bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of long-term responders in patients treated with pazopanib for advanced renal cell carcinoma (aRCC).
Authors: Park Jinhee , Jiao Xiaolong , Wilson Thomas , Ghate Sameer , Ahmad Qasim , Perez Jose Ricardo , Vogelzang Nicholas J. 
Published: March 2017

524 Background: The objective of this study was to characterize the long term responders to pazopanib (PAZ) treatment in aRCC patients treated in a real-world community oncology setting. Methods: This retrospective study used US Oncology’s (USON) iKnowMed electronic health record database (Nov 2009 – Oct 2014), supplemented with chart review. Eligible patients: Age ≥ 18 at first diagnosis of aRCC, treated with PAZ as first-line between 11/1/2009 – 8/31/2012, and had at least 2 office visits during the follow-up period. Patients were excluded if they were enrolled in a clinical trial and diagnosed or treated for other primary cancers during the study period. Long-term responders were defined as patients with progression free survival (PFS) ≥18 months. Predictors of long-term responders to PAZ were assessed using multivariate logistic regression analysis. Results: A total of 153 PAZ patients were included of which, 33 patients (22%) were identified as long-term responders. The median PFS in long-term responders and non-long-term responders was 27.2 months (95% CI: 23.0, 35.2) vs. 6.9 months (95% CI: 5.03-8.55), respectively. Long-term responders were more likely to have Eastern Cooperative Oncology Group (ECOG) score=0 at baseline (42.4% vs. 18.3%, p=0.004), and a history of nephrectomy (81.8% vs. 57.5%, p=0.010) than non-long-term responders. Other patient characteristics including age, gender, or comorbidities did not differ significantly between the two groups even though long-term responders tend to be slightly younger (mean 64.7 vs. 66.2), female (33% vs. 25%), and less likely to have a comorbid condition (36.4% vs. 51.7%) compared to non-long-term responders. In the multivariate analysis, the only predictors of long-term response were ECOG = 0 at baseline (vs. ECOG = 1 (OR: 0.38; 95% CI 0.16-0.89) and vs. ECOG≥2 (OR: 0.07, 95% CI: 0.01-0.54) and history of nephrectomy (OR: 3.33; 95% CI 1.28-8.65). Conclusions: A subset (22%) of PAZ patients had clinically relevant long term responses in a US community oncology setting. ECOG score of 0 and history of nephrectomy were predictors of long term response in PAZ.
Analysis of predictive clinical markers of outcome in patients with metastatic clear-cell renal cell carcinoma (mRCC) treated with tyrosine-kinases inhibitors (TKI) in first line: A C Camargo Cancer Center experience.
Authors: Ferreira Camila Nassif Martins , Rinck José Augusto , Albuquerque Christiane Silveira Marinho , Costa Tatiana Vieira , Urvanegia Ana Claudia Machado , Corassa Marcelo , Formiga Maria Nirvana Cruz , Lourenço Abbade Dettino Aldo , Tariki Milena Shizue , Pinto Flavio Augusto Ismael , Oliveira Thiago Bueno , Salvadori Marcela Marinelli 
Published: March 2017

525 Background: TKI have improved the prognosis of patients with mRCC, but rarely lead to durable response. Predictive clinical biomarkers have been studied in the last few years, but most are still controversial. Objective: Identify the role of the clinical and laboratorial biomarkers of prognosis and outcome in mRCC. Methods: A retrospective study with mRCC treated with VEGFR-TKi in first line at A C Camargo Cancer Center (Jan-07 to Apr-16). Studied biomarkers: induced hypertension (HTN), acquiried hypothyroidism, proteinuria, and neutrophil to lymphocyte ratio (NLR). Data were analized in relation to progression free survival (PFS), overall survival (OS), and objetive response rate (ORR) stratified by each marker. Results: We included 94 patients (76.6% sunitinib, 21.3% pazopanib, 2.1% sorafenib). Overall, ORR to VEGFR-TKI was 41.1%; clinical benefit rate was 82.1% (43% Stable disease). Median PFS was 11.4 months (mo)(CI 95% 8.7-14.1) and median OS was 32.1 mo(CI 95% 23.4-40.8). HTN was numerically associated with longer PFS (20.1 vs. 8.2 mo) and OS (37.2 vs. 28.2 mo), but not statistically significant. Only high level TSH (>10) was associated with significant longer PFS and OS, p=0.001 and p<0.001, respectively. There was no association between proteinuria and better outcome. Finally, NLR≥3 pre-treatment was independent prognostic factor, and NLR≥3 post treatment (12aweek) predicted poor OS (9.6 vs 33.9 mo). A “NLR conversion” (before ≥3, turn to <3) was associated with longer OS (28.2 vs. 11.6 mo, p=0.0012). Conclusions: TSH elevation is a good biomarker of better outcome in patients in treatment with TKI. NLR is an important inflamatory marker associated with shorter survival and NLR conversion can be an early biomarker of better outcome to mRCC patients in first line.
A phase 1 study of alpha-1,3-galactosyltransferase-expressing allogeneic renal cell carcinoma immunotherapy in patients with metastatic renal cell cancer.
Authors: Hammers Hans J. , Drake Charles G. , Zakharia Yousef , Kennedy Eugene Paul , Vahanian Nicholas N. , Link Charles J. , Agarwal Neeraj 
Published: March 2017

528 Background: HyperAcute Renal (HAR) immunotherapy consists of two allogeneic renal cancer cell lines that have been genetically modified to express the carbohydrate α(1,3)Gal, to which humans have an inherent pre-existing immunity. HAR is designed to leverage this mechanism to educate the immune system towards antigens expressed by the patient’s own tumor cells. Methods: This study is a Phase 1 dose escalation trial of HAR for patients with Renal cell carcinoma (RCC). Eligible patients had recurrent or metastatic RCC with a clear cell component. Trial was a standard 3+3 design with patients receiving weekly intradermal injection of HAR (150 x106 cells/300 x106 cells intradermally) for 4 weeks followed by biweekly injections for 10 weeks. After the initial determination of dose-limiting toxicity, an expansion cohort up to 14 patients was enrolled. The primary endpoint was safety and determination of a maximum tolerated dose (MTD). Secondary endpoints are efficacy and immunological correlates. Results: A total of 18 patients (4 low dose, 14 high dose) were enrolled. The MTD was set at 300 x106 cells intradermally with no dose limiting toxicity (DLT). The most frequently reported adverse events (regardless of attribution), occurring in ≥ 20% of subjects, were abdominal pain, fatigue, pain, and injection site reactions. The most frequently reported laboratory abnormality (regardless of attribution) was anemia in 20% of subjects. There have been 5 reported serious adverse events, none deemed related to HAR. Conclusions: RCC is considered an immunogenic tumor based on its response rate to immune checkpoint blockade and IL-2, occasional spontaneous regression, and the high level of tumor T cell infiltration. HAR was well tolerated in this patient population. Therefore, RCC is an appropriate tumor type to target with combination immunotherapy including HAR. Updated results will be presented. Clinical trial information: NCT02035358.
Contemporary incidence and epidemiologic trends of brain metastases at renal cell carcinoma diagnosis.
Authors: Sun Maxine , de Velasco Guillermo , Brastianos Priscilla Kaliopi , Moreira Raphael Brandao , Nguyen Paul L. , Trinh Quoc-Dien , Choueiri Toni K. 
Published: March 2017

529 Background: The incidence of brain metastases (BM) in patients with renal cell carcinoma (RCC) is hypothesized to have increased in the last two decades.Our objective was to provide an overview of recent incidence trends in patients with primary renal cell carcinoma (RCC) and BM at diagnosis using a nationally representative cancer cohort originating from the US. Secondary objectives include developing a tool for prediction of BM at diagnosis and to assess their oncological outcomes, and externally validating it in second database. Methods: All patients with a primary diagnostic confirmation of RCC within the Surveillance, Epidemiology, and End Results (SEER, 2010–2013) database and the National Cancer Database (NCDB, 2010–2012) were abstracted. The incidence proportions (% IP) and 95% confidence intervals (CI) of BM were calculated. A 1000-bootstrap corrected multivariable logistic regression models was developed for prediction of BM at diagnosis using the SEER cohort. Backward variable selection was conducted to identify the most parsimonious model. Model performance was evaluated via measures of predictive accuracy in the NCDB cohort. Results: The overall % IP of BM at RCC diagnosis was 1.51% (95% CI: 1.39–1.64) in the SEER and 1.37% (95% CI: 1.29–1.45%) in the NCDB. The odds of harbouring BM at RCC diagnosis varied significantly according to sociodemographic and clinical characteristics. Following backward variable selection within the SEER database, only histology, tumor size, and cN stages were retained in the final model. Predictive accuracy was adequate in the external validation cohort (C-statistic: 0.778). Median time to any death was 6.37 months in patients with BM. After adjusting for confounders, patients with BM were more likely to succumb to any death than those without BM at diagnosis (hazard ratio: 1.87, 95% CI: 1.71–2.05, p<0.001). Conclusions: The incidence of BM in patients with RCC is increasing. The oncological outcomes of such patients remain poor and their treatment management variable. A clinical risk model can predict the presence of BM at diagnosis and may justify baseline imaging in asymptomatic but high-risk patients.
Active surveillance: Do low-income patients adhere to the protocol?
Authors: Kraus Ryan , Ji Lingyun , Jennelle Richard , Groshen Susan , Ballas Leslie K 
Published: March 2017

53 Background: Use of active surveillance (AS) in low-risk prostate cancer (PC) is up from 10% in 2006 to 40% in 2013 according to the CaPSURE registry. The data that provides evidence for the use of AS were among patients adhering to follow-up schedules. There are no data illustrating if patients not on a study follow through with their AS. Based on our experience at a large safety-net hospital with a multi-ethnic, low-income population and a nearby university-based hospital, we hypothesize that AS patients at a safety-net hospital fail to follow-up more frequently than those at a university-based hospital. Methods: We performed a retrospective chart review of patients with non-metastatic prostate cancer who initiated AS at Los Angeles County Hospital (LAC) and Norris Cancer Center (NCC) between 1/1/2008-1/1/2015. Competing-risks regression analyses were used to examine the difference in the rates of AS patients being lost to follow-up (LTFU) between the two institutions, as well as the association between LTFU and patient characteristics, with patients who ended AS due to any reasons treated as competing risks. Results: We found 116 patients at LAC and 90 patients at NCC who met the AS criteria of this study. Patients at both hospitals had similar tumor characteristics. Patients at LAC and NCC differed, however, in median income, race, primary language spoken, median miles residing from hospital, and mean percent that graduated from high school in their zip code. There was a statistically significant difference between the rates of AS patients being LTFU at the two institutions. After two years, 48% of patients at LAC were LTFU vs. 16% of AS patients at NCC. Patients stay on AS for a median of 7.4 months at LAC vs. 22.8 months at NCC. On multivariable analysis (MVA), patients at NCC were more likely to be LTFU if they had a lower household income. At LAC, the MVA found that patients that lived further from LAC were significantly more likely to adhere to AS. Conclusions: Patients undergoing AS at LAC were LTFU at a high rate. AS can only be an effective strategy if patients actually undergo surveillance. We need further investigation to evaluate whether we should recommend AS at safety-net hospitals.
A phase II study of alternative sunitinib scheduling in patients with metastatic renal cell carcinoma.
Authors: Jonasch Eric , Slack Rebecca , Geynisman Daniel M. , Milowsky Matthew I. , Rathmell Kimryn , Stovall Summer , Juarez Donna , Plimack Elizabeth R. , Tannir Nizar M. , Rini Brian I. 
Published: March 2017

533 Background: Sunitinib is an oral antiangiogenic agent indicated for the treatment of metastatic renal cell carcinoma (mRCC). Sunitinib is given in a 4 week on, 2 week off (4/2) schedule. Significant toxicities are observed in patients in the 3rd and 4thweeks of therapy. We hypothesized that a 2 week on, 1 week off (2/1) schedule would provide improved toxicity without compromising efficacy. Methods: A multicenter, single arm study was performed, with all patients initiating sunitinib 50mg on a 2/1 schedule. Schedule and dose alterations were performed if grade > 3 toxicities were observed. The primary objective was to determine the percentage of patients who experienced grade > 3 fatigue, diarrhea, or HFS. The sample size of 60 patients was selected to ensure that the upper bound of a 95% confidence would fall below the standard schedule rate of 25%-30% if the sample rate was 10%-15%, respectively. Secondary outcomes included response rate (RR), progression free survival (PFS), and dose reductions. Results: Between August 2014 and April 2016, a total of 60 patients were enrolled, and 59 were treated. Patients had a median age of 65.5 years (ranging from 45-92). 24% of patients (14/59) had grade 3 or higher fatigue, diarrhea, or HFS (95% CI: 13.6%, 36.6%). This is similar to the average of the 4 week on, 2 week off schedule of 25%-30%, and the lower bound of the confidence interval is in the center of our target rate of 10%-15%. Among events that are at least possibly related to study drug, patients were most likely to experience the expected events of diarrhea (75% with 5 grade 3 events), fatigue (71% with 6 grade 3 events), and HFS (54% with 3 grade 3 events). 22 (37%) patients responded (25.0%, 50.9%). Among patients with secondary endpoint data available, median PFS was 19.3 months (95% CI: 8.2, NR) and 33/56 (59%) of patients underwent dose reduction. Conclusions: Sunitinib administered in a 2/1 schedule in this study did not result in a lower rate of grade 3 or higher fatigue, diarrhea, or HFS when compared to historical data from trials employing a 4/2 schedule. Efficacy data were comparable to studies employing a 4/2 schedule. Clinical trial information: NCT02060370.
Pathological determinants of oncologic outcomes in stage II renal cell carcinoma: An international multicenter analysis.
Authors: Hamilton Zachary , Han Daniel , Beksac Alp Tuna , Berquist Sean , Hassan Abd−elrahma , Field Charles , Bloch Aaron , Proudfoot James , Patterson Anthony , Ozen Haluk , Lane Brian R. , Derweesh Ithaar 
Published: March 2017

535 Background: Clinical Stage II Renal Cell Carcinoma (RCC) is a heterogeneous disease characterized by disparate oncological outcomes. The risk of progression and recurrence can vary widely. We analyzed risk factors associated with oncological outcomes in a contemporary cohort. Methods: Retrospective multicenter analysis of patients who underwent surgical excision of clinical stage 2 (T2) renal mass between 1998-2015. Patients with tumors amenable to nephron−sparing surgery, baseline chronic kidney disease, or bilateral renal masses were provided an option for partial nephrectomy (PN), otherwise radical nephrectomy (RN) was performed. Lymphadenectomy (LND) was performed at the discretion of the surgeon due to concern for lymphadenopathy on preoperative imaging or at time of surgery. Patients with pN+ disease and pathological pT upstaging/downstaging were excluded. Primary endpoint was Recurrence Free Survival (RFS). Univariable linear regression, Kaplan−Meier Analysis (KMA) log−rank test, and multivariable analysis (MVA) for factors related to RFS and overall survival (OS) were performed. Results: 695 patients were analyzed (mean age 59.3 years, median follow up 49.6 months, 61.4% male/38.6% female, 545 RN/150 PN, 193 LND/502 no LND). MVA for factors associated with worsened RFS revealed lymphovascular invasion (LVI, HR 2.27, p=0.002), positive margins (HR 2.67, p=0.008), and tumor grade 3/4 (HR 2.04, p<0.008). MVA for decreased OS revealed LVI (HR 2.58, p=0.003), positive margins (HR 2.34, p=0.044), and tumor grade 3/4 (HR 2.08, p=0.023) as risk factors. KMA revealed 5 year RFS of 76.1% for LVI negative and 46% for LVI positive patients (p<0.001), and 5 year RFS of 78.1% for Tumor Grade I/II and 53.7% for Tumor Grade III/IV (p<0.001). KMA revealed 5 year OS of 79.2% for LVI negative and 60.6% for LVI positive patients (p<0.001). Conclusions: For Stage II RCC, LVI, positive margin, and tumor grade III/IV are independently associated with worsened RFS and OS. Further investigation is requisite and may add weight to consider these specific stage II RCC patients as a higher risk subgroup with implications for staging revision and clinical trial design.
Treatment patterns after the use of the 17-gene Genomic Prostate Score assay in Veterans newly diagnosed with clinically low-risk prostate cancer.
Authors: Lynch Julie Ann , Rothney Megan , Salup Raoul , Ercole Cesar Emilio , Mathur Sharad , Duchene David , Basler Joseph W. , Hernandez Javier , Liss Michael Andre , Porter Michael P , Wright Jonathan L. , Risk Michael Christopher , Efimova Olga , Denes Bela Stephen , Febbo Phillip G. , Dash Atreya 
Published: March 2017

54 Background: Active surveillance (AS) is a recommended management approach for low risk prostate cancer (PCa). Studies have shown high rates of AS in the Veterans Administration (VA), but concerns about missing aggressive disease lead to variation between centers. The 17-gene Genomic Prostate Score (GPS) has been validated to predict likelihood of favorable pathology (LFP) in men with clinically low risk PCa. This study compared treatment patterns before and after introduction of the GPS to determine if the assay influenced treatment patterns. Methods: Men newly diagnosed with PCa who met NCCN criteria for very low (VL), low (L), or intermediate (INT) risk PCa were eligible. Chart review of men across 6 VA medical centers (VAMCs) established treatment in untested patients in 2013-2014. In 2015, Veterans at the same VAMCs were offered the assay in a prospective study measuring treatment recommendations before and after the assay and treatment implemented based on chart review. Results: There were 200 men in the untested cohort. Characteristics: age (median = 66, range:43-83), Gleason Score (GS) (3+3:64%, 3+4:37%), PSA (mean = 6.6, range:0.7-20), NCCN risk (VL:18%, L:37%, INT:46%). There were 190 men in the prospective study with complete data. NCCN risk group: age (median = 66, range:50-85), GS (3+3:74%, 3+4:26%), PSA (mean = 6.4, range:0.4-18.1), VL:22%, L:43%, INT:35%. GPS ranged from 0-61 and LFP ranged from 38%-91%. GPS identified 24 patients who had more favorable pathology and 13 patients who had less favorable pathology than would be expected using NCCN alone. 62% of untested Veterans pursued AS compared to 74% of tested Veterans. AS increases between untested and tested cohorts were 1% in VL, 16% in L, and 3% in INT. Conclusions: Both untested and tested patients had clinical characteristics representative of low risk PCa in the VA. Use of AS increased in tested Veterans compared to untested, with the largest increases observed in NCCN low risk patients. The 17-gene assay used biological information to provide refined risk estimates in tested Veterans, assisting physicians in appropriately identifying candidates for AS or immediate treatment.
Conditional biochemical recurrence-free survival and cancer-specific mortality after radical prostatectomy at long term follow-up.
Authors: Barreras Silvia Garcia , Sanchez-Salas Rafael , Nunes-Silva Igor , Secin Fernando P. , Srougi Victor , Baghdadi Mohammed , Barret Eric , Rozet François , Galiano Marc , Cathelineau Xavier 
Published: March 2017

55 Background: To estimate the conditional biochemical recurrence-free survival (BCR) rates and cancer-specific mortality (CSM) for men with clinically localized prostate cancer (PCa) treated with radical prostatectomy (RP) at our institution. Methods: A total of 3576 patients underwent laparoscopic radical prostatectomy (LARP) and 2619 men were treated with robotic radical prostatectomy (RARP) in the last 15 years. BCR of primary treatment was defined as PSA > 0.2 ng/dl. PCa death was defined as patients who died with metastasis in an androgen independent setting. Kaplan-Meier and Cox regression methods were used to estimate the conditional survival probabilities and CSM. Results: The median follow-up was 8.49 years (IQR 4.01-12.97). A total of 92 (1.48%) patients (80 LARP and 12 RARP) died of disease. Positive surgical margins (PSM) were identified in 1202 patients (19.4%); of these, 664 (55.24%) had organ confined disease and 523 (43.51%) had extraprostatic extension (EPE). BCR-free survival rate was found significantly higher with RARP (83% vs 77% for LARP at 10 years; p < 0.001). For patients with PSA < 10 ng/dl BCR-free survival at 10 years was 80% vs 64% for PSA 10-20 ng/dl, and 59% for PSA > 20ng/dl; p > 0.001. Conditional probability of BCR after surgery 1st year was 6.7%. Those who reach the 2nd year of surgery without recurrence had a relapse probability of 4%, (cumulative probability 9.8%) That probability falls to 3.5% after the 3rd year (cumulative probability 13%), 2% after the 4th year (cumulative probability 15%) and is 2.1% after the 5th year (cumulative probability 17%). After 10 years of follow-up without recurrence, the possibility of relapse was 0.8%, (cumulative probability 21%). Men without BCR had a clinical trend of higher CSM at 10 years (7% vs 2% no BCR; p 0.06). Within the patients who develop BCR, those with BCR in the first three years of follow-up had higher CSM (9% vs 4% for BCR after 3 years; p 0.04). Conclusions: BRC free survival outcomes are affected by risk factors associated with type of surgery and prognosis in PCa. The period elapsed from RP is associated with BCR-free survival and the risk of recurrence decrease with increasing survival.