bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment response comparisons between ATM and BRCA2 germline carriers for mCRPC.
Authors: Sokolova Alexandra , Marshall Catherine Handy , Lozano Rebeca , Grivas Petros , Higano Celestia S. , Lotan Tamara L. , Montgomery Robert B. , Nelson Peter , Olmos David , Schweizer Michael Thomas , Yezefski Todd , Yu Evan Y. , Paller Channing Judith , Castro Elena , Antonarakis Emmanuel S. , Cheng Heather H. 
Published: February 2020

63 Background: Over 10% of men with metastatic prostate cancer (PC) have germline DNA damage response gene alterations; most studies have reported BRCA2 alone or an aggregate of BRCA1, BRCA2 and ATM. Emerging data suggest ATM mutations have distinct effects and warrant individual gene evaluation. We hypothesize that, compared to patients (pts) carrying germline BRCA2 mutations (g BRCA2mut), pts carrying germline ATM mutations (g ATMmut) may have different treatment response to androgen-receptor-targeted agents, docetaxel, platinum therapy and PARP inhibitors (PARPi). Methods: This is an international, multicenter, retrospective case-control study of pts with PC who underwent clinical germline genetic testing between 2014-2019. We identified pts with g ATMmut and matched pts with g BRCA2mut by stage at diagnosis and year of testing. IRB-approved medical records review, χ² and log rank tests were performed. Results: 39 g ATMmut cases and 39 matched g BRCA2mut cases were identified for total of 78. A third (13/39) of pts in each cohort had metastases at diagnosis. Of those diagnosed with localized stage, 81% (21/26) of gATMmut and 73% (19/26) of g BRCA2mut developed metastasis (median times to metastasis 69 vs 49 months, respectively (p=0.1)). Pts in g ATMmut and g BRCA2mut cohorts had similar age, Gleason grade, and PSA at diagnosis. We did not observe a difference in PSA50 response rates to abiraterone, enzalutamide, docetaxel, or carboplatin for mCRPC (Table). g BRCA2mut pts were more likely to respond to PARPi for mCRPC; where available, somatic loss of heterozygosity (LOH) data will be reported at final presentation. Conclusions: While response to standard therapies appears similar between g ATMmut and g BRCA2mut cohorts, response to PARPi in g ATMmut appears to be attenuated compared to g BRCA2mut. More studies are needed and pts with g ATMmut warrant prioritization for novel treatment strategies.[Table: see text]
Safety and efficacy of tivozanib in first-line metastatic renal cell carcinoma: A multicenter compassionate use study.
Authors: Basso Umberto , Procopio Giuseppe , Fornarini Giuseppe , Massari Francesco , Bearz Alessandra , Fratino Lucia , Milella Michele , Bassanelli Maria , Sacco Cosimo , Bimbatti Davide , Verzoni Elena , Rizzo Mimma , Porta Camillo 
Published: February 2020

632 Background: Tivozanib-TIVO is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR-2, and VEGFR-3. TIVO was recently approved in Europe for the first line treatment of metastatic Renal Cell Carcinoma-RCC after a randomized trial demonstrated improved PFS and different safety profile compared to sorafenib. Methods: Retrospective analysis of safety and activity of TIVO administered within a compassionate use program to pts with metastatic RCC with no prior systemic treatment. Results: From Aug 2018 to Apr 2019, 64 pts have started TIVO at 1,34 mg daily (three weeks on, 1 week off) in 9 Italian Oncology Units. Median age was 67.5 years (range 40 to 85), 61% males, median creatinine clearance 63 ml/min(range 30-97). According to IDMC criteria, 27.5 % of pts were good prognosis, 60% intermediate and 10.5 % poor. Primary tumor had been removed in 70.5% of pts. Histology was clear cell 89.5%, papillary 4.5%, unclassified 6%. Response rate was 46.5%, stable disease 37.5%, progression 16%. Grade 3-4 toxicities were 4.5% hypertension, 3% mucositis, 1.5% diarrhea and 1.5% anorexia. Dose reduction to 0.89 mg was applied to 15.5% of pts. PFS and OS data will be presented at the Meeting. Conclusions: TIVO showed good activity and favorable safety profile in a real world cohort of unselected pts with metastatic RCC. Predictive biomarkers of response to antiangiogenic therapy are urgently needed in order to identify RCC pts who should receive VEGFR inhibitors in the first line.
Immune checkpoint inhibitors (ICI) in clear cell renal cell carcinoma (ccRCC) following high-dose interleukin-2 (IL-2).
Authors: Elias Roy , Bowman Isaac Alexander , Hammers Hans J. , Brugarolas James 
Published: February 2020

635 Background: IL-2 can be curative in a small subset of ccRCC patients (pts). Recent data suggest that ICIs may lead to long lasting responses, and ICI therapy following progression on IL-2 seems reasonable. However, data regarding the safety and efficacy of ICI following IL-2 is limited. Methods: ccRCC pts treated with ICI after first line were identified at UT Southwestern Medical Center from 2014 – 2018 and assessed by comparison to IL-2 naïve pts at the time of ICI initiation. Outcomes included objective response rates (ORR) determined by RECIST v1.1, time to next treatment (TNT) and overall survival (OS). Immune-related adverse events (irAEs) were graded per CTCAE v4.0. Comparisons were performed using Pearson Chi-square, independent t-tests, and Fischer’s exact tests as appropriate. The log-rank test was utilized for Kaplan-Meier survival analyses. Results: We identified 127 ccRCC pts treated with ICI after first line, 17.3% (22) who had received prior IL-2 and 83.7% (105) who were IL-2 naïve. Pts in the IL-2 group were younger (mean age, 56 vs. 63 years; p=0.003), and more heavily pretreated (median 2 prior lines vs. 1; p <0.0001). The distribution by IMDC criteria was similar with 86.4% (19) and 76.4% (81) in intermediate/ poor group in IL-2 vs. IL-2 naïve groups, respectively (p = 0.431). The ORR was 9.1% (2/22) vs. 21.2% (22/104) in the IL-2 vs. IL-2 naïve groups, respectively (p=0.244). The median TNT was 7.5 (95% CI: 1.8 to 13.2) vs. 9.2 (95% CI: 6.0 – 12.4; p= 0.667) months in the IL-2 vs. IL-2 naïve groups, respectively. The median OS was 26.4 (95% CI: 17.3 – 35.5) vs. 29.8 (23.1 to 36.4) months in the IL-2 vs. IL-2 naïve group, respectively. 18.2% (4) vs. 21.9% (23) pts developed a grade 3/4 irAE in the IL-2 vs. IL-2 naïve group, respectively (p=0.698). Conclusions: Our study suggests that ICI therapy following treatment with high-dose IL-2 remains efficacious and is not associated with an increased risk of irAEs.
Efficacy and safety of lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: Russian multicenter observational study ROSLERCM.
Authors: Volkova Maria , Abdelgafur Ahmed , Amoev Zurab , Aivazov Magomed , Babina Ksenia Gennadievna , Borisov Pavel S. , Evstigneeva Irina , Samuseva Olga Igorevna , Kalpynsky Alexei , Karabina Elena , Kirdakova Natalia , Kuzmina Evgeniya , Latipova Dilorom H. , Ovchinnikova Elena G. , Olshanskaya Anna Sergeevna , Protsenko Svetlana , Semiglazova Tatiana , Smirnov Roman , Usynin Evgeny , Chernyakova Irina ,   ROSLERCM
Published: February 2020

644 Background: an assessment of efficacy and safety of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) progressed during or following ≥1 line of antiangiogenic targeted therapy. Methods: Russian multicenter observational study included 73 consecutive patients with morphologically verified mRCC progressed during or following ≥1 line of antiangiogenic targeted therapy, treated with lenvatinib (18 mg/d) and everolimus (5 mg/d) in 20 Russian centers. Median age of the patients was 59 (23-73) years, a male-to-female ratio - 3:1. Most common histological type of kidney cancer was clear-cell RCC (71 (95.8%)). More than 2 lines of previous treatment were administered in 45 (61.6%) cases. Most patients were diagnosed with multiple metastases (71 (97.3%)) in >1 site (61 (83.6%)). Nephrectomy was performed in 87.7% (64/73) of cases. At the combined therapy start ECOG PS 2-4 was registered in 16 (20.5%), poor prognosis according to IMDC score – in 33 (45.2%) patients. Median follow-up was 9.7 (1-26) months. Results: objective response rate was 11% (8/73); tumor control was reached in 93.2% (68/73) of cases. Median objective response duration was 10.5 (4.3-16.8) months, tumor control duration – 10.0 (2.5-17.5) months. Median progression-free survival (PFS) achieved 16.9 (95% confidence intervals (CI): 12.1-20.6), overall survival (OS) – 20.8 (95% CI: 15.7-25.9) months. Any adverse events (AE) developed in 83.6% (61/73), AE grade 3-5 - in 23.3% (17/73) of cases. Most frequent AE grade 3-4 were diarrhea (10 (13.6%)) and arterial hypertension (6 (8.2%)). Unacceptable toxicity demanded treatment cancellation in 4.2% (3/73), therapy interruption – in 30.1% (22/73) and dose reduction – in 32.9% (24/73) of patients. Conclusions: unselected mRCC patients administered with combined targeted therapy in the real world practice were registered with lower objective response rate, similar survival and better tolerability comparing with population assigned for lenvatinib plus everolimus in the randomized phase II trial.
A novel multiplex score to predict outcomes of partial nephrectomy for multiple tumors.
Authors: Chalfin Heather , Yerram Nitin , Gurram Sandeep , Linehan W. Marston , Ball Mark Wayne 
Published: February 2020

656 Background: The RENAL nephrometry score (RNS) is widely used to describe renal mass complexity and inform patient counseling for partial nephrectomy (PN). However, in cases with multiple lesions (commonly seen in hereditary cancer syndromes) it is unknown which features drive postoperative complications. Here, we employed a novel scoring equation (Multiplex Score, MS) derived from RNS and assessed outcomes of multiplex PN at our institution. Methods: The MS was defined a priori as a weighted score (# low risk (LR) lesions) + 2*(# intermediate risk (IR)) + 4*(# high risk (HR)) based on published Clavien-Dindo III-V complication rates of 6.4%, 11.1%, and 21.9% for LR, IR, and HR RNS respectively. MS was dichotomized into favorable/unfavorable based on median score. Patient outcomes were maintained prospectively. Binary outcomes were evaluated with logistic regression and continuous outcomes were evaluated with linear regression. Results: From 10/2017-8/2019, 62 consecutive multiplex PN (median (range) # tumors = 4 (2-11), 65% robotic) were performed by a single surgeon. Median (range) MS was 6 (2-20). Of 13 complications, urine leak (N = 5, 8%) and bleed requiring embolization (N = 4, 6%) were the most common. Only 1 complication occurred in the favorable score group and MS was significantly associated with perioperative complication (OR 1.21, p = 0.018) and blood loss (242.42 mL, p < 0.001). Hilar clamping was omitted in 32 (52%) cases with median 18.5 min when used. Every 1 additional HR or IR tumor was associated with a 2 minute increase in clamp time (2.01, p = 0.048). Median clamp time for favorable/unfavorable cases was 0 vs. 10 minutes. Change in renal function was negligible in our cohort (median ΔCr 0 mg/dL, IQR -0.61–0.1). There were no conversions from partial to radical nephrectomy and open conversion was only done in 3 (7.5%) cases, all assigned unfavorable MS. Conclusions: The novel Multiplex Score associated well with complications, blood loss, and open conversion. This tool may facilitate standardized reporting of complexity for multiplex series, with special relevance for hereditary cancer syndromes.
Neutrophil-to-lymphocyte ratio as a predictor of oncologic outcomes in locally advanced non-metastatic clear cell renal carcinoma.
Authors: Rodrigues Gilberto , Sierra Pablo , Albuquerque Emanuel , Gallucci Fabio Pescarmona , Ilario Eder Nisi , de Carvalho Paulo Afonso , Muniz David Queiroz Borges , Sarkis Alvaro , Coelho Rafael , Cordeiro Mauricio , Nahas William Carlos 
Published: February 2020

661 Background: An elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with worse oncologic outcomes in several malignancies, its prognostic role in kidney cancer, specifically in the non metastatic setting is controversial. We aimed to evaluate if an elevated NLR in patients with locally advanced non metastatic clear cell renal cell carcinoma (CCRCC) is associated with a worse survival and/or a higher cancer recurrence rate. Methods: We retrospectively identified 880 nephrectomies performed between 01/2009 to 12/2016 in a single center, reviewed data from 478 consecutive radical nephrectomies (RN) for kidney tumors and identified 187 patients with locally advanced non-metastatic CCRCC patients (pT3-T4 N0M0). The cut-off point of NLR = 2.5 was obtained using the receiver operating curve analysis (ROC). NLR was obtained preoperatively and calculated by dividing absolute neutrophil count by absolute lymphocyte count. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method. Cox regression models were utilized to evaluate predictors of recurrence and survival. Results: Median follow up was 48.7 months. The 3 year OS was significantly lower for patients with NLR ≥ 2.5 than those with NLR < 2.5 (70% vs 85%, p = 0.049). In patients with a Fuhrman nuclear grade of differentiation of 3-4, the median time to recurrence was significantly shorter for patients with NLR ≥ compared to those with NLR < 4 (24 vs 55 months p 0.045). On multivariable analysis adjusted for NLR ≥ 2.5, microvascular invasion, sarcomatoid differentiation, tumor size and body mass index, only nuclear grade of differentiation was found to be an independent predictor for recurrence (hazard ratio= 2.18; 95% confidence interval [CI]: 1.07 – 4.92, p = 0.03). Conclusions: Patients with non-metastatic CCRCC with higher nuclear grade of differentiation and a high preoperative NLR have shorter RFS and worse OS compared to patients with lower NLR.
Does delay in time to surgery impact outcome in renal cell carcinoma: Analysis based on tumor size utilizing the National Cancer Database.
Authors: Patel Devin , Ghali Fady , Meagher Margaret , Bradshaw Aaron , Patel Sunil , Murphy James Don , Derweesh Ithaar 
Published: February 2020

664 Background: The impact of delay in treatment for localized renal cell carcinoma (RCC) is controversial. We sought to determine the survival impact of time to definitive surgical treatment stratified by tumor size in a group of young, healthy patients from the National Cancer Database (NCDB). Methods: The NCDB was queried for cases of localized RCC (cT1-T3N0M0) in patients <60 years of age with Charlson comorbidity score of 0 from 2004-2015. Quartiles were formed from the range of time to surgery of the entire cohort in days, with delayed treatment as the fourth quartile. Tumors were stratified into size of <2 cm, 2-4 cm, 4-7 cm and >10 cm. Overall survival (OS) between early and delayed groups was calculated with Kaplan-Meier analysis (KMA) and multivariable cox proportional hazards (MVA) and stratified by tumor size. Logistic regression was performed to determine factors associated with delay in surgical care. Results: 44,149 patients were analyzed. Median time to treatment was 35 days (IQR 19-61). Early (n = 33,144) and delayed (>61 days, n =11,005) groups had a mean follow-up of 61.5 and 57.5 months, respectively (p < 0.001). KMA showed worse 5-yr OS in patients with surgery delay versus no delay for tumors 2-4 cm in size (5-yr OS 49% vs. 54%; p<0.001), 4-7 cm (5-yr OS 47% vs. 53%; p<0.001), >7 cm (5-yr OS 45% vs. 49%;p=0.0002), but not for tumors <2 cm (5 yr OS 49% vs. 51%: p=0.5848). MVA showed worse OS with surgery delay compared to no surgery delay in patients with tumor size 2-4 cm (HR 1.24; 95%CI 1.09-1.42), 4-7 cm (HR 1.32; 95%CI 1.16- 1.50) and >7 cm (HR 1.14; 95%CI 1.01-1.30) but not tumors <2 cm (HR 0.83; 95% CI 0.65-1.05). Delay in treatment was higher with older age (OR 1.01; p<0.001), male gender (1.11; p<0.001), non-private insurance (OR 1.44; p<0.001), black race (OR 1.60; p<0.001), decreased education (OR 1.11; p<0.001) and tumors >2 cm (OR 1.23; p<0.001). Conclusions: In patients <60 years of age and CCI of 0, delay in treatment was associated with worse OS for tumors >2 cm but not for RCC <2 cm in size. While these findings support data suggesting that active surveillance for RCC < 2 cm in size is appropriate even in young and healthy patients, caution should be exercised in patients with tumors > 2 cm.
Prognostic understanding in advanced genitourinary cancer and its association with clinical characteristics.
Authors: Bergerot Cristiane Decat , Philip Errol James , Bergerot Paulo Gustavo , Salgia Nicholas , Salgia Meghan , Hsu Joann , Dizman Nazli , Pal Sumanta K. 
Published: February 2020

665 Background: Despite promotion of a shared decision-making model of care in oncology, studies suggest that many patients with advanced cancer still possess inaccurate perceptions of their prognosis. Such inaccuracies can influence treatment choices, patient satisfaction and care planning. Novel immunotherapies and targeted treatments, which can yield exceptional responses in a small proportion of patients, are making the difficult task of discussing prognosis with patients even more challenging. We sought to identify clinical factors associated with expectations of cure. Methods: A cross-sectional survey study was conducted among patients diagnosed with incurable genitourinary cancers. Patients’ expectations of cure were assessed based on 4 quartiles: (1) cure is very likely and is in the range of 76 to 100% certainty, (2) cure is likely and is in the range of 51 to 75% certainty, (3) cure is possible but not likely and is in the range of 26 to 50% certainty, and (4) cure is not at all likely and is in the range of 0 to 25% certainty. Linear regression was used to identify clinical factors associated with such expectations. Results: A total of 145 patients were enrolled in the study from July 2017 to September 2019. Most patients were male (76%), white (70%), married (81%) and well-educated (76%). Patients were diagnosed with advanced kidney (66%), bladder (20%) or prostate (14%) cancers. A high proportion of patients (73%) were receiving first or second line (1L/2L) therapy; predominantly immunotherapy (53%) and targeted therapy (24%). Overall, 47% had an inaccurate expectation of cure (in the range of 26 to 100%). Inaccurate expectations of cure were associated with older age (P=0.04) and were also more likely to be reported among patients receiving 1L/2L compared to those receiving later courses of therapy (P=0.009). Conclusions: Our findings highlight the high proportion of patients harboring inaccurate perceptions regarding prognosis, more pronounced with older age and within the first two lines of therapy for metastatic disease. These groups may be ideal target populations for more extensive counseling around prognosis.
Impact of facility volume on complications from immunotherapy for renal cell carcinoma.
Authors: Cone Eugene Blanchard , Wang Ye , Reese Stephen , Chang Steven Lee 
Published: February 2020

672 Background: Better outcomes have been generally associated with higher volume providers/hospitals. Recent work found an association between higher volume facilities and survival for advanced cancer patients. Volume and treatment complications for medical cancer therapy is unexplored. We studied a retrospective cohort of patients with metastatic renal cell carcinoma receiving immunotherapy at high and low volume hospitals. Methods: We used Premier Healthcare Data, which includes administrative data from all payors at over 700 community and academic hospitals, and captures 20% of all hospital discharges in the US, including infusions performed in hospital clinics. Using ICD9 codes we identified patients with metastatic renal cell carcinoma treated with nivolumab from 2015-17. Clinicodemographic data were obtained for patients and hospitals. The primary exposure was dichotomized hospital treatment volume (top quartile = high volume). Outcomes were immunotherapy-related complications for which the patient re-presented to the Emergency Department or was readmitted, and readmission for other cause. We performed mixed effects logistic regression adjusting for complex survey design to achieve national representation. Results: We included 15,724 weighted hospital encounters (5,835 at low-volume hospitals and 9,889 at high-volume hospitals). Urban, teaching hospitals were more likely to be high volume, but all patient factors were balanced. We observed 1,457 complications at high volume hospitals and 1,734 at low volume hospitals. There were no significant differences by volume of hospital in overall rates of complications (OR 0.92, 95% CI 0.82-1.09) or in rates of individual complications, with the exception of ocular complications (n=11, all low volume hospitals). We observed that high volume hospitals significantly reduced odds for readmission (OR 0.09, 0.03-0.24) unrelated to immunotherapy complications. Conclusions: We found no difference in immunotherapy-related complication rates by facility volume. This is reassuring for community administration of immunotherapy. Further study is needed to elucidate why we saw significantly more therapy-unrelated readmissions at lower volume hospitals.
Relative risk of pneumonitis associated with first-line use of immune checkpoint inhibitors in advanced renal cell carcinoma.
Authors: Jahan Nusrat , Mogollon-Duffo Francis , Meda Srikala , Hardwicke Fred L. , Tijani Lukman Aderoju 
Published: February 2020

676 Background: After approval in 2006, sunitinib remained the standard for the first line treatment of advanced renal cell carcinoma (aRCC) for a decade. Immune checkpoint inhibitors (ICI) have changed the landscape of aRCC management in recent years. Pneumonitis is a significant immune related adverse event (iRAE) associated with ICIs causing morbidity, mortality and treatment interruption. We conducted a meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of pneumonitis associated with first line use of ICIs for aRCCs. Methods: We conducted a systematic search using PUBMED, MEDLINE, EMBASE, and meeting abstracts as per PRISMA guidelines from inception until May 2019. Phase 3 RCTs using ICIs in the intervention arm for the first line treatment of aRCC and reporting the number of pneumonitis for both intervention and control arms were included in the analysis. We used the Mantel-Haenszel (MH) method utilizing random effects model to calculate pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value. Results: Three phase 3 RCTs, CheckMate 214, IMmotion151 and KEYNOTE-426, randomizing 2833 patients (1427 in the ICI arms and 1406 in the control arms) were included in the analysis. ICI regimens used in the study arms were as follows — CheckMate 214: nivolumab and ipilimumab, IMmotion151: atezolizumab and bevacizumab, and KEYNOTE-426: pembrolizumab and axitinib. Sunitinib was used for all the control arms. Randomization was 1:1 in all three studies. Pneumonitis of any-grade was reported in 56 (3.92%) patients in the ICI arms versus 1 (0.07%) patient in the control arms. The pooled RR of any grade pneumonitis was 22.11 (95% CI: 5.34-91.55, P<0.0001, I2=0%). Grade 3 and above pneumonitis was reported in 12 (0.84%) patients in the ICI arms versus 0 (0%) patient in the control arms with pooled RR of 8.39 (95% CI: 1.54-45.80, P=0.01, I2=0%). Conclusions: The relative risk of any-grade as well as high-grade pneumonitis are significantly higher with ICI based regimens compared to sunitinib for aRCC. Early detection and prompt intervention are vital to reduce morbidy and mortality associated with this iRAE.