bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent durvalumab and radiation therapy followed by adjuvant durvalumab in patients with locally advanced urothelial cancer of bladder (DUART): Btcrc-GU15-023.
Authors: Joshi Monika , Tuanquin Leonard , Kaag Matthew , Kilari Deepak , Holder Sheldon L. , Emamekhoo Hamid , Sankin Alexander , Merrill Suzanne B , DeGraff David , Warrick Joshua , Zheng Hong , Hauke Ralph J. , Gartrell Benjamin Adam , Stein Mark N. , Zakharia Yousef , Drabick Joseph J. 
Published: February 2020

513 Background: Bladder cancer (BC) patients (pts) who are cisplatin ineligible/unfit for surgery, unresectable have limited treatment options. In this study, we investigate if the combination of radiation therapy (RT) and checkpoint inhibitor, durvalumab (durva) is safe and effective in these pts. Our results from phase (ph) Ib suggested that the combination was safe. Here we present the response rate post durvaRT and updated treatment related adverse events (TRAEs) amongst our evaluable pts in ph II. Methods: This is a single arm ph Ib-II study for T2-4 N0-2 M0 pts. The ph II primary endpoints a) PFS rate at 1 yr b) disease control rate (DCR); secondary endpoints were a) CR post durvaRT b) PFS c) OS. Pts were treated with durva (1500mg) Q4 wks x2 doses along with definitive RT (64.8Gy, 36 fractions over 7 wks) to the bladder and involved nodes followed by adjuvant durva Q4 wks x 1 yr. Response was evaluated with CT scan and cystoscopy+biopsy post durvaRT. We anticipated that durvaRT followed by durva would increase PFS at 1 yr from 50% to 75% when compared to RT; we assumed DCR of about 75%. A total of 26 pts were needed to reach a statistical power of at least 80% at one-sided alpha of 5% and to allow for 10% drop out rate. Results: Total N = 26 patients (male 19; female 7, median age 74yr). At the time of data cut off, 21/26 pts were evaluable for response post durvaRT. Post completion of durvaRT time point, clinical CR was seen in 15/21 pts (71.4%); PR 1/21 pts (4.7%); SD 4/21 (19%); PD 1/21 (4.7%). DCR was seen in 20/21 pts (95%) post durvaRT. Median follow up from D1 to last follow up was 6.1 mos. Grade ≥ 3 TRAE amongst 26 pts: anemia (1/26), lipase/amylase (1/26), immune nephritis (1/26), dyspnea (gr 4, copd/immune), fatigue (1/26), lymphopenia (6/26). Other TRAEs: Fatigue was the most common TRAE (16/26); UTI (5/26); cystitis (3/26). No fatal TRAEs were observed. Conclusions: DurvaRT demonstrated promising efficacy with clinical CR of 71.4% and DCR of 95% in unresectable, cisplatin ineligible locally advanced BC. It was generally well tolerated. Ph II study has completed accrual and longer-term results will further our understanding of this regimen’s efficacy in locally advanced BC. Clinical trial information: NCT02891161.
Phase I experience with rogaratinib in patients (pts) with urothelial carcinoma (UC) selected based on FGFR mRNA overexpression.
Authors: Kempf Emmanuelle , Penel Nicolas , Tournigand Christophe , Gajate Pablo , Tan Daniel Shao-Weng , Cassier Philippe , Nogova Lucia , Cathomas Richard , Schostak Martin , Janitzky Andreas , Wermke Martin , Sayehli Cyrus , Navarro Alejandro , Park Se Hoon , Piciu Ana-Maria , Bender Sebastian , Nogai Hendrik , Ellinghaus Peter , Joerger Markus , Schuler Martin H. 
Published: February 2020

527 Background: Aberrant activation of the fibroblast growth factor receptor (FGFR) pathway is implicated in many cancers, including UC. In a recent Phase I dose-escalation study, rogaratinib, an oral pan-FGFR1-4 inhibitor, demonstrated favorable efficacy and safety in pts with solid cancers selected based on FGFR1-3 mRNA overexpression. We report results from the Phase I expansion cohort with rogaratinib in pts with UC selected by FGFR1-3 mRNA overexpression and/or FGFR3-activating mutations (NCT01976741). Methods: Pts with advanced/metastatic UC were screened for FGFR1-3 mRNA overexpression using RNA in situ hybridization (RNAscope) and NanoString assay in fresh or archival tumor samples. Pts received rogaratinib 800 mg po BID continuously. Tumor response and safety were assessed. Results: 74 pts with UC were treated with rogaratinib; 73.0% were male, median age was 66 years (range 45-85), and 93.2% had stage IV disease. Rogaratinib was well tolerated, with adverse events being mostly mild or moderate. The most common treatment-emergent adverse events (TEAEs) are shown in the Table. The most common drug-related TEAEs (any grade) were diarrhea (52.7%), increased blood phosphorus (41.9%), and decreased appetite and dry mouth (31.1% each). No ocular toxicities were reported. Increased blood creatinine and acute kidney injury (AKI), regardless of relatedness, were reported in 16.2% and 2.7% of pts, respectively; 1 case of AKI was confirmed as acute tubular necrosis. Of 72 evaluable pts, 15 (20.8%) achieved an objective response; complete and partial responses were observed in 1 (1.4%) and 14 (19.4%) pts, respectively. Stable disease was achieved by 34 pts (47.2%), with a disease control rate of 68.1%. Conclusions: Rogaratinib demonstrated a favorable safety and efficacy profile in pts with tumor FGFR1-3 mRNA-positive UC. TEAEs observed in >25% of pts. Clinical trial information: NCT01976741. [Table: see text]
Cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI) or targeted therapy (TT): A propensity score-based analysis.
Authors: Bakouny Ziad , Xie Wanling , Dudani Shaan , Wells Connor , Gan Chun Loo , Donskov Frede , Shapiro Julia , Davis Ian D. , Parnis Francis , Ravi Praful , Steinharter John A. , Agarwal Neeraj , Alva Ajjai Shivaram , Wood Lori , Kapoor Anil , Ruiz Morales Jose Manuel , Kollmannsberger Christian K. , Beuselinck Benoit , Heng Daniel Yick Chin , Choueiri Toni K. 
Published: February 2020

608 Background: The role of CN for mRCC treated with ICI is not well defined. Our aim was to evaluate the role of CN for mRCC treated by ICI or TT using a propensity score-based analysis. Methods: We retrospectively assessed patients who were diagnosed with de novo mRCC and who had started first line systemic therapy (ICI or TT) between 2009 and 2019 using the International Metastatic RCC Database Consortium (IMDC). Overall Survival (OS) was compared between patients receiving CN and those treated by systemic therapies alone, using the Kaplan-Meier method and Cox regressions, in the TT and ICI arms separately. In order to account for treatment selection bias, inverse probability of treatment weighting (IPTW) of propensity scores, based on 14 confounding variables, was used and variables were considered balanced if standardized mean difference (SMD) < 0.1. For variables with SMD≥0.1, residual confounding was adjusted for using multivariable models. Results: 3856 patients had been treated by TT (2470 CN+ & 1386 CN-) and 198 by ICI (143 CN+ & 55 CN-). Median follow-up was 38.5 months. After IPTW, baseline characteristics were largely balanced between the CN+ and CN- arms, in the TT and ICI groups (14/14 and 12/14 with SMD < 0.1, respectively). CN was associated with significantly improved OS in both the ICI (Hazard Ratio [HR] = 0.39 [0.19-0.83]) and TT (HR = 0.56 [0.51-0.62]) groups. The interaction term between CN and therapy type (ICI vs TT) was not statistically significant (p = 0.43). The point estimates of the HRs were consistent in sensitivity analyses using multivariable models. Conclusions: In a propensity score-based analysis, CN was found to be associated with a significant OS benefit in patients treated by either ICI or TT. While this study is not a substitute for randomized controlled trials (e.g. CARMENA), the results suggest that CN may still play a role in selected patients in the ICI era.[Table: see text]
Real-world outcomes in patients with metastatic renal cell carcinoma according to risk factors: Analysis of the STAR TOR registry.
Authors: Moran Michael , Hubbe Marcus , Rink Michael , Bergmann Lothar , Strauss Arne , Bernhardt Stephan , Schmid Marianne , Boegemann Martin , Schlack Katrin 
Published: February 2020

628 Background: Metastatic renal cell carcinoma (mRCC) treatment is partly informed by risk group. The two most commonly used prognostic models, the International Metastatic RCC Database Consortium (IMDC) and the Memorial Sloan-Kettering Cancer Center (MSKCC), stratify patients (pts) into favorable (0 risk factors [RFs]), intermediate (1–2 RFs) or high risk (≥3 RFs) groups. This study examined real-world outcomes according to IMDC and MSKCC RFs in sunitinib-treated pts with mRCC. Methods: Data were extracted on 19 June 2019 from a large, prospective German multicenter registry (STAR-TOR). Only pts with sufficient data for risk stratification by IMDC and MSKCC were included in this analysis. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The impact of RFs on survival was assessed using Cox’s regression analysis and the chi square test. Results: According to IMDC or MSKCC, 16.7% and 15.3%, 26.2% and 30.8%, 18.7% and 24.7%, and 38.5% and 29.2 of pts had 0, 1, 2 and ≥3 RFs, respectively. In IMDC intermediate pts, only < 1 year diagnosis to therapy (24.8%) was the most common RF; in MSKCC intermediate pts, < 1 year diagnosis to therapy with low hemoglobin (19.9%) were the most common. OS was not significantly different for pts with 0 vs 1 (p = 0.24), or 2 vs ≥3 (p = 0.16) IMDC RFs, but was significant according to MSKCC RFs (0 vs 1, p = 0.04; 2 vs ≥3, p < 0.01). OS was significantly longer for pts with 1 vs 2 RFs for IMDC (p = 0.03) and MSKCC (p = 0.04), but PFS was not (IMDC, p = 0.29; MSKCC, p = 0.12). OS was significantly longer for 0 vs 2, 0 vs ≥3, and 1 vs ≥3 RFs for IMDC and MSKCC RFs (all comparisons, p < 0.01). Similar results were observed for PFS with the exception of 0 vs 1 IMDC RF (p = 0.01). Conclusions: The intermediate risk group appears to be heterogeneous. OS for pts with 1 RF may align with the favorable risk group and pts with 2 RFs may align with the poor risk group.[Table: see text]
Effect of comorbidities/comedications on treatment outcomes with sunitinib in patients (pts) with metastatic renal cell carcinoma (mRCC): Subgroup analyses from the STAR-TOR registry.
Authors: Bernhardt Stephan , Hubbe Marcus , Rink Michael , Bergmann Lothar , Boegemann Martin , Moran Michael , Schlack Katrin , Strauss Arne , Schmid Marianne 
Published: February 2020

631 Background: Sunitinib remains an important treatment option for mRCC, but the effect of comorbidities/comedications on sunitinib treatment outcomes have not been fully explored. Methods: Data were collated from STAR-TOR, an ongoing real-world registry. Cutoff date for analysis was 19 June 2019. This subgroup analysis assessed the presence or absence of hypertension (HTN), and the use or non-use of statins and proton pump inhibitors (PPIs), determined at the time of entry to the registry. Treatment endpoints were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). OS and PFS were analyzed by Kaplan-Meier methods. Differences within subgroups were tested using Log-rank test for OS and PFS, and Fisher’s exact test for ORR. Results: 557 sunitinib-treated pts were analyzed; 366 had HTN and 191 did not, 130 used statins and 427 did not, and 165 used PPIs and 392 did not. Median (m) OS (95% confidence intervals) was similar in pts with and without HTN (25.4 [21.1, 31.5] vs 21.5 [15.2, 28.0] months; p = 0.215). mPFS (8.0 [6.5, 9.9] vs 6.3 [5.4, 8.2] months; p = 0.140) and ORR (31.2% vs 30.9%; p = 1.000) were also similar in pts with and without HTN. mOS was similar in pts who used statins vs those who did not (27.8 [20.2, 35.4] vs 24.0 [19.4, 27.3] months; p = 0.884), while mPFS was significantly longer in pts who used statins (9.4 [6.5, 13.6] vs 6.9 [5.7, 8.2] months; p = 0.044). ORR was 37.8% vs 29.0% in pts who did and did not use statins (p = 0.072). mOS was significantly shorter in pts who used PPIs vs those who did not (20.2 [14.9, 28.3] vs 25.7 [22.7, 33.0] months; p = 0.021). mPFS (5.8 [4.6, 8.2] vs 8.0 [6.5, 9.8] months; p = 0.091) and ORR (26.6% vs 33.0%; p = 0.177) were similar in pts who did and did not use PPIs. Conclusions: In sunitinib-treated pts with mRCC in a real-world registry, mPFS was significantly longer and there was a trend toward better ORR in pts who used statins, whereas mOS was significantly shorter and there was a trend toward shorter mPFS in pts who used PPIs. Common comedications may affect sunitinib treatment outcomes in pts with mRCC.
Preoperative metastatic disease burden to predict overall survival following cytoreductive nephrectomy independent of IMDC risk category.
Authors: Shapiro Daniel D. , Karam Jose A. , Spiess Philippe E. , Raman Jay D. , Westerman Mary E. , Sexton Wade J. , Zemp Logan , Bilotta Alyssa , Allen Glenn O. , Lauer Kate V. , Matin Surena F. , Wood Christopher G. , Abel E. Jason 
Published: February 2020

652 Background: Studies suggest that overall survival (OS) following cytoreductive nephrectomy (CN) is associated with preoperative tumor measurements including primary tumor diameter, number of metastatic sites, sum of metastatic tumor diameters and primary tumor percent of overall burden. Current risk models, however, do not account for tumor burden. This study evaluated associations between OS and preoperative tumor measurements for patients treated with CN during the targeted therapy era. Methods: Data for consecutive mRCC patients treated with CN at 4 institutions from 2006-2017 were analyzed after determining IMDC risk category, primary tumor (PT) diameter, number of metastatic sites, sum of metastatic tumor diameters and PT percentage of overall burden. Univariate and multivariable (MV) Cox models evaluated tumor measurement and IMDC risk associations with OS. Results: A total of 617 patients were available for analysis. Median PT diameter was 10.0 cm (IQR 7-13cm), number of metastatic sites was 2 (IQR 1-2), sum of metastatic tumor diameters was 4.5 cm (IQR 2-10cm) and PT percent of overall burden was 73.7% (IQR 60-85%). After univariate analysis, all 4 tumor burden measures were associated with OS (p≤0.001 for all). MV models evaluating IMDC risk category with individual tumor burden measurements demonstrated that all measures were predictive as continuous variables: PT diameter (HR 1.03, 95% CI 1.01-1.06, p=0.007), sum of metastatic tumor diameters (HR 1.04, 95% CI 1.02-1.05, p<0.001), PT percent of overall burden (HR 0.43, 95% CI 0.27-0.68, p<0.001), and number of metastatic sites (HR 1.52, 95% CI 1.25-1.85, p<0.001). Additional MV models were created using clinically significant tumor measurement cutoffs and IMDC risk groups. OS was independently associated with IMDC intermediate (HR 3.17, 95% CI 1.84-5.44, p<0.001) and poor risk (HR 3.85, 95% CI 2.21-6.70, p<0.001), PT percentage of overall burden <90% (HR 1.41, 95% CI 1.05-1.89, p=0.021), and >2 metastatic sites (HR 1.60, 95% CI 1.29-2.00, p<0.001). Conclusions: PT and metastatic disease burden are independently associated with OS following CN. Future risk models should include tumor burden measurements.
Selecting the surgical approach in complex reoperative partial nephrectomies: Does robotics have a role?
Authors: Gurram Sandeep , Telfer Siobhan , Li Winston , Chalfin Heather , Linehan W. Marston , Ball Mark Wayne 
Published: February 2020

658 Background: Minimally invasive surgery (MIS) has shown equal oncologic efficacy as the open approach for treating small renal masses but results in improved perioperative parameters. Surgical principles also dictate that the open technique should be considered when facing difficult surgeries though this is experience and not evidenced based. The goal of our study is to explore differences in outcomes amongst open or robotic approaches in complex reoperative partial nephrectomies. Methods: 194 patients who had prior renal surgery from 2008 to 2019 were identified, the majority of which presented with multiple tumors due to known or suspected hereditary kidney cancer syndrome. Patients were stratified into the following cohorts based on surgical history: open after open surgery, open after MIS, robotic after open surgery, and robotic after MIS. Perioperative outcomes were compared amongst cohorts. Results: Significant differences were noted in estimated blood loss (EBL), number of tumors resected, and postoperative complications as assessed by Clavien score. Univariate regression analysis of EBL showed that the number of tumors resected (p <.0001, coefficient: 111 ml), number of prior renal procedures (p=.012, coefficient: 419 ml), hilar clamping (p = .015, coefficient: 840 ml), and intended surgical approach (p = .001; coefficient: 905 ml) were significant. On multivariate analysis, number of tumors resected (p<.0001, coefficient: 97 ml) was the only significant factor. Univariate analysis on post-operative complications showed that number of prior surgeries (p = 0.03, OR: 1.5) and final intended approach (p < .0001, OR: 4.6) were significant. On multivariate analysis, the final intended surgical approach (p = .001, OR: 4.3) was shown to be significant. Conclusions: These data show that the surgical approach of prior procedures is not a significant factor that affects perioperative outcomes, but the use of robotic surgery was associated with decreased post-operative complications in reoperative renal surgery . While open surgery will likely continue to be the standard of care for complex reoperative procedures, these data suggest that robotic surgery is safe and well tolerated in select cases.
Mental perception of prostate cancer (PCa) disease in patients aged 60 years and older initiating gonadotropin-releasing hormone agonist (GnRHa) therapy.
Authors: Hennequin Christophe , Rozet Francois , Mongiat-Artus Pierre , Pello Leprince Ringuet Nathalie , Houchard Aude , Roupret Morgan 
Published: February 2020

67 Background: PCa mostly affects elderly men and impacts their health-related quality of life (HRQOL), but little is known on differences by age groups. Our purpose was to analyze HRQOL with EORTC QLQ-ELD-14 questionnaire, a 7-dimension questionnaire specific of elderly cancer patients. Methods: From March 2018, a prospective, multicenter, non-interventional study was conducted in France (PRISME, NCT03516110). Urologists, radiation oncologists and medical oncologists recruited, as part as the normal consultation process, patients who met the following inclusion criteria: aged 60 years and older, with histologically confirmed PCa, candidate for GnRHa therapy. Patients were included (1:2:1) in prespecified age groups ([60-70[, [70-75[, ≥ 75 years). They reported HRQOL using ELD-14. Results: Overall, 528 patients were included in the interim analysis of baseline results. Mean (±SD) age was 72.9±6.5 years. There were 145, 207 and 176 patients, respectively, in the [60-70[, [70-75[ and ≥ 75 years groups. 93.8% of patients had a Karnofsky score ≥ 80%; 73.4% had at least one comorbidity at baseline and 67.9% were receiving at least one concomitant systemic treatment. Reason for GnRHa initiation was high risk localized or locally advanced tumor in 57.6%, metastatic stage in 19.8%, biochemical recurrence after local treatment in 14.7%. ELD-14 results on dimensions were as follows: “Mobility” was significantly worse in the 75y+ group (21.2±25.0) than in the [60-70[ (8.8±18.0) and [70-75[ (11.1±17.4) groups. “Burden of illness” decreased with age, with mean scores of 37.7±27.7, 31.0±25.3, and 28.3±25.1 (significantly different between [60-70[and 75y+ groups). No difference were observed on “Worries about future”, “Worries about others”, “Family support” and “Maintaining purpose” (motivation and positive outlook), however there was a large variability (SD > 34) within each group for the last two dimensions. Conclusions: HRQOL interim analysis through ELD-14 showed few differences between age groups, and noticed variability within groups instead of between groups, meaning that mental perception of the disease could be more subject- than age-related.
Outcomes of systemic therapy in relapsed renal cell carcinoma (RCC) treated with adjuvant sunitinib (AS).
Authors: de Velasco Guillermo , Ruiz-Granados Álvaro , Reig Oscar , Massari Francesco , Climent Duran Miguel Angel , Verzoni Elena , Graham Jeffrey , Llarena Roberto , De Tursi Michele , Donskov Frede , Iglesias Clara , Pandha Hardev S. , Garcia del Muro Xavier , Procopio Giuseppe , Oudard Stephane , Castellano Daniel , Albiges Laurence 
Published: February 2020

701 Background: There are no available data on the usefulness of targeted therapy (TT) as the first-line treatment for patients with RCC recurrence after AS. We aim to explore the outcomes of systemic therapy with recurrent RCC after AS including re-exposure to sunitinib. Methods: A multi-institutional retrospective study was conducted on RCC patients who relapsed after AS. The primary end point was progression-free survival (PFS). Secondary end points were overall response rate (ORR) and overall survival (OS). Results: 34 relapses were recorded, 25 patients (73,5%) were male. 25 patients were treated with systemic therapy at first-line after relapse: 65% of patients received Vascular Endothelial Growth Factor (VEGF)-TT (including 7 patients retreated with sunitinib), 21,7% mTOR inhibitors and 13% immunotherapy. The median time to relapse was 20,3 months (IQR 5,2-20,4) from diagnosis, and 7,5 months (IQR 1,0-8,5) months from AS ending. At a median time of follow-up of 23,5 months, 24/25 patients had progressed on first-line systemic therapy. The median PFS was 12,0 months (IC95% 6,6-17,8 months). There was no statistical difference in PFS among the different treatments or the re-exposed to sunitinib. PFS was not statistically different between those relapsing on or after AS ( < 6 or > 6 months after AS). ORR was 20,3%. Median OS was 28,7 months (IC95% 24,4-33,0). Conclusions: This study suggests that TT may still improve PFS and OS in RCC patients who relapsed after AS.
Genomic landscape and immune microenvironment features of FH-deficient renal cell carcinoma.
Authors: Sun Guangxi , Zhang Xingming , Pan Xiuyi , Zhu Sha , Liu Zhenhua , Zhao Jinge , Armstrong Cameron M. , Zhang Haoran , Huang Rui , Yin Xiaoxue , Zhang Mengni , Shen Pengfei , Dai Jindong , Shen Yali , Nie Ling , Wei Qiang , Li Xiang , Yao Jin , Chen Ni , Zeng Hao 
Published: February 2020

717 Background: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare but aggressive subtype of RCC, and an understanding of their genomic landscape is lacking. Methods: Thirteen FH-deficient RCC and matched normal samples from our medical center were used for whole-exome sequencing and molecular profiling. Transcriptomic sequencing data were analyzed from The Cancer Genome Atlas (TCGA) RCC samples and two independent datasets of FH-mutated RCC. For each patient in our cohort, clinical outcomes were recorded, with median follow-up until March, 2019. Results: We identified FH-deficient RCC had high mutation burden, frequent somatic mutations in MUC4, MUC16, ANKRD6 and PRDM16 and germline pathologic FANCD2 mutation. In contrast to mainly RCC subtypes, FH-deficient RCC exhibited elevated mutational signatures of homologous recombination deficiency (7/13, 53%) and microsatellite instability (4/13, 30%). Moreover, we revealed that FH-deficient RCC was characteristic of an immunogenic tumor type, with high tumor-specific neoantigen burdens, enhanced immune cells infiltration but immunosuppressive microenvironment. In our cohort, 11 patients received systematic treatments; 63% (5/8) responded poorly to antiangiogenic or anti-mammalian target of rapamycin agents, but all (6/6) achieved benefit from immune checkpoint blockade monotherapy or combination with antiangiogenic agents. Conclusions: Our study provides a better understanding of the mutational landscape of FH-deficient RCC, highlighting the potential of immunotherapy for treating this patient populations.