bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing axitinib treatment selection following first-line sunitinib in metastatic renal cell carcinoma.
Authors: Bracarda Sergio , Bamias Aristotelis , Casper Jochen , Negrier Sylvie , Sella Avishay , Staehler Michael D. , Tarazi Jamal Christo , Felici Alessandra , Rosbrook Brad , Jardinaud-Lopez Monica , Escudier Bernard 
Published: February 2018

589 Background: The treatment landscape for metastatic renal cell carcinoma (mRCC) is continuously evolving, with several new first-line (1L) and second-line (2L) treatment options. In the AXIS trial, axitinib resulted in significantly longer progression-free survival (PFS) vs sorafenib in the 2L treatment of mRCC. In these post-hoc exploratory analyses of AXIS, possible key drivers for successful 2L treatment with axitinib after sunitinib were evaluated. Methods: AXIS was an open-label, randomized, phase III trial (NCT00678392) in patients (pts) with mRCC who failed 1 prior systemic therapy. Univariate and multivariate analyses evaluated potential predictive factors for improved PFS (investigator-assessed) and overall survival (OS) with axitinib. PFS (independent review), OS and objective response rate (ORR) for axitinib vs sorafenib according to these predictive factors were assessed. Results: In all, 389 pts received 1L sunitinib: 194 and 195 pts received 2L axitinib and sorafenib, respectively. Based on multivariate analyses of PFS and OS, predictive factors favoring 2L axitinib treatment were identified as: non-bulky disease (sum of the longest diameter < 98 mm), favorable/intermediate (Fav/Int) risk (Memorial Sloan Kettering Cancer Center or International Metastatic Renal Cell Carcinoma Database Consortium criteria), no bone and no liver metastases. Thus, pts were grouped according to these factors. In pts with favorable risk factors (n = 86), a significantly longer median (95% confidence interval [CI]) PFS was observed in axitinib (n = 39; 13.9 [7.8–17.7] mo) vs sorafenib pts (n = 47; 4.7 [3.5–6.7] mo; hazard ratio [HR] 0.476 [95% CI 0.263–0.863]; P= 0.0126). Median (95% CI) OS (32.4 [23.8–not evaluable] mo vs 35.0 [23.9–35.0] mo; HR 0.902 [95% CI 0.457–1.780]; P= 0.7661) and ORR (both 12.8%) were similar between the 2 groups. More pts had stable disease ≥20 weeks with axitinib (38.5%) vs sorafenib (21.3%). Conclusions: In the continuously changing treatment landscape for mRCC, axitinib remains a suitable 2L treatment option, particularly in pts with non-bulky disease, Fav/Int risk and no bone nor liver metastases, characterized by an impressive PFS. Clinical trial information: NCT00678392.
Epidural block in local kidney cancer as a way to preserve the adrenal function influencing urine formation processes.
Authors: Frantsiyants Elena , Kit Oleg Ivanovich , Kozlova Larisa S. , Rozenko Dmitry A. , Bandovkina Valeria A. , Cheryarina Natalia D. , Dimitriadi Sergey N , Ushakova Natalya D. , Rozenko Ludmila Ya. , Duritskiy Maksim N. 
Published: February 2018

592 Background: Our purpose was to study the dynamics of cortisol (C) and aldosterone (A) in the blood plasma in patients receiving surgery with the epidural block (EB) for local kidney cancer. Methods: 58 patients aged 56.5±8.7 years underwent partial nephrectomy with warm ischemia for 15-20 minutes (EB – 35 patients, standard anesthesia (SA) - 23 patients). EB involved catheterization of the epidural space at Th10-L1 with the following infusion of a mixture of ropivacaine 2 mg/ml and epinephrine 2 μg/ml at 6-10 ml/hr using a syringe doser, intraoperatively and within the first three postoperative days. The levels of C and A were studied by radioimmunoassay in the blood plasma of patients before the surgery (b/s), 40 min after the start of the surgery (40' s/s) and on days 1 and 3 after the surgery (a/s). Results were compared to the levels in the blood plasma of 32 healthy donors (N). Results: C and A exceeded N in all patients b/s (p < 0.01). C increased by an order of magnitude 40' s/s only in SA (p < 0.001), while A increased in all patients, compared to the levels b/s. C decreased by 1.5 times in EB on day 1 a/s; C in SA was similar to the levels b/s; A decreased to similar levels in all patients but was still higher than N by 1.4 times on average (p < 0.01). The C levels remained stable in all patients on day 3; A levels became normal in EB only, while in SA they were 2.1 times lower which caused the loss of salts and fluid. Conclusions: SA affected the regulation of the adrenal function by the central nervous system and urine formation processes in the kidney. In SA, abnormal C and A levels preserve for a longer period of time enhancing the water and salt imbalance in the body. Significant decrease of C and the normalization of A in EB indicate the preservation of the adrenal function influencing urine formation processes in the kidney. In local kidney cancer, it is advisable to use epidural block instead of standard anesthesia as the latter blocks regulatory functions of the central nervous system.
The impact of switching systemic treatment after radiosurgery (SBRT) for oligo-progressive, metastatic renal cell carcinoma (mRCC).
Authors: Barata Pedro C. , Kotecha Rupesh , Mendiratta Prateek , Juloori Aditya , Angelov Lilyana , Chao Samuel T. , Elson Paul , Koshkin Vadim S. , Ornstein Moshe Chaim , Gilligan Timothy D. , Grivas Petros , Wood Laura S. , Rini Brian I. , Garcia Jorge A. 
Published: February 2018

599 Background: Local therapy such as SBRT is increasingly applied to RCC metastases when progression involves a limited number of metastatic sites (oligo-progression; O-PD). We aimed to assess the clinical outcome of patients (pts) with O-PD who changed systemic treatment upon SBRT (SWITCH) compared with those who remained on same therapy after SBRT (STAY); and also with the group of pts who progressed systemically (PD-SYS) and changed systemic treatment as well. Methods: Retrospective analysis of clear-cell mRCC pts treated with SBRT to brain or spinal metastases was undertaken. Clinical outcomes and treatment duration on current therapy of pts in the SWITCH, STAY and PD-SYS groups were compared. Treatment duration was defined as the time interval between SBRT and discontinuation of current systemic therapy for STAY group and discontinuation of first subsequent therapy in the SWITCH and PD-SYS groups. Results: A total of 100 pts with mRCC who had SBRT were identified, including 44 in STAY, 23 in SWITCH and 33 in PD-SYS. Median age was 58 yrs (range 36-79), 76% men, 66% ECOG PS 0-1, 60% IMDC intermediate risk. 61 pts received SBRT to brain and 40 pts to spine with 87% local control rate. Most common systemic treatments at time of SBRT included anti-VEGF (72%), mTOR (11%), PD-1 inhibitors (10%), other (7%). Median treatment duration for STAY was 5.2 months (95% CI, 3.5-6.9) compared with 5.0 months (95% CI, 4.3-5.7) for SWITCH (p = 0.549) and 2.6 months (95% CI, 1.5-3.7) for the PD-SYS group (p = 0.002, compared to all O-PD pts). Median OS was 24.2 months (95% CI, 8.7-39.7) and 27.1 (95% CI, 12.7-41.9) months for STAY and SWITCH groups, respectively (p = 0.461) and 8.5 months (95% CI, 2.1-14.9) in the PD-SYS group (p = 0.014, compared to all O-PD pts). Conclusions: SBRT for pts with mRCC in brain or spine was feasible with excellent local control. The decision to allow pts to remain on their current systemic therapy did not compromise treatment duration or survival. Pts with progressive disease outside SBRT-treated sites had a worse outcome.
Pilot trial of ibrutinib plus nivolumab in patients (pts) with metastatic renal cell cancer (mRCC): Results from a dose-finding cohort.
Authors: Lara Primo , Parikh Mamta , Robles Daniel , Lara Frances , Meyers Frederick J. , Pan Chong-xian 
Published: February 2018

600 Background: Immune checkpoint inhibitor therapy (CPI) has transformed the management of pts with mRCC, with a fraction experiencing durable tumor responses. However, most eventually develop disease progression after either an initial response to CPI or while on CPI. Newer agents that modulate immune response can possibly potentiate CPI therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate CPI. We conducted an investigator-initiated pilot trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC pts, particularly in those previously exposed to CPI. Here we report initial safety and efficacy results from the dose-finding cohort. Methods: Pts with mRCC of any histologic subtype and who have completed at least one line of prior systemic therapy including prior CPI were eligible. Pts must have acceptable end-organ function and Zubrod PS of 0-2. Treatment consisted of nivolumab 240 mg IV q2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade(Gr) 3+ adverse event (AE) attributable to therapy. Results: As of 9/18/17, 12 pts have been enrolled, six to each dose level. Patient characteristics: Mean age = 62 years (range 44-78); Male sex = 7 (58%); White race = 9 (75%); Prior CPI = 11 (92%). Three pts experienced one DLT each in dose level 0 (all Gr3): elevated lipase, hypoalbuminemia, & nausea. Only 1 DLT has been seen thus far in dose level -1 (Gr3 infection). The most common Gr3+ AEs include anemia (n = 5), ALT elevation (4), AST elevation (3), nausea (3), hypoalbuminemia (2), esophagitis, infection, lipase increase, and vomiting (1 each). Two pts with prior CPI had partial tumor response (1 confirmed, 1 unconfirmed). Conclusions: Ibrutinib at a dose of 420mg orally once daily in combination with nivolumab 240mg IV q 2 weeks appears feasible and tolerable in mRCC patients. No unique immune-related AEs have been seen thus far. Anti-tumor activity was seen in 2 pts previously exposed to PD1-targeted therapy. Further evaluation of this combination is warranted. (Supported by Pharmacyclics and UCDCCC). Clinical trial information: NCT02899078.
Phase 1 study of glutaminase (GLS) inhibitor CB-839 combined with either everolimus (E) or cabozantinib (Cabo) in patients (pts) with clear cell (cc) and papillary (pap) metastatic renal cell cancer (mRCC).
Authors: Tannir Nizar M. , Fan Alice C. , Lee Richard J. , Carthon Bradley Curtis , Iliopoulos Othon , Mier James Walter , Patel Manish R. , Meric-Bernstam Funda , DeMichele Angela , Voss Martin Henner , Harding James J. , Srinivasan Ramaprasad , Shapiro Geoffrey , Telli Melinda L. , Munster Pamela N. , Carvajal Richard D. , Jenkins Yonchu , Whiting Samuel H. , Bendell Johanna C. , Bauer Todd Michael 
Published: February 2018

603 Background: CB-839 is a first-in-class inhibitor of GLS that targets tumor glutamine utilization, a pathway upregulated in kidney cancer. CB-839 combines with E or Cabo in pre-clinical RCC models to inhibit metabolic pathways resulting in enhanced anti-tumor activity. The CX-839-001 study includes cohorts evaluating the safety, efficacy and recommended Phase 2 dose (RP2D) of CB-839 in combination with E (CBE) or Cabo (CB-Cabo) in pts with mRCC. Here we report results from the CBE and CB-Cabo cohorts. Methods: Eligibility criteria included mRCC with cc or pap histology, ECOG 0-1, RECIST measurable disease and, for cc pts, treatment with at least 1 prior anti-VEGF therapy. Pts received escalating doses of CB-839 (PO BID) in a 3+3 design, either 400-800 mg with E (10 mg PO QD) or 600-800 mg with Cabo (60 mg PO QD). Tumor response (RECIST 1.1) was assessed every 8 wks. Results: 27 pts (22 cc, 3 pap, 2 other) were enrolled in CB-E escalation (n = 17) and expansion (n = 10) cohorts (7 at 400 mg, 13 at 600 mg, 7 at 800 mg) and 11 pts (9 cc, 2 pap) in CB-Cabo escalation cohorts (6 at 600 mg, 5 at 800 mg). Median prior lines of therapy was 2 for CBE (including 64% of cc pts with ≥2 prior anti-VEGF therapies) and 3 for CB-Cabo (range 0-6). A maximum tolerated dose was not reached; 800 mg was selected as the RP2D for CB-839. The most common treatment-related Gr≥3 AEs were fatigue (11%), anemia, hyperglycemia, and neutropenia (7% each) for CBE (N = 27) and diarrhea (14%) and platelet count decreased (14% including 1 DLT at 600 mg) for CB-Cabo (N = 7). Of 24 evaluable CBE pts there was 1 PR and 21 SD for a disease control rate (DCR = CR + PR + SD) of 92% with a median PFS of 7.1 mo (95% CI 4 - 11). For 9 evaluable CB-Cabo pts the ORR and DCR were 44% (4 PR) and 100%, respectively. Conclusions: The tumor metabolism inhibitor CB-839 combines with full dose of RCC targeted therapies, E and Cabo, with good tolerability and encouraging clinical activity in heavily-pretreated mRCC pts. CB-Cabo ORR and DCR of 44% and 100% are promising, and CBE DCR of 92% and PFS of 7.1 mo compare favorably to historical E monotherapy. Randomized Phase 2 studies have been initiated (CBE) or are planned (CB-Cabo). Clinical trial information: NCT02071862.
Sixteen-year percutaneous renal mass ablation trends: Results from the Ablation of Renal Masses Outcomes Registry (ARMOR).
Authors: Maxwell Aaron Wilhelm Palmer , Cornelis Francois H. , Baird Grayson L. , Jihad Marwah , Patel Dharam , Hurtado Elizabeth , Durack Jeremy C. 
Published: February 2018

620 Background: Existing data suggest that percutaneous renal mass ablation offers favorable rates of disease control with lower cost and fewer complications relative to surgical interventions. Despite increasing utilization, little is known about changes in practice patterns and patient selection over time as new technologies have emerged and indications for renal ablation have been refined. Methods: Institutional review board approval was granted with a waiver of informed consent to review data from the multinational Ablation of Renal Masses Outcomes Registry (ARMOR), which is composed of adult ablation patients with biopsied renal masses. Patient demographics, ablation modality, timing of renal biopsy, malignancy rate, method of anesthesia, and type of imaging guidance from 2001-2016 were reviewed. Analyses were conducted using generalized mixed modeling assuming normal or binary distribution with sandwich estimation, where observations were nested within participating institutions. Variables were modeled over time using SAS/GLIMMIX with significance set at α = 0.05. Results: Data from 768 patients at eleven institutions were available for review. Average patient age was 67.7±11.7 years (male:female, 1.9:1), which remained unchanged throughout the study period. Radiofrequency ablation (RFA) was the most commonly utilized modality from 2001-2007 but decreased thereafter, with cryoablation favored from 2008-2012. By 2016, RFA, microwave (MWA), and cryoablation were all used with relative equipoise, though a significant trend toward increased MWA utilization was found beginning in 2010 (OR: 1.28; p = 0.004). A significant increase in the frequency of same-day biopsy was observed relative to pre-ablation biopsy (OR: 1.16; p = 0.003) alongside a trend toward increasing rates of benign histology (p = 0.08). Use of CT guidance and general anesthesia increased by 4% and 5%, respectively. Conclusions: ARMOR data illustrate fluctuating practice patterns, with increasing use of microwave ablation technology. Growing utilization of concurrent renal mass biopsy and ablation may be contributing to the observed trend toward increased rates of ablation for benign tumors.
Racial diversity among histology of renal cell carcinoma at an urban medical center.
Authors: Wong Kevin , Shusterman Michael , Goel Sanjay , Negassa Abdissa , Lin Juan , Sharma Janaki Neela , Gartrell Benjamin Adam 
Published: February 2018

622 Background: Non-Hispanic Blacks (NHB) with renal cell carcinoma (RCC) are more likely to have papillary RCC (pRCC) than Non-Hispanic Whites (NHW). Little is known about the histology of RCC in Hispanics (H). The Montefiore-Einstein Cancer Center (MECC) serves a diverse population in the Bronx, NY. We sought to investigate histological subtype-specific associations with established RCC risk factors in an ethnically diverse patient population to elucidate prospective relationships between those factors and racial differences in RCC histology. Methods: : The MECC tumor registry was used to identify patients ≥18 years of age treated with partial or radical nephrectomy between January 2000 and December 2015. An institutional software program and individual chart review were used to obtain demographic data (including self-reported race, age, and sex), pathology data, and RCC risk factors (hypertension, diabetes, smoking status, renal function, weight). Data were modeled by multinomial logistic regression to estimate odds ratios (ORs) and 95% CIs. Results: 1010 RCC cases were identified (232 NHW, 383 NHB, 181 H, and 214 other). Histology was 530 clear cell (ccRCC), 257 papillary (pRCC), 100 chromophobe (cRCC), and 123 other. Individuals with pRCC compared to ccRCC were more likely to be NHB than NHW (OR 4.41; 95%CI 2.81,6.93) and more likely to have a higher Fuhrman grade (OR 1.5; 95%CI 1.03,2.07), but were less likely to be female (OR 0.50; 95%CI 0.35,0.72) or H than NHW (OR 0.518, 95%CI 0.271,0.991). Individuals with cRCC compared to ccRCC were also more likely to be NHB than NHW (OR 2.23, 95%CI 1.06,4.67) and to have higher Fuhrman grade (OR 1.82, 95%CI 1.06,3.14). Conclusions: In the MECC dataset, histology of RCC varies by race, confirming earlier reports that non-ccRCC is more common in NHB than NHW. We also report for the first time that pRCC is less common in H than NHW. These associations will be evaluated in additional larger national data sets and may help elucidate reasons for disparate RCC outcomes among various races and ethnicities.
Meaning and significance of low density area (LDA) of renal cell carcinoma (RCC) on computed tomography (CT).
Authors: Shibayama Keita , Kimura Go , Hayashi Tatsuro , Akatsuka Jun , Kimata Ryoji , Horiuchi Kazutaka , Hamasaki Tsutomu , Kondo Yukihiro 
Published: February 2018

628 Background: LDA in solid RCC on CT is often interpreted as ‘central necrosis’ in routine clinical practice. However, the details of clinicopathological (CP) features of LDA of RCC on CT and their prognostic significance have not been shown. We retrospectively investigated LDA of RCC to clarify the CP features and prognostic significance. Methods: Of 428 surgically treated patients for RCC between January 2007 and March 2017 at Nippon Medical School hospital, we found 267 cases who had dynamic CT performed before operation. Among them, we selected and analyzed 199 consecutive cases whose tumor had low density area and whose cancer status resulted in no evidence of disease after surgery. We first examined pathological features of LDA. Then, we examined the correlation between pathological features of LDA and CP parameters and prognosis. The differences of values between the three groups were examined with the Kruskal-Wallis test. Recurrence free survival (RFS) was examined with the Kaplan-Meyer curves and the log-rank test. Results: The histology of LDA was divided into two groups: central necrosis (+) or (-: NN). Central necrosis (+) group was further divided into two subgroups: with neutrophilic infiltration (NI+) and without NI (NI-). This means that, in the end, there were three groups according to microscopic findings: group A (NI+, n = 20, 10%), B (NI-, n = 55, 28%), C (NN, n = 124, 62%). The pathological features of the NN group were composed of hyaline degeneration, hydropic degeneration, fibrosis, scars, and so on. The results of the comparison between CP parameters among the three groups were as follows: C-reactive protein, WBC, platelet, and alkaline phosphatase are statistically higher, and hemoglobin, triglyceride, and albumin were statistically lower in group A. CT value was statistically lower in group A and B. Median follow-up was 35months, and 3-year RFS (group A, B, C, p value) was (49.8%, 77.9%, 94.3%, p < 0.0001). Conclusions: In RCC patients only about one-third of LDA on CT was shown to be central necrosis. Necrosis with NI was clinically most closely associated with poor prognosis. Central necrosis may be predictive from lower CT values compared to non-necrotic tissues.
Renal cell carcinoma (RCC) primary tumor shrinkage on vascular endothelial growth factor (VEGF)-targeted therapy (TT): A pooled analysis.
Authors: Bosse Dominick , Lin Xun , Simantov Ronit , Lalani Aly-Khan A. , Derweesh Ithaar , Chang Steven Lee , Choueiri Toni K. , McKay Rana R. 
Published: February 2018

629 Background: Cytoreductive nephrectomy (CRN) is an important treatment modality in patients (pts) with advanced RCC, however the role and timing in the context of VEGF-TT remains under investigation. The aim of this study is to determine the efficacy of VEGF-TT to induce primary tumor shrinkage in advanced RCC. Methods: We conducted a pooled analysis of 12 Pfizer-sponsored trials in pts with metastatic RCC treated with sunitinib, sorafenib, axitinib, bevacizumab, termsirolimus or interferon-α. Primary endpoint was the primary tumor objective response rate (ORR) by RECIST in pts who have not undergone prior nephrectomy. Kaplan-Meier method was used to estimate median overall survival (OS) of responders (PR or CR) v. non-responders. Cox regression adjusting for demographics, histology type, prior therapy, metastasis sites, IMDC risk factors and neutrophil-to-lymphocyte ratio was used to compare OS between pts with and without primary tumor ORR. Results: 565 (12%) out of 4736 pts included had their primary tumors intact, of which 360 (8%) received VEGF-TT. In pts with primary tumor intact, 87% had clear-cell RCC and IMDC risk group were 4% favourable, 33% intermediate, 39% poor, 24% unknown. 35% had bone metastasis and 32% had liver metastases. 65% had ECOG performance status ≥1. Compared to pts with prior nephrectomy, primary tumor intact pts were more likely to have bone or liver metastases or to be IMDC poor risk. Primary tumor ORR was 17% (95% exact CI, 14, 20) in all pts, 19% (95% exact CI, 16, 23) in first line treated pts and 23% (95% Exact CI, 19, 28) in pts treated with VEGF-TT (any line). Primary tumor ORR was 20% (95% exact CI, 15, 26) in IMDC intermediate risk pts and 9% (95% exact CI, 5 – 13) in the poor risk. No pts had PD as best response in their primary tumor at the time they stopped systemic therapy. Median OS was 33.98 months in pts with primary tumor ORR and 9.8 months in pts without ORR, adjusted HR 0.42 [95%CI, 0.28, 0.6; p < 0.0001]. Conclusions: VEGF-TT resulted in primary tumor shrinkage in 23% of pts with IMDC intermediate and poor risk advanced RCC who have not undergone CRN. VEGF-TT may potentially facilitate future CRN in select pts. Trials assessing the utility of CRN are underway.