed in this study. The authors studied the association between disease severity, expressed by TNM classification, and age at radiation exposure in a cohort of 483 patients younger than 8 years at the time of the Chernobyl accident who have been diagnosed with differentiated thyroid carcinoma since 1986 at the Center for Thyroid Cancer in Minsk. The associations between age at radiation exposure and TNM categories were compared among 4 groups of patients who were ages <2, 2.1-4, 4.1-6, and 6.1-8 years at the time of the accident. Multivariate discriminant analysis was performed to examine the effects of age at the time of the accident, gender, histology, tumor stage, and N classification on the frequency of distant metastasis. Younger age at the time of the Chernobyl accident was associated with greater extrathyroidal tumor extension (P<0.01) and more lymph node involvement (P<0.0001) and tended to be associated with more distant metastases (P = 0.09). Compared with patients who were ages 6.1-8 years at the time of the accident, patients who were younger than 2 years had significantly more extrathyroidal tumor invasion (P = 0.004), lymph node involvement (P = 0.004), and distant metastases (P = 0.05). The age at diagnosis increased with older age at the time of radiation exposure (linear regression analysis; correlation coefficient = 0. 67; P<0.001). Multivariate analysis revealed that younger age at the time of the accident (P = 0.001) and advanced locoregional tumor extension (P<0.001) were the only powerful factors influencing the risk for distant metastasis of this malignancy. The severity of disease was associated inversely with age at the time of radiation exposure in these cases of radiation-induced childhood thyroid carcinoma. Copyright 2000 American Cancer Society.

Primary and secondary leiomyosarcoma of the oral and perioral region--clinicopathological and immunohistochemical analysis of a rare entity with a review of the literature.

PubMed

Schütz, Anja; Smeets, Ralf; Driemel, Oliver; Hakim, Samer George; Kosmehl, Hartwig; Hanken, Henning; Kolk, Andreas

2013-06-01

Leiomyosarcoma (LMS) rarely occurs in the head and neck region. These tumors present with a wide range of clinical features, so the diagnosis is predicated on conventional microscopic findings coupled with immunohistochemical analysis. Clinical and histologic data of 7 patients with LMS of the head and neck were recorded retrospectively. In addition to routine immunohistochemistry, staining for cell cycle regulator proteins p16 and p21 was performed. Five LMSs (4 intraoral, 1 dermal cheek) occurred primarily in the oral and perioral region. Two LMSs (parietal and sinonasal) were diagnosed as metastases originating from the uterus and pelvis. Treatment of the primary LMSs consisted of radical tumor resection with clear margins. Distant metastases from LMSs were irradiated or excised as palliative treatment. Three of 5 patients (60%) with primarily excised LMS developed recurrence after an average of 7 months, with lung metastases occurring after 17 months. In 1 patient, cervical lymph node metastases were detected after 10 months. Of all patients, 5 died after an average survival period of 2.4 years. The mean survival period of the 5 patients with primary LMS of the head and neck was 3.3 years. All tumors were positive for vimentin and α-smooth muscle actin, with 57% of tumors showing positive nuclear expression of p16 and 71% of p21. Lack of p16 nuclear expression was associated with a shorter mean survival time (1.3 vs 4.3 yr for p16 positivity). Lung and cervical lymph node metastases often occur in LMS of the head and neck. Presurgical staging, including gynecologic examination, whole-body computed tomography, and sometimes positron-emission or computed tomography, to rule out LMS metastasis is mandatory. Surgical resection of the tumor should be given top priority. Lack of p16 reactivity may have a prognostic value for LMS because it was related to a trend toward poorer survival. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Retroperitoneal margin involvement by adenocarcinoma of the caecum and ascending colon: what does it mean?

PubMed

Scott, N; Jamali, A; Verbeke, C; Ambrose, N S; Botterill, I D; Jayne, D G

2008-03-01

Circumferential margin involvement (CRM) is a powerful predictor of local recurrence, distant metastasis and patient survival in rectal cancer. In this study, we aimed to determine the frequency of retroperitoneal margin involvement in right colon cancer and describe its relationship to tumour stage and outcome of surgical treatment. Two hundred and twenty-eight consecutive resections for adenocarcinoma of the ascending colon and caecum were identified between 1998 and 2006. Tumour involvement of the posterior retroperitoneal surgical resection margin (RSRM) was recorded and correlated with tumour stage, grade and clinical outcome. RSRM positive patients were compared with CRM positive rectal tumours resected in the same surgical unit. Nineteen of 228 right hemicolectomies (8.4%) showed tumour involvement of the RSRM (defined as < or = 1 mm). Approximately half of the RSRM positive patients underwent palliative resections because of synchronous distant metastases. Out of nine 'potentially curative' resections where the RSRM was involved, five patients subsequently developed metastatic recurrence and two isolated local recurrence. RSRM positivity was associated with advanced tumour stage and more extensive extramural spread than CRM positive rectal cancers. Retroperitoneal surgical resection margin involvement by caecal and ascending colon carcinoma is a marker of advanced tumour stage and associated with a high incidence of synchronous and metachronous distant metastasis. More aggressive surgery to obtain a clear margin or postoperative radiotherapy to the tumour bed is likely to benefit only a minority of patients.

Stereotactic radiosurgery for focal leptomeningeal disease in patients with brain metastases.

PubMed

Wolf, Amparo; Donahue, Bernadine; Silverman, Joshua S; Chachoua, Abraham; Lee, Jean K; Kondziolka, Douglas

2017-08-01

Leptomeningeal disease (LMD) is well described in patients with brain metastases, presenting symptomatically in approximately 5% of patients. Conventionally, the presence of LMD is an indication for whole brain radiation therapy (WBRT) and not suitable for stereotactic radiosurgery (SRS). The purpose of the study was to evaluate the local control and overall survival of patients who underwent SRS to focal LMD. We reviewed our prospective registry and identified 32 brain metastases patients with LMD, from a total of 465 patients who underwent SRS between 2013 and 2015. Focal LMD was targeted with SRS in 16 patients. The median imaging follow-up time was 7 months. The median volume of LMD was 372 mm 3 and the median margin dose was 16 Gy. Five patients underwent prior WBRT. Histology included non-small cell lung (8), breast (5), melanoma (1), gastrointestinal (1) and ovarian cancer (1). Follow-up MR imaging was available for 14 patients. LMD was stable in 5 and partially regressed in 8 patients at follow-up. One patient had progression of LMD with hemorrhage 5 months after SRS. Seven patients developed distant LMD at a median time of 7 months. The median actuarial overall survival from SRS for LMD was 10.0 months. The 6-month and 1-year actuarial overall survival was 60% and 26% respectively. Six patients underwent WBRT after SRS for focal LMD at a median time of 6 months. Overall, focal LMD may be may be treated successfully with radiosurgery, potentially delaying WBRT in some patients.

Vaginal metastasis presenting as postmenopausal bleeding.

PubMed

Ng, Qiu Ju; Namuduri, Rama Padma; Yam, Kwai Lam; Lim-Tan, Soo Kim

2015-08-01

Vaginal cancer is rare worldwide and represents 2% of all gynaecological cancers in Singapore. Primary vaginal malignancies are rare and vaginal metastases constitute the majority of vaginal malignancies. Most of these metastases arise from the cervix, endometrium or ovary, although they can also metastasise from distant sites such as the colon, breast and pancreas. We report a rare case of vaginal metastasis in a patient with previous gastric and rectal adenocarcinomas. An 89-year-old woman with a history of gastric and rectal malignancy presented with postmenopausal bleeding. A 2-cm vaginal tumour at the introitus was discovered upon examination. This case demonstrates the importance of performing a gynaecological examination during follow-up for patients with a history of malignancy. The prognosis for vaginal metastasis is poor, as it is often associated with disseminated disease. Depending on the extent of the lesions, radiotherapy or surgery can be considered.

ABCB1 identifies a subpopulation of uveal melanoma cells with high metastatic propensity

PubMed Central

Landreville, Solange; Agapova, Olga A.; Kneass, Zachary T.; Salesse, Christian; Harbour, J. William

2011-01-01

SUMMARY Metastasis of tumor cells to distant organs is the leading cause of death in melanoma. Yet, the mechanisms of metastasis remain poorly understood. One key question is whether all cells in a primary tumor are equally likely to metastasize or whether subpopulations of cells preferentially give rise to metastases. Here, we identified a subpopulation of uveal melanoma cells expressing the multidrug resistance transporter ABCB1 that are highly metastatic compared to ABCB1− bulk tumor cells. ABCB1+ cells also exhibited enhanced clonogenicity, anchorage independent growth, tumorigenicity and mitochondrial activity compared to ABCB1− cells. A375 cutaneous melanoma cells contained a similar subpopulation of highly metastatic ABCB1+ cells. These findings suggest that some uveal melanoma cells have greater potential for metastasis than others, and that a better understanding of such cells may be necessary for more successful therapies for metastatic melanoma. PMID:21575142

Primary hepatic neuroendocrine tumor after 4 years tumor-free follow-up.

PubMed

Lambrescu, Ioana Maria; Martin, Sorina; Cima, Luminita; Herlea, Vlad; Badiu, Corin; Fica, Simona

2015-06-01

A primary hepatic neuroendocrine tumour (PHNET) is a very rare disease. The liver represents the preferential site for neuroendocrine tumors' metastases. A 45-year old Caucasian female who presented with nausea, vomiting, diarrhea, accompanied by diffuse abdominal pain was found to have on contrast-enhanced computer tomography an encapsulated, partially cystic liver mass. The patient underwent an uneventful left atypical hepatic resection. Histopatological and immunohistochemical examination revealed a slowly growing (G1) hepatic neuroendocrine tumour. Post surgery, the specific neuroendocrine markers (serum Chromogranin A and 24h urinary 5 hydroxy-indolacetic acid) were within normal range. Further functional imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. The patient is presently after 4 years of follow-up with no local recurrence or distant metastases. The diagnosis of PHNET is a medical challenge that requires a thorough long term follow-up in order to exclude an occult primary neuroendocrine tumour.

The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma

NASA Astrophysics Data System (ADS)

Zhai, Weiwei; Lim, Tony Kiat-Hon; Zhang, Tong; Phang, Su-Ting; Tiang, Zenia; Guan, Peiyong; Ng, Ming-Hwee; Lim, Jia Qi; Yao, Fei; Li, Zheng; Ng, Poh Yong; Yan, Jie; Goh, Brian K.; Chung, Alexander Yaw-Fui; Choo, Su-Pin; Khor, Chiea Chuen; Soon, Wendy Wei-Jia; Sung, Ken Wing-Kin; Foo, Roger Sik-Yin; Chow, Pierce Kah-Hoe

2017-02-01

Hepatocellular carcinoma (HCC) has one of the poorest survival rates among cancers. Using multi-regional sampling of nine resected HCC with different aetiologies, here we construct phylogenetic relationships of these sectors, showing diverse levels of genetic sharing, spanning early to late diversification. Unlike the variegated pattern found in colorectal cancers, a large proportion of HCC display a clear isolation-by-distance pattern where spatially closer sectors are genetically more similar. Two resected intra-hepatic metastases showed genetic divergence occurring before and after primary tumour diversification, respectively. Metastatic tumours had much higher variability than their primary tumours, suggesting that intra-hepatic metastasis is accompanied by rapid diversification at the distant location. The presence of co-existing mutations offers the possibility of drug repositioning for HCC treatment. Taken together, these insights into intra-tumour heterogeneity allow for a comprehensive understanding of the evolutionary trajectories of HCC and suggest novel avenues for personalized therapy.

Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer

PubMed Central

Kim, Yi Rang; Kim, Seonghoon; Choi, Jin Woo; Choi, Sung Yong; Lee, Sang-Hee; Kim, Homin; Hahn, Sei Kwang; Koh, Gou Young; Yun, Seok Hyun

2015-01-01

Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm2 for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT. PMID:26000054

Primary Hepatic Malignant Fibrous Histiocytoma on PET/CT.

PubMed

Liu, Yachao; Xu, Baixuan

2018-06-01

Malignant fibrous histiocytoma is mainly presented in extremities, less commonly in posterior peritoneum, but primary presented in liver is very rare and often with a poor prognosis because of its high aggression. The features of clinical presentations and images are variable and the pre-operative diagnosis is difficult. Here, we report a primary hepatic malignant fibrous histiocytoma patient with no distant metastasis showed on pre-operative F-FDG PET/CT, however with many metastases showed on the post-operative F-FDG PET/CT.

Maintenance of Epithelial Stem Cells by Cbl Proteins

DTIC Science & Technology

2012-09-01

may be a potential mechanism behind inhibition of MEC differentiation in the absence of Cbl.   7   Figure 1. Flow cytometry analysis of hTERT...results in tumors at the implant site as well as distant metastases To assess whether ErbB2-dependent MPPS1 cells retain their oncogenic potential ...the levels of ErbB2 are not lost in this cell line during culture [ ]. This in itself suggested the potential dependence of oncogenic traits of MPPS1

68Ga-PSMA-HBED-CC-Avid Synchronous Urinary Bladder Paraganglioma in a Patient With Metastatic Prostate Carcinoma.

PubMed

Parihar, Ashwin Singh; Vadi, Shelvin Kumar; Mittal, Bhagwant Rai; Kumar, Rajender; Bal, Amanjit; Singh, Shrawan Kumar

2018-06-19

Ga-PSMA-HBED-CC PET/CT has proven to be a useful modality in patients with prostate carcinoma, especially in those with suspected recurrence and in detection of locoregional and distant metastases. However, with expanding use of this tracer, several recent reports of in vivo expression of PSMA in nonprostatic benign and malignant entities have been published. We report a patient with PSMA-avid synchronous urinary bladder paraganglioma and metastatic prostate carcinoma.

Is knowledge translation adequate? A quality assurance study of staging investigations in early stage breast cancer patients.

PubMed

Han, Dolly; Hogeveen, Sophie; Sweet Goldstein, Miriam; George, Ralph; Brezden-Masley, Christine; Hoch, Jeffrey; Haq, Rashida; Simmons, Christine E

2012-02-01

After primary surgery, patients diagnosed with early stage breast cancer undergo radiological investigations based on pathologic stage of disease to rule out distant metastases. Published guidelines can aid clinicians in determining which tests are appropriate based on stage of disease. We wished to assess the consistency of radiological staging in an academic community oncology setting with standard guidelines and to determine the overall impact of non-adherence to these guidelines. A retrospective cohort study was conducted for new breast cancer patients seen at a single institution between January 2009 and April 2010. Patients were included if initial diagnosis and primary surgery was at this institution. Pathologic stage and radiological tests completed were recorded. A literature review was performed and the results were compared with those from this study to determine overall adherence rates. Subsequently, a cost analysis was performed to determine the financial impact at this centre. 231 patients met eligibility criteria for inclusion in this study. A large proportion of patients were over-staged with 129 patients (55%) undergoing unnecessary investigations according to guidelines. Specifically, 59% of stage I patients and 58% of stage II patients were over-investigated. Distant metastases at the time of diagnosis were found in three patients, all of whom had stage III disease (1.3%). The literature reviewed revealed similar non-adherence rates in other centres. The estimated cost of such non-adherence is in the range of $78 (CDN) per new early stage breast cancer patient seen at this centre. This oncology centre has a low adherence to practice guidelines for staging investigations in breast cancer patients, with 55% of patients undergoing unnecessary tests. Very few patients had metastases at diagnosis, and all had pathological stage III disease. Efforts may need to focus on improving knowledge translation across clinical oncology settings to increase guideline adherence.

Successful treatment with pazopanib plus PD-1 inhibitor and RAK cells for advanced primary hepatic angiosarcoma: a case report.

PubMed

Qiao, Yu; Yang, Jihong; Liu, Lili; Zeng, Yixin; Ma, Jie; Jia, Jing; Zhang, Li; Li, Xiaoguang; Wu, Peihong; Wang, Wenchao; Liu, Dongge; Chen, Huan; Zhao, Yunbo; Xi, Huan; Wang, Yao

2018-02-21

Primary hepatic angiosarcoma (PHA) is a rare and aggressive solid tumor, with high rates of local recurrence and distant metastasis, and poor prognosis. There are no established treatment guidelines for PHA. A 78-year-old asymptomatic man with PHA that was successfully treated with pazopanib plus PD-1 inhibitor and RetroNectin-activated killer cells (RAK cells). After one month of treatment, there was a clear reduction in the size and number of the liver metastases; and after nearly 15 months, most of the lesions were stable, no new lesions had developed, and the side effect of treatment was minor. Pazopanib, PD-1 inhibitor and RAK cells could serve as a potential option for the treatment of advanced PHA.

Outcomes and toxicities in patients with intermediate-risk prostate cancer treated with brachytherapy alone or brachytherapy and supplemental external beam radiation therapy.

PubMed

Schlussel Markovic, Emily; Buckstein, Michael; Stone, Nelson N; Stock, Richard G

2018-05-01

To evaluate the cancer control outcomes and long-term treatment-related morbidity of brachytherapy as well as combination brachytherapy and external beam radiation therapy (EBRT) in patients with intermediate-risk prostate cancer. A retrospective review was conducted in a prospectively collected database of patients with intermediate-risk prostate cancer who were treated either with brachytherapy or brachytherapy and EBRT, with or without androgen deprivation therapy (ADT), in the period 1990-2014. Urinary and erectile dysfunction symptoms were measured using the International Prostate Symptom Score (IPSS), the Mount Sinai erectile function scale and the Sexual Health Inventory for Men (SHIM). Cancer control endpoints included biochemical failure and development of distant metastases. All statistical analyses were carried out using the Statistical Package for Social Science (SPSS). Survival curves were calculated using Kaplan-Meier actuarial methods and compared using log-rank tests. Cox regression multivariate analyses were used to test the effect of multiple variables on treatment outcomes. A total of 902 patients were identified, with a median follow-up of 91 months. Of these, 390 received brachytherapy and 512 received combination therapy with EBRT. In patients with one intermediate-risk factor, the addition of EBRT did not significantly affect freedom from biochemical failure or distant metastases. Among patients with two or three intermediate-risk factors, added EBRT did not improve freedom from biochemical failure. Significant differences in late toxicity between patients treated with brachytherapy vs combination brachytherapy and EBRT were identified including urge incontinence (P < 0.001), haematuria (P < 0.001), dysuria (P < 0.001), and change in quality-of-life IPSS (P = 0.002). These symptoms were reported by patients at any point during treatment follow-up. Analysis of patients who were potent before treatment using actuarial methods showed that patients receiving combination therapy more frequently experienced loss of potency, as measured by the Mount Sinai erectile function scale (P = 0.040). Brachytherapy monotherapy results in equal biochemical and distant control in both patients with one and more than one intermediate-risk features. While no significant benefit was shown, we believe that the addition of EBRT may prevent recurrence in patients with multiple intermediate-risk features and should be considered. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Androgen receptor status is highly conserved during tumor progression of breast cancer.

PubMed

Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

2015-11-09

With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.

A case of peritoneal metastasis during treatment for hypopharyngeal squamous cell carcinoma.

PubMed

Wakasaki, Takahiro; Omori, Hirofumi; Sueyoshi, Shintaro; Rikimaru, Fumihide; Toh, Satoshi; Taguchi, Kenichi; Higaki, Yuichiro; Morita, Masaru; Masuda, Muneyuki

2016-10-18

Advanced head and neck squamous cell carcinomas frequently develop distant metastases to limited organs, including the lungs, bone, mediastinal lymph nodes, brain, and liver. Peritoneal carcinomatosis as an initial distant metastasis from hypopharyngeal squamous cell carcinoma is quite rare. A 75-year-old man diagnosed with hypopharyngeal squamous cell carcinoma and his clinical stage was determined as T2N2cM0. Notably, the right retropharyngeal lymph node surrounded more than half of the right internal carotid artery. Concomitant conformal radiation therapy was administered for the primary hypopharyngeal lesion, and the whole neck and tumor response was evaluated at this point according to our algorithm-based chemoradioselection protocol. As the tumor responses at both the primary and lymph nodes were poor, with the right retropharyngeal lymph node in particular demonstrating mild enlargement, we performed a radical surgery: pharyngolaryngectomy, bilateral neck dissection, and reconstruction of the cervical esophagus with a free jejunal flap. Then, postoperative CRT was performed. During these therapies, the patient developed a fever and mild abdominal pain, which was associated with an increased C-reactive protein level. Contrast-enhanced computed tomography from the neck to the pelvis demonstrated mild peritoneal hypertrophy and ascites with no evidence of recurrent and/or metastatic tumor formation. We initially diagnosed acute abdomen symptoms as postoperative ileus. However, cytological examination of the refractory ascites resulted in a diagnosis of peritoneal carcinomatosis. Owing to rapid disease progress, the patient died 1.5 months after abdominal symptom onset. The present case is the second reported case of head and neck squamous cell carcinoma with peritoneal carcinomatosis as an incipient distant metastasis. Therefore, peritoneal carcinomatosis should be considered a differential diagnosis when acute abdomen is noted during treatment for head and neck cancers.

Asthma and risk of lethal prostate cancer in the Health Professionals Follow-Up Study.

PubMed

Platz, Elizabeth A; Drake, Charles G; Wilson, Kathryn M; Sutcliffe, Siobhan; Kenfield, Stacey A; Mucci, Lorelei A; Stampfer, Meir J; Willett, Walter C; Camargo, Carlos A; Giovannucci, Edward

2015-08-15

Inflammation, and more generally, the immune response are thought to influence the development of prostate cancer. To determine the components of the immune response that are potentially contributory, we prospectively evaluated the association of immune-mediated conditions, asthma and hayfever, with lethal prostate cancer risk in the Health Professionals Follow-up Study. We included 47,880 men aged 40-75 years with no prior cancer diagnosis. On the baseline questionnaire in 1986, the men reported diagnoses of asthma and hayfever and year of onset. On the follow-up questionnaires, they reported new asthma and prostate cancer diagnoses. We used Cox proportional hazards regression to estimate relative risks (RRs). In total, 9.2% reported ever having been diagnosed with asthma. In all, 25.3% reported a hayfever diagnosis at baseline. During 995,176 person-years of follow-up by 2012, we confirmed 798 lethal prostate cancer cases (diagnosed with distant metastases, progressed to distant metastasis or died of prostate cancer [N = 625]). Ever having a diagnosis of asthma was inversely associated with risk of lethal (RR = 0.71, 95% confidence interval [CI] = 0.51-1.00) and fatal (RR = 0.64, 95% CI = 0.42-0.96) disease. Hayfever with onset in the distant past was possibly weakly positively associated with risk of lethal (RR = 1.10, 95% CI = 0.92-1.33) and fatal (RR = 1.12, 95% CI = 0.91-1.37) disease. Men who were ever diagnosed with asthma were less likely to develop lethal and fatal prostate cancer. Our findings may lead to testable hypotheses about specific immune profiles in the etiology of lethal prostate cancer. © 2015 UICC.

Identification of Distant Metastatic Disease in Uterine Cervical and Endometrial Cancers with FDG PET/CT: Analysis from the ACRIN 6671/GOG 0233 Multicenter Trial.

PubMed

Gee, Michael S; Atri, Mostafa; Bandos, Andriy I; Mannel, Robert S; Gold, Michael A; Lee, Susanna I

2018-04-01

Purpose To assess the accuracy of staging positron emission tomography (PET)/computed tomography (CT) in detecting distant metastasis in patients with local-regionally advanced cervical and high-risk endometrial cancer in the clinical trial by the American College of Radiology Imaging Network (ACRIN) and the Gynecology Oncology Group (GOG) (ACRIN 6671/GOG 0233) and to compare central and institutional reader performance. Materials and Methods In this prospective multicenter trial, PET/CT and clinical data were reviewed for patients enrolled in ACRIN 6671/GOG 0233. Two central readers, blinded to site read and reference standard, reviewed PET/CT images for distant metastasis. Central review was then compared with institutional point-of-care interpretation. Reference standard was pathologic and imaging follow-up. Test performance for central and site reviews of PET/CT images was calculated and receiver operating characteristic analysis was performed. Generalized estimating equations and nonparametric bootstrap procedure for clustered data were used to assess statistical significance. Results There were 153 patients with cervical cancer and 203 patients with endometrial cancer enrolled at 28 sites. Overall prevalence of distant metastasis was 13.7% (21 of 153) for cervical cancer and 11.8% (24 of 203) for endometrial cancer. Central reader PET/CT interpretation demonstrated sensitivity, specificity, positive predictive value (PPV), and negative predictive value of 54.8%, 97.7%, 79.3%, and 93.1% for cervical cancer metastasis versus 64.6%, 98.6%, 86.1%, and 95.4% for endometrial cancer, respectively. By comparison, local institutional review demonstrated sensitivity, specificity, PPV, and negative predictive value of 47.6%, 93.9%, 55.6%, and 91.9% for cervical cancer metastasis and 66.7%, 93.9%, 59.3%, and 95.5% for endometrial cancer, respectively. For central readers, the specificity and PPV of PET/CT detection of cervical and endometrial cancer metastases were all significantly higher compared with that of local institutional review (P < .05). Central reader area under the receiver operating characteristic curve (AUC) values were 0.78 and 0.89 for cervical and endometrial cancer, respectively; these were not significantly different from local institutional AUC values (0.75 and 0.84, respectively; P > .05 for both). Conclusion FDG PET/CT demonstrates high specificity and PPV for detecting distant metastasis in cervical and endometrial cancer and should be included in the staging evaluation. Blinded central review of imaging provides improved specificity and PPV for the detection of metastases and should be considered for future oncologic imaging clinical trials. © RSNA, 2017.

Genetic Heterogeneity in Therapy-Naïve Synchronous Primary Breast Cancers and Their Metastases.

PubMed

Ng, Charlotte K Y; Bidard, Francois-Clement; Piscuoglio, Salvatore; Geyer, Felipe C; Lim, Raymond S; de Bruijn, Ino; Shen, Ronglai; Pareja, Fresia; Berman, Samuel H; Wang, Lu; Pierga, Jean-Yves; Vincent-Salomon, Anne; Viale, Agnes; Norton, Larry; Sigal, Brigitte; Weigelt, Britta; Cottu, Paul; Reis-Filho, Jorge S

2017-08-01

Purpose: Paired primary breast cancers and metachronous metastases after adjuvant treatment are reported to differ in their clonal composition and genetic alterations, but it is unclear whether these differences stem from the selective pressures of the metastatic process, the systemic therapies, or both. We sought to define the repertoire of genetic alterations in breast cancer patients with de novo metastatic disease who had not received local or systemic therapy. Experimental Design: Up to two anatomically distinct core biopsies of primary breast cancers and synchronous distant metastases from nine patients who presented with metastatic disease were subjected to high-depth whole-exome sequencing. Mutations, copy number alterations and their cancer cell fractions, and mutation signatures were defined using state-of-the-art bioinformatics methods. All mutations identified were validated with orthogonal methods. Results: Genomic differences were observed between primary and metastatic deposits, with a median of 60% (range 6%-95%) of shared somatic mutations. Although mutations in known driver genes including TP53, PIK3CA , and GATA3 were preferentially clonal in both sites, primary breast cancers and their synchronous metastases displayed spatial intratumor heterogeneity. Likely pathogenic mutations affecting epithelial-to-mesenchymal transition-related genes, including SMAD4, TCF7L2 , and TCF4 ( ITF2 ), were found to be restricted to or enriched in the metastatic lesions. Mutational signatures of trunk mutations differed from those of mutations enriched in the primary tumor or the metastasis in six cases. Conclusions: Synchronous primary breast cancers and metastases differ in their repertoire of somatic genetic alterations even in the absence of systemic therapy. Mutational signature shifts might contribute to spatial intratumor genetic heterogeneity. Clin Cancer Res; 23(15); 4402-15. ©2017 AACR . ©2017 American Association for Cancer Research.

Radiofrequency ablation of neuroendocrine liver metastases: the Middlesex experience.

PubMed

Gillams, A; Cassoni, A; Conway, G; Lees, W

2005-01-01

Current treatment options for neuroendocrine liver metastases are not widely applicable or not that effective. Image-guided thermal ablation offers the possibility of a minimally invasive, albeit palliative, treatment that decreases tumor volume, preserves most of the normal liver, and can be repeated several times. We report our experience with image-guided thermal ablation in 25 patients with unresectable liver metastases. Since 1990 we have treated 189 tumors at 66 treatment sessions in 25 patients (12 female, 13 male; median age, 56 years; age range, 26--78 years). Thirty treatments were performed with a solid-state laser, and 36 treatments were performed with radiofrequency ablation. All but one treatment was performed percutaneously under image guidance. Sixteen patients had metastases from carcinoid primaries, three from gastrinoma, two from insulinoma, and four from miscellaneous causes. Fourteen of 25 had symptoms from hormone secretion. Imaging follow-up was available in 19 patients at a median of 21 months (range, 4--75 months). There was a complete response in six patients, a partial response in seven, and stable disease in one; hence, tumor load was controlled in 14 of 19 patients (74%). Relief of hormone-related symptoms was achieved in nine of 14 patients (69%). The median survival period from the diagnosis of liver metastases was 53 months. One patient with end-stage cardiac disease died after a carcinoid crisis. There were eight (12%) complications: five local and three distant, four major and four minor. As a minimally invasive, readily repeatable procedure that can be used to ablate small tumors, preferably before patients become severely symptomatic, radiofrequency ablation can provide effective control of liver tumor volume in most patients over many years.

Multimodal treatment, including interferon beta, of nasopharyngeal carcinoma in children and young adults: preliminary results from the prospective, multicenter study NPC-2003-GPOH/DCOG.

PubMed

Buehrlen, Martina; Zwaan, Christian Michel; Granzen, Bernd; Lassay, Lisa; Deutz, Peter; Vorwerk, Peter; Staatz, Gundula; Gademann, Günther; Christiansen, Hans; Oldenburger, Foppe; Tamm, Miriam; Mertens, Rolf

2012-10-01

The authors report preliminary results from a prospective multicenter study (Nasopharyngeal Carcinoma [NPC] 2003 German Society of Pediatric Oncology and Hematology/German Children's Oncology Group [NPC-2003-GPOH/DCOG]). From 2003 to 2010, 45 patients (ages 8-20 years), including 1 patient with stage II NPC and 44 patients with stage III/IV NPC, were recruited to the study. The patient with stage II disease received radiotherapy (59.4 grays [Gy]). The patients with stage III/IV disease received 3 courses of neoadjuvant chemotherapy with cisplatin, 5-fluorouracil, and folinic acid. The cumulative irradiation dose was 54 Gy in 5 patients, who achieved complete remission after neoadjuvant chemotherapy, and 59.4 Gy in the remaining 40 patients. All patients received concomitant cisplatin during the first week and last week of irradiation. After irradiation, all patients received interferon beta for 6 months. Tumor response was evaluated by magnetic resonance imaging studies and positron emission tomography scans. After the completion of treatment, 43 of 45 patients were in complete remission. In 2 patients, only a partial response was achieved, followed by distant metastases (1 patient) or local progression and distant metastases (1 patient), 6 months and 10 months after diagnosis, respectively. Another patient developed a solitary pelvic bone metastasis 21 months after diagnosis. After a median follow-up of 30 months (range, 6-95 months), the event-free survival rate was 92.4%, and the overall survival was 97.1%. Acute toxicity consisted mainly of leucopenia, mucositis, and nausea; and late toxicity consisted of hearing loss and hypothyroidism. Combined therapy with neoadjuvant chemotherapy, radiochemotherapy, and interferon beta was well tolerated and resulted in a very good outcome that was superior to the outcomes of published results from all other pediatric NPC study groups. Copyright © 2012 American Cancer Society.

Salvage image guided radiation therapy to the prostate after cryotherapy failure.

PubMed

Hopper, Austin B; Sandhu, Ajay P S; Parsons, J Kellogg; Rose, Brent; Einck, John P

2018-01-01

Cryotherapy is an option for the primary treatment of localized prostate cancer, along with radical prostatectomy, external beam radiation therapy, and brachytherapy. Although it is known that local recurrence can occur in >20% of patients treated with primary cryotherapy, unfortunately there is a paucity of data on later salvage treatments. The use of external beam radiation therapy is an attractive option after cryotherapy failure, but there is little data on its efficacy and toxicity. We evaluated the biochemical control and complication rates of salvage dose-escalated image guided intensity modulated radiation therapy (IG-IMRT) after cryotherapy failure. Patients who were treated at our institution from 2005 to 2016 were reviewed for those who underwent cryotherapy as initial treatment followed by salvage IGRT. Patients were treated with dose-escalated IG-IMRT using standard treatment margins of 3 mm posterior and 7 mm in all other directions and daily cone beam computed tomography or kv imaging to implanted fiducial markers. Biochemical progression was defined in accordance with the Phoenix consensus conference definition. Eight patients were identified as having received post-cryotherapy salvage radiation within the study period. The median total dose was 77.7 Gy (range, 75.6-81.0 Gy). Median follow-up was 55 months (range, 6-88 months). Six patients remained biochemically controlled at the latest follow-up. One patient developed distant metastases after 22 months and one experienced biochemical failure at 30 months with no evidence of distant metastases. No patients experienced acute gastrointestinal toxicities of grade 2 or higher. There were no cases of late gastrointestinal or genitourinary toxicity. High-dose IG-IMRT results in high rates of salvage and extremely low rates of serious late toxicity for patients with locally recurrent prostate cancer after cryotherapy. Although the results are encouraging, given the small number of patients in this and other series, we remain cautious with regard to this treatment and believe the use of salvage radiation therapy after cryotherapy warrants further study.

Skin metastasis on the neck: an unusual presentation of recurrence of papillary thyroid carcinoma

PubMed Central

Soylu, Selen; Teksoz, Serkan; Ozcan, Murat; Bukey, Yusuf

2017-01-01

Skin metastasis of papillary thyroid carcinoma (PTC) is rare. Here, two cases of skin metastases of PTC are presented. Both of the patients were females, one is 83 and the other is 65 years old. The patients were admitted to the hospital with a movable skin lesion on anterior neck region. Free T3 and T4 levels were in normal levels and TSH levels were low in both patients. The 83-year-old patient underwent total thyroidectomy due to papillary thyroid cancer and received 131I ablation therapy and then thyroid suppression therapy. After the surgery, the patient lived without evidence of disease for 3 years and then skin metastasis occurred. The 65-year-old patient had a total thyroidectomy 5 years ago due to PTC then neck dissection due to metastasis 3 years later and then received 131I ablation therapy. Thyroid ultrasonography of both patients showed hypoechoic nodules with central vascularization. In the histological examination of both patients, cystic lesions filled with papillary structures were seen. Fine needle aspiration biopsy (FNAB) taken from both patients were papillary carcinoma with solid trabecular pattern. PTC tends to metastasize to regional lymph nodes but distant metastasis is rare. When distant metastasis develops, prognosis of the disease is poor. Therefore, skin metastasis of papillary thyroid cancer is a poor prognostic factor. If the patient does not have a thyroid malignancy history, diagnosis of PTC metastatic to the skin may be difficult since primary skin tumors such as apocrine tumors have similar histopathological features. However, in the presented cases since there was a PTC history, the diagnosis was easier with the help of histopathological examination. Skin metastasis of PTC should be kept in mind when differential diagnosis of atypical skin lesions are made especially in the patients with thyroid malignancy history. PMID:29142854

Preablation 131-I scans with SPECT/CT contribute to thyroid cancer risk stratification and 131-I therapy planning.

PubMed

Avram, Anca M; Esfandiari, Nazanene H; Wong, Ka Kit

2015-05-01

The use of preablation diagnostic radioiodine scans for risk stratification and radioiodine therapy planning for differentiated thyroid cancer (DTC) remains controversial. The objective was to assess the contribution of preablation diagnostic 131-I scans with SPECT/CT (Dx 131-I scan) to (1) the risk stratification and (2) the postoperative management of DTC. The study was designed as a prospective sequential patient series. The study was conducted at a University hospital. Three hundred twenty patients (pts) with DTC (219F; 101M, mean age 47.3 ± 16.4 y, range 10-90) were studied. Using clinical and histopathology information an endocrinologist performed risk stratification and determined postoperative management with respect to radioiodine therapy (RAI) planning. The decision to withhold or to administer RAI, and the recommended low, medium or high therapeutic 131-I activity were recorded. Dx 131-I scans were performed and interpreted by two nuclear medicine physicians as showing thyroid remnant, cervical nodal, or distant metastases. The endocrinologist then reperformed risk stratification and reformulated management after consideration of Dx 131-I scans and stimulated thyroglobulin (Tg) information. Main outcome measures were changes in risk stratification and management after Dx 131-I scans. Detection of unsuspected nodal and distant metastases and elevated stimulated Tg levels resulted in a change in the estimated risk of recurrence in 15% of patients, and management in 31% of patients, as compared to initial risk stratification and management based on histopathology alone. Both imaging data and stimulated thyroglobulin levels acquired at the time of Dx 131-I scans are consequential for 131-I therapy planning, providing information that changes risk stratification in 15% of patients as compared to recurrence risk estimation based on histopathology alone. Dx 131-I scans contribute to risk stratification by defining residual nodal and distant metastatic disease, changing clinical management in 29.4% of patients.

Alternative Lengthening of Telomeres and Loss of DAXX/ATRX Expression Predicts Metastatic Disease and Poor Survival in Patients with Pancreatic Neuroendocrine Tumors.

PubMed

Singhi, Aatur D; Liu, Ta-Chiang; Roncaioli, Justin L; Cao, Dengfeng; Zeh, Herbert J; Zureikat, Amer H; Tsung, Allan; Marsh, J Wallis; Lee, Kenneth K; Hogg, Melissa E; Bahary, Nathan; Brand, Randall E; McGrath, Kevin M; Slivka, Adam; Cressman, Kristi L; Fuhrer, Kimberly; O'Sullivan, Roderick J

2017-01-15

Pancreatic neuroendocrine tumors (PanNET) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing has identified recurrent mutations in the genes DAXX and ATRX, which correlate with loss of protein expression and alternative lengthening of telomeres (ALT). Both ALT and DAXX/ATRX loss were initially reported to be associated with a favorable prognosis; however, recent studies suggest the contrary. Our aims were to assess the prevalence and prognostic significance of ALT and DAXX/ATRX in both primary and metastatic PanNETs. Telomere-specific FISH and DAXX/ATRX IHC was performed on a multi-institutional cohort of 321 patients with resected PanNET and 191 distant metastases from 52 patients. These results were correlated with clinicopathologic features, including disease-free survival (DFS) and disease-specific survival (DSS). The prevalence of ALT and DAXX/ATRX loss in resected PanNETs was 31% and 26%, respectively, and associated with larger tumor size, higher WHO grade, lymph node metastasis, and distant metastasis (P < 0.001). The 5-year DFS and 10-year DSS of patients with ALT-positive and DAXX/ATRX-negative PanNETs were 40% and 50%, respectively, as compared with 96% and 89%, respectively, for wild-type PanNETs. Among distant metastases, ALT and DAXX/ATRX loss was 67% and 52%, respectively, and only occurred in the setting of an ALT-positive and DAXX/ATRX-negative primary PanNET. By multivariate analysis, both ALT and DAXX/ATRX loss were negative, independent prognostic factors for DFS. ALT and DAXX/ATRX loss in PanNETs was associated with shorter DFS and DSS and likely plays a significant role in driving metastatic disease. Clin Cancer Res; 23(2); 600-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Comprehensive imaging of tumor recurrence in breast cancer patients using whole-body MRI at 1.5 and 3 T compared to FDG-PET-CT.

PubMed

Schmidt, Gerwin P; Baur-Melnyk, Andrea; Haug, Alexander; Heinemann, Volker; Bauerfeind, Ingo; Reiser, Maximilian F; Schoenberg, Stefan O

2008-01-01

To compare the diagnostic accuracy for the detection of tumor recurrence in breast cancer patients using whole-body-MRI (WB-MRI) at 1.5 or 3T compared to FDG-PET-CT. Thirty-three female patients with breast cancer and suspicion of recurrence underwent FDG-PET-CT and WB-MRI. Coronal T1w-TSE- and STIR-sequences, HASTE-imaging of the lungs, contrast-enhanced T1w- and T2w-TSE-sequences of the liver, brain and abdomen were performed, using a WB-MRI-scanner at 1.5 (n=23) or 3T (n=10). Presence of local recurrence, lymph node involvement and distant metastatic disease was assessed using clinical and radiological follow-up as a standard of reference. Tumor recurrence was found in 20 of 33 patients. Overall 186 malignant foci were detected with WB-MRI and PET-CT. Both modalities revealed two recurrent tumors of the breast. PET-CT detected more lymph node metastases (n=21) than WB-MRI (n=16). WB-MRI was more precise in the detection of distant metastases (n=154 versus n=147). Sensitivity was 93% (172/186) and 91% (170/186) for WB-MRI and PET-CT, specificity was 86% (66/77) and 90% (69/77), respectively. Examination times for WB-MRI at 1.5 and 3T were 51 and 43 min, respectively, examination time for PET-CT was 103 min. WB-MRI and PET-CT are useful for the detection of tumor recurrence in the follow-up of breast cancer. WB-MRI is highly sensitive to distant metastatic disease. PET-CT is more sensitive in detecting lymph node involvement. Tumor screening with WB-MRI is feasible at 1.5 and 3T, scan time is further reduced at 3T with identical resolution.

Mint3 in bone marrow-derived cells promotes lung metastasis in breast cancer model mice.

PubMed

Hara, Toshiro; Murakami, Yoshinori; Seiki, Motoharu; Sakamoto, Takeharu

2017-08-26

Breast cancer is one of the most common cancers in women in the world. Although breast cancer is well treatable at the early stage, patients with distant metastases show a poor prognosis. Data from recent studies using transplantation models indicate that Mint3/APBA3 might promote breast cancer malignancy. However, whether Mint3 indeed contributes to tumor development, progression, or metastasis in vivo remains unclear. To address this, here we examined whether Mint3 depletion affects tumor malignancy in MMTV-PyMT breast cancer model mice. In MMTV-PyMT mice, Mint3 depletion did not affect tumor onset and tumor growth, but attenuated lung metastases. Experimental lung metastasis of breast cancer Met-1 cells derived from MMTV-PyMT mice also decreased in Mint3-depleted mice, indicating that host Mint3 expression affected lung metastasis of MMTV-PyMT-derived breast cancer cells. Further bone marrow transplant experiments revealed that Mint3 in bone marrow-derived cells promoted lung metastasis in MMTV-PyMT mice. Thus, targeting Mint3 in bone marrow-derived cells might be a good strategy for preventing metastasis and improving the prognosis of breast cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

A case of metastatic hemangiopericytoma occurring 16 years after initial presentation: with special reference to the clinical behavior and treatment of metastatic hemangiopericytoma.

PubMed

Fujita, Itsuo; Kiyama, Teruo; Chou, Kazumitsu; Kanno, Hitoshi; Naito, Zenya; Uchida, Eiji

2009-08-01

A 40-year-old woman was referred to our Department of Surgery because of an abdominal wall mass. Sixteen years earlier, she had undergone surgical resection of an inguinal tumor that had been diagnosed as a hemangiosarcoma. Fourteen months after the initial resection, the tumor recurred locally, and complete resection was performed. Twenty-nine months later, computed tomography showed multiple metastatic tumors in the lung. All these tumors were resected during thoracoscopic surgery. Thirteen years after the patient's 3rd operation, a firm mass was detected in the left lower quadrant of the abdominal wall. Magnetic resonance image showed a well-defined mass with heterogeneous contrast enhancement within the rectus abdominis muscle. Positron emission tomography-computed tomography demonstrated no recurrent tumors other than this mass. Complete resection was performed. Microscopic examination showed that this tumor was composed of hypercellular spindle cells and staghorn-shaped blood vessels. The average number of mitotic figures was 28 per 10 high-power fields. Immunohistochemical examination of the tumor showed focal positivity for CD34. Therefore, the tumor was diagnosed as a metastatic hemangiopericytoma with malignant potential. Careful long-term follow-up is required because metastases can develop after an extended disease-free interval. Aggressive surgical treatment is recommended for distant metastases.

Sarcoma of the prostate: a single institutional review.

PubMed

Janet, Nguyen L; May, Abdel-Wahab; Akins, Robin S

2009-02-01

We report the management and outcome of prostate sarcoma at 1 institution and analyze factors that may determine prognosis. The medical records of 10 patients with prostate sarcoma were reviewed to identify symptoms at presentation, diagnostic procedures, and staging methods. Histology, grade, tumor size, stage, and treatment modality were analyzed. Overall survival was assessed. Five patients had rhabdomyosarcoma (RMS) and five had other subtypes, including two with carcinosarcoma, two with high-grade sarcoma not-otherwise-specified, and one with leiyomyosarcoma. Eight patients presented with locally advanced disease and two with metastatic disease.The two metastatic patients received chemotherapy, and one also had hormonal ablation therapy. Of the eight with local disease, two had neoadjuvant chemotherapy and surgery, one had surgery alone, one had surgery and postoperative radiation, one had radiation alone, and three had chemoradiation.Chemotherapy consisted of vincristine, adriamycin, and cyclophosphomide for rhabdomyosarcoma and of cisplatin, adriamycin, and ifosphamide for the other subtypes. Radiation dose ranged from 40 Gy to 55.8 Gy.The median survival follow-up of the study is 46.5 months. The median survival for the rhabdomyosarcoma subgroup and nonrhabdomyosarcoma subroup is 142 months and 24 months, respectively. There were three deaths, of which two had metastatic disease at presentation and one later developed distant metastases after having surgery alone. One patient developed a local recurrence 47 months after chemoradiation and was successfully salvaged with surgery. In terms of tumor-related factors, the histologic subtype of prostate sarcoma appears to have prognostic significance. The overall survival for adults with non-RMS histologies is poor with a median survival of only 2 years. Pediatric patients with RMS faired much better with a median survival of over 10 years. We did not find any difference in outcome with regard to grade or tumor size. The presence of metastatic disease at diagnosis, however, is a poor predictor of outcome.In terms of treatment-related factors, surgery alone is inadequate treatment. One patient treated with surgery alone developed distant metastases 38 months later, then received chemotherapy and hormonal therapy, and died at 58 months. Patients who received combined modality treatment appear to fare better.Finally, these patients need long term follow-up. One patient developed a local recurrence 47 months after chemoradiation. This patient was successfully salvaged with surgery and is currently alive at 170 months.

High Pretreatment Plasma D-dimer Levels Are Associated With Poor Prognosis in Patients With Ovarian Cancer Independently of Venous Thromboembolism and Tumor Extension.

PubMed

Sakurai, Manabu; Satoh, Toyomi; Matsumoto, Koji; Michikami, Hiroo; Nakamura, Yuko; Nakao, Sari; Ochi, Hiroyuki; Onuki, Mamiko; Minaguchi, Takeo; Yoshikawa, Hiroyuki

2015-05-01

Elevated plasma D-dimer (DD) is associated with decreased survival among patients with breast, lung, and colon cancers. The present study clarifies the prognostic significance of pretreatment plasma DD levels in patients with epithelial ovarian cancer (EOC). We investigated pretreatment DD levels and other variables for overall survival using univariate and multivariate analyses in 134 consecutive patients with EOC stages II to IV who were initially treated between November 2004 and December 2010. The median follow-up period was 53 (7-106) months. Univariate analysis significantly associated elevated pretreatment DD (≥2.0 μg/mL) levels to poor 5-year overall survival rates irrespective of previously treated venous thromboembolism (72.2% vs 52.6%, P = 0.039). Cancer antigen 125 levels of 200 U/mL or higher (P = 0.011), distant metastases (P = 0.0004), residual tumors (P < 0.0001), and International Federation of Gynecology and Obstetrics stage III/IV (P = 0.0033) were also poor prognostic factors. Multivariate analysis independently associated DD levels of 2.0 μg/mL or higher (P = 0.041), distant metastases (P = 0.013), and residual tumors (P < 0.0001) with poor overall survival. High pretreatment DD levels are associated with poor overall survival in patients with EOC independently of venous thromboembolism and tumor extension and might comprise a promising prognostic biomarker for patients with EOC.

CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer.

PubMed

Xiang, Jingyu; Hurchla, Michelle A; Fontana, Francesca; Su, Xinming; Amend, Sarah R; Esser, Alison K; Douglas, Garry J; Mudalagiriyappa, Chidananda; Luker, Kathryn E; Pluard, Timothy; Ademuyiwa, Foluso O; Romagnoli, Barbara; Tuffin, Gérald; Chevalier, Eric; Luker, Gary D; Bauer, Michael; Zimmermann, Johann; Aft, Rebecca L; Dembowsky, Klaus; Weilbaecher, Katherine N

2015-11-01

The SDF-1 receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple-negative subtype. In line with previous reports, we found that tumoral CXCR4 expression in patients with locally advanced breast cancer was associated with increased metastases and rapid tumor progression. Moreover, high CXCR4 expression identified a group of bone marrow-disseminated tumor cells (DTC)-negative patients at high risk for metastasis and death. The protein epitope mimetic (PEM) POL5551, a novel CXCR4 antagonist, inhibited binding of SDF-1 to CXCR4, had no direct effects on tumor cell viability, but reduced migration of breast cancer cells in vitro. In two orthotopic models of triple-negative breast cancer, POL5551 had little inhibitory effect on primary tumor growth, but significantly reduced distant metastasis. When combined with eribulin, a chemotherapeutic microtubule inhibitor, POL5551 additively reduced metastasis and prolonged survival in mice after resection of the primary tumor compared with single-agent eribulin. Hypothesizing that POL5551 may mobilize tumor cells from their microenvironment and sensitize them to chemotherapy, we used a "chemotherapy framing" dosing strategy. When administered shortly before and after eribulin treatment, three doses of POL5551 with eribulin reduced bone and liver tumor burden more effectively than chemotherapy alone. These data suggest that sequenced administration of CXCR4 antagonists with cytotoxic chemotherapy synergize to reduce distant metastases. ©2015 American Association for Cancer Research.

Radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma: long-term outcomes over 10 years.

PubMed

Ohkubo, Yu; Saito, Yoshihiro; Ushijima, Hiroki; Onishi, Masahiro; Kazumoto, Tomoko; Saitoh, Jun-Ichi; Kubota, Nobuko; Kobayashi, Hirofumi; Maseki, Nobuo; Nishimura, Yu; Kurosumi, Masafumi

2017-07-01

This study aimed to assess the long-term outcomes of radiotherapy in patients with localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Twenty-seven patients with Stage I gastric MALT lymphoma were treated with radiotherapy from 1999 to 2010. The median age was 65 years (range: 31-84). Fifteen patients were Helicobacter pylori-negative. Thirteen patients were treated with definitive radiotherapy alone. The other 14 patients who had refractory or residual disease following a prior treatment received salvage radiotherapy. The median dose of the radiotherapy was 30 Gy in 20 fractions (range: 30-39.5 Gy). The median follow-up period was 121 months (range: 8-176 months). The 5- and 10-year overall survival rates for all patients were 92% and 87%, respectively. No patients died from MALT lymphoma. Three patients died of other diseases at 8, 33 and 74 months after radiotherapy (myocardial infarction, pneumonia and hepatocellular carcinoma, respectively). No cases of local recurrence were observed during the follow-up period. There were no serious late gastric, liver or kidney complications during a median follow-up period of over 10 years. Two patients remain alive with distant metastases: a lung metastasis and an abdominal lymph node metastasis at 104 months and 21 months after radiotherapy, respectively. Excellent long-term local control was observed in patients with localized gastric MALT lymphoma after radiotherapy. However, lifelong follow-up should be conducted to detect cases of late recurrence, especially distant metastases. © Oxford University Press 2017.

Adenoid cystic carcinoma of the lacrimal gland.

PubMed

Sanders, Jason C; Mendenhall, William M; Werning, John W

2016-01-01

This is a retrospective analysis of the 50-year University of Florida experience treating adenoid cystic carcinoma of the lacrimal gland with radiation therapy. Between 1965 and 2015, 8 patients with adenoid cystic carcinoma of the lacrimal gland received radiation therapy with curative intent. Four patients received postoperative radiation therapy and 4 received definitive radiation therapy alone. The median follow-up was 3.3 years (range, 0.3 to 11.2 years). All 4 patients who received postoperative radiation therapy received 74.4 Gy. The 4 patients who received radiation therapy alone received a median dose of 72.3 Gy (range, 70.0 to 74.4 Gy). The overall survival rates at 5 and 10 years were 25% and 13%, respectively. The cause-specific survival rates at 5 and 10 years were 29% and 14%, respectively. The local control and freedom from metastases rates at 5 and 10 years were both 43%. Local recurrences occurred in 50% of patients, and distant metastatic disease occurred in 38% of patients. No patients experienced acute complications of treatment that warranted a treatment break. Two patients experienced bone exposure as late complications of treatment. The results of this study illustrate the propensity for adenoid cystic carcinoma of the lacrimal gland to recur both locally and with distant metastases despite aggressive local treatment measures. This study also demonstrates the relatively poor outcomes for individuals with this type of tumor. Copyright © 2016 Elsevier Inc. All rights reserved.

Significance of lymph node capsular invasion in esophageal squamous cell carcinoma.

PubMed

Sakai, Makoto; Suzuki, Shigemasa; Sano, Akihiko; Tanaka, Naritaka; Inose, Takanori; Sohda, Makoto; Nakajima, Masanobu; Miyazaki, Tatsuya; Kuwano, Hiroyuki

2012-06-01

Extranodal invasion (ENI) has been reported to be associated with a poor prognosis in several malignancies. However, previous studies have included perinodal fat tissue tumor deposits in their definitions of ENI. To investigate the precise nature of ENI in esophageal squamous cell carcinoma (ESCC), we excluded these tumor deposits from our definition of ENI and defined tumor cell invasion through the lymph node capsule and into the perinodal tissues as lymph node capsular invasion (LNCI). The aim of the current study was to elucidate the significance of LNCI in ESCC. We investigated the associations between LNCI and other clinicopathologic features in 139 surgically resected ESCC. We also investigated the prognostic significance of LNCI in ESCC. LNCI was detected in 35 (25.2%) of 139 patients. The overall survival rate of the ESCC patients with LNCI was significantly lower than that of the ESCC patients with lymph node metastasis who were negative for LNCI. The survival difference between the patients with 1–3 lymph node metastases without LNCI and those with no lymph node metastasis was not significant. LNCI was significantly associated with distant organ recurrence. LNCI was also found to be an independent predictor of overall survival in addition to the number of lymph node metastases. LNCI in ESCC patients is an indicator of distant organ recurrence and a worse prognosis. LNCI could be used as a candidate marker for designing more precise staging and therapeutic strategies for ESCC.

Golgi-Related Proteins GOLPH2 (GP73/GOLM1) and GOLPH3 (GOPP1/MIDAS) in Cutaneous Melanoma: Patterns of Expression and Prognostic Significance.

PubMed

Donizy, Piotr; Kaczorowski, Maciej; Biecek, Przemyslaw; Halon, Agnieszka; Szkudlarek, Teresa; Matkowski, Rafal

2016-10-01

GOLPH2 and GOLPH3 are Golgi-related proteins associated with aggressiveness and progression of a number of cancers. Their prognostic significance in melanoma has not yet been analyzed. We performed immunohistochemical analysis for GOLPH2 and GOLPH3 in 20 normal skin, 30 benign nevi and 100 primary melanoma tissue samples and evaluated their expression in three compartments: cancer cells, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). High levels of both proteins in melanoma cells were associated with characteristics of aggressive disease, and shorter disease-free survival (DFS) and cancer-specific overall survival (CSOS). On the contrary, increased numbers of GOLPH2-positive and GOLPH3-positive TAMs were observed in thinner, non-ulcerated tumors, with brisk lymphocytic reaction and absent lymphangioinvasion. Distant metastases were not observed among patients with high numbers of GOLPH2-positive TAMs. Increased expression of either protein in TAMs was related to prolonged CSOS and DFS. Similarly, GOLPH3-expressing CAFs were more frequent in thin melanomas with low mitotic rate, without ulceration and lymphangioinvasion. Moreover, increased GOLPH3-positive CAFs correlated with the absence of regional or distant metastases, and with longer CSOS and DFS. GOLPH2 expression was not observed in CAFs. Our results suggest that GOLPH2 and GOLPH3 play a role in melanoma progression and are potential targets for molecular-based therapies.

Nonsurgical Strategies in Patients With NET Liver Metastases: A Protocol of Four Systematic Reviews.

PubMed

Limani, Perparim; Tschuor, Christoph; Gort, Laura; Balmer, Bettina; Gu, Alexander; Ceresa, Christos; Raptis, Dimitri Aristotle; Lesurtel, Mickael; Puhan, Milo; Breitenstein, Stefan

2014-03-07

Patients diagnosed with neuroendocrine tumors (NETs) with hepatic metastases generally have a worse prognosis as compared with patients with nonmetastasized NETs. Due to tumor location and distant metastases, a surgical approach is often not possible and nonsurgical therapeutic strategies may apply. The aim of these systematic reviews is to evaluate the role of nonsurgical therapy options for patients with nonresectable liver metastases of NETs. An objective group of librarians will provide an electronic search strategy to examine the MEDLINE, EMBASE, and The Cochrane Library (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials [CENTRAL]) databases. There will be no restriction concerning language and publication date. The qualitative and quantitative synthesis of the systematic review will be conducted with randomized controlled trials (RCT), prospective, and retrospective comparative cohort, and case-control studies. Case series will be collected in a separate database and only used for descriptive purposes. This study is ongoing and presents a protocol of four systematic reviews to assess the role of nonsurgical treatment options in patients with neuroendocrine liver metastases. These systematic reviews, performed according to this protocol, will assess the value of noninvasive therapy options for patients with nonresectable liver metastases of NETs in combination with invasive techniques, such as percutaneous liver-directed techniques and local ablation techniques. International Prospective Register of Systematic Reviews (PROSPERO): CRD42012002657; http://www.metaxis.com/PROSPERO/full_doc.asp?RecordID=2657 (Archived by WebCite at http://www.webcitation.org/6NDlYi37O); CRD42012002658; http://www.metaxis.com/PROSPERO/full_doc.asp?RecordID=2658 (Archived by WebCite at http://www.webcitation.org/6NDlfWSuD); CRD42012002659; www.metaxis.com/PROSPERO/full_doc.asp?RecordID=2659 (Arichived by Webcite at http://www.webcitation.org/6NDlmWAFM); and CRD42012002660; http://www.metaxis.com/PROSPERO/full_doc.asp?RecordID=2660 (Archived by WebCite at http://www.webcitation.org/6NDmnylzp).

Prognostic and functional role of subtype-specific tumor-stroma interaction in breast cancer.

PubMed

Merlino, Giuseppe; Miodini, Patrizia; Callari, Maurizio; D'Aiuto, Francesca; Cappelletti, Vera; Daidone, Maria Grazia

2017-10-01

None of the clinically relevant gene expression signatures available for breast cancer were specifically developed to capture the influence of the microenvironment on tumor cells. Here, we attempted to build subtype-specific signatures derived from an in vitro model reproducing tumor cell modifications after interaction with activated or normal stromal cells. Gene expression signatures derived from HER2+, luminal, and basal breast cancer cell lines (treated by normal fibroblasts or cancer-associated fibroblasts conditioned media) were evaluated in clinical tumors by in silico analysis on published gene expression profiles (GEPs). Patients were classified as microenvironment-positive (μENV+ve), that is, with tumors showing molecular profiles suggesting activation by the stroma, or microenvironment-negative (μENV-ve) based on correlation of their tumors' GEP with the respective subtype-specific signature. Patients with estrogen receptor alpha (ER)+/HER2-/μENV+ve tumors were characterized by 2.5-fold higher risk of developing distant metastases (HR = 2.546; 95% CI: 1.751-3.701, P = 9.84E-07), while μENV status did not affect, or only suggested the risk of distant metastases, in women with HER2+ (HR = 1.541; 95% CI: 0.788-3.012, P = 0.206) or ER-/HER2- tumors (HR = 1.894; 95% CI: 0.938-3.824; P = 0.0747), respectively. In ER+/HER2- tumors, the μENV status remained significantly associated with metastatic progression (HR = 2.098; CI: 1.214-3.624; P = 0.00791) in multivariable analysis including size, age, and Genomic Grade Index. Validity of our in vitro model was also supported by in vitro biological endpoints such as cell growth (MTT assay) and migration/invasion (Transwell assay). In vitro-derived gene signatures tracing the bidirectional interaction with cancer activated fibroblasts are subtype-specific and add independent prognostic information to classical prognostic variables in women with ER+/HER2- tumors. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Macroscopy predicts tumor progression in gastric cancer: A retrospective patho-historical analysis based on Napoleon Bonaparte's autopsy report.

PubMed

Dawson, Heather; Novotny, Alexander; Becker, Karen; Reim, Daniel; Langer, Rupert; Gullo, Irene; Svrcek, Magali; Niess, Jan H; Tutuian, Radu; Truninger, Kaspar; Diamantis, Ioannis; Blank, Annika; Zlobec, Inti; Riddell, Robert H; Carneiro, Fatima; Fléjou, Jean-François; Genta, Robert M; Lugli, Alessandro

2016-11-01

The cause of Napoleon Bonaparte's death remains controversial. Originally suggested to be gastric cancer, whether this was truly neoplastic or a benign lesion has been recently debated. To interpret findings of original autopsy reports in light of the current knowledge of gastric cancer and to highlight the significance of accurate macroscopy in modern-day medicine. Using original autopsy documents, endoscopic images and data from current literature, Napoleon's gastric situation was reconstructed. In a multicenter collection of 2071 gastric cancer specimens, the relationship between tumor size and features of tumor progression was assessed. Greater tumor size was associated with advanced pT, nodal metastases and Borrmann types 3-4 (p<0.001). The best cut-off for predicting pT3-4 tumors was 6.5cm (AUC 0.8; OR 1.397, 95% CI 1.35-1.446), and 6cm for lymph node metastases (AUC 0.775; OR 1.389, 95% CI 1.338-1.442). The 6cm cut-off of had a positive predictive value of 0.820 for nodal metastases and a negative predictive value of 0.880 for distant metastases. This analysis combines Napoleon's autopsy with present-day knowledge to support gastric cancer as his terminal illness and emphasizes the role of macroscopy, which may provide valuable information on gastric cancer progression and aid patient management. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Has the percutaneous vertebroplasty a role to prevent progression or local recurrence in spinal metastases of breast cancer?

PubMed

Roedel, Beatriz; Clarençon, Frédéric; Touraine, Sébastien; Cormier, Evelyne; Molet-Benhamou, Luc; Le Jean, Lise; Brisse, Hervé; Neuenschwander, Sylvia; Chiras, Jacques

2015-07-01

To evaluate the effectiveness of percutaneous vertebroplasty (PV) on the prevention of progression or local recurrence in patients with spinal metastases from breast cancer. Retrospective study on 55 patients between 27-78 years of age (mean age: 55 years) treated for metastatic breast cancer in the same institution (Curie institute, Paris, France), who underwent percutaneous vertebroplasty (PV) (number of vertebrae treated=137) for spinal metastases from January 2000 to December 2009 at the Pitié-Salpêtrière hospital. Statistical correlation between the local tumor progression/recurrence, and the presence of an epidural or a paravertebral metastatic extension at diagnosis, the rate of cement filling the lesion (<50%, ≥50% but incomplete, complete/almost complete) and radiotherapy was evaluated using Chi(2) and Fisher's exact test. The rate of local tumor progression/recurrence of the vertebrae treated by vertebroplasty was 14% (19/137). No statistically significant correlation between either the rate of cement filling of the lesion, or the presence of an epidural or paravertebral metastatic extension, and progression/local recurrence after vertebroplasty was found. No influence of radiotherapy in preventing local progression/recurrence was noted. Distant new bone metastases were observed in 47 out of 55 patients (86%). The low rate of local tumor progression/recurrence after a vertebroplasty may support the hypothesis of an antitumor effect of the cement. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Prognostic indicators of outcomes in patients with lung metastases from differentiated thyroid carcinoma during long-term follow-up.

PubMed

Sohn, Seo Young; Kim, Hye In; Kim, Young Nam; Kim, Tae Hyuk; Kim, Sun Wook; Chung, Jae Hoon

2018-02-01

Distant metastases, although uncommon, represent maximum disease-related mortality in differentiated thyroid carcinoma (DTC). Lungs are the most frequent sites of metastases. We aimed to evaluate long-term outcomes and identify prognostic factors in metastatic DTC limited to the lungs. This retrospective study included 89 patients with DTC and metastases limited to the lungs, who were treated between 1996 and 2012 at Samsung Medical Center. Progression-free survival (PFS) and cancer-specific survival (CSS) rates were evaluated according to clinicopathologic factors. Cox regression analysis was used to identify independent factors associated with structural progressive disease (PD) and cancer-specific death. With a median follow-up of 84 months, the 5- and 10-year CSS rates were 78% and 73%, respectively. Older age at diagnosis (≥55 years), radioactive iodine (RAI) nonavidity, preoperative or late diagnosis of metastasis and macro-nodular metastasis (≥1 cm) were predictive of decreased PFS and CSS. Multivariate analysis identified older age (P = .002), RAI nonavidity (P = .045) and preoperative (P = .030) or late diagnosis (P = .026) as independent predictors of structural PD. RAI avidity was also independent predictor of cancer-specific death (P = .025). Patients with DTC and metastatic disease limited to the lungs had favourable long-term outcomes. Age, RAI avidity and timing of metastasis were found to be major factors for predicting prognosis. © 2017 John Wiley & Sons Ltd.

Intercellular Communication by Exosome-Derived microRNAs in Cancer

PubMed Central

Hannafon, Bethany N.; Ding, Wei-Qun

2013-01-01

The development of human cancers is a multistep process in which normal cells acquire characteristics that ultimately lead to their conversion into cancer cells. Many obstacles must be overcome for this process to occur; of these obstacles, is the ability to survive an inhospitable microenvironment. It is recognized that the intercommunication between tumor cells and their surrounding microenvironment is essential to overcoming this obstacle and for the tumor to progress, metastasize and establish itself at distant sites. Exosomes are membrane-derived vesicles that have recently been recognized as important mediators of intercellular communication, as they carry lipids, proteins, mRNAs and microRNAs that can be transferred to a recipient cell via fusion of the exosome with the target cell membrane. In the context of cancer cells, this process entails the transfer of cancer-promoting cellular contents to surrounding cells within the tumor microenvironment or into the circulation to act at distant sites, thereby enabling cancer progression. In this process, the transfer of exosomal microRNAs to a recipient cell where they can regulate target gene expression is of particular interest, both in understanding the basic biology of cancer progression and for the development of therapeutic approaches. This review discusses the exosome-mediated intercellular communication via microRNAs within the tumor microenvironment in human cancers, with a particular focus on breast cancer exosomes. PMID:23839094

Hyperfractionated Radiotherapy with Concurrent Cisplatin/5-Fluorouracil for Locoregional Advanced Head and Neck Cancer: Analysis of 105 Consecutive Patients

PubMed Central

Zaboli, David; Tan, Marietta; Gogineni, Hrishikesh; Lake, Spencer; Fan, Katherine; Zahurak, Marianna L.; Messing, Barbara; Ulmer, Karen; Zinreich, Eva S.; Levine, Marshall A.; Tang, Mei; Pai, Sara I.; Blanco, Ray G.; Saunders, John R.; Best, Simon R.; Califano, Joseph A.; Ha, Patrick K.

2012-01-01

Objective. We reviewed a cohort of patients with previously untreated locoregional advanced head and neck squamous cell carcinoma (HNSCC) who received a uniform chemoradiotherapy regimen. Methods. Retrospective review was performed of 105 patients with stage III or IV HNSCC treated at Greater Baltimore Medical Center from 2000 to 2007. Radiation included 125 cGy twice daily for a total 70 Gy to the primary site. Chemotherapy consisted of cisplatin (12 mg/m2/h) daily for five days and 5-fluorouracil (600 mg/m2/20 h) daily for five days, given with weeks one and six of radiation. All but seven patients with N2 or greater disease received planned neck dissection after chemoradiotherapy. Primary outcomes were overall survival (OS), locoregional control (LRC), and disease-free survival (DFS). Results. Median followup of surviving patients was 57.6 months. Five-year OS was 60%, LRC was 68%, and DFS was 56%. Predictors of increased mortality included age ≥55, female gender, hypopharyngeal primary, and T3/T4 stage. Twelve patients developed locoregional recurrences, and 16 patients developed distant metastases. Eighteen second primary malignancies were diagnosed in 17 patients. Conclusions. The CRT regimen resulted in favorable outcomes. However, locoregional and distant recurrences cause significant mortality and highlight the need for more effective therapies to prevent and manage these events. PMID:22778748

Parotid adenoid cystic carcinoma: Retrospective single institute analysis.

PubMed

Mannelli, Giuditta; Cecconi, Lorenzo; Fasolati, Martina; Santoro, Roberto; Franchi, Alessandro; Gallo, Oreste

Adenoid cystic carcinoma (ACC) is a uncommon salivary malignant tumor. Our aim was to review our experience with parotid ACC, to identify clinical-pathological parameters predictive for outcome. We retrospectively reviewed 228 patients affected by parotid gland carcinomas surgically treated at our Institution. Forty-four ACC were included in this study. Multivariate analysis risk models were built to predict recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and disease free survival (DFS). Twenty-one patients (47.7%) died from ACC and 2.3% for other causes. The 41% presented local-regional recurrence, with a regional-RFP rate of 93%, and the 34% reported distant metastases (DM). The five and ten-year OS rates were 74% and 50%, respectively. Recurrences were mainly influenced by the presence of perineural invasion and nerve paralysis, whilst female gender and age<50 were predictors for good prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Serial or Parallel Metastasis of Cutaneous Melanoma? A Study of the German Central Malignant Melanoma Registry.

PubMed

Gassenmaier, Maximilian; Eigentler, Thomas Kurt; Keim, Ulrike; Goebeler, Matthias; Fiedler, Eckhard; Schuler, Gerold; Leiter, Ulrike; Weide, Benjamin; Grischke, Eva-Maria; Martus, Peter; Garbe, Claus

2017-12-01

For more than a century the Halstedian hypothesis of contiguous metastasis from the primary tumor through the lymphatics to distant sites shaped lymph node surgery for melanoma. We challenge this dogma of serial metastatic dissemination. A single-center series of 2,299 patients with cutaneous metastatic melanoma was investigated to analyze overall survival and distant metastasis-free survival of stage IV patients with or without primary lymphatic metastasis. Results were then compared with those of 2,134 patients from three independent centers of the German Central Malignant Melanoma Registry. A multivariate binary logistic regression model was used to identify risk factors for the initial metastatic pathway. Distant metastasis-free survival (hazard ratio = 1.02; 95% confidence interval = 0.91-1.14; P = 0.76) and overall survival (HR = 1.09; 95% CI = 0.96-1.23; P = 0.177) did not differ between stage IV patients with primary hematogenous or primary lymphatic metastasis. Melanoma localization was the only significant risk factor for the initial metastatic pathway. These findings indicate that regional and distant metastases originate from the primary tumor itself in a rather parallel than serial fashion and could explain the lack of survival benefit associated with immediate complete lymph node dissection in sentinel lymph node-positive melanoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Radical redo surgery for local rectal cancer recurrence improves overall survival: a single center experience.

PubMed

Schurr, Paulus; Lentz, Edda; Block, Suzette; Kaifi, Jussuf; Kleinhans, Helge; Cataldegirmen, Guellue; Kutup, Asad; Schneider, Claus; Strate, Tim; Yekebas, Emre; Izbicki, Jakob

2008-07-01

To date, the survival benefit of redo surgery in locally recurrent rectal adenocarcinoma remains unclear. In an institutional study, operations for recurrence were retrospectively analyzed. Survival was calculated using the Kaplan-Meier plot and Cox regression analysis. A total of 72 patients with local recurrence were explored or resected. In 38 patients, there was synchronous distant organ recurrence. Forty-five of 72 were re-resected and in 37 of 45 cases, R0 situations were achieved. In 11 of 38 metastasized patients, both local and distant organ recurrence were successfully removed. For obtaining tumor control, resections of inner genitals, bladder, and sacral bone were necessary in 10, 4, and 11 patients, respectively. Survival was better for patients re-resected with a median overall survival of 54.9 months, as compared with 31.1 months among non-resected patients (p = 0.0047, log-rank test). Subgroup analysis revealed that a benefit of re-resection was observed to a lesser extent in synchronous local and in distant disease. Cox analysis showed that initial Dukes stage and complete resections of local recurrences were independently determining prognosis (relative risk 1.762 and 0.689, p = 0.008 and p = 0.002, respectively). Radical surgery for local recurrence can improve survival if complete tumor clearance is achieved, and concomitant distant tumor load should not principally preclude re-resection.

Tumor-infiltrating monocytes/macrophages promote tumor invasion and migration by upregulating S100A8 and S100A9 expression in cancer cells.

PubMed

Lim, S Y; Yuzhalin, A E; Gordon-Weeks, A N; Muschel, R J

2016-11-03

Myeloid cells promote the development of distant metastases, but little is known about the molecular mechanisms underlying this process. Here we have begun to uncover the effects of myeloid cells on cancer cells in a mouse model of liver metastasis. Monocytes/macrophages, but not granulocytes, isolated from experimental liver metastases stimulated migration and invasion of MC38 colon and Lewis lung carcinoma cells. In response to conditioned media from tumor-infiltrating monocytes/macrophages, cancer cells upregulated S100a8 and S100a9 messenger RNA expression through an extracellular signal-related kinase-dependent mechanism. Suppression of S100A8 and S100A9 in cancer cells using short hairpin RNA significantly diminished migration and invasion in culture. Downregulation of S100A8 and S100A9 had no effect on subcutaneous tumor growth. However, colony size was greatly reduced in liver metastases with decreased invasion into adjacent tissue. In tissue culture and in the liver colonies derived from cancer cells with knockdown of S100A8 and S100A9, MMP2 and MMP9 expression was decreased, consistent with the reduction in migration and invasion. Our findings demonstrate that monocytes/macrophages in the metastatic liver microenvironment induce S100A8 and S100A9 in cancer cells, and that these proteins are essential for tumor cell migration and invasion. S100A8 and S100A9, however, are not responsible for stimulation of proliferation. This study implicates S100A8 and S100A9 as important mediators of tumor cell aggressiveness, and highlights the therapeutic potential of S100A8 and S100A9 for interference of metastasis.

Tumor-infiltrating monocytes/macrophages promote tumor invasion and migration by upregulating S100A8 and S100A9 expression in cancer cells

PubMed Central

Lim, S Y; Yuzhalin, A E; Gordon-Weeks, A N; Muschel, R J

2016-01-01

Myeloid cells promote the development of distant metastases, but little is known about the molecular mechanisms underlying this process. Here we have begun to uncover the effects of myeloid cells on cancer cells in a mouse model of liver metastasis. Monocytes/macrophages, but not granulocytes, isolated from experimental liver metastases stimulated migration and invasion of MC38 colon and Lewis lung carcinoma cells. In response to conditioned media from tumor-infiltrating monocytes/macrophages, cancer cells upregulated S100a8 and S100a9 messenger RNA expression through an extracellular signal-related kinase-dependent mechanism. Suppression of S100A8 and S100A9 in cancer cells using short hairpin RNA significantly diminished migration and invasion in culture. Downregulation of S100A8 and S100A9 had no effect on subcutaneous tumor growth. However, colony size was greatly reduced in liver metastases with decreased invasion into adjacent tissue. In tissue culture and in the liver colonies derived from cancer cells with knockdown of S100A8 and S100A9, MMP2 and MMP9 expression was decreased, consistent with the reduction in migration and invasion. Our findings demonstrate that monocytes/macrophages in the metastatic liver microenvironment induce S100A8 and S100A9 in cancer cells, and that these proteins are essential for tumor cell migration and invasion. S100A8 and S100A9, however, are not responsible for stimulation of proliferation. This study implicates S100A8 and S100A9 as important mediators of tumor cell aggressiveness, and highlights the therapeutic potential of S100A8 and S100A9 for interference of metastasis. PMID:27086923

Can Diffusion-Weighted Imaging and Related Apparent Diffusion Coefficient be a Prognostic Value in Women With Breast Cancer?

PubMed

Rabasco, Paola; Caivano, Rocchina; Simeon, Vittorio; Dinardo, Giuseppina; Lotumolo, Antonella; Gioioso, Matilde; Villonio, Antonio; Iannelli, Giancarlo; D'Antuono, Felice; Zandolino, Alexis; Macarini, Luca; Guglielmi, Giuseppe; Cammarota, Aldo

2017-02-07

To analyze diffusion-weighted imaging (DWI) and the related apparent diffusion coefficient (ADC) in women with breast cancer, correlating these values with the presence at 3 years of distant metastases, and to demonstrate that DWI-Magnetic Resonance Imaging (MRI) and related ADC values may represent a prognostic value in the study of women with breast cancer. Sixty women (aged 45-73 years) affected with breast cancer with a follow-up in 3 years were enrolled. On DWI, we obtained the ADC values, and these were correlated with the clinical condition of patients at 3 years. Moreover, tumour size, lymph node status, and molecular markers, including estrogens receptor, progesterone receptor, Ki-67 index, and human growth factor receptor 2 protein, were correlated with ADC values. This study was approved by the Scientific Committee of our institution. We considered patients with metastasis at 3 years (12 patients - 20%) and without metastasis (48 patients - 80%). The mean ADC value in patients with no metastases at 3 years was 1.06 ± 0.38, while for patients with metastases it was 0.74 ± 0.34 (p = .011). The receiver-operator curve analysis identified a value of 0.75 (<0.75 with risk to develop metastasis) as the best predictive cutoff for ADC values, with the highest sensitivity (81.25%) and higher specificity (66.67%). After regression analysis, ADC value, positivity to estrogen-progestin receptors, and presence of lymph nodes were the only prognostic factors found to be statistically significant. DWI-MRI and related ADC values may represent a prognostic value in women with breast cancer.

Impact of endoscopic stent insertion on detection of viable circulating tumor cells from obstructive colorectal cancer

PubMed Central

Yamashita, Shinya; Tanemura, Masahiro; Sawada, Genta; Moon, Jeongho; Shimizu, Yosuke; Yamaguchi, Toshiki; Kuwai, Toshio; Urata, Yasuo; Kuraoka, Kazuya; Hatanaka, Nobutaka; Yamashita, Yoshinori; Taniyama, Kiyomi

2018-01-01

The placement of a self-expanding metallic stent (SEMS) in obstructive colorectal cancer (OCRC) is acknowledged to be a safe and effective procedure for the relief of obstruction. However, there is concern that shear forces acting on the tumor during stent expansion may release cancer cells into the circulation, resulting in a poor prognosis. The aim of the present study was to determine whether colonic stent insertion increases viable circulating tumor cells (v-CTCs). A telomerase-specific replication-selective adenovirus-expressing GFP (TelomeScanF35) detection system was used to detect v-CTCs in 8 OCRC patients with a SEMS before and after stent insertion and after surgical resection. In 7 patients, a SEMS was inserted as a bridge to surgery (BTS), and in one patient, a SEMS was inserted for palliation. Surgical resection (R0) was performed in 7 patients. Four patients had no v-CTCs before SEMS placement, two of four measurable patients had an increased number of v-CTCs after SEMS placement (1–3 v-CTCs), and one of two patients with increased v-CTCs developed distant lymphatic metastasis despite curative resection. Four patients had v-CTCs (1–19 cells) before SEMS placement, and two of these four patients had an increase in the number of v-CTCs (20–21 cells) after SEMS placement, while one of the four patients died early with distant metastasis. The present study demonstrated that endoscopic stent insertion for OCRC may result in tumor cell dissemination into the peripheral circulation and may induce distant metastases. PMID:29391884

Impact of endoscopic stent insertion on detection of viable circulating tumor cells from obstructive colorectal cancer.

PubMed

Yamashita, Shinya; Tanemura, Masahiro; Sawada, Genta; Moon, Jeongho; Shimizu, Yosuke; Yamaguchi, Toshiki; Kuwai, Toshio; Urata, Yasuo; Kuraoka, Kazuya; Hatanaka, Nobutaka; Yamashita, Yoshinori; Taniyama, Kiyomi

2018-01-01

The placement of a self-expanding metallic stent (SEMS) in obstructive colorectal cancer (OCRC) is acknowledged to be a safe and effective procedure for the relief of obstruction. However, there is concern that shear forces acting on the tumor during stent expansion may release cancer cells into the circulation, resulting in a poor prognosis. The aim of the present study was to determine whether colonic stent insertion increases viable circulating tumor cells (v-CTCs). A telomerase-specific replication-selective adenovirus-expressing GFP (TelomeScanF35) detection system was used to detect v-CTCs in 8 OCRC patients with a SEMS before and after stent insertion and after surgical resection. In 7 patients, a SEMS was inserted as a bridge to surgery (BTS), and in one patient, a SEMS was inserted for palliation. Surgical resection (R0) was performed in 7 patients. Four patients had no v-CTCs before SEMS placement, two of four measurable patients had an increased number of v-CTCs after SEMS placement (1-3 v-CTCs), and one of two patients with increased v-CTCs developed distant lymphatic metastasis despite curative resection. Four patients had v-CTCs (1-19 cells) before SEMS placement, and two of these four patients had an increase in the number of v-CTCs (20-21 cells) after SEMS placement, while one of the four patients died early with distant metastasis. The present study demonstrated that endoscopic stent insertion for OCRC may result in tumor cell dissemination into the peripheral circulation and may induce distant metastases.

Postoperative irradiation of carcinoma of the head of the pancreas area: Short-time tolerance and results to precision high-dose technique in 18 patients

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

Nguyen, T.D.; Bugat, R.; Combes, P.F.

1982-07-01

During the period from January 1977-August 1979, 18 patients with biopsy-proven pancreas duct or ampullary adenocarcinoma with no distant or liver metastases underwent external beam radiation therapy following laparotomy. With the use of a 25 MEV photon beam and a four field ''box'' technique, the dose delivered to the target volume identified with radio-opaque clips at laparotomy was 6000 rad in six weeks, while largely sparing the spinal cord, kidney, liver and gut. All patients subjected to low fat, gluten free diet completed treatment as planned without any acute reaction. Three patients developed delayed pancreatic insufficiency. According to actuarial survivalmore » analysis and low morbidity such an approach may lead to increased survival in patients with pancreatic cancer.« less

Metastasis: recent discoveries and novel perioperative treatment strategies with particular interest in the hemostatic compound desmopressin.

PubMed

Alonso, D F; Ripoll, G V; Garona, J; Iannucci, N B; Gomez, D E

2011-11-01

Metastatic disease is responsible for most of cancer lethality. A main obstacle for therapy of advanced cancers is that the outcome of metastasis depends on a complex interplay between malignant and host cells. The perioperative period represents an underutilized window of opportunity for cancer treatment where tumor-host interactions can be modulated, reducing the risk of local recurrences and distant metastases. Blood-saving agents are attractive compounds to be administered during tumor surgery. Desmopressin (DDAVP) is a safe and convenient hemostatic peptide with proved antimetastastic properties in experimental models and veterinary clinical trials. The compound seems to induce a dual angiostatic and antimetastatic effect, breaking the cooperative function of cancer cells and endothelial cells during residual tumor progression. DDAVP is therefore an interesting lead compound to develop novel synthetic peptide analogs with enhanced antitumor properties.

[Draft of the best medical treatment in patients with low-risk thyroid cancer].

PubMed

Vlček, Petr; Nováková, Dagmar; Vejvalka, Jan; Zimák, Jaroslav; Křenek, Martin; Vošmiková, Květuše; Smutný, Svatopluk; Bavor, Petr; Astl, Jaromír; Lukáš, Jindřich

2015-09-01

The incidence of well-differentiated low-risk thyroid cancer have increased globally over the last three decades. Thyroid cancer treatment relates to a suitable surgical procedure and the use of adjuvant radio-iodine therapy in selected patients. Evaluation of prognostic factors and risk stratification are critical for determining appropriate treatment. Survival of patients with low-risk thyroid cancer is excellent. Appropriate choice of medical treatment resulted in full recovery in most patients. Relapse risk increases with the size of the primary tumor, along with the findings of the risk factors in men. Our study included a total of 1 980 patients in whom were diagnosed T1a and T1b tumors between the years 2003 to 2012. The population included 1 675 women (84.6 %) of average age of 45.22 years and 305 men (15.4 %) of average age of 50.0 years. The bulk of the file represented papillary carcinomas (1 868; 94.4 %), and smaller group of follicular carcinomas (112; 5.6 %). Patients were divided into four groups according to tumor size. Patients were evaluated according to risk factors: unifocality no other risk factors, multifocality - more bearings in thyroid tumor, metastases in regional lymph nodes, distant metastases or combination of risk factors. Group A: In the monitored set of 678 patients with papillary and follicular microcarcinoma up to 5 mm, during histological input, the findings revealed one bearing (unifocal type of cancer) in 566 patients. Multifocality was found in 112 patients, local nodal metastasis were demonstrated in 24 cases and pulmonary metastasis was discove-red in 1 case. Group B: In this group there were 576 study patients with papillary and follicular microcarcinoma size of 5-10 mm. Histological findings were captured input one bearing carcinoma in 434 patients, 142 patients with multifocality, in 53 cases of local nodal metastasis, and 1 case of bone metastases. Group C: In this group there were 467 study patients with papillary and follicular microcarcinoma size 10-15 mm. The histological initial finding captured unifocal type of cancer in 344 patients, multifocality in 123 patients, in 45 cases local metastases and in 3 cases of pulmonary metastases. Group D: 259 patients were monitored in this group with breast size 16-20 mm. At the initial finding was captured one bearing cancer in 188 patients, multifocality in 71 patients, in 24 cases evidence of local metastases and 2 patients had a case of distant lung metastases. In patients in whom risk factors were found, radioiodine treatment was indicated. This included 744 patients. In this group of patients after a year or more, relapse was observed in 74 patients (9.94 %). In 1 236 patients who did not undergo radioiodine treatment, there was a relapse in 49 patients (3.96 %). Based on our analysis, it is necessary to stratify the risk of relapse according to risk factors. In case of missed radioiodine therapy in patients with low-risk cancer without confirmed risk factors, it is also necessary to have regular clinical, laboratory and ultrasound examination. It is important to distinguish patients with risk factors that may contribute to disease recurrence. Only in this way, on one hand we prevent excessive treatment of patients with low-risk thyroid cancer which leads to increased cost of health care, and on the other hand prevent reduced level of care for patients with an increase in relapses.

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

Baere, Thierry de, E-mail: thierry.debaere@gustaveroussy.fr; Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp; Lencioni, Riccardo, E-mail: riccardo.lencioni@med.unipi.it

Transarterial chemoembolization with Lipiodol (Lipiodol TACE), also called conventional TACE, was developed in the early 1980s and widely adopted worldwide after randomized control trials and meta-analysis demonstrated superiority of Lipiodol TACE to best supportive care. Presently, there is no level one evidence that other TACE techniques are superior to Lipiodol TACE for intermediate stage hepatocellular carcinoma (HCC), which includes patients with preserved liver function and nonsurgical large or multinodular HCC without distant metastases. In addition, TACE is part of the treatment for progressive or symptomatic liver metastases from gastroenteropancreatic neuroendocrine tumors. When injected into the hepatic artery, Lipiodol has themore » unique property of selective uptake and retention in hyperarterialyzed liver tumors. Lipiodol/drug emulsion followed by particle embolization has been demonstrated to improve the pharmacokinetic of the drug and tumor response. Radio opacity of Lipiodol helps to monitor treatment delivery, with retention of Lipiodol serving as an imaging biomarker for tumor response. For 30 years, Lipiodol TACE has been inconsistently referenced in many publications with various levels of details for the method of preparation and administration, with reported progressive outcomes following improvements in the technique and the devices used to deliver the treatment and better patient selection. Consequently, there is no consensus on the standard method of TACE regarding the use of anticancer agents, embolic material, technical details, and the treatment schedule. In order to develop an internationally validated technical recommendation to standardize the Lipiodol TACE procedure, a worldwide panel of experts participated in a consensus meeting held on May 10, 2014.« less

German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors.

PubMed

Dralle, Henning; Musholt, Thomas J; Schabram, Jochen; Steinmüller, Thomas; Frilling, Andreja; Simon, Dietmar; Goretzki, Peter E; Niederle, Bruno; Scheuba, Christian; Clerici, Thomas; Hermann, Michael; Kußmann, Jochen; Lorenz, Kerstin; Nies, Christoph; Schabram, Peter; Trupka, Arnold; Zielke, Andreas; Karges, Wolfram; Luster, Markus; Schmid, Kurt W; Vordermark, Dirk; Schmoll, Hans-Joachim; Mühlenberg, Reinhard; Schober, Otmar; Rimmele, Harald; Machens, Andreas

2013-03-01

Over the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable ("low risk") papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages. The present German Association of Endocrine Surgeons practice guideline was developed on the basis of clinical evidence considering current national and international treatment recommendations through a formal expert consensus process in collaboration with the German Societies of General and Visceral Surgery, Endocrinology, Nuclear Medicine, Pathology, Radiooncology, Oncological Hematology, and a German thyroid cancer patient support organization. The practice guideline for the surgical management of malignant thyroid tumors includes recommendations regarding preoperative workup; classification of locoregional nodes and terminology of surgical procedures; frequency, clinical, and histopathological features of occult and clinically apparent papillary, follicular, poorly differentiated, undifferentiated, and sporadic and hereditary medullary thyroid cancers, thyroid lymphoma and thyroid metastases from primaries outside the thyroid gland; extent of thyroidectomy; extent of lymph node dissection; aerodigestive tract resection; postoperative follow-up and surgery for recurrence and distant metastases. These evidence-based recommendations for surgical therapy reflect various "treatment corridors" that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk.

Cancer and the metastatic substrate

PubMed Central

Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

2016-01-01

Seventy percent of cancer patients have detectable metastases when they receive a diagnosis and 90% of cancer deaths result from metastases. These two facts emphasise the urgency for research to study the mechanisms and processes that enable metastasis. We need to develop a greater understanding of the cellular and molecular mechanisms that cause metastasis and also we need to do more. We must also consider the micro- and macro-environmental factors that influence this disease. Studying this environmental context has led us to update the ‘seed and soil’ hypothesis which dates back to the 19th century. This theory describes cancerous cells as seeds and the substrate as the soil in target organs though this may seem antiquated. Nonetheless, the tissue specificity that researchers have recently observed in metastatic colonisation supports the validity of the seed and soil theory. We now know that the metastatic potential of a tumour cell depends on multiple, reciprocal interactions between the primary tumour and distant sites. These interactions determine tumour progression. Studies of metastasis have allowed us to develop treatments that focus on therapeutic effectiveness. These new treatments account for the frequent metastasis of some tumours to target organs such as bones, lungs, brain, and liver. The purpose of this review is first to describe interactions between the cellular and molecular entities and the target organ tumour environment that enables metastasis. A second aim is to describe the complex mechanisms that mediate these interactions. PMID:28105072

Photodynamic therapy and fluorescent diagnostics of breast cancer

NASA Astrophysics Data System (ADS)

Vakulovskaya, Elena G.; Letyagin, Victor P.; Umnova, Loubov V.; Vorozhcsov, Georgiu N.; Philinov, Victor

2004-06-01

Photodynamic Therapy (PDT) and fluorescent diagnostics (FD) using Photosense have been provided in 26 patients with breast cancer (BC) and in 108 patients with skin metastases of BC. In 22 patients with T1-T2N0M0 primary tumor PDT was preoperative treatment, with radical mastectomy 7-10 days after PDT. 4 patients had residual tumor after radiotherapy. FD was fulfilled with spectranalyser. We used semiconductive laser for PDT-λ=672+2nm, P=1,5 W, interstitial irradiation 2-24 hours after PS injection in light dose 150-200 J/cm3 in patients with primary tumor and multiple surface irradiations (1-4) with interval 24-48 hours and total light dose 400-600 J/cm2 for metastases. Partial regression of tumor with pathomorphosis of 2-4 degree has been found in 23 cases in first group. Treating metastases we had overall response rate of 86,9% with complete response (CR) in 51,5% and partial response in 35,4%. In a year after PDT in 52 patients with CR we had CR in 36,6%, local recurrences in 23,1%, progression (distant [lung or bone] metastasis) in 40,4% of cases. Our experience show pronounced efficacy of FD for detecting tumor borders and PDT for treating BC as preoperative modality and as palliation in cases of recurrencies.

Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma.

PubMed

Lyons, A J; Jones, J

2007-08-01

Carcinomas are characterized by invasion of malignant cells into the underlying connective tissue and migration of malignant cells to form metastases at distant sites. These processes require alterations in cell-cell and cell-extracellular matrix interactions. As cell adhesion molecules play a role in cell-cell and cell-extracellular matrix adhesion and interactions they are involved in the process of tumour invasion and metastases. In epithelial tissues, receptors of the integrin family mediate adhesion to the adjacent matrix whereas cadherins largely mediate intercellular adhesion. These and other cell adhesion molecules such as intercellular adhesion molecule-1, CD44, dystroglycans and selectins, are involved and undergo changes in carcinomas, which provide possible targets for anti-cancer drug treatments. In the extracellular matrix that is associated with tumours, laminin 5, oncofetal fibronectin and tenascin C appear. The degree of expression of some of these moieties indicates prognosis in oral cancer and offer targets for antibody-directed radiotherapy. Metalloproteases which degrade the extracellular matrix are increased in carcinomas, and their activity is necessary for tumour angiogenesis and consequent invasion and metastases. Metalloprotease inhibitors have begun to produce decreases in mortality in clinical trials. This report provides a brief overview of our current understanding of cell adhesion molecules, the extracellular matrix, tumour invasion and metastasis.

Major Vascular Abutment, Involvement or Encasement is not a Contraindication to Pancreatic Endocrine Tumor Resection

PubMed Central

Norton, Jeffrey A.; Harris, E. John; Chen, Yijun; Visser, Brendan C; Poultsides, George A; Kunz, Pamela C.; Fisher, George A; Jensen, Robert.T.

2010-01-01

Background There is considerable controversy about the treatment of patients with malignant functional or nonfunctional pancreatic endocrine tumors (PETs). Aggressive surgery with dissection and/or reconstruction of major vascular structures is a potentially efficacious antitumor therapy, but is rarely performed, and considered a contraindication to surgery by many. Hypothesis Aggressive resection of locally advanced PETs in which preoperative studies suggest major vascular involvement can be performed with acceptable morbidity and mortality rates and may lead to extended survival. Design The combined databases of the prospective NIH study on PETs (gastrinomas) (from 1982) and Stanford (all PETs)(from 2004) were queried. All patients with possible involvement of major vascular structures were reviewed and preoperative studies, operative findings and surgical results/outcomes correlated. Main Outcome Measures Surgical procedure, pathologic characteristics, complications, mortality rates, and disease-free and overall survival rates. Results Of 273 patients with PETs, 46 (17%) had preoperative CT evidence of major vascular involvement. There were 21 men (45%). Mean age was 42 years (range 24-76). 32 (57%) had functional tumors with 30 gastrinomas and 2 glucagonomas; the remainder (n=14) had nonfunctional PETs. 12 patients (26%) had MEN-1. 44 of 46 underwent surgery. The mean size for the primary PET on preoperative CT was 5.8 cm. The involved major vessel was as follows: portal vein (n=20, 43%), SMV or SMA (n=16, 35%), IVC (n=4, 9%), splenic vein (n=4, 9%) and heart (n=2, 4%). 42 (91%) patients had PET removed: 12 (27%) primary only, 30 (68%) with lymph nodes, and 18 (41%) with liver metastases. PETs were removed by either enucleation (n=5, 12%) or resection (n=36, 86%). Resections included distal or subtotal pancreatectomy in 23 (55%), Whipple in 10 (23%) and total in 2 (5%). 19 (45%) patients had concomitant liver resection: 10 (23%) wedge resection and 9 (21%) anatomic resections (lobectomy or trisegmentectomy). 9 (21%) had vascular reconstruction: each had reconstruction of the SMV and portal vein, while 1 had concomitant reconstruction of the SMA. There were no deaths, but 12 (28%) had complications. 18 (42%) were immediately disease-free and 5 recurred with follow-up leaving 14 (33%) long-term disease-free. The 10-year overall survival was 60%. Functional tumors had a better overall survival (p<0.0001), and liver metastases decreased overall survival (p<0.0001). Conclusions Aggressive surgery including superior mesenteric vein reconstruction, and liver resection can be done with acceptable morbidity and mortality rates for patients with advanced PETs. Although survival rates following surgery are excellent, most patients will develop recurrence. These findings suggest that surgical resection is indicated even in PETs with vascular invasion and nodal or distant metastases. Distant metastases decrease the probability of long-term survival, still 60% are alive at 10 years and one third remain disease-free. PMID:21690450

The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma

PubMed Central

Zhai, Weiwei; Lim, Tony Kiat-Hon; Zhang, Tong; Phang, Su-Ting; Tiang, Zenia; Guan, Peiyong; Ng, Ming-Hwee; Lim, Jia Qi; Yao, Fei; Li, Zheng; Ng, Poh Yong; Yan, Jie; Goh, Brian K.; Chung, Alexander Yaw-Fui; Choo, Su-Pin; Khor, Chiea Chuen; Soon, Wendy Wei-Jia; Sung, Ken Wing-Kin; Foo, Roger Sik-Yin; Chow, Pierce Kah-Hoe

2017-01-01

Hepatocellular carcinoma (HCC) has one of the poorest survival rates among cancers. Using multi-regional sampling of nine resected HCC with different aetiologies, here we construct phylogenetic relationships of these sectors, showing diverse levels of genetic sharing, spanning early to late diversification. Unlike the variegated pattern found in colorectal cancers, a large proportion of HCC display a clear isolation-by-distance pattern where spatially closer sectors are genetically more similar. Two resected intra-hepatic metastases showed genetic divergence occurring before and after primary tumour diversification, respectively. Metastatic tumours had much higher variability than their primary tumours, suggesting that intra-hepatic metastasis is accompanied by rapid diversification at the distant location. The presence of co-existing mutations offers the possibility of drug repositioning for HCC treatment. Taken together, these insights into intra-tumour heterogeneity allow for a comprehensive understanding of the evolutionary trajectories of HCC and suggest novel avenues for personalized therapy. PMID:28240289

Metastasis to the appendix from adenocarcinoma of the ascending colon: A case report.

PubMed

Li, Yingjie; Li, Mingshan; Li, Xiaoxia; Sang, Haiquan

2017-03-01

Metastasis of cancer cells involves shedding from the primary tumor through various means to distant tissues and organs with continued growth and formation of new metastatic tumors of the same cancer type as the original tumor. The common sites for colon cancer metastases include the pelvis, retroperitoneal lymph nodes, liver, and lungs; Colon cancer metastases to the appendix are rare, as reported in this case. A 45-year-old man was admitted to our department with a 24-hour history of abdominal distension and incomplete obstruction. Colonoscopy showed an elevated lesion in the ascending colon and the pathologic diagnosis was adenocarcinoma. This patient underwent a radical right hemi-colectomy. The post-operative pathologic examination revealed metastatic adenocarcinoma in all layers of the appendix, especially the muscularis mucosae. The diagnosis was adenocarcinoma of the ascending colon (pT4bN2bM0 stage IIIC) with metastatic adenocarcinoma of the appendix. An absent right colic artery with lymph node fusion might increase the risk of appendiceal cancer metastasis.

Primary peritoneal carcinoma metastasizing to breast: a single case report and literature review from clinic to biology

PubMed Central

Sun, Ji-Yuan; Gebre, Wondwossen; Dong, Yi-Min; Shaun, Xiao; Robbins, Rachel; Podrumar, Alida

2016-01-01

Primary peritoneal carcinoma (PPC) is a type of rare malignant epithelial tumor. Metastasis from PPC to breast has been rarely reported. PPC originates de novo from the peritoneal tissues rather than invasion or metastasis from adjacent or remote organs. PPCs have been implicated in many cases of carcinomas of unknown primary origin. It is similar to ovarian cancer (OvCa), because it shares the same common embryonic origin, the coelomic epithelium (mesodermal origin). The mechanism of oncogenesis remains elusive. In this article, we report a rare case of PPC in a patient 10 years after total abdominal hysterectomy and bilateral salpingooophorectomy for uterine leiomyoma, which was widely spread in the abdomen and metastasized to the colon, liver and distant organs including breast. The treatment is similar to that of primary ovarian cancer. We also reviewed the primary peritoneal cancer metastatic to breast and discuss the possible mechanisms and biology of primary peritoneal cancer, using experimental and animal model. PMID:27807506

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases

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

Mehta, Minesh P.; Tsao, May N.; Whelan, Timothy J.

2005-09-01

Purpose: To systematically review the evidence for the use of stereotactic radiosurgery in adult patients with brain metastases. Methods: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (ASCO) (1997-2004), ASTRO (1997-2004), andmore » the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. Results: For patients with newly diagnosed brain metastases, managed with whole-brain radiotherapy alone vs. whole-brain radiotherapy and radiosurgery boost, there were three randomized controlled trials, zero prospective studies, and seven retrospective series (which satisfied inclusion criteria). For patients with up to three (<4 cm) newly diagnosed brain metastases (and in one study up to four brain metastases), radiosurgery boost with whole-brain radiotherapy significantly improves local brain control rates as compared with whole-brain radiotherapy alone (Level I-III evidence). In one large randomized trial, survival benefit with whole-brain radiotherapy was observed in patients with single brain metastasis. In this trial, an overall increased ability to taper down on steroid dose and an improvement in Karnofsky performance status was seen in patients who were treated with radiosurgery boost as compared with patients treated with whole-brain radiotherapy alone. However, Level I evidence regarding overall quality of life outcomes using a validated instrument has not been reported. All randomized trials showed improved local control with the addition of radiosurgery to whole-brain radiotherapy. For patients with multiple brain metastases, there is no overall survival benefit with the use of radiosurgery boost to whole-brain radiotherapy (Level I-III evidence). Radiosurgery boost is associated with a small risk of early or late toxicity. In patients treated with radiosurgery alone (withholding whole-brain radiotherapy) as initial treatment, there were 2 randomized trials, 2 prospective cohort studies, and 16 retrospective series. There is Level I to Level III evidence that the use of radiosurgery alone does not alter survival as compared to the use of whole-brain radiotherapy. However, there is Level I to Level III evidence that omission of whole-brain radiotherapy results in poorer intracranial disease control, both local and distant (defined as remaining brain, outside the radiosurgery field). Quality of life outcomes have not been adequately reported. Radiosurgery is associated with a small risk of early or late toxicity. Radiosurgery as salvage for patients with brain metastases was reported in zero randomized trials, one prospective study, and seven retrospective series. Conclusions: Based on Level I-III evidence, for selected patients with small (up to 4 cm) brain metastases (up to three in number and four in one randomized trial), the addition of radiosurgery boost to whole-brain radiotherapy improves brain control as compared with whole-brain radiotherapy alone. In patients with a single brain metastasis, radiosurgery boost with whole-brain radiotherapy improves survival. There is a small risk of toxicity associated with radiosurgery boost as compared with whole-brain radiotherapy alone. In selected patients treated with radiosurgery alone for newly diagnosed brain metastases, overall survival is not altered. However, local and distant brain control is significantly poorer with omission of upfront whole-brain radiotherapy (Level I-III evidence). Whether neurocognition or quality of life outcomes are different between initial radiosurgery alone vs. whole-brain radiotherapy (with or without radiosurgery boost) is unknown, because this has not been adequately tested. There was no statistically significant difference in overall toxicity between those treated with radiosurgery alone vs. whole-brain radiotherapy and radiosurgery boost based on an interim report from one randomized study. There is insufficient evidence as to the clinical benefit/risks radiosurgery used in the setting of recurrent or progressive brain metastases, although radiographic responses are well-documented.« less

Clinical stage of oral cancer patients at the time of initial diagnosis.

PubMed

Shah, Irfan; Sefvan, Omer; Luqman, Uzair; Ibrahim, Waseem; Mehmood, Sana; Alamgir, Wajiha

2010-01-01

Squamous cell carcinoma is the most common oral cancer. Early diagnosis ensures better prognosis. Late diagnosis is however common around the world and contributes to the high morbidity and mortality related to oral cancer. The objective of this study was to determine the clinical stage of oral cancer patients at the time of diagnosis. This retrospective study was carried out on 334 oral cancer patients who presented to the outdoor departments of Armed Forces Institute of Dentistry, and Armed Forces Institute of Pathology, Rawalpindi from July 2008 to December 2009. The records that were reviewed included history and clinical examination findings. OPG and CT scans of the head and neck region, chest X-rays, abdominal ultrasounds and liver function tests. Size of the primary tumour, the size, number and laterality of the involved cervical lymph nodes and the presence/absence of distant metastases were documented and statistically analysed using SPSS-17. Out of the 334 patients, 203 (60.8%) were males and 131 (39.2%) females. The age range was from 21 to 88 years. Buccal mucosa was the most commonly involved site (32%). The primary tumour was 4 Cm or more in size, (T3/T4) 71.25% of the cases. Cervical lymph nodes were involved in 211 patients (63.2%) and distant metastases were present in 39 patients (11.7%). Overall, clinical stage IV was the most common (57.18%) followed by stage III (24.55%), stage II (13.77%) and stage I (4.49%). Oral cancers are diagnosed late (Stage III and IV) in Pakistan and need immediate public and professional attention.

MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells.

PubMed

Sánchez-Cid, Lourdes; Pons, Mònica; Lozano, Juan José; Rubio, Nuria; Guerra-Rebollo, Marta; Soriano, Aroa; Paris-Coderch, Laia; Segura, Miquel F; Fueyo, Raquel; Arguimbau, Judit; Zodda, Erika; Bermudo, Raquel; Alonso, Immaculada; Caparrós, Xavier; Cascante, Marta; Rafii, Arash; Kang, Yibin; Martínez-Balbás, Marian; Weiss, Stephen J; Blanco, Jerónimo; Muñoz, Montserrat; Fernández, Pedro L; Thomson, Timothy M

2017-10-13

MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo . MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells.

Malignant melanoma of the skin: long-term follow-up and time to first recurrence.

PubMed

Hohnheiser, Annika M; Gefeller, Olaf; Göhl, Jonas; Schuler, Gerold; Hohenberger, Werner; Merkel, Susanne

2011-03-01

Surgical excision can cure most patients with malignant melanoma of the skin. However, the risk of recurrence remains for years. The aim of our study was to identify factors that influence time to recurrence and survival after the first recurrence with a special interest in late recurrences. Data from 2487 patients with malignant melanoma and primary treatment between 1978 and 1997 at the Department of Surgery or the Department of Dermatology, University Hospital Erlangen, Germany, were prospectively collected in the Melanoma Registry of the University Hospital Erlangen. After a median follow-up period of 13 years, overall survival, the time to first recurrence and survival after the first relapse were examined in univariate and multivariate analyses. Overall survival was found to be significantly worse in older patients, men, melanoma of the head or trunk, and melanoma with high pT and pN categories. In 523 patients, relapse from malignant melanoma was observed after a median of 24 months. Among patients with recurrences, young age and low pT and pN categories proved to be independent factors that prolonged the disease-free interval. Advanced age at the time of the recurrence diagnosis, male sex, high pN category, and distant metastases as the first manifestation of recurrence were associated with a poor prognosis after the first recurrence. Although thin lesions have a favorable prognosis, among a cohort with recurrences they showed a relatively high rate of late recurrences. These late recurrences have an extremely poor prognosis when they present with distant metastases.

[Oncological outcomes of combined therapy in patients with cervical carcinoma FIGO stage IIB].

PubMed

Kornovski, Y; Ismail, E; Kaneva, M

2012-01-01

To establish the overall and disease-free survival and the role of surgery as well as in cervical cancer stage IIB (FIGO) patients submitted to combined radiotherapy and surgery. Between 2003-2011 86 patients with cervical cancer stage IIB had been operated on. Five patients were operated on after neoajuvant chemotherapy. Thirty one women (group 3) had primary pelvic surgery (radical hysterectomy class III and lymphonodulectomy) and adjuvant RT until 52 Gy and 50 women were operated on after preoperative RT (30 Gy) and were submitted to adjuvant RT until 52 Gy (group 4). After median follow of 45 months the acturial overall and disease-free survival (OS and DFS) were estimated as 75.6% and 77.9% respectively for all patients staged IIB (FIGO). In group 3 the incidence of local relapses and distant metastases was 9.7% and 12.9%, respectively and in group 4--local and distant recurrences were 6% and 14%, respectively. The acturial OS and DFS for group 3 were 80.6% and 77.5%, respectively and for group 4--76% and 80% (NS). Combinated treatment (RT and pelvic surgery) produce reliable local control of the disease (cervical cancer IIB stage) but is ineffective for metastases outside the small pelvis which is the cause of worse survival of patients with cervical cancer stage IIB (FIGO). Preoperative RT (group 4) doesn't change the OS and DFS significantly. The main indication for surgery in patients with cervical cancer stage IIB is the surgical staging (pelvic and paraaortic lymph node dissection) which enables the appropriate individual treatment planning.

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

Nemani, Deepika; Vapiwala, Neha; Hwang, W.-T.

Purpose: Little information has been reported regarding outcomes after treatment for patients with early-stage invasive breast cancer and a prior nonbreast malignancy. This report analyzes the outcomes in patients with Stage I and II breast cancer after breast conservation treatment (BCT) with a prior nonbreast malignancy. Methods and Materials: The study cohort comprised 66 women with invasive breast cancer and a prior nonbreast malignancy. All patients were treated with breast conservation surgery followed by definitive breast irradiation between 1978 and 2003. Median ages at diagnosis of invasive breast cancer and prior malignancy were 57 and 50 years, respectively. The medianmore » interval between the prior malignancy and breast cancer was 7.0 years. Median and mean follow-up times after BCT were 5.3 and 7.0 years. Results: The 5-year and 10-year overall survival rates were 94% (95% confidence interval [CI], 82-98%) and 78% (95% CI, 59-89%), respectively. There were 4 patients (6%) with local failure and 10 patients (15%) with distant metastases. The 10-year rate of local failure rate was 5% (95% CI, 2-16%) and freedom from distant metastases was 78% (95% CI, 61-88%). No obvious differences in survival or local control were noted compared with the reported results in the literature for patients with invasive breast cancer alone. Conclusions: Both overall survival and local control at 5 and 10 years were comparable to rates observed in early-stage breast cancer patients without a prior malignancy. Prior nonbreast malignancy is not a contraindication to BCT, if the primary cancer is effectively controlled.« less

Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases.

PubMed

Tsao, May N; Xu, Wei; Wong, Rebecca Ks; Lloyd, Nancy; Laperriere, Normand; Sahgal, Arjun; Rakovitch, Eileen; Chow, Edward

2018-01-25

This is an update to the review published in the Cochrane Library (2012, Issue 4).It is estimated that 20% to 40% of people with cancer will develop brain metastases during the course of their illness. The burden of brain metastases impacts quality and length of survival. To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) given alone or in combination with other therapies to adults with newly diagnosed multiple brain metastases. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase to May 2017 and the National Cancer Institute Physicians Data Query for ongoing trials. We included phase III randomised controlled trials (RCTs) comparing WBRT versus other treatments for adults with newly diagnosed multiple brain metastases. Two review authors independently assessed trial quality and abstracted information in accordance with Cochrane methods. We added 10 RCTs to this updated review. The review now includes 54 published trials (45 fully published reports, four abstracts, and five subsets of data from previously published RCTs) involving 11,898 participants.Lower biological WBRT doses versus controlThe hazard ratio (HR) for overall survival (OS) with lower biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 1.21 (95% confidence interval (CI) 1.04 to 1.40; P = 0.01; moderate-certainty evidence) in favour of control. The HR for neurological function improvement (NFI) was 1.74 (95% CI 1.06 to 2.84; P = 0.03; moderate-certainty evidence) in favour of control fractionation.Higher biological WBRT doses versus controlThe HR for OS with higher biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 0.97 (95% CI 0.83 to 1.12; P = 0.65; moderate-certainty evidence). The HR for NFI was 1.14 (95% CI 0.92 to 1.42; P = 0.23; moderate-certainty evidence).WBRT and radiosensitisersThe addition of radiosensitisers to WBRT did not confer additional benefit for OS (HR 1.05, 95% CI 0.99 to 1.12; P = 0.12; moderate-certainty evidence) or for brain tumour response rates (odds ratio (OR) 0.84, 95% CI 0.63 to 1.11; P = 0.22; high-certainty evidence).Radiosurgery and WBRT versus WBRT aloneThe HR for OS with use of WBRT and radiosurgery boost as compared with WBRT alone for selected participants was 0.61 (95% CI 0.27 to 1.39; P = 0.24; moderate-certainty evidence). For overall brain control at one year, the HR was 0.39 (95% CI 0.25 to 0.60; P < 0.0001; high-certainty evidence) favouring the WBRT and radiosurgery boost group.Radiosurgery alone versus radiosurgery and WBRTThe HR for local brain control was 2.73 (95% CI 1.87 to 3.99; P < 0.00001; high-certainty evidence)favouring the addition of WBRT to radiosurgery. The HR for distant brain control was 2.34 (95% CI 1.73 to 3.18; P < 0.00001; high-certainty evidence) favouring WBRT and radiosurgery. The HR for OS was 1.00 (95% CI 0.80 to 1.25; P = 0.99; moderate-certainty evidence). Two trials reported worse neurocognitive outcomes and one trial reported worse quality of life outcomes when WBRT was added to radiosurgery.We could not pool data from trials related to chemotherapy, optimal supportive care (OSC), molecular targeted agents, neurocognitive protective agents, and hippocampal sparing WBRT. However, one trial reported no differences in quality-adjusted life-years for selected participants with brain metastases from non-small-cell lung cancer randomised to OSC and WBRT versus OSC alone. None of the trials with altered higher biological WBRT dose-fractionation schemes reported benefit for OS, NFI, or symptom control compared with standard care. However, OS and NFI were worse for lower biological WBRT dose-fractionation schemes than for standard dose schedules.The addition of WBRT to radiosurgery improved local and distant brain control in selected people with brain metastases, but data show worse neurocognitive outcomes and no differences in OS.Selected people with multiple brain metastases from non-small-cell lung cancer may show no difference in OS when OSC is given and WBRT is omitted.Use of radiosensitisers, chemotherapy, or molecular targeted agents in conjunction with WBRT remains experimental.Further trials are needed to evaluate the use of neurocognitive protective agents and hippocampal sparing with WBRT. As well, future trials should examine homogeneous participants with brain metastases with focus on prognostic features and molecular markers.

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

Bednarz, Natalia; Eltze, Elke; Semjonow, Axel

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

Preoperative noninvasive EUS evaluation in patients with esophageal cancer considered for esophagectomy.

PubMed

Gheorghe, Cristian; Stanescu, Codrut; Gheorghe, Liana; Bancila, Ion; Herlea, Vlad; Becheanu, Gabriel; Voinea, Daniela; Iacob, Razvan; Lupescu, Ioana; Anghel, Rodica; Croitoru, Adina; Popescu, Irinel

2006-06-01

Worldwide, esophageal cancer ranks fifth in the mortality rate regarding tumor locations. EUS is an essential tool in the evaluation of these patients allowing accurate staging and permitting stratified treatment options. AIM. We have studied prospectively the impact of EUS in the evaluation and decision for therapy of patients with esophageal cancer diagnosed in our center. From March 2001 through March 2006, 220 patients were hospitalized at the Center of Gastroenterology and Hepatology, Fundeni Clinical Institute, with the diagnosis of esophageal cancer. Out of the 220 patients, 41 patients, with no major comorbidities contraindicating esophagectomy already having been screened by abdominal and thoracic CT to disclose distant metastases, had EUS with the definite purpose of staging esophageal carcinoma and selecting adequate therapy. Assuming that without preoperative staging by EUS, all 41 patients in the study group would have been offered surgical treatment, we evaluated the number of patients and the modality in which EUS resulted in changes to the therapeutic plan. Depth of invasion was recorded for the 41 patients as follows: T1 in 2 patients (4.9%), T2 in 6 patients (14.6%), T3 in 24 patients (58.5%), and T4 in 10 patients (22%). Regional lymph node (N) status as determined by EUS criteria was as follows: N0 in 7 patients (17%) and N1 in 34 patients (83%). Assessment of distant metastases (M) was recorded showing 4 patients with celiac axis lymph nodes metastases (M1). Preoperative EUS staging changed the decision for surgery in 18 of 41 patients (44%) (p<0.0001) and allowed primary esophagectomy in only 6 patients (15%) (p<0.0001). Compared to histopathology, the overall accuracy of EUS staging for pT1 and pT2 was 80% for staging pT3 and pT4 77% and for lymph node evaluation was approximately 75%. Esophageal EUS offers useful information to clinicians caring for patients with esophageal cancer, impacts clinical decision making, and should be used in appropriate settings to plan patients' care.

Molecular insights into melanoma brain metastases.

PubMed

Westphal, Dana; Glitza Oliva, Isabella C; Niessner, Heike

2017-06-01

Substantial proportions of patients with metastatic melanoma develop brain metastases during the course of their disease, often resulting in significant morbidity and death. Despite recent advances with BRAF/MEK and immune-checkpoint inhibitors in the treatment of patients who have melanoma with extracerebral metastases, patients who have melanoma brain metastases still have poor overall survival, highlighting the need for further therapy options. A deeper understanding of the molecular pathways involved in the development of melanoma brain metastases is required to develop more brain-specific therapies. Here, the authors summarize the currently known preclinical data and describe steps involved in the development of melanoma brain metastases. Only by knowing the molecular background is it possible to design new therapeutic agents that can be used to improve the outcome of patients with melanoma brain metastases. Cancer 2017;123:2163-75. © 2017 American Cancer Society. © 2017 American Cancer Society.

Salvage treatment for recurrent oropharyngeal squamous cell carcinoma.

PubMed

Röösli, Christof; Studer, Gabriela; Stoeckli, Sandro J

2010-08-01

This study evaluates the oncological outcome of patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after primary radiation therapy +/- chemotherapy, primary surgical therapy, and surgical therapy followed by radiation therapy +/- chemotherapy. A total of 156 patients (36%) of a cohort of 427 treated for OPSCC between 1990 and 2006 developed recurrent disease. Fifty-one patients (12%) qualified for salvage treatment. Study endpoints were 5-year overall survival (OS) and disease-specific survival (DSS). The 5-year OS and DSS rates after salvage treatment were 29% and 40%; after initial primary radiation therapy, 25% and 40%; after initial surgery followed by radiation therapy, 40% and 40%; and after initial surgery alone, 20% and 40%. Patients with an advanced OPSCC have a considerable risk for recurrence. Despite poor ultimate outcome, salvage treatment should be attempted in patients with resectable disease, good performance status, and absence of distant metastases. 2009 Wiley Periodicals, Inc. Head Neck, 2010.

Liquid biopsy utility for the surveillance of cutaneous malignant melanoma patients.

PubMed

Huang, Sharon K; Hoon, Dave S B

2016-03-01

Cutaneous melanoma is one of the highest incident-rate cancers with increasing prevalence in Western societies. Despite the advent of new approved therapeutics, the 5-year overall survival rate of stage IV melanoma patients remains below 15%. Current treatments for late stage disease have shown higher efficacy when treated at a lower disease burden. Thus, blood-based biomarkers capable of detecting melanoma prior to clinically evident distant metastasis, will improve the treatment and outcomes for melanoma patients. To that end, effective treatment of melanoma necessitates identification of patients at risk for developing distant metastases. Furthermore, employing blood biomarkers that monitor cancer progression over the course of treatment is a promising solution to post-treatment drug resistance often developed in melanoma patients. Non-invasive blood biomarker assays allow for regular dynamic monitoring of disease. "Liquid Biopsy" of blood, which exploits circulating tumor cells (CTCs), cell-free circulating tumor DNA (ctDNA) and cell-free circulating microRNA (cmiRNA), has been shown to detect prognostic factors for relapse in AJCC stage III and stage IV melanoma patients. Moreover, molecular characterization of CTC and analysis of various forms of ctDNA present promising potential in development of individualized therapy for melanoma patients. New approaches such as massive parallel sequencing (MPS) provide a comprehensive view of the disease progression, allowing for the selection of therapeutic options for individual patients. With advancements of improving molecular assays, liquid biopsy analysis as a powerful, routine clinical assay for melanoma patients, is highly promising prospective. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer.

PubMed

Wang, Shu-Lian; Liao, Zhongxing; Liu, Helen; Ajani, Jaffer; Swisher, Stephen; Cox, James D; Komaki, Ritsuko

2006-09-14

To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy (median: 64.8 Gy) to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume (PTV) of the gross tumor volume boost was 91.2%-98.2% of the prescription dose (standard deviation [SD]: 3.7%-5.7%). The minimum dose received by the PTV of the clinical tumor volume was 93.8%-104.8% (SD: 4.3%-11.1%) of the prescribed dose. With a median follow-up of 15 mo (range: 3-21 mo), all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula. Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

The management of metastatic radioiodine-refractory differentiated thyroid cancer requires an integrated approach including both directed and systemic therapies.

PubMed

Cooray, Shamil D; Topliss, Duncan J

2017-01-01

A 58-year-old man with metastatic radioiodine-refractory differentiated thyroid cancer (DTC) presented with left thigh and right flank numbness. He had known progressive and widespread bony metastases, for which he received palliative radiotherapy, and multiple bilateral asymptomatic pulmonary metastases. CT scan and MRI of the spine revealed metastases at right T10-L1 vertebrae with extension into the central canal and epidural disease at T10 and T11 causing cord displacement and canal stenosis but retention of spinal cord signal. Spinal surgery was followed by palliative radiotherapy resulting in symptom resolution. Two months later, sorafenib received approval for use in Australia and was commenced and up-titrated with symptomatic management of mild adverse effects. Follow-up CT scan three months after commencement of sorafenib revealed regression of pulmonary metastases but no evident change in most bone metastases except for an advancing lesion eroding into the right acetabulum. The patient underwent a right total hip replacement, intra-lesional curettage and cementing. After six months of sorafenib therapy, CT scanning showed enlarging liver lesions with marked elevation of serum thyroglobulin. Lenvatinib was commenced and sorafenib was ceased. He now has stable disease with a falling thyroglobulin more than 5 years after metastatic radioiodine-refractory DTC was diagnosed. In DTC, 5% of distant metastases become radioiodine-refractory, resulting in a median overall survival of 2.5-3.5 years. Tyrosine kinase inhibitor (TKI) therapy has recently been demonstrated to increase progression-free survival in these patients but poses some unique management issues and is best used as part of an integrated approach with directed therapy. Directed therapies may have greater potential to control localised disease and related symptoms when compared to systemic therapies.Consider TKI therapy in progressive disease where benefits outweigh risks.Active surveillance and timely intervention are required for TKI-related adverse effects.There is a need for further research on the clinical application of TKI therapy in advanced DTC, including comparative efficacy, sequencing and identifying responders.

Incidence of bone metastases and survival after a diagnosis of bone metastases in breast cancer patients.

PubMed

Harries, M; Taylor, A; Holmberg, L; Agbaje, O; Garmo, H; Kabilan, S; Purushotham, A

2014-08-01

Bone is the most common metastatic site associated with breast cancer. Using a database of women with breast cancer treated at Guy's Hospital, London 1976-2006 and followed until end 2010, we determined incidence of and survival after bone metastases. We calculated cumulative incidence of bone metastases considering death without prior bone metastases as a competing risk. Risk of bone metastases was modelled through Cox-regression. Survival after bone metastases diagnosis was calculated using Kaplan-Meier methodology. Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean). Incidence of bone metastases was significantly higher in younger women, tumour size >5 cm, higher tumour grade, lobular carcinoma and ≥ four positive nodes, but was not affected by hormone receptor status. Median survival after bone metastases diagnosis was 2.3 years in women with bone-only metastases compared with <1 year in women with visceral and bone metastases. There was a trend for decreased survival for patients who developed visceral metastases early, and proportionately fewer patients in this group. Incidence of bone metastases has decreased but bone metastases remain a highly relevant clinical problem due to the large number of patients being diagnosed with breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Coexistent Superscan and Lincoln Sign on Bone Scintigraphy.

PubMed

Kulkarni, Mukta; Soni, Atul; Shetkar, Shubhangi; Amer, Momin; Mulavekar, Amruta; Joshi, Prathamesh

2017-08-01

A 70-year-old man underwent Tc-methylene diphosphonate scintigraphy for staging of adenocarcinoma prostate. Scintigraphy revealed diffuse increased tracer uptake in skeletal system along with faint renal visualization, a pattern compatible with metastatic superscan. The scintigraphy also revealed increased radiotracer uptake in the body of the mandible-Lincoln sign or black beard sign. Radiological imaging revealed sclerotic lesions throughout the skeleton including the mandible, confirming widespread skeletal metastases. Lincoln sign is previously described in monostotic Paget disease of the mandible and in contiguous spread of oral malignancy. We describe this pattern in distant metastatic involvement from carcinoma prostate with coexistent superscan pattern.

Multimodality management of soft tissue tumors in the extremity

PubMed Central

Crago, Aimee M.; Lee, Ann Y.

2016-01-01

Most extremity soft tissue sarcomas present as a painless mass. Workup should generally involve cross-sectional imaging with MRI, as well as a core biopsy for pathologic diagnosis. Limb-sparing surgery is the standard of care, and may be supplemented with radiation for histologic subtypes at higher risk for local recurrence and chemotherapy for those at higher risk for distant metastases. This article reviews the work-up and surgical approach to extremity soft tissue sarcomas, as well as the role for radiation and chemotherapy, with particular attention given to the distinguishing characteristics of some of the most common subtypes. PMID:27542637

The Breast International Group 1-98 trial: big results for women with hormone-sensitive early breast cancer.

PubMed

Monnier, Alain M

2007-05-01

As there is a risk for relapse in early breast cancer, especially at 1-3 years post surgery, the need for adjuvant therapy is clear. In terms of disease-free survival, aromatase inhibitors have emerged as superior to tamoxifen for the adjuvant treatment of hormone-sensitive breast cancer in several Phase III clinical trials. Of these trials, the Breast International Group (BIG) 1-98 trial stands out as unique in design, as it is the only trial to address whether an aromatase inhibitor is more effective as initial adjuvant therapy or as sequential therapy with an aromatase inhibitor and tamoxifen in either order and in rigor of end points and safety evaluations. When compared with tamoxifen, letrozole has been shown to significantly reduce recurrence risk in the overall population by 19% and also significantly reduced recurrence risk in the patient subgroups at increased risk: node-positive and previously chemotherapy-treated patients. Letrozole is the only aromatase inhibitor to demonstrate a significant 27% reduction in the risk of distant metastases (p = 0.001) in the clinically relevant, hormone receptor-positive population in the initial adjuvant setting. Recent results also suggest that letrozole in particular reduces the risk of distant metastases early on after initial surgery for breast cancer. This is important, as early distant metastatic events compose the majority of early recurrences and are a well-recognized predictor of breast cancer death. Letrozole has been found to be well tolerated in the initial adjuvant treatment setting, and these data have been confirmed by long-term safety data from the monotherapy analysis in the BIG 1-98 study. Thus far, the results from the BIG 1-98 trial provide clear support for the use of letrozole in the initial adjuvant treatment of breast cancer. Future studies will provide the definitive answer to questions of which initial adjuvant therapy is superior (i.e., anastrozole or letrozole) and information as to the optimal treatment strategy (i.e., initial adjuvant aromatase inhibitor therapy or sequential adjuvant aromatase inhibitor therapy).

Can Biannual Ultrasound Surveillance Detect Smaller Second Cancers or Detect Cancers Earlier in Patients with Breast Cancer History?

PubMed

You, Jai Kyung; Song, Mi Kyung; Kim, Min Jung; Kim, Eun-Kyung; Moon, Hee Jung; Youk, Ji Hyun; Yoon, Jung Hyun; Park, Vivian Youngjean; Park, Seho; Kim, Seung Il; Park, Byeong-Woo

2018-07-01

The aim of the work described here was to evaluate whether surveillance with biannual ultrasound (US) plus annual mammography (biannual group) for women with a history of breast cancer surgery results in earlier detection or in the detection of smaller second cancers than annual US plus mammography (annual group). Additionally, we compared the prevalence of distant metastases or palpable second cancers between the biannual and annual groups. The institutional review board of our institution approved this retrospective study, and patient consent was waived. Between January 2011 and December 2012, we retrospectively reviewed the clinical and imaging follow-up of 3023 patients with mammographic and US surveillance after breast cancer surgery to assess second cancers detected by local surveillance (locoregional recurrence, contralateral breast cancer or distant metastasis). The biannual and annual groups were divided with respect to the mean surveillance interval and compared with respect to clinicopathologic findings. Multivariable logistic regression with propensity score methods was used to examine the effect of the type of surveillance on outcomes. As for the size of the second cancer, no difference was seen between the biannual and annual groups (12.8 ± 6.6 mm vs. 14.1 ± 7.1 mm, p = 0.461); neither was there a significant difference between the groups in the presence of symptoms at the time of diagnosis of the second cancer (17.0% [8/47] vs. 10% [2/20], p = 0.711). Regardless of detection by local surveillance, the prevalence of distant metastases did not differ between the two groups (1.1% [27/2370] vs. 1.0% [7/653], p = 0.88) on univariate or multivariate analysis. The results of our retrospective study indicate that second cancers detected by biannual US surveillance in patients with a history of breast cancer surgery are not smaller and do not occur earlier than those detected by annual US surveillance. However, a randomized controlled study is required to verify these results before they can be generalized to clinical practice. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Impact of systemic targeted agents on the clinical outcomes of patients with brain metastases

PubMed Central

Johnson, Adam G.; Ruiz, Jimmy; Hughes, Ryan; Page, Brandi R.; Isom, Scott; Lucas, John T.; McTyre, Emory R.; Houseknecht, Kristin W.; Ayala-Peacock, Diandra N.; Bourland, Daniel J.; Hinson, William H.; Laxton, Adrian W.; Tatter, Stephen B.; Debinski, Waldemar; Watabe, Kounosuke; Chan, Michael D.

2015-01-01

Background To determine the clinical benefits of systemic targeted agents across multiple histologies after stereotactic radiosurgery (SRS) for brain metastases. Methods Between 2000 and 2013, 737 patients underwent upfront SRS for brain metastases. Patients were stratified by whether or not they received targeted agents with SRS. 167 (23%) received targeted agents compared to 570 (77%) that received other available treatment options. Time to event data were summarized using Kaplan-Meier plots, and the log rank test was used to determine statistical differences between groups. Results Patients who received SRS with targeted agents vs those that did not had improved overall survival (65% vs. 30% at 12 months, p < 0.0001), improved freedom from local failure (94% vs 90% at 12 months, p = 0.06), improved distant failure-free survival (32% vs. 18% at 12 months, p = 0.0001) and improved freedom from whole brain radiation (88% vs. 77% at 12 months, p = 0.03). Improvement in freedom from local failure was driven by improvements seen in breast cancer (100% vs 92% at 12 months, p < 0.01), and renal cell cancer (100% vs 88%, p = 0.04). Multivariate analysis revealed that use of targeted agents improved all cause mortality (HR = 0.6, p < 0.0001). Conclusions Targeted agent use with SRS appears to improve survival and intracranial outcomes. PMID:26087184

Bone-Induced Expression of Tumoral Integrin beta3 Enables Targeted Nanotherapy of Breast Cancer Metastases

NASA Astrophysics Data System (ADS)

Ross, Michael H.

Breast cancer is the most common cancer for women worldwide, representing approximately 25% of all new cancer cases in this population. While early detection and removal of breast cancer still confined to the primary site results in a good prognosis, approximately one- third of patients will develop distant metastases. In these patients, overall survival is markedly reduced. Of the common sites for breast cancer metastasis, the skeletal system is the most frequent. Treating breast cancer bone metastases has proven particularly difficult for several reasons, such as dissemination of metastases throughout the skeleton, poor drug localization to sites of interest, a lack of tumor-specific targets expressed across breast cancer subtypes, and the chemo-protective nature of the bone microenvironment. This dissertation is focused on investigating a potential tumor-target expressed on breast cancer bone metastases, and to improve drug treatment efficacy against tumor cells in the bone microenvironment. Integrins are heterodimeric cell surface receptors, composed of an alpha and beta subunit from a large family of selectively-compatible integrin subunits. As a heterodimeric complex, integrins can bind to components of the extracellular matrix or to other cells. One particular integrin complex, integrin alphavbeta3, is composed of the tightly regulated integrin subunit beta3 and the more widely expressed alphav subunit. I examined the expression of integrin beta3 on primary breast cancer as compared to metastases in murine cancer models, and observed that integrin expression is significantly elevated on bone metastases as compared to the primary tumors or visceral metastases. In addition, I evaluated tumor-associated integrin beta3 expression on a tissue microarray (TMA) composed of primary breast cancer and patient-matched bone metastatic tissue from 42 patients. Across nearly all patients, tumor-associated integrin beta3 expression was significantly elevated on bone metastases as compared to the primary tumor. For the first time, I demonstrate that tumor-associated integrin beta3 is elevated on bone metastases across all breast cancer subtypes, supporting the translational potential of targeting integrin beta3 in breast cancer patients with bone metastases. Integrin beta3 was weakly expressed on tumor cells in vitro and on tumor cells in the primary mammary fat pad (MFP). Additional analysis demonstrated that integrin beta3 on circulating tumor cells is dispensable for strong expression of integrin beta3 on subsequent bone metastases, suggested that integrin beta3 may be induced within the bone microenvironment. I identified transforming growth factor beta (TGF-beta) to be a potent inducer of integrin beta3 in vitro, and further demonstrate canonical TGF-beta signaling through the SMAD2 and SMAD3 (SMAD2/3) pathway is responsible for breast cancer upregulation of integrin beta3 induction on bone metastases, both in vitro and in vivo. Utilizing this information, I sought to evaluate the targeting potential of nanotherapy coated with a targeting ligand specific for integrin alphavbeta3. Nanotherapy has the potential to increase therapeutic efficacy and reduce toxicity versus traditional chemotherapies by enhancing drug delivery to specific targets of interest. I explored the localization potential of two nanoparticles with significantly different sizes: polysorbate (tween) 80 micelle nanoparticles (MPs, 12.5 nm) or perfluorocarbon (PFC) nanoparticles ( 250 nm). The smaller integrin alphavbeta3- targeted micelle nanoparticle (alphavbeta3-MP) could more effectively penetrate breast cancer bone metastases than larger integrin alphavbeta3-targeted PFC nanoparticles (alphavbeta3-PFCs). With these observations, I evaluated whether alphavbeta3-MP-mediated drug delivery could more effectively attenuate bone metastatic tumor burden and bone destruction than free drug delivery. Using the chemotherapeutic agent docetaxel (DTX), a potent microtubule inhibitor that is a first-line therapy for metastatic breast cancer, I observe that DTX is only weakly tumor- suppressive in our mouse model of breast cancer metastases. However, treating mice bearing breast cancer metastases with alphavbeta3-MP-delivery of a docetaxel-prodrug (DTX-PD) significantly reduced bone tumor burden and bone destruction, and with less hepatotoxicity. I observed a significant decrease in bone-residing tumor cell proliferation in mice treated with alphavbeta3-MP- delivery of DTX-PD, without overt osteoclast killing or inhibition of osteoclast formation. Together, these results provide support that nanotherapy-mediated attenuation of bone metastases and bone destruction occurs through enhanced drug efficacy against breast cancer cells within the bone. In this Dissertation, Chapter 1 will provide an overview of breast cancer, bone metastases, integrins, and the therapeutic potential of nanotherapy. In Chapter 2, my work on the expression and physiologic regulation of integrin beta3 on breast cancer during metastases will be explored. In Chapter 3, the role of the cytokine TGF-beta in regulating tumoral expression of integrin beta3 will be discussed. And in Chapter 4, I discuss the use of integrin alphavbeta3-targeted nanotherapy directed against breast cancer metastases. Collectively, I provide evidence that chemotherapeutic efficacy against breast cancer cells within bone can be enhanced by exploiting the expression of tumoral integrin beta3 at that metastatic site.

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

Koyfman, Shlomo A.; Tendulkar, Rahul D.; Chao, Samuel T.

Purpose: To assess the imaging and clinical outcomes of patients with single brainstem metastases treated with stereotactic radiosurgery (SRS). Materials and Methods: We retrospectively reviewed the data from patients with single brainstem metastases treated with SRS. Locoregional control and survival were calculated using the Kaplan-Meier method. Prognostic factors were assessed using a Cox proportional hazards model. Results: Between 1997 and 2007, 43 patients with single brainstem metastases were treated with SRS. The median age at treatment was 59 years, the median Karnofsky performance status was 80, and the median follow-up was 5.3 months. The median dose was 15 Gy (range,more » 9.6-24), and the median conformality and heterogeneity index was 1.7 and 1.9, respectively. The median survival was 5.8 months from the procedure date. Of the 33 patient with post-treatment imaging available, a complete radiographic response was achieved in 2 (4.7%), a partial response in 8 (18.6%), and stable disease in 23 (53.5%). The 1-year actuarial rate of local control, distant brain control, and overall survival was 85%, 38.3%, and 31.5%, respectively. Of the 43 patients, 8 (19%) died within 2 months of undergoing SRS, and 15 (36%) died within 3 months. On multivariate analysis, greater performance status (hazard ratio [HR], 0.95, p = .004), score index for radiosurgery (HR, 0.7; p = .004), graded prognostic assessment score (HR, 0.48; p = .003), and smaller tumor volume (HR, 1.23, p = .002) were associated with improved survival. No Grade 3 or 4 toxicities were observed. Conclusion: The results of our study have shown that SRS is a safe and effective local therapy for patients with brainstem metastases.« less

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.

Increasing time to postoperative stereotactic radiation therapy for patients with resected brain metastases: investigating clinical outcomes and identifying predictors associated with time to initiation.

PubMed

Yusuf, Mehran B; Amsbaugh, Mark J; Burton, Eric; Nelson, Megan; Williams, Brian; Koutourousiou, Maria; Nauta, Haring; Woo, Shiao

2018-02-01

We sought to determine the impact of time to initiation (TTI) of post-operative radiosurgery on clinical outcomes for patients with resected brain metastases and to identify predictors associated with TTI. All patients with resected brain metastases treated with postoperative SRS or fractionated stereotactic radiation therapy (fSRT) from 2012 to 2016 at a single institution were reviewed. TTI was defined as the interval from resection to first day of radiosurgery. Receiver operating characteristic (ROC) curves were used to identify an optimal threshold for TTI with respect to local failure (LF). Survival outcomes were estimated using the Kaplan-Meier method and analyzed using the log-rank test and Cox proportional hazards models. Logistic regression models were used to identify factors associated with ROC-determined TTI covariates. A total of 79 resected lesions from 73 patients were evaluated. An ROC curve of LF and TTI identified an optimal threshold for TTI of 30.5 days, with an area under the curve of 0.637. TTI > 30 days was associated with an increased hazard of LF (HR 4.525, CI 1.239-16.527) but was not significantly associated with survival (HR 1.002, CI 0.547-1.823) or distant brain failure (DBF, HR 1.943, CI 0.989-3.816). Fifteen patients (20.5%) required post-operative inpatient rehabilitation. Post-operative rehabilitation was associated with TTI > 30 days (OR 1.48, CI 1.142-1.922). In our study of resected brain metastases, longer time to initiation of post-operative radiosurgery was associated with increased local failure. Ideally, post-op SRS should be initiated within 30 days of resection if feasible.

[Regression and therapy-resistance of primary liver tumors and liver metastases after regional chemotherapy and local tumor ablation].

PubMed

Fischer, H-P

2005-05-01

High dosage regional chemotherapy, chemoembolization and other methods of regional treatment are commonly used to treat unresectable primary liver malignancies and liver metastases. In liver malignancies of childhood neoadjuvant chemotherapy is successfully combined with surgical treatment. Chemotherapy and local tumor ablation lead to characteristic histomorphologic changes: Complete destruction of the tumor tissue and its vascular bed is followed by encapsulated necroses. After selective eradication of the tumor cells under preservation of the fibrovasular bed the tumor is replaced by hypocellular edematous and fibrotic tissue. If completely damaged tumor tissue is absorbed quickly, the tumor area is replaced by regenerating liver tissue. Obliterating fibrohyalinosis of tumor vessels, and perivascular edema or necrosis indicate tissue damage along the vascular bed. Degenerative pleomorphism of tumor cells, steatosis, hydropic swelling and Malloryhyalin in HCC can represent cytologic findings of cytotoxic cellular damage. Macroscopic type of HCC influences significantly the response to treatment. Multinodular HCC often contain viable tumor nodules close to destroyed nodules after treatment. Encapsulated uninodular tumors undergo complete necrosis much easier. Large size and a tumor capsule limitate the effect of percutaneous injection of ethanol into HCC. In carcinomas with an infiltrating border, especially in metastases of adenocarcinomas and hepatic cholangiocarcinoma cytostatic treatment damages the tumor tissue mainly in the periphery. Nevertheless the infiltrating rim, portal veins, lymphatic spaces and bile ducts as well as the angle between liver capsule, tumor nodule and bordering parenchyma are the main refugees of viable tumor tissue even after high dosage regional chemotherapy. This local resistance is caused by special local conditions of vascularization and perfusion. These residues are the source of local tumor progression and distant metastases. Besides intrinsic cellular mechanisms architectural, and microenvironmental factors relevantly limitate the effect of intensive locoregional therapy.

Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center.

PubMed

Suki, Dima; Khoury Abdulla, Rami; Ding, Minming; Khatua, Soumen; Sawaya, Raymond

2014-10-01

Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990-2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2-77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan-Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24-34 months) and 9 months (95% CI 6-11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3-1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6-11 months). The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy.

A prospective protocol for nasopharyngeal carcinoma in children and adolescents: the Italian Rare Tumors in Pediatric Age (TREP) project.

PubMed

Casanova, Michela; Bisogno, Gianni; Gandola, Lorenza; Cecchetto, Giovanni; Di Cataldo, Andrea; Basso, Eleonora; Indolfi, Paolo; D'Angelo, Paolo; Favini, Francesca; Collini, Paola; Potepan, Paolo; Ferrari, Andrea

2012-05-15

Nasopharyngeal carcinoma (NPC) is very rare in childhood. It differs from its adult counterpart in the prevalence of the nonkeratinizing, undifferentiated subtype and by an advanced clinical stage at onset and better chances of survival. The risk of long-term treatment-related toxicity also may be a more important issue in younger individuals. A prospective chemoradiotherapy protocol for pediatric NPC was started in Italy in 2000 within the framework of the Rare Tumors in Pediatric Age (TREP) project. Three courses of cisplatin/5-fluorouracil induction chemotherapy were followed by radiotherapy (doses up to 65 grays) with concomitant cisplatin. Forty-six patients (ages 9-17 years) were considered eligible for the study over a 10-year period. The ratio of observed to expected cases based on epidemiological data was approximately 1 for both children and adolescents. All but 1 patient had lymph node involvement, and 5 patients had distant metastases. The rate of response to primary chemotherapy was 90%. The 5-year overall and progression-free survival rates were 80.9% and 79.3%, respectively (median follow-up, 62 months). The only statistically significant prognostic variable was the presence or absence of distant metastases. A 65% incidence of late sequelae was reported. This study demonstrates the feasibility and efficacy of a prospective protocol even for such rare tumors as pediatric NPC. The use of lower radiotherapy doses than those used in adults did not affect locoregional failure rates. Long-term follow-up will be needed to obtain more information on both survival and treatment sequelae. The next objective will be to establish broader, international prospective cooperation schemes. Copyright © 2011 American Cancer Society.

Osteosarcoma subtypes: Magnetic resonance and quantitative diffusion weighted imaging criteria.

PubMed

Zeitoun, Rania; Shokry, Ahmed M; Ahmed Khaleel, Sahar; Mogahed, Shaimaa M

2018-03-01

Osteosarcoma (OS) is a primary bone malignancy, characterized by spindle cells producing osteoid. The objective of this study is to describe the magnetic resonance imaging (MRI) features of different OS subtypes, record their attenuation diffusion coefficient (ADC) values and to point to the relation of their pathologic base and their corresponding ADC value. We performed a retrospective observational lesion-based analysis for 31 pathologically proven osteosarcoma subtypes: osteoblastic (n = 9), fibroblastic (n = 8), chondroblastic (n = 6), para-osteal (n = 3), periosteal (n = 1), telangiectatic (n = 2), small cell (n = 1) and extra-skeletal (n = 1). On conventional images we recorded: bone of origin, epicenter, intra-articular extension, and invasion of articulating bones, skip lesions, distant metastases, pathological fractures, ossified matrix, hemorrhage and necrosis. We measured the mean ADC value for each lesion. Among the included OS lesions, 51.6% originated at the femur, 29% showed intra-articular extension, 16% invaded neighboring bone, 9% were associated with pathological fracture and 25.8% were associated with distant metastases. On MRI, all lesions showed ossified matrix, 35.5% showed hemorrhage and 58% showed necrosis. The mean ADC values for OS lesions ranged from 0.74 × 10 -3  mm 2 /s (recorded for conventional osteoblastic OS) to 1.50 × 10 -3  mm 2 /s (recorded for telangiectatic OS) with an average value of 1.16 ± 0.18 × 10 -3  mm 2 /s. Conventional chondroblastic OS recorded higher values compared to the other two conventional subtypes. Osteosarcoma has different pathologic subtypes which correspondingly vary in their imaging criteria and their ADC values. Copyright © 2018. Production and hosting by Elsevier B.V.

The role of FDG PET/CT in patients with locoregional breast cancer recurrence: a comparison to conventional imaging techniques.

PubMed

Aukema, T S; Rutgers, E J Th; Vogel, W V; Teertstra, H J; Oldenburg, H S; Vrancken Peeters, M T F D; Wesseling, J; Russell, N S; Valdés Olmos, R A

2010-04-01

The aim of this study was to evaluate the impact of (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) on clinical management in patients with locoregional breast cancer recurrence amenable for locoregional treatment and to compare the PET/CT results with the conventional imaging data. From January 2006 to August 2008, all patients with locoregional breast cancer recurrence underwent whole-body PET/CT. PET/CT findings were compared with results of the conventional imaging techniques and final pathology. The impact of PET/CT results on clinical management was evaluated based on clinical decisions obtained from patient files. 56 patients were included. In 32 patients (57%) PET/CT revealed additional tumour localisations. Distant metastases were detected in 11 patients on conventional imaging and in 23 patients on PET/CT images (p < 0.01). In 25 patients (45%), PET/CT detected additional lesions not visible on conventional imaging. PET/CT had an impact on clinical management in 27 patients (48%) by detecting more extensive locoregional disease or distant metastases. In 20 patients (36%) extensive surgery was prevented and treatment was changed to palliative treatment. The sensitivity, specificity, accuracy, positive and negative predictive values of FDG PET/CT were respectively 97%, 92%, 95%, 94% and 96%. PET/CT, in addition to conventional imaging techniques, plays an important role in staging patients with locoregional breast cancer recurrence since its result changed the clinical management in almost half of the patients. PET/CT could potentially replace conventional staging imaging in patients with a locoregional breast cancer recurrence. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Clinical and Organizational Factors in the Initial Evaluation of Patients With Lung Cancer

PubMed Central

Jim Yeung, Sai-Ching; Tanoue, Lynn T.; Gould, Michael K.

2013-01-01

Background: This guideline is intended to provide an evidence-based approach to the initial evaluation of patients with known or suspected lung cancer. It also includes an assessment of the impact of timeliness of care and multidisciplinary teams on outcome. Methods: The applicable current medical literature was identified by a computerized search and evaluated using standardized methods. Recommendations were framed using the approach described by the Guidelines Oversight Committee of the American College of Chest Physicians. Data sources included MEDLINE and the Cochrane Database of Systematic Reviews. Results: Initial evaluation should include a thorough history and physical examination; CT imaging; pulmonary function tests; and hemoglobin, electrolyte, liver function, and calcium levels. Additional testing for distant metastases and paraneoplastic syndromes should be determined on the basis of these results. Paraneoplastic syndromes may have an adverse impact on cancer treatment, so they should be controlled rapidly with the goal of proceeding with definitive cancer treatment in a timely manner. Although the relationship between timeliness of care and survival is difficult to quantify, efforts to deliver timely care are reasonable and should be balanced with the need to attend to other dimensions of health-care quality (eg, safety, effectiveness, efficiency, equality, consistency with patient values and preferences). Quality care will require multiple disciplines. Although it is difficult to assess the impact, we suggest that a multidisciplinary team approach to care be used, particularly for patients requiring multimodality therapy. Conclusions: The initial evaluation of patients with lung cancer should include a thorough history and physical examination, pulmonary function tests, CT imaging, basic laboratory tests, and selective testing for distant metastases and paraneoplastic syndromes. PMID:23649435

External validity of two nomograms for predicting distant brain failure after radiosurgery for brain metastases in a bi-institutional independent patient cohort.

PubMed

Prabhu, Roshan S; Press, Robert H; Boselli, Danielle M; Miller, Katherine R; Lankford, Scott P; McCammon, Robert J; Moeller, Benjamin J; Heinzerling, John H; Fasola, Carolina E; Patel, Kirtesh R; Asher, Anthony L; Sumrall, Ashley L; Curran, Walter J; Shu, Hui-Kuo G; Burri, Stuart H

2018-03-01

Patients treated with stereotactic radiosurgery (SRS) for brain metastases (BM) are at increased risk of distant brain failure (DBF). Two nomograms have been recently published to predict individualized risk of DBF after SRS. The goal of this study was to assess the external validity of these nomograms in an independent patient cohort. The records of consecutive patients with BM treated with SRS at Levine Cancer Institute and Emory University between 2005 and 2013 were reviewed. Three validation cohorts were generated based on the specific nomogram or recursive partitioning analysis (RPA) entry criteria: Wake Forest nomogram (n = 281), Canadian nomogram (n = 282), and Canadian RPA (n = 303) validation cohorts. Freedom from DBF at 1-year in the Wake Forest study was 30% compared with 50% in the validation cohort. The validation c-index for both the 6-month and 9-month freedom from DBF Wake Forest nomograms was 0.55, indicating poor discrimination ability, and the goodness-of-fit test for both nomograms was highly significant (p < 0.001), indicating poor calibration. The 1-year actuarial DBF in the Canadian nomogram study was 43.9% compared with 50.9% in the validation cohort. The validation c-index for the Canadian 1-year DBF nomogram was 0.56, and the goodness-of-fit test was also highly significant (p < 0.001). The validation accuracy and c-index of the Canadian RPA classification was 53% and 0.61, respectively. The Wake Forest and Canadian nomograms for predicting risk of DBF after SRS were found to have limited predictive ability in an independent bi-institutional validation cohort. These results reinforce the importance of validating predictive models in independent patient cohorts.

Treatment patterns and outcomes of Stage IIIB/IIIC melanoma in France, Germany and the UK: A retrospective and prospective observational study (MELABIS).

PubMed

Harries, Mark; Mohr, Peter; Grange, Florent; Ehness, Rainer; Benjamin, Laure; Siakpere, Obukohwo; Barth, Janina; Stapelkamp, Ceilidh; Pfersch, Sylvie; McLeod, Lori; Wolowacz, Sorrel; Kaye, James A; Kontoudis, Ilias

2017-05-01

Real-world data on treatment patterns/outcomes in patients with advanced melanoma, while scarce, are useful for health technology assessments that govern patient access in many countries. We collected retrospective data on treatment patterns among patients in France, Germany and the UK with Stage IIIB/IIIC melanoma with macroscopic lymph node involvement, whose primary melanoma and regional lymph node metastases had been completely resected. Patients ≥18 years were diagnosed between 1 January 2009 and 31 December 2011. Data were obtained from patients' medical records and a patient survey. Forty-nine centres provided data on 558 patients: 53.6% had Stage IIIB disease; 58.2% were of working age (<65 years), 22.5% reported a change in employment status due to melanoma, 8% were on long-term sick leave; and 35.1% were deceased over the study period. Overall median distant metastases-free survival was 23.4 months and median disease-free survival was 13.3 months. Hospitalisation frequency increased during distant metastatic/terminal disease phases. Adjuvant therapy was received by 7.0% (14/199) of patients in France, 2.6% (5/195) in the UK, and 33.5% (55/164) in Germany. Low-dose interferon was used more frequently than other regimens. High-dose interferon was associated with discontinuation in 28.6% and dose delay/reduction in 33.3% of patients. Rapid disease progression combined with increased use of healthcare resources in later phases of disease result in a high burden-of-illness for patients and healthcare providers. The use of adjuvant interferon therapy varies considerably in this population in the countries studied, highlighting the need for improved treatments for melanoma. © 2017 John Wiley & Sons Ltd.

Prognostic Value of External Beam Radiation Therapy in Patients Treated With Surgical Resection and Intraoperative Electron Beam Radiation Therapy for Locally Recurrent Soft Tissue Sarcoma: A Multicentric Long-Term Outcome Analysis

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

Calvo, Felipe A.; School of Medicine, Complutense University, Madrid; Sole, Claudio V., E-mail: cvsole@uc.cl

Background: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. Methods and Materials: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). Results: From 1986 to 2012, a totalmore » of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically involved margin resection status (P=.04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P=.03). Conclusion: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy.« less

Role of External Beam Radiotherapy in Patients With Advanced or Recurrent Nonanaplastic Thyroid Cancer: Memorial Sloan-Kettering Cancer Center Experience

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

Terezakis, Stephanie A.; Lee, Kyungmouk S.; Ghossein, Ronald A.

2009-03-01

Purpose: External beam radiotherapy (EBRT) plays a controversial role in the management of nonanaplastic thyroid cancer. We reviewed our institution's outcomes in patients treated with EBRT for advanced or recurrent nonanaplastic thyroid cancer. Methods and Materials: Between April 1989 and April 2006, 76 patients with nonanaplastic thyroid cancer were treated with EBRT. The median follow-up for the surviving patients was 35.3 months (range, 4.2-178.4). The lesions were primarily advanced and included Stage T2 in 5 (7%), T3 in 5 (7%), and T4 in 64 (84%) patients. Stage N1 disease was present in 60 patients (79%). Distant metastases before EBRT weremore » identified in 27 patients (36%). The median total EBRT dose delivered was 6,300 cGy. The histologic features examined included medullary in 12 patients (16%) and nonmedullary in 64 (84%). Of the 76 patients, 71 (93%) had undergone surgery before RT, and radioactive iodine treatment was used in 56 patients (74%). Results: The 2- and 4-year overall locoregional control rate for all histologic types was 86% and 72%, respectively, and the 2- and 4-year overall survival rate for all patients was 74% and 55%, respectively. No significant differences were found in locoregional control, overall survival, or distant metastases-free survival for patients with complete resection, microscopic residual disease, or gross residual disease. Grade 3 acute mucositis and dysphagia occurred in 14 (18%) and 24 (32%) patients, respectively. Late adverse toxicity was notable for percutaneous endoscopic gastrostomy tube use in 4 patients (5%). Conclusion: The results of our study have shown that EBRT is effective for locoregional control of selected locally advanced or recurrent nonanaplastic thyroid malignancies, with acceptable acute toxicity.« less

99mTc-EDDA/HYNIC-TOC in the management of medullary thyroid carcinoma.

PubMed

Parisella, Maria; D'Alessandria, Calogero; van de Bossche, Bieke; Chianelli, Marco; Ronga, Giuseppe; Papini, Enrico; Mikolajczak, Renata; Letizia, Claudio; De Toma, Giorgio; Veneziani, Augusto; Scopinaro, Francesco; Signore, Alberto

2004-04-01

An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC) can be achieved by several conventional radiological modalities (e.g., ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI] as well as by radioisotopic procedures, such as positron emission tomography (PET), scintigraphy with different types of radiopharmaceuticals, and radiolabeled receptor-ligands in particular. The aim of this study was to evaluate the clinical utility of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative, to detect recurrences of disease or distant metastases in MTC. Images obtained of 5 patients with high levels of serum calcitonin were compared to findings obtained with other diagnostic procedures: 111In-octreotide, 99mTc-DMSA-V, 18F-flouro-D-deoxyglucose-PET, and CT/MRI. 99mTc-EDDA/HYNIC-TOC was positive in all patients and showed 15 areas of pathological uptake in the cervical and mediastinal regions. 111In-octreotide was positive in 3 of 3 patients and showed 4 areas, compared to 8 of 99mTc-EDDA/HYNIC-TOC. 99mTc-V-DMSA was positive in 3 of 4 patients but showed 6 pathological areas, compared to 13 of 99mTc-EDDA/HYNIC-TOC. 18F-FDG-PET was positive in 5 of 5 patients but showed only 11 areas, compared to 15 of 99mTc-EDDA/HYNIC-TOC. The CT scan was positive in only 2 patients. In conclusion, 99mTc-EDDA/HYNIC-TOC detected more sites of pathological uptake than other modalities, showed better imaging properties than 111In-octreotide, and might be the radiopharmaceutical of choice for providing a rationale for radioisotopic therapy.

Risk Profile of the RET A883F Germline Mutation: An International Collaborative Study.

PubMed

Mathiesen, Jes Sloth; Habra, Mouhammed Amir; Bassett, John Howard Duncan; Choudhury, Sirazum Mubin; Balasubramanian, Sabapathy Prakash; Howlett, Trevor A; Robinson, Bruce G; Gimenez-Roqueplo, Anne-Paule; Castinetti, Frederic; Vestergaard, Peter; Frank-Raue, Karin

2017-06-01

The A883F germline mutation of the rearranged during transfection (RET) proto-oncogene causes multiple endocrine neoplasia 2B. In the revised American Thyroid Association (ATA) guidelines for the management of medullary thyroid carcinoma (MTC), the A883F mutation has been reclassified from the highest to the high-risk level, although no well-defined risk profile for this mutation exists. To create a risk profile for the A883F mutation for appropriate classification among the ATA risk levels. Retrospective analysis. International collaboration. Included were 13 A883F carriers. The intervention was thyroidectomy. Earliest age of MTC, regional lymph node metastases, distant metastases, age-related penetrance of MTC and pheochromocytoma (PHEO), overall and disease-specific survival, and biochemical cure rate. One and three carriers were diagnosed at age 7 to 9 years (median, 7.5 years) with a normal thyroid and C-cell hyperplasia, respectively. Nine carriers were diagnosed with MTC at age 10 to 39 years (median, 19 years). The earliest age of MTC, regional lymph node metastasis, and distant metastasis was 10, 20, and 20 years, respectively. Fifty percent penetrance of MTC and PHEO was achieved by age 19 and 34 years, respectively. Five- and 10-year survival rates (both overall and disease specific) were 88% and 88%, respectively. Biochemical cure for MTC at latest follow-up was achieved in 63% (five of eight carriers) with pertinent data. MTC of A883F carriers seems to have a more indolent natural course compared with that of M918T carriers. Our results support the classification of the A883F mutation in the ATA high-risk level. Copyright © 2017 Endocrine Society

Expression of NF-κB p50 in Tumor Stroma Limits the Control of Tumors by Radiation Therapy

PubMed Central

Crittenden, Marka R.; Cottam, Benjamin; Savage, Talicia; Nguyen, Cynthia; Newell, Pippa; Gough, Michael J.

2012-01-01

Radiation therapy aims to kill cancer cells with a minimum of normal tissue toxicity. Dying cancer cells have been proposed to be a source of tumor antigens and may release endogenous immune adjuvants into the tumor environment. For these reasons, radiation therapy may be an effective modality to initiate new anti-tumor adaptive immune responses that can target residual disease and distant metastases. However, tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice, there is an influx of tumor macrophages that ultimately polarize towards immune suppression. We demonstrate using in vitro models that this polarization is mediated by transcriptional regulation by NFκB p50, and that in mice lacking NFκB p50, radiation therapy is more effective. We propose that despite the opportunity for increased antigen-specific adaptive immune responses, the intrinsic processes of repair following radiation therapy may limit the ability to control residual disease. PMID:22761754

Protective, elective lung irradiation in non-metastatic Ewing's sarcoma.

PubMed

Marinova, L; Hristozova, I; Mihaylova, I; Perenovska, P

2015-07-01

Ewing's sarcoma in childhood is a disease from family of the peripheral primitive neuroectodermal tumours. For a period of 16 y (1984-2000), 34 children with Ewing's sarcoma were treated and followed in our department. Twenty-seven of these patients were without distant metastases. Complex treatment was applied to all these patients-chemotherapy VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin), local radiotherapy to a total dose of 50-56 Gy +/- surgery. After, a local tumour control was achieved in 11 children with non-metastatic Ewing's sarcoma, elective whole lung irradiation to a total dose of 12-15 Gy was applied. Our experience in these 11 patients with non-metastatic Ewing's sarcoma, in whom elective lung irradiation was applied, showed significant reduction in the lung metastases, improved free of disease survival and overall survival. The achieved good treatment results necessitate extending this treatment approach through defining the risk groups of patients, suitable for elective lung radiotherapy combined with chemotherapy in non-metastatic Ewing's sarcoma. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The novel WHO 2010 classification for gastrointestinal neuroendocrine tumours correlates well with the metastatic potential of rectal neuroendocrine tumours.

PubMed

Jernman, Juha; Välimäki, Matti J; Louhimo, Johanna; Haglund, Caj; Arola, Johanna

2012-01-01

Approximately 10-15% of gastroenteropancreatic neuroendocrine tumours (NETs, carcinoids) occur in the rectum, some of which are potentially able to metastasize. The new WHO 2010 classification of NETs applies to all gastroenteropancreatic NETs, but no reports have studied its correlation with the prognosis of rectal NETs. We retrospectively classified 73 rectal NETs according to the novel WHO 2010 and the previous WHO 2000 classifications. The aim was to assess the validity of the classifications in distinguishing indolent rectal NETs from metastasising tumours. Using the WHO 2010 criteria, we identified 61 G1 tumours, none of which had metastasised during follow-up. Of 11 G2 tumours, 9 had shown distant metastases. The only G3 neuroendocrine carcinoma that occurred had been disseminated at initial presentation. Our results show that rectal NETs classified as G1 according to the WHO 2010 classification have an indolent clinical course, whereas G2 NETs often metastasise. The WHO 2010 classification of NETs predicts the metastatic potential of rectal NETs better than the WHO 2000 classification. Copyright © 2011 S. Karger AG, Basel.

Metastasis to the appendix from adenocarcinoma of the ascending colon

PubMed Central

Li, Yingjie; Li, Mingshan; Li, Xiaoxia; Sang, Haiquan

2017-01-01

Abstract Rationale: Metastasis of cancer cells involves shedding from the primary tumor through various means to distant tissues and organs with continued growth and formation of new metastatic tumors of the same cancer type as the original tumor. The common sites for colon cancer metastases include the pelvis, retroperitoneal lymph nodes, liver, and lungs; Colon cancer metastases to the appendix are rare, as reported in this case. Patient concerns and diagnoses: A 45-year-old man was admitted to our department with a 24-hour history of abdominal distension and incomplete obstruction. Colonoscopy showed an elevated lesion in the ascending colon and the pathologic diagnosis was adenocarcinoma. Interventions and outcomes: This patient underwent a radical right hemi-colectomy. The post-operative pathologic examination revealed metastatic adenocarcinoma in all layers of the appendix, especially the muscularis mucosae. The diagnosis was adenocarcinoma of the ascending colon (pT4bN2bM0 stage IIIC) with metastatic adenocarcinoma of the appendix. Lessons: An absent right colic artery with lymph node fusion might increase the risk of appendiceal cancer metastasis. PMID:28296772

First Case of the Cervical Lymph Node as the Only Site of Metastasis from Anal Cancer.

PubMed

Wang, Bo; Jaiswal, Sunny; Saif, Muhammad W

2017-05-30

Anal squamous cell carcinoma was a previously uncommon malignancy that has steadily increased in incidence with the increased prevalence of human papillomavirus (HPV) and human immunodeficiency virus (HIV). Anal squamous cell carcinoma is typically characterized by local and regional involvement and distant metastases are far less common. Here, we report a case of a 36-year-old female initially diagnosed with anal squamous cell carcinoma manifesting as an anal mass along with an enlarged inguinal lymph node. After receiving chemoradiation therapy, she remained disease-free until recently, when she presented with an isolated left infraclavicular lymph node found on physical examination followed by a biopsy that was consistent with recurrent anal squamous cell carcinoma. The positron emission tomography-computed tomography (PET-CT) uptake of her original left inguinal lymph node was decreased, suggesting improved regional disease, and no other metastases were found. Our case represents a rare occurrence of metastatic anal squamous cell carcinoma to an isolated distal lymph node and reminds physicians not to forget a unusual site of metastasis and prevent any delay in treatment.

Lymph Nodes and Survival in Pancreatic Neuroendocrine Tumors (pNET)

PubMed Central

Krampitz, Geoffrey W.; Norton, Jeffrey A.; Poultsides, George A.; Visser, Brendan C.; Sun, Lixian; Jensen, Robert T.

2012-01-01

Background The significance of lymph node metastases on survival of patients with pNET is controversial. Hypothesis Lymph node metastases decrease survival in patients with pNET. Design Prospective databases of the National Institutes of Health (NIH) and Stanford University Hospital (SUH) were queried. Main Outcome Measures Overall survival, disease-related survival, and time to development of liver metastases Results 326 underwent surgical exploration for pNET at the NIH (n=216) and SUH (n=110). 40 (13%) and 305 (94%) underwent enucleation and resection, respectively. Of the patients who underwent resection, 117 (42%) had partial pancreatectomy and 30 (11%) had a Whipple procedure. 41 also had liver resections, 21 wedge resections and 20 lobectomies. Average follow-up was 8 years (range 0.3–28.6 years). The 10-year overall survival for patients with no metastases or lymph node metastases only was similar at 80%. As expected, patients with liver metastases had a significantly decreased 10-year survival of 30% (p<0.001). The time to development of liver metastases was significantly reduced for patients with lymph node metastases alone compared to those with none (p<0.001). For the NIH cohort with longer follow-up, disease-related survival was significantly different for those patients with no metastases, lymph node metastases alone, and liver metastases (p<0.0001). Extent of lymph node involvement in this subgroup showed that disease-related survival decreased as a function of number of lymph nodes involved (p=0.004). Conclusion As expected, liver metastases decrease survival of patients with pNET. Patients with lymph node metastases alone have a shorter time to development of liver metastases that is dependent on the number of lymph nodes involved. With sufficient long-term follow-up, lymph node metastases decrease disease-related survival. Careful evaluation of number and extent of lymph node involvement is warranted in all surgical procedures for pNET. PMID:22987171

The biology and therapeutic management of melanoma brain metastases.

PubMed

Abate-Daga, Daniel; Ramello, Maria C; Smalley, Inna; Forsyth, Peter A; Smalley, Keiran S M

2018-07-01

The recent years have seen significant progress in the development of systemic therapies to treat patients with advanced melanoma. Use of these new treatment modalities, which include immune checkpoint inhibitors and small molecule BRAF inhibitors, lead to increased overall survival and better outcomes. Although revolutionary, these therapies are often less effective against melanoma brain metastases, and frequently the CNS is the major site of treatment failure. The development of brain metastases remains a serious complication of advanced melanoma that is associated with significant morbidity and mortality. New approaches to both prevent the development of brain metastases and treat established disease are urgently needed. In this review we will outline the mechanisms underlying the development of melanoma brain metastases and will discuss how new insights into metastasis biology are driving the development of new therapeutic strategies. Finally, we will describe the latest data from the ongoing clinical trials for patients with melanoma brain metastases. Copyright © 2018 Elsevier Inc. All rights reserved.

Comprehensive Clinical Staging for Resectable Lung Cancer: Clinicopathological Correlations and the Role of Brain MRI.

PubMed

Vernon, Jordyn; Andruszkiewicz, Nicole; Schneider, Laura; Schieman, Colin; Finley, Christian J; Shargall, Yaron; Fahim, Christine; Farrokhyar, Forough; Hanna, Waël C

2016-11-01

In our model of comprehensive clinical staging (CCS) for lung cancer, patients with a computerized tomography scan of the chest and upper abdomen not showing distant metastases will then routinely undergo whole body positron emission tomography/computerized tomography and magnetic resonance imaging (MRI) of the brain before any therapeutic decision. Our aim was to determine the accuracy of CCS and the value of brain MRI in this population. A retrospective analysis of a prospectively entered database was performed for all patients who underwent lung cancer resection from January 2012 to June 2014. Demographics, clinical and pathological stage (seventh edition of the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, and metastasis staging manual), and costs of staging were collected. Correlation between clinical and pathological stage was determined. Of 315 patients with primary lung cancer, 55.6% were female and the mean age was 70 ± 9.6 years. When correlation was analyzed without consideration for substages A and B, 49.8% of patients (158 of 315) were staged accurately, 39.7% (125 of 315) were overstaged, and 10.5% (32 of 315) were understaged. Only 4.7% of patients (15 of 315) underwent surgery without appropriate neoadjuvant treatment. Preoperative brain MRI detected asymptomatic metastases in four of 315 patients (1.3%). At a median postoperative follow-up of 19 months (range 6-43), symptomatic brain metastases developed in seven additional patients. The total cost of CCS in Canadian dollars was $367,292 over the study period, with $117,272 (31.9%) going toward brain MRI. CCS is effective for patients with resectable lung cancer, with less than 5% of patients being denied appropriate systemic treatment before surgery. Brain MRI is a low-yield and high-cost intervention in this population, and its routine use should be questioned. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Intensity-modulated radiotherapy for cervical node squamous cell carcinoma metastases from unknown head-and-neck primary site: M. D. Anderson Cancer Center outcomes and patterns of failure.

PubMed

Frank, Steven J; Rosenthal, David I; Petsuksiri, Janjira; Ang, K Kian; Morrison, William H; Weber, Randal S; Glisson, Bonnie S; Chao, K S Clifford; Schwartz, David L; Chronowski, Gregory M; El-Naggar, Adel K; Garden, Adam S

2010-11-15

Conventional therapy for cervical node squamous cell carcinoma metastases from an unknown primary can cause considerable toxicity owing to the volume of tissues to be irradiated. In the present study, hypothesizing that using intensity-modulated radiotherapy (IMRT) would provide effective treatment with minimal toxicity, we reviewed the outcomes and patterns of failure for head-and-neck unknown primary cancer at a single tertiary cancer center. We retrospectively reviewed the records of 52 patients who had undergone IMRT for an unknown primary at M.D. Anderson Cancer Center between 1998 and 2005. The patient and treatment characteristics were extracted and the survival rates calculated using the Kaplan-Meier method. Of the 52 patients, 5 presented with Stage N1, 11 with Stage N2a, 23 with Stage N2b, 6 with Stage N2c, 4 with Stage N3, and 3 with Stage Nx disease. A total of 26 patients had undergone neck dissection, 13 before and 13 after IMRT; 14 patients had undergone excisional biopsy and presented for IMRT without evidence of disease. Finally, 14 patients had received systemic chemotherapy. All patients underwent IMRT to targets on both sides of the neck and pharyngeal axis. The median follow-up time for the surviving patients was 3.7 years. The 5-year actuarial rate of primary mucosal tumor control and regional control was 98% and 94%, respectively. Only 3 patients developed distant metastasis with locoregional control. The 5-year actuarial disease-free and overall survival rate was 88% and 89%, respectively. The most severe toxicity was Grade 3 dysphagia/esophageal stricture, experienced by 2 patients. The results of our study have shown that IMRT can produce excellent outcomes for patients who present with cervical node squamous cell carcinoma metastases from an unknown head-and-neck primary tumor. Severe late complications were uncommon. Copyright © 2010 Elsevier Inc. All rights reserved.

Intensity-Modulated Radiotherapy for Cervical Node Squamous Cell Carcinoma Metastases From Unknown Head-and-Neck Primary Site: M. D. Anderson Cancer Center Outcomes and Patterns of Failure

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

Frank, Steven J., E-mail: sjfrank@mdanderson.or; Rosenthal, David I.; Petsuksiri, Janjira

2010-11-15

Purpose: Conventional therapy for cervical node squamous cell carcinoma metastases from an unknown primary can cause considerable toxicity owing to the volume of tissues to be irradiated. In the present study, hypothesizing that using intensity-modulated radiotherapy (IMRT) would provide effective treatment with minimal toxicity, we reviewed the outcomes and patterns of failure for head-and-neck unknown primary cancer at a single tertiary cancer center. Methods and Materials: We retrospectively reviewed the records of 52 patients who had undergone IMRT for an unknown primary at M.D. Anderson Cancer Center between 1998 and 2005. The patient and treatment characteristics were extracted and themore » survival rates calculated using the Kaplan-Meier method. Results: Of the 52 patients, 5 presented with Stage N1, 11 with Stage N2a, 23 with Stage N2b, 6 with Stage N2c, 4 with Stage N3, and 3 with Stage Nx disease. A total of 26 patients had undergone neck dissection, 13 before and 13 after IMRT; 14 patients had undergone excisional biopsy and presented for IMRT without evidence of disease. Finally, 14 patients had received systemic chemotherapy. All patients underwent IMRT to targets on both sides of the neck and pharyngeal axis. The median follow-up time for the surviving patients was 3.7 years. The 5-year actuarial rate of primary mucosal tumor control and regional control was 98% and 94%, respectively. Only 3 patients developed distant metastasis with locoregional control. The 5-year actuarial disease-free and overall survival rate was 88% and 89%, respectively. The most severe toxicity was Grade 3 dysphagia/esophageal stricture, experienced by 2 patients. Conclusion: The results of our study have shown that IMRT can produce excellent outcomes for patients who present with cervical node squamous cell carcinoma metastases from an unknown head-and-neck primary tumor. Severe late complications were uncommon.« less

More α Than β for Prostate Cancer?

DOE PAGES

Fendler, Wolfgang P.; Cutler, Cathy

2017-09-21

Radionuclide therapy for prostate cancer started more than 70 y ago (1). Nuclear medicine has since evolved considerably to provide a multitude of new imaging and therapy options. The past decade witnessed an unprecedented expansion of radioligands for prostate cancer. Milestones include the first α-emitter for treatment of symptomatic bone metastases (2) and theranostic vectors directed at the prostate-specific membrane antigen (PSMA) or bombesin receptor (3–5). However, current radionuclide therapies are applied at a late stage of the disease aiming at palliation. Despite recent advances for treatment of metastatic prostate cancer, cure remains an unmet need of the 21st century.more » Cancer spreads early and develops slowly as submillimeter occult lesions. Lesions grow at distant sites and become detectable only when significant morphologic or metabolic alterations have formed, often years to decades after the initial spread (6). Effective ablation of small metastases is critical for cure and presents a specific challenge for β-emitting radionuclide therapy. Millimeter-range β-particles deliver insufficient amounts of radiation to millimeter-size tumor lesions, as energy deposition extends and dilutes beyond lesion boundaries (Fig. 1). α-radiation, because of its micrometer range, targets millimeter-size tumor volumes at higher relative yield (Fig. 1). Further evidence points to a superior biologic effectiveness for α-therapy based on high-linear-energy transfer resulting in frequent double-strand DNA breaks (7). However, are basic advantages of α-therapy associated with a clinical benefit?« less

More α Than β for Prostate Cancer?

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

Fendler, Wolfgang P.; Cutler, Cathy

Radionuclide therapy for prostate cancer started more than 70 y ago (1). Nuclear medicine has since evolved considerably to provide a multitude of new imaging and therapy options. The past decade witnessed an unprecedented expansion of radioligands for prostate cancer. Milestones include the first α-emitter for treatment of symptomatic bone metastases (2) and theranostic vectors directed at the prostate-specific membrane antigen (PSMA) or bombesin receptor (3–5). However, current radionuclide therapies are applied at a late stage of the disease aiming at palliation. Despite recent advances for treatment of metastatic prostate cancer, cure remains an unmet need of the 21st century.more » Cancer spreads early and develops slowly as submillimeter occult lesions. Lesions grow at distant sites and become detectable only when significant morphologic or metabolic alterations have formed, often years to decades after the initial spread (6). Effective ablation of small metastases is critical for cure and presents a specific challenge for β-emitting radionuclide therapy. Millimeter-range β-particles deliver insufficient amounts of radiation to millimeter-size tumor lesions, as energy deposition extends and dilutes beyond lesion boundaries (Fig. 1). α-radiation, because of its micrometer range, targets millimeter-size tumor volumes at higher relative yield (Fig. 1). Further evidence points to a superior biologic effectiveness for α-therapy based on high-linear-energy transfer resulting in frequent double-strand DNA breaks (7). However, are basic advantages of α-therapy associated with a clinical benefit?« less

Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

PubMed

Miao, Hui; Hartman, Mikael; Bhoo-Pathy, Nirmala; Lee, Soo-Chin; Taib, Nur Aishah; Tan, Ern-Yu; Chan, Patrick; Moons, Karel G M; Wong, Hoong-Seam; Goh, Jeremy; Rahim, Siti Mastura; Yip, Cheng-Har; Verkooijen, Helena M

2014-01-01

In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic). We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53) to 0.63 (95% CI, 0.60-0.66). The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

Patterns of failure after the reduced volume approach for elective nodal irradiation in nasopharyngeal carcinoma.

PubMed

Seol, Ki Ho; Lee, Jeong Eun

2016-03-01

To evaluate the patterns of nodal failure after radiotherapy (RT) with the reduced volume approach for elective neck nodal irradiation (ENI) in nasopharyngeal carcinoma (NPC). Fifty-six NPC patients who underwent definitive chemoradiotherapy with the reduced volume approach for ENI were reviewed. The ENI included retropharyngeal and level II lymph nodes, and only encompassed the echelon inferior to the involved level to eliminate the entire neck irradiation. Patients received either moderate hypofractionated intensity-modulated RT for a total of 72.6 Gy (49.5 Gy to elective nodal areas) or a conventional fractionated three-dimensional conformal RT for a total of 68.4-72 Gy (39.6-45 Gy to elective nodal areas). Patterns of failure, locoregional control, and survival were analyzed. The median follow-up was 38 months (range, 3 to 80 months). The out-of-field nodal failure when omitting ENI was none. Three patients developed neck recurrences (one in-field recurrence in the 72.6 Gy irradiated nodal area and two in the elective irradiated region of 39.6 Gy). Overall disease failure at any site developed in 11 patients (19.6%). Among these, there were six local failures (10.7%), three regional failures (5.4%), and five distant metastases (8.9%). The 3-year locoregional control rate was 87.1%, and the distant failure-free rate was 90.4%; disease-free survival and overall survival at 3 years was 80% and 86.8%, respectively. No patient developed nodal failure in the omitted ENI site. Our investigation has demonstrated that the reduced volume approach for ENI appears to be a safe treatment approach in NPC.

Patterns of failure after the reduced volume approach for elective nodal irradiation in nasopharyngeal carcinoma

PubMed Central

Seol, Ki Ho

2016-01-01

Purpose To evaluate the patterns of nodal failure after radiotherapy (RT) with the reduced volume approach for elective neck nodal irradiation (ENI) in nasopharyngeal carcinoma (NPC). Materials and Methods Fifty-six NPC patients who underwent definitive chemoradiotherapy with the reduced volume approach for ENI were reviewed. The ENI included retropharyngeal and level II lymph nodes, and only encompassed the echelon inferior to the involved level to eliminate the entire neck irradiation. Patients received either moderate hypofractionated intensity-modulated RT for a total of 72.6 Gy (49.5 Gy to elective nodal areas) or a conventional fractionated three-dimensional conformal RT for a total of 68.4–72 Gy (39.6–45 Gy to elective nodal areas). Patterns of failure, locoregional control, and survival were analyzed. Results The median follow-up was 38 months (range, 3 to 80 months). The out-of-field nodal failure when omitting ENI was none. Three patients developed neck recurrences (one in-field recurrence in the 72.6 Gy irradiated nodal area and two in the elective irradiated region of 39.6 Gy). Overall disease failure at any site developed in 11 patients (19.6%). Among these, there were six local failures (10.7%), three regional failures (5.4%), and five distant metastases (8.9%). The 3-year locoregional control rate was 87.1%, and the distant failure-free rate was 90.4%; disease-free survival and overall survival at 3 years was 80% and 86.8%, respectively. Conclusion No patient developed nodal failure in the omitted ENI site. Our investigation has demonstrated that the reduced volume approach for ENI appears to be a safe treatment approach in NPC. PMID:27104162

Prevalence and Risk Factors of Ovarian Metastases in Breast Cancer Patients < 41 Years of Age in the Netherlands: A Nationwide Retrospective Cohort Study.

PubMed

Peters, Inge T A; van Zwet, Erik W; Smit, Vincent T H B M; Liefers, Gerrit Jan; Kuppen, Peter J K; Hilders, Carina G J M; Trimbos, J Baptist

2017-01-01

Breast cancer is one of the primary indications for cryopreservation and subsequent autotransplantation of ovarian tissue. The safety of this fertility preservation method remains questionable, as the presence of disseminated breast tumor cells cannot yet be excluded in the ovarian autografts. We explored the prevalence of ovarian metastases among young breast cancer patients and determined risk factors for the development of ovarian metastases. Using the nationwide database of the Dutch Pathology Registry (PALGA), we identified a cohort of 2648 women with primary invasive breast cancer at age < 41 years in the period 2000-2010 in the Netherlands who subsequently underwent an oophorectomy. From this source population, all cases who had histologically confirmed ovarian metastases were included. For each case of whom clinical data were available, one control without ovarian metastases who matched the time interval between breast cancer diagnosis and oophorectomy was selected. Data were collected on patient characteristics, diagnosis, treatment and follow-up. Ovarian metastases were found in 63 out of 2648 patients who met the inclusion criteria. The risk of developing ovarian metastases increased with time passed since breast cancer diagnosis. Multivariate logistic regression analyses showed significant association between tumor stage and the development of ovarian metastases (p = 0.024). The prevalence of ovarian metastases was 2.4% among young breast cancer patients. Early ovary removal may reduce the risk of developing ovarian metastases. In breast cancer patients with tumors > 5 cm and/or inflammatory carcinoma, we recommend a cautious approach to ovarian tissue autotransplantation.

Roles of stromal microenvironment in colon cancer progression.

PubMed

Taketo, Makoto Mark

2012-05-01

Although our understanding of epithelial cancer cells has advanced significantly, our understanding of the cancer microenvironment is still fragmentary. In contrast to our intuitive impression that our body always suppresses cancer growth, recent pieces of evidence show that cancer often exploits our body reactions to expand, invade local tissues and metastasize to distant organs. Accordingly, investigations of such body reactions in the tumour microenvironment should help us to design novel therapeutic strategies that can be combined with the traditional therapeutics targeted at the cancer cells themselves. In this article, I am going to review our recent efforts in search of novel therapeutic strategies against colon cancer using mouse models.

Immunohistochemical features of the gastrointestinal tract tumors

PubMed Central

Wong, Hannah H.

2012-01-01

Gastrointestinal tract tumors include a wide variety of vastly different tumors and on a whole are one of the most common malignancies in western countries. These tumors often present at late stages as distant metastases which are then biopsied and may be difficult to differentiate without the aid of immunohistochemical stains. With the exception of pancreatic and biliary tumors where there are no distinct immunohistochemical patterns, most gastrointestinal tumors can be differentiated by their unique immunohistochemical profile. As the size of biopsies decrease, the role of immunohistochemical stains will become even more important in determining the origin and differentiation of gastrointestinal tract tumors. PMID:22943017

Clinical data from the real world: efficacy of Crizotinib in Chinese patients with advanced ALK-rearranged non-small cell lung cancer and brain metastases.

PubMed

Xing, Puyuan; Wang, Shouzheng; Hao, Xuezhi; Zhang, Tongtong; Li, Junling

2016-12-20

Brain metastasis in non small cell lung cancer (NSCLC) patients is often considered as a terminal stage of advanced disease. Crizotinib is a small-molecule tyrosine kinase inhibitor (TKI) for ALK-rearranged NSCLC patients. Herein, we conducted a retrospective study to explore how Crizotinib affects the control of brain metastases and the overall prognosis in advanced ALK-rearranged NSCLC patients with brain metastases in Chinese population. A total of 34 patients were enrolled, of whom 20 (58.8%) patients had baseline brain metastases before Crizotinib treatment. Among patients with brain metastases before Crizotinib, overall survival (OS) after brain metastases was significantly longer than that of patients with brain metastases after Crizotinib (median OS, not reached vs. 10.3 months, respectively, p = 0.001). There was also a significant difference in systemic progression-free survival (PFS) between patients developing brain metastases before and after Crizotinib treatment (21.2 months vs. 13.9 months, p = 0.003). In conclusion, ALK-rearranged NSCLC patients with brain metastases before Crizotinib may benefit more from Crizotinib than those developing brain metastases during Crizotinib treatment.

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline

PubMed Central

Tsao, May N.; Rades, Dirk; Wirth, Andrew; Lo, Simon S.; Danielson, Brita L.; Gaspar, Laurie E.; Sperduto, Paul W.; Vogelbaum, Michael A.; Radawski, Jeffrey D.; Wang, Jian Z.; Gillin, Michael T.; Mohideen, Najeeb; Hahn, Carol A.; Chang, Eric L.

2012-01-01

Purpose To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Methods and Materials Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. Results The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. Conclusions Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone). PMID:25925626

Role of epithelial-mesenchymal transition involved molecules in the progression of cutaneous melanoma.

PubMed

Murtas, Daniela; Maxia, Cristina; Diana, Andrea; Pilloni, Luca; Corda, Claudia; Minerba, Luigi; Tomei, Sara; Piras, Franca; Ferreli, Caterina; Perra, Maria Teresa

2017-12-01

Epithelial-mesenchymal transition (EMT) has been suggested to have a driving role in the acquisition of a metastatic potential by melanoma cells. Important hallmarks of EMT include both E-cadherin downregulation and increased expression of N-cadherin. This switch in distinct classes of adhesion molecules leads melanoma cells to lose contact with adjacent keratinocytes and interact instead with stromal fibroblasts and endothelial cells, thus promoting dermal and vascular melanoma invasion. Consequently, tumor cells migrate to distant host tissues and establish metastases. A key regulator in the induction of EMT in melanoma is the Notch1 signaling pathway that, when activated, is prompt to upregulate N-cadherin expression. By means of this strategy, melanoma cells gain enhanced survival, proliferation and invasion properties, driving the tumor toward a more aggressive phenotype. On the basis of these statements, the present study aimed to investigate the possible association between N-cadherin and Notch1 presence in primary cutaneous melanomas and lymph node metastases. Our results from immunohistochemical analysis confirmed a positive correlation between N-cadherin and Notch1 presence in the same tumor samples. Moreover, this study highlighted that a concomitant high expression of N-cadherin and Notch1, both in primary lesions and in lymph node metastases, predicts an adverse clinical outcome in melanoma patients. Therefore, N-cadherin and Notch1 co-presence can be monitored as a predictive factor in early- and advanced-stage melanomas and open additional therapeutic targets for the restraint of melanoma metastasis.

Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival

PubMed Central

Tobin, N. P.; Harrell, J. C.; Lövrot, J.; Egyhazi Brage, S.; Frostvik Stolt, M.; Carlsson, L.; Einbeigi, Z.; Linderholm, B.; Loman, N.; Malmberg, M.; Walz, T.; Fernö, M.; Perou, C. M.; Bergh, J.; Hatschek, T.; Lindström, L. S.; Hatschek, Thomas; Fernö, Mårten; Lindström, Linda Sofie; Hedenfalk, Ingrid; Brandberg, Yvonne; Carstensen, John; Egyhazy, Suzanne; Stolt, Marianne Frostvik; Skoog, Lambert; Hellström, Mats; Maliniemi, Maarit; Svensson, Helene; Åström, Gunnar; Bergh, Jonas; Bjöhle, Judith; Lidbrink, Elisabet; Rotstein, Sam; Wallberg, Birgitta; Einbeigi, Zakaria; Carlsson, Per; Linderholm, Barbro; Walz, Thomas; Loman, Niklas; Malmström, Per; Söderberg, Martin; Malmberg, Martin; Carlsson, Lena; Umeå; Lindh, Birgitta; Sundqvist, Marie; Malmberg, Lena

2015-01-01

Background We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. Patients and methods The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and β-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. Results A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and β-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3–10.9] and HER2-enriched (HR 4.4; 95% CI 1.5–12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. Conclusions We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information. ClinicalTrials.gov This is the translational part of the Swedish multicenter and randomized trial TEX, clinicaltrials.gov identifier nct01433614 (http://www.clinicaltrials.gov/ct2/show/nct01433614). PMID:25361981

Incidence of Brain Metastases on Follow-up 18F-FDG PET/CT Scans of Non-Small Cell Lung Cancer Patients: Should We Include the Brain?

PubMed

Nia, Emily S; Garland, Linda L; Eshghi, Naghmehossadat; Nia, Benjamin B; Avery, Ryan J; Kuo, Phillip H

2017-09-01

The brain is the most common site of distant metastasis from lung cancer. Thus, MRI of the brain at initial staging is routinely performed, but if this examination is negative a follow-up examination is often not performed. This study evaluates the incidence of asymptomatic brain metastases in non-small cell lung cancer patients detected on follow-up 18 F-FDG PET/CT scans. Methods: In this Institutional Review Board-approved retrospective review, all vertex to thigh 18 F-FDG PET/CT scans in patients with all subtypes of lung cancer from August 2014 to August 2016 were reviewed. A total of 1,175 18 F-FDG PET/CT examinations in 363 patients were reviewed. Exclusion criteria included brain metastases on initial staging, histologic subtype of small-cell lung cancer, and no follow-up 18 F-FDG PET/CT examinations. After our exclusion criteria were applied, a total of 809 follow-up 18 F-FDG PET/CT scans in 227 patients were included in the final analysis. The original report of each 18 F-FDG PET/CT study was reviewed for the finding of brain metastasis. The finding of a new brain metastasis prompted a brain MRI, which was reviewed to determine the accuracy of the 18 F-FDG PET/CT. Results: Five of 227 patients with 809 follow-up 18 F-FDG PET/CT scans reviewed were found to have incidental brain metastases. The mean age of the patients with incidental brain metastasis was 68 y (range, 60-77 y). The mean time from initial diagnosis to time of detection of incidental brain metastasis was 36 mo (range, 15-66 mo). When MRI was used as the gold standard, our false-positive rate was zero. Conclusion: By including the entire head during follow-up 18 F-FDG PET/CT scans of patients with non-small cell lung cancer, brain metastases can be detected earlier while still asymptomatic. But, given the additional scan time, radiation, and low incidence of new brain metastases in asymptomatic patients, the cost-to-benefit ratio should be weighed by each institution. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Advances in Lymphatic Imaging and Drug Delivery

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

Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.

2011-09-10

Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastlymore » improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.« less

EMT and induction of miR-21 mediate metastasis development in Trp53-deficient tumours

PubMed Central

Bornachea, Olga; Santos, Mirentxu; Martínez-Cruz, Ana Belén; García-Escudero, Ramón; Dueñas, Marta; Costa, Clotilde; Segrelles, Carmen; Lorz, Corina; Buitrago, Agueda; Saiz-Ladera, Cristina; Agirre, Xabier; Grande, Teresa; Paradela, Beatriz; Maraver, Antonio; Ariza, José M.; Prosper, Felipe; Serrano, Manuel; Sánchez-Céspedes, Montse; Paramio, Jesús M.

2012-01-01

Missense mutations in TP53 gene promote metastasis in human tumours. However, little is known about the complete loss of function of p53 in tumour metastasis. Here we show that squamous cell carcinomas generated by the specific ablation of Trp53 gene in mouse epidermis are highly metastatic. Biochemical and genome-wide mRNA and miRNA analyses demonstrated that metastases are associated with the early induction of epithelial-mesenchymal transition (EMT) and deregulated miRNA expression in primary tumours. Increased expression of miR-21 was observed in undifferentiated, prometastatic mouse tumours and in human tumours characterized by p53 mutations and distant metastasis. The augmented expression of miR-21, mediated by active mTOR and Stat3 signalling, conferred increased invasive properties to mouse keratinocytes in vitro and in vivo, whereas blockade of miR-21 in a metastatic spindle cell line inhibits metastasis development. Collectively these data identify novel molecular mechanisms leading to metastasis in vivo originated by p53 loss in epithelia. PMID:22666537

[Breast cancer in Sub-Saharan African women: review].

PubMed

Ly, Madani; Antoine, Martine; André, Fabrice; Callard, Patrice; Bernaudin, Jean-François; Diallo, Dapa A

2011-07-01

Breast cancer is the second most frequent cancer in Sub-Saharan African women with an incidence of 15-53 per 100,000 women. Using PubMed, we reviewed all the articles published on this topic between 1989 and 2009. Breast cancer is usually diagnosed in women younger than in developed countries (mean age: 42-53 years), with later stages (III or IV, i.e. with axillary nodes and distant metastases). Reported tumors are mostly invasive ductal carcinomas with aggressive characteristics: grade III histoprognosis, absence of hormonal receptors or HER2 expression. According to the new breast cancer classification, nearly half of these tumors should be classified as triple negative. However, studies are rare and require confirmation. In conclusion, data on epidemiology and biology of breast cancer in Sub-Saharan African women are still scarce and need more extensive studies. In these countries, the pattern of breast cancer will likely change in the future, according to the evolution of lifestyle namely urbanisation. There is a great need for commitment of research and clinical resources in Sub-Saharan Africa in order to develop specific strategies.

Brain metastasis from squamous cell carcinoma of the head and neck: a review of the literature in the genomic era.

PubMed

Barrett, Thomas F; Gill, Corey M; Miles, Brett A; Iloreta, Alfred M C; Bakst, Richard L; Fowkes, Mary; Brastianos, Priscilla K; Bederson, Joshua B; Shrivastava, Raj K

2018-06-01

Squamous cell carcinoma of the head and neck (HNSCC) affects nearly 500,000 individuals globally each year. With the rise of human papillomavirus (HPV) in the general population, clinicians are seeing a concomitant rise in HPV-related HNSCC. Notably, a hallmark of HPV-related HNSCC is a predilection for unique biological and clinical features, which portend a tendency for hematogenous metastasis to distant locations, such as the brain. Despite the classic belief that HNSCC is restricted to local spread via passive lymphatic drainage, brain metastases (BMs) are a rare complication that occurs in less than 1% of all HNSCC cases. Time between initial diagnosis of HNSCC and BM development can vary considerably. Some patients experience more than a decade of disease-free survival, whereas others present with definitive neurological symptoms that precede primary tumor detection. The authors systematically review the current literature on HNSCC BMs and discuss the current understanding of the effect of HPV status on the risk of developing BMs in the modern genomic era.

Factors affecting survival of women diagnosed with breast cancer in El-Minia Governorate, Egypt.

PubMed

Seedhom, Amany Edward; Kamal, Nashwa Nabil

2011-07-01

This study was conducted to determine breast cancer survival time and the association between breast cancer survival and socio-demographic and pathologic factors among women, in El-Minia, Egypt. While there has been much researches regarding prognostic factors for breast cancer but the majority of these studies were from developed countries. El-Minia has a population of approximately 4 million. To date, no research has been performed to determine breast cancer survival and the factors affecting it in El-minia. This retrospective study used data obtained from the cancer registry in the National Institute of Oncology in El-Minia and included 1207 women diagnosed with first primary breast cancer between 1(st) January 2005 and 31(st) December 2009 and followed to 30(th) June 2010. The association between survival and sociodemographic and pathological factors and distant metastasis at diagnosis, and treatment options was investigated using unifactorial chi-square test and multi-factorial (Cox regression) analyses. Kaplan-Meier analysis was used to compare survival time among different groups. Median survival time was 83.8 ± 3.2. Cox regression showed that high vs low educational level (Hazard ratio (HR)= 0.35, 95% CI; 0.27-0.46), metastases to bone (HR = 3.22, 95% CI: 1.71-6.05), metastases to lung (HR= 2.314, 95% CI: 1.225-4.373), tumor size (≤ 2 cm vs ≥ 5 cm: HR = 1.4, 95% CI: 1.1-1.8) and number of involved nodes (1 vs > 10 HR = 5.21, 95%CI: 3.1-9.01) were significantly related to survival. The results showed the need to develop screening programs and standardized treatment regimens in a tax-funded health care system.

Interstitial laser immunotherapy for treatment of metastatic mammary tumors in rats

NASA Astrophysics Data System (ADS)

Figueroa, Daniel; Joshi, Chet; Wolf, Roman F.; Walla, Jonny; Goddard, Jessica; Martin, Mallory; Kosanke, Stanley D.; Broach, Fred S.; Pontius, Sean; Brown, Destiny; Li, Xiaosong; Howard, Eric; Nordquist, Robert E.; Hode, Tomas; Chen, Wei R.

2011-03-01

Thermal therapy has been used for cancer treatment for more than a century. While thermal effect can be direct, immediate, and controllable, it is not sufficient to completely eradicate tumors, particularly when tumors have metastasized locally or to the distant sites. Metastases are the major cause of treatment failure and cancer deaths. Current available therapies, such as surgery, radiation, and chemotherapy, only have limited curative effects in patients with late-stage, metastatic cancers. Immunotherapy has been considered as the ultimate approach for cancer treatment since a systemic, anti-tumor, immunological response can be induced. Using the combination of photothermal therapy and immunotherapy, laser immunotherapy (LIT),a novel immunotherapy modality for late-stage cancer treatment, has been developed. LIT has shown great promise in pre-clinical studies and clinical breast cancer and melanoma pilot trials. However, the skin color and the depth of the tumor have been challenges for effective treatment with LIT. To induce a thermal destruction zone of appropriate size without causing thermal damage on the skin, we have developed interstitial laser immunotherapy (ILIT) using a cylindrical diffuser. To determine the effectiveness of ILIT, we treated the DMBA-4 metastatic tumors in rats. The thermal damage in tumor tissue was studied using TTC immersion and hematoxolin and eosin (H & E) staining. Also observed was the overall survival of the treated animals. Our results demonstrated that the ILIT could impact a much larger tumor area, and it significantly reduced the surface damage compared with the early version of non-invasive LIT. The survival data also indicate that ILIT has the potential to become an effective tool for the treatment of deeper, larger, and metastatic tumors, with reduced side effects.

INCIDENCE OF PULMONARY AND SKIN METASTASES IN WOMEN WITH BREAST CANCER WHO RECEIVED POSTOPERATIVE IRRADIATION

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

Dao, T.L.; Kovaric, J.

1962-07-01

The effect of x-ray treatment (total dose of 4500 r over a 3-week period) was evaluated in 354 patients, some of whom had previously undergone mastectomy. In clinically and pathologically comparable cases, ipsilateral pulmonary iaetastases and skin metastases in patients who had radical mastectomy were 14 and 34%, respectively, whereas in patients who received irradiation after mastectomy, incidences of metastases at those 2 sites were 37 and 52%. A similar change of patterns of metastases in lungs and skin was also observed in patients who have had simple mastectomy and irradiation. The increase in the incidence of ipsilateral skin andmore » pulmonary metastases is ascribed to the effect of irradiation, and the observations strongly support the postulate that irradiation favors development of metastases in the lungs. The fact that metastases developed in the skin within the portals of irradiation, and in the ipsilateral lung in the same patients, is evidence that the lymphatic and vascular obstructions due to fibrosis contribute to the development of the metastases in these tissues. The different patterns of skin and lung metastases in nonirradiated patients render additional support to the theory. The incidence of these injuries in 50 irradiated patients was: 18 had permanent disability of the upper extremities; 14 had necrosis of the bones with fractures of the clavicle and ribs; 25 had initial pneumonitis and subsequently pulmonary fibrosis; and 40 had skin changes, ranging from desquamation to ulceration. No significant difference was demonstrated in the survival of patients with cancer of the breast who received radical irradiation in addition to mastectomy. Furthermore, irradiation may favor the development of metastases in the lungs and skin, and cause disabling injuries. (TCO)« less

Factors affecting local recurrence and distant metastases of invasive breast cancer after breast-conserving surgery in Chiang Mai University Hospital.

PubMed

Ditsatham, Chagkrit; Somwangprasert, Areewan; Watcharachan, Kirati; Wongmaneerung, Phanchaporn; Khorana, Jiraporn

2016-01-01

The purpose of this study was to collect data regarding breast cancer profiles and factors that affect local recurrence and distant metastasis after breast-conserving surgery (BCS) in Chiang Mai University Hospital. This study was a retrospective review in a single institution of newly diagnosed invasive breast cancer patients who were treated with BCS between April 9, 2001 and December 25, 2011. A total of 185 patients treated with BCS were included in this study, with an average age of 46.83 years. The average recurrence age was 41.1 years and the average nonrecurrence age was 47.48 years, with a recurrence rate of 10.27%. Premenopause was significant in recurrence (P=0.047), as well as non-estrogen-expression patients (P=0.001) and patients who did not receive antihormonal treatment (P=0.011). The recurrence rate in our institute was 10.27%. Factors affecting recurrence after BCS included young age, premenopausal status, nonexpression of the estrogen receptor, and patients who had not received antihormonal treatment. The recurrence rate was higher in the first 90 postoperative months.

Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation

PubMed Central

Balistreri, Giuseppe; Gramolelli, Silvia; Tatti-Bugaeva, Olga; Paatero, Ilkka; Niiranen, Otso; Tuohinto, Krista; Perälä, Nina; Taiwo, Adewale; Zinovkina, Nadezhda; Repo, Pauliina; Icay, Katherine; Ivaska, Johanna; Saharinen, Pipsa; Hautaniemi, Sampsa; Lehti, Kaisa

2018-01-01

Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasive Bowes cells, to lymphatic endothelial cells (LEC) in 3D co-culture facilitates melanoma distant organ metastasis in mice. To dissect the underlying molecular mechanisms, we established LEC co-cultures with different melanoma cells originating from primary tumors or metastases. Notably, the expansively growing metastatic melanoma cells adopted an invasively sprouting phenotype in 3D matrix that was dependent on MMP14, Notch3 and β1-integrin. Unexpectedly, MMP14 was necessary for LEC-induced Notch3 induction and coincident β1-integrin activation. Moreover, MMP14 and Notch3 were required for LEC-mediated metastasis of zebrafish xenografts. This study uncovers a unique mechanism whereby LEC contact promotes melanoma metastasis by inducing a reversible switch from 3D growth to invasively sprouting cell phenotype. PMID:29712618

A Systematic Review of the Modifying Effect of Anaesthetic Drugs on Metastasis in Animal Models for Cancer

PubMed Central

Geessink, Florentine J.; Ritskes-Hoitinga, Merel; Scheffer, Gert Jan

2016-01-01

Background Distant metastasis or local recurrence after primary tumour resection remain a major clinical problem. The anaesthetic technique used during oncologic surgery is suggested to influence the metastatic process. While awaiting the results of ongoing randomised controlled trials (RCTs), we have analyzed the evidence regarding the influence of anaesthetic drugs on experimental tumour metastasis in animal studies. Methods PubMed and Embase were searched until April 21st, 2015. Studies were included in the systematic review when they 1) assessed the effect of an anaesthetic drug used in clinical practice on the number or incidence of metastasis in animal models with experimental cancer, 2) included an appropriate control group, and 3) presented unique data. Results 20 studies met the inclusion criteria (published between 1958–2010). Data on number of metastases could be retrieved from 17 studies. These studies described 41 independent comparisons, 33 of which could be included in the meta-analysis (MA). The incidence of metastases was studied in 3 unique papers. From these 3 papers, data on 7 independent comparisons could be extracted and included in the MA. Locally administered local anaesthetics appear to decrease the number of metastases (SMD -6.15 [-8.42; -3.88]), whereas general anaesthetics (RD: 0.136 [0.045, 0.226]), and more specifically volatile anaesthetics (SMD 0.54 [0.24; 0.84]), appear to increase the number and risk of metastases in animal models for cancer. Conclusions Anaesthetics influence the number and incidence of metastases in experimental cancer models. Although more high quality experimental research is necessary, based on the currently available evidence from animal studies, there is no indication to suggest that locally administered local anaesthetics are harmful during surgery in cancer patients. Volatile anaesthetics, however, might increase metastasis in animal models and clinical trials investigating this possibly harmful effect should receive priority. The results of our systematic review in animal studies are broadly consistent with clinical reports that anaesthetic technique does seem to affect the tumour metastasis process. PMID:27227779

Does Stereotactic Radiosurgery Have a Role in the Management of Patients Presenting With 4 or More Brain Metastases?

PubMed

Soike, Michael H; Hughes, Ryan T; Farris, Michael; McTyre, Emory R; Cramer, Christina K; Bourland, J D; Chan, Michael D

2018-06-01

Stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) are effective treatments for management of brain metastases. Prospective trials comparing the 2 modalities in patients with fewer than 4 brain metastases demonstrate that overall survival (OS) is similar. Intracranial failure is more common after SRS, while WBRT is associated with neurocognitive decline. As technology has advanced, fewer technical obstacles remain for treating patients with 4 or more brain metastases with SRS, but level I data supporting its use are lacking. Observational prospective studies and retrospective series indicate that in patients with 4 or more brain metastases, performance status, total volume of intracranial disease, histology, and rate of development of new brain metastases predict outcomes more accurately than the number of brain metastases. It may be reasonable to initially offer SRS to some patients with 4 or more brain metastases. Initiating therapy with SRS avoids the acute and late sequelae of WBRT. Multiple phase III trials of SRS vs WBRT, both currently open or under development, are directly comparing quality of life and OS for patients with 4 or more brain metastases to help answer the question of SRS appropriateness for these patients.

Head and neck mucosal melanoma: experience with 42 patients, with emphasis on the role of postoperative radiotherapy.

PubMed

Meleti, Marco; Leemans, C René; de Bree, Remco; Vescovi, Paolo; Sesenna, Enrico; van der Waal, Isaäc

2008-12-01

Treatment of head and neck mucosal melanoma remains a challenge. Surgery has traditionally been the main therapeutic approach. The role of postoperative radiotherapy has never been clearly established. The experience with a group of 42 patients (16 males, 26 females) with a primary head and neck mucosal melanoma is reported. Eleven of 19 patients (57.9%) receiving surgery alone developed a regional lymphatic metastasis. For patients receiving postoperative radiotherapy (19 patients), regional metastatic spread occurred in 4 patients (21%). Percentages of local failure were 57.9% (11/19) and 26.3% (5/19) for patients treated with surgery alone and for those treated with surgery and radiotherapy, respectively. Distant metastases occurred in 10 of 19 patients (52.6%) receiving surgery alone and in 9 of 19 patients (47.3%) receiving both therapies. The present evaluation confirms a poor prognosis for patients with head and neck mucosal melanoma, independent of the treatment modality. (c) 2008 Wiley Periodicals, Inc.

Uterine cervical cancer with brain metastasis as the initial site of presentation.

PubMed

Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

2015-07-01

Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

Ectopic production of beta-HCG by a maxillary squamous cell carcinoma.

PubMed

Scholl, P D; Jurco, S; Austin, J R

1997-12-01

Paraneoplastic syndromes of the head and neck are rare. Hypercalcemia and leukocytosis have been described. The literature was reviewed, and a case of a squamous cell carcinoma of the maxilla producing beta human chorionic gonadotropin (beta-HCG) is presented. A 47-year-old white man with a T4N1M0 squamous cell carcinoma of the left maxilla was treated with a maxillectomy and neck dissection for an N1 positive neck. After completing his planned radiotherapy, he developed distant metastases, which included an axillary node that stained positive for human beta-HCG. Retrospective review of the primary specimen showed beta-HCG positivity in an anaplastic component of the tumor along with vascular invasion. The first case in the literature of a paraneoplastic syndrome with beta-HCG production in association with squamous cell carcinoma of the maxilla is presented. This case history fits the aggressive nature of beta HCG producing tumors elsewhere in the body.

Radiology of colorectal cancer.

PubMed

Pijl, M E J; Chaoui, A S; Wahl, R L; van Oostayen, J A

2002-05-01

In the past 20 years, the radiology of colorectal cancer has evolved from the barium enema to advanced imaging modalities like phased array magnetic resonance imaging (MRI), virtual colonoscopy and positron emission tomography (PET). Nowadays, primary rectal cancers are preferably imaged with transrectal ultrasound or MRI, while barium enema is still the most often used technique for imaging of colonic cancers. Virtual colonoscopy is rapidly evolving and might considerably change the imaging of colorectal cancer in the near future. The use of virtual colonoscopy for screening purposes and imaging of the colon in occlusive cancer or incomplete colonoscopies is currently under evaluation. The main role of PET is in detecting tumour recurrences, both locally and distantly. Techniques to fuse cross-sectional anatomical (computer tomography (CT) and MRI) and functional (PET) images are being developed. Apart from diagnostic imaging, the radiologists has added image-guided minimally invasive treatments of colorectal liver metastases to their arsenal. The radio-frequency ablation technique is now widely available, and can be used during laparotomy or percutaneously in selected cases.

Microenvironmental regulation of the progression of oral potentially malignant disorders towards malignancy

PubMed Central

Ai, Ruixue; Tao, Yan; Hao, Yilong; Jiang, Lu; Dan, Hongxia; Ji, Ning; Zeng, Xin; Zhou, Yu; Chen, Qianming

2017-01-01

Oral potentially malignant disorders (OPMD) develop in a complex tissue microenvironment where they grow sustainably, acquiring oral squamous cell carcinoma (OSCC) characteristics. The malignant tumor depends on interactions with the surrounding microenvironment to achieve loco-regional invasion and distant metastases. Unlike abnormal cells, the multiple cell types in the tissue microenvironment are relatively stable at the genomic level and, thus, become therapeutic targets with lower risk of resistance, decreasing the risk of OPMD acquiring cancer characteristics and carcinoma recurrence. However, deciding how to disrupt the OPMD and OSCC microenvironments is itself a daunting challenge, since their microenvironments present opposite capacities, resulting in diverse consequences. Furthermore, recent studies revealed that tumor-associated immune cells also participate in the process of differentiation from OPMD to OSCC, suggesting that reeducating stromal cells may be a new strategy to prevent OPMD from acquiring OSCC characteristics and to treat OSCC. In this review, we discuss the characteristics of the microenvironment of OPMD and OSCC as well as new therapeutic strategies. PMID:29113419

Head-to-Head Comparison of Chest X-Ray/Head and Neck MRI, Chest CT/Head and Neck MRI, and 18F-FDG PET/CT for Detection of Distant Metastases and Synchronous Cancer in Oral, Pharyngeal, and Laryngeal Cancer.

PubMed

Rohde, Max; Nielsen, Anne L; Johansen, Jørgen; Sørensen, Jens A; Nguyen, Nina; Diaz, Anabel; Nielsen, Mie K; Asmussen, Jon T; Christiansen, Janus M; Gerke, Oke; Thomassen, Anders; Alavi, Abass; Høilund-Carlsen, Poul Flemming; Godballe, Christian

2017-12-01

The purpose of this study was to determine the detection rate of distant metastasis and synchronous cancer, comparing clinically used imaging strategies based on chest x-ray + head and neck MRI (CXR/MRI) and chest CT + head and neck MRI (CHCT/MRI) with 18 F-FDG PET/CT upfront in the diagnostic workup of patients with oral, pharyngeal, or laryngeal cancer. Methods: This was a prospective cohort study based on paired data. Consecutive patients with histologically verified primary head and squamous cell carcinoma at Odense University Hospital from September 2013 to March 2016 were considered for the study. Included patients underwent CXR/MRI and CHCT/MRI as well as PET/CT on the same day and before biopsy. Scans were read masked by separate teams of experienced nuclear physicians or radiologists. The true detection rate of distant metastasis and synchronous cancer was assessed for CXR/MRI, CHCT/MRI, and PET/CT. Results: A total of 307 patients were included. CXR/MRI correctly detected 3 (1%) patients with distant metastasis, CHCT/MRI detected 11 (4%) patients, and PET/CT detected 18 (6%) patients. The absolute differences of 5% and 2%, respectively, were statistically significant in favor of PET/CT. Also, PET/CT correctly detected 25 (8%) synchronous cancers, which was significantly more than CXR/MRI (3 patients, 1%) and CHCT/MRI (6 patients, 2%). The true detection rate of distant metastasis or synchronous cancer with PET/CT was 13% (40 patients), which was significantly higher than 2% (6 patients) for CXR/MRI and 6% (17 patients) for CHCT/MRI. Conclusion: A clinical imaging strategy based on PET/CT demonstrated a significantly higher detection rate of distant metastasis or synchronous cancer than strategies in current clinical imaging guidelines, of which European ones primarily recommend CXR/MRI, whereas U.S. guidelines preferably point to CHCT/MRI in patients with head and neck squamous cell carcinoma. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

[Selective biopsy of the sentinel lymph node in breast cancer: without axillary recurrences after a mean follow-up of 4.5 years].

PubMed

Bañuelos Andrío, Luis; Rodríguez Caravaca, Gil; Argüelles Pintos, Miguel; Mitjavilla Casanova, Mercedes

2014-01-01

To analyze the rate of axillary recurrences (AR) in patients with early breast cancer who had not undergone an axillary node dissection (ALND) because of a negative sentinel lymph node biopsy (SLNB). The study includes 173 patients operated on for breast cancer and selective node biopsy. In 32 patients the SLNB was positive and undergone subsequent ALND. We followed up 141 patients with negative SLNB without LDN, with a median follow up of 55 months (range 74-36). The detection rate of SLN was of 99.42%. After a median follow-up of 4.5 years, there were no axillary recurrences. Two patients developed local recurrence, other two patients developed distant metastases and four patients developed a metachronous tumor. Four patients died, none of them because of breast cancer. The results obtained support the SLNB as an accurate technique in the axillary stratification of patients with breast cancer, offering in the cases of negative SLNB a safe axillary control after 4.5 year follow-up. Copyright © 2013 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer.

PubMed

Dawood, Shaheenah; Lei, Xiudong; Litton, Jennifer K; Buchholz, Thomas A; Hortobagyi, Gabriel N; Gonzalez-Angulo, Ana M

2012-10-01

This retrospective study sought to define the incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer (TNBC). A total of 2448 patients with stage I through III TNBC who were diagnosed between 1990 and 2010 were identified. We computed the cumulative incidence of developing brain metastases as a first site of recurrence at 2 and 5 years. Cox proportional hazards models were fitted to determine factors that could predict for the development of brain metastases as a first site of recurrence. The Kaplan-Meier product limit method was used to compute survival following a diagnosis of brain metastases. At a median follow-up of 39 months, 115 (4.7%) patients had developed brain metastases as a first site of recurrence. The cumulative incidence at 2 and 5 years was 3.7% (95% confidence interval [CI] = 2.9%-4.5%) and 5.4% (95% CI = 4.4%-6.5%), respectively. Among patients with stage I, II, and III disease, the 2-year cumulative incidence of brain metastases was 0.8%, 3.1%, and 8%, respectively (P < .0001). The 5-year cumulative incidence was 2.8%, 4.6%, and 9.6% among patients with stage I, II, and III disease, respectively (P < .0001). In the multivariable model, patients with stage III disease had a significant increase in the risk of developing brain metastases as a first site of recurrence (hazards ratio = 3.51; 95% CI = 1.85-6.67; P = .0001) compared to patients with stage I disease. Those with stage II disease had a nonsignificant increased risk of developing brain metastases as a first site of recurrence (hazards ratio = 1.61; 95% CI = 0.92-2.81; P = .10) compared with patients with stage I disease. Median survival following a diagnosis of brain metastases was 7.2 months (range, 5.7-9.4 months). Patients with nonmetastatic TNBC have a high early incidence of developing brain metastases as a first site of recurrence, which is associated with subsequent poor survival. Patients with stage III TNBC in particular would be an ideal cohort in which to research preventive strategies. Copyright © 2012 American Cancer Society.

Lymphoepithelioma-like Carcinoma of the Breast: A Case Report

PubMed Central

Top, Ömer Erdinç; Vardar, Enver; Yağcı, Ayşe; Deniz, Senem; Öztürk, Rafet; Zengel, Baha

2014-01-01

Lymphoepithelioma-like carcinoma carries similar histopathological features with lymphoepithelioma typically located in the nasopharynx. Lymphoepithelioma-like carcinoma of the breast can be mistaken for breast lymphoma or medullary carcinoma due to the undifferentiated appearance of tumor cells and presence of prominent lymphoid component. Lymphoepithelioma-like carcinoma is rare, and the similarity between medullary carcinoma of the breast makes it difficult to distinguish these two tumors. In the presented case, neither lymph node nor distant metastases were detected. Breast lymphoepithelioma-like carcinoma is extremely rare with only 21 reported cases in the literature. Herein we present a 59-year-old woman with lymphoepithelioma-like carcinoma of the breast along with the cases previously published in the literature. PMID:28331666

Breast cancer lung metastasis: Molecular biology and therapeutic implications.

PubMed

Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

2018-03-26

Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

PET/MR Imaging in Gynecologic Oncology.

PubMed

Ohliger, Michael A; Hope, Thomas A; Chapman, Jocelyn S; Chen, Lee-May; Behr, Spencer C; Poder, Liina

2017-08-01

MR imaging and PET using 2-Deoxy-2-[ 18 F]fluoroglucose (FDG) are both useful in the evaluation of gynecologic malignancies. MR imaging is superior for local staging of disease whereas fludeoxyglucose FDG PET is superior for detecting distant metastases. Integrated PET/MR imaging scanners have great promise for gynecologic malignancies by combining the advantages of each modality into a single scan. This article reviews the technology behind PET/MR imaging acquisitions and technical challenges relevant to imaging the pelvis. A dedicated PET/MR imaging protocol; the roles of PET and MR imaging in cervical, endometrial, and ovarian cancers; and future directions for PET/MR imaging are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

SU-F-R-53: CT-Based Radiomics Analysis of Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

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

Huynh, E; Coroller, T; Narayan, V

Purpose: Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable non-small cell lung cancer (NSCLC) patients and has demonstrated excellent local control and survival. However, some patients still develop distant metastases and local recurrence, and therefore, there is a clinical need to identify patients at high-risk of disease recurrence. The aim of the current study is to use a radiomics approach to identify imaging biomarkers, based on tumor phenotype, for clinical outcomes in SBRT patients. Methods: Radiomic features were extracted from free breathing computed tomography (CT) images of 113 Stage I-II NSCLC patients treated with SBRT.more » Their association to and prognostic performance for distant metastasis (DM), locoregional recurrence (LRR) and survival was assessed and compared with conventional features (tumor volume and diameter) and clinical parameters (e.g. performance status, overall stage). The prognostic performance was evaluated using the concordance index (CI). Multivariate model performance was evaluated using cross validation. All p-values were corrected for multiple testing using the false discovery rate. Results: Radiomic features were associated with DM (one feature), LRR (one feature) and survival (four features). Conventional features were only associated with survival and one clinical parameter was associated with LRR and survival. One radiomic feature was significantly prognostic for DM (CI=0.670, p<0.1 from random), while none of the conventional and clinical parameters were significant for DM. The multivariate radiomic model had a higher median CI (0.671) for DM than the conventional (0.618) and clinical models (0.617). Conclusion: Radiomic features have potential to be imaging biomarkers for clinical outcomes that conventional imaging metrics and clinical parameters cannot predict in SBRT patients, such as distant metastasis. Development of a radiomics biomarker that can identify patients at high-risk of recurrence could facilitate personalization of their treatment regimen for an optimized clinical outcome. R.M. had consulting interest with Amgen (ended in 2015).« less

Lung metastases

MedlinePlus

Metastases to the lung; Metastatic cancer to the lung; Lung cancer - metastases ... Metastatic tumors in the lungs are cancers that developed at other places in the body (or other parts of the lungs). They then spread through the bloodstream or lymphatic ...

Malignant perivascular epithelioid cell tumor of the retroperitoneum

PubMed Central

Wu, Ji-Hua; Zhou, Jin-Lian; Cui, Yan; Jing, Qing-Ping; Shang, Le; Zhang, Jian-Zhong

2013-01-01

Perivascular epithelioid cell tumors (PEComas) are a rare type of mesenchymal neoplasms characterized by a proliferation of perivascular cells with an epithelioid phenotype and expression of myo-melanocytic markers. The majority of PEComas seem to be benign and usually their prognosis is good. Malignant cases are extremely rare, exhibiting a malignant course with local recurrences and distant metastases. We herein report a case of a malignant PEComa arising in the retroperitoneum. The patient was a 55-year-old woman experiencing abdominal discomfort for approximately one month. Ultrasound and computer tomography (CT) scans of the abdomen revealed a solid mass arising from the retroperitoneum. Microscopically, the tumor was composed of epithelioid cells mixed with spindled cells. The nucleus had significant atypia, and the mitoses were obvious. The focal intravascular tumor embolus was visible. Immunohistochemically, the epithelioid tumor cells were positive for HMB45 and Melan-A, and the spindled tumor celLs were positive for SMA and desmin. Seven months after a surgical resection, an ultrasound revealed liver metastases. In conclusion, the malignant PEComas of the retroperitoneum is a very rare neoplasm with unique morphological and immunohistochemical characteristics. It should be differentiated from other epithelioid cell tumors of the retroperitoneum. PMID:24133607

Malignant perivascular epithelioid cell tumor of the retroperitoneum.

PubMed

Wu, Ji-Hua; Zhou, Jin-Lian; Cui, Yan; Jing, Qing-Ping; Shang, Le; Zhang, Jian-Zhong

2013-01-01

Perivascular epithelioid cell tumors (PEComas) are a rare type of mesenchymal neoplasms characterized by a proliferation of perivascular cells with an epithelioid phenotype and expression of myo-melanocytic markers. The majority of PEComas seem to be benign and usually their prognosis is good. Malignant cases are extremely rare, exhibiting a malignant course with local recurrences and distant metastases. We herein report a case of a malignant PEComa arising in the retroperitoneum. The patient was a 55-year-old woman experiencing abdominal discomfort for approximately one month. Ultrasound and computer tomography (CT) scans of the abdomen revealed a solid mass arising from the retroperitoneum. Microscopically, the tumor was composed of epithelioid cells mixed with spindled cells. The nucleus had significant atypia, and the mitoses were obvious. The focal intravascular tumor embolus was visible. Immunohistochemically, the epithelioid tumor cells were positive for HMB45 and Melan-A, and the spindled tumor celLs were positive for SMA and desmin. Seven months after a surgical resection, an ultrasound revealed liver metastases. In conclusion, the malignant PEComas of the retroperitoneum is a very rare neoplasm with unique morphological and immunohistochemical characteristics. It should be differentiated from other epithelioid cell tumors of the retroperitoneum.

Clinical stage, therapy, and prognosis in canine anal sac gland carcinoma.

PubMed

Polton, Gerry A; Brearley, Malcolm J

2007-01-01

Reports of canine anal sac gland carcinoma (ASGC) describe varied clinical presentations and management and differing responses to therapy. A unifying approach to clinical stage determination and management of this disease has yet to be presented. An ordinal clinical staging scheme for canine ASGC can be devised on the basis of responses to therapy for a retrospective cohort of affected dogs. 130 dogs with naturally occurring ASGC. A simplified clinical stage system and a management algorithm for canine ASGC were derived from retrospective evaluation of a cohort of 80 dogs; applicability of both was then prospectively evaluated in a cohort of 50 dogs. Retrospective evaluation revealed 4 statistically significant negative prognostic indicators for survival: lack of therapy, presence of distant metastases, presence of lymph node metastases, and primary tumor size. Lymph node extirpation was a statistically significant positive prognostic indicator by bivariate analysis. In both retrospective and prospective analyses, the modified clinical stage scheme revealed a significant association with survival time. The clinical staging scheme permits differentiation between groups in terms of prognosis and, therefore, decisions on therapy. This will facilitate application of appropriate therapy and enhanced communication and collaboration in further investigations of ASGC.

Metastatic volume: an old oncologic concept and a new prognostic factor for stage IV melanoma patients.

PubMed

Panasiti, V; Curzio, M; Roberti, V; Lieto, P; Devirgiliis, V; Gobbi, S; Naspi, A; Coppola, R; Lopez, T; di Meo, N; Gatti, A; Trevisan, G; Londei, P; Calvieri, S

2013-01-01

The last melanoma staging system of the 2009 American Joint Committee on Cancer takes into account, for stage IV disease, the serum levels of lactate dehydrogenase (LDH) and the site of distant metastases. Our aim was to compare the significance of metastatic volume, as evaluated at the time of stage IV melanoma diagnosis, with other clinical predictors of prognosis. We conducted a retrospective multicentric study. To establish which variables were statistically correlated both with death and survival time, contingency tables were evaluated. The overall survival curves were compared using the Kaplan-Meier method. Metastatic volume and number of affected organs were statistically related to death. In detail, patients with a metastatic volume >15 cm(3) had a worse prognosis than those with a volume lower than this value (survival probability at 60 months: 6.8 vs. 40.9%, respectively). The Kaplan-Meier method confirmed that survival time was significantly related to the site(s) of metastases, to elevated LDH serum levels and to melanoma stage according to the latest system. Our results suggest that metastatic volume may be considered as a useful prognostic factor for survival among melanoma patients.

Tumor Volume Is a Prognostic Factor in Non-Small-Cell Lung Cancer Treated With Chemoradiotherapy

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

Alexander, Brian M.; Othus, Megan; Caglar, Hale B.

2011-04-01

Purpose: To investigate whether primary tumor and nodal volumes defined on radiotherapy planning scans are correlated with outcome (survival and recurrence) after combined-modality treatment. Methods and Materials: A retrospective review of patients with Stage III non-small-cell lung cancer treated with chemoradiation at Brigham and Women's Hospital/Dana-Farber Cancer Institute from 2000 to 2006 was performed. Tumor and nodal volume measurements, as computed by Eclipse (Varian, Palo Alto, CA), were used as independent variables, along with existing clinical factors, in univariate and multivariate analyses for association with outcomes. Results: For patients treated with definitive chemoradiotherapy, both nodal volume (hazard ratio [HR], 1.09;more » p < 0.01) and tumor volume (HR, 1.03; p < 0.01) were associated with overall survival on multivariate analysis. Both nodal volume (HR, 1.10; p < 0.01) and tumor volume (HR, 1.04; p < 0.01) were also associated with local control but not distant metastases. Conclusions: In addition to traditional surgical staging variables, disease burden, measured by primary tumor and nodal metastases volume, provides information that may be helpful in determining prognosis and identifying groups of patients for which more aggressive local therapy is warranted.« less

Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

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

Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.

2012-10-01

Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competingmore » risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests. Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients. Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.« less

[Benefits of the classical approach in surgery for pulmonary metastases].

PubMed

Horák, P; Pospísil, R; Poloucek, P

2011-03-01

Distant metastases remain a significant problem in the treatment of malignancies. Surgical management of pulmonary metastases is considered valuable from the oncological view only on condition that R0 resection can be achieved. The whole spectrum of resection procedures can be used, however most commonly, extraanatomic lung resections are employed. It has not been fully evaluated whether the same efficacy can be obtained with thoracoscopic procedures. The aim was to compare the study complication rates with literature data. The secondary aim was to evaluate the benefit of intraoperative lung palpation examination. The authors present a retrospective study in a group of subjects operated for secondary pulmonary malignancies in the Motol Charles University 2nd Medical Faculty and Faculty Hospital Surgical Clinic, from 2003 to 2007. The authors compared the patient group's morbidity and 30-day mortality rates with literature data. Preoperative CT findings, intraoperative palpation findings and histological examination findings were assessed. Postoperative morbidity of the operated subjects was 16.5%, postoperative 30-day mortality was 0%. The authors compared the preoperative diagnostic data based on CT, the intraoperative findings and histological findings. During the total of 77 surgical procedures, including open and VATS procedures, the authors performed intraoperative palpation examination and detected 60 foci (24.6% out of the total removed foci) previously undetected on CT. All of the foci were of less than 5mm and in 55 cases, the foci were proved metastases. The outcome data showing low postoperative morbidity rates and nul 30-day mortality have confirmed that pulmonary metastasectomy is a safe method, a part of the complex oncological management. A surgeon's palpation finding is considered unsubstitutable in the detection of all lung foci and for necessary orientation in order to identify the safety margin in wedge resections. Therefore, the authors prefer the open or videoassissted approach to purely miniinvasive procedures.

What Is the Optimal Treatment of Large Brain Metastases? An Argument for a Multidisciplinary Approach

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

Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.

2012-11-01

Purpose: Single-modality treatment of large brain metastases (>2 cm) with whole-brain irradiation, stereotactic radiosurgery (SRS) alone, or surgery alone is not effective, with local failure (LF) rates of 50% to 90%. Our goal was to improve local control (LC) by using multimodality therapy of surgery and adjuvant SRS targeting the resection cavity. Patients and Methods: We retrospectively evaluated 97 patients with brain metastases >2 cm in diameter treated with surgery and cavity SRS. Local and distant brain failure (DF) rates were analyzed with competing risk analysis, with death as a competing risk. The overall survival rate was calculated by themore » Kaplain-Meier product-limit method. Results: The median imaging follow-up duration for all patients was 10 months (range, 1-80 months). The 12-month cumulative incidence rates of LF, with death as a competing risk, were 9.3% (95% confidence interval [CI], 4.5%-16.1%), and the median time to LF was 6 months (range, 3-17 months). The 12-month cumulative incidence rate of DF, with death as a competing risk, was 53% (95% CI, 43%-63%). The median survival time for all patients was 15.6 months. The median survival times for recursive partitioning analysis classes 1, 2, and 3 were 33.8, 13.7, and 9.0 months, respectively (p = 0.022). On multivariate analysis, Karnofsky Performance Status ({>=}80 vs. <80; hazard ratio 0.54; 95% CI 0.31-0.94; p = 0.029) and maximum preoperative tumor diameter (hazard ratio 1.41; 95% CI 1.08-1.85; p = 0.013) were associated with survival. Five patients (5%) required intervention for Common Terminology Criteria for Adverse Events v4.02 grade 2 and 3 toxicity. Conclusion: Surgery and adjuvant resection cavity SRS yields excellent LC of large brain metastases. Compared with other multimodality treatment options, this approach allows patients to avoid or delay whole-brain irradiation without compromising LC.« less

Clear cell sarcoma: the Roswell Park experience.

PubMed

Finley, J W; Hanypsiak, B; McGrath, B; Kraybill, W; Gibbs, J F

2001-05-01

Clear cell sarcoma of the tendons and aponeuroses (CCSTA) is an aggressive, rare soft-tissue tumor with approximately 300 reported cases. Although it appears to be histogenetically related to melanoma, its clinical behavior resembles soft tissue sarcoma with a propensity for lymph node metastases. We report our experience at a tertiary cancer center. Eight cases of CCSTA evaluated at Roswell Park Cancer Institute between 1970 and 1998 were reviewed retrospectively. Patient data analyzed included patient age, gender, anatomic location, size of tumor, development of local, regional and distant recurrence, and patient status at last follow up. Six of eight patients were alive at 2 years, while three of seven patients were alive at 5 years. Of the patients alive with no evidence of recurrence, two had tumors of less than 2 cm, and the remaining patient had incomplete information regarding tumor size. Five patients recurred within 2 years of definitive surgical management. Four had tumors > 5 cm. All five patients progressed to metastatic disease at a median follow up of 20 months (range 1-108 months) following definitive surgical management and all eventually died of their disease at a median of 3 months (range 0-24 months) from presentation with metastatic disease. Four of five patients with lesions > 5 cm received adjuvant chemotherapy with intent to cure, but all eventually died of disease at 4, 22, 34, and 41 months from initial presentation. CCSTA is an aggressive tumor of the soft tissues. Early recognition and management are associated with an excellent long-term prognosis. Tumors greater than 5 cm warrant aggressive surgical management and treatment, and are at high risk of the development of distant disease. Aggressive multiagent chemotherapy appeared to have no impact on outcome. Other adjuvant therapeutic options including immunotherapy should be investigated. Copyright 2001 Wiley-Liss, Inc.

G protein-coupled estrogen receptor (GPER) regulates mammary tumorigenesis and metastasis

PubMed Central

Marjon, Nicole A.; Hu, Chelin

2014-01-01

The role of 17β-estradiol (E2) in breast cancer development and tumor growth has traditionally been attributed exclusively to the activation of ERα. Although targeted inhibition of ERα is a successful approach for patients with ERα+ breast cancer, many patients fail to respond or become resistant to anti-estrogen therapy. The discovery of the G protein-coupled estrogen receptor (GPER1) suggested an additional mechanism through which E2 could exert its effects in breast cancer. Studies have demonstrated clinical correlations between GPER expression in human breast tumor specimens and increased tumor size, distant metastasis, and recurrence, as well as established a proliferative role for GPER in vitro; however, direct in vivo evidence has been lacking. To this end, a GPER null mutation [GPER knockout (KO)] was introduced, through interbreeding, into a widely used transgenic mouse model of mammary tumorigenesis [MMTV-PyMT (PyMT)]. Early tumor development, assessed by the extent of hyperplasia and proliferation, was not different between GPER wild-type/PyMT (WT/PyMT) and those mice harboring the GPER null mutation (KO/PyMT). However, by 12-13 weeks of age, tumors from KO/PyMT mice were smaller with decreased proliferation compared to those from WT/PyMT mice. Furthermore, tumors from the KO/PyMT mice were of histologically lower grade compared to tumors from their WT counterparts, suggesting less aggressive tumors in the KO/PyMT mice. Finally, KO/PyMT mice displayed dramatically fewer lung metastases compared to WT/PyMT mice. Combined, these data provide the first in vivo evidence that GPER plays a critical role in breast tumor growth and distant metastasis. PMID:25030371

An endogenous inhibitor of angiogenesis derived from a transitional cell carcinoma: clipped beta2-glycoprotein-I.

PubMed

Beecken, Wolf-Dietrich C; Engl, Tobias; Ringel, Eva M; Camphausen, Kevin; Michaelis, Martin; Jonas, Dietger; Folkman, Judah; Shing, Yuen; Blaheta, Roman A

2006-09-01

Invasive cell carcinoma of the bladder often develops after complete transurethral excision of superficial transitional cell carcinoma. It has been postulated that primary tumors release angiogenesis-blocking proteins which suppress distant metastases. We have identified an endogenous protein which might be responsible for tumor dormancy. A transitional cell carcinoma cell line was developed (UMUC-3i) which inhibits the growth of a tumor implant at a distant site in SCID mice. Conditioned media of UMUC-3i cultured cells was first pooled and then fractioned, and the capacity of individual components to block endothelial cell growth was tested. The protein fraction responsible for blocking endothelial cell growth was identified by N-terminal amino acid sequencing as well as by mass-spectrometry. The effects of the purified protein in preventing endothelial cell proliferation and tube formation in an in vitro angiogenesis assay was investigated. The plasma protein beta(2)-glycoprotein-I (beta(2)gpI) was isolated and identified from conditioned medium of UMUC-3i cultured cells. Based on the in vitro angiogenesis assay, beta(2)gpI strongly inhibited endothelial cell growth and tube formation, whereby the inhibitory activity corresponded to the clipped version of beta(2)gpI (cbeta(2)gpI). Clipping was induced by adding plasmin at a molar ratio 1:15 (plasmin:substrate). Further analysis indicated that cbeta(2)gpI effects were mediated by annexin II surface receptors expressed on endothelial cells. cbeta2gpI may be involved in blocking angiogenic processes and bladder cancer progression. In this case, cbeta2gpI may be a promising tool in bladder cancer therapy.

Oncologic outcomes of patients with positive surgical margin after partial nephrectomy: a 25-year single institution experience.

PubMed

Petros, Firas G; Metcalfe, Michael J; Yu, Kai-Jie; Keskin, Sarp K; Fellman, Bryan M; Chang, Courtney M; Gu, Cindy; Tamboli, Pheroze; Matin, Surena F; Karam, Jose A; Wood, Christopher G

2018-07-01

To evaluate oncologic outcomes and management of patients with microscopic positive surgical margin (PSM) after partial nephrectomy (PN) for renal cell carcinoma (RCC). We reviewed our database to identify patients who underwent PN between 1990 and 2015 for RCC and had PSM on final pathology. A 1:3 matching was performed to a negative surgical margin (NSM) cohort. Kaplan-Meier method and log-rank test were used to estimate survival and differences in outcomes, respectively. Cox proportional hazards models were conducted to estimate the Hazards ratio. A total of 2297 patients underwent PN at our institution, of which 1863 (81%) had RCC. Microscopic PSM was found in 34 (1.8%) RCC patients who were matched to 100 patients with NSM. Of these 34 patients, local recurrence (n = 4), distant kidney recurrences (n = 4), and metastases (n = 5) developed during a median follow-up of 62 months. Bilateral tumors/tumors in a solitary kidney (n = 12/13, 92%), and multifocal tumors (n = 7/13, 54%) were found in patients who developed recurrence/metastasis. PSM patients were at a higher risk of shorter overall survival (p = 0.001), local recurrence-free survival (p = 0.003), distant recurrence-free survival (p = 0.032) and metastasis-free survival (p = 0.018). There was statistically significant association between PSM and bilateral tumors, prior treated RCC at presentation and higher nephrometry score in multivariable model. There was a low rate of microscopic PSM in our large cohort of patients undergoing PN despite tumor complexity. Higher nephrometry score, bilateral tumors, and prior treated RCC independently predicted PSM which showed worse survival, recurrence and metastasis compared to patients with NSM.

Predicting Survival of De Novo Metastatic Breast Cancer in Asian Women: Systematic Review and Validation Study

PubMed Central

Miao, Hui; Hartman, Mikael; Bhoo-Pathy, Nirmala; Lee, Soo-Chin; Taib, Nur Aishah; Tan, Ern-Yu; Chan, Patrick; Moons, Karel G. M.; Wong, Hoong-Seam; Goh, Jeremy; Rahim, Siti Mastura; Yip, Cheng-Har; Verkooijen, Helena M.

2014-01-01

Background In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. Materials and Methods We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic). Results We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48–0.53) to 0.63 (95% CI, 0.60–0.66). Conclusion The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making. PMID:24695692

P14.21 Can vascular risk factors influence number of brain metastases?

PubMed Central

Berk, B.; Nagel, S.; Kortmann, R.; Hoffmann, K.; Gaudino, C.; Seidel, C.

2017-01-01

Abstract BACKGROUND: Up to 30-40% of patients with solid tumors develop cerebral metastases. Number of cerebral metastases is relevant for treatment and prognosis. However, factors that determine number of metastases are not well defined. Distribution of metastases is influenced by blood vessels and cerebral small vessel disease can reduce number of metastases. Aim of this pilot study was to analyze the influence of vascular risk factors (arterial hypertension, diabetes mellitus, smoking, hypercholesterolemia) and of peripheral arterial occlusive disease (PAOD) on number of brain metastases. METHODS: 200 patients with pre-therapeutic 3D-brain MRI and available clinical data were analyzed retrospectively. Number of metastases (NoM) was compared between patients with/without vascular risk factors (vasRF). Results: Patients with PAOD had significant less brain metastases than patients without PAOD (NoM=4.43 vs. 6.02, p=0.043), no other single vasRF conferred a significant effect on NoM. NoM differed significantly between different tumor entities. CONCLUSION: Presence of PAOD showed some effect on number of brain metastases implying that tumor-independent vascular factors can influence brain metastasation.

CCR7 and CXCR4 Expression in Primary Head and Neck Squamous Cell Carcinomas and Nodal Metastases – a Clinical and Immunohistochemical Study

PubMed Central

Al-Jokhadar, Maya; Al-Mandily, Ahmad; Zaid, Khaled; Maalouf, Elie Azar

2017-01-01

Background: Squamous cell carcinomas (SCCs) are common head and neck malignancies demonstrating lymph node LN involvement. Recently chemokine receptor overxpression has been reported in many cancers. Of particular interest, CCR7 appears to be a strong mediator of LN metastases, while CXCR4 may mediate distant metastases. Any relations between their expression in primary HNSCCs and metastatic lymph nodes need to be clarified. Aims: To investigate CCR7 andCXCR4 expression in primary HNSCCs of all tumor sizes, clinical stages and histological grades, as well as involved lymph nodes, then make comparisons, also with control normal oral epithelium. Materials and Methods: The sample consisted of 60 formalin-fixed, paraffin-embedded specimens of primary HNSCCs, 77 others of metastasi-positive lymph nodes, and 10 of control normal oral epithelial tissues. Sections were conventionally stained with H&E and immunohistochemically with monoclonal anti-CCR7 and monoclonal anti-CXCR4 antibodies. Positive cells were counted under microscopic assessment in four fields (X40) per case. Results: There was no variation among primary HNSCC tumors staining positive for CCR7 and CXCR4 with tumor size of for CCR7 with lymph node involvement. However, a difference was noted between primary HNSCC tumors stained by CXCR4 with a single as compared to more numerous node involvement. CXCR4 appear to vary with the clinical stagebut no links were noted with histological grades. Staining for primary HNSCC tumors and metastatic lymph nodes correlated. PMID:28547946

Differential Impact of Whole-Brain Radiotherapy Added to Radiosurgery for Brain Metastases

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

Kong, Doo-Sik; Lee, Jung-Il, E-mail: jilee@skku.ed; Im, Yong-Seok

2010-10-01

Purpose: The authors investigated whether the addition of whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) provided any therapeutic benefit according to recursive partitioning analysis (RPA) class. Methods and Materials: Two hundred forty-five patients with 1 to 10 metastases who underwent SRS between January 2002 and December 2007 were included in the study. Of those, 168 patients were treated with SRS alone and 77 patients received SRS followed by WBRT. Actuarial curves were estimated using the Kaplan-Meier method regarding overall survival (OS), distant brain control (DC), and local brain control (LC) stratified by RPA class. Analyses for known prognostic variables weremore » performed using the Cox proportional hazards model. Results: Univariate and multivariate analysis revealed that control of the primary tumor, small number of brain metastases, Karnofsky performance scale (KPS) > 70, and initial treatment modalities were significant predictors for survival. For RPA class 1, SRS plus WBRT was associated with a longer survival time compared with SRS alone (854 days vs. 426 days, p = 0.042). The SRS plus WBRT group also showed better LC rate than did the SRS-alone group (p = 0.021), although they did not show a better DC rate (p = 0.079). By contrast, for RPA class 2 or 3, no significant difference in OS, LC, or DC was found between the two groups. Conclusions: These results suggest that RPA classification should determine whether or not WBRT is added to SRS. WBRT may be recommended to be added to SRS for patients in whom long-term survival is expected on the basis of RPA classification.« less

Psoas abscess secondary to retroperitoneal distant metastases from squamous cell carcinoma of the cervix with thrombosis of the inferior vena cava and duodenal infiltration treated by Whipple procedure: A case report and review of the literature.

PubMed

Mehdorn, Matthias; Petersen, Tim-Ole; Bartels, Michael; Jansen-Winkeln, Boris; Kassahun, Woubet Tefera

2016-08-11

Psoas abscess is a rare clinical disease of various origins. Most common causes include hematogenous spread of bacteria from a different primary source, spondylodiscitis or perforated intestinal organs. But rarely some abscesses are related to malignant metastatic disease. In this case report we present the case of a patient with known squamous cell carcinoma of the cervix treated with radio-chemotherapy three years prior. She now presented with a psoas abscess and subsequent complete inferior vena cava thrombosis, as well as duodenal and vertebral infiltration. The abscess was drained over a prolonged period of time and later was found to be a complication caused by metastases of the cervical carcinoma. Due to the massive extent of the metastases a Whipple procedure was performed to successfully control the local progress of the metastasis. As psoas abscess is an unspecific disease which presents with non-specific symptoms adequate therapy may be delayed due to lack of early diagnostic results. This case report highlights the difficulties of managing a malignant abscess and demonstrates some diagnostic pitfalls that might be encountered. It stresses the necessity of adequate diagnostics to initiate successful therapy. Reports on psoas abscesses that are related to cervix carcinoma are scarce, probably due to the rarity of this event, and are limited to very few case reports. We are the first to report a case in which an extensive and complex abdominal procedure was needed for local control to improve quality of life.

Undifferentiated carcinoma of the esophagus: a clinicopathological study of 16 cases☆

PubMed Central

Singhi, Aatur D.; Seethala, Raja R.; Nason, Katie; Foxwell, Tyler J.; Roche, Robyn L.; McGrath, Kevin M.; Levy, Ryan M.; Luketich, James D.; Davison, Jon M.

2015-01-01

Summary Undifferentiated carcinoma of the esophagus is a rare histologic variant of esophageal carcinoma. Using criteria based on studies of undifferentiated carcinomas arising at other sites, we have collected 16 cases of resected esophageal undifferentiated carcinomas. Patients ranged in age from 39 to 84 years (mean, 65.5 years) and were predominantly male (94%). The tumors were characterized by an expansile growth pattern of neoplastic cells organized in solid sheets and without significant glandular, squamous, or neuroendocrine differentiation. The neoplastic cells had a syncytial-like appearance, little intervening stroma, and patchy tumor necrosis. In a subset of cases, the tumor cells adopted a sarcomatoid (n = 2), rhabdoid (n = 1), or minor component (<5%) of glandular morphology (n = 3). In 1 case, reactive osteoclast-like giant cells were found interspersed among the neoplastic cells. Lymphovascular invasion, perineural invasion, and lymph node metastases were identified in 88%, 56%, and 81% of cases, respectively. In 12 (75%) specimens, the background esophageal mucosa was notable for Barrett esophagus. Consistent with the epithelial nature of these neoplasms, cytokeratin positivity was identified in all cases. In addition, SALL4 expression was present in 8 (67%) of 12 cases. Follow-up information was available for 15 (94%) of 16 patients, all of whom were deceased. Survival after surgery ranged from 1 to 50 months (mean, 11.9 months). Before death, 67% patients had documented locoregional recurrence and/or distant organ metastases. In summary, esophageal undifferentiated carcinomas are aggressive neoplasms and associated with a high incidence of recurrence and/or metastases and a dismal prognosis. PMID:25582499

IMP3 can predict aggressive behaviour of lung adenocarcinoma

PubMed Central

2012-01-01

Background Lung cancer most often presents as an inoperable tumour and the diagnosis is usually performed on a small biopsy/cytology specimen. In the group of non small cell lung cancer - not otherwise specified, adenocarcinoma phenotype can be determined immunohistochemically using TTF-1 and Napsin A. Expression of oncofetal protein IMP3 in human cancer is associated with poor differentiation and aggressive behaviour. In the present study expression of IMP3 was correlated with expression of TTF-1 and Napsin A, histological subtype and clinical stage of lung adenocarcinoma. We were interested whether distant metastases are associated with IMP3 overexpression, regardless of the histologic subtype of adenocarcinoma. Methods In retrospective study, consecutive series of 105 patients with advanced lung adenocarcinoma diagnosed from 2006 to 2009 in Clinical Hospital Center Split, Croatia, were analysed. Clinical data were collected from the Pulmology Department and time of death from the Mortality Registry. Paraffin blocks of bronchoscopic biopsies were collected from the Institute of Pathology and 15 cases excluded from the analysis due to insufficient material. Expression of IMP3, Napsin A and TTF-1 were analysed by indirect enzyme immunohistochemistry. Statistical analysis was performed and P values less than 0.05 considered significant. Results Of 90 patients, 71 (78%) were males and 19 (22%) females. Median age for males was 61.5 years (min-max 43–83) and for females 61 years (min-max 44–86). Pleural effusion was found in 15 (16.6%) and distant metastases in 45 (50%) cases. According to histological subtypes, there were 34 acinar, 2 lepidic, 2 papillary and 52 solid subtypes. IMP3 overexpression was found in 63 cases (70%) and was correlated with solid subtype (P = 0.002) and negative/weak Napsin A expression (P = 0.004). Strong Napsin A expression correlated with TTF-1 expression (P = 0.003) and lower histological grades (P = 0.031). Patients with IMP3 overexpression more often had distant metastases than patients with negative IMP3, 55.5% versus 33.3% (P = 0.033). Non solid subtypes with IMP3 overexpression developed distant metastasis more common than non solid subtypes with negative IMP3, 72% versus 35% (P = 0.028). Conclusions Expression of IMP3 correlates with solid subtype and with distant metastases regardless of histological subtype of lung adenocarcinoma. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/1966211581795258 Zusammenfassung Hintergrund Das Lungenkarzinom kommt meistens als nicht resektabler Tumor vor und die Diagnose kann nur in kleinen Biopsaten oder zytologisch gestellt werden. In der Gruppe der nicht kleinzelligen Lungenkarzinome kann der nicht anders spezifizierte Adenokarzinom Phänotyp mit Hilfe der Antikörper TTF-1 und Napsin A diagnostiziert werden. Die Expression des onkoföetalen Proteins IMP3 ist bei humanen Karzinomen mit agressivem Verhalten und metastatischem Potential verbunden. In dieser Studie korreliert die Expression von IMP3 mit TTF-1, Napsin A, histologischem Typ und klinischem Staging des Lungenkarzinoms. Wir waren daran interessiert, ob Fernmetastasen mit IMP3 Überexpression assoziiert sind, unabhängig von der histologischen Subtyp von Adenokarzinom. Methode In der retrospektiven Studie wurden die von 2006 bis 2009 im Klinischem Krankenhaus Split, Kroatien diagnostizerte Adenokarzinome der Lunge von 105 Patienten analysiert. Die klinischen Daten stammten aus der Abteilung für Pulmologie und im Falle des Todes vom Todesregister. Die Paraffinblöcke der primären Lungenbiopsate dieser Patienten wurden im Institut für Pathologie mit der indirekter Enzym - Immunohistochemie mittels Kombination der Antikörper gegen IMP3, Napsin A und TTF1 untersucht. 15 Fälle aus der Analyse aufgrund unzureichender Material ausgeschlossen. Es wurde eine statistische Untersuchung durchgeführt und Werte weniger als 0.05 P wurden als statistisch signifikant bezeichnet. Ergebnisse Von 90 Patienten mit Lungencarcinom waren 71 (78%) mänlich, durchschnittliches Alter war für Männer 61.5 Jahre (min-max 43–83) und 61 Jahre für Frauen (min-max 44–86). Pleurale Effusionen fand man in 15 Fällen (16.6%) und Fernmetastasen in 45 (50%) Fällen. Histologische Sybtypen waren: 2 lepidic Karzinome, 34 azinäre Karzinome, 2 papilläre und 52 solide Karzinome. IMP3 war exprimiert in 63 Fälle (70%). Positive IMP3 Expression war mit solidem Typ (P = 0.002) und negativer Napsin A Expression (P = 0.004) assoziert. Napsin A Expression war mit niedrigem Gradus (P = 0.031) und positiver TTF-1 Expression (P = 0.003) assoziert. Patienten mit IMP3 Überexpression öfter hatten Fernmetastasen als Patienten mit negativen IMP3, 55.5% versus 33.3% (P = 0.033). Non solide Subtyp mit IMP3 Überexpression entwickelten Fernmetastasen Meer häufiger als nicht festem Subtyp mit negativen IMP3, 72% versus 35% (P = 0.028). Schlussworte Die Expression von IMP3 ist mit negaativer Expression von Napsin A, solidem Subtyp und Metastasen verbunden und hat praktische predictive Werte in der pathologischen Diagnose des Adenokarzinoms der Lunge. Die Expression von IMP3 korreliert mit soliden Subtyp und mit Fernmetastasen unabhängig von histologische Subtyp Lungenadenokarzinom. PMID:23190601

Prognostic factors of HER2-positive breast cancer patients who develop brain metastasis: a multicenter retrospective analysis.

PubMed

Hayashi, Naoki; Niikura, Naoki; Masuda, Norikazu; Takashima, Seiki; Nakamura, Rikiya; Watanabe, Ken-ichi; Kanbayashi, Chizuko; Ishida, Mayumi; Hozumi, Yasuo; Tsuneizumi, Michiko; Kondo, Naoto; Naito, Yoichi; Honda, Yayoi; Matsui, Akira; Fujisawa, Tomomi; Oshitanai, Risa; Yasojima, Hiroyuki; Yamauchi, Hideko; Saji, Shigehira; Iwata, Hiroji

2015-01-01

The clinical course and prognostic factors of HER2-positive breast cancer patients with brain metastases are not well known because of the relatively small population. The aim of this study was to determine prognostic factors associated with HER2-positive patients who develop brain metastases. This retrospective study assessed the largest dataset to date of 432 HER2-positive patients who were diagnosed with brain metastases from 24 institutions of the Japan Clinical Oncology Group, Breast Cancer Study Group. The median age of the 432 patients was 54 years (range, 20-86 years). Of the patients, 162 patients (37.5 %) had ER-positive/HER2-positive (ER+HER2+) breast cancer, and 270 (62.5 %) had ER-negative/HER2-positive (ER-HER2+) breast cancer. The median brain metastasis-free survival period from primary breast cancer was 33.5 months in both groups. The median survival after developing brain metastasis was 16.5 and 11.5 months in the ER+HER2+ and ER-HER2+ groups, respectively, (p = 0.117). Patients with >3 brain metastases had significantly shorter overall survival in both ER+HER2+ (p < 0.001) and ER-HER2+ (p = 0.018) groups. Treatment with trastuzumab before developing brain metastases was not associated with survival duration after developing brain metastases (p = 0.571). However, patients treated with both trastuzumab and lapatinib after developing metastasis had significantly longer survival than patients treated with trastuzumab alone, lapatinib alone, or no HER2-targeting agent (p < 0.001). For HER2-positive patients with brain metastases, regardless of the use of trastuzumab before developing brain metastasis, treatment with both trastuzumab and lapatinib might improve survival.

Oropharyngeal Squamous Cell Carcinoma Treated With Radiotherapy or Radiochemotherapy: Prognostic Role of TP53 and HPV Status

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

Fallai, Carlo, E-mail: carlo.fallai@istitutotumori.mi.i; Perrone, Federica; Licitra, Lisa

Purpose: To study the prognostic value of the TP53 mutation and human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC). Methods and materials: The TP53 mutation and HPV status were analyzed in 78 cases of locoregionally advanced OPSCC. The possible correlation of these factors with locoregiownal control, relapse-free survival, disease-specific survival, and overall survival (OS) was also investigated. Results: Of these 78 cases, 22 had disruptive and 22 had non-disruptive (silent) TP53 mutations; the remaining 34 cases had wild-type (WT) TP53. HPV 16 DNA was found in 9 cases (11%), but all HPV-positive (HPV+) cases carried a functionalmore » p53 protein, except for 1 case that had a silent mutation. HPV+ patients fared better than HPV-negative (HPV-) patients in terms of all survival parameters, with highly statistically significant differences between the groups. Specifically, no distant metastases were observed in the HPV+ patients, whereas they occurred in 17% of the HPV- patients. However, no difference was observed between the WT TP53 and mutation group, even when this was analyzed in terms of disruptive and non-disruptive mutations. Regardless, treatment with chemotherapy nearly doubled the 5-year OS rates, both in the mutation (42% vs. 22%) and WT (30 vs. 16%) group, but only the mutation group showed improvement in all survival parameters. In addition, the second tumor-free 5-year survival rate was 72% in HPV- cases, but no second tumors were observed in HPV+ and WT p53 cases. Conclusions: Patients with HPV+ OPSCC have an excellent prognosis after radiochemotherapy, but cisplatin-based chemotherapy may not confer a satisfactory outcome, especially in WT cases, thereby justifying the additional or alternative use of taxanes and epidermal growth factor receptors inhibitors. Uncommon distant metastases and second tumors in the HPV+ group may be cause for clinicians to review the follow-up policies in these patients.« less

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

Therapeutic options in locally advanced thyroid carcinoma. Our experience.

PubMed

Avenia, Nicola; Monacelli, Massimo; Sanguinetti, Alessandro; Santoprete, Stefano; Pecoriello, Roberta; Ragusa, Mark; Puma, Francesco

2012-01-01

Thyroid cancer is the most common endocrine malignancy with an incidence equal to 1% of all malignant tumors. Prognostic factors affecting survival are manifold, including in several classifications (AMES, AGES, CORN and TNM). In this sense, the invasion of adjacent structures is one of the most important variables. The authors describe the experience of a single center in surgical treatment of advanced thyroid cancer. Between 1986 and 2010 , 1565 patients were undergoing surgery with thyroid cancer. In particular, 1403 interventions were made for differentiated cancer, 97 for medullary carcinoma, 25 for insular carcinoma, 29 for anaplastic carcinoma, 2 for plasmacytoma, and 7 for lymphoma and 2 for angiosarcoma. Among these 896 showed invasion of adjacent structures and / or distant metastases. There were no perioperative deaths or major complications. Surgical procedures consisted of: 13 loboistmectomy, 519 total thyroidectomy (TT), 325 TT with lymphadenectomy of the central compartment, 7 TT with radical lymphectomy, 621 TT with functional lymphectomy, 6 TT with breast lumpectomy, 5 TT with with video-assisted lung metastasectomy, 16-TT with resection and tracheal anastomosis, 6 TT with laryngotracheal resection, 3 TT with laryngectomy, 4 TT with trachetomy, 28 TT with respiratory stent placement, 12 tracheotomy. At present, 1328 patients were free of disease, while 104 showed recurrence. Total of 133 deaths were recorded, all linked to disease relapse. The role of surgery in the treatment of advanced thyroid cancer is still undeniable. In the presence of extracapsular trespassing, in fact, the adoption of interventions demolition permits long-term survival, given the lack of aggressiveness of the tumor differentiated representing the majority of cases. The aim of surgical radicalization addition, even in the presence of distant metastases, it is justified by the possibilities offered by the therapeutic radioiodine treatment, which is not feasible in the presence of significant amounts of thyroid tissue which picks. In the presence of undifferentiated tumors, finally, endoscopic or surgical treatment may be indicated by simple purpose of palliation of respiratory symptoms.

Comparison of differentiated thyroid cancer in children and adolescents (≤20 years) with young adults.

PubMed

Alzahrani, Ali S; Alkhafaji, Dania; Tuli, Mahmoud; Al-Hindi, Hindi; Sadiq, Bakr Bin

2016-04-01

Age is a major prognostic factor in differentiated thyroid cancer (DTC). It is not clear if paediatric DTC has a different histopathological profile and outcome than DTC in adult patients <45 years of age. To assess whether DTC in children and adolescents differs from young age group by comparing paediatric DTC (age ≤ 20) with DTC in patients >20 to <45 years of age. We studied all cases of paediatric DTC seen during the period 1998-2011. We compared this group with a large sample of 213 consecutive adult patients in the age group >20 to <45 years seen during the period 1998-1999 in terms of their pathological features, extent of the disease and long-term outcome. Both groups were managed by the same team at a single institution. A total of 310 DTC were studied including 97 paediatric patients [median age 17 years (range, 8-20)] and 213 young adult patients [median age 33 years (range, 20·5-44·9)]. There was no difference in gender distribution, tumour subtypes, size and tumour multifocality, but there was a significantly higher rate of extrathyroidal extension [40/75 (53·3%) vs 81/213 (38·0%), P = 0·03], lymph node [57/73 (78%) vs 102/183 (55·7%), P < 0·0001] and distant metastases [16/97 (16·5%) vs 8/213 (3·8%), P < 0·0001] in the paediatric than the adult groups. Kaplan-Meier analysis showed a higher risk of persistent/recurrent disease in the paediatric group than adults (log-rank test 0·03). However, there was no mortality secondary to DTC in both groups. Paediatric DTC is distinct from DTC in the young adults (age >20 to <45 years). It is characterized by a higher rate of extrathyroidal extension, lymph node and distant metastases and a higher risk of persistent/recurrent DTC. © 2015 John Wiley & Sons Ltd.

Prognostic factors in ectopic Cushing's syndrome due to neuroendocrine tumors: a multicenter study.

PubMed

Davi', Maria Vittoria; Cosaro, Elisa; Piacentini, Serena; Reimondo, Giuseppe; Albiger, Nora; Arnaldi, Giorgio; Faggiano, Antongiulio; Mantovani, Giovanna; Fazio, Nicola; Piovesan, Alessandro; Arvat, Emanuela; Grimaldi, Franco; Canu, Letizia; Mannelli, Massimo; Ambrogio, Alberto Giacinto; Pecori Giraldi, Francesca; Martini, Chiara; Lania, Andrea; Albertelli, Manuela; Ferone, Diego; Zatelli, Maria Chiara; Campana, Davide; Colao, Annamaria; Scaroni, Carla; Terzolo, Massimo; De Marinis, Laura; Cingarlini, Sara; Micciolo, Rocco; Francia, Giuseppe

2017-04-01

Evidence is limited regarding outcome of patients with ectopic Cushing's syndrome (ECS) due to neuroendocrine tumors (NETs). We assessed the prognostic factors affecting the survival of patients with NETs and ECS. Retrospective analysis of clinicopathological features, severity of hormonal syndrome, treatments from a large cohort of patients with NETs and ECS collected from 17 Italian centers. Our series included 110 patients, 58.2% female, with mean (±s.d.) age at diagnosis of 49.5 ± 15.9 years. The main sources of ectopic ACTH were bronchial carcinoids (BC) (40.9%), occult tumors (22.7%) and pancreatic (p)NETs (15.5%). Curative surgery was performed in 56.7% (70.2% of BC, 11% of pNETs). Overall survival was significantly higher in BC compared with pNETs and occult tumors ( P  = 0.033) and in G1-NETs compared with G2 and G3 ( P  = 0.007). Negative predictive factors for survival were severity of hypercortisolism ( P  < 0.02), hypokalemia ( P  = 0.001), diabetes mellitus ( P  = 0.0146) and distant metastases ( P  < 0.001). Improved survival was observed in patients who underwent NET removal ( P  < 0.001). Adrenalectomy improved short-term survival. Multiple factors affect prognosis of ECS patients: type of NET, grading, distant metastases, severity of hypercortisolism, hypokalemia and diabetes mellitus. BCs have the highest curative surgical rate and better survival compared with occult tumors and pNETs. Hypercortisolism plays a primary role in affecting outcome and quality of life; therefore, prompt and vigorous treatment of hormonal excess by NET surgery and medical therapy should be a key therapeutic goal. In refractory cases, adrenalectomy should be considered as it affects outcome positively at least in the first 2 years. © 2017 European Society of Endocrinology.

Induction chemotherapy in metastatic neuroblastoma--does dose influence response? A critical review of published data standards, options and recommendations (SOR) project of the National Federation of French Cancer Centres (FNCLCC).

PubMed

Pinkerton, C R; Blanc Vincent, M P; Bergeron, C; Fervers, B; Philip, T

2000-09-01

The purpose of this study was to determine, from a review of published data, whether in stage 4 neuroblastoma in children over 1 year of age, the dose or scheduling of induction chemotherapy influenced the response rate in distant metastases. Publications relating to induction chemotherapy since the introduction of cisplatin/epipodophyllotoxin combinations were identified using Medline, Current Contents and personal reference lists. Thirteen publications were identified which described 17 regimens involving 948 children. The doses and the scheduling of the various regimens were compared with a standard regimen OPEC (vincristine, cisplatin, teniposide, cyclophosphamide). These were correlated with the reported response rates in the bone marrow. Due to a lack of standardisation in the nature of restaging investigations, timing of restaging and definitions of response it was difficult to compare all studies. The complete response rate at distant metastases ranged from less than 40% to over 90%. For individual drugs; the comparative doses given in each course ranged up to 4.2 g/m(2) for cyclophosphamide, 280 mg/m(2) for cisplatin, 600 mg/m(2) for etoposide and 4.5 mg/m(2) for vincristine. There was no evidence of any positive correlation between response rate in the marrow and either the dose of any individual drug or the schedule used. In contrast to a previous study which included a number of older studies where disease assessment was even more variable, this analysis has failed to show any justification for the routine use of very intensive induction regimens in this disease. Such an approach should only be taken in the context of randomised trials in which timing and methods of reassessment can be standardised. Until such studies demonstrate superiority either in terms of response rate or progression-free survival lower morbidity regimens should remain the standard therapy.

Outcomes and Prognostic Variables in Adenoid Cystic Carcinoma of the Head and Neck: A Recent Experience

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

Gomez, Daniel R.; Hoppe, Bradford S.; Wolden, Suzanne L.

2008-04-01

Purpose: To analyze the recent experience of patients with adenoid cystic carcinoma treated with radiation therapy at Memorial Sloan-Kettering Cancer Center. Methods and Materials: From 1990 to 2004, a total of 59 patients with a diagnosis of primary adenoid cystic carcinoma of the head and neck received radiation therapy at our institution. The subsite distribution was oral cavity, 28% (n = 17); paranasal sinuses, 22% (n = 13); parotid, 14% (n = 8); submandibular, 14% (n = 8); oropharynx, 10% (n = 6); sublingual, 3% (n = 2); nasopharynx, 3% (n = 2); and other, 5% (n = 3). Tmore » Stage distribution was T1, 34% (n = 20); T2, 19% (n = 11); T3, 14% (n = 8); and T4, 34% (n = 20). Twenty-nine percent of patients (n = 17) were treated with intensity-modulated radiation therapy; 25% (n =15), with three-dimensional conformal therapy, and the remainder, with conventional techniques. Ninety percent (n = 53) of patients received treatment including the base of skull. Results: Median follow-up for surviving patients was 5.9 years. Five-year and 10-year rates of local control and distant metastases-free survival were 91%/81% and 81%/49%, respectively. Five-year and 10-year rates of disease-free and overall survival were 76%/40% and 87%/65%, respectively. On univariate analysis, stage T4 (p = 0.004) and gross/clinical nerve involvement (p = 0.002) were associated with decreased progression free survival, whereas stage T4 and lymph node involvement were associated with decreased overall survival (p = 0.046 and p < 0.001, respectively). Conclusions: Radiation therapy in combination with surgery produces excellent rates of local control, although distant metastases account for a high proportion of failures. Routine treatment to the base of skull reduces the significance of histologic perineural invasion, but major nerve involvement remains an adverse prognostic factor.« less

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

PubMed

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

2018-06-01

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

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

PubMed

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

2016-01-15

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

[Immunohistochemical hormonal mismatch and human epidermal growth factor type 2 [HER2] phenotype of brain metastases in breast cancer carcinoma compared to primary tumors].

PubMed

Joubert, C; Boissonneau, S; Fina, F; Figarella-Branger, D; Ouafik, L; Fuentes, S; Dufour, H; Gonçalves, A; Charaffe-Jauffret, E; Metellus, P

2016-06-01

Phenotype changes between primary tumor and the corresponding brain metastases are recent reported data. Breast cancer, with biological markers predicting prognosis and guiding therapeutic strategy remains an interesting model to observe and evaluate theses changes. The objective of our study was to compare molecular features (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor type 2, [HER2]) between brain metastases and its primary tumor in patients presenting with pathologically confirmed breast cancer. This retrospective study was based on the immunohistochemical analysis of the brain metastases paraffin embedded samples stored in our institutional tumor bank, after surgical resection. The level of expression of hormonal receptors and HER2 on brain metastases were centrally reviewed and compared to the expression status in primary breast cancer from medical records. Forty-four samples of brain metastases were available for analysis. Hormonal receptor modification status was observed in 11/44 brain metastases (25%) for ER and 6/44 (13.6%) for PR. A modification of HER2 overexpression was observed in brain metastases in 6/44 (13.6%). Molecular subtype modification was shown in 17 cases (38.6%). A significant difference was demonstrated between time to develop brain metastases in cases without status modification (HER2, ER and PR) (med=49.5months [7.8-236.4]) and in cases in which brain metastases status differs from primary tumor (med=27.5months [0-197.3]), (P=0.0244, IC95=3.09-51.62, Mann and Whitney test). the main interest of this study was to focus on the molecular feature changes between primary tumor and their brain metastases. Time to develop brain metastases was correlated to phenotypic changes in brain metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Interventional radiology in bone metastases.

PubMed

Chiras, J; Shotar, E; Cormier, E; Clarençon, F

2017-11-01

Interventional radiology plays a significant role in the treatment of bone metastases by various techniques, percutaneous or endovascular. Vertebroplasty is the most well-studied technique for stabilisation of spine metastases as it induces satisfactory stabilisation of the vertebra and offers clear improvement of the quality of life. Due to the success of this technique cementoplasty of other bones, mainly pelvic girdle, has been largely developed. The development of reinforced cementoplasty allows treatment of pre-fractural osteolysis of some long bones. The heat due to the polymerisation of the cement induces carcinolytic effect but this effect is not as important as that which results from radiofrequency destruction. This last technique appears currently as the most important development to definitively destroy bone metastases and is progressively replacing percutaneous alcoholic destruction of such lesions. Angiographic techniques, such as endovascular embolisation, can also be very useful to reduce the risk of surgical treatment of hyper vascular metastases. Chemoembolisation is currently developed to associate pain relief induced by Endovascular embolisation and the carcinolytic effect obtained by local endovascular chemotherapy. All these techniques should develop largely during the next years. © 2017 John Wiley & Sons Ltd.

CT texture features of liver parenchyma for predicting development of metastatic disease and overall survival in patients with colorectal cancer.

PubMed

Lee, Scott J; Zea, Ryan; Kim, David H; Lubner, Meghan G; Deming, Dustin A; Pickhardt, Perry J

2018-04-01

To determine if identifiable hepatic textural features are present at abdominal CT in patients with colorectal cancer (CRC) prior to the development of CT-detectable hepatic metastases. Four filtration-histogram texture features (standard deviation, skewness, entropy and kurtosis) were extracted from the liver parenchyma on portal venous phase CT images at staging and post-treatment surveillance. Surveillance scans corresponded to the last scan prior to the development of CT-detectable CRC liver metastases in 29 patients (median time interval, 6 months), and these were compared with interval-matched surveillance scans in 60 CRC patients who did not develop liver metastases. Predictive models of liver metastasis-free survival and overall survival were built using regularised Cox proportional hazards regression. Texture features did not significantly differ between cases and controls. For Cox models using all features as predictors, all coefficients were shrunk to zero, suggesting no association between any CT texture features and outcomes. Prognostic indices derived from entropy features at surveillance CT incorrectly classified patients into risk groups for future liver metastases (p < 0.001). On surveillance CT scans immediately prior to the development of CRC liver metastases, we found no evidence suggesting that changes in identifiable hepatic texture features were predictive of their development. • No correlation between liver texture features and metastasis-free survival was observed. • Liver texture features incorrectly classified patients into risk groups for liver metastases. • Standardised texture analysis workflows need to be developed to improve research reproducibility.

Percutaneous laser ablation of benign and malignant thyroid nodules.

PubMed

Papini, Enrico; Bizzarri, Giancarlo; Pacella, Claudio M

2008-10-01

Percutaneous image-guided procedures, largely based on thermal ablation, are at present under investigation for achieving a nonsurgical targeted cytoreduction in benign and malignant thyroid lesions. In several uncontrolled clinical trials and in two randomized clinical trials, laser ablation has demonstrated a good efficacy and safety for the shrinkage of benign cold thyroid nodules. In hyperfunctioning nodules, laser ablation induced a nearly 50% volume reduction with a variable frequency of normalization of thyroid-stimulating hormone levels. Laser ablation has been tested for the palliative treatment of poorly differentiated thyroid carcinomas, local recurrences or distant metastases. Laser ablation therapy is indicated for the shrinkage of benign cold nodules in patients with local pressure symptoms who are at high surgical risk. The treatment should be performed only by well trained operators and after a careful cytological evaluation. Laser ablation does not seem to be consistently effective in the long-term control of hyperfunctioning thyroid nodules and is not an alternative treatment to 131I therapy. Laser ablation may be considered for the cytoreduction of tumor tissue prior to external radiation therapy or chemotherapy of local or distant recurrences of thyroid malignancy that are not amenable to surgical or radioiodine treatment.

Analysis of Local Control in Patients Receiving IMRT for Resected Pancreatic Cancers

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

Yovino, Susannah; Maidment, Bert W.; Herman, Joseph M.

2012-07-01

Purpose: Intensity-modulated radiotherapy (IMRT) is increasingly incorporated into therapy for pancreatic cancer. A concern regarding this technique is the potential for geographic miss and decreased local control. We analyzed patterns of first failure among patients treated with IMRT for resected pancreatic cancer. Methods and Materials: Seventy-one patients who underwent resection and adjuvant chemoradiation for pancreas cancer are included in this report. IMRT was used for all to a median dose of 50.4 Gy. Concurrent chemotherapy was 5-FU-based in 72% of patients and gemcitabine-based in 28%. Results: At median follow-up of 24 months, 49/71 patients (69%) had failed. The predominant failuremore » pattern was distant metastases in 35/71 patients (49%). The most common site of metastases was the liver. Fourteen patients (19%) developed locoregional failure in the tumor bed alone in 5 patients, regional nodes in 4 patients, and concurrently with metastases in 5 patients. Median overall survival (OS) was 25 months. On univariate analysis, nodal status, margin status, postoperative CA 19-9 level, and weight loss during treatment were predictive for OS. On multivariate analysis, higher postoperative CA19-9 levels predicted for worse OS on a continuous basis (p < 0.01). A trend to worse OS was seen among patients with more weight loss during therapy (p = 0.06). Patients with positive nodes and positive margins also had significantly worse OS (HR for death 2.8, 95% CI 1.1-7.5; HR for death 2.6, 95% CI 1.1-6.2, respectively). Grade 3-4 nausea and vomiting was seen in 8% of patients. Late complication of small bowel obstruction occurred in 4 (6%) patients. Conclusions: This is the first comprehensive report of patterns of failure among patients treated with adjuvant IMRT for pancreas cancer. IMRT was not associated with an increase in local recurrences in our cohort. These data support the use of IMRT in the recently activated EORTC/US Intergroup/RTOG 0848 adjuvant pancreas trial.« less

Tumor-Infiltrating T Cells and the PD-1 Checkpoint Pathway in Advanced Differentiated and Anaplastic Thyroid Cancer

PubMed Central

Bastman, Jill J.; Serracino, Hilary S.; Zhu, Yuwen; Koenig, Michelle R.; Mateescu, Valerica; Sams, Sharon B.; Davies, Kurtis D.; Raeburn, Christopher D.; McIntyre, Robert C.; Haugen, Bryan R.

2016-01-01

Context: Five to 10% of patients with differentiated thyroid cancers (DTC) develop invasive and/or distant metastatic disease that is marginally improved with standard therapies. Prognosis is poor for patients with anaplastic thyroid cancer, with a median survival of 3–5 months. We suggest that a paradigm shift is necessary in the treatment of advanced cases. Objective: We hypothesized that a T-cell response is generated in advanced thyroid cancer and may be a viable therapeutic target. Design: Primary DTCs were analyzed by quantitative RT-PCR (n = 92) for expression of CD3, CD8, forkhead box (Fox)-P3, programmed death (PD)-1, PD-1 ligand-1, and PD-1 ligand-2 and biopsied for cellular analysis by flow cytometry (n = 11). Advanced pT4 cases (n = 22) and metastases (n = 5) were analyzed by immunohistochemistry. Setting: The study was conducted at the University of Colorado Hospital. Patients: Thyroid cancer patients undergoing thyroidectomy or completion surgery for advanced disease between 2002 and 2013 participated in the study. Intervention: There were no interventions. Main Outcome Measure: Immune markers were analyzed for association with disease severity. Results: Immune markers were commonly expressed at the RNA level. PD-L1 was higher (P = .0443) in patients with nodal metastases. FoxP3+ (P < .0001), PD-1+CD8+ (P = .0058), and PD-1+CD4+ (P = .0104) T cells were enriched in DTC biopsies. CD8+ and FoxP3+ T cells were detected by immunohistochemistry in all pT4 tumors and a subset of metastases. PD-1+ lymphocytes were found in 50% of DTCs. PD-L1 was expressed by tumor and associated leukocytes in 13 of 22 cases, and expression was more diffuse in anaplastic thyroid cancer (P = .0373). BRAFV600E mutation was associated with higher frequencies of tumor-associated lymphocytes (P = .0095) but not PD-L1 expression. Conclusions: PD-1 checkpoint blockades may have therapeutic efficacy in patients with aggressive forms of thyroid cancer. PMID:27045886

Epithelial-mesenchymal transition: a hallmark in metastasis formation linking circulating tumor cells and cancer stem cells.

PubMed

Książkiewicz, Magdalena; Markiewicz, Aleksandra; Zaczek, Anna J

2012-01-01

The occurrence of either regional or distant metastases is an indicator of poor prognosis for cancer patients. The mechanism of their formation has not yet been fully uncovered, which limits the possibility of developing new therapeutic strategies. Nevertheless, the discovery of circulating tumor cells (CTCs), which are responsible for tumor dissemination, and cancer stem cells (CSCs), required for tumor growth maintenance, shed light on the metastatic cascade. It seems that CTCs and CSCs are not necessarily separate populations of cancer cells, as CTCs generated in the process of epithelial-mesenchymal transition (EMT) can bear features characteristic of CSCs. This article describes the mechanisms of CTC and CSC formation and characterizes their molecular hallmarks. Moreover, we present different types of EMT occurring in physiological and pathological conditions, and we demonstrate its crucial role in providing CTCs with a CSC phenotype. The article delineates molecular changes acquired by cancer cells undergoing EMT that facilitate metastasis formation. Deeper understanding of those processes is of fundamental importance for the development of new strategies of early cancer detection and effective cancer treatment approaches that will be translated into clinical practice. Copyright © 2012 S. Karger AG, Basel.

[Role of sentinel lymph nodes and lymphatic mapping of colorectal cancer].

PubMed

Ivanov, K; Kolev, N; Ignatov, V; Temelkov, T; Madzhov, R

2005-01-01

The accuracy of staging of colorectal cancer is dependable of number of lymph nodes, colected and investegated from the pathologist. Moreover 50% of newfounded cases with colorectal cancer are diagnosed as I or II stage of the desease. Between 15% and 20% of these patients develop regional or distant metastases around 5 years after the examination, despite of the radical surgery. This may be due to pathological "understaging" (decrease of the stage), becouse of missed micrometastases, which size often is smaller than 5 mm. High accurate and specific pathologoanatomical methods for "ultrastaging" are cost-expensive, therefore their selective application to labeled sentinel lymph nodes has a economical benefit and saves a time. Moreover it is decreasing the understaging effect, assosiated with convectional pathologoanatomical investigaton. In the future, the technical progress will develop the intensive competiton between the sentinel lymph node mapping and the improved imaging diagnostic techniques as flurodeoxyglucose (18FDG), positron emision tomography (PET), or the other molecular imaging techniques. Unfortunately, the limited spatial resolution of these techniques, do not allow to be used for tumor staging as sentinel lymph node techniques. Therefore the sentinel lymphnode mapping become the choice of the lymphnode staging technique.

Body Mass Index and Locoregional Recurrence in Women with Early-Stage Breast Cancer.

PubMed

Warren, Laura E G; Ligibel, Jennifer A; Chen, Yu-Hui; Truong, Linh; Catalano, Paul J; Bellon, Jennifer R

2016-11-01

Higher body mass index (BMI) has been associated with increased distant recurrence and decreased survival for women with breast cancer. However, the relationship between BMI and locoregional recurrence (LRR) has been less well studied and was therefore the subject of this investigation. The study identified 878 women with early-stage invasive breast cancer who underwent breast-conservation therapy (BCT) between June 1997 and October 2007. Time from diagnosis to LRR was calculated using a competing risk analysis with contralateral breast cancer (CBC), distant metastases (DM), and death as the competing risks. Gray's competing risks analysis, which included an interaction term between menopausal status and BMI, was used to identify significant risk factors for the development of LRR. After a median follow-up period of 10.8 years, LRR was diagnosed as a first event for 45 women. In a multivariable analysis, BMI was positively associated with LRR but only in premenopausal women. Specifically, when these women were compared with normal- and underweight women, both the overweight women (hazard ratio (HR), 2.97; 95 % confidence interval (CI) 1.04-8.46; p = 0.04) and the obese women (HR, 3.36; 95 % CI 1.07-10.63; p = 0.04) showed a higher risk of LRR. A similar association between BMI and disease-free survival was noted for premenopausal but not postmenopausal women. For premenopausal women with invasive breast cancer who undergo BCT, BMI is an independent prognostic factor for LRR. If confirmed, these findings suggest that more aggressive treatment strategies may be warranted for these women.

Solitary liver metastasis from follicular variant papillary thyroid carcinoma: A case report and literature review

PubMed Central

Djenic, Brano; Duick, Daniel; Newell, James O.; Demeure, Michael J.

2014-01-01

Introduction Papillary (PTC) and follicular (FTC) thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Sites of metastases from FTC are usually osseous and those from PTC are in regional nodal basins and the lungs. Visceral metastases are rare and when they do occur, they tend do so in multiple sites. We present the case of a patient with a follicular variant of PTC and a solitary metastasis to the liver then review the relevant literature. Presentation of case An otherwise healthy 68-year-old woman was diagnosed with follicular variant papillary thyroid cancer in 2003 and subsequently underwent thyroidectomy. The patient’s endocrinologist conducted surveillance of her thyroid cancer. In 2012, due to rise in thyroglobulin, a whole body radioiodine scan was obtained which revealed an iodine-avid left liver lobe mass. Three cycles of radioiodine ablation therapy were unsuccessful and eventually the patient was referred for surgical resection. Metastatic evaluation including a PET scan was negative with the exception of an isolated enhancing 4 cm mass in segment 4B of the liver. Anatomic segmental resection of liver was performed without complications. Intraoperative ultrasonography was used to guide resection of the liver mass. Pathology reports confirmed metastatic follicular variant of PTC. Surgical margins were free of tumor. Patient was discharged home and is doing well one year after surgery. The latest thyroglobulin level was undetectable. Discussion Post-operative surveillance by PCP, endocrinologist or surgeon for patients with thyroid carcinoma should be performed routinely. If identified, a solitary liver metastasis from primary thyroid carcinoma should be considered for surgical resection. Due to sparse data available in literature, collecting more data to establish algorithms for treatment of such rare metastatic cancers may be able to aid physicians to achieve better outcomes. Conclusion Rare distant sites of metastases from DTC include eyes, pharynx, skin, muscle, ovaries, adrenal glands, kidneys, esophagus, pancreas and liver. Isolated, resectable liver metastases from PTC are exceedingly rare. Literature review revealed only 10 reported cases of liver metastases from DTC. As in our patient, solitary liver metastasis from PTC should be considered for surgical resection which offers the best chance for prolonged survival. PMID:25536153

The Molecular Biology of Adenoid Cystic Carcinoma

PubMed Central

Liu, Jia; Shao, Chunbo; Tan, Marietta L.; Mu, David; Ferris, Robert L.; Ha, Patrick K.

2011-01-01

Background Adenoid cystic carcinoma (ACC) is an unusual salivary gland malignancy that remains poorly understood. Standard treatment, including surgery with postoperative radiation therapy have attained reasonable local control rates, but the propensity for distant metastases has limited any improvement in survival over time. Our understanding of the molecular mechanisms driving adenoid cystic carcinoma is quite rudimentary, due to the infrequent nature of its occurrence. Methods An extensive literature review was performed on salivary gland adenoid cystic carcinoma and basic science research findings. Results This review highlights many findings that are emerging about the carcinogenesis of ACC including cytogenetics, tumor suppressor genes, oncogenes, epigenetic alterations, mitochondrial alterations, and biomarker studies. Conclusions While there have been many discoveries, much still remains unknown about this rare malignancy. PMID:22006498

Lymphoepithelioma-like carcinoma of the vulva, an underrecognized entity? Case report with a single inguinal micrometastasis detected by sentinel node technique.

PubMed

Bösmüller, Hans; Haitchi-Petnehazy, Sophie; Gruber, Christine; Roithmeier, Franz; Stummvoll, Wolfgang; Webersinke, Gerald

2011-01-10

This report describes an unusual EBV-negative lymphoepithelioma-like carcinoma of the vulva in a 73-year-old patient. The lesion was localised at the right minor labium and was resected by partial vulvectomy. A synchronous sentinel lymph node biopsy revealed a single micrometastasis in the right inguinal region, which prompted local radiotherapy. Follow-up nine months later showed only slight vulvar atrophy, without signs of local recurrence or distant metastases.Although lymphoepithelioma-like carcinomas of the skin and the female genital tract are presumed to have a better prognosis than their counterparts in the upper aerodigestive tract, possibly due to earlier detection and therapy, this case documents their potential for early metastasis.

Are metastases from metastases clinical relevant? Computer modelling of cancer spread in a case of hepatocellular carcinoma.

PubMed

Bethge, Anja; Schumacher, Udo; Wree, Andreas; Wedemann, Gero

2012-01-01

Metastasis formation remains an enigmatic process and one of the main questions recently asked is whether metastases are able to generate further metastases. Different models have been proposed to answer this question; however, their clinical significance remains unclear. Therefore a computer model was developed that permits comparison of the different models quantitatively with clinical data and that additionally predicts the outcome of treatment interventions. The computer model is based on discrete events simulation approach. On the basis of a case from an untreated patient with hepatocellular carcinoma and its multiple metastases in the liver, it was evaluated whether metastases are able to metastasise and in particular if late disseminated tumour cells are still capable to form metastases. Additionally, the resection of the primary tumour was simulated. The simulation results were compared with clinical data. The simulation results reveal that the number of metastases varies significantly between scenarios where metastases metastasise and scenarios where they do not. In contrast, the total tumour mass is nearly unaffected by the two different modes of metastasis formation. Furthermore, the results provide evidence that metastasis formation is an early event and that late disseminated tumour cells are still capable of forming metastases. Simulations also allow estimating how the resection of the primary tumour delays the patient's death. The simulation results indicate that for this particular case of a hepatocellular carcinoma late metastases, i.e., metastases from metastases, are irrelevant in terms of total tumour mass. Hence metastases seeded from metastases are clinically irrelevant in our model system. Only the first metastases seeded from the primary tumour contribute significantly to the tumour burden and thus cause the patient's death.

[Interventional radiology in bone metastases].

PubMed

Chiras, Jacques; Cormier, Evelyne; Baragan, Hector; Jean, Betty; Rose, Michèle

2007-02-01

Interventional radiology takes a large place in the treatment of bone metastases by numerous techniques, percutaneous or endovascular. Vertebroplasty appears actually as the most important technique for stabilisation of spine metastases as it induces satisfactory stabilisation of the vertebra and offer clear improvement of the quality of life. Due to the success of this technique cementoplasty of other bones, mainly pelvic girdle, largely develop. The heath due to the polymerisation of the cement induce carcinolytic effect but this effect is not as important as that can be created with radiofrequency destruction. This last technique appears actually as the most important development to destroy definitively some bone metastases and replace progressively alcoholic destruction of such lesions. Angiographic techniques appear more confidential but endovascular embolization is very useful to diminish the risk of surgical treatment of hyper vascular metastases. Chemoembolization is actually developped to associate the relief of pain induced by endovascular embolization and the carcinolytic effect obtained by local endovascular chemotherapy. All these techniques should develop largely during the next years and their efficacy and safety should improve largely by treating earlier the metastasis.

Palliative surgery for head and neck cancer with extensive skin involvement.

PubMed

Jang, David W; Teng, Marita S; Ojo, Bukola; Genden, Eric M

2013-05-01

To evaluate the role of regional and free tissue transfer for the palliative management of head and neck cancer with extensive skin involvement. Case Series. A retrospective review was performed of patients treated for head and neck cancer with involvement of the skin at the Mount Sinai Medical Center over a 5-year period (2006-2010). Only patients with extensive skin involvement and unresectable tumors who underwent palliative resection and reconstruction were included in the review. Subjects were analyzed for age, gender, performance status, primary site, tumor histology, extent of invasion, type of reconstruction, hospital course, wound complications, adjuvant therapy, survival, and cause of death. Twenty-five patients met the inclusion criteria for the review. Fourteen patients (56%) underwent regional flap reconstruction, and 11 patients (44%) underwent free flap reconstruction. The average length of stay was 7 days. Twenty-four patients (96%) had a medically uncomplicated postoperative hospital course. Nineteen patients (76%) were treated with adjuvant palliative radiotherapy and/or chemotherapy. Long-term follow-up was achieved for 19 patients. The median follow up in this group was 9.5 months. Eleven of the 21 patients (52%) developed wound complications postoperatively. Eight of these were minor wound dehiscences, while three developed major wound complications. Four patients (16%) had distant metastasis at the time of surgery, and the median time to develop distant metastases after surgery was 6 months. Median survival time was 9.5 months. Twenty-two patients (88%) were discharged in the care of their families with appropriate pain management and without the need for extensive wound care. For unresectable tumors with extensive skin involvement, palliative resection and reconstruction is a reasonable treatment option. Although survival may not be affected, addressing the odor, bleeding, pain, and infection associated with skin involvement has the potential to improve a patient's quality of life. 4. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary.

PubMed

McDowell, Lachlan J; Young, Richard J; Johnston, Meredith L; Tan, Tze-Jian; Kleid, Stephen; Liu, Chen S; Bressel, Mathias; Estall, Vanessa; Rischin, Danny; Solomon, Benjamin; Corry, June

2016-04-15

The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear. One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes. The median follow-up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high-risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85-1.36; P = .528), cancer-specific (hazard ratio, 1.12; 95% CI, 0.77-1.64; P = .542), or progression-free survival (hazard ratio, 1.03; 95% CI, 0.83-1.29; P = .783). Distant metastasis-free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status. p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High-risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site. © 2016 American Cancer Society.

Imaging macrophage distribution and density in mammary tumors and lung metastases using fluorine-19 MRI cell tracking.

PubMed

Makela, Ashley V; Foster, Paula J

2018-09-01

The presence of tumor-associated macrophages (TAMs) correlates with breast cancer progression and metastatic spread. Metastasis-associated macrophages (MAMs) are also recruited to distant sites, where they support metastatic growth. In this study, we demonstrate that in vivo fluorine-19 ( 19 F)-based MRI cell tracking can evaluate the density and distribution of macrophages within murine breast cancer tumors and associated metastases. Three murine breast cancer cell lines with different metastatic potentials (4T1, 168FARN, and 67NR) were implanted into the mammary fat pad in mice. In vivo whole body 19 F MRI was performed on tumor-bearing mice 24 hours post-intravenous injection of a perfluorocarbon (PFC) agent, which was taken up by macrophages in situ. TAMs were detected mainly in the periphery of primary tumors, and higher numbers of TAMs were detected in the more aggressive 4T1 tumors. Tumors had significantly greater 19 F spins/mm 3 when they were smaller, suggesting more TAM infiltration in early-stage tumors. 19 F signal was observed within lung metastases in mice with 4T1 tumors, and fluorescence microscopy confirmed the presence of PFC-positive macrophages. This study shows for the first time proof of the ability to use MRI cell tracking to visualize MAMs in the lungs. The ability to detect and monitor the number of TAMs in individual tumors with 19 F MRI would allow for identification of breast tumors with heavy infiltration of TAMs and could be used as a biomarker for decisions about how to best treat these patients as well as for monitoring responses to therapy. Magn Reson Med 80:1138-1147, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

Current Dosing Paradigm for Stereotactic Radiosurgery Alone After Surgical Resection of Brain Metastases Needs to Be Optimized for Improved Local Control

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

Prabhu, Roshan; Shu, Hui-Kuo; Winship Cancer Institute, Emory University, Atlanta, GA

2012-05-01

Purpose: To describe the use of radiosurgery (RS) alone to the resection cavity after resection of brain metastases as an alternative to adjuvant whole-brain radiotherapy (WBRT). Methods and Materials: Sixty-two patients with 64 cavities were treated with linear accelerator-based RS alone to the resection cavity after surgical removal of brain metastases between March 2007 and August 2010. Fifty-two patients (81%) had a gross total resection. Median cavity volume was 8.5 cm{sup 3}. Forty-four patients (71%) had a single metastasis. Median marginal and maximum doses were 18 Gy and 20.4 Gy, respectively. Sixty-one cavities (95%) had gross tumor volume to planningmore » target volume expansion of {>=}1 mm. Results: Six-month and 1-year actuarial local recurrence rates were 14% and 22%, respectively, with a median follow-up period of 9.7 months. Six-month and 1-year actuarial distant brain recurrence, total intracranial recurrence, and freedom from WBRT rates were 31% and 51%, 41% and 63%, and 91% and 74%, respectively. The symptomatic cavity radiation necrosis rate was 8%, with 2 patients (3%) undergoing surgery. Of the 11 local failures, 8 were in-field, 1 was marginal, and 2 were both (defined as in-field if {>=}90% of recurrence within the prescription isodose and marginal if {>=}90% outside of the prescription isodose). Conclusions: The high rate of in-field cavity failure suggests that geographic misses with highly conformal RS are not a major contributor to local recurrence. The current dosing regimen derived from Radiation Therapy Oncology Group protocol 90-05 should be optimized in this patient population before any direct comparison with WBRT.« less

The Results of the Combine Treatment of Patients with Liver Bilobar Metastases from Colorectal Cancer Using Radiofrequency Ablation.

PubMed

Kaganov, Oleg Igorevich; Kozlov, Sergei Vasilevich; Orlov, Andrei Evgenyevich; Blinov, Nikita Vyacheslavovich

2018-06-01

Colorectal cancer (CRC) is the third most common cancer worldwide. The mortality from CRC remains very high. The main cause of such a high mortality is a disseminate process with the appearance of distant metastases. In this regard, the treatment of metastatic lesions is recognized as an important trend in modern oncology. The program of study included 176 patients with colorectal cancer after primary tumor removal with the malignant progression-multiple (more than 4) bilobar liver metastases. The research was organized in Samara Regional Oncology Centre from 2001 to 2014. By the treatment method, patients were divided into two groups. Main group got the combined (chemotherapy + radiofrequency ablation (RFA)) treatment ( n  = 98). In control group, only chemotherapy was applied ( n  = 78). One-, two-, and three-year OS were 73.5, 25.1, and 7.2% in the main group and 39.6, 6.3, and 2.1% in the control group. The RFA application allowed us to reach the index of 4-year survival 1.8% in the main group, while we received only 2.1 of 3-year survival in the control group. The OS median reached 18 months in the main group and 11 months in the control group. So, the OS curves in two comparing groups were significantly different according to statistics (log-rank test 3.77, р  = 0.000). The application of RFA in combination with chemotherapy in the treatment of bilobar metastasis colorectal cancer allows to improve the performance of disease-free survival and overall survival significantly, compared with the group of patients who received only chemotherapy.

Proton Beam Therapy as a Nonsurgical Approach to Mucosal Melanoma of the Head and Neck: A Pilot Study

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

Zenda, Sadamoto, E-mail: szenda@east.ncc.go.jp; Kawashima, Mitsuhiko; Nishio, Teiji

2011-09-01

Purpose: The aim of this pilot study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the head and neck. Methods and Materials: Patients with mucosal melanoma of the head and neck with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. Results: Fourteen consecutive patients were enrolled from January 2004 through February 2008. Patient characteristics were as follows: median age 73 years old (range, 56 to 79 years); male/female ratio, 7/7;more » and T stage 1/2/3/4, 3/2/0/9. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 21%) and mild dermatitis (grade 3, 0%). As for late toxicity, 2 patients had a unilateral decrease in visual acuity, although blindness did not occur. No treatment-related deaths occurred throughout the study. Initial local control rate was 85.7%, and, with a median follow-up period of 36.7 months, median progression-free survival was 25.1 months, and 3-year overall survival rates were 58.0%. The most frequent site of first failure was cervical lymph nodes (6 patients), followed by local failure in 1 patient and lung metastases in 1 patient. On follow-up, 5 patients died of disease, 4 died due to cachexia caused by distant metastases, and 1 patient by carotid artery perforation cause by lymph nodes metastases. Conclusions: Proton beam radiotherapy showed promising local control benefits and would benefit from ongoing clinical study.« less

Seven-month prostate-specific antigen (PSA) is prognostic in patients with prostate cancer initially diagnosed with distant metastases.

PubMed

Nieder, Carsten; Haukland, Ellinor; Pawinski, Adam; Norum, Jan

2018-03-05

Recent research suggests that prostate-specific antigen (PSA) ≤ 0.2 ng/dl at 7 months is prognostic for better survival with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer regardless of chemotherapy with docetaxel. These results were derived from a group of clinical trial participants. Therefore, we performed a confirmatory analysis in patients treated outside of trials. Furthermore, we limited inclusion to those who presented with metastases at the initial diagnosis of prostate cancer (synchronous metastases). A retrospective analysis of a comprehensive regional database was performed. The oncology care in this region (Nordland County, Northern Norway) was provided by one center. Patients who were diagnosed between January 01, 2004 and December 31, 2016 were included. Of 101 patients, 90 were alive at 7 months and had their PSA value measured. Their median age was 68.5 years. Only six patients (7%) achieved PSA ≤ 0.2 ng/dl at 7 months. The median value was 4.05 ng/dl. Median overall survival was shortest in patients with PSA > 4.0 ng/dl (22 months). For patients with PSA between 0.3 and 4.0 ng/dl, median survival was 54 months (p = 0.0001). No further increase was seen in the small group with lower PSA. Statistical significance was also found for a cutoff of ≤ 1.0 ng/dl (55 vs. 32 months). PSA at 7 months predicts overall survival. Given that only 7% of patients achieved PSA ≤ 0.2 ng/dl, confirmation of this particular cutoff requires additional studies in other populations.

Tolerance and outcomes of stereotactic radiosurgery combined with anti-programmed cell death-1 (pembrolizumab) for melanoma brain metastases.

PubMed

Nardin, Charlee; Mateus, Christine; Texier, Mathieu; Lanoy, Emilie; Hibat-Allah, Salima; Ammari, Samy; Robert, Caroline; Dhermain, Frederic

2018-04-01

Anti-programmed cell death-1 (anti-PD1) antibodies are currently the first-line treatment for patients with metastatic BRAF wild-type melanoma, alone or combined with the anti-CTLA4 monoclonal antibody, ipilimumab. To date, data on safety and the outcomes of patients treated with the anti-PD1 monoclonal antibodies, pembrolizumab (PB), or nivolumab, combined with stereotactic radiosurgery (SRS), for melanoma brain metastases (MBM) are scarce. We retrospectively reviewed all patients with MBM treated with PB combined with SRS between 2012 and 2015. The primary endpoint was neurotoxicity. The secondary endpoints were local, distant intracranial controls and overall survival (OS). Among 74 patients with MBM treated with SRS, 25 patients with a total of 58 MBM treated with PB combined with SRS within 6 months were included. Radiation necrosis, occurring within a median time of 6.5 months, was observed for four MBM (6.8%) in four patients. No other significant SRS-related adverse event was observed. After a median follow-up of 8.4 months, local control was achieved in 46 (80%) metastases and 17 (68%) patients. Perilesional oedema and intratumour haemorrhage appearing or increasing after SRS were associated with local progression (P<0.001). The median OS was 15.3 months (95% confidence interval: 4.6-26). The timing between SRS and PB administration did not seem to influence the risk of radiation necrosis, intracranial control or OS. SRS combined with PB was well tolerated and achieved local control in 80% of the lesions. Prolonged OS was observed compared with that currently yielded in this population of patients. Prospective studies are required to explore further the optimal ways to combine immunotherapy and SRS.

Divergent expression of bacterial wall sensing Toll-like receptors 2 and 4 in colorectal cancer.

PubMed

Paarnio, Karoliina; Väyrynen, Sara; Klintrup, Kai; Ohtonen, Pasi; Mäkinen, Markus J; Mäkelä, Jyrki; Karttunen, Tuomo J

2017-07-14

To characterize the expression of toll-like receptors (TLR) 2 and 4 in colorectal cancer (CRC) and in normal colorectal mucosa. We analysed tissue samples from a prospective series of 118 unselected surgically treated patients with CRC. Sections from formalin fixed, paraffin embedded specimens were analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent assessors evaluated separately expression at the normal mucosa, at the invasive front and the bulk of the carcinoma, and in the lymph node metastases when present. Expression levels in different locations were compared and their associations with clinicopathological features including TNM-stage and the grade of the tumour and 5-year follow-up observations were analysed. Normal colorectal epithelium showed a gradient of expression of both TLR2 and TLR4 with low levels in the crypt bases and high levels in the surface. In CRC, expression of both TLRs was present in all cases and in the major proportion of tumour cells. Compared to normal epithelium, TLR4 expression was significantly weaker but TLR2 expression stronger in carcinoma cells. Weak TLR4 expression in the invasive front was associated with distant metastases and worse cancer-specific survival at 5 years. In tumours of the proximal colon the cancer-specific survival at 5 years was 36.9% better with strong TLR4 expression as compared with those with weak expression ( P = 0.044). In contrast, TLR2 expression levels were not associated with prognosis. Tumour cells in the lymph node metastases showed higher TLR4 expression and lower TLR2 expression than cells in primary tumours. Tumour cells in CRC show downregulation of TLR4 and upregulation of TLR2. Low expression of TLR4 in the invasive front predicts poor prognosis and metastatic disease.

Development of transplantable human chordoma xenograft for preclinical assessment of novel therapeutic strategies.

PubMed

Bozzi, Fabio; Manenti, Giacomo; Conca, Elena; Stacchiotti, Silvia; Messina, Antonella; Dagrada, GianPaolo; Gronchi, Alessandro; Panizza, Pietro; Pierotti, Marco A; Tamborini, Elena; Pilotti, Silvana

2014-01-01

Chordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies. In this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor. All 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and post treatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors. Overall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies.

Reviewing and Reconsidering Invasion Assays in Head and Neck Cancer

PubMed Central

Inglehart, Ronald C.; Scanlon, Christina S.; D’Silva, Nisha J.

2014-01-01

Head and neck squamous cell carcinomas (HNSCC) are malignant tumors that arise from the surface epithelium of the oral cavity, oropharynx and larynx, primarily due to exposure to chemical carcinogens or the human papilloma virus. Due to their location, dental practitioners are well-positioned to detect the lesions. Deadlier than lymphoma or melanoma, HNSCC is incompletely understood. For these reasons, dental practitioners and researchers are focused on understanding HNSCC and the processes driving it. One of these critical processes is invasion, the degradation of the basement membrane by HNSCC cells with subsequent movement into the underlying connective tissue, blood vessels or nerves. Cancer cells metastasize to distant sites via the blood vessels, lymphatics and nerves. Metastasis is associated with poor survival. Since invasion is essential for development and metastasis of HNSCC, it is essential to understand the mechanism(s) driving this process. Elucidation of the mechanisms involved will facilitate the development of targeted treatment, thereby accelerating development of precision/ personalized medicine to treat HNSCC. Robust in vitro and in vivo assays are required to investigate the mechanistic basis of invasion. This review will focus on in vitro and in vivo assays used to study invasion in HNSCC, with special emphasis on some of the latest assays to study HNSCC. PMID:25448226

A preclinical mouse model of invasive lobular breast cancer metastasis.

PubMed

Doornebal, Chris W; Klarenbeek, Sjoerd; Braumuller, Tanya M; Klijn, Christiaan N; Ciampricotti, Metamia; Hau, Cheei-Sing; Hollmann, Markus W; Jonkers, Jos; de Visser, Karin E

2013-01-01

Metastatic disease accounts for more than 90% of cancer-related deaths, but the development of effective antimetastatic agents has been hampered by the paucity of clinically relevant preclinical models of human metastatic disease. Here, we report the development of a mouse model of spontaneous breast cancer metastasis, which recapitulates key events in its formation and clinical course. Specifically, using the conditional K14cre;Cdh1(F/F);Trp53(F/F) model of de novo mammary tumor formation, we orthotopically transplanted invasive lobular carcinoma (mILC) fragments into mammary glands of wild-type syngeneic hosts. Once primary tumors were established in recipient mice, we mimicked the clinical course of treatment by conducting a mastectomy. After surgery, recipient mice succumbed to widespread overt metastatic disease in lymph nodes, lungs, and gastrointestinal tract. Genomic profiling of paired mammary tumors and distant metastases showed that our model provides a unique tool to further explore the biology of metastatic disease. Neoadjuvant and adjuvant intervention studies using standard-of-care chemotherapeutics showed the value of this model in determining therapeutic agents that can target early- and late-stage metastatic disease. In obtaining a more accurate preclinical model of metastatic lobular breast cancer, our work offers advances supporting the development of more effective treatment strategies for metastatic disease.

Metastasis Dormancy in Estrogen Receptor-Positive Breast Cancer

PubMed Central

Zhang, Xiang H.-F.; Giuliano, Mario; Trivedi, Meghana V.; Schiff, Rachel; Kent Osborne, C.

2013-01-01

About 20-40% of breast cancer patients eventually develop recurrences in distant organs, which are often not detected until years to decades after the primary tumor diagnosis. This phenomenon is especially pronounced in ER+ breast cancer, suggesting that ER+ cancer cells may stay dormant for a protracted period of time, despite adjuvant therapies. Multiple mechanisms have been proposed to explain how cancer cells survive and remain in dormancy , and how they become reactivated and exit dormancy. These mechanisms include angiogenic switch, immunosurveillance, and interaction with extracellular matrix (ECM) and stromal cells. How to eradicate or suppress these dormant cancer cells remains a major clinical issue because of the lack of knowledge about the biological and clinical nature of these cells. Herein, we review the clinical manifestation of metastasis dormancy in ER+ tumors, the current biological insights of tumor dormancy obtained from various experimental models, and the clinical challenges to predict, detect, and treat dormant metastases. We also discuss future research directions toward a better understanding of the biological mechanisms and clinical management of ER+ dormant metastasis. PMID:24298069

Comparison of International Guidelines on Mucosal Melanoma of the Head and Neck: A Comprehensive Review of the Role of Radiation Therapy.

PubMed

Pittaka, Maria; Kardamakis, Dimitrios; Spyropoulou, Despina

2016-01-01

Mucosal melanomas of the head and neck are rare pathological entities that correlate with poor prognosis due to their high propensity for local failure and distant metastases. The exact role of radiation therapy in the management of mucosal melanoma patients has not yet been fully proven, even though in everyday clinical practice these patients are referred for radiotherapy, in an effort to improve locoregional control. The guidelines of various societies on the role of radiation therapy for the treatment of mucosal melanoma of the head and neck region are very limited. We reviewed and analyzed the guidelines developed in the U.S.A. (National Comprehensive Cancer Network), Canada (Cancer Care Ontario and Canadian Medical Association), Europe (European Society for Medical Oncology and European Society for Radiotherapy and Oncology) and Australia and New Zealand (Cancer Council Australia) and isolated evidence for the management of mucosal melanomas of the head and neck region with radiation therapy worldwide. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Tumor cell migration in complex microenvironments

PubMed Central

Polacheck, William J.; Zervantonakis, Ioannis K.; Kamm, Roger D.

2012-01-01

Tumor cell migration is essential for invasion and dissemination from primary solid tumors and for the establishment of lethal secondary metastases at distant organs. In vivo and in vitro models enabled identification of different factors in the tumor microenvironment that regulate tumor progression and metastasis. However, the mechanisms by which tumor cells integrate these chemical and mechanical signals from multiple sources to navigate the complex microenvironment remain poorly understood. In this review, we discuss the factors that influence tumor cell migration with a focus on the migration of transformed carcinoma cells. We provide an overview of the experimental and computational methods that allow the investigation of tumor cell migration, and we highlight the benefits and shortcomings of the various assays. We emphasize that the chemical and mechanical stimulus paradigms are not independent and that crosstalk between them motivates the development of new assays capable of applying multiple, simultaneous stimuli and imaging the cellular migratory response in real-time. These next-generation assays will more closely mimic the in vivo microenvironment to provide new insights into tumor progression, inform techniques to control tumor cell migration, and render cancer more treatable. PMID:22926411

Nanobiotechnology for the Therapeutic Targeting of Cancer Cells in Blood.

PubMed

Li, Jiahe; Sharkey, Charles C; Huang, Dantong; King, Michael R

During metastasis, circulating tumor cells migrate away from a primary tumor via the blood circulation to form secondary tumors in distant organs. Mounting evidence from clinical observations indicates that the number of circulating tumor cells (CTCs) in the blood correlates with the progression of solid tumors before and during chemotherapy. Beyond the well-established role of CTCs as a fluid biopsy, however, the field of targeting CTCs for the prevention or reduction of metastases has just emerged. Conventional cancer therapeutics have a relatively short circulation time in the blood which may render the killing of CTCs inefficient due to reduced exposure of CTCs to drugs. Nevertheless, over the past few decades, the development of nanoparticles and nanoformulations to improve the half-life and release profile of drugs in circulation has rejuvenated certain traditional medicines in the emerging field of CTC neutralization. This review focuses on how the principles of nanomedicine may be applied to target CTCs. Moreover, inspired by the interactions between CTCs and host cells in the blood circulation, novel biomimetic approaches for targeted drug delivery are presented.

Overuse of surgery in patients with pancreatic cancer. A nationwide analysis in Italy

PubMed Central

Balzano, Gianpaolo; Capretti, Giovanni; Callea, Giuditta; Cantù, Elena; Carle, Flavia; Pezzilli, Raffaele

2016-01-01

Background According to current guidelines, pancreatic cancer patients should be strictly selected for surgery, either palliative or resective. Methods Population-based study, including all patients undergoing surgery for pancreatic cancer in Italy between 2010 and 2012. Hospitals were divided into five volume groups (quintiles), to search for differences among volume categories. Results There were 544 hospitals performing 10 936 pancreatic cancer operations. The probability of undergoing palliative/explorative surgery was inversely related to volume, being 24.4% in very high-volume hospitals and 62.5% in very low-volume centres (adjusted OR 5.175). Contrarily, the resection rate in patients without metastases decreased from 86.9% to 46.1% (adjusted OR 7.429). As for resections, the mortality of non-resective surgery was inversely related to volume (p < 0.001). Surprisingly, mortality of non-resective surgery was higher than that for resections (8.2% vs. 6.7%; p < 0.01). Approximately 9% of all resections were performed on patients with distant metastases, irrespective of hospital volume group. The excess cost for the National Health System from surgery overuse was estimated at 12.5 million euro. Discussion. Discrepancies between guidelines on pancreatic cancer treatment and surgical practice were observed. An overuse of surgery was detected, with serious clinical and economic consequences. PMID:27154812

Lymph node dissection for melanoma using tumescence local anaesthesia: an observational study.

PubMed

Kofler, Lukas; Breuninger, Helmut; Häfner, Hans-Martin; Schweinzer, Katrin; Schnabl, Saskia M; Eigentler, Thomas K; Leiter, Ulrike

2018-04-01

The possibility that tumescence local anaesthesia (TLA) may lead to dissemination of tumour cells in lymph nodes is presently unclear. To evaluate whether infiltration by TLA influences metastatic spread and survival probability, compared to general anaesthesia (GA), based on lymph node dissection in melanoma patients. In total, 281 patients (GA: 162; TLA: 119) with cutaneous melanoma and clinically or histologically-confirmed metastases in regional lymph nodes were included. All patients underwent complete lymph node dissection. Median follow-up was 70 months. The rate of lymph node recurrence at the dissection site was 25.3% in the GA group and 17.6% in the TLA group (p = 0.082). No significant difference was found concerning 10-year melanoma-specific survival (GA: 56.2%, TLA: 67.4%; p = 0.09), disease-free survival (GA: 72.8 %, TLA: 81.1%; p = 0.095), or lymph node-free survival (GA: 72.8%, TLA: 81.1%; p = 0.095). Distant metastases-free survival appeared to be slightly reduced in the TLA group (GA: 49.9%, TLA: 64.0%; p = 0.025). No differences were identified between the GA and TLA groups regarding prognostic outcome for overall survival or disease-free survival.

A first reported case of metastatic anorectal amelanotic melanoma with a marked response to anti-PD-1 antibody nivolumab: A case report.

PubMed

Tokuhara, Katsuji; Nakatani, Kazuyoshi; Tanimura, Hirotsugu; Yoshioka, Kazuhiko; Kiyohara, Takahiro; Kon, Masanori

2017-01-01

Anorectal amelanotic melanoma (AAMM) is a rare disease with poor prognosis. A standard treatment strategy for AAMM has not been established. We report a case of successful treatment of AAMM with nivolumab. A 67-year-old man was referred for colonoscopy which revealed type I tumor in the rectum. AAMM was diagnosed with immunostaining histopathological biopsy findings. Enhanced computed tomography (ECT) revealed the rectal tumor without distant organ metastasis. We performed laparoscopy-assisted abdominoperineal resection. ECT at three months after surgery revealed liver metastases and right ischial bone metastasis. Although we had started dacarbazine monotherapy, black spots that were suspicious of skin metastases had appeared on systemic skin. Therefore, we started nivolumab therapy. ECT at 3 months after initiation of nivolumab showed shrinkage of liver metastasis. We have continued strict follow-up every 2 months and checked no oncologic progression at 17 months after initiation of nivolumab. The anti-PD-1 antibody have improved prognosis of malignant melanoma. However, there are no reports of nivolumab for treatment of AAMM. Our patient is the first reported case of AAMM treated with nivolumab. We consider that nivolumab will be effective for non-cutaneous malignant melanoma. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Role of computed tomography angiography in detection and staging of small bowel carcinoid tumors

PubMed Central

Bonekamp, David; Raman, Siva P; Horton, Karen M; Fishman, Elliot K

2015-01-01

Small-bowel carcinoid tumors are the most common form (42%) of gastrointestinal carcinoids, which by themselves comprise 70% of neuroendocrine tumors. Although primary small bowel neoplasms are overall rare (3%-6% of all gastrointestinal neoplasms), carcinoids still represent the second most common (20%-30%) primary small-bowel malignancy after small bowel adenocarcinoma. Their imaging evaluation is often challenging. State-of-the-art high-resolution multiphasic computed tomography together with advanced postprocessing methods provides an excellent tool for their depiction. The manifold interactive parameter choices however require knowledge of when to use which technique. Here, we discuss the imaging appearance and evaluation of duodenal, jejunal and ileal carcinoid tumors, including the imaging features of the primary tumor, locoregional mesenteric nodal metastases, and distant metastatic disease. A protocol for optimal lesion detection is presented, including the use of computed tomography enterography, volume acquisition, computed tomography angiography and three-dimensional mapping. Imaging findings are illustrated with a series of challenging cases which illustrate the spectrum of possible disease in the small bowel and mesentery, the range of possible appearances in the bowel itself on multiphase data and extraluminal findings such as the desmoplastic reaction in mesentery and hypervascular liver metastases. Typical imaging pitfalls and pearls are illustrated. PMID:26435774

Carcinoid heart disease in patients without hepatic metastases.

PubMed

Bernheim, Alain M; Connolly, Heidi M; Pellikka, Patricia A

2007-01-15

Most carcinoid tumors originate in the gut. Carcinoid heart disease typically occurs when tumor progression results in the formation of hepatic metastases, which allow vasoactive substances to reach the heart without being metabolized in the liver. Except for patients with primary ovarian carcinoid tumors, the occurrence of carcinoid heart disease without hepatic metastases has been reported only anecdotally. From a retrospective analysis of 265 patients, 4 patients were identified who developed carcinoid heart disease in the absence of liver metastases or primary tumors located in the ovaries. All 4 patients had metastases to the retroperitoneal lymph nodes and had carcinoid syndrome. The reasons for referral to cardiac evaluation by transthoracic echocardiography were findings on auscultation in 3 patients and exertional dyspnea in 1 patient. In conclusion, cardiac symptoms or findings on auscultation should prompt further evaluation by transthoracic echocardiography in these patients, although the classic prerequisites for development of carcinoid heart disease are lacking.

Hepatic perfusion changes in mice livers with developing colorectal cancer metastases.

PubMed

Kruskal, Jonathan B; Thomas, Peter; Kane, Robert A; Goldberg, S Nahum

2004-05-01

To evaluate whether intrahepatic flow alterations occur during formation of hepatic colorectal cancer metastases and to identify possible causes of these alterations. Intravital imaging of exteriorized livers was performed in 72 live mice. Three groups of mice were studied: a sham-operated control group (n = 24), a group with nonmetastasizing subcutaneous gliomas (n = 24), and a group with developing hepatic CX-1 colon cancer metastases (n = 24). Microvascular flow parameters, leukocyte-endothelial interactions, and wall shear stress were directly measured in hepatic sinusoids and postsinusoidal venules at 2-day intervals prior to and during the development of metastases. The Kruskal-Wallis test was used initially to test for overall equality of medians in each data group. Single posttest comparisons of independent samples were performed with the Mann-Whitney test, with an overall statistical significance of .05. Prior to the development of visible colorectal cancer metastases, significant (P <.05) reductions occurred in sinusoidal and postsinusoidal flow and wall shear rates, coupled with increased leukocyte rolling and adherence. With tumor growth, flow was further compromised in 92% of tumors larger than 0.5 mm in diameter by extrinsic compression of sinusoids and portal venules and narrowing caused by adherent leukocytes. Significant intrahepatic flow alterations occur in mouse livers prior to growth of visible metastases and provide a rational explanation for elevation in the Doppler perfusion index that occurs prior to tumor formation.

Radiation Port Cutaneous Metastases: Reports of Two Patients Whose Recurrent Visceral Cancers Presented as Skin Lesions at the Site of Previous Radiation and Literature Review

PubMed Central

Hoyt, Brian Spencer; Cohen, Philip Randolph

2014-01-01

Radiation therapy is associated with a variety of complications, including the development of primary skin cancers in the radiated region. However, it is rare for patients with visceral cancers who are treated with radiation therapy to subsequently develop cutaneous metastasis within the radiation port. We describe two patients with internal malignancies who developed cutaneous metastases within their radiation ports following radiotherapy. In addition, we used PubMed to perform an extensive literature review and identify additional reports of cutaneous metastasis within a radiation port. We excluded patients who developed melanoma or primary skin cancers in the radiation port. We also excluded patients with non-solid organ malignancies. Herein, we summarize the characteristics of 23 additional patients who experienced radiation port cutaneous metastases and explore possible mechanisms for the occurrence of radiation port cutaneous metastases. PMID:24700938

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

Hata, Masaharu, E-mail: mhata@syd.odn.ne.j; Omura, Motoko; Koike, Izumi

Purpose: Extramammary Paget's disease (EMPD) is a relatively rare malignancy that usually arises in the genital areas. Wide surgical excision remains the standard and most reliable curative treatment of EMPD. However, surgery is sometimes not possible, because many patients are elderly, and complete excision can be difficult owing to the tumor location. We, therefore, performed a review to determine the role of radiotherapy (RT) for EMPD. Methods and Materials: A total of 22 patients with EMPD in their external genitalia (4 men and 18 women, age 52-94 years at RT) underwent RT with curative intent. Nine patients had regional lymphmore » node metastases. A total dose of 45-70.2 Gy (median, 60) was delivered to the pelvis, including the tumors, in 25-39 fractions (median, 33). Results: In all but 3 patients, the irradiated tumors were controlled during a follow-up period of 8-133 months (median, 42). Of the 22 patients, 13 developed recurrences, including local progression within the radiation field in 3 and lymph node and/or distant metastases outside the radiation field in 10, at 3-43 months after treatment. The 2- and 5-year local progression-free rates were 91% and 84%, respectively. Of the 22 patients, 7 patients had died at 33-73 months after RT. The cause of death was tumor progression in 4, infectious pneumonia in 2, and renal failure in 1 patient. The overall and cause-specific survival rates were 100% for both at 2 years and 53% and 73% at 5 years, respectively. No therapy-related Grade 3 or greater toxicity was observed. Conclusions: RT is safe and effective for patients with EMPD. It appears to contribute to prolonged survival as a result of good tumor control.« less

Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma.

PubMed

Czepczyński, Rafał; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikołajczak, Renata; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy; Signore, Alberto

2007-10-01

Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and compared with (99m)Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. (99m)Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.

CD117 expression in operable oesophageal squamous cell carcinomas predicts worse clinical outcome

PubMed Central

Fan, Huijie; Yuan, Yuan; Wang, Junsheng; Zhou, Fuyou; Zhang, Mingzhi; Giercksky, Karl-Erik; Nesland, Jahn M; Suo, Zhenhe

2013-01-01

Aims To investigate the aberrant expression of CD117 in oesophageal squamous cell carcinoma (SCC) and its prognostic significance. Methods and results Immunohistochemical staining for CD117 was performed on tissue microarray and routine tissue sections from 157 oesophageal SCC patients and 10 normal oesophageal epithelia adjacent to tumour. The positive rate of CD117 expression was 29.9% in oesophageal SCC tissues, whereas no CD117 expression was detected in the 10 normal oesophageal epithelia. CD117 expression was significantly associated with T stage (P < 0.001), distant metastasis (P = 0.015), lymph node metastasis (P = 0.019), and clinical stage (P = 0.021). Progression-free survival in the patients with CD117-positive tumours was shorter than that in the patients with CD117-negative tumours (P = 0.010). In univariate analyses, CD117 expression was the most significant factor for overall survival of oesophageal SCC patients (P < 0.001), followed by lymph node metastasis (P = 0.001), T stage (P = 0.002), clinical stage (P = 0.006), distant metastasis (P = 0.020), and histological grade (P = 0.027). Multivariate analyses verified that CD117 expression was an independent prognostic marker for oesophageal SCC patients (P = 0.002). In addition, CD117 expression predicted poorer survival in patients without distant metastases. Conclusions CD117 expression in operable oesophageal SCC may be a valuable prognostic marker, and detection of its expression in clinical samples may be useful in defining a subclass of oesophageal SCCs with extremely poor clinical outcome, which may require a specially targeted treatment modality. PMID:23570416

Pattern of distant extrahepatic metastases in primary liver cancer: a SEER based study.

PubMed

Wu, Wenrui; He, Xingkang; Andayani, Dewi; Yang, Liya; Ye, Jianzhong; Li, Yating; Chen, Yanfei; Li, Lanjuan

2017-01-01

Background and Aims : Primary liver cancer remains still the common cause of cancer-related deaths globally and the prognosis for patients with extrahepatic metastasis is poor. The aim of our study was to assess extrahepatic metastatic pattern of different histological subtypes and evaluate prognostic effects of extrahepatic metastasis in patients with advanced disease. Methods: Based on the Surveillance, Epidemiology and End Results (SEER) database, eligible patients diagnosed with primary liver cancer was identified between 2010 to 2012. We adopted Chi-square test to compared metastasis distribution among different histological types. We compared survival difference of patients with different extrahepatic metastasises by Kaplan-Meier analysis. Cox proportional hazard models were performed to identify other prognostic factors of overall survival. Results: We finally identified 8677 patients who were diagnosed with primary liver cancer from 2010 to 2012 and 1775 patients were in distant metastasis stages. Intrahepatic cholangiocarcinoma was more invasive and had a higher percentage of metastasis compared with hepatocellular carcinoma. Lung was the most common metastasis and brain was the least common site for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Extrahepatic metastasis could consider as an independent prognostic factor for patients with liver cancer. Patients with brain metastasis had the worst prognosis, compared with other metastasis in overall survival (OS) and cancer-specific survival (CSS) analysis. Conclusions: Different histological subtypes of liver cancer had different metastasis patterns. There were profound differences in risk of mortality among distant extrahepatic metastatic sites. Results from our studies would provide some information for follow-up strategies and future studies.

Detection of Local, Regional, and Distant Recurrence in Patients With PSA Relapse After External-Beam Radiotherapy Using {sup 11}C-Choline Positron Emission Tomography

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

Breeuwsma, Anthonius J., E-mail: a.j.breeuwsma@uro.umcg.n; Departments of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen; Pruim, Jan

2010-05-01

Purpose: An elevated serum prostate-specific antigen (PSA) level cannot distinguish between local-regional recurrences and the presence of distant metastases after treatment with curative intent for prostate cancer. With the advent of salvage treatment such as cryotherapy, it has become important to localize the site of recurrence (local or distant). In this study, the potential of {sup 11}C-choline positron emission tomography (PET) to identify site of recurrence was investigated in patients with rising PSA after external-beam radiotherapy (EBRT). Methods and Materials: Seventy patients with histologically proven prostate cancer treated with EBRT and showing biochemical recurrence as defined by American Society formore » Therapeutic Radiology and Oncology consensus statement and 10 patients without recurrence underwent a PET scan using 400 MBq {sup 11}C-choline intravenously. Biopsy-proven histology from the site of suspicion, findings with other imaging modalities, clinical follow-up and/or response to adjuvant therapy were used as comparative references. Results: None of the 10 patients without biochemical recurrence had a positive PET scan. Fifty-seven of 70 patients with biochemical recurrence (median PSA 9.1 ng/mL; mean PSA 12.3 ng/mL) showed an abnormal uptake pattern (sensitivity 81%). The site of recurrence was only local in 41 of 57 patients (mean PSA 11.1 ng/mL at scan), locoregionally and/or distant in 16 of 57 patients (mean PSA 17.7 ng/mL). Overall the positive predictive value and negative predictive value for {sup 11}C-choline PET scan were 1.0 and 0.44 respectively. Accuracy was 84%. Conclusions: {sup 11}C-choline PET scan is a sensitive technique to identify the site of recurrence in patients with PSA relapse after EBRT for prostate cancer.« less

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

PubMed Central

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

2016-01-01

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