bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose escalation of cabozantinib as a viable option for the treatment of mRCC.
Authors: Boegemann Martin , Krabbe Laura-Maria , Schrader Andres Jan , Semjonow Axel , Klaile Yvonne , Schlack Katrin 
Published: February 2018

636 Background: Cabozantinib (C) is a tyrosin kinase inhibitor (TKI) specific for VEGFR, MET and AXL. The phase-3 registration trial METEOR showed that C significantly improved progression-free and overall survival compared to Everolimus in patients with advanced/metastatic renal cell carcinoma (RCC) after failure of at least one VEGFR TKI and C was granted approval. In METEOR, starting dose for C was 60 mg once daily and dose de-escalation to 40 or 20 mg or stopping of C was done based on toxicity. The median dose was 43 mg. The dose had to be reduced in 62% of patients. By packing insert of C the recommended starting dose is 60 mg. We assumed that starting with 40 mg of C and escalating to 60 mg after getting accustomed to side effects may lead to a higher median dose of C. Methods: We report 20 RCC patients all started with C 40 mg and escalated to 60 mg when possible. We calculated the median time on therapy and the median dose and determined the best response. Results: The median time on C was 77 days for the patients having stopped therapy (n = 9). The median dose of C for the whole cohort was 46.0 mg. For the patients still on therapy (n = 11), the median dose was 47.7 mg. Eleven (55%) patients could be escalated to 60 mg (10 (91%) remained on 60 mg) and only 5 (25%) of patients had to be de-escalated to 20 mg. C did not have to be stopped due to toxicity. For best response, 47% reached partial remission, 13% stable and 40% progressive disease. Conclusions: Starting with 40 mg of C and escalating to 60 mg when possible may lead to a higher median dose of C compared to standard vice versa and seems to achieve responses comparable with the METEOR trial. These findings are limited by the small number of patients but warrant a prospective trial directly comparing both the escalating and de-escalating dosing schemes.
Imaging modalities used for follow-up of localized renal cell carcinoma (RCC) and subsequent effect on overall survival after recurrence: RECUR-database analysis.
Authors: Beisland Christian , Dabestani Saeed , Stewart Grant , Bensalah Karim , Guðmundsson Eirikur , Lam Thomas B , Gietzmann William , Zakikhani Paimaun , Marconi Lorenzo , Fernandèz-Pello Sergio , Monagas Serenella , Williams Samuel P , Torbrand Christian , Powles Thomas , van Werkhoven Erik , Meijer Richard Paul , Volpe Alessandro , Staehler Michael D. , Ljungberg Borje , Bex Axel 
Published: February 2018

637 Background: Cross-sectional imaging (CSI) has emerged as preferred imaging modality for staging and follow-up (FU). Moreover, the 2017 EAU RCC guidelines discourage the use of Chest X-Ray (CXR). In an international database (RECUR) data were collected to compare imaging modalities in contemporary FU, and to explore if more frequent use of CSI translates into improved overall survival (OS) after recurrence. Methods: Consecutive non-metastatic RCC patients treated with curative intent at 12 institutes across 8 European countries between 2006 and 2011, with at least 4 years of FU were included. Leibovich or UICC risk group (RG) (low, intermediate, high), recurrence characteristics, type of FU imaging (CSI (CT or MRI) vs. Conventional (CXR or Ultrasound)) and survival data were recorded. Isolated local, solitary and oligometastatic recurrences were considered potentially curable (PC) while all others were considered probably incurable (PI). Patients were analysed according to type of imaging that resulted in detection of recurrence (CSI vs. conventional) and if > or < 50% of all FU imaging were CSI based. Landmark analysis of OS after recurrence was performed for CSI and conventional imaging. Results: In 1612 patients, 336 (21%) had a recurrence. Of these, 122 were PC and 213 PI. Of the 17333 FU imaging procedures performed, 7953 were CT (46%), 6540 (38%) were CXR, 183 (1%) were MRI and 2651 (15%) were Ultrasound (US) investigations. The overall CT thorax/CXR- ratio decreased significantly across the risk groups, being 1.0, 0.46 and 0.35 in the high, intermediate and low RG, respectively (p < 0.001). Moreover, between the high RG and the other RG`s the overall CT Abd/US-ratio also decreased (3.2, 1.7 and 1.7, respectively)(p < 0.001). There was no significant difference in OS between patients with PC or PI recurrences based on type of imaging with which the recurrence was detected, nor on the ratio of CSI ( > / < 50%) during FU. Conclusions: More than 50% of FU imaging was conventional, with CSI more often used in high risk groups. The present study suggests that the type of imaging (conventional vs. CSI) for detection of recurrence does not affect subsequent OS.
Effects of patient gender on urologist decision-making regarding treatment of the localized renal mass introduction and objective.
Authors: Shah Ankur , Ulmer William , Feustel Paul , O'Malley Rebecca Leigh 
Published: February 2018

646 Background: Gender disparity in the proportion of patients receiving nephron sparing strategies (NSS) for the treatment of localized renal masses has been demonstrated in large population series as well as in single centers of excellence. Reasons for the discrepancy remain elusive. We aimed to assess urologist treatment patterns for localized renal masses in both genders to gauge the existence of provider-based gender biases. We hypothesize that female patients may be recommended more aggressive treatment due to provider biases related to patient gender. Methods: Urologists were randomly emailed 1 of 2 surveys including 6 vignettes of various patients with renal masses. Both surveys were identical other than the vignette patient gender (VPG) which was male in 50% and female in 50%. Self-selected respondents chose the single best treatment option from the following choices: active surveillance (AS), percutaneous or laparoscopic ablation (ABL), partial nephrectomy (PN), and radical nephrectomy (RN). Fisher’s exact test was used to assess differences in treatment recommended based on VPG. Nominal logistic regression was performed to assess the magnitude of differences. Results: Of the 423 urologists who completed the survey there was an even response to both surveys (210 vs. 213). Most respondents were male (93%), married (89%) and in private practice (44%). Age and time practicing were evenly distributed and median number of nephrectomies done per year was 15. There were no significant differences in demographics between the respondents of the 2 surveys. When comparing AS, ABL, PN, and RN the only vignette that differed based on VPG was question 3 (p = 0.019). Comparison of any NSS vs. RN in question 3 showed male VPG was 1.67 times more likely to be recommended RN (p = 0.040). Urologist gender had no effect on these findings. Conclusions: In this survey study of practicing urologists we found that male patient gender increased recommendations for radical surgery and less nephron sparing strategies in a hypothetical older patient with a localized renal mass. Provider biases do not appear to be solely responsible for gender disparities seen in the treatment of a localized renal mass.
Phase II study of sequential first-line pazopanib (PAZ) followed by everolimus (EVE) in patients (pts) with advanced or metastatic renal cell carcinoma (RCC) (CATChEz Study).
Authors: de Souza Paul L. , Wong Shirley , Sewak Sanjeev , Kotasek Dusan , Keam Bhumsuk , Chung Jinsoo , Erbeck Noelle , Han Jackie , Dezzani Luca , Ahmad Qasim , Mainwaring Paul N. 
Published: February 2018

648 Background: EVE following failure of sorafenib or sunitinib for RCC was first approved by the FDA in 2009. CATChEz (NCT01545817) was designed to test the activity of EVE following first-line PAZ in pts with advanced or metastatic RCC who had not received prior systemic therapy. Methods: From 2012 to 2016, pts received first-line PAZ followed by EVE until progressive disease (PD), death, unacceptable toxicity, consent withdrawal, or study termination. Pts with PD during or within 6 months of stopping PAZ were eligible for EVE. Pts off study treatment were evaluated for PD, survival, and updates on anticancer treatment every 8 weeks until death or end of study. The primary efficacy endpoint was median progression-free survival (mPFS) for the second-line EVE treatment period; secondary endpoints included other survival measures, and safety evaluations were for second-line EVE and grade 3/4 toxicities attributable to PAZ and EVE. Results: Of 74 pts who started first-line PAZ, 38 received ≥1 dose of second-line EVE. The primary endpoint of mPFS from the start of second-line EVE and the secondary endpoint of mPFS with first-line PAZ (Table) were consistent with previous reports; no unexpected adverse events (AEs) were reported. All pts had ≥1 treatment-emergent AE, 83.8% had grade ≥3 AEs, and 71.6% had serious AEs. Of 34 total deaths, 29 were due to PD and 5 were due to AEs (2 related to EVE [lower respiratory tract infection; pulmonary sepsis]; 3 unrelated to study treatment). Conclusions: Efficacy and safety outcomes were consistent with published phase III data. The CATChEz study supports sequential first-line use of PAZ followed by EVE for the treatment of pts with advanced or metastatic RCC. Clinical trial information: NCT01545817. [Table: see text]
Correlation between depression/anxiety and somatic circulating tumor DNA (ctDNA) alterations in patients with metastatic renal cell carcinoma (mRCC).
Authors: Bergerot Cristiane Decat , Bergerot Paulo Gustavo , Clark Karen L. , Loscalzo Matthew J. , Lanman Richard B. , Banks Kimberly , Pal Sumanta K. 
Published: February 2018

649 Background: A correlation between depression/anxiety and survival has been established in patients (pts) with mRCC (Cohen et al PLoS One 2012). We hypothesize that frequently encountered genomic alterations (GAs) in mRCC may identify pts with these psychological disorders. Methods: Data was obtained from pts with mRCC who received ctDNA profiling as a part of routine clinical care at progression using a CLIAA-certified platform evaluating 73 genes. Genomic alterations (GAs) were pooled for the entire cohort. ICD-9 diagnoses corresponding to anxiety and depression (300 and 311, respectively) were derived from detailed chart review, including review of established diagnoses and medication history. The chi-square test was used to determine the association between frequent GAs (those occurring in ≥5% of the study population) and the presence of depression and anxiety. Results: ctDNA results from 52 pts with mRCC were assessed (gender: 69.2% M, 30.8% F; average age: 58; histology: 84.6% clear cell, 15.4% non-clear cell). The most commonly used 1st-line treatment was sunitinib (46.1%). GAs were detected in 55.8% of pts. The most frequent GAs in the overall cohort included TP53 (21.1%), VHL (17.3%) and EGFR (7.7%). 5 and 8 pts were coded as having depression and anxiety, respectively. The average number (range) of ctDNA alterations detected was 1.1 (0-4) in patients with depression/anxiety and 1.6 (0-10) in those without (P = 0.001). The presence of VHL mutation was found to occur exclusively in pts with no depression/anxiety (P = 0.05), while 13 patients (25%) lacking VHL GAs had these psychological disorders. Conclusions: The absence of VHL alterations have been associated with poorer survival in pts with RCC (Patard et al Int J Cancer 2008), and our findings suggest that these patients may further have higher rates of depression/anxiety. Our data imply that patients bearing mutations in VHL may a prime target for early psychosocial interventions.
Activity of third line (3L) therapy in patients with metastatic non-clear-cell renal cell carcinoma (mnccRCC).
Authors: Guida Annalisa , Le Teuff Gwénaël , Colomba Emeline , Silva Carolina Alveosta , Salviat Flore , Baciarello Giulia , Derosa Lisa , Loriot Yohann , Fizazi Karim , Di Palma Mario , Massard Christophe , Escudier Bernard , Albiges Laurence 
Published: February 2018

650 Background: Medical treatment of patients (pts) with mnccRCC remains uncertain, with no established standard treatment. In addition, no data on late line of treatment have been reported. The aim of this study was to investigate clinical outcome for patients receiving 3L therapy in mnccRCC Methods: Retrospective data analysis was performed using the IGRECC (Institut Gustave Roussy REnal Cell Carcinoma) database to describe clinical features and outcomes of 3L therapy in mnccRCC pts. Kaplan Meier estimation was applied for progression-free survival (PFS) and overall survival (OS) Results: Out of all pts with mRCC treated with a targeted therapy from 2005 to 2016, 202/1027 (20%) had mnccRCC. 117 (58%) received 2L therapy and 62 (30%) received 3L therapy. These pts had papillary RCC (61%), unclassified RCC (19), Xp11translocation renal cell carcinoma (13%) and chromophobe tumors (7%). The most common 3L therapies were: everolimus (29%), sorafenib (18%), other drugs in clinical trials (16%), sunitinib (11%), axitinib (10%) and cabozantinib (10%). Baseline characteristics are displayed in Table 1. With a median follow-up of 47 months (mo) (min: 0.7 max: 74), the median PFS is 5 mo (95%CI 2.7 - 5.8) and the median OS is 11.7 mo (95%CI 10 - 20). Pts with a favourable, intermediate and poor risk International Metastatic Renal Cell Cancer Database Consortium (IMDC) score had a median OS of 21 mo (95%CI 8 – NR), 11.9 mo (95%CI 10 – 25), and 6.2 mo (95%CI 2 – 8), respectively (p < 0.0001). One patient (2%) obtained a partial response and 26 pts (51%) achieved a stable disease, among 51 evaluable pts Conclusions: This is the first report investigating the impact of 3L systemic therapy in a rare population. Selected pts could benefit of more lines of therapy and IMDC score appears to stratify well prognostic groups, especially poor risk patients. [Table: see text]
Integrating a paradigm shift into treatment of renal cell cancer: Effect of online CME on oncologists' knowledge and competence.
Authors: Herrmann Tara , Warren Charlotte , Kadkhoda Haleh , Pacheco Erin , McDermott David F. 
Published: February 2018

651 Background: The objective of this study was to determine the effect of online, case-based, continuing medical education (CME) on the knowledge and competence of oncologists regarding the management of metastatic renal cell cancer (mRCC). Methods: Oncologists participated in a text-based online CME activity composed of 2 patient cases with interactive questions. Evidence-based educational feedback was provided following each response. Three multiple-choice knowledge/competence and 1 self-efficacy question were selected from the set of intra-activity questions to be repeated after participation. These were used to assess the impact of the education in the form of a repeated pairs, in which each participant served as his/her own control. The analysis included: For all questions combined, McNemar’s chi-square test assessed the differences from pre- to post-assessment; P values <.05 are considered statistically significant; Effect size was calculated using Cramer’s V by determining the change in proportion of participants who answered questions correctly; The activity launched online 9/2016 and data collected through 10/2016. Results: Upon completion of the activity, an improvement was observed in oncologists’ ability to: Identify the most appropriate evidence-based regimen for a patient with mRCC that has progressed on a first line TKI (60% vs 18%, P =0.019); Recognize the symptoms of an irAE in a patient receiving an immune checkpoint inhibitor (55% vs 85%, P <0.001); Elicit patient preferences, goals, and values to help decide the best course of action in their care and disease management (26% vs 83%, P <0.001); Feel more confident in selecting the most appropriate option for a patient with mRCC whose disease has progressed on therapy (+17%). Conclusions: An online, interactive, case-based CME activity improved the knowledge/competence of oncologists, showing that unique educational methodologies and platforms, available on-demand, can be effective tools for advancing clinical decision making in the rapidly changing environment of mRCC disease management. Additional studies are needed to assess whether improved aptitude translates to improved performance during clinical practice.
Rheumatologic immune-related adverse events (irAE) in patients (pts) with genitourinary (GU) malignancies treated with immune checkpoint inhibitors (CPI).
Authors: Ornstein Moshe Chaim , Calabrese Cassandra , Wood Laura S. , Kirchner Elizabeth , Tyler Allison Janine , Profusek Pam , Allman Kimberly D , Kontzias Apostolos , Grivas Petros , Garcia Jorge A. , Calabrese Leonard , Rini Brian I. 
Published: February 2018

652 Background: Rheumatologic irAEs in pts treated with CPIs present a clinical challenge. We describe the clinical characteristics, treatment, and outcomes of rheumatologic irAEs in CPI-treated GU malignancy pts. Methods: Pts with GU malignancies who were treated with CPIs and developed grade ≥ 2 (per CTCAEv4) rheumatologic irAEs (i.e., arthralgias and myalgias) were retrospectively reviewed. Patient-, disease-, and rheumatologic-related data were collected and analyzed. Results: Twenty-three pts were identified; 19 (83%) had renal cell carcinoma (RCC) and 4 (17%) had urothelial carcinoma (UC). The majority (70%) were male; median age at diagnosis was 56 (range, 36-78). All RCC pts had clear cell histology and all had prior nephrectomy; 1 UC pt had prior cystectomy. Most RCC pts (58%) received antiangiogenic therapy prior to CPI treatment and 50% of UC pts received prior chemotherapy. CPI therapy included anti-PD-L1 (30%), anti-PD-1 (43%), and combined PD-1 / CTLA-4 antibodies (26%). Median time from CPI initiation to rheumatologic irAE was 5.1 months (range, 0.23 – 51.3). Most (74%) patients had 2-4 muscle or joint groups involved. CPI was held in in 20 (87%) pts who developed rheumatologic irAEs. Most (96%) pts were treated with prednisone. Median initial prednisone dose was 40mg/d (range, 10-90mg/d) and median duration of prednisone therapy was 43.6 weeks (range, 2.5–206). Treatment intensification with methotrexate (14%), infliximab (14%), tocilizumab (9%), and etanercept (9%) was required in some pts for rheumatologic symptom control. Of the patients whose CPI was held for rheumatologic irAEs, 30% restarted CPI therapy following symptoms improvement, 15% switched to a subsequent therapy, and 55% have an ongoing sustained response to therapy (median 9.1 months; range, 0.63 - 46.1) despite no subsequent anti-cancer therapy. Conclusions: Rheumatologic irAEs in CPI-treated GU malignancy pts vary in timing of presentation, severity, and treatment. Multidisciplinary teams that include a rheumatologist are critical for optimal pt management. Larger pt populations are needed to assess the predictive/prognostic impact of these irAEs on outcome.
A cost-benefit analysis for sonographic screening for renal tumors.
Authors: Roizman Shmuel , Leshno Moshe , Haifler Miki , Rappaport Yishai Hode , Zisman Amnon 
Published: February 2018

665 Background: In the last 2 decades, the rates of metastatic Renal Cell Carcinoma (RCC) at diagnosis declined from 33% to 17%This fact is attributed to massive penetration of cross sectional imaging leading to a marked stage migration. The cost of targeted therapy for metastatic RCC patients is very high. These trends led us to hypothesize that screening for RCC with ultrasound may be cost effective. Objective: To assess the cost effectiveness of screening with ultrasound for renal tumors in the general population over 60 years of age. Methods: Using the Markov model, a mathematical framework was set up describing the course of disease with and without screening for RCC using abdominal ultrasonography. Quality Adjusted Life Year (QALY) and financial costs were the outputs of the model. Results: Average costs for the screening strategy was 137.4 U$ and for non-screening was 31.4 U$. Screening and non-screening strategy would add an average of 21.7396 and 21.7385 QALY, respectively. An increase of 0.001 QALY equates to Incremental Cost Effectiveness Ratio (ICER) of 86,4 U$ per QALY, Currently, the cost which is considered cost effective for 1 QALY point is approximately 27,548.21 U$. The two variables most influential on the model output were prevalence of RCC and US cost. Conclusions: To our knowledge, this is the sole cost benefit screening study performed for RCC in the targeted therapy era. Screening for renal tumors using abdominal ultrasonography at a cost of 35.81 U$ per exam is cost effective. Our findings are highly suggestive that early screening for RCC may be cost effective for preventing RCC metastatic disease and nevertheless will save lives.
A biopsy-based genomic classifier to predict biochemical failure after definitive radiation without hormone therapy in a prospective cohort of intermediate risk prostate cancer.
Authors: Chua Melvin , Murgic Jure , Hosni Ali , Salcedo Adriana , Kamel-Reid Suzanne , Berlin Alejandro , Pintile Melania , Fraser Michael , Van Der Kwast Theodorus , Boutros Paul Christopher , Bristow Robert G. 
Published: February 2018

68 Background: Recently, NCCN adopted the Zumsteg-Spratt subclassification to define NCCN favorable and unfavorable intermediate-risk prostate cancer (IR-PCa). NCCN unfavorable disease is recommended to receive combination androgen deprivation therapy (ADT) and radiotherapy. To determine if genomics could help identify a subset who may safely avoid ADT, we evaluated the Decipher genomic classifier (GC) in IR-PCa treated with dose-escalated image-guided radiotherapy (DE-IGRT) alone. Methods: Our cohort comprised of 121 patients with NCCN favorable (N = 49, 40%) and unfavorable (N = 74, 60%) IR-PCa, who received 78 Gy without ADT. Diagnostic needle biopsies with the highest Gleason score (GS) and %tumor involvement were macrodissected for RNA extraction. GC scores were determined from the Decipher prostate cancer classifier assay (GenomeDx Biosciences, San Diego, CA). Primary clinical endpoint was biochemical relapse ([BCR], PSA nadir + 2ng/ml) post-DE-IGRT. We compared association with BCR against known clinicopathologic prognostic indices and the NCCN risk strata. Results: With a median follow up of 7.5y, 24 (19%) patients experienced BCR. Individual clinical indices did not predict BCR-free survival rate (BFS). NCCN risk strata was however associated with a small but significant difference in BFS (5-y 93%, favorable vs 88%, unfavourable, P = 0.046). GC scores stratified 85 (70%), 19 (16%), and 17 (14%) men into low, intermediate, and high risk of recurrence; 5-y BFS were 95%, 89%, and 59%, respectively (P < 0.001). On multivariable analysis, a hazard ratio of 4.71 (95% CI 1.81-12.28, P = 0.0015) for BCR was observed for the GC high risk group compared to low/intermediate; NCCN risk strata and intraductal variant did not achieve significance. Conclusions: In IR-PCa men treated with DE-IGRT monotherapy, Decipher GC was an independent predictor of BCR. While most men in this our cohort were stratified as NCCN unfavorable IR-PCa, the majority were GC low risk with excellent outcomes from DE-IGRT alone. In contrast, a minority with GC high risk had suboptimal outcomes, and may benefit from ADT intensification.