bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world utilization and safety of ipilimumab plus nivolumab (I+N) in metastatic renal cell carcinoma (mRCC) patients: Results from the Canadian Kidney Cancer Information System (CKCis).
Authors: Thana Myuran , Basappa Naveen S. , Ghosh Sunita , Kollmannsberger Christian K. , Heng Daniel Yick Chin , Graham Jeffrey , Soulieres Denis , Hansen Aaron Richard , Lalani Aly-Khan A. , Castonguay Vincent , Reaume M. Neil , Bjarnason Georg A. , Breau Rodney H. , Pouliot Frederic , Kapoor Anil , Wood Lori 
Published: February 2020

633 Background: I+N is now standard of care for first line treatment of intermediate/poor risk mRCC patients (pts). Real world data is vital to understand drug usage, toxicity and outcomes in non-trial pts. This project describes the amount and tolerability of treatment delivered including discontinuation rates, reasons for discontinuation and outcomes from the CKCis database. Methods: Pts in CKCis, a prospective Canadian database from 15 academic centers, who received first line I+N were included. The number of doses of I+N, number of pts who received single-agent nivolumab (N) and duration of single agent N were determined. Reasons for treatment discontinuation, including the rate, type, and grade of toxicities were identified. Efficacy outcomes included time to failure (TTF – time to progression, death, or second line therapy), overall response rate (ORR) and overall survival (OS). Results: The cohort consists of 182 pts. Median age was 63 yrs, 71% had clear cell histology, 11% were on a clinical trial, the IMDC risk distribution was 5% good, 63% intermediate, 32% poor. Median follow up was 8.8 m. All 4 I+N doses were received by 30% of pts of which 78% went on to receive single-agent N. Less than 4 doses of I+N were received by 70% of pts of which 28% went on to receive single-agent N. The median time on single agent N was 5.7 m. In the entire cohort, 21% of patients discontinued therapy due to toxicity. The most common toxicity events were colitis (56% of all events), pneumonitis (19%), and hepatitis (8%). There were no toxicity-related deaths. Median OS has not been reached (22 events to date). Median TTF was 12.4 m. ORR was 32% (5% complete responses). 26% of pts received second line treatment, the most common being sunitinib in 79%. Conclusions: In this real world cohort, the majority of mRCC pts did not receive all 4 doses of I+N, contrasting with clinical trial reporting, yet many of these pts went on to receive single agent N. Discontinuation rates due to toxicity were similar to those reported in CheckMate 214. Further follow up is ongoing and efficacy outcomes analyzed on the basis of treatment quantity/duration will be presented.
Genomic profiling of prostate cancer at a diverse academic center.
Authors: Lopez Robert , Ferrari Anna C. , Goel Sanjay , Peeke Stephen , Sharma Janaki Neela , Shenoy Niraj Konchady , Gartrell Benjamin Adam 
Published: February 2020

64 Background: According to recent reports, ~1 in 4 patients with metastatic prostate cancer may harbor alterations in DNA damage repair (DDR) genes. Clinical trial data demonstrates that prostate cancer patients with DDR mutations may respond to poly-ADP ribose polymerase (PARP) inhibitors. Less is known about the mutational profile in minority patients with prostate cancer. We sought to determine the genomic profile of prostate cancer in an ethnically diverse patient population at a single center. Methods: We performed a retrospective review of men with prostate cancer at the Montefiore-Einstein Cancer Center who had next generation sequencing (NGS) with FoundationOne solid tumor testing between 2/2016 - 8/2019. Individual chart review was used to obtain clinical and demographic data including self-reported race/ethnicity. Results: NGS was attempted on archival tissue from 95 patients and results were obtained for 85. Among patients with results, the self-reported race/ethnicity was: Hispanic (H) 37.6%, Non-Hispanic Black (NHB) 52.9%, Non-Hispanic White (NHW) 4.7%, and Other (O) 4.7%. At the time of tissue sampling, 61 patients had metastatic disease and 10 were castration-resistant. 63 samples were from the prostate, 7 from bone, 7 from lymph node, 3 from liver and 5 from other soft tissue sites. The most commonly altered genes included: TP53 (26%), TMPRSS2-ERG fusion (23%), and PTEN (17%). Alterations in the androgen receptor were identified in 5 samples (all with CRPC). 32.8% had alterations in DDR genes including BRCA2 9 (10.6%), ATM 7 (8.2%), ATR 4 (4.7%), BRIP1 2 (2.3%), CDK12 3 (3.5%), FANCA 2 (2.3%), and PALB2 1 (1.2%). Alterations in mismatch repair genes (MSH2, MLH1, MSH6, PMS2) were present in 4 (4.7%) patients (3 of these were MSI-H). In samples where tumor mutational burden (TMB) was reported, 4 (4.7%) were TMB-high (3 MSI-H and 1 with POLE mutation). Conclusions: DDR gene mutations are common in this primarily minority population. As DDR mutations become more common in the CRPC setting, our data may underestimate the frequency of DDR mutations as only 10 patients had CRPC at the time of tissue sampling. Minority men, like all men, with prostate cancer should be considered for genomic analysis as results are likely to guide therapeutic decisions.
Sites of metastasis and survival in metastatic renal cell carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC).
Authors: Dudani Shaan , de Velasco Guillermo , Wells Connor , Gan Chun Loo , Donskov Frede , Porta Camillo , Fraccon Anna , Pasini Felice , Hansen Aaron Richard , Bjarnason Georg A. , Beuselinck Benoit , Pal Sumanta K. , Hotte Sebastien J. , Lalani Aly-Khan A. , Yuasa Takeshi , Kanesvaran Ravindran , Reaume M. Neil , Canil Christina M. , Choueiri Toni K. , Heng Daniel Yick Chin 
Published: February 2020

642 Background: Across a variety of malignancies, sites of metastatic involvement are known to be associated with differences in survival. We sought to characterize the frequency and survival of patients with different sites of metastases in mRCC. Methods: Patients with mRCC starting treatment between 2002-2019 were identified and sites of metastatic involvement at time of systemic therapy initiation were documented. The primary outcomes of interest were prevalence of metastatic site involvement and overall survival (OS). Multivariable Cox regression models were performed to adjust for imbalances in IMDC risk factors. Results: A total of 10,320 patients were included. Median age at diagnosis was 60, 73% were male, 87% had clear-cell histology and 80% underwent nephrectomy. The most common sites of metastases were: lung (71%), lymph nodes (49%), bone (36%), liver (21%), adrenal (9%), brain (9%), pancreas (5%), pleura (4%) and thyroid (0.6%). Survival by metastatic site and adjusted hazard ratios are presented in Table. Conclusions: Metastases to endocrine organs (pancreas, thyroid, adrenal) are infrequent but are associated with the longest median OS, whereas bone, liver, pleura and brain metastases are associated with median OS < 18 months. These benchmark values are useful for patient counseling and study design. Sites of metastatic involvement may reflect differences in underlying disease biology, and further work to investigate differences in immune, molecular and genetic profiles between metastatic sites is encouraged.[Table: see text]
Treatment duration and response of advanced renal cell carcinoma (aRCC) patients (pts) who have completed first-line (1L) treatment (tx): Results from a cross-sectional real-world study.
Authors: Zanotti Giovanni , Kim Ruth , Krulewicz Stan , Hall Jennifer P. , Leith Andrea , Bailey Abigail , Liu Frank Xiaoqing , Kearney Mairead 
Published: February 2020

643 Background: In 2019, there was an estimated 73,820 new cases of kidney cancers in the US. The tx landscape for aRCC is changing rapidly. Recently approved txs for 1L aRCC include new targeted agents and immuno-oncology (IO) therapies. We examine outcomes for pts who completed 1L tx. Methods: Real-world data were drawn from the RCC Disease Specific Programme; a cross-sectional survey administered to US oncologists, nephrologists and urologists. Physicians completed pt record forms (PRFs) for up to the next 8 consulting aRCC pts receiving drug tx, from February - September 2019, plus additional optional PRFs for pts receiving/who had received either 1L tx of nivolumab/ipilimumab combination or cabozantinib, where these pts were available. Results: Physicians (n=82) provided data on 687 pts; 230 had progressed from 1L tx and were on 2L tx at time of data collection. Of those receiving 2L tx, 61% male; mean age was 66.4 years (SD=11.0); 43% stage IV at diagnosis. At 1L, 72% (n=165) had received tyrosine kinase inhibitor (TKI) monotherapy; 16% (n=37) IO+IO, 3% (n=7) TKI+IO and 9% (n=20) other regimens. Mean 1L duration was 10.3 months (SD=9.4) and mean time to 2L initiation was 13.7 months (SD=21.1). 1L treatment responses were: 6% complete response, 21% partial response, 16% stable disease, and the remainder relapsed/progressed (44%) or unknown response (13%). Most common 2L regimens were TKI (37%) or IO (34%) monotherapy. 47% of 1L TKI monotherapy pts received 2L IO monotherapy. 86% of 1L IO+IO pts received 2L TKI monotherapy. Conclusions: Some pts with aRCC progress to 2L; many experience poor clinical outcomes with 1L txs, highlighting high unmet need in 1L for more efficacious txs. Optimal tx strategy (and sequencing) continues to evolve. Approval of IO+TKI therapies, approved during the fieldwork period, has broadened the therapeutic landscape for 1L aRCC. Whilst the proportion of 1L pts receiving IO+TKI therapies is still low, the adoption of these in 1L is likely to transform the management of aRCC. Further research is needed to determine the optimum tx sequence in these pts with high unmet need.
A real-world experience of immune checkpoint inhibitors (ICI) in metastatic renal cell carcinoma (mRCC).
Authors: Elias Roy , Levonyak Nicholas , Christie Alana , Bowman Isaac Alexander , Kapur Payal , Hannan Raquibul , Hammers Hans J. , Brugarolas James 
Published: February 2020

647 Background: ICI therapy has changed the treatment landscape in mRCC. Here we present the safety and efficacy of ICIs used in an academic medical center (UT Southwestern Medical Center) and affiliated county hospital (Parkland Hospital). Methods: All mRCC patients (pts) treated with at least one dose of ICI from 2014 - 2018 were identified. Baseline characteristics were collected at the start of ICI. Outcomes included objective response rate (ORR) as determined by RECISCT v1.1, time to next treatment (TNT) and overall survival (OS). Immune-related adverse events (irAE) were graded according to CTCAE v4.0. Kaplan-Meier methods and Cox proportional hazards regression models were used to estimate survival and generate hazard ratios (HR). Results: We identified 177 pts with mRCC, including 31 at the county hospital, who received at least one dose of ICI. 140 (79.1%) pts were intermediate or poor risk by IMDC, and 149 (84.2%) had clear cell histology. 127 (71.8%) received nivolumab monotherapy, 40 (22.6%) received ipilimumab and nivolumab, and 10 (5.6%) received ICI with a tyrosine kinase inhibitor. ICI was given in the 1st line in 34 (19.2%) pts, 2nd line in 77 (43.5%) pts, and the 3rd or later line in 29 (16.4%) pts. The ORR was 18.6% (33/177), and there were 6 (3.4%) complete responses. The median TNT and OS was 8.9 (95% CI; 7.1-10.6) and 26.7 (95% CI; 22.4-30.9) months, respectively. In multivariate analysis (MVA) of TNT including sex, nephrectomy status, IMDC risk group, histology, and number of organs involved, only number of organs involved (HR: 1.27; 95% CI: 1.12-1.45; p = 0.0003) and non-ccRCC subtype (HR: 2.63; 95% CI: 1.63-4.24; p <0.0001) retained statistical significance. MVA of OS revealed similar findings, with number of involved organs (HR: 1.49; 95% CI: 1.97-7.45; p < 0.0001) and non-ccRCC subtype (HR: 3.83; 95% CI: 1.97-7.45; p <0.0001) correlating with worse survival. irAEs were observed in 77 pts (43.5%) with 42 (23.7%) pts experiencing a grade 3/4 irAE. Conclusions: ICI therapy is safe and efficacious in the real world setting. Clinical and laboratory variables, including the IMDC risk score, do not consistently predict outcomes in this heterogeneous cohort.
Fear of cancer recurrence among patients and survivors diagnosed with localized renal cell carcinoma.
Authors: Bergerot Cristiane Decat , Battle Dena , Philip Errol James , Bergerot Paulo Gustavo , Smith Allan 'Ben' , Rathmell Kimryn , Shuch Brian M. , Derweesh Ithaar , Jonasch Eric , Msaouel Pavlos , Pal Sumanta K. , Staehler Michael D. , Stern Adam P. 
Published: February 2020

649 Background: Fear of cancer recurrence (FCR) is considered one of the most pervasive and burdensome sources of distress for patients. Whereas it can be considered an adaptive response to real threats associated with diagnosis, treatment and disease, numerous studies have suggested that elevated levels can be dysfunctional. Despite this extensive body of research, little is known regarding FCR among individuals diagnosed with renal cell carcinoma (RCC). The current study sought to describe the prevalence of FCR among patients with RCC. Methods: Patients with localized RCC participated in an international survey from 07/19 to 09/19, through an online platform devised by a non-profit patient advocacy group (KCCure). Patients were assessed for FCR using the FCR-7, a 7-item measure, ranging from 0 to 28. A cutoff score of 17 indicates a moderate level of FCR, while a cutoff of 27 indicates severe level of FCR. Linear regression was used to determine the association between FCR and patients’ characteristics. Results: A total of 1150 patients participated in this survey, of which 412 had localized disease and were assessed for FCR. The majority were female (79%), with a median age of 54 years old (range, 30-80), and well-educated (58%). Patients were predominantly from US (85%), Canada (4%) and Germany (2%) and lived in suburban (48%) or rural areas (32%). More than half of participants were diagnosed with disease stage I (56%) and the remainder were divided between stage II (19%) and III (24%). More than half of patients (55%) reported a moderate or severe level of FCR. Younger patients (p=0.001) and those of female gender (p=0.004) were more likely to report higher levels of FCR. Conclusions: To our knowledge, this is the first study to quantify the degree of FCR among patients and survivors diagnosed with localized RCC. Importantly, high rates of FCR were associated with female gender and younger age, possibly driven by the fact that women may be more open to disclosing emotional symptoms and younger patients are still to pass through many life milestones and thus fear may be more pronounced. Targeted assessment and interventions are needed to address this highly prevalent form of distress among those diagnosed with RCC.
Retrospective study to identify clinical factors related to a high benefit of axitinib in mRCC: Results from AXILONG Spanish real-world study.
Authors: Pinto Alvaro , Iglesias Gomez Clara , Climent Miguel Ángel , Gallardo Diaz Enrique , Garcia del Muro Xavier , Alonso Gordoa Teresa , Llinares Legido Julia Inmaculada , Suarez Rodriguez Cristina , Anguera Georgia , Muñoz-Langa José , Lainez Nuria , Rodriguez Sanchez Angel , Martínez Ortega Esther , Villalobos Maria L. , Reig Torras Oscar 
Published: February 2020

650 Background: AXILONG is a Pfizer observational multi-institutional retrospective study, evaluating clinical factors which could be related with a higher benefit of axitinib in pretreated mRCC patients in two pre-specified subgroups with extreme response to axitinib. Methods: Medical records from 157 patients treated in 40 Spanish hospitals with axitinib under clinical practice were retrospectively reviewed and included in the study. Of note, patients had to had an extreme response with axitinib, which means being a long responder (LR) to axitinib, defined as those patients who achieved a median Progression Free Survival (mPFS) of 9 months or longer, or refractory patients (RP) those who achieved a Progression Disease (PD) as best response. Results: In this analysis, we describe the results of a subgroup of patients who received axitinib in second-line after sunitinib, which represents the 68,2% (n=107) of the patients included in the whole study. The 55,1% (n=59) of this subgroup were LR and the 44,9% (n=48) were RP. In this sub-group of patients, the mPFS in LR was 18,7 months (95%CI; 12,9-24,4) and the overall response rate (ORR) was 43,9% (3,5% CR). Median overall survival (mOS) since the start of axitinib was 28,2 months for both sub-groups included, being 44,8 months in the LR patients and 7,3 months in the RP (95% CI, 12.79–34.65; p <0,001). In this population the 1st line mPSF was 27,2 months in LR and 10,9 months in RP (95%CI; 12,97-20,15; p ≤0,001). Conclusions: Despite the limitations of the AXILONG study there were a subgroup of patients who can be considered long responders o axitinib in whom we can obtain a high benefit in terms of efficacy, when treating with the sequence sunitinib-axitinib. Clinical trial information: NCT03538717 .[Table: see text]
Association of robotic partial nephrectomy for clinical T2a renal mass with improved trifecta outcome compared to open partial nephrectomy: A single surgeon comparative analysis.
Authors: Ghali Fady , Elbakry Amr A. , Hamilton Zachary , Nasseri Ryan , Eldefrawy Ahmed , Ryan Stephen T. , Yim Kendrick , Patel Sunil , Bradshaw Aaron , Meagher Margaret , Reddy Madhumitha , Lee Hak J. , Derweesh Ithaar 
Published: February 2020

653 Background: We compared surgical quality and functional outcomes of robotic partial nephrectomy (RPN) and open PN (OPN) for cT2a renal masses (cT2aRM). Methods: Retrospective analysis of 150 consecutive patients [RPN 59/OPN 91] from 6/2008 to 6/2016. Main outcome was achievement of Trifecta [negative surgical margin, no major urologic complications, and ≥90% preservation of estimated glomerular filtration rate (eGFR)]. Multivariable analysis was performed to identify factors of Trifecta attainment. Results: Mean tumor size (RPN 7.9 vs. OPN 8.4 cm, p=0.139) and median RENAL score (p=0.361) were similar. No difference was noted for positive margins (RPN 3.4% vs. OPN 1.1%, p=0.561), DeGFR (RPN -6.2 vs. OPN -7.8, p=0.543), and ≥90% eGFR recovery (RPN 54.1% vs. OPN 47.2%, p=0.504). RPN had lower blood loss (p=0.015), hospital stay (p=0.013), and Clavien ≥3 complications (RPN 5.1% vs. OPN 16.5%, p=0.041). Trifecta rate was significantly higher in RPN (47.5% vs. 34.0%, p=0.041). Multivariable analysis demonstrated decreasing RENAL score (OR 1.11, p<0.001), RPN (OR 1.2, p=0.013), and decreasing EBL (OR 1.02, p=0.016) to be associated with Trifecta attainment. Conclusions: RPN provided similar functional and oncologic precision to OPN, while being associated with improvements in major complications, the latter of which was reflected in a higher rate of Trifecta achievement for RPN. RPN may be considered to be a first-line option for select patients with cT2aRM when feasible and safe.
Cost analysis of post-nephrectomy follow-up schedules from three North American clinical practice guidelines for localized renal cell carcinoma (RCC).
Authors: Thana Myuran , Dragomir Alice , Kassouf Wassim , Wood Lori 
Published: February 2020

657 Background: Several guidelines have been developed for follow up of patients after nephrectomy for RCC. The direct financial cost of following recommendations in three North American guidelines were estimated in this analysis. Methods: Recommendations from the American Urological Association (AUA), Canadian Urological Association (CUA), and National Comprehensive Cancer Network (NCCN) for post-radical nephrectomy care were compiled. Data regarding costs of testing and physician visits were obtained from the Ontario Health Insurance Plan Schedule of Benefits. Both the cost per patient completing five years of surveillance (scenario A), and the estimated cost adjusted for attrition from predicted recurrences (scenario B) were calculated. A sensitivity analysis was performed and will be presented. Results: For five years of follow up of a single patient in both scenarios, the costs are summarized in the table. For scenario A, follow up costs ranged from $515-1112 for T1N0, $1639-2746 for T2N0, $1856-2746 for T3/4 and $1918-2746 TxN+. For scenario B, costs were $497-1051 for T1N0, $1259-2198 for T2N0, $1008-1595 for T3/4N0 and $1043-1595 for TxN+. Conclusions: The AUA, CUA, and NCCN guidelines showed considerable differences in their associated costs, particularly when expected recurrences were accounted for. The NCCN recommendations are predicted to be the costliest to implement, irrespective of stage.[Table: see text]
Prevalence of pathogenic germline risk variants (PVs) in 1,829 renal cell carcinoma (RCC) patients (pts).
Authors: Abou Alaiwi Sarah , Nassar Amin , Adib Elio , Akl Elie , Groha Stefan , Esplin Edward D. , Nielsen Sarah , Yang Shan , McGregor Bradley Alexander , Pomerantz Mark , Gusev Alexander , Rana Huma Q. , Sonpavde Guru , Garber Judy Ellen , Freedman Matthew L. , Choueiri Toni K. 
Published: February 2020

659 Background: Hereditary RCCs account for 3-5% of all RCC cases. The prevalence and significance of germline PVs of RCC have not been fully characterized. Methods: We evaluated the frequency of pathogenic and likely pathogenic variants, referred to as PVs, in 1829 high-risk RCC pts who underwent targeted clinical germline testing (1-134 genes) at a commercial laboratory. PVs, including single nucleotide variants/indels/ copy number variants, were confirmed using orthogonal technology in accordance with Invitae’s standard operating practices. Actionable genes were defined as established cancer-predisposition genes that confer a higher risk for any cancer phenotype and for which enhanced screening and family genetic testing are recommended by the National Comprehensive Cancer Network. We focused our analysis on genes tested in more than 100 pts (n=93). Results: Among 1892 pts, 54.9% were male, and 68.9% were Caucasians, with median age 50 (range:1-87) years at RCC diagnosis. 11.8% (n=215) of pts had at least 2 primary RCCs, and 30.7% (n= 561) had a personal history of another cancer. The cumulative frequency of pts with PVs was 17.7%. PVs in known RCC susceptibility genes such as FH, FLCN, and SDHB were detected in 1.8% (29/1622), 1.22% (120/1634) and 0.64% (11/1727) of pts respectively. PVs in other cancer-associated genes were most frequently reported in CHEK2 (loss-of-function variants, 30/1276, 2.4%), MUTYH (19/1124, 1.7%), and BRCA2 (17/1276, 1.33%). PVs in DNA-damage repair genes (DRG) accounted for 71.8% of PVs and, overall, were detected in 12.7% of pts. Among the DRG, PVs in the homologous recombination pathway (ATM, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, NBN, PALB2, RECQL4, WRN) were the most prevalent (7.8%) whereas the mismatch repair pathway (MLH1, MSH2, MSH6, PMS2) was altered in only 0.7% of pts. Of the examined cohort, 9.7% of pts had ≥1 actionable PV. In non-Caucasians, BRCA2 PVs were the most common (6/273, 2.20%). Conclusions: PVs were identified in 17.7% of RCC subjects, most of which (71.8%) were in DRG, with »10% of pts having actionable variants. Our work is concordant with known RCC susceptibility genes and potentially highlights novel risk genes that should be validated in future studies.