bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a composite biomarker-based calculator to predict the probability of pathologic complete response (pT0) after neoadjuvant pembrolizumab (pembro) in muscle invasive bladder cancer (MIBC).
Authors: Necchi Andrea , Meeks Joshua J. , Bandini Marco , Fall Leigh Ann , Raggi Daniele , Briganti Alberto , Farè Elena , Giannatempo Patrizia , McLaughlin Kimberly A. , Das Arighno , Marandino Laura , Gallina Andrea , Salonia Andrea , Gandaglia Giorgio , Fossati Nicola , Ross Jeffrey S. , Montorsi Francesco , Dittamore Ryan , Davicioni Elai , Gibb Ewan
Published: February 2020

539

Background: The PURE01 study (NCT02736266) evaluates the use of pembro before radical cystectomy (RC) in MIBC. We assessed selected individual and combined biomarkers for predicting pT0 response after pembro, and developed a tool that may be used as an aid for clinical decision-making. Methods: Patients (pts) enrolled in the PURE01 were clinical (c) stage T≤4aN0M0 MIBC. Analysis to date included a comprehensive genomic profiling (FoundationONE assay), programmed cell-death-ligand-1 (PD-L1) combined positive score assessment (CPS, Dako 22C3 antibody) and whole transcriptome (Decipher assay) and RNA-seq profiling of pre/post therapy samples. Multivariable logistic regression analyses (MVA) evaluated baseline cT-stage and biomarkers in association with pT0 response. Corresponding coefficients were used to develop a risk calculator based on the tumor mutational burden (TMB), CPS, Immune190 signature score, and cT-stage. Decision-curve analysis was performed. Results: Complete biomarker data was available for 84 pts. Increasing TMB, CPS, and Immune190 scores showed a linear positive correlation with the pT0 probability in logistic regression (p=0.02, p=0.004, p=0.02). The c-index of the risk calculator was 0.79. Decision-curve analysis found the net-benefit of the model was higher than the “treat-all” option within the clinically-meaningful threshold probabilities of achieving a pT0 of 40-60%. Within this range, adding the Immune190 score improved the model over TMB and CPS. A significant decrease in median TMB values was observed (p=0.005) in 24 matched RC, versus a non-significant change in median CPS in 38 matched RC. Molecular subtyping switching was observed in 20/31 matched cases (64.5%), most frequently to the luminal-infiltrated subtype (80%). Conclusions: The study presents the first composite biomarker-based pT0 probability calculator for optimal pt selection. Pending validation, the model may be used to recommend neoadjuvant pembro to very selected MIBC pts. The observed changes in biomarker features in post-therapy samples may have an impact on future adjuvant strategies. Clinical trial information: NCT02736266.
Veterans affairs (VA) prostate cancer treatment (Tx) sequencing (VAPCaTS): A real-world study.
Authors: Freedland Stephen J. , De Hoedt Amanda M. , DerSarkissian Maral , Chang Rose , Satija Ambika , Nguyen Catherine , Park Suna , Aillaud Aurore , Drea Edward Joseph , Duh Mei S. , Polascik Thomas J. , Szatrowski Ted P.
Published: February 2020

54

Background: Limited real-world data are available on tx sequence for patients (pts) with metastatic hormone-sensitive PC (mHSPC) treated with androgen deprivation therapy (ADT) plus docetaxel (D) or abiraterone (A) who progress to metastatic castrate-resistant prostate cancer (mCRPC). Methods: VA electronic medical records were used to retrospectively analyze 240 men treated for mHSPC with ADT and D (n=208; selected to be overrepresented) from 07/2014-08/2018 or ADT and A (n=32) from 12/2016-09/2018 and receiving at least one tx after progressing to mCRPC. Results: For D and A cohorts respectively, median age at mHSPC diagnosis was 65.2 and 70.8 yrs; 62% and 77% were white; 98% and 100% had bone metastases (mets), 40% and 34% had lymph node mets, 21% and 16% had lung mets, and 20% and 6% had liver mets; median follow-up after ADT start was 2.2 and 1.4 yrs. Pts in D and A cohorts had 56% and 36% low, 33% and 45% intermediate, and 11% and 19% high Halabi risk scores at mCRPC, respectively. Among all pts, max mCRPC tx lines was 6; 106 (44%) had only one line, 71 (30%) had two lines, and 63 (26%) pts had ≥ three lines. Across all mCRPC tx lines, 71 (30%) received a taxane at some point (47 D, 40 cabazitaxel [C]). Txs for first and second line mCRPC are shown in the Table. For D pts who received androgen-receptor targeted agents (ARTA) as first mCRPC tx and received any second mCRPC tx, 70 (62%) were treated with back-to-back ARTA. For A pts, 25 (78%) received back-to-back ARTA as first mCRPC tx. Conclusions: Most pts received ARTA as first mCRPC tx, and a large proportion of pts were treated with back-to-back ARTA. Longer follow-up is needed to assess which sequences are associated with optimal outcomes.[Table: see text]
Prognostic value of hypoxia gene expression in bladder cancer patients.
Authors: Chang Hyun , Lee Seung-Hyun , Koo Taeryool , Kim Moon Ho , Sung Soo-Yoon
Published: February 2020

548

Background: The prognostic value of hypoxia in bladder cancer remains unknown. We aimed to evaluate the potential role of hypoxia gene signature as prognostic factors in bladder cancer patients. Methods: We investigated the hypoxia gene signature and clinicopathologic features of The Cancer Genome Atlas (TCGA) bladder urothelial carcinoma (n = 408) using the Kaplan-Meier survival curves and multivariate Cox regression analyses. The clinicopathologic data and the processed data of hypoxia gene signature were obtained from TCGA Bladder urothelial carcinoma database. Results: Hypoxia gene signature score was significantly associated with overall survival (OS) and progression-free survival (PFS). Higher score resulted in shorter OS and PFS in Kaplan-Meier survival curves with Log-rank test ( P < 0.01 and P <0.05, respectively). In multivariate analysis containing clinical prognostic variables, higher hypoxia gene signature score predicted poor OS (adjusted HR= 1.58, 95% CI 1.15 - 2.19; P <0.01). Conclusions: Hypoxia gene signature was an independent prognostic factor in bladder cancer. Prospective studies are needed to evaluate the prognostic role of hypoxia in bladder cancer patients.
PD-L1 expression level in Chinese upper tract urothelial cancer (UTUC) patients and its correlation with pathological and clinical features.
Authors: Yang Kaiwei , He Qun , Li Dong , Yu Wei , Song Yi , Yang Xinyu , Hu Xiyue , Zhu Jun , Li Ting , He Zhisong
Published: February 2020

553

Background: UTUC is a potentially lethal malignancy and PD1-1/PD-L1 antibodies have shown promising efficacy. Although it had been explored in patients of their PD-L1 expression level who were enrolled in clinical trials, most of them were not Chinese. China has a larger patient population in CKD patients, yet may cause a different level of PD-L1 expression. Methods: Patients of locally resectable disease were enrolled and tumor tissues were collected for VENTANA PD-L1 (SP263) Assay (Roch). High and Low expression levels were determined according to the interpretation guide. Clinical and pathological data were collected and statistical analyses were done by SPSS 20. Results: A total of 190 patients diagnosed with UTUC were enrolled. Forty-one (21.6%) patients were identified as high PD-L1 expression. PD-L1 expression were significantly higher in high tumor grade (p=0.001), higher T stage (≤T2 vs. >T3, p=0.002), with divergent differentiation (squamous/ glandular/ sarcomatoid vs. pure UC, p=0.005), higher neutrophil/lymphocyte ratio (NLR≤3 vs. >3, p=0.045) and higher platelet/lymphocyte ratio (PLR<150 vs.≥150, p=0.006). Notably, patients with CKD stage 3 or higher (eGFR <60ml/min/1.73m2) had comparable PD-L1 high expression population (p=0.34). The HR for metastatic free survival was 2.65 in high expression patients (95% CI 1.17~5.97, p=0.019). Conclusions: China has a large population of UTUC with CKD stage 3 or higher who are ineligible for cisplatin and call for new treatment such as PD-L1/PD1 antibody. No difference was found in different CKD groups. UTUC seems to have lower proportion of PD-L1 high expression compared to bladder cancer. Whether it is due to more N-linked glycosylation that masked the detection or there might be other reasons inlayed stilled remain further study to find out.[Table: see text]
Association of positive Ki-67 and PD-L1 expressions in post neoadjvuant chemotherapy (NAC) radical cystectomy samples with lack of tumor downstaging (TD) and shorter overall survival (OS) in patients with muscle-invasive bladder cancer (MIBC).
Authors: Rubino Selene , Sexton Wade J. , Kim Youngchul , Zhou Junmin , Dhilon Jasreman , Spiess Philippe E. , Poch Michael Adam , Manley Brandon J , Li Roger , Pow-Sang Julio M. , Gilbert Scott Michael , Zhang Jingsong
Published: February 2020

554

Background: Previous chart review studies have reported that adjuvant chemotherapy after NAC did not clearly increase OS in MIBC cases characterized by a lack of TD. There is an unmet need to develop biomarkers to guide adjuvant therapy for this patient population. High levels of expression of cell proliferation marker Ki-67 are associated with poor outcome in chemotherapy naïve bladder cancer. Expression of PD-L1 has been studied as a potential predictive biomarker for anti-PD1 or PD-L1 therapies in metastatic MIBC. We therefore studied Ki-67 and PD-L1 expression in post NAC radical cystectomy samples at Moffitt Cancer Center and correlate them with TD and OS. Methods: Tissue microarrays (TMAs) were constructed from 116 post NAC cystectomy samples. The expressions of Ki-67 were evaluated with immunohistochemistry (IHC) and considered positive if any of the cores per sample were stained positive for Ki-67. The Dako 22C3 assay was used for PD-L1 IHC and the combined positive score of 10 or above was considered positive for PD-L1. Results: The median survival of this cohort of 116 patients was 33.4 months (range: 1.13 -127 months). 40 patients (35%) had TD and 21 patients (18%) achieved pathological complete response. Using Cox regression for OS, positive Ki-67 expression in post NAC radical cystectomy sample was associated with poorer OS (hazard ratio=2.412, 95% CI:1.076-5.408, p=0.033), independent of the pathological N stage. Patients with Ki67/PD-L1 double-negative tumors had a significantly longer median OS of 98.2 months versus 29.9 and 26.9 months in PD-L1-/Ki67+ and PD-L1+/Ki67+ tumors respectively (Log-rank test, p=0.0361). Lack of TD was significantly associated with positive Ki-67 (P<0.001) and positive PD-L1 (p=0.003) in the post NAC samples with a multi-variable logistic regression model. Conclusions: Positive Ki-67 and PD-L1 expressions in post NAC radical cystectomy samples were associated with inferior OS and absence of TD. Adjuvant anti-PD1 therapy either alone or in combination with chemotherapy would be indicated for this subset of patients.
Outcomes of advanced plasmacytoid urothelial carcinoma receiving systemic therapy.
Authors: Andrews Erik , Curran Catherine , Grivas Petros , Diamantopoulos Leonidas Nikolaos , Drakaki Alexandra , Jain Rohit K. , Tandon Ankita , Agarwal Neeraj , Tripathi Abhishek , Santos Victor Sacristan , Hussain Syed A. , Sonpavde Guru
Published: February 2020

580

Background: Plasmacytoid urothelial carcinoma (pUC) is an aggressive variant with poor outcomes reported in small retrospective studies. Patients (pts) with plasmacytoid-predominant tumor histology have generally been excluded from clinical trials. Given the lack of systematic data regarding outcomes in metastatic pUC, we conducted a retrospective multicenter study to broadly examine outcomes. Methods: Pts who underwent any systemic therapy for metastatic pUC were eligible from collaborating institutions. Data were collected for demographics, clinical and pathological variables. Descriptive statistics were reported to examine tumor regression, time to treatment discontinuation or failure (TTF), and overall survival (OS). Results: 52 pts with metastatic pUC were evaluable from 7 institutions. The ECOG-PS ranged from 0-3 (median 1), median age was 65 (range 46 – 85), and 14 pmts (26.9%) were female. The histology consisted of predominant urothelial, predominant plasmacytoid, and pure plasmacytoid carcinoma in 35 (67.3%), 14 (26.9%) and 3 (5.8%) pts, respectively. The median OS for evaluable pts according to histology were 234 (n=21), 203 (n=11), and 12 (n=1) days (d), respectively. The sites of metastasis (mets) were liver +/- other, non-liver visceral +/- soft tissue/lymph node (ST/LN), and ST/LN only in 5 (9.6%), 36 (69.2%), and 11 (21.2%) pts, respectively. Cisplatin-based chemotherapy (cis-chemo), PD1/L1 inhibitor (i), or other non-cis-chemo was administered in 20 (41.7%), 13 (27.1%), and 15 (31.3%) pts, respectively (therapy unknown in 4 pts). Overall best response PR, CR, SD, and PD were seen in 3 (7%), 3 (7%), 7 (16.3%), and 30 (69.8%) pts, respectively. The overall median TTF and median OS were 91 and 232 d, respectively. The median TTF for cisplatin-based chemo, non-cisplatin based chemo and PD1/L1 inhibitors was 96.5, 122.5 and 73.5 d, respectively and the median OS was 236 (n=12), 221 (n=12) and 161 (n=8) d, respectively. Conclusions: The clinical outcomes of pts with metastatic pUC are dismal and appear worse than conventional UC without plasmacytoid component. Further progress will be possible only with better understanding of tumor biology and rational drug development.
A retrospective review of the effect of metformin in metastatic prostate cancer.
Authors: Lam So Yi , Lee Chung-Shien , Liu Wingsze , Sison Cristina , Miao Emily , Zhu Xinhua
Published: February 2020

62

Background: Current treatments of metastatic prostate cancer are mainly hormone therapy and chemotherapy. The anticancer potential of metformin on metastatic prostate cancer remains obscure. In this study, we aim to investigate the significance of patients with prostate cancer taking metformin in addition to their current treatment. Methods: An IRB approved retrospective review of metastatic prostate cancer patients was conducted. Patients were categorized into metastatic castration resistant prostate cancer (mCRPC) or hormone-sensitive prostate cancer (mHSPC). Patients were further stratified to those who received metformin vs. those who did not. Progression free survival (PFS) was evaluated based on PCWG3 and RECIST criteria. 6-month (6MO) PSA response and overall survival (OS) were also evaluated in this study. Results: A total of 281 subjects were included for analysis with a mean age of 70±10. Patients were known to have either mHSPC (n = 205) or mCRPC (n = 75), and taking metformin (n = 66) or not (n = 215). There was no significant difference between metformin groups with respect to PSA response at 6MO (p < 0.73). Among those with a recorded 6MO PSA response, 70.4% (38/54) had a response in the metformin group and 72.9% (140/192) had a response in the non-metformin group. Overall median PFS was estimated to be 17 months, with no significant difference in PFS between metformin groups (16.6 vs 17.3; p < 0.88). Within the mHSPC group, metformin users had a lower risk of progression relative to non-users (HR = 0.89; 95% CI: 0.62 to 1.29). Within the mCRPC group, metformin users had a significantly higher risk of progression relative to non-users (HR = 2.65; 95% CI: 1.4 to 5.0). Median overall survival was estimated to be 81.5 months. There was a significant difference in survival time between metformin groups (148.5 vs 69.4; p < 0.02). Conclusions: No significant differences were found in 6MO PSA response or PFS. There was a significant difference in OS amongst patients who were in the metformin group and those who were not.
Does pathologic upstaging to PT3A portend a worsened prognosis when compared to non-upstaged PT3A renal cell carcinoma: Analysis of the National Cancer Database.
Authors: Patel Devin , Ghali Fady , Meagher Margaret , Bradshaw Aaron , Patel Sunil , Keiner Cathrine , Miller Nathan , Dutt Raksha , Murphy James Don , Derweesh Ithaar
Published: February 2020

624

Background: Pathological T3a (pT3a) renal cell carcinoma (RCC) is often diagnosed at the time of final pathological analysis, though impact of lack pre-treatment detection on surgical outcomes is unclear. We sought to compare outcomes of pathologically upstaged pT3a RCC with pT3a RCC recognized clinically. Methods: We queried the National Cancer Database for incident cases of pT3a pN0/x pM0/x renal cell carcinoma (RCC) treated with radical (RN) or partial nephrectomy (PN) between 2009-2015. Tumors were staged using the AJCC staging system, 7th edition. Pathologically upstaged tumors were defined as those that had a clinical stage of T1 or T2. Non-upstaged tumors had a clinical stage of T3a. Multivariable Cox proportional hazards and Kaplan-Meier survival analysis were performed to study the impact of clinical to pathological upstaging in pT3a tumors on overall survival (OS) in patients treated with RN and PN. Results: A total of 19,538 pT3a tumors were identified of which 7,231 (37%) had concordant clinical stage (non-upstaged) and 12,307 (63%) had lower clinical stage (upstaged). Patients with upstaged tumors had longer time from diagnosis to surgery (31.5 vs. 23.8 days; p<0.001), smaller tumor size (6.7 vs. 7.4 cm; p<0.001), higher rates of treatment with partial nephrectomy (18% vs. 11%; p<0.001), and higher rates of negative margins (92% vs. 89%; p<0.001). On multivariate analysis, age (HR 1.06; p<0.001), Charlson Comorbidity Index (HR 1.51; p=0.006) and positive margin status (HR 1.55; p<0.001) were associated with worse OS. Pathological upstaging was an independent predictor of improved OS following both PN (HR 0.74; 95% CI 0.59-0.91; p=0.006) and RN (HR 0.87; 95% CI 0.82-0.93; p<0.001). Kaplan-Meier analysis showed higher OS for tumors that were upstaged following both PN (5-year OS 73 vs. 70%; p=0.0083) and RN (5-year OS 67 vs. 64%; p<0.001). Conclusions: Most pT3a RCC are pathologically upstaged. Pathological pT3a tumors that were correctly detected clinically were associated with worsened outcomes. While our findings require further confirmation, they call for consideration and refinement of risk stratification protocols in pT3a RCC.
Prospective observational study on pazopanib in patients treated for advanced/metastatic renal cell carcinoma (RCC): APOLON Study.
Authors: Barthelemy Philippe , Albiges Laurence , Escudier Bernard , Lebret Thierry , Bigot Pierre , Stein Ulrich , Dourthe Louis-Marie , De La Cruz Jeannine , Tindel Malka , Thiery-Vuillemin Antoine
Published: February 2020

629

Background: Pazopanib (PZP), has been granted for advanced or metastatic RCC. In addition to pivotal clinical trials, real-world evidence (RWE) is required to evaluate effectiveness and safety in clinical routine practices. Methods: APOLON is a non-interventional, multicentric prospective study to assess PZP Progression-Free Survival (PFS) (8-month PFS rate as primary endpoint), Overall Survival (OS), Objective Response Rate (ORR), tolerability, subsequent post-pazopanib therapy sequences. It is conducted in France with 55 sites (hospital or private practitioners) in patients with mRCC, naïve to anti-VEGF therapy, who initiated PZP treatment. Data are collected at baseline and at 1, 2-3, 6, 9, 12, 18, 24, 30, 36 months (mo). Patients (n= 218) were recruited from Nov 2017 to Jan 2019. This interim analysis presents results 6 months after last patient was enrolled. Results: Patients were 71,1% males, with a median age of 69.6 years. They had clear-cell type RCC for 97.7% with a favourable (26.4%), intermediate (52.9%) or poor (20.7%) IMDC risk score. Comorbidities were: hypertension (75.1%), diabetes (26%), arterial disorders (20.1%), other pathologies (47.3%); 81.7% received co-medications. ECOG-PS was 0 (42.9%), 1 (40%), 2 (15.7%), Metastases were mainly located in lungs (62.8%), bones (28.9%), mediastinal (17.9%)/abdominal (17%) lymph nodes, glands (pancreas, thyroid, adrenals) (17.4%). Of them, 56% had an history of partial/total nephrectomy, 28.1% previous local treatments for metastases. Median PFS, assessed by investigator, was 11.3 mo (95%CI: 8.7-13), with an 8-mo PFS rate at 62.9%. ORR was 47.2% and 1-year OS rate was 71.2%. Treatment-related serious adverse events were reported in 17.3% of patients. No new safety signal was identified. After a median follow-up of 8.8 mo, of the 121 patients with discontinuation, 74 received post-PZP lines comprising firstly nivolumab (67.6%), cabozantinib (16.2%), sunitinib (10.8%), other (5.6%). Conclusions: APOLON study represents real-life population including elderly and frail patients with clinically meaningful ORR and PFS with PZP. Reported adverse events were consistent with known safety PZP profile.
Multicenter retrospective analysis of patients with metastatic renal cell carcinoma (mRCC) and bone metastases treated with ipilimumab and nivolumab.
Authors: Desai Kunal , Brown Landon Carter , Wei Wei , Allman Kimberly D. , Martin Allison , Wood Laura S. , Gupta Shilpa , Gilligan Timothy D. , Garcia Jorge A. , Kao Chester , Kinsey Emily Noelle , Healy Patrick , Kephart Julie , Harrison Michael Roger , Ramalingam Sundhar , Armstrong Andrew J. , George Daniel J. , Rini Brian I. , Zhang Tian , Ornstein Moshe Chaim
Published: February 2020

648

Background: Ipilimumab & nivolumab (I+N) followed by nivolumab maintenance is approved as front-line therapy for intermediate and poor-risk metastatic renal cell carcinoma (mRCC). Bone metastases (BM) are present in up to 30% of mRCC patients (pts) and remain a clinical challenge. We present a multicenter experience of mRCC pts with BMs treated with I+N. Methods: Patients with mRCC and bone metastases treated with (I+N) at Duke Cancer Network and Cleveland Clinic were retrospectively reviewed. Patient demographics, tumor histology, IMDC risk stratification, RECIST-defined ORR and adverse events were collected. Fisher’s exact test was used to determine predictors of response (alpha 0.05). Results: Forty-eight pts with mRCC and radiographically confirmed BMs were included in the analysis: 81% male; median age 54 (range: 41-81); 77% clear cell histology; IMDC risk 17%/52%/31% favorable/intermediate/poor, respectively. I+N was used as first-line medical therapy in 63% of pts and ≥ second-line in remaining pts. Best response on I+N per RECIST criteria: objective response rate (ORR) 23% (0% CR); 23% stable disease (SD); 44% progressive disease (PD). Median duration of treatment was 64 days with 27% of pts still on I+N. PD was the most common reason for discontinuation (38%) followed by adverse events (19%). Nearly half of pts (48%) experienced at least one irAE attributed to I+N therapy. None of the factors examined above was significantly associated with response to treatment. Conclusions: I+N has clinical activity and is well tolerated in mRCC pts with bone metastases; however ORR in this population is lower than expected and 44% pts had PD as best response. Therefore, identifying prognostic factors & improving novel therapies for this cohort of patients are priorities, given overall poorer outcomes in this population.
Prognostic role of Oncological Multidimensional Prognostic Index (Onco-MPI) in elderly patients with urological cancers.
Authors: Bimbatti Davide , Maruzzo Marco , Tierno Giuseppina , Bergo Eleonora , Pierantoni Francesco , Brunello Antonella , Basso Umberto , Zagonel Vittorina
Published: February 2020

66

Background: MPI is an effective tool for geriatric assessment in elderly patients (pts). An oncological version of MPI (Onco-MPI) has been validated by our group in pts with cancer. We evaluate here the prognostic role of Onco-MPI in pts affected by urological cancer. Methods: Pts aged ≥70 years with prostate, renal and urothelial cancer (bladder or upper urinary tract) referred to the Medical Oncology 1 Unit from Jan 2005 to Aug 2019 received a basal comprehensive geriatric assessment (CGA). Onco-MPI was calculated by a validated algorithm as a weighted linear combination of the CGA domains as previously described, identifying 3 different prognostic groups: low (scores 0.0-0.46), intermediate (scores 0.47-0.63) and high risk (scores 0.64-1.0). Results: A total of 643 pts were included; 382 with prostate, 121 renal and 140 urothelial cancer. Median age was 77 years (68-95). ECOG PS was 0 in 44%, 1 in 34.2% and >1 in 21.6%; 19.3% had stage I or II disease, 29.7% stage III and 51% stage IV. Median overall survival (OS) was 35.4 months (95% CI 29.5-41.2). Onco-MPI score (low vs medium vs high risk) was significantly associated with OS in the overall population as well as in the subgroups of patients with prostate, renal or urothelial cancer (table). In pts with prostate cancer the majority of pts were low risk (93%) and only few intermediate (7%), no one was high risk. Conclusions: Onco-MPI confirmed its prognostic role in elderly pts with prostate, renal and urothelial carcinoma. It may be therefore valuable both in clinical practice for driving decision-making, and in geriatric clinical trials thanks to its standardization.[Table: see text]
Utilization of renal mass biopsy in patients with localized renal cell carcinoma: A population-based study utilizing the National Cancer Database.
Authors: Patel Devin , Ghali Fady , Patel Sunil , Miller Nathan , Bradshaw Aaron , Meagher Margaret , Rivera-Sanfeliz Gerant , Murphy James Don , Derweesh Ithaar
Published: February 2020

662

Background: Recent guidelines suggest an increasing role for renal mass biopsy (RMB) in the management of renal cell carcinoma (RCC) prior to ablative therapy and in patients in whom active surveillance (AS) is being considered. Methods: We queried the National Cancer Database for cases of localized (cT1-cT3N0M0) RCC between 2004-2015. Unadjusted temporal trends in receipt of RMB were characterized over the study period based on type of treatment [partial nephrectomy (PN), radical nephrectomy (RN), ablation, and surveillance], tumor size, age and Charlson Comorbidity Index and compared using analysis of variance. Multivariable logistic regression was used to test for the association between patient, tumor and treatment variables and use of RMB. Results: 338,252 patients were analyzed, with 11.9% (40,276) undergoing RMB. Use of RMB increased from 1,586 (7.6%) in 2004 to 5,629 (16.2%) in 2015 (p<0.001). On treatment strategy, use of RMB increased the greatest in association with ablation from 27% to 63% across the study period (p<0.001). On tumor size, use of RMB increased the greatest for tumors 2-4 cm from 9% to 20% (p<0.001). Conversely, utilization of RMB increased proportionally across different age (p=0.17) and comorbidity (p=0.18) groups over time. Multivariable logistic regression revealed that year of diagnosis (OR 1.06; p<0.001), black race (OR 1.04; p=0.02), higher education (OR 1.09; p<0.001) and insured status (OR 1.23; p<0.001) were associated with increased RMB. However, increasing age (p=0.23) and comorbidity (p=0.35) were not. Compared to tumors <2 cm in size, tumors 2-4 cm (OR 1.36; p<0.001), 4-7 cm (OR 1.18; p<0.001) and >7 cm (OR 1.05; p=0.03) were associated with higher RMB. Compared to treatment with RN, treatment with PN was not associated with increased RMB (p=0.92); however, treatment with ablation (OR 10.90; p<0.001) and with surveillance (OR 4.83; p<0.001) were. Conclusions: The largest increase in RMB was associated with ablation treatment. Rates of RMB for tumors <2 cm and for older, sicker patients not undergoing treatment have correspondingly increased less, indicating RMB may not be as highly used for surveillance.
Exploring motivation to pursue genomic profiling among patients with metastatic genitourinary cancers.
Authors: Philip Errol James , Bergerot Cristiane Decat , Bergerot Paulo Gustavo , Salgia Meghan , Salgia Nicholas , Dizman Nazli , Hsu Joann , Pal Sumanta K.
Published: February 2020

663

Background: Genomic profiling (GP) is becoming more widespread in oncologic care, yet little is known regarding patients’ motivations to pursue or accept such testing. The current study examined patients’ reasons to pursue GP in the context of advanced genitourinary disease, and their potential association with demographic characteristics and psychiatric symptoms (anxiety and depression). Methods: Patients were recruited from a single institution after receiving a standardized dialogue about GP from their oncologist. Patients were included if they had received GP in the context of routine clinical care. Patients’ reasons for pursuing GP were assessed, as well as anxiety and depression via the PROMIS measures. The Kruskal-Wallis test was used. Results: A cohort of 90 patients (median 64 years old; 76% male; 71% white) with metastatic genitourinary cancers (61% renal cell carcinoma, 22% urothelial carcinoma and 17% prostate cancer) were enrolled. Demographic characteristics and psychosocial symptoms were associated with the pursuit of GP. Older and female patients tended to report that their physician’s recommendation was a primary driver of their decision (p<0.05), while younger patients sought to avoid unnecessary treatment and side-effects (p=0.04). In addition, patients experiencing anxiety and depression reported that GP adoption was driven by a desire to predict disease outcomes (p<0.05). Conclusions: The current study provides novel insight into the motivations underlying patients’ adoption of GP. The importance of a physicians’ recommendation may be indicative of the lasting influence of a paternalistic model of care, while the desire to avoid of side-effects can help guide effective discussions concerning the role of GP in care planning. The association between anxiety/depression and the hope that GP can predict disease outcomes reinforces the importance of ensuring patients possess an accurate understanding of this testing paradigm.
Utilization of palliative care in patients with genitourinary malignancies.
Authors: Mariam Roy Arya , Konda Manojna , Goel Akshay , Verma Rashmi
Published: February 2020

669

Background: Palliative care provides support and improves the quality of life of patients who has terminal illness such as cancer. Studies have shown that integrating palliative care into cancer care soon after the diagnosis of metastatic cancer can improve the quality of life and also prolong survival. The objective of the study was to analyze the acceptance of palliative care and to determine the factors affecting the utilization of palliative care in patients with genitourinary (GU) cancers. Methods: The National Inpatient Sample Database for the year 2016 was queried for the data. Patients who were admitted with a principal diagnosis of Malignant Neoplasm of Prostate (MNP), Renal Cell Carcinoma (RCC), Malignant Neoplasm of Ureter (MNU) were identified using ICD-10 codes and those who had Encounter for Palliative Care (PC) was also identified. Results: A total of 58765 hospitalizations were identified with MNP (n=39853), RCC (n=17786), MNU (n= 1126) during the study period. The total PC utilization for the above patients were 6.4% (n= 3785). Among those, 6.7% (n=1186), 6.3% (n=2531), 6.03% (n=68) from the groups RCC, MNP, MNU respectively received PC. The mean age for the PC utilization was 73 years (MNP= 72 yrs, RCA= 63 yrs, UCC= 73 yrs). Females received more PC when compared to males (6.7% vs 6.4%). Among those who had PC 27.4% (n=1029) died in the hospital. Interestingly, patients who had Medicare and Medicaid had more PC encounters when compared to those with private insurance (OR= 1.21, P= 0.001). Patients admitted on the weekend received more PC when compared to those who admitted during weekdays (OR= 1.12, P= 0.001). Patients admitted to hospitals in the West received more PC than other regions (OR= 1.42, P=0.03). Impact of race, teaching vs non-teaching hospital admissions were not found to be statistically significant in the utilization of PC in the above GU cancers. Conclusions: Medicare and Medicaid patients, weekend admissions, admissions to hospitals in the West received more palliative care. Further studies are needed to reveal the role of socioeconomic status and insurance in the utilization of palliative care in GU malignancies.
Efficacy of immune checkpoint inhibitors (ICI) treatment in special populations of metastatic renal cell carcinoma (mRCC).
Authors: Araujo Daniel Vilarim , Malone Eoghan Ruadh , Sacher Adrian G. , Fallah-Rad Nazanin , Sridhar Srikala S. , Hansen Aaron Richard
Published: February 2020

673

Background: Immunotherapies involving a PD-1/PD-L1 immune-checkpoint inhibitor (ICI) are highly effective treatments for mRCC and are now standard of care. Nevertheless, special populations such as patients (pts) with renal impairment (RI) and elderly age were either excluded or underrepresented in registration trials. Here we investigate the efficacy of ICI in mRCC with RI and age above 70 years (yrs). Methods: We utilized the mRCC Princess Margaret database to select pts treated with an ICI agent from May 2005 to May 2018. Renal impairment (RI) was defined as a baseline creatinine > 1.5 ULN or clearance of creatinine < 40 mL/min. Pts were classified as elderly if their age was over 70yrs at the time of ICI initiation. Descriptive statistics and survival analysis were performed. Results: Of 387 pts, 74 received an ICI agent or combination. Mean age was 61yrs and median creatinine was 105 umol/L. Fifty-four pts (73%) were treated with single agent PD-1/PD-L1 ICI and 46 (62%) received treatment as 2nd line. Respectively, 19 (26%), 43 (58%) and 12 (16%) pts were classified as International Metastatic RCC Database Criteria (IMDC) prognostic groups good, intermediate and poor. Of 73 pts with available creatinine levels, 7 (9.5%) were classified as having RI. Ten pts (13.5%) were > 70yrs. Despite not statistically different, pts with RI had worse median overall survival (OS) compared to pts without RI: 7.8 months (m) vs. 28.3m (p=.10). There was no OS difference between pts > 70yrs compared to ≤ 70yrs: not reached (NR) vs. 28m (p=.65). Both RI and elderly patients had no differences in distribution of IMDC prognostic groups compared controls. Conclusions: RI was associated with a non-statistical detriment in OS of mRCC treated with ICI. RI may be a surrogate for comorbid factors that impact OS and needs further analysis in a larger patient sample. Age does not affect ICI efficacy in our cohort. Larger studies to confirm our findings in these special populations are necessary.
Relative risk of hematological toxicities in patients with advanced renal cell carcinoma treated with upfront immune checkpoint inhibitors.
Authors: Jahan Nusrat , Ball Somedeb , Quirch Miguel , Rehman Shabnam , Thein Kyaw Zin , Tijani Lukman Aderoju
Published: February 2020

675

Background: Sunitinib was the standard first-line treatment of advanced renal cell carcinoma (aRCC) for the past decade, but it has been associated with significant hematological toxicities. Immune checkpoint inhibitors (ICI) based regimens have become the new preferred treatment for aRCC in the first-line setting. We conducted a meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of hematological toxicities associated with upfront use of ICI-based regimens for aRCC. Methods: We conducted a systematic search at 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 were included. 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: Four phase 3 RCTs, CheckMate 214, IMmotion151, JAVELIN Renal 101 and KEYNOTE-426, randomizing 3706 patients were included in the analysis of anemia and thrombocytopenia. CheckMate 214 did not report the number of neutropenia. Hence, other 3 RCTs that included 2624 patients were analyzed for neutropenia. Following regimens were used in the study arms — CheckMate 214: nivolumab+ipilimumab, IMmotion151: atezolizumab+bevacizumab, JAVELIN Renal 101: axitinib+avelumab; and KEYNOTE-426: axitinib+ pembrolizumab. Sunitinib was used in the control arms for all the studies. The pooled RR of any-grade hematological toxicities are as follows — anemia: 0.31 (95% CI:0.24-0.41, P< 0.00001, I2=39%); thrombocytopenia: 0.11 (95% CI: 0.06-0.19, P<0.00001, I2=63%); neutropenia: 0.08 (95% CI: 0.05-0.13, P<0.00001, I2=0%). The pooled RR of grade 3 and higher hematological toxicities are as follows — anemia: 0.14 (95% CI:0.08-0.25, P< 0.00001, I2=0); thrombocytopenia: 0.06 (95% CI:0.02-0.16, P<0.00001, I2=4%); neutropenia: 0.06 (95% CI: 0.02-0.16, P<0.00001, I2=0%). Conclusions: ICI-based regimens have significantly reduced risk of any-grade as well as high-grade hematological toxicities compared to sunitinib in patients with aRCC.
Response to systemic therapy in patients with metastatic fumarate hydratase (FH) deficient renal cell carcinoma (RCC).
Authors: Gleeson Jack Patrick , Nikolovski Ines , Kotecha Ritesh , Ged Yasser , Shapnik Natalie , Knezevic Andrea , Feldman Darren R. , Lee Chung-Han , Voss Martin H , Chen Ying-Bei , Motzer Robert J. , Carlo Maria Isabel
Published: February 2020

686

Background: FH-deficient RCC (FHRCC) is characterized by unique pathologic features and lack of FH staining on immunohistochemistry (IHC). Most cases are associated with germline FH mutations and poor prognosis, but there is limited data on the efficacy of systemic therapy. Methods: Patients with metastatic FHRCC, defined by presence of FH germline or somatic mutation with loss of FH by IHC [FH and 2-succino-cysteine (2SC)], were identified from an institutional database. Clinical and treatment data was obtained from electronic records. The primary outcome was best objective response rate to first, second or third-line systemic therapy by blinded investigator RECIST v1.1 assessment. Results: 32 patients (median age 46; range 20-74; M:F, 20:12) were identified. All patients had evidence of FH-deficiency by IHC, 23 (72%) had germline FH mutations, 9 (28%) had somatic only FH mutations. 20 patients (62.5%) presented with de novo metastatic disease. Most common sites of metastasis were retroperitoneal lymph nodes (82%), lung (78%) and peritoneal spread (70%); no patients developed brain metastases. Median overall survival (OS) from diagnosis of metastatic disease is 28.1 months (95% CI: 14.9, 33.8). Median follow-up is 14.8 months. 25 patients were evaluable for response to first-line therapy, 5 to second-line and 4 to third-line therapy (Table). Most common first-line therapies were combination mTOR/VEGFR (50%) and VEGFR monotherapy (20%). ORR to first, second and third-line therapy was 40%, 20% and 25%, with no complete responses. 8 patients who received IO monotherapy were evaluable; 3 had stable disease, no responses were seen. Conclusions: Patients with FHRCC show distinct patterns of disease progression with primary peritoneal spread. Although there was high ORR to VEGFR/mTOR inhibitor combinations, there were limited responses to IO monotherapy.[Table: see text]
A randomized, double-blinded clinical trial of royal jelly intake for anticancer effects and suppressing adverse events in renal cell carcinoma patients treated with tyrosine kinase inhibitors.
Authors: Miyata Yasuyoshi , Ohba Kojiro , Matsuo Tomohiro , Mitsunari Kensuke , Sakai Hideki
Published: February 2020

697

Background: Royal jelly (RJ) is a honey bee product secreted from the mandibular glands and hypopharyngeal glands of worker honeybees. RJ has anti-allergy, anti-inflammatory, and immunomodulatory effects. RJ has been reported to improve the anti-cancer effects and suppress the adverse effects of chemotherapeutic agents. The main aim is to clarify the clinical effects of oral intake of RJ in renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKIs). Methods: A randomized, controlled, double-blinded clinical trial with reduction of tumor size and frequencies of adverse events as endpoints was performed in 33 RCC patients who received TKIs in Nagasaki University Hospital. Patients were divided into RJ (n = 16) and placebo (n = 17) groups, and there was no significant difference in all clinical and pathological parameters between the two groups. RJ and placebo were orally administered for 3 months. Results: In this study, 21, 8, and 3 patients were treated with sunitinib, pazopanib, and axitinib, respectively; only 1 patient was treated with sorafenib. Frequencies and severities of fatigue and anorexia in the RJ group was significantly lower than those in the placebo group ( P = 0.003 and 0.015, respectively). Such significant differences between the 2 groups were detected in patients treated with sunitinib, but not in those treated with other TKIs. The number of patients who were given an initial dose of TKIs in the RJ and placebo groups were 7 (43.8%) and 2 (11.8%), respectively, and the relative dose intensity (RDI) of the RJ group (88.6%) was significantly higher ( P = 0.016) than that in the placebo group (68.6%). Regarding anti-cancer effects, the frequency of partial response in the RJ group (n = 5; 41.7%) was higher than that in the placebo group (2; 18.2%); however, such difference was not significant ( P = 0.056). Conclusions: RJ intake can increase RDI. Although a significant difference was not observed, RJ intake observed a trend for improving anti-cancer effects by increasing RDI and maintaining quality of life.
Nivolumab in metastatic nonclear cell renal cell carcinoma: First results of the AcSe prospective study.
Authors: Albiges Laurence , Pouessel Damien , Beylot-Barry Marie , Bens Guido , Pannier Diane , Gavoille Céline , Oudard Stephane , Chevret Sylvie , Hoog Labouret Natalie , Legrand Frédéric , Simon Clotilde , Lamrani-Ghaouti Assia , Escudier Bernard , Marabelle Aurelien , Flechon Aude ,   GETUG
Published: February 2020

699

Background: AcSe Nivolumab (N), is a non-randomised, open-label, multicentric study to investigate the efficacy and safety of nivolumab monotherapy in patients (pts) with specific rare cancers (NCT03012581). We report on the non-clear cell renal cell carcinoma (RCC) cohort. Methods: Primary endpoint was objective response rate (ORR) at 12 weeks according to RECIST1.1. All pts receives N at 240mg IV every 2 weeks. Secondary endpoints included progression free survival (PFS), overall survival (OS), best response, and safety. Results: Between 07/2017 and 02/2019, 50 pts have been enrolled across 13 institutions. Median age was 61.4 years old, 70% were male. ECOG PS was 0, 1, 2, in 29%, 63% and 8% of pts respectively. Histological types were papillary (pRCC) type 2 (41%), chromophobe (18%), pRCC type I (10%), pRCC unclassified (8%), collecting duct carcinoma (CDC) (8%), and others (including predominant sarcomatoid, renal medullary carcinoma, MITF associated RCC, unclassified RCC). N was used in first line in 16%, second line in 54% and third line or beyond in 30%. IMDC risk group was 14%, 70% and 16% for good, intermediate and poor risk respectively. With a median follow up of 10.4 months (mo), 42 pts had discontinued N. The 12 weeks-ORR was 6% (3 PR), with stable disease in 49% and PD in 44% of pts. The best ORR was 10%. Median PFS was 3.9 mo (IC95% [2.9; 8.3]). At time of analysis, 25 pts (50%) had died and 12-months OS rate was 47.7% (IC95% [33.5; 67.8]). Overall, 31 pts (62%) have presented at least one grade ≥ 3 AE. No new safety signal with N was reported. 12 weeks-ORR and best ORR according to distinct histology are presented in table 1. Pts with PR were 1pRCC type 2, 1pRCC type 1, 1 CDC, 1 MITF RCC and 1 unclassified. Conclusions: We report the first prospective study of N single agent in non-clear cell RCC. N demonstrates limited activity in a pretreated and heterogeneous non- clear cell RCC population. Interestingly 1/4 CDC developed PR while no response was noted in chromophobe RCC. Clinical trial information: NCT03012581. [Table: see text]
Outcomes after first-line therapy for immune/immune or immune/VEGF combinations.
Authors: Jackson-Spence Francesca , Jovaisaite Agne , Grant Michael , Liu Wing-Kin , Butters Thomas , Powles Thomas , Szabados Bernadett
Published: February 2020

706

Background: The introduction of first line immune combination or immune/VEGF therapy in metastatic renal cancer has changed treatment landscape. Here we compare outcomes of these combinations with patients treated with first line sunitinib. The focus is on the impact of subsequent treatments. Methods: This retrospective analysis was performed at Barts Cancer Institute for consecutive patients from April 2015 when front line immune therapy was first used at our institution. Only patients enrolled on reported prospective trials were included to avoid selection bias. Patients were treated with VEGF targeted therapy (n=35) (group V), PD-1 + CTLA4 (n=15) (group I/I) or a combination of PD-L1 + VEGF TKI inhibitor (n=29) (group I/V). The primary analysis focused on the proportion of patients who received second line therapy and their outcome. Results: 79 patients received first line therapy for clear cell RCC. IMDC good, intermediate and poor risk occurred in 27.8%, 60.8% and 11.4% respectively. Front line response rates for V, I/I and I/V groups were 34.3%, 46.7% and 65.5% and PFS in V, I/I and I/V groups were 11mo (95%CI 6-16), 18mo (95% CI 0-41) and 36mo (95% CI 13-59), respectively (P= 0.016). OS in the 3 groups were immature but not significantly different. Second line therapy occurred in 87.5%, 92.9% and 81.8% in the V, I/I and I/V groups respectively (in those who progressed after initial therapy). Second line response rate post first line V, I/I and I/V were 11%, 0% and 0% respectively as per RECIST 1.1. 63% of patients receiving VEGF front line therapy subsequently received immune therapy. 95% of patients receiving first line immune/immune or immune/VEGF combination therapy received VEGF therapy in the second line. Only 70% of patients who progressed on second line therapy got 3rd line therapy across all arms. Conclusions: Response rates after front line immune combination therapy are modest. The sequencing of PD-1 therapy after VEGF monotherapy appears particularly relevant in outcomes. A high proportion of patients are sequencing therapy and reaching third line which may help improve outcomes.