bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary malignant melanoma of the female urethra: Twenty years of surgical and medical management at a tertiary referral center.
Authors: Nichols Paige , Miest Tanner , Montgomery Brian D. , Sharma Vidit , Lightner Deborah , Lomas Derek 
Published: February 2020

430 Background: Malignant melanoma of the female urethra accounts for less than 1% of all melanoma and less than 4% of urethral cancer. Due to limited data regarding management and outcomes of this condition, we evaluated the management and outcomes of urethral melanoma in females over the last 20 years at our institution. Methods: Patients were identified via retrospective review of the medical record. Those with metastatic disease at initial diagnosis were excluded. We evaluated primary and adjuvant treatments, disease recurrence and overall survival. Results: Fifteen women (median age 71, range 55, 82) were identified. Majority of masses involved the distal urethra (86.6%). All patients underwent primary surgical resection (60.0% partial urethrectomy, 40.0% radical urethrectomy). Disease recurrence and metastatic spread occurred in 73.3% (median 7 months, IQR 4, 12) and 60% (median 6 months, IQR 3, 9) of patients, respectively. 90.9% of patients with recurrence received adjuvant therapy: 5 chemotherapy and radiation, 4 chemotherapy only, 1 anterior exenteration. Of the 9 patients undergoing chemotherapy, treatment regimens were varied and included checkpoint inhibitors (2/9), platinum-based chemotherapy (3/9), tyrosine kinase inhibitors (2/9), taxels (2/9), and alkylating agents (1/9). Median overall survival was 27 months (IQR 7.5, 57.5). Conclusions: Malignant melanoma of the urethra is locally aggressive with a high likelihood of recurrence and metastases resulting in poor long-term survival. Despite high recurrence rates, our data highlight the lack of consensus adjuvant treatment regimens. Future research is required to identify neoadjuvant, combination, and adjuvant treatment approaches to improve disease outcomes.
The association between allopurinol use and urologic malignancies: A nested case-control study.
Authors: Keizman Daniel , Wolf Ido , Dresler Hadas , Sarid David , Peer Avivit , Rouvinov Keren , Neiman Victoria , Margalit Ofer , Shacham-Shmueli Einat , Mamtani Ronac , Haynes Kevin , Yang Yu-Xiao , Boursi Ben 
Published: February 2020

435 Background: Oxidative stress may be involved in tumorigenesis processes. Uric acid is an important natural antioxidant that may reduce oxidative stress. Allopurinol is a commonly used uric acid lowering agent. There are conflicting data regarding the association between allopurinol use and cancer incidence. In the present nested case control study, we aimed to evaluated the association between allopurinol use and urologic malignancies in a large western population. Methods: conducted a nested case-control study within a population-representative database from the United Kingdom (THIN). Study cases were defined as individuals with any diagnostic code of prostate cancer, bladder cancer, or renal cell carcinoma. For every case, four eligible controls were matched on age, gender, practice site, time of diagnosis, and duration of follow-up. Exposure of interest was any allopurinol use prior to cancer diagnosis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for urologic malignancies were estimated using conditional logistic regression. Adjustment was performed for factors including smoking, BMI, and diabetes. Results: The study population included: for bladder cancer 13440 and 52421 matched controls, prostate cancer 27212 cases and 105940 controls, RCC 1547 cases and 6066 controls. Allopurinol use was associated with a significantly increase of risk for bladder cancer (adjusted OR 1.2, 95%CI 1.09-1.32, p<0.001). prostate cancer (adjusted OR 1.1, 95%CI 1.03-1.,17, p=0.003), RCC (adjusted OR 1.32, 95%CI 1-1..75, p=0.05). In a sensitivity analyses we observed similar associations when alopurinol use was initiated more than two years prior to cancer diagnosis, for bladder cancer (adjusted OR 1.2, 95%CI 1.08-1.33, p=0.001), prostate cancer (adjusted OR 1.09, 95%CI 1.02-1.16, p=0.01), RCC (adjusted OR 1.09, 95%CI 0.78-1.53, p=0.62). Conclusions: Allopurinol use may be associated with an increased risk for urologic malignancies.
Atezolizumab in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy: Results of real-life experience.
Authors: Tural Deniz , Olmez Omer Fatih , Sumbul Ahmet Taner , Artac Mehmet , Ozhan Nail , Akar Emre , Cakar Burcu , Kostek Osman , Paksoy Nail , Erman Mustafa , Coskun Hasan Senol , Selcukbiricik Fatih , Keskin Özge , Paksoy Turkoz Fatma , Oruc Kerem , Bayram Selami , Yilmaz Ugur , Bilgetekin Irem , Yildiz Birol , Kilickap Saadettin ,   Turkish Oncology Group (TOG)
Published: February 2020

451 Background: Anti-tumor activity and manageable safety profile of atezolizumab (ATZ) has been demonstrated in the previous clinical trials in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. In this study, we reported the results of real-life data of urothelial carcinoma patients in Turkey who were treated with ATZ. Methods: Data of the patients with metastatic urothelial carcinoma registered to ATZ Expanded-Access Program and treated with at least one course of ATZ from 36 oncology centers in Turkey were collected. The primary endpoint was the overall response rate (ORR); secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of the ATZ treatment and safety. Results: Data of 115 eligible patients were analyzed. Of the patients, 100 (87%) were male and 13% were female. The median age was 65.3 years (37-86). Most of the patients (92.3%) had received only one chemotherapy regimen prior to ATZ. The median follow-up time was 23.5 months. The complete response rate to ATZ, partial response rate, and ORR were 8.7% (n=10), 20.0% (n=23), and 28.7% (n=33), respectively. The median duration of response was 20.4 months (95% CI 6.47–28.8). Of the thirty-three patients who responded to treatment, 20 (60%) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 months (95% 2.25–5.49) and 9.8 months (95% 6.7–12.9), respectively. The 12-month PFS rate was 22.3% and the 24-month PFS rate was 16.9%. The 12-month OS rate was 42.2% and the 24-month OS rate was 23.5%, respectively. Sixty-four percent of patients experienced a treatment-related adverse event of any grade, and 24 (20%) of patients had a grade 3–4 treatment-related adverse event. Because of treatment-related side effects, dose reduction was performed in 9 (7.8%) patients and ATZ was discontinued in 8 patients (7.0%). Adverse event that required systemic steroid use was reported in only 7 (6.1%) patients. Four patients (3.5%) died due to treatment-related causes. Conclusions: ATZ is an effective and tolerable treatment for patients with metastatic platinum-resistant urothelial carcinoma.
Real-world evidence of the impact of prior antibiotic exposure on immune checkpoint inhibitor outcomes in patients with metastatic urothelial cancer.
Authors: Hoffman-Censits Jean H. , Harshman Lauren Christine , Metcalf Meredith , Abou Alaiwi Sarah , Meyer Craig S. , Yang Erru , Satram Sacha , Ogale Sarika , Faber Kathleene , Ma Esprit 
Published: February 2020

452 Background: Prior research suggests that systemic antibiotic (ABX) exposure may impact gut microbiome and potentially result in suboptimal immune checkpoint inhibitor (ICI) treatment outcomes. A recent real-world analysis demonstrated that cumulative ABX exposure was associated with poorer outcomes across multiple tumor types independent of known prognostic clinical factors. Given the paucity of real-world data, we set out to evaluate the association of prior ABX exposure with ICI treatment outcomes among patients with metastatic urothelial cancer (mUC). Methods: This was a retrospective analysis using Truven Health MarketScan Commercial, Medicare Supplemental, and Coordination of Benefits (Medicare) databases. Patients with mUC, ≥18 years old, who received first line (1L) ICI therapy between 1/1/2016 and 12/31/2018 were analyzed. Prior ABX exposure was defined as any use in the 90 days prior to 1L ICI therapy initiation. Time to treatment discontinuation was used as a proxy to quantify ICI treatment outcomes. Results: Among the 304 ICI treated patients, 128 (42%) had ABX exposure within 90 days prior to ICI initiation. Statistically significant differences in baseline co-morbidities and urinary tract infections (36% vs. 17%; p<0.001) were observed between patients with vs. without ABX exposure. The median time to treatment discontinuation was shorter for patients with ABX exposure (7.9 months) vs. without (9.3 months). In adjusted regression analysis, there was no statistically significant difference in time to treatment discontinuation between patients with vs. without ABX exposure (p=0.95). These findings were consistent in a sensitivity analysis looking at ABX exposure 30 and 60 days prior to 1L ICI initiation. Conclusions: In this real-world analysis of patients with mUC, those with ABX exposure within 90 days prior to 1L ICI initiation demonstrated similar outcomes to those without ABX exposure. While there was a shorter time to treatment discontinuation in the patients with vs. without ABX exposure, findings were not statistically significant. Further research is warranted to investigate the impact of concomitant ABX use on ICI outcomes.
Response to systemic therapy and survival outcomes in de-novo (D1) metastatic castration-sensitive prostate cancer (mCSPC) versus mCSPC with prior local therapy (D0).
Authors: Hahn Andrew W , Kessel Adam , McFarland Taylor Ryan , Swami Umang , Nussenzveig Roberto , Esther John , Goel Divyam , Sirohi Deepika , Maughan Benjamin Louis , Agarwal Neeraj 
Published: February 2020

46 Background: A real-world study (n= 436, PMID: 29707790) suggest that D1 mCSPC has worse outcomes than D0 mCSPC. The objective of our study is to validate these findings in a real-world setting, and compare clinical and tumor genomic characteristics associated with D1 vs. D0 mCSPC. Methods: In this retrospective study, eligible patients had mCSPC, received androgen deprivation therapy (ADT) +/- intensification with docetaxel or novel hormonal therapy. D1 mCSPC was diagnosed as those with distant metastasis at the first diagnosis of prostate cancer. Progression-free survival (PFS) was per PCWG2 criteria or clinical progression, and overall survival (OS) was date of death or last follow up from start of ADT for mCSPC. Baseline clinical characteristics were compared using the t test. Survival was compared using the log-rank test with Kaplan-Meier methods. Results: Of 396 eligible patients, 242 had D1 mCSPC. Men with D1 mCSPC were younger, had significantly higher median PSA, Gleason score, and alkaline phosphatase at diagnosis of mCSPC, and had significantly shorter PFS and OS with standard ADT, as well as intensified ADT, compared to men with D0 mCSPC (Table). Conclusions: These findings validate data from a previous real-world study that D1 CSPC is associated with inferior prognosis and outcomes on systemic therapy compared to D0 mCSPC. These data may aid with counseling and treatment selection, as well as patient stratification in future trials in mCSPC. Comparison of comprehensive genomic profiling data, obtained through CLIA certified labs, will be presented at the meeting.[Table: see text]
Improving quality of health-related quality of life (HRQOL) reporting in phase III randomized controlled trials (RCTs) of metastatic urothelial carcinoma (mUC).
Authors: Jiang Di Maria , Wong Bryan , Bellmunt Joaquim , Powles Thomas , Morgans Alicia K. , Vaughn David J. , Sridhar Srikala S. 
Published: February 2020

467 Background: HRQOL data are increasingly used to guide patient care and health policy. However, their utility can be compromised by inadequate quality of HRQOL reporting (QHR). We aimed to systematically evaluate QHR in phase III RCTs of mUC. Methods: A comprehensive systematic review following PRISMA guidelines identified published manuscripts of phase III RCTs of mUC in English between 1985 - 2019. Supplementary material, references and companion publications were reviewed. QHR was quantified using: 1) 2013 CONSORT-PRO extension (CPE), and 2) 2003 Minimum Standard Checklist for Evaluating HRQOL Outcomes in Cancer Clinical Trials (MSC). Both scores range from 0-11, with higher scores indicating higher QHR. QHR is “probably robust” if MSC score is ≥8 and all 3 mandatory items (baseline compliance, missing data, and psychometric properties) are reported; “limited” if MSC score is 5-7; and “very limited” if MSC score is ≤4. Results: HRQOL data was collected in 7/21 (33%) mUC phase III RCTs. All reported HRQOL data as secondary/exploratory endpoints. Generic instruments included EORTC QLQ-C30 alone (n=3) or combined with EQ-5D (n=2)/McGill pain questionnaire (n=1). Disease-specific FACT-Bl was used in 1 RCT. Both checklists showed strong correlation (Spearman coefficient 0.94, p=0.001). QHR was often limited, however has improved in recent years (Table). No RCT stated HRQOL-specific hypotheses. Only 1 reported instrument validity and mode of administration. Few provided domain specific results (n=2) and statistical methods for handling missing data (n=3). Implications for clinical practice were only discussed in 3 RCTs. Conclusions: QHR has improved over time however many critical methodological deficiencies remain in mUC phase III RCTs. The use of standard checklists are encouraged to further enhance QHR and promote high quality HRQOL research. [Table: see text]
Impact of inflammatory bowel disease on urologic oncology surgical outcomes and costs of care.
Authors: Goldberg Ilana , Chang Steven Lee , Kundu Shilajit , Singer Eric A. 
Published: February 2020

470 Background: Recent studies suggest an association between genitourinary malignancies and inflammatory bowel disease (IBD). Our objective was to investigate clinical and financial impacts of IBD on common major urologic cancer surgeries: radical prostatectomy (RP), radical cystectomy (RC), radical nephrectomy (RN), and partial nephrectomy (PN). Methods: Using ICD9 codes, the Premier Hospital Database was queried for patients who underwent one of four surgeries: RP, RC, RN, or PN from 2003 to 2015. The cohort was segregated into IBD patients and non-IBD patients. Multivariable logistic regression models were used to determine the independent impact of IBD on complication rates (by Clavien-Dindo classification and organ system) and readmission rates. Hospital cost differences between the two cohorts, adjusted to 2016 US dollars, were examined with multivariable quantile regression models. Results: Our study population included 220,192 patients with urological malignancies, 5165 (0.4%) of whom had IBD. After controlling for clinicodemographic variables, there were significantly higher odds for any complication (Clavien ≥1) for IBD patients compared to non-IBD controls for RC (Odds ratio [OR]: 3.04, 95% confidence interval [CI]: 1.25-7.43), RN (OR: 1.57, 95% CI: 1.1-2.23), and PN (OR: 1.5, 95% CI: 1.02-2.22). Specifically, IBD patients had significantly more gastrointestinal, infectious, and soft tissue complications. Readmission rates were significantly higher for IBD patients who underwent RC (OR: 2.50, 95% CI: 1.17-5.35) and PN (OR: 1.81, 95% CI: 1.17-2.80). Hospital costs were significantly elevated for IBD patients, ranging from +$893 (95% CI: 108-1677) to +$6261 (95% CI: 1861-10660). Conclusions: There was a significantly higher overall complication rate for IBD patients undergoing RC, RN, or PN compared to the non-IBD cohort. Hospital readmission rates were significantly higher for the IBD cohort who underwent RC and PN. Hospital costs associated with surgery were also increased for IBD patients. These findings may be important when counseling IBD patients about surgical outcomes and during development of enhanced recovery pathways or bundled payment programs.
Real-world survival improvements in patients with newly diagnosed metastatic prostate cancer treated in the United States.
Authors: Cattrini Carlo , Zanardi Elisa , Rubagotti Alessandra , Zinoli Linda , Capaia Matteo , Barboro Paola , Boccardo Francesco 
Published: February 2020

48 Background: New drugs have become available for the treatment of metastatic prostate cancer (mPCa) during the last two decades. Here, we explored the clinical outcomes of de novo mPCa in 3 large cohorts of patients diagnosed in 3 treatment eras: pre-docetaxel 2000-2003 (T1), docetaxel 2004-2010 (T2) and new androgen-receptor signalling inhibitors (ARSi) + cabazitaxel 2011-2016 (T3). Methods: The USA Surveillance Epidemiology and End Results (SEER) Incidence Data were investigated using the SEER*Stat software. We used the Kaplan – Meier method, log-rank test, Cox regression, hazard ratio (HR) and confidence intervals (CI) to analyse overall survival (OS) and cancer-specific survival (CSS). The maximum follow-up time point was 5 years. Results: A total 34.034 patients with de novo mPCa were analysed for OS, of these 6.621 T1, 12.711 T2 and 14.702 T3. Median OS was 29 months (mo) [95% CI: 28.5-29.5], 28 mo [27.0-28.9], 28 mo [27.3-28.7] and 31 mo [30.2-31.8] in whole, T1, T2 and T3 cohorts, respectively. In the multivariable model, adjusted for age and race, T3 patients showed better OS compared to T1 and T2 patients (HR: 0,92 [95% CI: 0,88-0,95] and 0,92 [0,89 to 0,95], respectively, p<0.001). A total of 33.641 patients were analysed for CSS, of these 6.514 T1, 12.540 T2 and 14.587 T3. Median CSS was 36 mo [35.3-36.7], 34 mo [32.6-35.3], 34 mo [33.0-35.0] and 38 mo [36.9-39.1] in whole, T1, T2, T3 cohorts, respectively. T3 patients had better CSS compared to T1 and T2 patients (HR: 0,93 [0,89-0,97] and 0,92 [0,89 to 0,96], respectively, p<0.001). No difference in OS or CSS was found between T1 and T2 cohorts. Conclusions: The prognosis of patients with de novo mPCa remains poor, with a median CSS of 3 years and a 5-year CSS of 35%. Approximately 8% decrease in the risk of death was found in the era of ARSi and cabazitaxel. The recent intensification of therapy in metastatic hormone-sensitive setting might lead to better outcomes in the next years.[Table: see text]
Type, timing, and risk factors associated with immune-related adverse event development in patients with advanced genitourinary cancers treated with immune checkpoint inhibitor.
Authors: Qin Qian , Patel Vaibhav G. , Mellgard George , Parikh Anish B. , Wang Bo , Alerasool Parissa , Garcia Philip , Jaladanki Suraj , Leiter Amanda , Carroll Emily , Brooks Danielle , Shimol Jennifer Ben , Eisenberg Elliot , Gallagher Emily J. , Galsky Matt D. , Oh William K. , Tsao Che-Kai 
Published: February 2020

480 Background: Immune related adverse events (IRAEs) with immune checkpoint inhibitor (ICI) therapy are well recognized, but predictors for IRAEs are not well defined. We aim to characterize the type, timing, and clinical risk factors associated with (w/) IRAEs in ICI-treated, advanced urothelial carcinoma (UC) and renal cell carcinoma (RCC) patients (pts). Methods: We retrospectively reviewed charts of pts w/ advanced UC and RCC who received at least 2 ICI doses at our institution from 1/1/10 to 10/31/18. Patient baseline characteristics, treatment course, and clinical outcomes were collected. IRAEs were identified and graded (GR) based on CTCAE (v.4.0). Fisher’s exact test was used to study the differences between pts w/ versus without IRAE. Results: Of the 71 pts identified (UC n = 53; RCC n = 18), 27 pts (38%) developed IRAEs with 42 total events (38% GR1, 60% GR2, and 2% GR≥3) [table]. The majority of pts with dermatitis (70%) also developed a secondary, systemic IRAE(s). Systemic steroid (SS) was required in 17 events. The median time to any IRAE was 17.5 weeks (w, range 1-93). ECOG ≤ 1 predicted IRAE development (p < 0.05). No other characteristics (demographics, co-morbidities, metastatic sites, ICI type, line of therapy, and duration of ICI > 12w) were associated with IRAE. Conclusions: In our study, good function status is associated with the development of IRAE. Time to IRAE ranged from immediately to 93w after initiating ICI. Clinical validation with additional datasets will be needed to confirm these findings. [Table: see text]
Conditional immune adverse event rate in urothelial and renal cell carcinoma patients treated with immune checkpoint inhibitors.
Authors: Nuzzo Pier Vitale , Pond Gregory Russell , Abou Alaiwi Sarah , Nassar Amin , Flippot Ronan , Curran Catherine , Kilbridge Kerry L. , Wei Xiao X. , McGregor Bradley Alexander , Harshman Lauren Christine , Choueiri Toni K. , Sonpavde Guru 
Published: February 2020

481 Background: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). While the incidence and prevalence of irAEs have been well characterized in the literature, much less is known about the cumulative incidence (CI) rate of irAEs. We sought to evaluate the CI of irAEs in metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma (mRCC) patients (pts) treated with ICIs. Methods: We identified a cohort of mUC and mRCC pts who received ICIs at DFCI. irAEs were classified using CTCAE v.5.0 guidelines. The CI rate was a defined measure that accounted for elapsed time since treatment initiation and estimated the risk of irAE development conditioned on time elapsed without experiencing an irAE, accounting for the competing risk of death. Incidence and CI of irAEs at each monthly landmark time was calculated. Prognostic factors of irAE were assessed using the Fine and Gray method. Results: A total of 470 pts was treated with ICIs between July 2013 and October 2018 [mUC: 199 (42.3%); mRCC: 271 (57.7%)]. 341 (72.6%) pts received ICI monotherapy, 86 (18.3%) received ICIs in combination with targeted therapies, and 43 (9.2%) received a combination of two ICIs. Overall, 186 pts (39.5%) experienced any irAE at any time point. Common irAEs included hypothyroidism (n=42 [22.6%]), skin (n=36 [19.4%]), colitis (n=35 [18.8%]), transaminitis (n=32 [17.2%]), and pneumonitis (n=14 [7.5%]). The risk of developing an irAE over time was as follows: 33.5% if no irAE within the 1st month(mo), 27.3% if no irAE in 3mo, 18.8% if no irAE in 6mo, and 16.4% if no irAE by 12mo. No difference was observed in CI based on type of cancer (mUC vs mRCC) or agent (PD1 vs. PD-L1). Multivariable analysis showed that ICI combined with ICI or other agents vs. ICI monotherapy (p<0.001), firstline therapy (p=0.013) and PD-1 vs. PD-L1 inhibitors (p=0.008) were statistically correlated with the development of irAEs. Conclusions: This study quantitates the incidence of developing irAEs with ICI conditioned on time elapsed without irAE development. Although the incidence of irAEs decreased over time on therapy, irAEs require continuous vigilant monitoring because of the long tail in its incidence.