bluuebunny/crossref_metadata_2025_split huggingface dataset:
CheckMate 025 phase III trial: Outcomes by key baseline factors and prior therapy for nivolumab (NIVO) versus everolimus (EVE) in advanced renal cell carcinoma (RCC).
Authors: Motzer Robert J. , Sharma Padmanee , McDermott David F. , George Saby , Hammers Hans J. , Srinivas Sandhya , Tykodi Scott S. , Sosman Jeffrey Alan , Procopio Giuseppe , Plimack Elizabeth R. , Castellano Daniel E. , Gurney Howard , Donskov Frede , Bono Petri , Wagstaff John , Gauler Thomas Christoph , Ueda Takeshi , Zhao Huanyu , Waxman Ian M , Escudier Bernard 
Published: February 2017

498 Background: Based on assessment by an independent Data Monitoring Committee, a phase III trial of NIVO (n=410) vs EVE (n=411) in previously treated patients with advanced or metastatic RCC (NCT01668784) was halted early as it met its endpoint; superior overall survival (OS) was seen with NIVO vs EVE. We present outcomes by key baseline factors, prior therapy, and subsequent anticancer therapy. Methods: Patients with 1 or 2 prior anti-angiogenic therapies and measurable disease (RECIST v1.1) were randomized 1:1 to NIVO 3 mg/kg IV every 2 weeks or EVE 10 mg orally once daily. Primary endpoint was OS. A key secondary endpoint was objective response rate (ORR). Results: The Table shows OS and ORR by key baseline factors. Median follow-up was 17-18 mo. 77% and 23% of patients received 1 or 2 prior anti-angiogenic therapies, respectively, for advanced RCC, mainly sunitinib (63%) or pazopanib (32%). In patients who had prior sunitinib, median OS was 23.6 mo for NIVO vs 19.8 mo for EVE; in those who had prior pazopanib, median OS was not estimable (NE) for NIVO vs 17.6 mo for EVE. For those who had prior IL-2 (10%), median OS was NE for NIVO vs 17.2 mo for EVE. Outcomes by subsequent anticancer therapy are planned. Conclusions: A consistent OS benefit with NIVO vs EVE was found across baseline factors (Karnofsky performance status [KPS], Heng risk group, number of prior therapies), and specific prior therapies (sunitinib, pazopanib, IL-2) in previously treated patients with advanced RCC. ORR benefit with NIVO was also seen across baseline factors. Clinical trial information: NCT01668784. [Table: see text]
Analysis of real-world treatment adherence in a cohort of 2,395 patients with metastatic renal cell carcinoma (mRCC).
Authors: Margolis Jay , Princic Nicole , Doan Justin , Lenhart Gregory , Motzer Robert J. 
Published: February 2017

517 Background: Given recent European data highlighting the importance of real-world dose intensity(Cancer Med 2014; 3(6): 1517-26.), we sought to investigate real-world adherence in patients with mRCC from a US perspective. Methods: In this retrospective cohort study, patients with newly diagnosed mRCC were selected from the MarketScan Commercial and Medicare Supplemental administrative claims databases based on an index event from 1/1/2006 to 3/31/2014. First line (1L) therapy was defined as first prescription record post-index for any approved mRCC therapy; change in line of therapy was defined as a therapy switch. Adherence was measured using the medication possession ratio (MPR) during each and all lines. MPR was defined as total days of supply during the treatment period divided by total treatment period until the start of last treatment. Nonadherence was defined as an MPR <80%. Results: A total of 2,395 mRCC patients were identified as initiating 1L therapy. Across all treatments the mean MPR was 0.77 ± 0.20, which increased over time from 0.73 in 2006 to 0.81 in 2013. More than 50% of patients were nonadherent. During 1L, patients treated with sunitinib had significantly lower mean MPR compared with most other treatments (table). Adherence was higher during 2L (0.85 ± 0.18) vs 1L (0.80 ± 0.19). A larger proportion of patients who initiated therapy with temsirolimus were adherent compared with those who initiated with sunitinib (62% vs 38%). Additional analyses are being conducted to address adherence with alternative dosing schedules. Conclusions: Over half of treated mRCC patients were found to be nonadherent to therapy. Adherence was significantly better with IV administered temsirolimus relative to the reference oral therapy, sunitinib. Real-world analysis of treatment adherence provides information for clinicians in monitoring and optimizing targeted therapy. [Table: see text]
Cancer detection between peripheral zone and transitional zone targeted biopsies: Preliminary results from a prospective cohort of men undergoing MRI-US fusion biopsy.
Authors: Nahar Bruno , Soodana-Prakash Nachiketh , Pavan Nicola , Rai Samarpit , Munera Felipe , Castillo Rosa P , Balise Raymond R , Manoharan Murugesan , Kava Bruce , Satyanarayana Ramgopal , Gonzalgo Mark L. , Ritch Chad , Parekh Dipen , Punnen Sanoj 
Published: February 2017

56 Background: Multiparametric MRI has emerged as a popular imaging modality to localize prostate cancer. Nevertheless, interpretation of MRI is subjective, with concerns for false positives, particularly in the transitional zone (TZ), where hyperplastic changes may be confused for suspicion of cancer. We analyzed a prospective cohort of men undergoing MRI-US fusion biopsy and compared cancer detection rate between lesions seen in the peripheral zone (PZ) and the TZ. Methods: 133 men with elevated PSA or positive DRE underwent MRI-US fusion biopsy with average of 2 cores taken per target for the detection of prostate cancer between October 2014 and July 2015. Each targeted lesion in the PZ and TZ was previously classified by radiologists according to the MRI PI-RADS score and grouped according to their level of suspicion as probably benign (1-2), indeterminate (3) or probably malignant (4-5). Histopathology from targeted cores were categorized as no cancer, non-significant cancer (Gleason 6) and significant cancer (Gleason ≥ 7). We compared the cancer detection rates between lesions in PZ and TZ lesions, based on PI-RADS score. Results: We identified 143 lesions in the PZ and 82 lesions in the TZ. Among lesions found in the TZ, 57.3% were reported as probably malignant, compared to 44.7% of lesions seen in the PZ. Cancer was diagnosed in 23% of the lesions in the PZ, compared to only in 9.7% in the TZ (p<0.01). With respect to significant cancer there was a trend towards higher detection of significant cancer in the PZ (13.29% vs. 6.10% p=0.12) compared to TZ. Furthermore, lesions in the PZ with a PI-RADS score > 4 were associated with a three-fold increase in the odds of detecting cancer compared to lesions with PI-RADS < 4 (OR 3.08; CI 95% 1.29 – 7.31, p<0.011), whereas in the TZ there was no increased risk of cancer with higher PI-RADS scores (OR 1.0 CI 95% 0.20 – 4.84, p<1.0). Conclusions: To our knowledge this is the first study to address a concern regarding an increased likelihood of false positives when reporting the presence and aggressiveness of cancer in the TZ versus the PZ. This may lead to unnecessary biopsies in men undergoing MRI of the prostate.
Differential overall survival (OS) results in RECORD-3 study based on three distinct mRCC molecular subgroups classified by BAP1 and/or PBRM1 mutations.
Authors: Hsieh James , Chen David , Wang Patricia , Chen Yingbei , Marker Mahtab , Patel Parul , Chevinsky Michael , Bhanot Umesh , Pinciroli Patrizia , Berger Michael F. , Cheng Emily , Lee William , Knox Jennifer J. , Voss Martin Henner , Voi Maurizio , Motzer Robert J. 
Published: February 2017

561 Background: PBRM1 and BAP1, both of which encode chromatin modulating proteins, have recently been identified as frequently mutated tumor suppressor genes in RCC. However, their correlation with outcomes of targeted therapies is unknown. We explored correlations between overall survival (OS) and mutations in archival tumor samples from RECORD-3, a randomized phase 2 trial comparing first-line everolimus (EVE) then sunitinib (SUN) to first-line SUN then EVE at progression in 471 treatment-naïve mRCC patients (J Clin Oncol 2014; 32:2764). Methods: Somatic mutations in exons of 341 cancer related genes were identified by a next generation sequencing (NGS) assay (MSK IMPACT). Association between genotypes and OS was assessed by Cox PH models and log-rank tests. Results: DNA of 258 archival tumor and 181 matched germline samples was successfully analyzed (median coverage 530X). Three molecular subgroups Gr1 (BAP1 MT [mutant], PBRM1 WT [wild-type]/MT; 17.4%), Gr2 (PBRM1 MT, BAP1 WT; 38.4%), and Gr3 (PBRM1 WT, BAP1 WT; 44.2%) with different OS outcomes after sequential EVE-SUN or SUN-EVE were identified (Table). In the sequential EVE-SUN arm, median OS (months) was shortest with Gr1 (9.8; 95% CI, 7.8–20.0), longest with Gr2 (39.6; 95% CI, 31.7–not estimable), and intermediate with Gr3 (18.1; 13.7–30.0), whereas in the SUN-EVE arm there was no significant difference among groups. When comparing OS between treatment sequences within molecular groups, a trend suggested differences for EVE-SUN vs SUN-EVE in Gr1 (HR 1.5), Gr2 (0.8), and Gr3 (1.2), although comparisons were not statistically significant. Conclusions: Our results suggest that these genotypes may represent distinct RCC molecular subtypes with potentially different predictive/prognostic values on targeted therapies. Different treatment sequences may be considered depending on the genotypes. Clinical trial information: NCT00903175. [Table: see text]
Validation of the Decipher prostate cancer classifier for predicting 10-year postoperative metastasis from analysis of diagnostic needle biopsy specimens.
Authors: Magi-Galluzzi Cristina , Yousefi Kasra , Haddad Zaid , Palmer-Aronsten Beatrix , Lam Lucia L.C. , Buerki Christine , Li Jianbo , Kattan Michael W. , Stephenson Andrew J. , Davicioni Elai , Klein Eric A. 
Published: February 2017

59 Background: Accurate riskstratification after diagnosis of prostate cancer (PCa) is key to optimal treatment decision-making. Decipher is an extensively validated genomic classifier of metastasis after radical prostatectomy (RP). Here, we evaluate its ability to predict metastasis from analysis of prostate needle biopsy diagnostic tumor tissue specimens in a cohort of intermediate risk PCa patients treated with RP. Methods: Fifty-seven patients with available diagnostic biopsy specimens were identified from a previously reported post-RP validation study of Decipher in a cohort of 169 patients treated at Cleveland Clinic. The core with at least 1mm tumor of the highest Gleason grade was sampled and subjected to whole transcriptome analysis. Decipher was calculated based on a locked random forest model. Cox multivariable (MVA) proportional hazards model and survival c-index were used to evaluate the performance of Decipher. Results: 61% of patients had biopsy Gleason score 6 and 67% of patients had NCCN intermediate risk disease. With a median 8 years follow up, 8 patients metastasized and 3 of these patients died of PCa. Decipher had a c-index of 0.80 (95% confidence interval [CI], 0.58-0.95) compared to 0.58 (95% CI, 0.18-0.91) for biopsy Gleason score and 0.57 (0.57; 95% CI, 0.23-0.89) for preoperative PSA at 10 years post-RP for prediction of metastasis. A combined model consisting of Decipher, preoperative PSA, and Gleason score had a c-index of 0.84 (95% CI, 0.68-0.96). On MVA, Decipher was the only significant predictor of metastasis when adjusting for age, preoperative PSA and biopsy Gleason score (Decipher hazard ratio per 10% increase: 1.72; 95% CI, 1.04–2.83; P = 0.02). Conclusions: Decipher was able to predict metastatic outcome from diagnostic biopsy specimens in a cohort of primarily intermediate risk men treated with RP. This additional genomic information may help identify patients who may not be optimal candidates for active surveillance and better identify appropriate first line therapy for men with intermediate risk disease.
Detection of prostate cancer with the [68Ga]-labeled bombesin antagonist RM2 in patients undergoing radical prostatectomy.
Authors: Stephens Andrew , Loidl Wolfgang C. , Beheshti Mohsen , Jambor Ivan , Kemppainen Jukka , Bostrom Peter , Kahkonen Esa , Berndt Mathias , Mueller Andre , Minn Heikki , Langsteger Werner 
Published: February 2017

80 Background: Gastrin-releasing-peptide receptor (GRPr) is overexpressed in prostate carcinoma (PCa) and offer new means to detect prostate cancer. The bombesin derivative RM2 (DOTA-4-amino-1-carboxymethylpiperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) is a GRPr antagonist with high binding affinity (Kd 3 nM). A first-in-man study was performed to assess tumor targeting potential of [68Ga]RM2 in patients with local PCa using PET/CT. Based on promising results a Phase I/II study in local PCa was initiated. Methods: In the initial study eleven men with biopsy-proven PCa scheduled for radical prostatectomy were enrolled. The patients (pt) received an i.v. dose of 140 MBq of [68Ga]RM2 followed by dynamic imaging for at least 60 min p.i. The PET assessment included visual evaluation of [68Ga]RM2 intra-prostatic and nodal uptake as well as quantification. An ongoing Phase I/II study is designed to enroll 30+50 biopsy-positive PCa patients. The initial 30 pt have been enrolled, stratified into high, intermediate and low risk of prostate Ca recurrence as defined by NCCN criteria. Results: High uptake of [68Ga]RM2 is seen in pancreas and the urinary system with low background in the rest of the body. Despite of high bladder activity focal or multifocal intraprostatic uptake was detectable. In the first study 10 of 11 pt had positive scans. Subsector analysis of PET positivity vs. pathology yielded a sensitivity, specificity and accuracy of 89, 81, and 83%, respectively. SUVmax was measured in 14 lesions from 9 pts, classified in two groups according to postoperative Gleason score (GS). The higher GS group showed a trend toward higher SUV-values, 10.0 ± 6.7 vs. 6.2 ± 2.5 (t-test: t = -1.21, p-value = 0.28). Both of which were elevated compared to normal tissue 1.2 ± 0.8 The ongoing study is designed with a power of 95% to discriminate between the two GS groups with statistical significance (p = 0.05). Conclusions: [68Ga]RM2 is a promising new tracer with a high detection rate for PCa. Preliminary data indicates higher uptake in more aggressive cancers. The current study is assessing the diagnostic accuracy and impact of presurgical risk assessment on tumor detection in newly diagnosed PCa patients. Clinical trial information: NCT02483884.
Genetic ancestry and odds of prostate cancer diagnosis in African American and European American men.
Authors: Nyame Yaw A. , Murphy Adam , Batai Ken , Shah Ebony , Ruden Maria , Hollowell Courtney M.P. , Kajdacsy-Balla Andre , Catalona William , Kittles Rick 
Published: February 2017

86 Background: Although ethnic differences in disease incidence among African American (AA) men may reflect differences in screening behaviors and behavioral and socioeconomic factors, genetic ancestry may be a factor. This study will investigate the association between West African and Native American genetic ancestry and PCa diagnosis. Methods: We enrolled 40-79 year-old men who were undergoing prostate biopsy or routine PSA screening at outpatient urology clinics in Chicago, IL. Blood was drawn at the time of enrollment for the genotyping of 105 ancestry informative markers. West African (WAA), European (EA), and Native American (NAA) genetic ancestry was estimated using the Bayesian Markov Chain-Monte Carlo method implemented in the program STRUCTURE. Univariate analysis was performed by Wilcoxon rank-sum test for continuous variables. Unconditional binary logistic regression models were used to estimate odds ratios for the likelihood of PCa diagnosis and for the odds of having high-risk PCa relative to controls, adjusting for age, body mass index (BMI), alcohol-use, and family history of PCa. Results: 857 men were enrolled; 34.5 % were diagnosed with PCa, 50.9 % were controls and 14.6 % were men with negative prostate biopsies. AAs comprised 27% of the sample. The median was 63 years (IQR 57 – 68). Among AA men, the median genetic WAA proportion was 0.78 (IQR 0.69 – 0.83) and NAA was 0.04 (IQR 0.02 – 0.09). There was no significant difference in genetic WAA among AA men with and without PCa diagnosis (p = 0.54); however, genetic NAA was significantly lower among PCa cases (median 0.034 vs 0.057,p = 0.03) compared to controls. Among EA men, the media NAA was 0.067 (IQR (0.03 – 0.10). Similarly among EA men, genetic NAA was significantly lower among cancer cases (0.04 vs. 0.08, p < 0.001). On logistic regression, WAA ≥ 88% was associated with increased odds of PCa in AA men (OR 2.6 95% CI 1.1 – 6.7). In both AAs (OR 0.5, 95% CI 0.2 – 1.1) and EAs (OR 0.3, 95 % 0.2 – 0.6), men in the highest genetic NAA quintile had a decreased risk of PCa on logistic regression compared to men in the lowest quintile. Conclusions: Our study reveals that NAA is protective against PCa diagnosis among all men. Additionally, AA men with a high degree of WAA demonstrate an increased risk of PCa. Future work will focus on determining the association of known prostate cancer risk SNPs such as the 8q24 regions and genetic ancestry.
Early salvage versus adjuvant post-prostatectomy radiation therapy: Long-term results of a large institutional experience.
Authors: Buscariollo Daniela , Drumm Michael , Claymann Rebecca , Rodin Danielle , Galland-Girodet Sigolene , Feldman Adam S. , Dahl Douglas M. , McGovern Francis J. , Olumi Aria F. , Eidelman Alec , Niemierko Andrzej , Shipley William U. , Zietman Anthony L. , Efstathiou Jason A. 
Published: February 2017

99 Background: Randomized trials and consensus statements support consideration of adjuvant radiation therapy (ART) after radical prostatectomy (RP) for adverse pathologic features (pT3, positive margins), although its use remains low. Whether early salvage radiation therapy (ESRT) is as effective as ART remains unknown. The objective of this study was to compare outcomes after ART and ESRT. Methods: We performed a retrospective institutional analysis of 719 consecutive patients receiving post-RP RT from 1992 to 2013. ESRT was defined as RT for biochemical failure (BF) with post-RP PSA ≤ 0.5 ng/ml. All included ART and ESRT patients had adverse surgical pathologic features. Outcomes examined were freedom from BF (FFBF; rising PSA ≥ 0.2 ng/ml with subsequent confirmation), freedom from subsequent androgen deprivation therapy (FFADT), freedom from distant metastases (FFDM), and overall survival (OS). ART and ESRT were compared using multivariable analyses (MVA) with propensity score (PS) matching for pre-RP PSA, age at RT, Gleason score, pT-stage, and margin status. Results: 537 patients received salvage RT, of whom 195 received ESRT; 181 patients received ART. Median follow-up from RP was 7.0 and 8.1 years in the ART and ESRT cohorts, respectively. Median time to BF after RT was 4.4 and 4.7 years in the ART and ESRT cohorts, respectively. On MVA, ART was associated with improved 10-year FFBF (74 vs 60%, HR 0.36 [95% CI: 0.23-0.58], P < 0.0001) and 10-yr FFADT (91 vs 83%, HR 0.37 [95% CI: 0.18-0.76], P = 0.007). There were no significant differences in FFDM (96 vs 92%, HR 0.58 [95% CI: 0.19-1.7], P = 0.3), and OS (98 vs 95%, HR 1.24 [95% CI: 0.4-3.89], P = 0.7). After PS matching, ART (n = 169) remained significantly associated with improved FFBF (p < 0.0001) and FFADT (p = 0.01), compared to ESRT (n = 176). Conclusions: Post-prostatectomy RT confers excellent long-term prostate cancer control, a finding supported by the long follow-up in this series. ART is associated with improved FFBF and FFADT compared to ESRT, although there were no statistically significant differences in FFDM and OS. Optimal timing of postoperative RT further awaits the results of ongoing randomized trials.
Rehabilitation strategies following oesophageal cancer: The ReStOre trial—A feasibility study.
Authors: Guinan Emer M. , Doyle Suzanne , O'Neill Linda , O'Sullivan Jacintha , Reynolds Prof John V , Hussey Juliette M. 
Published: February 2017

176 Background: Esophageal cancer is an examplar model of complex cancer care with defined quality of life (QOL) consequences. While prognosis for this aggressive disease is poor, survival is slowly improving leading to the emergence of a unique group of cancer survivors with complex rehabilitation needs. The ReStOre trial will implement a multi-disciplinary programme to improve functional performance and QOL for esophageal cancer survivors. This pilot work examines the feasibility of the proposed intervention. Methods: This study was a single-arm feasibility study. Patients who had completed curative treatment for esophageal cancer including esophagectomy and who had node-negative post-surgical pathology received a letter of invitation to participate. The programme consisted of 12 weeks supervised and home-based exercise, dietetic counselling and education sessions from the multi-disciplinary team. Feasibility outcomes included recruitment rates, adherence, adverse events and retention. Other outcomes, including cardiopulmonary fitness (maximal cardiopulmonary exercise test and six minute walk test (6MWT)), QOL (EORTC questionnaire) and body composition (bioimpedence analysis), were assessed pre- and post-intervention. Results: Twelve participants (mean (standard deviation (SD) age 61.4 (7.29) years, 8 male) consented to participate, representing a recruitment rate of 55%. Mean class attendance was 82% and mean adherence to the home exercise programme was 118%. No adverse events occurred and all participants completed programme. Aerobic fitness improved by 3.71(2.7) ml/kg/min (19.0 ml/kg/min pre-intervention, 22.7 ml/kg/min post-intervention, p < 0.001). 6MWT distance improved by 56.3 (35.3)m (p < 0.001). Global and functional QOL scores increased while symptom scores decreased. Body composition remained stable. Conclusions: The ReStOre trial demonstrated high feasibility and acceptability in this complex cohort. Improvements in functional performance and QOL were evident without compromise to body composition. While current results are limited due to the selected population and single-arm design they will guide the design of the forthcoming larger randomised controlled trial.