bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of PD-1 and PD-L1 protein expression in matched primary and metastatic renal cell carcinoma tumors.
Authors: Rini Brian I. , Yearly Jennifer , Dhakal Hari , Przybycin Christopher 
Published: February 2017

418 Background: Therapy targeting programmed death (PD)-1 and PD-L1 proteins has activity in metastatic renal cell carcinoma (mRCC). Expression of these proteins on tumor and infiltrating immune cells is associated with a higher response to drugs inhibiting this pathway. However, these associations have been made based on primary tumor expression, while therapy is directed against metastatic deposits. Methods: Patients with mRCC and metastases (all clear cell; 3 with sarcomatoid changes) who had undergone resection of both the primary and at least one metastatic tumor were included. Samples were evaluated for PD-1 and PD-L1 expression by immunohistochemistry using anti-PD-1 clone NAT105 and Merck proprietary anti-PD-L1 clone 22C3. Stained sections were scored for PD-1 and PD-L1 using a semi-quantitative 0 to 5 scale (0 = negative, 1 = rare, 2 = low, 3 = moderate, 4= high, 5 = very high). PD-1 expression was limited to cells with lymphoid morphology, PD-L1 expression was evaluated for both tumor and non-tumor (inflammatory, endothelial) cells. Linear regression analysis was performed to assess significance of correlations. Results: Fifty matched primary and metastatic RCC tissue sets were analyzed with 48 evaluable matched pairs. PD-1 score greater than 3 (considered positive) was detected in 9 primary tumors (18%) and 9 metastatic sites (18%). PD-L1 score greater than 3 was detected in 9 primary tumors (18%) and 12 metastatic sites (24%). There was a correlation between PD-1 scores for primary and metastatic pairs (R2=0.194; p<0.002) and between PD-L1 scores for primary and metastatic pairs (R2=0.319; p<0.0001). There was an association between PD-1 score and PD-L1 score for primary tumors (R2=0.513; p<0.0001) and for metastatic sites (R2=0.449; p<0.0001). For PD-1 score, there were 10 pairs (21%) in which either the primary or metastatic site score was ≥3, but the matched pair was < 3. For PD-L1 score, there were 9 pairs (19%) in which either the primary or metastatic site score was ≥3, but the matched pair was < 3. Conclusions: The expression of PD1 and PD-L1 in primary clear cell RCC tumors is correlated with metastatic site expression, although there are a substantial percentage of tumors with discordance.
Temporal trends in the management of localized prostate cancer: From 2004 to 2011.
Authors: Gray Phillip John , Lin Chun Chieh , Jemal Ahmedin , Efstathiou Jason Alexander 
Published: February 2017

42 Background: The management of localized prostate cancer (PC) is evolving. We sought to analyze recent management trends using a large national database. Methods: Data on patients presenting with a new diagnosis of PC between 2004 and 2011 were extracted from the National Cancer Data Base. Patients with nodal or distant metastases were excluded. Patients were categorized as low risk (LR), intermediate risk (IR) or high risk (HR) according to the National Comprehensive Cancer Network’s (NCCN) guidelines. Multivariate logistic regression was performed to identify factors associated with the receipt of surgery or radiotherapy. Results: 823,977 patients met the study criteria; 38.5% were LR, 42.7% IR and 18.9% HR. Between 2004 and 2011, for LR patients, rates of observation after diagnosis increased from 12.4% to 18.5% and receipt of radical prostatectomy (RP) increased from 40.3% to 54.4% (p for trend both <.001). In contrast, receipt of brachytherapy decreased from 24.4% to 11.4% and receipt of external beam radiation therapy (EBRT) decreased from 18.2% to 13.4% (p both <.001). For IR patients rates of observation increased from 6.1% to 7.3% and RP from 48.1% to 58.5% (p both <.001) while receipt of brachytherapy decreased from 12.1% to 6.4% (p <.001) and receipt of EBRT plus androgen deprivation therapy (ADT) fell from 14.7% to 8.7%. For HR patients, receipt of RP increased from 30.6% to 41.3% (p < .001) while receipt of EBRT plus ADT decreased from 30.4% to 28.0% (p <.001). On multivariate analysis factors predicting for a lower odds of receiving RP vs. radiotherapy (p all <.001) included black race (OR 0.52 vs. white), lack of insurance or insurance through Medicaid (OR 0.66 and 0.50 vs. private insurance) and residing in low income level areas (OR 0.85 for areas in the lowest national quartile vs. the highest). Conclusions: Utilization of radical prostatectomy for patients with localized PC increased significantly across risk groups from 2004 to 2011 while utilization of radiotherapy decreased. Rates of observation have increased in LR disease but remain low overall. Markers of poor socioeconomic status appear associated with receipt of radiotherapy. Further work is needed to elucidate the causes and appropriateness of these trends.
Randomized phase II trial of sunitinib four-week on and two-week off versus two-week on and one-week off in metastatic clear cell type renal cell carcinoma: RESTORE trial.
Authors: Lee Jae-Lyun , Kim Min Kyoung , Park Inkeun , Ahn Jin-Hee , Lee Dae Ho , Ryoo Hun-Mo , Song Cheryn , Hong Bum-Sik , Hong Jun Hyuck , Ahn Hanjong 
Published: February 2017

427 Background: Standard sunitinib schedule, 4-week on followed by 2-week off (schedule 4/2), is associated with troublesome toxicities, and maintenance of sunitinib dose intensity has been challenging, especially in patients with Asian ethnicity. To determine the efficacy and safety of an alternative dosing schedule, 2-week on and 1-week off (schedule 2/1), we conducted a randomized phase II study. Methods: Treatment-naïve patients ≥18 years with clear cell type, mRCC were randomly assigned 1:1 to schedule 4/2 or schedule 2/1 after stratification for MSKCC risk group. The primary endpoint was failure-free survival (FFS) at 6 months. Results: From November 2007 to February 2014, 76 patients were enrolled (38 to schedule 4/2 and 38 to schedule 2/1). Two patients in schedule 4/2 were later found to be ineligible due to brain metastases and excluded from the analysis. FFS at 6 months was 44% in schedule 4/2 and 63% in schedule 2/1. Patients with schedule 2/1 were treated for a median of 7.7 months (95% CI, 3.0-12.3) of initial assigned schedule, while patients with schedule 4/2 were treated for a median of 5.7 months (95% CI, 5.0-6.5) (HR=0.54, 95% CI, 0.32-0.91, p=0.021). Seven patients in the schedule 4/2 crossed over to the schedule 2/1. Neutropenia (all grade 61% vs. 37%; grade 3-4 28% vs. 11%, p=0.0368) and fatigue (all grade 83% vs. 58%, p=0.0167) were more frequently observed with schedule 4/2. There is a strong tendency of lower incidence of mucositis (all grade, 86% vs.71%, p=0.116), and hand-foot syndrome (grade 3-4, 33% vs. 18%, p=0.143) and rash (all grade, 56% vs. 34%, p=0.0648) with schedule 2/1. Eighteen patients (ORR, 47%) in the schedule 2/1 achieved a partial response (PR) while one patient had a complete response and 11 patients had a PR (ORR, 36%, 95% CI) in the schedule 4/2. With a median follow-up duration of 47 months, the median time-to-progression was 15.1 months in the schedule 2/1 and 10.1 months in the schedule 4/2 (HR=0.69, 95% CI, 0.39-1.20). Conclusions: Sunitinib given with the schedule 2/1 is associated with less toxicity and longer FFS than the schedule 4/2 without compromising the efficacy in terms of ORR and PFS (NCT00570882). Clinical trial information: NCT00570882.
Surgical management for local retroperitoneal recurrence after radical nephrectomy in the targeted therapy era.
Authors: Thomas Arun Z. , Adibi Mehrad , Borregales Leonardo , Hoang Ly N , Tamboli Pheroze , Matin Surena F. , Karam Jose A. , Wood Christopher G. 
Published: February 2017

431 Background: Isolated local retroperitoneal recurrence (RPR) after radical nephrectomy (RN) for renal cell carcinoma (RCC) poses a therapeutic challenge. We examined the role of aggressive surgical resection of localized RPR in the modern era of targeted therapy for metastatic RCC. Methods: We retrospectively reviewed clinico-pathological data of patients from our RCC database from 2004-2014. We identified 67 patients with localized RPR after radical nephrectomy (RN) who underwent surgical resection. We assessed patient demographics, clinical and pathological features, location of RPR, perioperative complications and outcomes, recurrence free, cancer-specific and overall survival. Results: Median follow up after RPR resection was 33 months (range 3-120). Median recurrence free survival after RPR was 20 months (range 1-120). One, 3 and 5-year cancer specific survival was 95% 77% and 50%, respectively. Neoadjuvant and salvage targeted therapy were administered in 29 (43.3%) and 28 (41.8%) patients, respectively. Multivariate analysis identified that pathological tumor stage and nodal stage at nephrectomy, maximum diameter of RPR mass and abnormal lactate dehydrogenase levels were associated with an increased risk of cancer specific death. Patients with 0, 1, and greater than 1 adverse risk factors demonstrated cancer specific survival of 100%, 74%, 50% at 3 years and 100%, 57%, 19% at 5 years. Conclusions: This study is the largest series of patients to undergo RPR resection in the targeted therapy era. We found that clinic-pathological factors at the time of nephrectomy as well as RPR resection are important prognosticators. Aggressive surgical resection offers potential cure in a substantial number of patients with RPR.
Impact of statins and survival outcomes in patients with metastatic renal cell carcinoma.
Authors: McKay Rana R. , Lin Xun , Albiges Laurence K. , Fay Andre Poisl , Kaymakcalan Marina Dusevic , Mickey Suzanne S , Ghoroghchian Paiman Peter , Bhatt Rupal Satish , Simantov Ronit , Choueiri Toni K. , Heng Daniel Yick Chin 
Published: February 2017

435 Background: A growing body of evidence has demonstrated the antineoplastic activity of statins. The objective of this study was to investigate the impact of statin use on survival in patients with metastatic renal cell carcinoma (mRCC) treated in the modern therapy era. Methods: We conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Statistical analyses were performed using Cox regression adjusted for age, sex, race, histology, prior therapy, body-mass index, and other known prognostic factors and the Kaplan-Meier method. Results: We identified 4,736 patients treated with sunitinib (n=1,059), sorafenib (n=772), axitinib (n=896), temsirolimus (n=457), temsirolimus + interferon-alpha (n=208), bevacizumab + temsirolimus (n=393), bevacizumab + interferon-alpha (n=391), or interferon-alpha (n=560), of whom 511 were statin users. Overall, statin users demonstrated a statistically significant improvement in overall survival (OS) but not progression-free survival (PFS) compared to non-users (OS: 25.6 versus 18.9 months; p=0.015; adjusted hazard ratio [aHR] 0.787; 95% CI, 0.648-0.955; PFS: 7.9 versus 6.9 months; p=0.823, aHR 1.018; 95% CI, 0.867-1.196). When stratified by therapy type, a benefit in OS was demonstrated in statin users compared to non-users in individuals receiving therapy targeting vascular endothelial growth factor (28.4 versus 22.2 months, p=0.023; aHR 0.749; 95% CI, 0.584-0.961) or mammalian target of rapamycin (18.6 versus 14.0; p=0.035; aHR 0.657; 95% CI, 0.445-0.972), but not in those receiving interferon-alpha (15.6 versus 14.8 months; p=0.410; aHR 1.292; 95% CI 0.703-2.275). Adverse events were similar between statin users and non-users. Conclusions: In the largest RCC analysis to date, we demonstrate that statin use improved survival outcomes in patients with mRCC treated in the targeted therapy era. Statins could represents a potential adjunct therapeutic option for patients with metastatic RCC; however, this hypothesis needs to be corroborated with preclinical work exploring the mechanisms underlying their anti-cancer effects and well-designed clinical trials investigating the clinical benefits of adding statins to modern therapies.
Active surveillance in asymptomatic or minimally symptomatic renal cell carcinoma: Retrospective analyses of a cohort of three oncological centers from Spain.
Authors: Jove Maria , Etxaniz Olatz , Sala Nuria , Font Albert , Jimenez Colomo Laura , Saigi Maria , Recalde Sabela , Navarro-Perez Valentín , Barretina Ginesta Maria Pilar , Ochoa de Olza Maria , Mulet Nuria , Garcia del Muro Xavier 
Published: February 2017

441 Background: Some patients (pt) with metastatic renal cell carcinoma (mRCC) have an indolent course. Treatment toxicities can worsen quality of life. Active surveillance (AS) in paucisymptomatic pts is an option often used but few data is available. Our aim is to analyze the impact of initial AS in a sequential therapy strategy in terms of overall survival (OS). Methods: Data frompt diagnosed with mRCC from January 2005 to December 2013 in 3 centres of Spain were retrospectively analyzed. AS subgroup was defined as pt with ≥6 months (m) between diagnosis and first-line (L) treatment (tto) start. A descriptive analysis and median OS (mOS) were performed comparing pt with or without AS (AS vs. tto <6m). OS curve and medians were estimated using Kaplan Meier Method. A multivariate cox regression analyses with different prognostic factors was also realized. Results: From a cohort of 277 pt with mRCC, 69 pt (25%) were on initial AS and 208 pts on tto <6m (75%). Median time on observation until systemic tto was started on pt on AS was 14 m 95%CI (17.6-26.02). Pt characteristics of AS vs tto <6 m were: median age 63/60; males 70/72%; histology: 94/76% clear cell, 3/12% papillar, 0/4% chromophob; M1 at diagnosis: 22/48%; prognosis (Heng risk criteria): 0/17.% poor, 38.5/57% intermediate, 61.5/25% good; prior nephrectomy: 93/73%; number of metastatic locations (loc): 87/68% ≤2 loc, 12.5/32.5% ≥3 loc; lines of treatment: first L 46/53%, second L 38/23%, and third L 16/24%. When comparing exposure in months to each tto L, pt on AS had longer period of tto in second L (10.06/4.14 m, p=0.014). mOS were: 62 m 95%CI (52.97-71.03) vs. 22 m 95% CI (19.87-24.12) for AS/tto <6 m respectively (p<0.001) with statistical significance after multivariate analysis (Cox regression, HR=0.39; 95% CI, 0.25-0.63). Factors that independently influence on OS were: ≥2 M1 sites and papillar histology, negatively, and prior nephrectomy and >1 year from diagnosis to M1, positively. Conclusions: Our results suggest that AS before starting first L of tto is not a detrimental action in a selected population of mRCC pt with good risk characteristics allowing them to remain free of therapy’s toxicity during a long time period.
Twenty-year trends in survival for metastatic kidney cancer.
Authors: Macleod Liam Connor , Holt Sarah , Wright Jonathan L. , True Lawrence D. , Tykodi Scott S. , Lin Daniel W. , Gore John L. 
Published: February 2017

454 Background: Since the 1990s, the therapies for metastatic renal cell carcinoma (mRCC) expanded from immunotherapies to survival-extending targeted therapies. Targeted therapy is most efficacious in clear cell RCC. Trial results likely overestimate population norms. Population-based studies on histologically limited cohorts omit a large proportion of patients, giving an overly optimistic prognosis. To clarify the changing prognosis of mRCC we examine a heterogeneous RCC cohort from the Surveillance Epidemiology and End Results (SEER) registry. Methods: mRCC patients were identified from SEER diagnosed calendar years 1990-2009. Cases were primary renal tumors confirmed by histology/cytology, not diagnosed on autopsy. Survival was analyzed by treatment era (cytokine 1990-2005, targeted 2006-2009) and classified by histology. Multivariate Cox regression identified factors independently associated with overall survival (OS). Results: Of 14,521 mRCC patients identified, clear cell mRCC represented 4,136 (median OS 12 months). Non-clear cell RCC represented 10,385 cases (median OS 4 months) of which 8,860 were designated NOS. For clear cell mRCC unadjusted median OS improved from 11 to 14 months pre/post targeted era (p<0.001). For non-clear cell mRCC there was no improvement pre/post targeted era (p=0.56). However, when RCC NOS was removed, median OS improved slightly from 6 to 7 months pre/post targeted era (p<0.001). On multivariable analysis cases diagnosed 2006-2009 were associated with improved OS compared to 1990-2005 (HR 0.90, 95% CI 0.86, 0.94). Female gender (HR 1.06 95%CI 1.02-1.10), unmarried status (HR 1.12 95%CI 1.08-1.15), non-receipt of surgery (HR 1.46, 95%CI 1.44-1.49), T3/4 primary tumor (HR 1.25, 95%CI 1.18-1.32), and higher grade (HR 1.43, 95%CI 1.25-1.63) were also significantly associated with decreased OS. Conclusions: Median mRCC OS in SEER in the targeted therapy era is lower than survival reported in clinical trials, but has improved. These discrepancies are likely related to variation in the availability of optimal treatment strategies including cytoreductive nephrectomy and biopsy-based implementation of targeted therapies in a heterogeneous health care delivery environment.
Efficacy of targeted therapies after PD1/PD-L1 inhibitors in metastatic clear cell renal cell carcinoma (mRCC): A multi-institution retrospective cohort.
Authors: Albiges Laurence , Fay Andre Poisl , Xie Wanling , McDermott David F. , Heng Daniel Yick Chin , Dariane Charles , De Velasco Guillermo , Lester Renee Elizabeth , Escudier Bernard , Choueiri Toni K. 
Published: February 2017

456 Background: Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors showed activity in mRCC and are currently in development in first-line and previously treated patients (pts). Whether these drugs will modify efficacy of subsequent targeted therapy (TT) including VEGFR tyrosine kinase inhibitors (TKI) or mTOR inhibitors is unknown. Methods: Medical records of RCC patients treated with investigational PD-1 or PD-L1 inhibitors who received subsequent treatment with TT were reviewed in 4 institutions. Baseline characteristics at the time of subsequent therapy and outcome data including time to treatment failure (TTF), best response, 1 and 2 year overall survival (OS) were retrospectively collected. Results: Of 89 pts who received PD-1/PD-L1 inhibitors, 56 patients (M/F 39/17, clear-cell 53, IMDC good 3/intermediate 16/poor 11/unknown 26) have received a subsequent therapy after PD-1/PD-L1 blockade, while 7 patients are still on therapy and 26 patients did not receive subsequent therapy. Among these 26 patients, 12 died from disease and 14 are still alive off-systemic therapies. 43 pts received VEGFR TKI and 13 received mTOR inhibitors as first subsequent TT. Median follow up from start of the subsequent TT is 16.1 months (range: 0.2, 30.6 months). TT post PD-1/PD-L1 was administered as second line in 9 patients (16%), third line in 24 patients (43%), > fourth line in 23 patients (41%). Median TTF was 6.9 months (range: 0.2+, 23.0), and was 6.9 and 5.7 months in patients who received VEGFR TKI and mTOR inhibitors respectively. One-year and 2-year OS from the initiation of subsequent TT was 58% (95% CI: 41-72%) and 36% (95% CI: 18%-54%), respectively. Investigator-assessed best response to subsequent TT was evaluated in 53 out of 56 patients: PR (n=7, 13%), SD (n=33, 62 %), and PD (n=13, 25%). Conclusions: This is the first report of TT efficacy after PD-1/PD-L1 inhibition. In this selected population, median TTF suggests a sustained benefit of both VEGFR TKI and mTOR inhibitors after PD-1/PDL1 inhibition.
Clinical outcome of patients with metastatic renal cell carcinoma who interrupted VEGFR-TKI after achieving stable disease or better response.
Authors: Koo Dong Hoe , Park Inkeun , Lee Jae-Lyun , Ahn Jin-Hee , Lee Dae Ho , You Dalsan , Jeong In Gab , Song Cheryn , Hong Bum-Sik , Hong Jun Hyuck , Ahn Hanjong 
Published: February 2017

459 Background: The purpose of the this study is to evaluate the clinical outcome of VEGFR-TKIs interruption in patients with metastatic renal cell carcinoma (mRCC) after achieving stable disease (SD) or better response. Methods: A retrospective analysis of medical records and imaging studies was performed on all patients with mRCC treated with VEGFR-TKIs between January 2008 and July 2014 (n=505). Patients who achieved SD or better response under VEGFR-TKI and later discontinued VEGFR-TKIs for any reason with the exception of disease progression were included in the analysis. Outcomes analyzed were progression free survival (PFS) after VEGFR-TKIs discontinuation, patterns of disease progression, time to subsequent therapy (TST), response to VEGFR-TKI resumption, and time to treatment failure (TTF) after TKI resumption. Results: We identified 32 patients (sunitinib=20, sorafenib=7, and pazopanib=5). The responses to VEGFR-TKIs were CR (n=4), PR (n=11), SD (n=15), and controlled but non-measurable (n=2). Median time to interruption from the initiation of VEGFR-TKI therapy was 16.6 months (95% CI, 12.8-20.3). The main causes of VEGFR-TKI interruption was toxicity (n=19, 59.4%), will to have treatment holiday (n=7, 21.8%), patient’s refusal (n=3, 9.4%), and others (n=3, 9.4%). At the time of analysis, 16 patients had disease progression and 1 patient was dead. With a median follow-up duration of 56.6 months (range, 12.6-167.4), median PFS from VEGFR-TKI interruption was 23.8 months (95% CI, 12.5-35.0), and the median TST was 26.2 months (95% CI, 15.9-36.6). The progression was observed in pre-existing lesions in 7 patients (43.7%) or new lesions developed in 9 (56.3%). Among 11 patients who received VEGFR-TKI resumption, 2 patients (18.2%) achieved a PR and the stable disease was observed in 9 (81.8%) with a median TTF of VEGFR-TKI resumption of 6.2 months (95% CI, 4.0-8.4). Conclusions: In patients with mRCC controlled with VEGFR-TKIs, VEGFR-TKI could be interrupted at least temporarily when clinically warranted.
Open partial nephrectomy with modified technique: Comparison to results from contemporary laparoscopic series.
Authors: Voegeli Thomas Alexander , Demming Richard 
Published: February 2017

473 Background: To evaluate the surgical and oncological outcome of patients undergoing a modified procedure of open partial nephrectomy which was done with a new technique leaving out selective suturation of renal calices and vessels. Methods: We analyzed 120 consecutive open partial nephrectomies (2005-2010) which were performed with a modified technique at a mid-volume center. This technique included the use of an absorbable non-woven textile consisting of polyglycolic acid, extra-large needles and argon plasma coagulation. The surgical and oncological outcome was evaluated by statistical analysis of the medical records. Results: The mean patient age was 62.8 years (52.6% male). Mean pathological tumor size was 3.0 cm (± 1.4 cm), 53.3% of the tumors were renal cell carcinoma. The mean operative time was 101.7 minutes (±33.6 min) and the mean blood loss was 283.9 ml (±368.5 ml). Ischemia was performed in 23.1% with a mean warm ischemia time of 13.3 minutes ( ± 6.4 min). The operative complication rate was 1.7 %. Topical hemostatic agents were used in 20.2 %. The most frequent postoperative complications were bleeding (5%), pleural effusion (4.2%), urinoma (2.5%), pneumonia (2.5%), wound infection (2.5%) and acute renal failure (2.5%). Five-year cancer specific survival rate was 94.1%. Conclusions: The modified technique of open partial nephrectomy can be performed with high surgical and oncologic safety. Duration of the procedure and ischemia time are short. Due to the rare use of hemostatic agents, the costs can be reduced. Open partial nephrectomy with this technique achieve better results than reported from contemporary reported laparoscopic series, especially regarding warm ischemia and time needed for surgery.