bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a prognostic nomogram for progression-free and overall survival in patients with advanced renal cell carcinoma (aRCC) treated with pazopanib.
Authors: Kattan Michael W. , Sternberg Cora N. , Mehmud Faisal , Bhatt Kamalnayan , Chakrabarti Debasis , McCann Lauren , Motzer Robert John 
Published: February 2017

405 Background: Pazopanib, an oral multikinase inhibitor, demonstrated noninferiority to sunitinib in patients with aRCC in COMPARZ (NCT00720941), a randomized, phase III trial (NEJM 2013;369:722). The purpose of this study was to develop and validate prognostic nomograms based on outcome data from COMPARZ for predicting the probability of 12-month progression-free survival (PFS) and 30-month overall survival (OS) for aRCC patients who received pazopanib. Methods: Statistical modeling was performed on a dataset consisting of 557 patients from the pazopanib arm of COMPARZ. A Cox proportional hazards regression model was fit using predictors thought to be prognostic. These predictors included neutrophil count, platelet count, LDH, and alkaline phosphatase, all relative to ULN; calcium; albumin; hemoglobin; Karnofsky score; months from diagnosis to treatment; number of metastatic sites; and presence of lung, liver, and bone metastases. Data from patients on the sunitinib arm of COMPARZ and the pazopanib arm of the VEG105192 trial (NCT00334282; J Clin Oncol 2010;28:1061) were used for validation. Missing values were imputed using chained equations. For validation with the VEG105192 dataset, bootstrap-corrected estimates of discrimination and calibration were calculated following 1000 resamples. The Cox model was plotted as a nomogram. Results: Prognostic nomograms were developed and validated for predicting the probability of 12-month PFS and 30-month OS in aRCC patients based on a Cox regression model. Calibration plots suggested reasonable correspondence between predicted probabilities and actual proportions of PFS and OS. The concordance index for 12-month PFS was 0.636 with sunitinib patients and 0.635 for pazopanib patients; the concordance index was 0.692 for 30-month OS (sunitinib patients). When examining the PFS and OS nomograms, albumin, calcium, and LDH levels appeared to be the most influential predictors of outcome. Conclusions: The nomograms predict, with reasonable accuracy, treatment outcomes in patients with aRCC receiving pazopanib, based on their baseline clinical characteristics.
Toxicity analysis of lymph node irradiation for prostate cancer patients treated with IMRT.
Authors: Johnson Matthew E. , Li Tianyu , Kutikov Alexander , Buyyounouski Mark K. , Sobczak Mark L. , Viterbo Rosalia , Horwitz Eric M. 
Published: February 2017

41 Background: The radiation target for intensity modulated radiation therapy (IMRT) in high-risk prostate cancer (HRPC) includes both the prostate and seminal vesicles (SV). Inclusion of the regional lymph nodes (LN) has considerable variation in daily practice. Currently used prescriptions are 80 Gy to prostate and proximal SV, with 56Gy to the distal SV with (P/SV+LN) or without the pelvic LN (P/SV). The same P/SV prescription is used for intermediate risk prostate cancer (IRPC). We report the association between inclusion of the LN and toxicity for men treated from 2001 to 2009. Methods: 1,160 men treated for HRPC and IRPC with IMRT were identified in our clinical database. All patients had simulation with both CT and MRI, and utilized daily image guidance. Toxicity data were obtained from chart review. Statistical analysis was performed utilizing log rank test. Results: 408 patients were in the P/SV+LN group. There was no difference between the groups in regard to age, race, RT duration, or smoking. Median prescription dose was 78 Gy in both groups. Median follow-up was 44 months. A higher rate of late GI toxicity was seen in the group of patients treated to P/SV+LN (p<0.01), see Table. No difference was seen in toxicity >grade 2 for acute GU (33.1% vs. 30.2%, p=0.31), acute GI (5.9% vs. 3.5%, p=0.05), or late GU toxicity (13.7% vs. 13.0%, p=0.74) for P/SV+LN vs. P/SV alone at 5 years. MVA was performed for late GI toxicity controlling for radiation dose, length of radiation course, and use of androgen deprivation. Inclusion of LN RT remained a significant predictor of late GI toxicity (HR=2.0, p=0.02). For those with late GI toxicity, the most common symptoms were bleeding (69.5%), increased frequency of bowel movements (26.6%), fecal incontinence (15.7%), and proctitis (14.9%). Conclusions: Delivery of 56 Gy to the pelvic LN results in a significant increase in grade 2 or higher late GI toxicity with a HR of 2.0 in the setting of treatment with IMRT. A decision to treat the pelvic LN in HRPC should be weighed against the increase in late GI toxicity. [Table: see text]
Loss of BAP1 and PBRM1 protein expression and its association with clear cell renal cell carcinoma-specific survival.
Authors: Joseph Richard Wayne , Kapur Payal , Serie Daniel , Eckel-Passow Jeanette , Ho Thai Huu , Brugarolas James , Parker Alexander S. 
Published: February 2017

414 Background: While mutations in PBRM1 (~40%) and BAP1(~10%) are associated with clinical outcomes and pathologic features in clear cell renal cell carcinoma (ccRCC), the impact of protein expression of these genes remains unknown. Herein, we quantify PBRM1/BAP1 protein expression in a large cohort of patients with localized ccRCC and associate expression with cancer-specific survival (CSS) and pathologic features. Methods: We utilized the Mayo Clinic Renal Registry and identified 1,416 patients who underwent nephrectomy to treat clinically localized ccRCC between 1/3/1990 and 4/14/2009. We used immunohistochemistry (IHC) to detect PBRM1/BAP1 expression, and a central pathologist blinded to the outcomes scored tumors as either positive or negative. Tumors with heterogeneous or equivocal staining were excluded from this analysis. We generated Cox proportional hazard regression models for associations with ccRCC-SS, and we employed Mann-Whitney U tests for associations with pathologic features. Results: Of the 1,416 samples, 1,232 (87%) were PBRM1/BAP1 positive or negative, 163 (11%) had heterogeneous staining, and 21 (1%) could not be assessed. The distribution and association of PBRM1/BAP1 phenotypes with clinical outcomes are listed in the table below. PBRM1+/BAP1+ tumors have the best CSS, and PBRM1-/BAP1- have the worst. In addition, PBRM1/BAP1 expression strongly associated with the tumor size, stage, grade, and tumor necrosis (p<0.0001). Conclusions: This study is the first and largest to quantify PRBM1/BAP1 protein expression in ccRCC tumors. We were able to quantify PBRM1/BAP1 through IHC in the vast majority of tumors (87%), and PRBM1/BAP1 expression strongly associates with both CSS and pathologic tumor characteristics. Our data confirms our previous findings of the importance of PRBM1/BAP1 in the molecular pathogenesis of ccRCC. [Table: see text]
Positive surgical margins after partial nephrectomy for renal cell carcinoma: Results from Canadian Kidney Cancer Information System database.
Authors: Bansal Rahul K. , Kapoor Anil , Finelli Antonio , Rendon Ricardo A. , Moore Ronald Brian , Breau Rodney H. , Lacombe Louis , Kawakami Jun , Drachenberg Darrel E , Black Peter C. , Pautler Stephen E. , Liu Zhihui , Tanguay Simon 
Published: February 2017

420 Background: Partial nephrectomy (PN) is the standard of care for small renal masses (SRMs) whenever feasible. The occurrence of a positive surgical margin (PSM) on a pathological specimen is not uncommon and an ideal management is unknown. We conducted this study to examine the rate of PSM, predictors of PSM and their oncological outcomes after PN for renal cell carcinoma (RCC), using the Canadian Kidney Cancer information system (CKCis) database. Methods: We accessed the prospectively maintained CKCis database for 1066 patients who underwent PN for RCC in major academic centers all across Canada. Demographics, clinical, pathological and follow-up data were noted for patients with PSM and negative surgical margins (NSM). Multivariate logistic regression analysis was performed to assess predictors of PSM. Results: Out of 1066 patients, 59 (5.5%) had PSM, 928 (87%) had NSM and records of 79 (7.4%) patients were not available. Mean patient age was 61 years and 59 years in the PSM and NSM group respectively, and in each group 63% of the patients were males. Mean tumor size was 3.6cm (range 1.1 – 9.5) and 3.3cm (range 0.5 – 16.2) in PSM and NSM group respectively. PSM group had 5 (8%) grade 1, 28 (47%) grade 2, 16 (27%) grade 3 and 5 (8%) grade 4 tumors as compared to 127 (14%), 458 (50%), 207 (23%) and 27 (3%) respectively in NSM group. Four (6.7%) patients from the PSM group and 49 (5.3%) patients from the NSM group had local and/or systemic progression of disease. There were two cancer specific deaths in NSM group and none in PSM group. Fifty two (88%) and 861 (93%) patients were alive at mean follow-up of 18.5 (range 0 – 91.7) and 28.9 months (range 0 – 315.5) in PSM and NSM group respectively. For the multivariate logistic regression analysis; Fuhrman grade 4 predicted presence of PSM whereas age, operative technique, tumor size, tumor stage did not. Conclusions: Results from the CKCis database suggest that PSM after PN are common but does not result in adverse oncological outcomes. Presence of Fuhrman grade 4 may be associated with PSM on final pathological specimen.
Interpreting first-line options in mRCC: A look into the German RCC-registry.
Authors: Goebell Peter J. , Mueller Lothar , Overkamp Friedrich , Lueck A. , Vogt Michele , Marschner Norbert 
Published: February 2017

429 Background: During the last few years, several efficacious therapeutic options have been developed for patients with metastatic renal cell carcinoma (mRCC). Due to the variety of multiple new targeted therapeutic options evidence based solely on randomized clinical trails is lacking. Registry data represents an important supplement providing insight into the treatment course and evidence on various outcomes. However, results provided by registry data may be influenced by many factors such as patient characteristic and comorbidities. Matched-pair analyses provide an interesting tool to compare different treatment options. Material & Methods: Over 100 oncology and urology outpatient centers in Germany are actively participating in this registry. The enrolment of the first 1000 mRCC patient data-sets with a maximum follow-up of three years has recently been completed. Among other information, data on patient and tumor characteristics, all systemic antineoplastic treatments, dosages, as well as response rates, progression free survival and overall survival are documented. Results: At the start of systemic therapy mean age were 66.2 years for male and 69.0 years for female patients, respectively. For all patients at least one comorbidity was indicated (Charlson Comorbidity Index 1.0). More than 94% of patients had metastases at inclusion. Investigating the most prominent TKIs used in sequential treatment in the registry, we identified time from initial diagnosis to treatment start as one of the most important factors predicting overall survival. Surprisingly, when controlling for this factor in a matched-pair analysis together with age, gender and risk, outcome in terms of progression-free survival appears to be similar in first line treatment with either Sunitinib or Sorafenib. Conclusions: Registry data can provide missing pieces of evidence on treatment outcomes. The registry demonstrates once more its hypothesis generating character and thus adds to the body of evidence as established from clinical trials. A direct comparison of efficacy can only be provided by clinical trails whereas registry data represent effectiveness of real-life treatment.
Prognostic impact of C-reactive protein (CRP) in metastatic prostate cancer (MPC): A systematic review and meta-analysis.
Authors: Naik Gurudatta , Morgan Charity , Rocha Pedro Filipe Simoes da , Templeton Arnoud J. , Pond Gregory Russell , Sonpavde Guru 
Published: February 2017

43 Background: Serum C-reactive protein (CRP), a marker of inflammation, appears to demonstrate a prognostic impact in small studies of metastatic prostate cancer (MPC). We conducted a meta-analysis to better quantitate its prognostic impact. Methods: A systematic review was conducted to identify publications and presentations exploring the association of baseline serum CRP and overall survival (OS) in MPC, both castration-sensitive and castration-resistant. The hazard ratio (HR) and 95% confidence interval (CI) with P values were pooled. HRs were selectively extracted from multivariable analyses. Estimates of HRs were weighted and pooled using the generic inverse variance and random-effect models. Heterogeneity among trials was assessed using Cochrane’s Q statistic and the I2 statistic was used to quantify inconsistency among trials. The assumption of homogeneity was considered invalid for P<0.1. All statistical tests were two-sided, and P<0.05 was considered significant Results: Six studies comprising 659 evaluable patients were eligible. The first authors were Prins (N=119), Pond (N=112), Ito (N=80), Nakashima (N=126), Beer (N=160), and McArdle (N=62). The Nakashima and McArdle studies evaluated castration-sensitive men, while the remaining four studies evaluated castration-resistant men receiving docetaxel-based chemotherapy. The primary endpoint was OS except the McArdle study, which used cancer specific survival. All HRs were derived from multivariate analyses except the Pond study, which was a bivariate analysis. Men with higher CRP had significantly worse OS than those with lower CRP (HR = 1.42, P<0.001, 95% CI: 1.17 to 1.73; I2 = 72.6%, p = 0.003). In trials of castration-sensitive men receiving hormonal therapy, high CRP yielded a HR = 1.92 (P=0.005, 95% CI: 1.22 to 3.03; I2 = 0). In castration-resistant men receiving chemotherapy, high CRP yielded HR=1.35 (p=0.003, 95% CI: 1.11 to 1.65; I2 = 79%), P for subgroup difference=0.20. Conclusions: This meta-analysis suggests a strong prognostic impact for CRP on OS in men with both castration-sensitive and castration-resistant prostate cancer. Prospective validation is justified, given the affordability, ready availability and large dynamic range of CRP.
Surgeons’ preferences and practice patterns regarding intra-operative frozen section during partial nephrectomy.
Authors: Sidana Abhinav , Donovan James , Gaitonde Krishnanath 
Published: February 2017

436 Background: Intra−operative frozen section (FS) evaluation for tumor margin during partial nephrectomy (PN) is a matter of controversy in urologic oncology. We evaluate the preferences and practice patterns of urologists regarding intra−operative FS during PN. Methods: A 17 item questionnaire was designed to collect information on surgeons’ preferences and practice patterns regarding FS during PN. The survey was sent to the members of the Society of Urologic Oncology and the Endourological Society. Univariate and multivariate logistic regression analysis was done to identify the predictors determining the preferences. Results: 197 responses were received. 69% and 58% of respondents chose to obtain FS (always or sometimes) during Open Partial Nephrectomy (OPN) and Laparoscopic Partial Nephrectomy (LPN) respectively. There was a strong correlation between surgeons’ preferences during OPN and LPN. Younger surgeons are less likely to obtain FS during OPN (p<0.05). For surgeons who did not routinely obtain FS, “confidence about complete resection” was the most common reason (79%), followed by “no change in management with positive margins” (35%). Majority (75%) believed the margins to be negative if surgical margin was free of tumor microscopically by one cell layer. Older surgeons considered negative margins to be free of tumor microscopically by >= 5mm. Surgeons who performed more than 25 PNs annually were less likely to fulgurate the tumor bed after resection (p=0.025) while more likely to send an additional specimen from tumor bed for FS analysis (p=0.007). 54% and 42% of respondents would repeat FS for positive microscopic margins during OPN and LPN respectively. 95% of the respondents would not recommend additional treatment for positive margins on final pathology. Conclusions: Despite recent literature pointing to low clinical utility of intraoperative FS analysis, more than half of the surgeons still opt for intraoperative FS. Surgeon’s age and volume influence preferences and practice pattern in regards to FS analysis to some extent. Fellowship training, surgical approach and region of practice do not appear to dictate a surgeon’s preferences in regards to intra-operative FS during PN.
EVERSUN: A phase II trial of everolimus alternating with sunitinib as first-line therapy for advanced renal cell carcinoma (aRCC) (ANZUP trial 0901).
Authors: Davis Ian D. , Long Anne , Martin Andrew , Espinoza David , Yip Sonia , Kichenadasse Ganessan , Thompson Jennifer F. , Harrison Michelle L. , Lowenthal Raymond M. , Pavlakis Nick , Azad Arun , Kannourakis George , Steer Christopher , Goldstein David , Shapiro Jeremy David , Stockler Martin R. ,   Australian & New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: February 2017

438 Background: We hypothesized that alternating inhibitors of the VEGFR and mTOR pathways would delay the development of resistance in aRCC. Methods: Single-arm, two-stage, multicenter, phase II trial to determine the activity, feasibility, and safety of sunitinib 50mg daily 4 weeks (wk) on / 2wk off, alternating with everolimus 10mg daily for 5 wk on / 1 wk off. Participants had aRCC of MSKCC good or intermediate risk. Primary endpoint: proportion alive and free of progression at 6 months (PFS6m). Secondary endpoints included feasibility, tumour response, overall survival (OS), and adverse events (AE). Imaging was done every 6 wk till wk 24, then q12wk. Planned sample size of 55 allowed distinction between a PFS6m rate of ≤64% versus ≥84% with type 1 and type 2 error rates of 5%. Results: We recruited 55 eligible participants from Sept 2010 to Aug 2012: mean age 61, male 71%, good risk 16%, intermediate risk 84%. Feasibility: 80% could start cycle 2 within 14 weeks; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 wks of any treatment. Efficacy: PFS6m was 29/55 (53%; 95% CI: 40%-66%). The OR rate was 7/55 (13%; 95% CI 4%-22%, all partial). After a median follow-up of 20 months, 47 of 55 had progressed with a median PFS of 8 months (95% CI: 5 to 10), and 30 of 55 had died with a median OS of 17 months (95% CI: 12 to undefined). Safety: AEs were consistent with those expected for each single agent. The most common grade 3 or 4 AE (number of participants) were hypertension (13), anaemia (9), oral mucositis (7), fatigue (n=7), GGT increase (n=6), pain (n=5), and platelet count decreased (n=5). Conclusions: The EVERSUN regimen was feasible and safe, but its activity did not meet prespecified values to warrant further research. This study supports the current approach of continuing first line anti-VEGF therapy until progression or prohibitive toxicity before switching to another drug. EVERSUN is an ANZUP Cancer Trials Group Ltd. trial coordinated by the NHMRC Clinical Trials Centre (ACTRN12609000643279). Clinical trial information: ACTRN12609000643279.
Phase II trial of neoadjuvant axitinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma.
Authors: Karam Jose A. , Devine Catherine E , Urbauer Diana L , Lozano Marisa , Ahrar Kamran , Tamboli Pheroze , Tannir Nizar M. , Wood Christopher G. 
Published: February 2017

441^ Background: Previous studies have shown minimal impact of tyrosine kinase inhibitors on primary renal tumors. In this phase II trial, we investigate the safety and role of the axitinib in downsizing tumors in patients with non-metastatic clear cell renal cell carcinoma (RCC) prior to surgical resection. Methods: Patients with clinical stage T2-T3b N0 M0 biopsy-proven RCC were eligible for this study. Patients received axitinib daily for 12 weeks prior to surgery. The primary outcome was objective response rate. Secondary outcomes included safety, tolerability, feasibility of administration of axitinib and quality of life (using FKSI-15). A dedicated radiologist independently reviewed all CT scans to evaluate for response using RECIST. Results: Twenty-four patients were treated between 2011 and 2013. All patients had biopsy-proven clear cell RCC. Twenty-three patients continued axitinib for 12 weeks, and underwent surgery as planned without delay. One patient stopped treatment before 12 weeks due to adverse events (AEs) and was taken to surgery early. Median reduction of primary renal tumor size was 28.3% (range 5.3-42.9%). Eleven patients (45.8%) experienced a partial response by RECIST, and 13 patients had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. No grade 4 AEs were observed. Intraoperatively, no complications or unusual bleeding were encountered. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted, while no grade 4 or 5 complications occurred. FKSI-15 did change over time (p < 0.0001), with quality of life worsening in comparison to the screening assessment by week 7 (p = 0.0004). However, by week 19, quality of life was not found to be statistically different from screening (p = 0.3344). Conclusions: Axitinib was clinically active and well tolerated in the neoadjuvant setting in patients with locally advanced non-metastatic ccRCC. Clinical trial information: NCT01263769.