bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical and functional outcomes of brachytherapy for young men (≤50) with prostate cancer.
Authors: Shasha Daniel , Boo Dorothy , Perlow Leora , Salant Robert , Harrison Louis Benjamin 
Published: February 2017

245 Background: NCCN guidelines endorse prognostic risk grouping to select therapy, and lend equal support to surgery and radiation therapy (RT). Despite this, the optimal treatment of prostate cancer in young men remains contentious, with the majority treated surgically. This may be because there are few reports of RT outcomes with long follow-up (FU) in this cohort. Thus, we report long-term biochemical and functional outcomes after prostate brachytherapy (BT) +/- supplemental therapies in men ≤ 50 years old. Methods: With IRB approval we analyzed outcomes of 47 patients ≤ 50 yrs old (median 48, range 48-50) implanted with curative intent by a single physician (DS) at Beth Israel Medical Center (New York City) between 2000-2009. Supplemental external beam therapy (45-50.4 Gy) was delivered to patients with NCCN intermediate risk (IR) and high risk (HR) disease, and to select patients with high volume low risk (LR) disease. Androgen deprivation therapy (ADT) was used in all HR patients, for pre-implant prostate downsizing, and for biopsy demonstrating very high volume disease. Biochemical failure (BF) was defined as “nadir +2.” Genitourinary (GU), gastrointestinal (GI) and erectile functional outcomes are included. Results: Median follow up (FU) was 5.2 yrs (range: 2-11). Only 1 patient experienced BF, thus, overall freedom from BF was 97.9%. Grade 2 acute and late 2 GU toxicity were reported in 10.6 % (n = 5) and 8.5% (n = 4), respectively. Grade 2 proctitis was seen 4.3 % (n=2). Erectile function was preserved in 41 of 47 men (87.2 %) with or without phosphodiesterase-5 inhibitors. Conclusions: With median FU of 5.2 years, excellent biochemical control with minimal toxicity was achieved in men ≤ 50 years old. The finding of only a single patient exhibiting BF over the 11 years of FU in this study is highly encouraging. Erectile preservation rates were high, and acute and late GI and GU toxicity were low. These results support prostate BT as an excellent option for patients in this age group.
First-line chemotherapy with gemcitabine, etoposide, and cisplatin in combined-multimodality treatment for patients with advanced urothelial carcinoma.
Authors: Urakami Shinji , Yonese Junji , Fujii Yasuhisa , Yamamoto Shinya , Yuasa Takeshi , Kitsukawa Shinichi , Sakura Mizuaki , Yano Akihiro , Saito Kazutaka , Masuda Hitoshi , Fukui Iwao 
Published: February 2017

262 Background: We had previously reported the phase I/II study of a combination regimen of gemcitabine, etoposide, and cisplatin (GEP) in second-line treatment for patients with advanced UC. This study sought to examine the combination chemotherapy of GEP as first-line treatment for advanced urothelial carcinoma (UC) to assess efficacy, feasibility, prognostic factors, and the impact of postchemotherapy surgery on outcomes. Methods: Forty-two patients were treated with GEP as first-line treatment for metastatic or unresectable locally advanced UC. GEP was recycled every 4 weeks. Etoposide and cisplatin were given on days 1 through 3 at doses of 60 mg/m2 and 20 mg/m2, respectively, and gemcitabine was given on days 1, 8, and 15 at a dose of 800 mg/m2. Results: The median patient age was 64 years. Twenty-three male patients and 19 female patients were included. The primary cancer site is urinary bladder in 21 patients, and upper urinary tract in 21 patients. Nineteen had visceral/bone metastases, 16 had disease restricted to lymph nodes, and the remaining 7 had unresectable disease at primary site. The median number of GEP courses was 4. Thirty of 42 assessable patients (71.4%) demonstrated objective responses. At a median follow-up of 14.6 months, the median overall survival time (OS) was 16.2 months. Twenty-four of 30 responders underwent postchemotherapy surgeries. Median OS in the patients with postchemotherapy surgery was 25.4 months. In the multivariable analysis, anemia and visceral/bone metastasis were significant pretreatment prognostic factors for OS. In addition, being male and anemic were independent poor prognostic factors in patients with postchemotherapy surgery. Grade 3-4 neutropenia, anemia and thrombocytopenia occurred in 84%, 73% and 57%. There were no treatment-related deaths. Conclusions: GEP as first-line chemotherapy in combined-multimodality treatment is active and moderately tolerable for advanced UC. Postchemotherapy surgery may yield favorable outcomes in patients who achieved objective responses. Anemia and visceral/bone metastasis were independent pretreatment predictors for OS.
Cisplatin-based combination chemotherapy in elderly patients with metastatic urothelial cancer.
Authors: Bamias Aristotelis , Krege Susanne , Lin Chia-Chi , Hahn Noah M. , Ecke Thorsten , Moshier Erin L. , Sonpavde Guru , Godbold James H. , Oh William K. , Koutras Angelos , Pu Yeong-Shiau , Galsky Matt D. 
Published: February 2017

269 Background: Cisplatin-based combination chemotherapy is considered standard first-line treatment for patients with metastatic urothelial carcinoma. However, cisplatin-based chemotherapy is frequently avoided in elderly patients due to concerns regarding treatment-related toxicities. We analyzed the efficacy, and tolerability, of cisplatin-based chemotherapy in two age groups (< 70 versus ≥ 70 years old). Methods: Individual patient data was pooled from eight phase II and III trials evaluating cisplatin-based first-line chemotherapy in patients with metastatic urothelial carcinoma. Toxicities, treatment delivery, response proportions, and survival outcomes were compared between patients < 70 versus ≥ 70 years old. Results: Of the 543 patients included in the analysis, 162 patients (30%) were ≥ 70 years old. Patients ≥ 70 years old had a significantly lower baseline calculated creatinine clearance (57 vs. 73 ml/min, p<0.0001). All other baseline characteristics, including PS and visceral metastases were well balanced between the two age groups. Patients ≥ 70 years received a median of 1 cycle less of chemotherapy compared with younger patients (median cycles 5 versus 6; p = 0.004). There was no significant difference in the proportions of patients experiencing Grade 3-4 renal failure, febrile neutropenia, or treatment-related death. Response rate among patients ≥ 70 years old was 50% compared to 52% for patients < 70 years old (p=0.65). There was no significant difference in survival between the age groups (p=0.91). The median survival of the patients ≥ 70 years old was 12.1 months compared to 12.8 months for patients < 70 years old. There was no significant difference in survival between age groups when controlling for baseline performance status and/or the presence of visceral metastases. Conclusions: Elderly patients, with adequate renal function and other baseline characteristics suitable for clinical trial enrollment, tolerate cisplatin-based chemotherapy similarly, and achieve comparable clinical outcomes, compared with their younger counterparts. Cisplatin-based therapy need not be withheld from such patients.
Cisplatin-associated nephrotoxicity in clinical trials using serum creatinine (SCr) versus calculated glomerular filtration rate (GFR) as inclusion criterion: A meta-analysis.
Authors: Dahal Arati , Bellows Brandon Kyle , Sonpavde Guru , Galsky Matt D. , Agarwal Neeraj 
Published: February 2017

272 Background: Treatment with cisplatin (CIS) is associated with increased risk of nephrotoxicity and SCr is commonly used to screen patients for renal dysfunction prior to enrollment in trials using CIS. However, GFR is known to better estimate renal function than SCr. The objective of this trial-level meta-analysis was to indirectly compare incidence of WHO grade ≥3 nephrotoxicity associated with CIS therapy when renal function was assessed using SCr vs. calculated GFR during screening for these trials. Methods: A PubMed literature search was used to identify randomized trials comparing treatment regimens including CIS to those without CIS. Studies were included if they were performed between 1990 and 2005, reported SCr or GFR as inclusion criteria, and reported WHO grade ≥3 nephrotoxic events for both the CIS and non-CIS treatment arms. Studies were excluded if they were review articles, observational, phase 1, non-randomized, did not have a comparator group, or were not reported in English. Inverse variance weighted fixed effects (FE) and random effects (RE) methods were used to estimate the relative risk (RR) associated with CIS vs. non-CIS containing regimens with sub-group analyses of studies using SCr, GFR, and either SCr or GFR for screening. Results: The literature search identified 2359 studies. After exclusion criteria, 549 were reviewed and 24 studies (N=5524 patients) met all inclusion criteria for analysis. Of these, 16 studies used SCr (N=3955), 3 used GFR (N=692), and 5 used SCr or GFR (N=877) for screening. Overall incidence proportion of nephrotoxicity was higher for CIS vs. non-CIS regimens (2.1% vs. 0.7%). Overall RR for CIS vs. non-CIS regimens was 2.49 (95%CI 1.37-4.51, p=0.003). In sub-group analyses, the RR was 2.63 (95%CI 1.29-5.39, p=0.008) for SCr compared to 2.39 (95%CI 0.53-10.64, p=0.26) for GFR and 2.03 (95%CI 0.46-9.02, p=0.35) for either SCr or GFR. The RRs did not differ between the FE and RE methods. Conclusions: This indirect comparison meta-analysis shows CIS is associated with a higher likelihood of nephrotoxicity vs. non-CIS regimens, and may be higher when SCr is used instead of GFR as eligibility criteria.
Prediction of survival in patients with muscle-invasive bladder cancer (MIBC) by neutrophil (NTP) infiltration in benign lymph nodes (LNs).
Authors: Pal Sumanta Kumar , Liang Wei , Jove Richard , Yuh Bertram E. , Chan Kevin , Wilson Timothy G. , McConkey David James , Lerner Seth P. 
Published: February 2017

273 Background: In preclinical models, NTPs appear to establish a pre−metastatic niche that fosters the invasion of metastases (Kowanetz et al PNAS 2010). This observation still requires clinical validation in MIBC. Methods: Benign LN tissue was obtained from patients (pts) who had undergone cystectomy and LN dissection for documented MIBC. Immunohistochemical (IHC) staining for CD15, a NTP marker, was performed for the entire cohort. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3), vascular endothelial growth factor receptor−1 (VEGFR1), and CD68 (a macrophage marker) were further assessed in an initial cohort (detailed subsequently) via IHC. Positively staining cells were counted and averaged over 8 high power fields (hpfs). Pts were stratified by the median cell count for each biomarker. Analyses of overall survival (OS) were performed using the Kaplan−Meier method and log−rank test. Results: In an initial cohort of 19 pts who had received no neoadjuvant chemotherapy (NC), a median CD15 count of 284/hpf was noted. Median OS was higher in those pts with low CD15 as compared to high CD15 (158.7 mos v 36.9 mos, P=0.02). Median OS was also improved in those with high pSTAT3 v low pSTAT3 (not reached v 106.4 mos, P=0.04), but no difference was noted in OS in groups stratified by clinical stage, VEGFR1 staining, or CD68 staining. To determine if the prognostic value of CD15 staining was retained in pts with exposure to NC, the cohort was expanded to include an additional 36 pts who had received either preoperative GC (n=17) or MVAC (n=19) chemotherapy. In this group, no significant difference in OS was noted based using the previously applied CD15 cutoff. Conclusions: NTP recruitment to benign LNs may be prognostic of OS in pts with MIBC who have not received NC. pSTAT3, a putative mediator of NTP recruitment, may play a role in this phenomenon. VEGFR1 and CD68, which may mediate pre−metastatic niche through a different mechanism, do not predict OS in our dataset (Kaplan et al Nature 2005). Bolstered by these findings, the prognostic value of NTP recruitment will be examined prospectively in SWOG 1011, a trial comparing limited v extended LN dissection in pts with MIBC.
Peroxisome proliferator-activated receptor gamma (PPARG) gene amplifications in urothelial carcinoma (UC).
Authors: Bambury Richard M. , Iyer Gopa , Riester Markus , Werner Lillian , Schultz Nikolaus , Stack Edward C. , Park Rachel , Loda Massimo , Ostrovnaya Irina , Kantoff Philip W. , Bajorin Dean F. , Solit David B. , Michor Franziska , Bellmunt Joaquim , Rosenberg Jonathan E. 
Published: February 2017

279 Background: PPARy is a steroid hormone receptor encoded by the PPARG gene (Chr 3p25). Data are conflicting regarding its role in UC. Some studies suggest activation has antiproliferative effects, and preclinical data indicate a potential role for PPARy agonists in cancer treatment. However, recent findings show that use of the PPARy agonist thiazolidinones (TZD) in type 2 diabetes is associated with increased risk of developing UC. To define the spectrum of PPARy aberrations in UC, DNA was evaluated to detect copy number gains/losses (CNG/CNL) of PPARG in three clinically annotated UC cohorts. Methods: Cohort A contained 97 patients with high-grade UC. Cohort B contained 94 patients with primary bladder tumors who developed metastatic UC. Cohort C had 33 patients with metastatic UC, including both primary and paired metastatic tissue for 14 patients. DNA from all tumors was subjected to copy number analysis (array comparative genomic hybridization for cohorts A and B and molecular inversion probe array for cohort C) to identify focal areas of CNG/CNL. Statistical analysis using RAE (cohort A) or GISTIC 2.0 (with CNG defined as log2 copy number ratio >0.8) in cohorts B/C was used to identify significant alterations. Results: The region containing PPARG showed CNG in 7%, 10%, and 15% of cohorts A, B and C, respectively. In cohort A, RAE p value was 5.36E-05 at the amplicon containing PPARG. In cohorts B and C GISTIC 2.0 q values were 9.75E-12 and 6.04E-10. PPARG CNG had no impact on survival in the cohorts with available survival data (A and B). Paired biopsies from primary and metastatic sites showed discordance in PPARG CNG in 2 cases. In 1 case CNG was present in the metastasis but not in the primary and in 1 case the opposite occurred. Conclusions: PPARG shows significant CNGs in 7-15% of UC. Notably the RAF1 locus (a known oncogene) lies close to PPARG and could also represent the driver alteration within this amplicon. Investigation of the functional relevance of these CNGs is clearly warranted as it may be a driver of bladder cancer growth and progression. Determination of PPARG CNG status in UCs in a TZD treated population may provide mechanistic insights into the increased incidence of UC in patients treated with these agents.
The effect of therapeutic anticoagulation on overall survival (OS) in men receiving docetaxel chemotherapy for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Pratz Caroline F. , Brodsky Robert A. , Antonarakis Emmanuel S. 
Published: February 2017

28 Background: Anticoagulants have been postulated to possess antitumor activity, although clinical data supporting this claim are conflicting. We sought to examine the effect of therapeutic anticoagulation on OS in men with mCRPC receiving first-line docetaxel chemotherapy. Methods: We retrospectively reviewed the records of 247 consecutive mCRPC patients who received first-line docetaxel chemotherapy between 1/1/1998 and 1/1/2010. Information on anticoagulant use, type of anticoagulant administered, indication for anticoagulation, and duration of anticoagulation were captured. Univariate and multivariable Cox proportional hazards regression models were developed to investigate the effect of anticoagulant use on OS. Results: In all, 29/247 men (11.7%) received anticoagulation (LMW heparin: 17/247; warfarin: 12/247). The indication was DVT in 15/247, PE in 9/247, and both DVT and PE in 5/247 men. In univariate analysis, anticoagulant use was associated with improved OS (any anticoagulant, HR 0.61 [95%CI 0.40–0.94] P=0.024; LMW heparin, HR 0.58 [95%CI 0.34–0.99] P=0.048; warfarin, HR 0.82 [95%CI 0.55–1.28] P=0.23). Median OS was 20.9 mo (with any anticoagulant) versus 17.1 mo (with no anticoagulant). In multivariable analysis, anticoagulant use remained a significant predictor of OS after adjusting for other prognostic factors (Table). Conclusions: Anticoagulant use is an independent predictor of OS in men with mCRPC receiving docetaxel. This finding is surprising given that the occurrence of venous thrombosis might be expected to negatively influence OS. If validated, these data may provide the impetus to explore the antitumor potential of anticoagulants in prospective clinical trials. [Table: see text]
Antioxidant stimulation as the adaptation mechanism in patients with metastatic urothelial cancers (MUC) treated with gemcitabine and cisplatin (GC).
Authors: Palacka Patrik , Kucharska Jarmila , Mego Michal , Obertova Jana , Rajec Jan , Svetlovska Daniela , Sycova-Mila Zuzana , Mataseje Anna , Mardiak Jozef , Gvozdjakova Anna 
Published: February 2017

281 Background: The role of oxidative stress inpatients with MUC treated with GC is unknown. The objective of this ongoing study is to determinate plasma antioxidants, lipid peroxidation, and lipids in pts. with MUC before and after GC treatment, and to compare them with control. Methods: From May 2010 – January 2012, 42 MUC patients were enrolled into this study. The median of age was 65 years (range 44–81), median of metastasis sites was 2 (range 1–7). All patients were treated with gemcitabine 1000 mg/m2 i.v. days 1 and 8 with cisplatin 75 mg/m2 i.v. day 1, the new cycle of treatment started on day 22. Plasma samples were collected before and after 3 cycles of chemotherapy with GC. The control consisted of 22 subjects without cancer with age median 61 years (range 39–66). Results: In MUC patients, plasma γ-tocopherol before treatment were significantly lower (1.77±0.70 vs 2.13±0.70 μmol/L, P<0.04) and plasma TBARS higher vs control (5.76±1.32 vs 4.51±0.56 μmol/L, P<0.001). When compared baseline plasma levels to values after 3 cycles of GC, significant changes were noticed: γ-tocopherol (1.77±0.70 vs 2.29±1.14 μmol/L, P<0.04), α-tocopherol (24.23±5.14 vs 29.25±6.24 μmol/L, P<0.003), CoQ10-TOTAL (0.43±0.15 vs 0.56±0.16 μmol/L, P=0.003). TBARS concentrations were significantly decreased (5.76±1.32 vs 4.85±1.08 μmol/L, P=0.01). The concentrations of plasma lipids after GC were increased: Cholesterol (4.61±0.99 vs 5.47±1.21 mmol/L, P<0.004), TAG (1.30±0.65 vs 1.74±0.81 mmol/L, P<0.02), LDL cholesterol (2.94±0.73 vs 3.46±0.86 mmol/L, P<0.02), VLDL cholesterol (0.59±0.30 vs 0.81±0.37 mmol/L, P<0.02), and HDL cholesterol (1.08±0.39 vs 1.24±0.43 mmol/L, NS). Conclusions: GC in patients with MUC stimulated antioxidant defence system, increased plasma lipids, and decreased lipid peroxidation. The antioxidant stimulation might be one of the adaptation mechanisms that protect organism and might prevent or reduce chemotherapy side-effects. Acknowledgement: Study is supported by VEGA 1/0614/12 and Ministry of Health, Slovakia, grant 2007/29-UK-06.
Bladder cancer: Predicting response to BCG.
Authors: Nunez-Nateras Rafael , Stanton Melissa L. , Ferrigni Erin N. , Protheroe Cheryl A. , Lee Nancy A. , Lee James J. , Castle Erik P. 
Published: February 2017

287 Background: Our preliminary immunohistochemical studies of bladder cancer patients have shown that the inflammatory/immune responses associated with bladder cancer appear to be Th2-polarized as judged by the preponderance of tumor infiltrating GATA-3+ (Th2) vs. T-bet+ (Th1) T cells, as well as by evidence of tumor-associated eosinophil infiltration and activation. The standard-of-care treatment for Tis bladder cancer is intravesical administration of BCG, a Th1-polarizing immunomodulator. The aim of the present study was to assess the Th2/Th1 ratio correlation with response to BCG therapy in patients with Tis bladder cancer. Methods: Two groups of patients were studied. Group A included 20 patients that responded to BCG, and Group B included 20 patients that did not respond to therapy. Response to BCG was determined as presence/absence of disease at 6 months post-BCG therapy. The initial diagnostic biopsies of these patients were subjected to immunohistochemical analysis using commercially available antibodies specific for Th2 (GATA-3+) and Th1 (T-bet+) lymphocytes, and our unique monoclonal antibody specific for eosinophil peroxidase (EPX-mAb). Ten random high powered (400X) fields at the maximum focus of mononuclear infiltration were examined and the number of GATA 3+ and T-bet+ tumor infiltrating T cells were counted to define the G/T ratio for each patient sample. Eosinophils and their degranulation activity were counted in the same fields. Results: Patients with response to BCG therapy had a G/T ratio of ≥ 3 and patients with non-response to BCG therapy had a G/T ratio of ≤ 1.5. Correlation of these scores with subsequent patient outcomes following BCG immune therapy demonstrated that patient responsiveness (i.e., tumor elimination at 6 months) trended with the higher G/T ratio patients. In addition, initial biopsies of BCG responsive patients display a higher number of eosinophils and degranulation relative to BCG non-responsive patients. Conclusions: Evaluations of initial biopsies revealed a strong correlation between Th1 and Th2 immune response with BCG therapy outcomes. The development of specific and novel tools to identify/measure Th2 immune responses in Tis bladder cancer provides a unique opportunity to predict outcomes at the time of diagnosis.
Correlation of abnormal upper tract cytology and tumor histology in patients who have undergone a nephroureterectomy for urothelial carcinoma with disease recurrence in the bladder.
Authors: Sverrisson Einar Freyr , Kim Timothy , Espiritu Patrick , Sexton Wade Jeffers , Pow-Sang Julio , Dhillon Jasreman , Spiess Philippe E. 
Published: February 2017

288 Background: 15-50% of patients with upper tract urothelial carcinomas (UTUC) will have a bladder recurrence. Abnormal upper tract cytology (UTC) is an indicator of higher grade tumors but has not been associated with bladder recurrence. We were interested in investigating the role of UTC as a predictor of bladder cancer recurrences in patients with no prior history of bladder cancer presenting with UTUC. Methods: Of 67 patients who had an UTC collected prior to their nephroureterectomy (NU) in 2004-2012, we identified 17 patients with a recurrent disease in the bladder who met the criteria of having no previous history of bladder cancer at the time of their NU. UTC and histology were reviewed and analyzed with the bladder pathology data. Positive or suspicious cytology was defined as abnormal and atypical or reactive as benign. Results: 15 (88%) of 17 patients (11 men and 6 women) who met our criteria were diagnosed with bladder cancer within one year after their NU (average 7.5 months (range 2-26)). 10 (59%) of 17 patients had abnormal UTC with a calculated sensitivity and specificity of 59% and 22%, respectively. 7 (70%) of 10 patients with abnormal UTC compared to 5 (71%) of 7 patients with benign cytology had high grade (HG) bladder cancer (p=1.0). Muscle invasive tumors were found in 5 (29%) of 17 patients and 3 (60%) of those had abnormal UTC. All six women had HG bladder cancer compared to 6 of 10 men (p=0.23). HG tumors were slightly more common in the bladder compared to the upper tract (75% vs 65%, p=0.70) and 14 (87.5%) of 16 bladder tumors had the same tumor grade in the upper tract. Conclusions: Abnormal UTC is a poor predictor of bladder recurrence in patients with a history of UTUC. The majority of patients who developed bladder recurrence presented within one year from NU with HG disease which underscores the importance of aggressive surveillance and the consideration of prophylactic intravesical therapy at the time of NU in this patient cohort.