bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in terms of progression-free survival (PFS) and overall survival (OS) in patients treated with first-line sorafenib, sunitinib, and pazopanib for late relapsing (>5 years) renal cell carcinoma.
Authors: Santoni Matteo , Porta Camillo , Procopio Giuseppe , Cerbone Linda , Basso Umberto , De Giorgi Ugo , Rizzo Mimma , Ortega Cinzia , Massari Francesco , Iacovelli Roberto , di Lorenzo Giuseppe , Milella Michele , Sabbatini Roberto , Atzori Francesco , De Vivo Rocco , Berardi Rossana , Santini Daniele , Cascinu Stefano 
Published: February 2017

421 Background: Aim of this retrospective study was to investigate the clinico-pathological features and the outcome of patients (pts) with late relapsing renal cell carcinoma (LateR-RCC) treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) as first line therapy. Methods: Data were collected from 19 Italian centers involved in the treatment of metastatic RCC. Late relapse was defined as >5 yr after initial radical nephrectomy. MSKCC prognostic categories were assessed before starting first-line treatment with VEGFR-TKI. Overall survival (OS) and progression free-survival (PFS) were estimated with the Kaplan-Meyer method with 95% CI and curves were compared with log-rank test. A Cox-regression model was applied to the data with a univariate and multivariate approach. Variables included in the univariate analysis were gender, age, time from surgery, MSKCC risk-group and targeted therapy employed at first line. Results: A total of 2,490 pts were screened and 269 pts (11%) were identified as LateR-RCC and treated with first-line VEGFR-TKI. Median age was 66 yr (range 29-87). Median time to recurrence was 7.9 yr. MSKCC prognostic category was good in 63% of pts, intermediate in 31% and poor in 6%. First-line therapy consisted of sunitinib in 190 pts (71%), sorafenib in 58 pts (21%) and pazopanib in 21 pts (8%). The median PFS was 20.0 months (95% CI 17.0−25.1) for sunitinib and 14.1 months for both sorafenib (95% CI 11.0−29.0) and pazopanib (95% CI 11.2−NR). At multivariate analysis, only MSKCC prognostic group was an independent prognostic factor for OS (HR: 2.07; 95% CI, 1.52–2.82 p < 0.001) and PFS (HR 2.54; 95% CI, 1.93−3.36 p < 0.001), whereas first line TKI was not significantly associated with OS (HR: 0.94; 95% CI, 0.38–1.82 p = 0.895) and PFS (HR 0.77; 95% CI, 0.43−1.99 p= 0.547). Conclusions: No significant differences were found in terms of OS and PFS in pts with LateR-RCC treated with first-line sorafenib, sunitinib or pazopanib. Our data may be considered in the long-term management of these patients.
A single-arm, phase II, multicenter trial of sunitinib maleate (SU) in locally advanced or metastatic pheochromocytoma/paraganglioma (PC/PG): Interim results.
Authors: Leibowitz-Amit Raya , Joshua Anthony Michael , Ezzat Shereen , Bourdeau Isabelle , Olney Harold , Oosting Sjoukje , Ruether Joseph D. , Chin Soo , Palmieri Cristina , Seah Jo-An , Assa Sylvia L , Krzyzanowska Monika , Knox Jennifer J. 
Published: February 2017

431 Background: Metastatic PC/PG is rare and may be sporadic or have a genetic basis. Treatment remains challenging in the absence of well-controlled randomized trials. Case reports suggest clinical activity of SU in this setting. We aim to prospectively evaluate radiological and biochemical response to SU, and assess its toxicity profile in PC/PG. Methods: This is an ongoing single-arm, phase II, multicenter, investigator-initiated clinical trial, enrolling patients (pts) with metastatic or unresectable locally advanced malignant PG or PC with ECOG PS 0-2, no previous treatment with tyrosine kinase inhibitors, and evidence of radiological progression or disease-related symptoms. All pts receive 50mg SU daily at standard dosing, following blood pressure stabilization, and are assessed for radiological and biochemical response (with urine metanephrines, catecholamines or serum chromogranin A) q12 weeks until disease progression, unacceptable toxicity or pts withdrawal. Futility was defined as no documented responses within the first 14 patients and would have led to trial cessation. Results: Since May 2009, 14 pts enrolled in 3 academic hospitals (Canada and the Netherlands). Interim results of 10 pts are presented (pts characteristics are tabulated). Two pts had symptoms related to hormonal-excess and both had clinical improvement on SU. All 10 pts had biochemical evidence of hormonal excess, of which 5 had biochemical response (50%). Best radiological responses achieved were partial response (3/10 pts; 30%, 1 unconfirmed), stable disease > 3 months (6/10; 60%) and progressive disease (1/10; 10%). Adverse events were consistent with known side-effects of SU. Seven pts had toxicity-related dose reductions, contributing to treatment cessation in two. Conclusions: This trial surpassed the pre-specified futility stopping rule with the current documented responses on SU and with durable patient benefit seen. Updated data will be presented and discussed. Clinical trial information: NCT00843037. [Table: see text]
Phase I trial of sunitinib (S) and temsirolimus (T) in metastatic renal cell carcinoma (mRCC).
Authors: Campbell Matthew T. , Millikan Randall E. , Altinmakas Emre , Xiao Lianchun , Tannir Nizar M. 
Published: February 2017

433 Background: Anti-VEGF agents and mTOR inhibitors are mainstay therapies in mRCC. Pre-clinical data suggests synergistic anti-tumor effect when combining these 2 classes. A previous phase I trial using sunitinib (S) 25 mg/d 4 wks on, 2 wks off, and temsirolimus (T) 15 mg/wk was stopped after 2 of the first 3 pts developed dose limiting toxicity (DLT). Methods: Pts with any subtype mRCC (PS 0-1) were eligible. Each cycle consisted of daily S for 14 days on, 7 days off, and weekly T. The continuous reassessment method (CRM) was used. The primary objective was to find the maximum tolerated doses (MTD) of S and T. The total planned accrual was 60 pts. Results: Accrual was stopped after 20 pts received study drugs. Median age was 63.5 years; 13 pts received prior targeted therapy, 7 pts were treatment naïve; median number of prior treatments 1 (range 0-6). Treatment cohorts (#pts, S, T, dose in mg): 2 (S12.5,T6), 1 (S25,T12.5), 1 (S12.5,T8), 8 (S12.5alt25,T9), 2 (S25,T6), 2 (S25alt37.5,T6), 2 (S37.5,T6), 2 (S37.5,T8). Dose reduction was required in 6 of 20 pts; the most common DLT was mucositis in 3 of 20 pts, followed by thrombocytopenia in 2 of 20 pts. The mean number of cycles for all pts was 6.6±5.36, with mean time on study 159±120 days. One pt experienced DLT in cycle 1 and received no study related imaging, 1 had a partial response, 16 pts had stable disease, and 2 pts had progressive disease (PD) as best response. A total of 21 grade 3/4 adverse events (AEs) attributed to drug occurred in 11 of 20 pts. Reasons for study discontinuation were PD in 12 pts, toxicity in 6 pts, and pt preference in 2 pts. There were no treatment related deaths. Conclusions: The MTD of S and T using the CRM were not reached due to premature trial closure. However, we believe S 37.5 mg/d, 2 wks on, 1 wk off, and T 8-10 mg weekly may well be close to MTD. Clinical trial information: NCT01122615.
Contemporary outcomes of pT3 renal cell carcinoma: A Canadian multi-institutional experience.
Authors: Nayak Jasmir , Gardiner Clare , Liu Zhihui , Tanguay Simon , Kapoor Anil , Finelli Antonio , Rendon Ricardo A. , Black Peter C. , Klotz Laurence , Moore Ronald Brian , Kawakami Jun , Breau Rodney H. , Drachenberg Darrel E 
Published: February 2017

434 Background: A large, multi-institutional analysis was undertaken to examine the pathological and oncological outcomes for patients with pT3 renal cell carcinoma (RCC) treated surgically. Materials and Methods: Institutional databases on patients surgically treated for RCC were obtained from 14 centers across 6 Canadian provinces forming the Canadian Kidney Cancer Information System (CKCis) database. Data were collected on 2204 patients and included patient characteristics, peri-operative information, pathological and oncological outcomes. Results: Of the 2,204 patients, 498 (22.6%) patients had pT3 disease according to the 2009 TNM staging system. Mean pathological tumor size was 8.6 cm. 443 (89.0%) patients underwent a radical nephrectomy (RN) and 55 (11.0%) underwent a partial nephrectomy (PN). Of those treated with RN, 247 (55.8%) were open, 159 (35.9%) laparoscopic and 1 (0.2%) robotic. In the PN group, 37 (67.3%), 14 (25.5%) and 4 (7.3%) patients were treated open, laparoscopic and robotically, respectively. Average operative time was 184 mins, with an average blood loss of 650 cc. Of the pT3 lesions, 365 (73.3%) were pT3a, 97 (19.5%) pT3b and 12 (2.4%) pT3c. 109 (22%) patients had a metastatic diagnosis before or at the time of nephrectomy. Of the remaining 389 patients, 68.9% remained free of disease after a median follow-up of 1.3 years. Common sites of metastatic disease included lung, lymph nodes and bone (77%, 35%, and 25%, respectively). Clear cell RCC was the predominant histopathology (74%). There were no peri-operative (<30 days) mortalities. Complications were found in 14.1% of patients. Systemic therapy was initiated in 132 (26.5%) of patients, most commonly with Sunitinib in 106 (80%) patients. Conclusions: Locally advanced, pT3 renal cell carcinoma is an aggressive disease that is associated with high rates of metastatic disease. Despite this, a significant portion remained disease free at the time of our follow-up.
Circulating microRNAs associated with docetaxel-resistant castration resistant prostate cancer.
Authors: Horvath Lisa , Lin Hui-Ming , Castillo Lesley , Mahon Kate Lynette , Chiam Karen , Lee Brian Yong , Nguyen Quoc , Qu Wenjia , Boyer Michael J. , Stockler Martin R. , Pavlakis Nick , Marx Gavin M. , Hiriyanna Gowda Girish Mallesara , Gurney Howard , Clark Susan J. , Swarbrick Alex , Daly Roger J. 
Published: February 2017

44 Background: Despite a range of new treatments, docetaxel (DTX) remains the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, only 50% of patients respond to docetaxel at the cost of potentially significant toxicity. Therefore, there is a need for new biomarkers to identify early response to therapy. This study aims to determine if circulating microRNAs are associated with DTX chemotherapy outcome in CRPC. Methods: Global microRNA profiling was performed on DTX-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards measured the levels of 46 candidate microRNAs in plasma/serum from 97 CRPC patients, collected pre- and three weeks post-cycle one of DTX. Responses were defined by the PCWG1 serum prostate-specific antigen (PSA) response criteria; partial response (PR), stable disease (SD), progressive disease (PD). Multiple T-test, Mann-Whitney U, Kaplan-Meier, Receiver Operating Characteristic (ROC), and Cox regression analyses were used to assess the associations between microRNA levels and clinical outcomes. Results: Eighteen microRNAs were associated with PSA response or overall survival (p<0.05). DTX non-responders (PD+SD) and patients with shorter survival had high pre-DTX levels of miR-200 family members (miR-200a, miR-200b, miR-200c, miR-429; p<0.05), or decreased/unchanged post-DTX levels of miR-17 family members (miR-19b, miR-20a, miR-20b; p<0.05). The combined levels of miR-20a, miR-146a, miR-200b, miR-200c, miR-222, and miR-301b predicted PSA response (ROC AUC 0.74, 95% CI 0.64-0.84). Pre-DTX miR-200a levels (HR 3.0, 95%CI 1.6-5.8; p=0.001) and post-DTX change in miR-20a (HR 3.4, 95%CI 1.8-6.3; p=0.0002) were independent predictors of overall survival when modeled with hemoglobin levels (HR 2.6, 95%CI 1.4-5.1; p=0.02), PSA response (HR 2.1, 95%CI 1.1-3.9; p=0.03), and visceral metastases (HR 2.0, 95%CI 1.1-3.5; p=0.03). Conclusions: Circulating microRNAs are potential early predictors of DTX chemotherapy outcome and may be useful in stratifying patients in future clinical trials. These microRNAs may also be involved in DTX resistance and represent potential therapeutic targets.
Cell cycle progression score to predict metastatic progression of clear cell renal cell carcinoma after resection.
Authors: Askeland Eric J. , Chehval Vincent A. , Askeland Ryan W. , Sangale Zaina , Gangnang Fosso Placede , Xu Nafei , Rajamani Saradha , Stone Steven , Brown James A. 
Published: February 2017

442 Background: Clear cell renal cell carcinoma (ccRCC) is primarily treated surgically when organ confined, but requires close follow-up to evaluate for recurrence. Expression levels of cell cycle progression (CCP) genes have prognostic value in certain cancers. We evaluated the prognostic value of the CCP expression in surgically resected ccRCC. Methods: Medical records were retrospectively reviewed. Patients with metastasis or lymph node involvement at surgery were excluded. Cases developed metastasis within 5 years of resection; controls were followed for at least 4.5 years without recurrence. Specimens were re-reviewed by a single pathologist. Tumor FFPE slides were macrodissected and RNA extracted. CCP score, sex, age, T stage, Fuhrman Nuclear grade (FNG), tumor size, smoking status, lymphovascular invasion (LVI), and time to metastasis were available for analysis. Univariate and multivariate analyses were used to evaluate association with metastatic progression. Subsequently, the tumor transcriptome was interrogated for other informative biomarkers using next-generation sequencing (NGS). Funding was by Myriad Genetics. Results: Twenty-six cases and 38 controls were evaluated. Median time to metastasis was 1.68 years (IQR 1.06-3.69) for the case group. Median follow-up was 6.69 years for controls. Univariate analysis revealed that LVI (OR 4.64, p=0.005), FNG (OR 4.16, p=0.0099) and CCP score (OR 2.65, p=0.0091) were significantly associated with progression to metastasis. In multivariate analysis, age (p=0.026), tumor size (p=0.022) and CCP score (p=0.026) were statistically significant. A step-wise multivariate model including age, CCP, tumor size and LVI had an AUC of 0.84, which decreased to 0.78 if CCP score was excluded. CCP scores calculated by qPCR and NGS were correlated (rho = 0.91). However, no other genes showed a significant association with metastasis or TNM stage (after correcting for multiple testing) in univariate analysis or after adjusting for CCP score. Conclusions: The cell cycle progression score predicts metastatic progression after resection of ccRCC and appears to add significant prognostic information to standard clinical and pathological variables.
A pilot study of supraphysiologic testosterone (T) and oral etoposide (E) in men with castrate-resistant prostate cancer (CRPC).
Authors: Schweizer Michael Thomas , Antonarakis Emmanuel S. , Wang Hao , Spitz Avery N. , Cao Haiyi , Pacheco Alberto , Eisenberger Mario A. , Carducci Michael Anthony , Denmeade Samuel R. 
Published: February 2017

45 Background: Prostate cancer (PC) cells become resistant to chronic castration via an adaptive increase in androgen receptor (AR) expression, a liability that can be exploited therapeutically. Mechanistically, supraphysiologic androgens can induce PC cell death through topoisomerase 2 (topo2) mediated double-strand DNA breaks and disruption of DNA relicensing due to persistence of AR at origins of replication during the cell cycle. Methods: We evaluated parenteral T in combination with the topo2 inhibitor E in men with CRPC and low metastatic burden (≤5 bone and <10 soft tissue metastases). To rapidly cycle from supraphysiologic (>1500 ng/dL) to near castrate T levels, men received intramuscular T cypionate 400 mg on day (D) 1 and oral E 100 mg D 1-14 of a 28 D cycle. After 3 cycles, men with declining PSA could continue T alone every 28 D. The primary endpoint was PSA response, defined as a PSA below baseline, after cycle 3. Secondary endpoints included objective response rates and safety. Results: Sixteen men enrolled of which 14 completed 3 cycles of T+E and were evaluable for response. 7/14 went on the T-only expansion stage. After 3 cycles, 6/14 men had a PSA response. 7 (50%) had a PSA response at any timepoint [4 (29%) had PSA declines ≥50%] (table). In men with RECIST-evaluable disease, 2 had progressive and 3 had stable disease (SD), 4 had partial (PR) and 1 had a complete response (CR). Median response duration was 248 D (range, 80 to 359 D). Post T, 10/12 men had a PSA decline to subsequent androgen ablative therapies. Most adverse events (AEs) were ≤grade 2 and considered effects of E. One man died from neutropenic sepsis before completing the 1st cycle. AEs possibly related to T included lower extremity edema (n=1), priapism (n=1) and asymptomatic pulmonary embolism (n=2). No one developed new pain on T. Conclusions: T with or without E demonstrated preliminary efficacy in patients with CRPC as manifested by PSA and objective responses. This regimen is generally safe. Cyclic T-based therapies warrant further study. Clinical trial information: NCT01084759. [Table: see text]
Validation of the CAIX score as a prognostic biomarker for lymphatic spread and cancer-specific survival.
Authors: Chamie Karim , Said Jonathan W. , Belldegrun Arie S. , Pantuck Allan J. 
Published: February 2017

454 Background: We recently developed a novel CAIX density scoring system that was found to be a significant prognostic biomarker in a cohort of patients with high-risk clear cell renal cell carcinoma (ccRCC). We sought to validate the association of CAIX score with lymphatic spread and survival in a cohort of patients with ccRCC. Methods: We reviewed the clinical and pathologic records of 418 patients who underwent radical nephrectomy at UCLA between 1985 and 1999. Clinical features included age, gender, race/ethnicity, and ECOG performance status. Pathologic features included TNM stage, nuclear grade, UCLA Integrated Staging System (UISS), and CAIX staining. CAIX score was stratified into low (0–99), intermediate (100–199), and high (200–300). We examined the association between the CAIX score, disease severity, and survival using logistic and Cox regression analyses, respectively. Results: Mean CAIX score was 237.4 (SD 98.3). Approximately 26% of patients with low CAIX scores had lymphatic involvement, compared with 28% of those with intermediate scores, and 8% with high scores, p<0.01. On multivariate analysis, patients with high CAIX scores had a significantly lower risk of lymphatic involvement (OR 0.19, p<0.01). When compared with those with low CAIX scores, patients with high CAIX scores were significantly less likely to recur (HR 0.53, p=0.02) or die (HR 0.41, p<0.01). Patients with intermediate scores were no less likely to recur HR 0.93, p=0.85) or die of their disease (HR 0.69, p=0.34). Lastly, patients with high-risk non-metastatic ccRCC were less likely to recur (HR 0.04, p<0.01). Conclusions: The CAIX score can help identify the majority of patients presenting with lymphatic spread and serves as a statistically significant prognostic biomarker for recurrence-free and disease-free survival after nephrectomy. We recommend that utility CAIX score be quantified for all patients with high-risk disease.
Trends in cytoreductive nephrectomy in the eras of immuno and targeted therapy.
Authors: Minnillo Brian J. , Zhu Hui , Maurice Matthew J. , Abouassaly Robert 
Published: February 2017

472 Background: Since the publication of randomized studies demonstrating a survival advantage in patients with metastatic renal cell carcinoma (mRCC) treated with immunotherapy, cytoreductive nephrectomy (CN) has played an integral role in the management of these patients. Our objective is to describe the use of CN in the eras of immuno and targeted therapy for mRCC. Methods: Using the National Cancer Data Base (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, we identified patients with histologically confirmed mRCC. We examined patient, provider and disease factors associated with CN. We also assessed short-term surgical outcomes of CN. A multivariable logistic regression was used to evaluate factors associated with CN. Results: From 1998 to 2011, 30.1%(17,714) of the 58,810 patients with mRCC underwent CN (Table). Over this timeframe, there was a gradual increase in the proportion undergoing surgery (17.3% to 35.7%). In those who underwent CN, the mean length-of-stay (LOS) was 6.1 days. The 30-day readmission rate and 30-day mortality were 5.6% and 3.8%, respectively. On multivariate analysis, patients who were treated at an academic facility (OR 1.94, 95% CI 1.79-2.11, p <.0001) were more likely to be treated with CN. After adjusting for covariates, patients of African American race (OR 0.52, 95% CI 0.48-0.56, p <.0001), a tumor size of >14cm (OR 0.57, 95%CI 0.52-0.62, p<.0001), or a Charlson/Deyo score of ≥ 2 (OR 0.62, 95% CI 0.57-0.68, p < .0001) were less likely to be treated surgically. Conclusions: Cytoreductive nephrectomy for mRCC appears to be steadily increasing over time, particularly in academic medical centers, even after adjusting for potential confounders. Despite this population’s advanced disease, LOS, 30-day readmission rate and 30-day mortality are relatively low. Our results suggest that CN utilization remains high in the era of targeted therapy. [Table: see text]
Bilateral multifocal papillary type I renal cell carcinoma: Clinical characteristics and association with chronic renal insufficiency.
Authors: Su Daniel , Okoro Chinonyerem , George Arvin , Linehan W. Marston , Metwalli Adam R. 
Published: February 2017

482 Background: Patients with bilateral multifocal (BMF) RCC are at risk for multiple surgeries, progressive loss of renal tissue and chronic renal insufficiency. Although BMF papillary type I RCC is commonly associated with Hereditary Papillary Renal Cell Carcinoma (HPRC), with mutation of the MET proto-oncogene, sporadic (non-familial) BMF Pap1 RCC is far more common. Here we describe the histologic and clinical phenotype as well as clinical management of a population of patients with BMF RCC that has papillary type I histology that is distinct from the HPRC population. Methods: From 2000 to 2013, patients who were evaluated at the National Cancer Institute and were diagnosed with BMF on cross sectional imaging were included. Patients who tested negative for MET proto-oncogene mutation, who have a pathologic diagnosis of papillary type I were included. Phenotypic manifestations and clinical management were analyzed. Results: 61 patients with an average age of 54.3 years were identified. A disproportionate number (22, 36%) of these patients were of African American descent. Fifty seven (93%) were male. Two patients were found to have had metastatic disease on presentation (3%); 17 patients underwent unilateral radical nephrectomy for renal mass (28%) even though the average largest tumor diameter was only 2.9 cm. 12 patients (19%) underwent partial nephrectomy. The average preoperative serum creatinine was 1.48 mg/dl and average eGFR 62.2 ml/min, there was no difference between in eGFR in African American patients and Caucasian patients (62.09 ml/min and 63 ml/min). This population had an average of 2 tumors per side, many patients also had numerous cysts on both kidneys. Conclusions: BMF papillary type I RCC represents a novel entity which disproportionally affects African Americans. These patients often present with renal insufficiency and are at significant risk for further renal deterioration. As a small percentage of these patients with BMF papillary type I will present with metastatic disease, active surveillance until the largest renal tumor reaches 3 cm is recommended.