bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of distance to a high-volume center on receipt of treatment for invasive bladder cancer.
Authors: Lomboy Jason , Macey Matthew , Sukhu Troy , Meyer Anne-Marie , Meng Ke , Nielsen Matthew Edward , Pruthi Raj , Wallen Eric , Woods Michael , Smith Angela 
Published: February 2017

461 Background: Regionalization of major surgery such as cystectomy has spurred interest in the association of high-volume centers (HVC) & improved postoperative outcomes. However, concerns have been raised regarding access to care, with increasing travel distance playing a role in treatment selection. Our objective was to evaluate the effect of distance to closest HVC on treatment selection for muscle-invasive bladder cancer (MIBC). Methods: Using a linked data resource combining NC Cancer Registry with administrative claims data from Medicare, Medicaid, and private insurance plans, we included adult patients diagnosed with Stage 2 bladder cancer from 2003-2008. We created 2 mutually exclusive treatment groups (standard: cystectomy or chemo-radiation; non-standard: other or no treatment). HVCs were identified as those performing > 15 cystectomies during the study period. Nearest distance was calculated by using straight-line distance between zip code of the patient and closest HVC. Bivariable analyses and multivariable logistic regression were used to evaluate the effect of nearest distance to a HVC on receipt of non-standard treatment for MIBC. Results: 274 patients with confirmed MIBC were identified, with n = 123 undergoing standard and n = 151 non-standard treatment. Mean age of patients in the standard group was 73.1 vs. 77.7 in the non-standard group (p < 0.001). Groups also differed by race and insurance type (minority patients and those with Medicaid or Medicare were more likely to receive non-standard treatment). However, no significant difference was noted for comorbidity, gender, or education. Patients who underwent non-standard therapy had shorter distances to a HVC (73% have a distance of < 30 miles) vs. those who received standard therapy (56%, < 30 miles) (p < 0.004). On multivariable analysis, distance > 30 miles to a HVC was associated with lower likelihood to undergo non-standard therapy (p = 0.005), even when controlling for age, gender, race, comorbidity, insurance and other factors. Conclusions: Distance to HVC is not associated with increased likelihood of receipt of standard therapy for MIBC. Regionalization of care may not significantly impact access to care as previously hypothesized.
Small cell carcinoma of the bladder: Comparison of survival in various treatment modalities at Fox Chase Cancer Center (FCCC) from 1995 to 2015.
Authors: Ghatalia Pooja , Jung Kyungsuk , Litwin Samuel , Bilusic Marijo 
Published: February 2017

465 Background: Small cell carcinoma of the bladder (SCBC) is a rare but aggressive neuroendocrine neoplasm. It accounts for only 0.35-0.70% of all bladder tumors. Because of its low incidence, there has been no consensus on the standard treatment of SCBC. We hypothesized that patients (pts) treated over the past 10 years would have better outcomes than those treated earlier, given recent treatment advances in oncology. Methods: We performed retrospective analysis of pts treated at FCCC with confirmed pathologic diagnosis of either SCBC or mixed urothelial and SCBC from 1995 to 2015. Kaplan-Meier estimates were made of the median times and log rank tests were used to compare OS and PFS. Results: We identified 38 pts, 10 women and 28 men who met inclusion criteria. The mean age at diagnosis was 68.2 years, all were Caucasians and 26 pts were smokers. Three pts (8%) had Stage I, 22 (58%) had Stage II, 6 (16%) had Stage III and 7 pts (18%) had Stage IV disease. Radical cystectomy was performed in 26 pts, 3 pts underwent surgery followed by radiation therapy, and 5 pts received primary radiation therapy alone. All but 1 pt received chemotherapy: 32 pts received neoadjuvant chemotherapy, 3 pts received adjuvant chemotherapy and 2 pts received both adjuvant and neoadjuvant chemotherapy. The number of prior lines of therapy, including perioperative chemotherapy as a line, was 1 in 25 pts, 2 in 7, 3 in 2 and 4 in 3 pts. Sixteen pts progressed after the primary treatment with the median time to progression of 7.7 months. The median OS was 397 days (95% CI: (309,633)), and median PFS was 332 days (95% CI: (427,608)). OS estimates are based on all 38 pts; PFS are based on 21 pts. There was no difference in OS (p = 0.752) in 19 pts who were treated before 12/31/2010 vs 19 pts treated after 12/31/2010. No difference was detected in PFS (p = 0.37) based on the earliest 10 (up to February 2010) vs final 11 pts (after February 2010) for whom data was available. Conclusions: No significant improvement in the treatment of SCBC or pt outcomes over the past 10 years was observed. Further data analysis will be aimed at comparing different treatment modalities and pt outcomes.
Evaluation of c-kit (CD 117) expression as a prognostic factor in testicular germ cell tumors: An Izmir Oncology Group (IZOG) study.
Authors: Salman Tarik , Yildiz Elif , Yildiz Ibrahim , Yavuzer Dilek , Unlu Mehtat , Varol Umut , Akyol Murat , Yildiz Yasar , Bayoglu Vedat , Kucukzeybek Yuksel , Alacacioglu Ahmet 
Published: February 2017

476 Background: Little progress has been made in the management of testicular germ cell tumors (TGCTs). c-kit (CD 117) is a good target for cancer treatment and possesses an impressive role in the current oncological practice. We aimed to evaluate c-kit expression in early stage TGCTs as a prognostic factor. Methods: Patients with TGCTs who were referred to the Medical Oncology Clinic were included in our study before starting chemotherapy. Immunohistochemistry was performed on formalin-fixed and paraffinembedded three-micrometer thick sections with CD 117 Rabbit Anti c-kit in vitro gene kit. Biochemically, we utilized AFP and β-HCG Immunlite 2000 device with solid phase chemiluminescent immunometric method, and LDH Roche models with the DP-standardized UV method. AFP 0-15 ng/ml, β-HCG < 0.1 mlu/ml and LDH 240-480 mg/dl were considered as normal values. Results: Sixty-five patients were included in our study. Forty-one (63%) patients had nonseminoma tumors (NSGCTs) and 24 (37%) had seminoma. Statistically significant c-kit expression was found in patients with seminoma (p<0.0001). There was no difference between negative or positive c-kit expression in terms of clinicopathological characteristics, including preoperative serum levels of AFP, β-HCG, LDH, lymph node involvement, distant metastasis, and IGCCCG risk classification. No correlation was found between these parameters and 5-year progression free survival (PFS) rate except for tumor stage, presence of lymph node metastasis and IGCCCG score (p=0.001, p=0.04, and p=0.0001, respectively). Five-year PFS rate of patients with positive CD 117 was 72.2% (95% CI, 54.6-89.8), and6.6% (95% CI, 31.2-82.1) for those without CD 117 expression involvement (p=0.12). Conclusions: So far, there has been no significant breakthrough in the treatment of cisplatinrefractory TGCTs in the era of targeted therapies. No prognostic importance of c-kit expression has been found in our study. However, we believe that c-kit expression, in numerical terms, can be considered as a good prognostic factor for patients with TGCTs. The fact that all seminoma cases displayed positive c-kit expression is what we think has driven this result.
High incidence of early metabolic syndrome in germ cell tumor: Report from a tertiary cancer center in India.
Authors: Biswas Bivas , Dabkara Deepak , Ganguly Sandip , Dwary Amit Dutt , Ghosh Indranil , Sen Saugata , Mukhopadhyay Sumit , Mukherjee Satyadip , Gupta Sujoy , Mallick Indranil , Mondal Pradip , De Monish 
Published: February 2017

488 Background: Late metabolic syndrome is well known in survivors of testicular germ cell tumor (GCT). Literature about early metabolic syndrome is scarce. Methods: Single institutional review of testicular GCT between June’2011 and December’2014. Patients with minimum post-treatment follow-up of 6 months were screened for signs of metabolic syndrome as per National Cholesterol Education Program (NCEP), if they had recorded blood pressure ≥130/85 mm of Hg and/or ≥10% weight gain from baseline. Partial metabolic syndrome was defined as - at least one abnormal criteria as per NCEP. Results: Sixty-three patients of testicular GCT completed treatment and were eligible for evaluation. Twenty-five patients fulfilled the screening criteria with median follow-up of 15 months (range: 6-40); median age of 35 years (range: 24-65). Treatment protocol was combined platinum based chemotherapy in 68% (n=17/25), single agent carboplatin in 20% (n=5/25), and surveillance only in 12% (n=3/25). Complete metabolic syndrome was found in 36% (n=9/25), partial metabolic syndrome in 44% (n=11/25). Blood pressure ≥130/85 mm of Hg was found in 64% (n=16/25), serum triglyceride ≥1.7 mmol/L in 61% (n=14/23), serum HDL cholesterol <1 mmol/L in 76% (n=16/21), and fasting plasma glucose ≥5.6 mmol/L in 30% (n=6/20). Median weight gain was 5 Kg (range: 2-14). Conclusions: Features of early metabolic syndrome (complete or partial) were detected in 80% of testicular GCT survivors in symptomatic and screened patients, and also in those who were in surveillance or who received single agent carboplatin only. So, all testicular GCT survivors should be screened for early metabolic syndrome and early intervention should be initiated as it may have significant long-term effects on mortality and morbidity.
Significance of serum N-glycan profiling as a diagnostic marker in testicular germ cell tumor.
Authors: Hatakeyama Shingo , Yoneyama Takahiro , Hashimoto Yasuhiro , Koie Takuya , Ohyama Chikara 
Published: February 2017

489 Background: Specific tumor marker for seminoma is still lacking. Moreover, 10% to 15% of the patients with non-seminomatous germ cell tumor (NSGCT) can be expected to have normal marker levels. Glycan-based biomarkers for testicular germ cell tumor (TGCT) have not yet been established. We examined whether the serum N-glycan profiling can be applied to detection in patient with TGCT. Methods: We performed a N-glycan structural analysis of sera from 14 patients with GCT and age-matched 28 healthy volunteers using the glycoblotting methods and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The intensity of the N-glycans was compared between the TGCT patients and the volunteers to select TGCT associate N-glycans. Optimal cut-off values were determined by receiver operating characteristic (ROC) curves. Selected N-glycans were divided according to cut-off values, and positive numbers of TGCT associated N-glycan was added up to risk classification. Results: Six (43%) had seminoma, and eight (57%) patients had NSGCT in this study. The numbers of patients in stage I, II, III were 5, 2, and 4, respectively. Three patients had extragonadal tumor. The numbers of patients in IGCCC good, intermediate and poor risk were 10, 1, and 3, respectively. There were 3 patients (21%) with negative in any tumor markers. We identified 70 kinds of N-glycans in sera from healthy volunteers and GCT patients. A total 6 of N-glycans; m/z 2336.85, 2378.86, 2890.05, 3195.16, 3341.22, 3560.30 were selected as significantly high intensity in the patient with TGCT than in the healthy volunteers, with the area under the curve (AUC) of 0.81, 0.83, 0.86, 0.84, 0.81, and 0.78, respectively. Tumor associated N-glycans were classified as positive or negative, and scored from 0 to 6 points. Optimal cut-off score for detection was determined by ROC curve, and score > 3 were selected (AUC 0.90, P < 0.001). Based on this classification, 2 of 3 patients with negative tumor markers were categorized as a carrier for TCGT. Conclusions: Although the present study is small and preliminary, serum N-glycan analysis is a potential approaches to discover new biomarkers for TGCT. Further validation study is warranted.
Prognostic value of copy-number alterations of the Cohesin complex in intermediate-risk prostate cancer recurrence.
Authors: So Jonathan , Chua Melvin , Lalonde Emilie , Mahamud Osman , Berlin Alejandro , Dal Pra Alan , Orain Michèle , Hovington Helene , Bergeron Alain , Fradet Yves , Têtu Bernard , Meng Alice , Zhang Junyan , Zafarana Gaetano , Livingstone Julie , Pintilie Melania , van der Kwast Theodorus , Fraser Michael , Boutros Paul , Bristow Robert G. 
Published: February 2017

49 Background: The Cohesin complex plays a critical role in mitotic progression and post-replicative DNA damage repair. It serves to bring together sister chromatids both in metaphase and in homologous recombination repair following ionizing radiation. The complex has also been shown to be phosphorylated in the ATM/BRCA1 pathway. The expression of various proteins in the complex are dysregulated in many cancers: breast, prostate, etc. Interestingly, in breast cancer cell lines, Cohesin is required for MYC activation in response to estrogen. Our study sought to correlate copy number alterations in this pivotal complex with biochemical relapse in prostate cancer patients. Methods: Our cohort consists of 284 patients with D’ Amico-classified intermediate-risk prostate cancer, treated with image-guided radiotherapy (IGRT, N = 143) or radical prostatectomy (RadP, N = 141). Pre-treatment biopsies and prostatectomy samples were analyzed using the Affymetrix Oncoscan array. The Phoenix and AUA criteria was used to define biochemical relapse for RadP and IGRT patients respectively. Results: Copy number alterations of RAD21, SMC1B, and STAG1 were observed in 18% (n = 52), 6.3% (n = 18), and 12% (n = 35) of the cohort respectively. They were predominantly losses in SMC1B, but gains in RAD21 and STAG1. All three genes in the Cohesin complex were associated with increased risk of biochemical relapse: RAD21 on chromosome 8 (HR = 1.93, 95% CI 1.23, 3.02, Wald’s p = 0.004), SMC1B on chromosome 22 (HR = 3.37, 95% CI 1.91, 5.94, Wald’s p < 10-4), and STAG1 on chromosome 3 (HR = 1.74, 95% CI 1.04, 2.89, Wald’s p < 0.05). However, when controlled for percent genome alteration and pre-treatment serum PSA levels, only copy number loss of SMC1B was a significant predictor of biochemical relapse (HR = 2.95, 95% CI 1.62, 5.38, Wald’s p < 10-3). Conclusions: We identified a novel association of copy-number alterations in members of the Cohesin complex with biochemical recurrence following radical prostatectomy or image-guided radiotherapy. This points to the central role of Cohesin in cell-cycle and DNA damage pathways promoting prostate cancer progression.
Survival outcomes of patients with metastatic germ cell tumor (mGCT) treated from 1998 to 2012: The Indiana University (IU) experience.
Authors: Adra Nabil , Ku Kimberly Peihsi , Kalra Maitri , Althouse Sandra , Hanna Nasser H. , Einhorn Lawrence H. , Albany Costantine 
Published: February 2017

491 Background: Patients with mGCT’s treated between 1975-1990 were classified by the International Germ Cell Cancer Collaborative Group (IGCCCG) into good, intermediate, and poor risk. This study attempts to identify prognostic factors in a contemporary cohort of patients with mGCT treated at IU. Methods: Retrospective analysis of all patients with GCT seen at IU from 1998-2012. 1,341 consecutive patients with mGCT were identified of whom 615 patients received initial chemotherapy at IU and were eligible for analysis. All patients in this cohort were treated with cisplatin-based combination chemotherapy. Kaplan-Meier methods were used for analysis of 5 year progression free survival (PFS) and overall survival (OS). Results: Median age was 29. Median follow up time 5 years. Good, intermediate, and poor risk disease had median AFP of 8, 1822, 291 and median hCG of 8, 5000, 12837 respectively. 89 (14%) patients had seminoma and 526 (86%) had non-seminomatous GCT (NSGCT). Primary site was testis/retroperitoneal in 565 (92%) and mediastinum in 48 (8%). The 5 year PFS and OS for patients with poor risk excluding primary mediastinal NSGCT (PMNSGCT) was 52% and 78% respectively. In contrast, 5 year PFS and OS for patients with PMNSGCT was 49% and 58% respectively. The results comparing outcomes of patients in IGCCCG versus patients at IU are depicted in the table below. Conclusions: In this contemporary retrospective dataset from Indiana University there was improvement in OS for men with poor risk mGCT, possibly due to improved salvage chemotherapy. Only patients with PMNSGCT continue to have poor outcomes and pose a therapeutic challenge due to lack of effective salvage therapy. [Table: see text]
Gene-expression signatures as prognostic for relapse in stage I testicular germ cell tumors (TGCT).
Authors: Lewin Jeremy Howard , Bedard Philippe L. , Hamilton Robert James , Chung Peter W. M. , Moore Malcolm J. , Jewett Michael A.S. , Anson-Cartwright Lynn , Virtanen Carl , Winegarden Neil , Haibe-Kains Benjamin , Warde Padraig Richard , Sweet Joan , Hansen Aaron Richard 
Published: February 2017

493 Background: Genomic signatures may compliment pathological features in identifying appropriate patients who may benefit from adjuvant therapy in Stage I (SI) TGCT. This study aimed to identify a gene expression pattern to differentiate between relapsed (R) and non-relapsed (NR) SI TGCT. Methods: Patients with SI non-seminoma (NS) and seminoma (S) were identified from an institutional database from 2000 to 2012. All patients were managed with active surveillance. NR-NS and NR-S patients were defined as having no evidence of relapse after 2 and 3 years of surveillance respectively. Following pathology review, RNA extraction and gene expression analysis was performed on archived paraffin embedded tumor and normal testicular tissue using Illumina Whole Genome DASL Human HT-12 V4 BeadChip. Hierarchical clustering analysis, ANOVA and t-tests were used to evaluate candidate genes and expression patterns that could differentiate NR and R samples. Results: 57 patients (12 R-NS, 15 R-S, 15 NR-NS, 15 NR-S) were identified with median relapse time of 5.6 (2.5-18.1) and 19.3 (4.7-65.3) months in NS and S cohorts respectively. 3 additional normal testis samples were included. Poor prognostic factors were more frequent in R versus NR cases (NS: vascular invasion [5/12 vs 0/15]; S: median size [4cm vs 2.8cm]). Unsupervised hierarchical clustering of 22822 probes randomly separated S from NS, indicating no batch effect. One-way ANOVA revealed 4525 significantly varying probes (p < 0.05) however, no statistically significant gene expression profile differentiated the 4 cohorts. A discriminative gene expression profile between R and NR cases was discovered when combining NS and S samples using 10 (p = 0.03) and 30 (p = 0.03) probe signatures with a 10 fold cross-validation. However, this profile was not observed in the S and NS cohorts individually. Conclusions: A discriminating signature for R and NR was identified for SI testis tumors, but not separately for NS and S. Biological relevance of these signatures is to be determined. Further studies are required to corroborate this profile in NS and S. If validated, these expression patterns could help identify patients beyond standard pathological risk algorithms for optimal management.
Re-irradiation of the pelvis for a genitourinary second malignant neoplasm or a local recurrence after full-dose pelvic radiotherapy for a pelvic cancer: Experience in a high-volume cancer center.
Authors: Kamran Sophia C. , Curreri Stephanie A. , Muralidhar Vinayak , Nguyen Paul L. , Martin Neil E. , Boyajian Richard , Harshman Lauren Christine , Efstathiou Jason A. , Beard Clair 
Published: February 2017

494 Background: Re-irradiation (re-RT) with external beam RT following prior pelvic RT has not been reported, given both an absence of guidelines and concerns for toxicity. We sought to characterize bladder and bowel toxicities among patients treated with high-dose palliative re-RT for genitourinary secondary malignant neoplasms (SMN) or local recurrence (LR) following prior RT for pelvic cancer and to assess the response to re-RT with regard to palliation of symptoms. Methods: With IRB approval, the records of 28 consecutive patients with advanced pelvic malignancies given palliative re-RT between 2008-2014 were retrospectively analyzed. Descriptive analyses focused on toxicities and symptom control; responses were evaluated by two independent observers. Results: The cohort contained 27 males and 1 female. Initial cancers included 19 prostate, 4 ureteral, 2 bladder, 2 rectal and 1 penile carcinoma and 1 large cell lymphoma. Median initial RT dose was 63.5 Gy (range, 30-75.6 Gy; 8 unknown). The median time between initial RT and re-RT was 9.5 years (range, 0.2-32 years). At re-RT, there were 16 LRs and 12 SMNs including 14 bladder, 11 prostate, 3 ureteral and 1 penile cancers. Indications for re-RT were most commonly pain and bleeding. Given the severity of symptoms and bulk of disease at the time of re-RT, hypofractionated higher-dose RT was given. Median re-RT dose was 50 Gy (range, 27.5-66 Gy). For patients who received < 60 Gy, the median daily re-RT dose was 250 cGy. Re-RT was well-tolerated; there were no grade 2-4 toxicities. After treatment, 24 patients (92%) had complete resolution of their symptoms. Relief was durable in 67% of patients. Median overall survival was 5.8 months (range, 0.3-38.9 months) and 89% of patients were followed until death. Median follow-up was 5.2 months (range, 0.23-30.2 months). Conclusions: This institutional series suggests that moderate- to high-dose re-RT with median cumulative doses ≥ 100 Gy may achieve successful palliation of pelvic symptoms without undue toxicity in patients previously treated with high-dose RT. These results require validation in a larger prospective cohort.
Discontinuing VEGF-targeted therapy (VEGF-TT) for progression versus toxicity impacts outcomes of second-line therapies in metastatic renal cell carcinoma (mRCC).
Authors: de Velasco Guillermo , Xie Wanling , Donskov Frede , Albiges Laurence , Beuselinck Benoit , Srinivas Sandhya , Agarwal Neeraj , Lee Jae-Lyun , Brugarolas James , Wood Lori , Kollmannsberger Christian K. , Rha Sun Young , North Scott A. , Kanesvaran Ravindran , Rini Brian I. , Broom Reuben James , Yamamoto Haru , Kaymakcalan Marina Dusevic , Heng Daniel Yick Chin , Choueiri Toni K. 
Published: February 2017

503 Background: A significant minority of mRCC patients prematurely discontinue first-line (1L) VEGF-TT due to toxicity. Whether clinical outcomes differ in patients receiving second line (2L) TT based on reason for discontinuation of 1L are unknown. Methods: Patients from 15 International mRCC Database Consortium (IMDC) centers who started 2L TT were included and the reason for discontinuation of 1L collected. Treatment outcomes of 2L, including response, time to treatment failure (TTF) and overall survival (OS) were assessed. Results: 1124 patients were identified: 866 patients (77%) discontinued 1L VEGF-TT due to progression, 208 patients (19%) due to toxicity. 50 patients (4%) who discontinue due to other reasons were excluded. The reason for discontinuation of 1L did not differ by IMDC risk group at start of 1L VEGF-TT (p=0.54) or 2L therapy (p=0.52). Median time from 1L VEGF-TT initiation to start of 2L in patients who progressed or stopped prematurely due to toxicity was 9.8 and 7.9 months, respectively. Compared to patients who stopped 1L VEGF-TT due to progression, patients who stopped due to toxicity had longer drug free interval between 1L and 2L (1.4 vs. 0.7 months; p<0.001), greater clinical benefit (CR/PR/SD) in second line (68% vs. 56%; adjusted OR: 1.58 (95%CI:1.07,2.35), p=0.023) and longer OS (17.4 vs. 11.2 months; adjusted HR: 0.69 (0.56,0.84), p=0.0002) adjusted for type of therapy, time to initiation of 2L, IMDC risk group and number of metastases at 2L (Table). Conclusions: mRCC patients with VEGF TT discontinuation 1L due to toxicity have better outcomes with 2L therapy than patients who stop therapy because of progression. These findings should be taken in consideration when designing clinical trials for second-line therapies in mRCC. [Table: see text]