bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world outcomes of metastatic urothelial carcinoma (mUC) patients (pts) treated with first or second-line immunotherapies (IO) in the United States (US).
Authors: Boyd Marley , Annavarapu Srinivas , Doshi Gurjyot K. , Imai Kentaro , Sbar Eric , Godwin James Luke , Li Haojie , Sonpavde Guru 
Published: May 2019

e16025 Background: While clinical trials have affirmed benefit of IO for mUC, limited real-world evidence exists to describe the current treatment landscape and clinical outcomes. This study evaluated these trends in a network of community oncology practices, the US Oncology Network (USON). Methods: This was a retrospective study of adult mUC pts who initiated IO regardless of PD-L1 expression in the first- (1L cohort) or second-line (2L cohort) setting between 5/1/2016-1/31/2018. Using data from USON’s electronic heath record, descriptive and Kaplan-Meier analyses were conducted to evaluate baseline characteristics, treatment patterns and clinical outcomes. Results: Among the 254 pts in the 1L cohort, median (range) age at IO initiation was 74 (42, 90+), 71% were male, 77% were Caucasian, and 18.1% and 5.9% had ECOG performance status (PS) 2 and 3/4, respectively. Among the 179 pts in the 2L cohort, median (range) age at IO initiation was 71 (29, 90+), 76% were male, 76% were Caucasian and 20.7% and 2.2% had ECOG PS 2 and 3/4, respectively. Nearly all pts received IO monotherapy. Median (range) follow-up durations from IO initiation were 4.3 (0, 22; 1L cohort) and 3.6 (0, 19; 2L cohort) months (mo), during which time 39% (1L cohort) and 37% (2L cohort) of pts died. Median overall survival (95% confidence interval [CI]) was 9.9 (7.5, 15.7) mo for the 1L IO cohort and 8.3 (6.4, not reached) mo for the 2L IO cohort. Six-mo survival probabilities (95% CI) were 61.6% (54.5%, 67.9%; 1L cohort) and 60.7% (51.4%, 68.8%; 2L cohort). In total, 52.8% of 1L pts and 53.6% of 2L pts were alive and did not advance to next line of therapy, and 11% of 1L and 13% of 2L cohort pts advanced to the next line of therapy. Median (95% CI) treatment durations were 2.3 (1.9, 3.0) and 3.3 (2.7, 3.9) mos for the 1L and 2L cohorts, respectively. Six-mo ongoing treatment probabilities (95% CI) were 28.9% (23.3%, 34.7%; 1L cohort) and 34.0% (26.1%, 42.1%; 2L cohort). Conclusions: Outcomes of real-world mUC pts receiving IO were as expected, with majority of pts alive and a small minority receiving post-IO therapy. Future research should examine how pt and tumor (PD-L1 expression) characteristics influence treatment and outcomes.
Genomic analysis of urothelial cancer and associations with treatment choice and outcome.
Authors: Sarid David , Berger Raanan , Levartovsky Meital , Gadot Moran , Maurice-Dror Corinne , Collin Maya , Peer Avivit , Perets Ruth , Purim Ofer , Sarfaty Michal , Rosenbaum Eli , Neiman Victoria , Ligumsky Hagai , Rouvinov Keren , Romanov Ialyzaveta , Mermershtain Wilmosh , Shani Shrem Noa , Vainer Gilad Wolf , Leibowitz-Amit Raya 
Published: May 2019

e16026 Background: The use of next generation sequencing (NGS) is in a constant rise, without clear evidence to its utility in guiding treatment choices in urologic malignancies. While platinum-based chemotherapy (chemo) is still the mainstay of treatment, anti-PD1/L1 antibodies (IO) and FGFR3 inhibitors are emerging therapeutic options. Here our aim was to retrospectively assess the utility of next-generation sequencing (NGS) in selecting advanced treatment lines and define the response rates (RR) to chemo and IO in a real-life cohort. Methods: Metastatic urothelial carcinoma (UC) patients (pts) receiving first-line chemo were included. Paraffin-embedded pathological samples were subjected to FoundationOne genomic analysis (Roche) and to PD-L1 IHC staining using the FDA-approved Ventana's companion diagnostic test. Reports were anonymized and analysis was performed using Excel (Microsoft Office). Response was defined as either a clinically or radiologically-significant improvement. Results: 60 pts were included in this analysis with a median age of 69, of which 87.7% were men and 70% were current or past-smokers. RR to first line chemo or IO was 66% (95% CI 50-82) and 33% (95% CI 12-64), respectively. RR to second-line IO was 14% ((95% CI 4-40). Median TMB was 10 Mut/Mb (range 1-62) with no difference between smokers and non-smokers. 31% pts had tumor PD-L1 staining of > 5% and 3.7% were MSI-high. 107 genes were altered across all pts. The median number of genomic alterations (mutations (muts), amplifications (amps), deletions (dels) and re-arrangements) was 7 (range 2-17). The most frequent were TERT promotor and TP53 mutations, occurring in in 39 (69.6%) and 30 (53.6%) pts, respectively. FGFR3 alterations were found in 9 (15%) pts (7 mut and 2 fusions), 12 pts (20%) had alterations in ERBB2/Her2 (6 amps, 3 muts, 3 equivocal amps), BRCA1 mutations were found in 6 (10%) pts, and TSC1 alterations were found in 6 (10%) pts (4 muts and 2 dels). Altogether, about 40% of patients had potentially actionable alterations; of these, to date, the treatment of 8 patients (13%) was consequently altered. The RR to IO was non-significantly higher in pts with TMB > 10 (29% VS 20%, p = 0.1) across all pts in this cohort. Conclusions: RR to first-line chemo is higher than to first-line IO, and the association between TMB and response to IO is still debatable in UC. NGS can yield potentially 'actionable' alterations in about 40% of UC pts, and can change the treatment paradigm in the third of them.
Population-based outcomes comparing radical cystectomy with trimodal therapy for patients diagnosed with localized muscle-invasive bladder cancer.
Authors: Dafashy Tamer , Phillips Daniel , Shan Yong , Hudgins Hogan K , Jazzar Usama , Ray-Zack Mohamed Danny , Kaul Sapna , Kerr Preston , Kamat Ashish M. , Tyler Douglas S. , Freedland Stephen J. , Swanson Todd A. , Mehta Hemalkumar B , Williams Stephen Bentley 
Published: May 2019

e16029 Background: Radical cystectomy is the guideline-recommended treatment for muscle-invasive bladder cancer; however, use of trimodal therapy, which utilizes a combination of surgery, radiation, and chemotherapy, has increased in recent years with conflicting survival outcomes. Methods: Utilizing data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, a total of 2,963 patients aged 66 years or older diagnosed with clinical stage T2-4a bladder cancer from January 1, 2002 to December 31, 2011 were analyzed. Conventional regression, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to compare radical cystectomy and trimodal therapy for overall and cancer-specific survival, and cost. Results: Patients who underwent TMT had significantly decreased overall (conventional regression: Hazard Ratio (HR) 1.54, 95% Confidence Interval (CI), 1.39-1.71; PSM: HR 1.49, 95% CI 1.31-1.69; IPTW: HR 1.54, 95% CI 1.39-1.71) and cancer-specific (conventional regression: HR 1.51, 95% CI 1.40-1.63; PSM: HR 1.55, 95% CI 1.32-1.83; IPTW: HR 1.51, 95% CI 1.40-1.63) survival. Median total costs were significantly higher with trimodal therapy than with radical cystectomy at 6-month ($171,401 vs. $99,890, p < 0.001). Conclusions: Using population-based data and different analytic methods to control for imbalance between study groups, we found that trimodal therapy was associated with decreased overall and cancer-specific survival at increased costs compared to radical cystectomy.
Sarcopenia as a predictor of perioperative outcomes following radical cystectomy in a contemporary cohort of patients with bladder cancer.
Authors: Drury Nicholas Brent , Worrilow William Mills , Beano Hamza Mustafa , Robinson Myra M. , Ignatoff Jeffrey , Britt Peter , Wilder Jessica , Hensel Caitlin , Sylvestre Dana , Gaston Kris E , Clark Peter E , Riggs Stephen Boyd 
Published: May 2019

e16031 Background: Sarcopenia has gained considerable recognition as an important prognostic factor for complications, longer hospital stay, and survival following cystectomy for bladder cancer. However, inconsistent cutoff values to define sarcopenia have been utilized throughout the literature. Our aim was to evaluate sarcopenia as a predictor of outcomes following radical cystectomy with urinary diversion (RCUD) using the international consensus definition, Martin criteria, and Mayr criteria, as a standardized cutoff value would potentially reduce bias across studies. Methods: A retrospective analysis of patients treated with RCUD at our institution between 2010 and 2017 was performed. Sarcopenia was defined according to the aforementioned criteria and assessed by measuring total psoas area (TPA) on preoperative computerized tomography. The impact of sarcopenia on perioperative outcomes, cancer-specific survival (CSS), and overall survival (OS) was evaluated with univariate and multivariate regression models. Results: Of 258 patients who underwent RCUD, 195 had available computed tomography scans within 90 days of surgery. The median TPA scores among men and women were 578.0 and 459.6 mm2/mm2, respectively. The overall incidence of sarcopenia according to the international consensus definition, Martin criteria, and Mayr criteria was 36.4% (71/195), 24.1% (47/195), and 31.3% (61/195), respectively. Regardless of definition, significant differences were not observed in length of stay, high grade complications, readmissions, and discharge destination (all P > .05). Furthermore, sarcopenia was not significantly associated with CSS or OS. The median follow-up time was 4.1 years (95% CI: 3.6 - 4.4). The 5-year CSS and OS were 46.3% and 66.2%, respectively. Conclusions: Irrespective of definition, we were unable to externally validate sarcopenia as a predictor of perioperative outcomes in our contemporary cohort. Future studies will evaluate the impact of our evolving perioperative care pathway on oncological outcomes, including its ability to mitigate the effects of sarcopenia through reducing the physiological and mental demands of surgery.
Risk factors for renal failure (RF) during high-dose chemotherapy (HDCT) and outcomes for patients (pts) with relapsed germ-cell tumors (rGCT).
Authors: Zhang Kevin Juan , Hanna Nasser H. , Abu Zaid Mohammad Issam , Abonour Rafat , Albany Costantine , Einhorn Lawrence H. , Adra Nabil 
Published: May 2019

e16042 Background: Pts with rGCT can be cured with salvage chemotherapy (CT). We evaluated risk factors and outcomes of pts who developed RF during HDCT for rGCT. Methods: All pts were planned to receive 2 consecutive courses of HDCT per protocol (N Engl J Med 2007;357:340-8). Characteristics and outcomes of pts sustaining grade ≥3 RF were analyzed and compared with those not sustaining grade ≥3 RF. Results: 21 (4%) of 473 pts had grade ≥3 RF: median age 38 (range 25-70), median creatinine 1.2 (0.6-1.8), median creatinine clearance (CrCl) 94 (48-216), median body mass index 27.1 (19.9-34.2). Median # prior standard-dose cisplatin-based CT cycles 5 (4-8) and median total dose of cisplatin 1000mg (600-1976). 10/21 pts had history of renal disease prior to HDCT, 4 had hypertension, 2 had diabetes, 2 had solitary kidney and 5 had stent or nephrostomy tube for obstruction. 20/21 pts developed neutropenic fever. 5 required total parenteral nutrition and 18 required hemodialysis (HD) during HDCT. 6 of 21 died during HDCT. 10 of 15 pts who survived HDCT had renal function recover to baseline, 2 came off HD but renal function was not restored to baseline, and 3 continued to be on HD at most recent f/u. In comparison to pts (n = 452) who did not experience grade ≥3 RF, pts (n = 21) who did experience grade ≥3 RF were more likely treated with HDCT ≥ 3rd line setting (38% vs 15%), had ECOG PS 1/2 (53% vs 18%), less likely to receive both courses of HDCT (33% vs 94%), more likely to experience GI (62% vs 11%), hepatic (43% vs 3%), pulmonary (38% vs 2%), and infectious (95% vs 1%) grade ≥ 3 toxicities; treatment-related death was also higher in this group (29% vs 2%). With a median f/u of 10 months after HDCT, 5 pts had no evidence of disease (NED), 3 were alive with disease, 6 died of disease, 6 died from complications of HDCT, and 1 lost to follow up. Conclusions: Irreversible RF during HDCT for rGCT is uncommon, but is associated with higher rates of infectious, GI, hepatic, pulmonary complications and treatment-related death. These pts are more heavily pre-treated, have lower baseline PS, and are likely to have history of renal disease prior to HDCT. However, most surviving pts recovered their renal function and 5/21 remain alive with NED.
High DNA damage levels to predict hematologic toxicity in testicular germ cell tumor (TGCT) patients treated with first-line chemotherapy.
Authors: Mego Michal , Hapakova Nikola , Sestakova Zuzana , Holickova Andrea , Miskovska Vera , Chovanec Michal , Rejlekova Katarina , Svetlovska Daniela , Kalavska Katarina , Obertova Jana , Palacka Patrik , De Angelis Valentina , Sycova Zuzana , Mardiak Jozef , Chovanec Miroslav 
Published: May 2019

e16055 Background: TGCTs are an excellent example of chemosensitive disease. However, cisplatin-based chemotherapy has significant side effects, including myelosuppression. Previously, we found endogenous DNA damage level in peripheral blood mononuclear cells (PBMCs) to be an independent prognostic marker. We tested the hypothesis that patients with high endogenous DNA damage levels in PBMCs have an increased risk of developing hematologic toxicity. Methods: 120 chemotherapy-naïve patients with TGCTs treated in the National Cancer Institute and the St. Elisabeth Cancer Institute in Bratislava, Slovakia, from 2012 to 2018 were enrolled. All patients received platinum-based chemotherapy with G-CSF support. On the day of starting treatment, we measured the endogenous DNA damage levels in PBMCs using the Comet assay. We used a cut-off level of 5.25, a value previously found to stratify patients based on their prognosis. We monitored hematologic toxicity during the 1st cycle of chemotherapy. The mean and SEM were calculated for all variables. Results: Patients with high DNA damage levels ( > 5.25) had more significant hematologic toxicity with significantly lower nadir white blood cell count (6.0±1.1×109/L vs 9.8±1.0×109/L p = 0.001), absolute neutrophil count (4.1±1.0×109/L vs 7.0±0.9×109/L p = 0.013) and absolute lymphocyte count (ALC, 1.1±0.1×109/L vs 1.5±0.1×109/L p < 0.001). ALCs on day 0 (1.5±0.1×109/L vs 1.8±0.1×109/L p = 0.005) and day 22 (2.0±0.1×109/L vs 2.4±0.1×109/L p = 0.046) were also significantly lower in patients with high DNA damage levels. There were no significant differences in hemoglobin levels or platelet counts between the two groups. Neutrophil to lymphocyte ratio and systemic immune-inflammation index were lower at nadir in patients with high DNA damage levels, however, these differences were not statistically significant (p = 0.08 and p = 0.10, respectively). Conclusions: This study shows that higher endogenous DNA damage levels correlate with an increased risk of hematologic toxicity. The Comet assay data can be used to select patients for closer monitoring due to a higher risk of acute chemotherapy-related complications.
Delivery of bleomycin among patients with testicular cancer: A population-based study of pulmonary monitoring and toxicity.
Authors: Booth Christopher M. , Raphael Michael J. , Wei Xuejiao , Robinson Andrew George , Bedard Philippe L. , Karim Safiya , Lougheed M. Dianne 
Published: May 2019

e16056 Background: Bleomycin is commonly used to treat testicular cancer and can be associated with severe pulmonary toxicity. There is limited information about how clinicians monitor patients during treatment and the incidence of pulmonary toxicity in routine practice. Methods: The Ontario Cancer Registry was linked to electronic records of treatment to identify all incident cases of testicular cancer treated with orchiectomy and bleomycin, etoposide, and cisplatin (BEP) chemotherapy in the province of Ontario during 2005-2010. Health-administrative databases were used to describe use of pulmonary function tests (PFTs), chest imaging and physician visits. Results: 475 patients were treated with orchiectomy and chemotherapy. Complete chemotherapy records were available for 93% (368/394) of men treated with BEP. Bleomycin was omitted among 32% (116/368) of patients. PFTs were performed in 17% (63/368), 17% (61/368) and 29% (106/368) of patients before BEP, during BEP, and within 2 years of finishing BEP, respectively. During chemotherapy, 62% of patients (227/368) had chest imaging. In the two years following BEP, 23% (85/368) had a physician visit for respiratory symptoms; this rate was substantially higher among men with greater exposure to bleomycin; 40% (24/60) for 10-12 doses bleomycin vs 21% (53/250) for 7-9 doses vs 14% (8/58) for 1-6 doses (p = 0.002). Two percent of men (8/368) had visit codes for pulmonary fibrosis. Conclusions: A substantial proportion of men treated with BEP will seek medical attention after chemotherapy for respiratory symptoms and this is associated with cumulative dose of bleomycin. Use of PFTs and chest imaging during treatment is common. Whether PFT test results or clinical symptoms are leading to bleomycin dose omission is uncertain.
Impact of cisplatin-related adverse health outcomes (AHOs) on employment outcomes and self-reported health (SRH) among testicular cancer survivors (TCS).
Authors: Kerns Sarah L. , Fung Chunkit , Fossa Sophie D. , Dinh Paul C , Monahan Patrick O. , Sesso Howard D. , Frisina Robert D. , Feldman Darren R. , Hamilton Robert James , Vaughn David J. , Martin Neil E. , Huddart Robert A , Kollmannsberger Christian K. , Sahasrabudhe Deepak M. , Ardeshirrouhanifard Shirin , Einhorn Lawrence H. , Travis Lois B. ,   The Platinum Study Group
Published: May 2019

e16058 Background: We aim to provide new information on cisplatin-related AHOs and employment status in TCS and evaluate impact on SRH. Methods: 1,815 TCS ³1 year post-chemotherapy underwent physical exam, audiometry, renal function evaluation, and completed questionnaires. Therapy data were obtained from medical records. A cumulative burden of morbidity score (CBMPt) assessed the number and severity of platinum-related AHOs (peripheral sensory neuropathy (PSN), hearing loss, tinnitus, and renal function) with grading per CTCAE v4.03. Multivariable regression assessed relations between CBMPt score, individual AHOs and employment status as well as SRH, adjusting for sociodemographic/clinical factors. Unemployment in TCS was compared with subjects in the Behavioral Risk Factor Surveillance System (BRFSS) of similar age/race/ethnicity. Results: Almost 1 in 10 TCS were either on disability leave (2.4%) or unemployed (6.8%) at a median age of 37 yr (median follow-up: 4 yr). TCS with tinnitus (OR = 3.1, grade 3 vs. 0, P = 0.04), renal dysfunction (OR = 13.5, grade 3 vs. 0, P = 0.01), or pain (OR = 7.2 and 40.9, grade 2 or 3 vs. 0, respectively; P < 0.001 each) had significantly greater odds of disability leave vs. full-time employment after adjusting for sociodemographic/clinical factors; pain was strongly correlated with PSN (Pearson r2= 0.40; P < 0.001). CBMPt score was associated with disability leave (OR = 1.5, P = 0.04), but not with unemployment. A significantly higher percentage of TCS were unemployed vs. BRFSS norms (e.g. 3.6% of TCS age 35-39 vs. 2.0% in BRFSS). PSN (OR = 2.2, grade 3 vs. 0, P = 0.02), self-reported hearing loss (OR = 1.8, grade 2/3 vs. 0, P = 0.04), and pain (OR = 2.8 and 8.5, grade 2 or 3 vs. 0, respectively; P < 0.01 each) were each associated with increased odds of unemployment vs. full-time employment. Cisplatin-related AHOs and pain were associated with significantly worse SRH (P < 0.05). Conclusions: Our findings have new, important implications regarding productivity loss and socioeconomic costs in TCS. Survivorship care strategies should include inquiries about employment status, and every effort made to assist affected TCS in returning to the work force.
Utilization of mental health services among survivors of testicular cancer: A population-based study.
Authors: Booth Christopher M. , Raphael Michael J. , Wei Xuejiao , Soares Claudio , Bedard Philippe L. , Leveridge Michael , Siemens D. Robert , Robinson Andrew George 
Published: May 2019

e16062 Background: Testicular cancer survivors may experience long-term psychological distress related to their diagnosis and treatment. Measurement of mental health service use (MHS) is an objective way to quantify the incurred burden of psychological distress. Here we describe patterns of MHS use among survivors of testicular cancer in a single-payer health system. Methods: The Ontario Cancer Registry was linked to electronic treatment records to identify all incident cases of testicular cancer treated with orchiectomy in the Canadian province of Ontario during 2004-2010. Mental health clinical visits were identified from records of hospital admission, emergency room visits and out-patient physician billing records. Results: The study cohort included 1877 patients; mean age was 35 and 61% had pure seminoma. Two thirds of patients (66%, 1230/1877) were initially treated with active surveillance. In the 2-year period prior to orchiectomy, 24% (443/1877) of patients had MHS use. Post-orchiectomy, the prevalence of MHS use was 18% (331/1877), 23% (431/1877) and 30% (572/1877) at 6, 12 and 24 months, respectively. The use of MHS was greatest in the peri-diagnostic/surgical period. Rates of MHS visits, 3 months before, 0-3 months after, 4-6 months after and 2 years after orchiectomy were 11%, 14%, 10%, and 6%, respectively. Post-orchiectomy MHS use was greatest among those with baseline MHS use. The prevalence of MHS use for patients with and without baseline MHS use was 40% (175/443) vs 11% (156/1434, p < 0.001) at 6 months; 51% (225/443) vs 14% (206/1434, p < 0.001) at 12 months; and 61% (271/443) vs 21% (301/1434, p < 0.001) at 24 months post-orchiectomy. Post-orchiectomy MHS use did not vary by initial treatment strategy (active surveillance vs upfront treatment, p = 0.435). Older patients were more likely to have MHS visits at all time periods than younger patients; MHS rates at 6 months were 15% (93/631) vs 18% (112/625) vs 20% (126/621) for ages 16-29, 30-39, and 40+ years respectively (p = 0.035). Conclusions: MHS use among survivors of testicular cancer is common, particularly in the peri-diagnostic and surgical period. The rate of MHS use is highest among those patients with a history of prior MHS use. Clinicians should screen for the presence of psychological distress among survivors of testicular cancer.