bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized phase II study of flutamide with or without PSA-TRICOM in nonmetastatic castration-resistant prostate cancer (CRPC).
Authors: Bilusic M. , Gulley J. L. , Heery C. , Apolo A. B. , Arlen P. M. , Rauckhorst M. , McMahon S. , Dahut W. L. , Schlom J. , Madan R. A. 
Published: February 2017

163 Background: PSA-TRICOM is a vector-based, therapeutic cancer vaccine regimen consisting of recombinant poxviruses containing the transgenes for prostate-specific antigen (PSA) and 3 T-cell co-stimulatory molecules (TRICOM). A previous randomized, placebo-controlled phase II study demonstrated an 8.5-month improvement in median survival (25.1 months for PSA-TRICOM group vs. 16.6 months for control group) in men with metastatic CRPC. Methods: This study is currently enrolling patients with non-metastatic CRPC on testosterone suppression therapy who have a rising PSA. Patients are stratified by PSA doubling time and randomized to androgen receptor antagonist alone (flutamide) or flutamide plus PSA-TRICOM. Flutamide is given at the standard dose of 400 mg TID while PSA-TRICOM is given by monthly subcutaneous injections. The primary endpoint of the study is time to treatment failure (TTF) which is defined as biochemical recurrence (PSA rise) or development of metastatic lesions on scans. Results: The first 26 patients enrolled are evaluated in this analysis. For flutamide alone (n = 13), the median age at enrollment was 64.7 years and median Gleason Score was 8. For flutamide + PSA-TRICOM (n = 13), the median age at enrollment was 67.1 years and median Gleason score was 8. Median time to progression is 223 days for Fluatmide + PSA- TRICOM (range 70-638) vs. 85 days for Flutamide alone (56-372). Progression for 11/12 flutamide alone patients and 9/10 fluatmide + PSA-TRICOM patients has been by PSA rise only. Conclusions: Preliminary evidence suggests improvement in time to treatment failure using combination of hormonal therapy with flutamide + PSA-TRICOM vaccine compared to fluatmide alone in patients with non-metastatic CRPC. This trial will continue to accrue a total of 62 patients and also will evaluate immunological responses. No significant financial relationships to disclose.
Agent orange as a risk factor for positive prostate biopsy.
Authors: Ansbaugh N. J. , Shannon J. , Mori M. , Farris P. E. , Collins L. , Garzotto M. 
Published: February 2017

178 Background: Agent Orange (AO), a defoliate contaminated with the known carcinogen dioxin, has become a prominent concern as veterans of the Vietnam War who were exposed to AO are now reaching the age at which prostate cancer is most prevalent. While sufficient evidence has linked AO exposure to many diseases, only limited but suggestive evidence exists to support a positive association between AO and prostate cancer. Despite mixed findings, recent studies have found that the risk of prostate cancer in those exposed to AO was as high as twice the risk in those not exposed. The goal of this study was to examine this association between AO exposure and prostate cancer in a cohort of men referred for a prostate biopsy. Methods: In this retrospective cohort-design, risk factors were identified using historical clinical data from a population of veterans referred to the Portland VA Hospital for a prostate biopsy between 1993 and 2010. In addition to AO exposure, covariates included prostate specific antigen density (PSAD), results of the digital rectal exam (DRE), age at biopsy, family history, body mass index (BMI), race, and medication use. Outcomes of the biopsies were defined as either positive or negative according to the pathology report and risk factors were compared between individuals found to have prostate cancer and those without cancer. Multiple logistic regression was used to evaluate the effect of AO on risk of prostate cancer after adjustment for confounders. Results: Of the 2,720 veterans who underwent prostate biopsy, 896 (32.9%) were found to have prostate cancer. After adjustment for significant confounders including PSAD, DRE, age at biopsy, and family history of prostate cancer, veterans with prostate cancer were 49% more likely to have been exposed to AO as compared to those without prostate cancer (odds ratio = 1.49; 95% CI: 1.06-2.11, p=0.022). Conclusions: Agent Orange exposure was associated with a significant increase in prostate cancer detection in men referred for a prostate biopsy. The limitations in identifying biologically significant levels of AO exposure in this study may suggest potential for underestimation of the true risk. This study supports the findings of recent studies suggesting that AO exposure increases the risk of prostate cancer. No significant financial relationships to disclose.
Prostate cancer–specific mortality after definitive radiation therapy: Who dies of disease?
Authors: Kim M. M. , Hoffman K. E. , Levy L. B. , Frank S. J. , Choi S. , Nguyen Q. N. , Pugh T. , McGuire S. E. , Lee A. , Kuban D. A. 
Published: February 2017

181 Background: A competing risks analysis was undertaken to identify patient subgroups at greatest risk of dying from prostate cancer (CAP) after treatment with definitive external beam radiation therapy (RT) +/− androgen deprivation therapy (ADT) in the PSA era, and to determine which factors predict for survival from disease. Methods: A total of 2,675 men with localized CAP treated with RT +/− ADT at M. D. Anderson Cancer Center from 1987-2007 were evaluated. Prostate cancer-specific mortality (PCSM) and other cause mortality rates were calculated after stratifying patients according to NCCN risk group, RT dose, use of ADT, and age at treatment. In total, 21% had low-risk, 40% had intermediate-risk, and 39% had high-risk disease. Multivariate analysis (MVA) was performed using Cox regression modeling. Results: Median age was 68.5 years and median follow-up was 6.4 years. For patients with low-risk disease, only 0.2% died of CAP 10 years after treatment. None of the low-risk patients <70 years old who received ≥72 Gy died of CAP. The majority of deaths in the intermediate-risk group were also due to other causes; men ≥70 years old who received <72 Gy had the highest 10-year PCSM (5%). High-risk patients <70 years old who received <72 Gy without ADT had similar 10-year rates of CAP (15.2%) and non-CAP (18.5%) mortality. Men with high-risk disease <70 years old treated with higher doses >72 Gy were twice as likely to die from non-CAP causes (15.9%) than die from CAP (8.6%). In older men ≥70 years old with high risk disease, dose-escalation with ADT reduced 10-year PCSM from 14% to 4%, and most deaths were due to other causes (41% and 20%). On MVA, dose (p=0.002), ADT (p=0.007), PSA (p<0.0001) and Gleason score (p<0.0001) were predictive of PCSM in the high-risk group. Conclusions: Men with low- and intermediate-risk CAP treated with definitive RT are unlikely to die of disease. PCSM is higher in men with high-risk disease but can be reduced with dose escalation and ADT, although patients are still twice as likely to die of other causes. No significant financial relationships to disclose.
Prostate cancer screening and incidence among men younger than age 50.
Authors: Li J. , German R. , King J. , Joseph D. , Thompson T. , Wu X. , Tai E. , Ajani U. 
Published: February 2017

183 Background: Prostate cancer has long been considered as a disease of older men. However, age at diagnosis with prostate cancer has continued to decline. Since the introduction of prostate-specific antigen (PSA) test in 1986, the prostate cancer incidence rate has steadily and dramatically increased in men under age 50. This study aims to better understand demographic variations in prostate cancer screening and incidence, and clinical characteristics of prostate cancers in men under age 50. Methods: We examined prostate cancer testing data from the Behavioral Risk Factor Surveillance System (2002, 2004, 2006, and 2008) and prostate cancer incidence data from the CDC's National Program of Cancer Registries and the NCI's Surveillance, Epidemiology, and End Results programs (2001-2006). We estimated the weighted percentage of self-reported cancer testing using SUDAAN and age-adjusted cancer incidence rates and trends using SEER-STAT. Statistical significance for trends was determined by the annual percentage change (APC) differing form zero. Results: A total of 29,176 prostate cancer cases were identified from 2001-2006 among men under age 50. Of these, 551 (1.9%) were among men under age 40. Incidence rates remained stable from 2001-2006; however the incidence of well-differentiated tumors decreased significantly (APC=−24.7) during this time period. About 44% of men aged 40-49 years old reported having a prostate cancer test in the past two years. Prostate cancer testing and incidence rates were highest among men who were black, non-Hispanic, or lived in the northeast. Black men had more than a 2-fold increase in cancer incidence than white men. Conclusions: The magnitude of prostate cancer testing and incidence in men under age 50 reveals significant health/public health problems in this younger population. This study demonstrates substantial regional differences in prostate cancer testing and incidence in men under age 50. It also confirms that prostate cancer testing and incidence varies by race and ethnicity. We observed a large disparity in prostate cancer incidence between blacks and whites. The incidence rate remained stable over time; the dramatic decrease occurred in well-differentiated cancers. No significant financial relationships to disclose.
Prostate cancer hypoxia as a predictor of early biochemical and local failure after radiotherapy.
Authors: Milosevic M. , Bristow R. G. , Menard C. , Chung P. W. , Bayley A. , McLean M. , Toi A. , Gospodarowicz M. K. , Catton C. , Warde P. R. 
Published: February 2017

20 Background: Tumor hypoxia is an important determinant of patient outcome in many human malignancies, and has been associated with radioresistance and the development of metastases. The aim of this study was to determine the predictive effect of hypoxia in prostate cancer patients treated with RT. Methods: A total of 256 patients with clinically localized prostate cancer underwent pre-treatment, transrectal, ultrasound-guided measurement of tumor oxygen using a needle electrode. The median pO2 (mpO2) was 6.7 mm Hg and the median hypoxic proportion <10 mm Hg (HP10) was 0.63. Most patients were treated with IMRT to the prostate alone using doses in the range of 75.6-79.8 Gy. Sixty-one received neoadjuvant and concurrent hormonal therapy. The Phoenix definition of biochemical relapse was used, and the median follow-up was 5.4 years. Results: The 5-year bRFR was 78%. High PSA and Gleason score were independently associated with biochemical relapse, and formed the baseline clinical multivariate model. The effect of hypoxia was found to vary with the duration of patient follow- up. HP10, when added to the clinical multivariate model as a time-dependent variable, was a significant, independent predictor of early bRFR (p=0.015). The predictive effect of hypoxia diminished with increasing follow-up and was lost by 36 to 48 months. The relationship between hypoxia and early biochemical recurrence was more pronounced when the analysis was restricted to 144 patients with bulk tumor at the site of the oxygen measurements (p=0.008). Prostate biopsy was performed in 73 patients a median of 36 months after completing RT. Hypoxia was the only factor predictive of local recurrence in this sub-group, with the effect being greatest early in follow-up (p=0.038). Conclusions: This is the largest clinical study of prostate cancer hypoxia with direct measurement of tumor oxygen levels. It suggests that hypoxia in the index tumor increases the risk of recurrence early after completing RT but not at longer times. The results imply a complex interaction between hypoxia and local vs. distant failure, which may be better elucidated with longer follow-up. No significant financial relationships to disclose.
Primary genitourinary small cell carcinoma: Clinicopathologic and survival outcomes from SEER database.
Authors: Thota R. , Birdsong S. , Subbiah S. 
Published: February 2017

200 Background: Small cell carcinoma of genitourinary system (SCC) is a highly aggressive and rare entity. The aim of the study is to characterize the clinicopathologic characteristics and evaluate the treatment outcomes of SCC in adult patients. Methods: Retrospective analysis of 732 patents diagnosed with small cell carcinoma of bladder from 1973 to 2007 was done via SEER database. Demographics, stage, type of treatment received and cancer-specific mortality were examined. Results: 732 patients were identified with SCC of genitourinary tract of which 341 were small cell bladder cancer, 336 were small cell prostate cancer and 55 were small cell renal cancer. Of these 644 patients were males and 88 were females. Median age of diagnosis is 73 years for bladder, 72 years for prostate and 70 years for renal cancer. Majority of the patients were Caucasians (89%) followed by African Americans (6%) and other races (4.98%). Grading of the tumor revealed that 12 patients had well differentiated tumor, 18 patients had moderately differentiated tumor, 191 patients had poorly differentiated, 292 patients had undifferentiated tumor and 219 patients had unknown grade. Pathological T-stages were as follows: T1= 34 (4.6%), T2= 102 (14%), T3= 43 (9%), T4= 41 (5.6%), 38.4% unknown T stage and 67 (9%) patients had metastatic disease. In majority of the patients the treatment received was unknown (565), 90 patients received external beam radiation, and 76 patients received surgery. Cancer-specific mortality was 54% in bladder cancer, 71% in prostate cancer and 78.6% in renal cancer. Median overall survival for all stages was 15.8 months in bladder cancer, 11.3 months in prostate cancer and 8 months in renal cancer. Conclusions: Results show that SCC is a highly aggressive tumor with poor prognosis. Clinical trials involving multiple institutes are needed to accrue enough patients so that treatment paradigms for this uncommon disease can be developed. No significant financial relationships to disclose.
Significant interaction between testosterone recovery (TR) and biochemical progression-free survival (BPFS) in intermediate- and high-risk patients with prostate cancer treated with radiation therapy (RT) and androgen deprivation therapy (ADT).
Authors: Shasha D. , Nabhani T. , Rauth S. J. , Salant R. , Harrison L. B. 
Published: February 2017

202 Background: To examine the interaction testosterone-recovery-free survival (TRFS) and BPFS in patients with intermediate and high-risk prostate cancer treated with combined external beam radiation therapy (EBRT), prostate implant (PI), and ADT. Methods: We prospectively collected data between 1998 and 2010 from 1,564 patients with clinically localized prostate cancer treated by a single physician (DS). 294 patients with NCCN intermediate or high-risk prostate cancer were treated with EBRT, PI, and ADT. 60% of these patients had intermediate-risk disease. Initial prostate-specifc antigen (PSA), Gleason Score (GS), AJCC tumor stage (TStage), and RT parameters were recorded. PSA, and testosterone (T) were measured at each follow-up visit. BPFS was scored using the Phoenix definition. Testosterone recovery occurred when the serum T level rose above 150ng/ml. TR was dichotomized at 2 years. Survival was evaluated using Cox-regression analysis. Results: Median age was 66 yrs-old, intraquartile range (IQR) was 60-71. Median ADT duration (ADTD) was 1.31 years (IQR 0.25-2.35). Testosterone recovery (TR) was seen in 73% of patients. Median TRFS was 3.1 years (IQR 1.94-4.12). Median BPFS was 4.96 years (IQR 3.39-9.12). Overall BPFS was 90% in this patient population. Three patients experienced metastatic failure. There were no prostate cancer deaths. On univariate analysis ADTD (p=0.05), TRFS (p=0.04), GS (p=0.02), and PSA (p=0.05) were significantly associated with BPFS. On multivariable analysis TRFS (p=0.009), TStage (p=0.02), GS (p=0.02), and PSA (p=0.04) were significantly associated with BPFS. Conclusions: Prolonged testosterone suppression after combination EBRT/PI/ADT is strongly associated with improved BPFS. The physiological implications of this finding warrant further study. No significant financial relationships to disclose.
Prognostic clinical parameters to predict the necessity of reconstructive vascular surgery for patients who undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for advanced nonseminatous germ cell tumors (NSGCT).
Authors: Heidenreich A. , Schrader M. , Dieckmann K. , Winter C. , Pfister D. A. ,   German Testicular Cancer Study Group
Published: February 2017

229 Background: PC-RPLND remains an integral part of the multimodality treatment for advanced NSGCT. The need to resect and to replace the major retroperitoneal vessels must be known preoperatively to enable complete resection of the residual masses. Methods: PC-RPLND was performed in 411 patients with NSGCT and normalized (81%) or plateauing (19%) tumor markers following 3-4 cycles PEB/PEI. PC-RPLND was performed in 5 institutions with a variable surgical frequency of 14 to 158 PC-RPLNDs. Good, intermediate, and poor prognosis according to the IGCCCG criteria was identified in in 59.8%, 21.2%, and 19% respectively. Results: Resection of the inferior vena cava was performed in 28 (6.81%), resection of the abdominal aorta was necessary in 13 (3.16%) patients. In 29/41 (70.7%) adjunctive surgical procedures such as nephrectomy, small bowel resection, ureteral resection had to be performed to ensure complete resection of the residual masses. Histologically vital cancer or mature teratoma was identified in 78.1% of the resected vascular specimens. Mean time of surgery was 295 (243-615) Min., mean blood loss was 690 (350 – 3400) ml. Good prognosis was identified in 15.4%, intermediate and poor prognosis was present in 41%and 43.6%, resp. Of all 411 patients involvement of the major retroperitoneal vessels was found in 3.2%, 18.4% and 21.8% with good, intermediate, and poor prognosis, resp. The mean tumor diameter was 5.9 (1.0 – 32) cm for the entire cohort and 9.8 (4-32) cm for the cohort of patients with vascular surgery. Significant prognosticators to predict vascular involvement were identified by multivariate analysis: intermediate/poor prognosis, number of cycles of chemotherapy, tumor diameter > 14cm, circumferential encasement of > 50% of the vessel diameter. Conclusions: Complete resection of the inferior vena cava or the abdominal aorta during PC-RPLND is necessary in about 10% of patients. The identified predictors enable already preoperatively a risk adapted interdisciplinary approach for complete resection of the residual masses in an experienced centre. No significant financial relationships to disclose.
Multi-institutional quality-of-care initiative for nonmetastatic, muscle-invasive, transitional cell carcinoma of the bladder: Phase I.
Authors: Feifer A. , Taylor J. M. , Shouery M. , Steinberg G. D. , Stadler W. M. , Schoenberg M. , Zlotta A. , Lerner S. P. , Bajorin D. F. , Bochner B. ,   B.C.A.N. Muscle-invasive Bladder Cancer Quality of Care Consortium
Published: February 2017

240 Background: Evidence supports multimodality treatment for muscle invasive bladder cancer [MIBC] with the strongest evidence (level 1) existing for cisplatin-based neoadjuvant chemotherapy. Although reflected in guidelines for the management of MIBC, little is known about the variation of actual practice patterns among academic institutions. We thus evaluated treatment variation among 14 academic centers in the management of patients with MIBC. Methods: Retrospective data were collected for centralized analysis. All patients who underwent radical cystectomy for clinical T2-4 N0M0 MIBC from 2003–2008 were eligible for inclusion. Specific endpoints for analysis included: rates of neoadjuvant and adjuvant therapy, cisplatin use, number of cycles and rates of pelvic lymphadenectomy. Results: 14 institutions participated and data on 4,541 patients who met inclusion criteria were tabulated. Overall 34% of patients received perioperative chemotherapy. The overall use of neoadjuvant and adjuvant therapy was 12% and 22%, respectively. In a subset analysis of those patients with specific chemotherapy agent information provided (n=3,120), 59% of patients managed with perioperative chemotherapy received cisplatin. Of those who received treatment in the neoadjuvant setting, cisplatinum was received in 65% of cases (supported by level 1 evidence). 80% of patients who received perioperative chemotherapy received at least 3 cycles. At radical cystectomy 95% of patients received a bilateral PLND. Conclusions: In this cohort of academic North American centers, 66% of potentially eligible bladder cancer patients undergoing radical cystectomy did not receive perioperative chemotherapy. Only 12% of patients received neoadjuvant chemotherapy, and 35% of those patients received a non-cisplatin based regimens. Despite level 1 evidence that cisplatin based neoadjuvant chemotherapy is associated with a survival advantage, only a small percentage of eligible patients undergoing radical cystectomy for muscle invasive, resectable disease receive combined treatment. Further study is needed clarify specific reasons for the treatment variation observed in academic centers. No significant financial relationships to disclose.
Phase II study of everolimus (RAD001) in metastatic transitional cell carcinoma (TCC) of the urothelium.
Authors: Milowsky M. I. , Regazzi A. M. , Garcia-Grossman I. R. , Trout A. , Flaherty A. , Gerst S. , Bajorin D. F. 
Published: February 2017

245 Background: Second-line chemotherapy has limited activity in advanced TCC with a median progression free survival (PFS) of 2-3 months. We have previously demonstrated the overexpression of activated mTOR pathway markers in invasive TCC specimens (BJU Int. 2010 Jul 26). Everolimus selectively inhibits mTOR, a central regulator of cell growth, proliferation, survival, and angiogenesis. This trial was designed to assess the efficacy of everolimus in patients (pts) with advanced TCC. Methods: The primary objectives of this single-institution phase II trial of everolimus in pts with TCC who have failed prior chemotherapy are 1) to measure PFS as determined by RECIST and 2) to evaluate toxicity. Prior therapy is restricted to ≤ 4 chemotherapy drugs. Pts receive everolimus 10 mg oral daily continuously (1 cycle = 4 weeks). A Simon 2-stage design requires ≥13 of 23 pts to be progression free at 2 months to proceed to maximal accrual of 37. Results: 43 pts (31 M, 12 F) with a median age of 65 yrs (32-84) and median KPS of 90 (70-90) were enrolled between 02/16/2009 and 09/30/2010. Primary tumor sites include bladder (32 pts) and ureter/renal pelvis (11 pts). Prior therapy included 28 pts with 2 drugs, 13 with 3 and 2 with 4. 34 pts have visceral metastases including lung (21), liver (19), and bone (5), and 9 pts have lymph node only disease. 8 pts who received ≤ 1 cycle secondary to rapid progression or toxicity unrelated to everolimus were deemed inevaluable for PFS endpoint and were replaced. To date, 33 pts are evaluable for the primary PFS endpoint; 2 pts are too early for PFS assessment. 22 of 33 pts are progression-free at 2 months. The median PFS for 33 evaluable pts is 2.9 months (1.4-9). One partial response has been seen. The most common grade 3-4 toxicities at least possibly related to everolimus include: anemia (7), infection (6), hyperglycemia (5), lymphopenia (4), hypophosphatemia (4), fatigue (3), hyponatremia (3), mucositis (2), dehydration (2), renal (2) and liver (2). Conclusions: Everolimus has clinical activity in pts with advanced TCC. An ongoing analysis of pretreatment tumor tissue specimens for markers of activated mTOR pathway will be correlated with PFS. [Table: see text]