bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
Integrative genomic profiling of RCC treated with second-line nivolumab.
Authors: Vats Pankaj , Dhanasekaran Saravana , Malik Rohit , Zhang Yupin , Cao Xuhong , Su Fengyun , Wang Rui , Ali Alicia , Erickson Stephanie , Dahl Megan , Voliva Charles , Mehra Rohit , Chinnaiyan Arul , Alva Ajjai Shivaram 
Published: February 2020

720 Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer comprising up to 80% of RCC. Anti-vascular endothelial growth factor receptor (VEGFR) is a common therapy. Immune checkpoint inhibitor therapy with anti-PD1 antibody Nivolumab is a standard second line option in mccRCC. Overall response rate with Nivolumab however is only 25%. Since there is a critical need to develop and refine predictive biomarkers for anti-PD1 checkpoint inhibitor immunotherapy, we undertook a genomics based approach to gain further insights. Methods: Archival pre-treatment tissues from 37 metastatic mccRCC patients who had received anti-VEGFR first and then Nivolumab were collected and profiled by integrated next generation sequencing (NGS) including whole exome sequencing and RNA sequencing. Integrative NGS analysis was used to discover somatic mutations, indels, copy-number alterations and gene expression changes among the samples in this cohort. In-addition, we characterized the T-Cell clone type by adaptive immunoSEQ TCR sequencing on the matched tumor/benign adjacent tissue samples. Clinical outcome data was correlated with high throughput sequencing results to delineate the characteristics of responders and non-responders. Results: Integrative NGS profiling and analysis of ccRCC tumors revealed 1) the characteristic copy number alteration including frequent loss at 3p, 8p21.3 and 9p21.3 as well as gain at 5q, and 12p12.1. 2) a low mutational burden 3) tumors with PBRM1 mutation were relatively enriched in the “No Clinical Benefit Category”. 4) CD8 immunohistochemistry showed significant enrichment of CD8+ cells ( pval-0.05) in the clinical benefit group compared to patients with no-clinical benefit. The clinical benefit group tended to have higher number of TCR clones. Conclusions: Integrative genomic sequencing analysis of ccRCC tumors in Nivolumab treated patients revealed CD8 expression as a putative biomarker. Greater T-cell clonotypes & clonal expansion correlated with clinical benefit. PBRM1 mutant status did not select for clinical benefit. A model combining CD8 expression with T-cell characteristics was developed.
Circulating immune cell populations and cytokines in patients with metastatic variant histology renal cell carcinoma (vRCC) treated with atezolizumab plus bevacizumab (AB): Dynamic changes on therapy and association with outcomes from a phase II trial.
Authors: Flippot Ronan , Bakouny Ziad , Wei Xiao X. , Braun David A. , McGregor Bradley Alexander , Steinharter John A. , Harshman Lauren Christine , Vaishampayan Ulka N. , Severgnini Mariano , McDermott David F. , Hodi F. Stephen , Lee Gwo-Shu Mary , Van Allen Eliezer Mendel , Signoretti Sabina , Choueiri Toni K. , McKay Rana R. 
Published: February 2020

740 Background: Metastatic vRCC are aggressive tumors with poor prognosis. Our phase 2 trial of AB in vRCC showed a response rate of 33%. We investigated on-therapy changes in circulating immune cells and cytokines and their association with outcomes. Methods: Blood was collected at baseline (C1D1) and on-therapy (C3D1). Peripheral blood mononuclear cells were analyzed for cell type, expression of immune checkpoints, markers of activation, proliferation and function using flow cytometry; circulating cytokines by multiplex immunoassay. Relationship with progression-free (PFS) and overall survival (OS) was assessed by cox regression models. Results: Baseline and on-therapy samples were collected from all 60 patients. High baseline levels of immunosuppressive cytokines IL1α, IL6, CCL4 and IL13, as well as high baseline levels of CD4+ lymphocytes expressing CD69, were associated with inferior PFS and OS (Table). However, a decline in these markers on-therapy was not predictive of outcomes. On-therapy assessments showed an increase in the IFN-γ inducible cytokine CXCL10 (p<0.0001) as well as an increase in VEGF-A (p<0.0001) consistent with induction of antitumor immunity and inhibition of angiogenesis. A decrease in PD-L1 expression on circulating CD8+ lymphocytes was associated with shorter PFS and OS (Table), suggesting a potential resistance mechanism. Conclusions: High baseline levels of immunosuppressive cytokines and CD4+ CD69+ lymphocytes portended worse survival in patients treated with AB. Early changes in PD-L1 expression on circulating CD8+ lymphocytes may inform resistance to therapy. Correlation of circulating and tissue-based biomarkers is ongoing. Clinical trial information: NCT02724878. [Table: see text]
Comparative circulating tumor DNA (ctDNA) genomic profiling in 110 patients with advanced renal cell carcinoma.
Authors: Kotecha Ritesh , Gedvilaite Erika , Murray Samuel J. , Foster Ashley , Motzer Robert J. , Tsui Dana , Voss Martin H 
Published: February 2020

743 Background: Circulating tumor DNA (ctDNA) profiling is a non-invasive method to genomically assess solid tumors. Key benchmarks are required to assess applications in RCC management. To evaluate this tool broadly, we performed a large cohort analysis using a comparative approach to correlate clinical characteristics and matched oncogenomics of primary tumor and ctDNA. Methods: Pts with prior NGS sequenced mutational profiles from tumor (nephrectomy or metastatic tissues) underwent a single-time point plasma collection for ctDNA extraction. ctDNA targeted NGS sequencing was performed using MSK-IMPACT, with bi-directional cross genotype comparison using Waltz 2.0. Liberal (1-2 reads) and stringent (≥3 reads) filters were applied, with a cut-off of <30% allele frequency to remove germline alterations. Relevant clinical parameters were analyzed for correlation with ctDNA alteration frequency and load. Results: 110 metastatic clear-cell RCC pts, of whom available IMDC-risk was favorable (25%), intermediate (45%), or poor (4%) were included. 96% of pts had a nephrectomy prior to ctDNA collection, and most were heavily pre-treated (mean: 3 therapies, R: 0-8). The median time from diagnosis to ctDNA collection was 22.1 months (R: 2.3-215), and the median time from site specific tissue sequencing was 23.8 months (R: 1-177). 587 alterations were identified across the entire cohort in primary tissues, and 65% of pts had ≥1 alteration in ctDNA by liberal criteria. Detection rates for VHL and PBRM1 alterations were different in primary tissue and ctDNA (both liberal and stringent) with VHL altered in 92%, 43% and 50%, respectively; and PBRM1 altered in 50%, 25%, 21%, respectively. Conclusions: This large cohort analysis shows comparable mutational profiles of RCC-specific alterations in primary tissue and ctDNA, and highlights challenges of liquid biopsy approaches in RCC. Future efforts to correlate clinical outcomes with algorithm-based metrics will enhance the utility of this tool.[Table: see text]