bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of metagene based on gene expression with response to atezolizumab (atezo) for metastatic urothelial carcinoma (mUC).
Authors: Ravi Arvind , Ravi Praful , Nassar Amin , Abou Alaiwi Sarah , Curran Catherine , Mariathasan Sanjeev , Tayama Daren , Shen Xiaodong , Banchereau Romain , Price Rich , Getz Gad , Sonpavde Guru 
Published: February 2020

569 Background: Despite the benefits of PD1/L1 inhibitors in metastatic urothelial carcinoma (mUC), the durable benefits accrue mostly to a minority of patients (pts) who attain ≥partial response (PR) by RECIST 1.1. There is a pressing need to identify pts with a low probability of response, who may be diverted to other regimens or trials. Biomarkers associated with response such as PD-L1 expression, intrinsic subtype and tumor mutational burden (TMB) are suboptimal. We studied the ability of agnostic gene expression analysis for association with response. Methods: A retrospective cohort of FFPE tumor samples that underwent RNAseq utilizing pts from the phase II IMvigor210 trial were analyzed. In this study, pts received atezo, a PD-L1 inhibitor, in either the post-platinum or first line cisplatin-ineligible setting. All reads were collapsed to gene level transcript per million (TPM) values, followed by feature selection based on enrichment observed in patients with PR vs progressive disease (PD) as well as complete response (CR) vs PD. A transcriptional biomarker was then designed based on these gene-level enrichment scores, followed by generation of a synthetic “metagene” reflecting a composite of the top single gene predictors. Results: A total of 298 pts were evaluable from the IMvigor210 dataset. The favorable and unfavorable composite biomarker ‘metagene’ was robustly associated with high or low probability of ≥PR, regardless of line of atezolizumab therapy (Table). Area Under the Curve (AUC) for this biomarker was 0.73. Notably, an indeterminate category of the metagene was associated with ≥PR in an intermediate proportion of pts, consistent with meaningful discrimination of response categories. Conclusions: A metagene based on tumor gene expression robustly identified pts with mUC who exhibited ≥PR with atezo. With validation across other PD1/L1 inhibitors and refinement in combination with clinical factors, the metagene may enable the selection of the most suitable pts with mUC for PD1/L1 inhibitors.[Table: see text]
Genomic correlates of response to PD-1 axis inhibitors (IO) in metastatic urothelial cancer (mUC) using explainable artificial intelligence (AI).
Authors: Wesolowski Sergiusz , Nussenzveig Roberto , Santos Victor Sacristan , Esther John , Goel Divyam , Swami Umang , Gupta Sumati , Maughan Benjamin Louis , Yandell Mark , Grivas Petros , Agarwal Neeraj 
Published: February 2020

570 Background: AI is increasingly being used in clinical cancer genomics research. Probabilistic Graphical Models (PGMs) are AI algorithms that capture multivariate, mutli-level dependencies in complex patterns in large datasets while retaining human interpretability. We hypothesize that PGMs can identify clinical and genomic features that correlate with IO response in patients (pts) with mUC. Methods: In this retrospective study eligibility criteria were: diagnosis of mUC, receipt of IO for mUC, comprehensive genomic profiling data available from CLIA certified labs. The Bayesian Network (BN, PGM based AI) was used to discover clinical characteristics and selected genomic alterations relevant to IO response by RECIST 1.1 (investigator assessed). Results: Overall, 95 pts (73 men) with mUC were evaluated. 45 (47%) were ever smokers.The presented BN correctly captured the clinical landscape of mUC explaining significant relationship between included variables (p<0.0001). Ever smokers and pts with de novo metastasis had higher TMB and better response to IO. Inactivating MLL2 alterations were more prevalent in non-smokers, and negatively correlated with response to IO. FGFR3 alterations did not predict response to IO. Significant associations are presented in Table. Conclusions: These hypothesis-generating data (by a novel approach, i.e. PGM based AI) showed that smoking and high-TMB were associated with improved response to IO; in contrast, inactivating MLL2 alternations and visceral metastasis predicted inferior response. FGFR3 alterations did not correlate with response. This model validated previous findings and found new hypothesis-generating relationship, such as altered MLL2 gene; external validation is needed.[Table: see text]
Comparing progression-free survival (PFS) in second-line (2L) urothelial carcinoma (UC) treatments from single-arm trials: Importance of using appropriate methods.
Authors: Kapetanakis Venediktos , Prawitz Thibaud , Schlichting Michael , Ishak K. Jack , Phatak Hemant , Kasturi Vijay , Yu Ting , Bharmal Murtuza 
Published: February 2020

573 Background: Population-adjusted comparisons of PFS from single-arm trials of cancer treatments can be derived using matching-adjusted indirect comparison (MAIC); however, results are still susceptible to bias, particularly if the trials had different tumor assessment schedules (favoring longer intervals). This is shown with an MAIC of avelumab vs atezolizumab, nivolumab, durvalumab, pembrolizumab or chemotherapy in 2L UC. Methods: The MAIC used patient-level data for avelumab from the JAVELIN Solid Tumor trial (NCT01772004) and compared PFS with published curves for other treatments to obtain population-adjusted hazard ratios (HRs). The first assessment was scheduled at 6 weeks for avelumab and durvalumab and at 8 or 9 weeks for the others. The MAIC was repeated after aligning the first assessment time for avelumab to each comparator’s schedule with the Assessment Schedule Matching (ASM) method. Results: Naïve analyses (Table) suggest similar PFS for avelumab vs comparators. MAIC based on population adjustment (PA) altered the HR of avelumab vs atezolizumab and nivolumab (23.0% and 9.2% reductions in HR, respectively) but had little effect in other comparisons. ASM adjustment led to further changes in HR (13.2-32.7% reductions from naïve) favoring avelumab in MAICs where schedules differed. Of note, assessment schedule differences fully accounted for differences in PFS between avelumab and pembrolizumab. Conclusions: Indirect comparisons of PFS from single-arm trials must include adjustment for differences in both population characteristics and tumor assessment schedules. In this 2L UC MAIC, adjustment reversed some naïve comparisons, revealing more favorable PFS with avelumab up to 30%. Clinical trial information: NCT01772004. [Table: see text]
The impact of marital status on the survival of transitional cell carcinoma of the bladder.
Authors: Saad Anas M. , Baidoun Firas , Gad Mohamed M. , Ruhban Inas A. , Jazieh Khalid , Al-Husseini Muneer J. , Ornstein Moshe Chaim , Rini Brian I. , Gupta Shilpa 
Published: February 2020

578 Background: Marital status is one of the multiple lifestyle factors that affect the survival of several malignancies. Prior literature has demonstrated that married individuals have better survival in cases of transitional cell carcinoma (TCC). In this study, we aim to demonstrate the association in a large cohort of patients. Methods: Data of TCC patients with known marital status who were diagnosed between 1973 and 2015 in the US was obtained using the Surveillance Epidemiology and End Results (SEER) database. We compared the overall and cancer-specific survival of patients according to their marital status using Kaplan-Meier test and multivariable covariate-adjusted Cox models. Results: We reviewed 204,862 TCC patients, of which 64.26%, 10.64%, 1.01%, 7.31%, and 16.78% were married, single, separated, divorced, and widowed, respectively. Married patients had the highest overall survival (median 123 months), followed by single patients (median 111 months), divorced (median 102 months), separated (median 60 months), and widowed (median 43 months). Bladder cancer-specific survival followed relatively similar trends with married patients having significantly better survival when compared to other groups. When we adjusted for age, sex, race, stage, grade, and undergoing cancer-targeted surgery, married patients had better survival outcomes when compared to single patients (HR = 1.322, p-value < 0.001), separated patients (HR = 1.409, p-value < 0.001), divorced patients (HR = 1.358, p-value < 0.001), and widowed patients (HR = 1.242, p-value < 0.001). Conclusions: Our results demonstrate a clear survival advantage in cases of transitional cell carcinoma of the bladder with married individuals having the highest overall and cancer-specific median survival. These results shed the light on the lifestyle and the psychosocial factors, including the social support that married patients may have comparing to unmarried patients, and their effect on the disease prognosis and survival. Understanding the social and psychological factors associated with the observed disparity may help enhance management plans for affected patients.
Genitourinary oncology referral patterns to the cancer associated thrombosis clinic: The Cleveland Clinic experience.
Authors: Sheng Iris Yeong- Fung , Angelini Dana E , Khorana Alok A. , Gilligan Timothy D. , Rini Brian I. , Garcia Jorge A. , Ornstein Moshe Chaim , Gupta Shilpa 
Published: February 2020

583 Background: Cancer related thrombosis affects ~20% of all cancer patients. It is our standard practice to refer cancer patients with suspected venous thromboembolism (VTE) to our Cancer Associated Thrombosis (CAT) clinic. Referrals are based on a clinical suspicion of VTE or a Khorana score ≥3. We sought to evaluate the characteristics of patients with genitourinary (GU) cancer referred to the CAT clinic and their association with immunotherapy. Methods: The study population comprised of all cancer patients referred to the CAT clinic with a diagnosis of prostate cancer (Pca), bladder cancer (BC) or renal cell cancer (RCC) from August 1, 2014 to October 15, 2019. Results: Of the 147 patients with GU cancers referred to CAT clinic, 43 had a VTE (14/40 BC, 14/44 RCC, 15/63 PCa). Of which, 83% were DVT, 5% were PE, and 12% had both. The majority had stage 4 disease (98%), no prior clotting history, and ECOG 0-2 (86%). Average BMI was 28.63 and 22 patients had smoking histories (average 11 pack years). Major histology per cancer type were adenocarcinoma (100%) in PCa, 86.7% clear cell in RCC and 85.7% urothelial carcinoma in BC. Lower extremity pain or swelling (67%) was the major reason for referral. Thirty-four of the 43 patients were on active treatment; 7 patients on immunotherapy (average 4.9 months) and 13 patients on chemotherapy (average 2.6 cycles) at the time of VTE diagnosis. Of the chemotherapy regimens, patients were on the combination of gemcitabine with carboplatin (54%), docetaxel (23%), or cabazitaxel (23%). Atezolizumab was the most commonly used immunotherapy agent (57%). Other immunotherapy agents associated were nivolumab (29%) and the combination of ipilimumab with nivolumab (14 %). There was no VTE-related mortality. Conclusions: Our single center experience shows 16% of VTE events in patients with GU cancers were associated with immunotherapy and 33% were associated with cytotoxic chemotherapy. There is a growing body of literature exploring the association between thromboembolic events and immunotherapy. As more patients with GU cancers are treated with immunotherapy, it will be interesting to see how this influences the rate of CAT clinic referral and prevalence rates of VTE.
Prevalence and landscape of actionable genomic alterations in renal cell carcinoma.
Authors: Attalla Kyrollis , DiNatale Renzo G. , Reznik Eduard , Fong Christopher , Sanchez-Vega Francisco , Silagy Andrew W. , Weng Stanley , Coleman Jonathan , Lee Chung-Han , Carlo Maria Isabel , Russo Paul , Chan Timothy An-thy , Motzer Robert J. , Schultz Nikolaus D. , Voss Martin H , Hakimi A. Ari 
Published: February 2020

616 Background: We report our experience with next-generation sequencing to characterize the prevalence and genomic landscape of actionable genomic alterations in renal cell carcinoma (RCC). Methods: A query of our institutional clinical sequencing database was performed to include tumor samples sequenced across all cancers. Actionable alterations with clinical or biologic evidence supporting an association with response to targeted therapy were stratified by level of evidence using an oncology knowledge database (OncoKB). Results: Data from 35,668 patients was included, and the 15 cancer types with the highest prevalence of actionable alterations were selected for subsequent analysis (28,027 patients). Of these cancers, RCC ranked 13th in prevalence of actionable alterations. Of 708 RCC samples included, 259 (37%) were from metastatic sites. However, of the remaining 449 primary samples, 208 (29%) belonged to patients who had metastatic disease at the time of sequencing. Although 69% of patients with any RCC harbored at least one known oncogenic mutation, only 90/687 (13%) harbored alterations for which compelling clinical data currently exist to justify the use of a standard or an investigational agent (levels of evidence 1 to 3B). This represents an increase from the previously reported prevalence (5% in 2017). The most common histologic subtype, clear cell RCC harbored the vast majority of actionable alterations (52/421; 12%). Regarding the specific genes that harbor these alterations, 31 level 2A alterations were identified, all of which were TSC1/TSC2 mutations; 30 level 2B alterations were identified, of which PIK3CA (22) and BRCA1/BRCA2 (5) mutations were most common; 11 level 3A alterations, all of which were MTOR mutations, and 8 level 3B alterations, of which AKT1 (4) mutation was most common. Conclusions: Although the prevalence of actionable mutations in RCC seems to have doubled in recent years, the role of genetic testing in identifying candidates for targeted therapy in RCC is currently limited relative to other cancer types, emphasizing the need for additional research in this area to further inform targeted therapy decisions.
Overall survival results for durvalumab and savolitinib in metastatic papillary renal cancer.
Authors: Suarez Rodriguez Cristina , Larkin James M. G. , Patel Poulam , Valderrama Begona Pérez , Rodriguez-Vida Alejo , Glen Hilary , Thistlethwaite Fiona , Ralph Christy , Srinivasan Gopalakrishnan , Mendez Vidal Maria Jose José , Carter Abigail , Tyson Charlotte , Prendergast Aaron , Mousa Kelly , Powles Thomas 
Published: February 2020

619 Background: There is a strong rationale for investigating MET and PD-L1 inhibition in metastatic papillary renal cancer (PRC). We previously reported response rates (RR) and progression free survival (PFS) for savolitinib (MET inhibitor) and durvalumab (PD-L1 inhibitor) together. Here we report overall survival (OS) data available 12 months after the last patient was enrolled. Methods: This single arm phase I/II trial explores durvalumab (1500mg Q4W) and savolitinib (600mg OD) together in PRC, with a 4wk savolitinib run in. Treatment naïve or previously treated patients with metastatic PRC were included. Confirmed RR (RECIST v1.1), PFS, tolerability (CTCAE v4.03) and overall survival (OS) were analysed. MET and PD-L1 biomarkers were explored (NCT02819596). Results: 42 patients were enrolled with 41 receiving at least one dose of study treatment. Safety and efficacy analyses were performed on these 41 patients. The median follow up was 14.3 months. IMDC good, intermediate and poor risk disease occurred in 29%, 63%, and 7% of patients respectively. Overall confirmed RR was 27% while median PFS was 4.9 months (95% CI: 2.5 – 12.0 months). Median OS was 12.3 months (95% CI: 5.8 – 21.3 months). Confirmed RR and median OS in the previously untreated cohort (N=27) were 33% and 12.3 months (95% CI: 4.7 – not reached (NR) months) respectively. Treatment related Grade 3/4 toxicity occurred in 34% of patients. No new safety signals were seen. PD-L1 and MET expression were not associated with higher RR (25% and 40% respectively) or longer OS. Conclusions: The combination of savolitinib and durvalumab has clinical activity in PRC and outcomes were not enhanced in biomarker positive cancers. Clinical trial information: NCT02819596.
The impact of metastasis location on overall survival among patients with renal cell carcinoma.
Authors: Patel Devin , Ghali Fady , Meagher Margaret , Meagher Margaret , Bradshaw Aaron , Patel Sunil , Keiner Cathrine , Miller Nathan , Dutt Raksha , Murphy James Don , Derweesh Ithaar 
Published: February 2020

621 Background: Current staging guidelines define all patients with metastatic renal cell carcinoma (RCC) as a singular group. We sought to compare the impact of metastatic disease location on overall survival (OS) in patients with RCC. Methods: We queried our institutional database of consecutive patients with metastatic RCC. A confirmatory analysis was performed using the National Cancer Database (NCDB) for cases between 2010 to 2015. Only cases from which all metastatic disease location was known were used. Patients were grouped into having brain or bone metastases, liver or lung metastases or other metastases. From our institutional database, we performed a univariate analysis to determine the impact of metastasis location on OS. From the NCDB, univariable and multivariable Cox proportional hazards and Kaplan-Meier survival analysis with log-rank testing was performed. Multivariable models were adjusted for age, comorbidity, race, gender, and treatment with either palliative care, chemotherapy or immunotherapy. Results: A total of 95 patients were analyzed from our institutional database, with 30 (31.9%) having brain/bone metastases, 20 (21.3%) having lung/liver metastases, and 44 (46.8%) having other site metastases. On univariate analysis, patients with brain/bone metastases had significantly worse OS (HR 1.87; 95% CI 1.01-3.47). However, no significant difference was seen in patients with liver/lung metastases (HR 1.44; 95% CI 0.64-3.27). A total of 25,528 patients met inclusion for our NCDB analysis, of which 12,119 (47.5%) had brain/bone metastases, 10,004 (39.2%) had liver/lung metastases, and 3,405 (13.3%) had other site metastases. On univariate analysis, patients with lung/liver (HR 1.46; 95% CI 1.38-1.53) and patients with bone/brain (HR 1.69; 95% CI 1.60-1.77) had progressively worse OS with non-overlapping confidence intervals. Multivariable analysis again showed that patients with lung/liver disease (HR 1.51; 95% CI 1.43-1.59) and brain/bone disease (HR 1.66; 95% CI 1.60-1.75) had progressively worse OS. Conclusions: Our results highlight the heterogeneity of patients with metastatic renal cell carcinoma. Location of metastatic disease may drive differences in survival.
Progression-free survival (PFS) and overall survival (OS) across ethnicities for patients with metastatic renal cell carcinoma (mRCC) receiving targeted therapies (TT) as first-line (1L) treatment.
Authors: Salgia Nicholas , Dizman Nazli , Bergerot Paulo Gustavo , Bergerot Cristiane Decat , Hsu Joann , Pal Sumanta K. 
Published: February 2020

645 Background: Recent efforts have sought to characterize differences in clinical and pathological characteristics across ethnicities in mRCC (Batai et al CGUC 2018), however, the relationship between ethnicity and treatment outcomes has yet to be explored. We sought to compare survival outcomes across ethnic groups for patients receiving 1L TT for treatment of mRCC. Methods: Patients receiving 1L systemic treatment for mRCC were retrospectively identified from a single institution database from 2009 to present. Patient ethnicity data were collected from electronic health records. Due to the demographics of the patient population, ethnicity was categorized as Non-Hispanic Caucasian American (CA), Hispanic American (HA), or Asian American (AsA). Patients prescribed tyrosine kinase and/or mTOR inhibitors as 1L therapy were included for analysis. PFS and OS were analyzed across ethnic groups and comparisons were performed using the Kaplan Meier Survival Function in SPSS. Results: Of 294 (77:217 F:M) patients with documented survival data, 183 (62%) were CA, 82 (28%) HA, and 29 (10%) AsA. The most frequently used TTs were sunitinib (63%), temsirolimus (10%), pazopanib (7%), sorafenib (5%), and cabozantinib (4%). Median PFS for CA was 5.6 months (95% Confidence Interval [CI]: 4.1-7.1) vs. 4.7 months (95% CI: 3.1-6.2) for HA vs. 4.7 months (95% CI: 2.1-7.3) for AsA. Median OS was 32.0 months (95% CI: 26.2-37.8) for CA vs. 31.7 months (95% CI: 21.1-42.4) for HA vs. 51.7 months (95% CI: 31.6-71.8) for AsA. No significant difference in PFS or OS was calculated across the three ethnic groups (p=0.652 and p=0.435, respectively). Conclusions: The lack of a statistically significant difference in both PFS and OS across ethnic groups is a promising assessment for the current landscape of health disparities in mRCC. As these data are distinct from recent findings identifying disparities in other malignancies (e.g., prostate cancer), multicenter collaborations should be encouraged to validate these findings.
The role of cytoreductive nephrectomy (CN) for patients with metastatic renal cell carcinoma (mRCC) in the setting of retroperitoneal lymphadenopathy: An analysis of the National Cancer Database (NCDB).
Authors: Reddy Akshay , Sparks Andrew D , Whalen Michael Joseph 
Published: February 2020

688 Background: Recent evidence has suggested systemic therapy alone (ST) may be comparable to CN in treating mRCC. This study aims to understand oncologic outcomes and survival of those with node positive mRCC treated with ST compared to CN and explore the role of LAD at the time of surgery. Methods: A retrospective cohort analysis of patients who had undergone either ST or CN for clinically node-positive mRCC was performed using the NCDB. The CN group was subdivided into no LND vs. LND (based on reported lymph node yield, “LNY” (i.e. 0 vs. ≥1). Demographic and clinicopathological variables were compared to adjust for confounding covariates in multivariable analysis. Patients who underwent palliative treatments or LAD without nephrectomy were excluded. Results: The majority of CN were performed via open approach (70.1%). CN was associated with decreased mortality hazard relative to ST, while no difference in survival was detected between LAD and no LAD (Table). Median LNY was 2. Inpatient stay was significantly longer for LAD relative to no LAD (median 5 vs. 4 days; P=0.02). CN was associated with increased odds of 30 day hospital readmission relative to ST (aOR=8.6; 95% CI: 5.5 – 13.4; P<0.01), while LAD was significantly associated with decreased odds of 30 day hospital readmission relative to no LAD (aOR=0.6; 95% CI: 0.4 – 0.9; P=0.02). Conclusions: CN is associated with a significant survival advantage but potentially greater complications compared to those receiving ST in node-positive mRCC. Despite offering diagnostic information via a more aggressive approach, there does not appear to be therapeutic benefit of LAD with CN in the metastatic setting where patients receive concomitant ST.[Table: see text]