bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intraoperative conversion from partial to radical nephrectomy: Predictive factors and outcomes.
Authors: Petros Firas G. , Keskin Sarp K. , Yu Kai-Jie , Fellman Bryan M. , Metcalfe Michael J. , Matin Surena F. , Karam Jose A. , Wood Christopher G. 
Published: March 2017

483 Background: Predictive risk factors for intraoperative conversion from partial to radical nephrectomy (RN) are poorly quantified. We evaluated preoperative predictors of conversion in a cohort of patients undergoing planned partial nephrectomy (PN). Methods: A prospectively maintained database was reviewed to identify patients who were scheduled to undergo (open, laparoscopic, or robot-assisted) PN that were converted to RN between 1990 and 2015. Reasons for conversion were collected from the operative report. Patient demographics and perioperative variables were evaluated including body mass index (BMI), tumor size, nephrometry score, hilar tumors, procedure type, intraoperative complications, and oncologic outcome. Results: A total of 2298 patients underwent successful PN. The rate of conversion to RN was 4% (n=99) patients. The median patient age was 60 years and median BMI was 30 kg/m2. The median American Society of Anesthesiologists (ASA) score was 3 and median Charlson Comorbidity Index (CCI) was 2. The median tumor size for the converted cases was 4.5 cm (1.0-10.1) and median nephrometry score was 9. Histology was clear cell-RCC in 79% of the tumors. A total of 30 patients had completely endophytic tumors. The most common reasons for conversion were hilar/renal sinus extension of the renal mass in 38 (38%) patients, positive surgical margin on frozen section or gross assessment in 27 (27%) patients, insufficient renal remnant in 27 (27%) patients, and excessive intraoperative bleeding in 7 (7%) patients. RN was performed open in 79, laparoscopically in 9, and robot-assisted in 11 cases. Intraoperative complications occurred in 1 (1%) patient underwent an attempted robot-assisted PN resulted in an injury to a major renal artery branch requiring conversion to RN. Patients were followed up for a median of 33 months. In the converted cohort, evidence of disease at last follow-up was found in 13 (13%) patients. Conclusions: The rate of conversion to RN was low in patients undergoing PN in this series. The most common reason for conversion was hilar/renal sinus extension of these complex renal masses while positive surgical margin and insufficient renal remnant were contributing equally at lower rates.
Is RECIST-defined progression free-survival a meaningful endpoint in the era of immunotherapy?
Authors: Johal Sukhvinder , Santi Irene , Doan Justin , George Saby 
Published: March 2017

488 Background: Progression-free survival (PFS) is often used as a primary endpoint in oncology clinical trials as a surrogate for overall survival. Traditionally, the Response Evaluation Criteria in Solid Tumors (RECIST) have defined disease progression as a significant increase in the size of tumor lesions and the development of new lesions. However, some patients starting immunotherapy have shown initial increased size of tumor lesions followed by tumor regression, due to the unique mechanism of action of immunotherapies. This initial “pseudo-progression” could be classified inaccurately as disease progression, as evidenced by benefit from the treatment beyond progression approach ( JAMA Oncol 2016). The phase III CheckMate 025 trial of nivolumab versus everolimus in patients with advanced renal cell carcinoma allowed treatment beyond progression if there was investigator-assessed clinical benefit and tolerability. The purpose of our study was to test if treatment duration for an immunotherapy was different from RECIST-defined PFS, and as such, could potentially explain the apparent lack of correlation between RECIST progression and overall survival shown in CheckMate 025. Methods: Using 1-year data from CheckMate 025, Kaplan–Meier methodology was used to estimate the median duration of PFS and time to treatment discontinuation (TTD). Stratified log-rank test was used to assess the difference in treatments. Results: For all patients, the median PFS with nivolumab was 4.6 months (95% CI, 3.7–5.4 months) and median TTD was 6.2 months (95% CI, 5.6–7.7 months). For everolimus, the median PFS was 4.4 months (95% CI, 3.7–5.5 months) and median TTD was 3.9 months (95% CI, 3.7–4.6 months). Conclusions: Patients in CheckMate 025 had significantly longer survival with nivolumab than with everolimus, but with similar PFS. Our analysis demonstrated that while PFS was similar to TTD with everolimus, there was a significant difference between the 2 measures for nivolumab, suggesting that RECIST-defined PFS may not be the proper endpoint to define progression for immunotherapies. Further evaluation of the association of TTD and other immune-related progression endpoints with overall survival is warranted. Clinical trial information: NCT01668784.
Real world experience of immuno-oncology agents in metastatic renal cell carcinoma: Results from the IMDC.
Authors: Yip Steven , Wells Connor , Moreira Raphael Brandao , Wong Alex , Srinivas Sandy , Beuselinck Benoit , Porta Camillo , Sim Hao-Wen , Ernst D. Scott , Rini Brian I. , Yuasa Takeshi , Basappa Naveen S. , Kanesvaran Ravindran , Wood Lori , Soulieres Denis , Canil Christina M. , Kapoor Anil , Fu Simon Yuen Fai , Choueiri Toni K. , Heng Daniel Yick Chin 
Published: March 2017

492 Background: Immuno-oncology (IO) checkpoint inhibitors have demonstrated efficacy in metastatic renal cell cancer (mRCC) treatment. Real world data is required to assess outcomes when applied to the general population. Methods: A retrospective analysis was performed using the IMDC database. It included mRCC patients treated with IO agents, including atezolizumab (Atezo), avelumab, ipilimumab, nivolumab (Nivo), and pembrolizumab (Pembro). Some patients were treated with combination therapy with a targeted agent. Patients may have received IO therapy as first-, second-, third-, or fourth-line treatment. Overall survival (OS), treatment duration, and overall response rates (ORR) were calculated. Results: 255 patients with mRCC treated with IO therapy were included. The ORR to IO therapy in those patients who were evaluable was 29% (32% first-, 22% second-, 33% third-, and 32% fourth-line therapy). Patients treated with second-line IO therapy were divided into favorable, intermediate, and poor risk using IMDC criteria; the corresponding median OS rates were not reached, 26.7 mo, and 12.1 mo, respectively (p<0.0001). Conclusions: Response rates to IO therapies appear to remain consistent no matter which line of therapy it is used in. Within second-line treatment, IMDC criteria appear to stratify patients appropriately into favorable, intermediate, and poor risk groups. Survival data are premature and will be updated. In contrast to Nivo clinical trial data, where median treatment duration was 5.5 mo, longer treatment length is observed in real world practice. [Table: see text]
Proton pump inhibitors (PPIs) and survival outcomes in patients with metastatic renal cell carcinoma (mRCC).
Authors: Lalani Aly-Khan A. , McKay Rana R. , Lin Xun , Simantov Ronit , Kaymakcalan Marina D. , Choueiri Toni K. 
Published: March 2017

493 Background: PPIs are potent inhibitors of gastric acid secretion and can affect the bioavailability of orally administered cancer targeting therapies, such as vascular endothelial growth factor tyrosine-kinase inhibitors (VEGF-TKIs). Smaller preclinical and clinical studies have attempted to assess the interaction between VEGF-TKIs and PPIs in patients with advanced cancers; however, these studies are limited and larger analyses from rigorous datasets have been lacking. We investigate the impact of PPI use on survival in patients with mRCC treated with oral VEGF-TKIs. Methods: A pooled analysis of mRCC patients treated on phase II and III clinical trials was conducted. The primary outcome was to assess overall survival (OS) between PPI users, defined as patients receiving a PPI at baseline, compared to non-PPI users. Secondary outcomes included progression-free survival (PFS), objective response rates (ORR), and adverse events. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method. Results: Our cohort consisted of 2,188 patients treated with sunitinib (n = 952), axitinib (n = 626), or sorafenib (n = 610), of whom 120 were PPI users. Overall, PPI users demonstrated similar OS compared to non-PPI users (median 24.1 vs. 21.3 months, adjusted hazard ratio [aHR] 1.051, 95% confidence interval (CI) 0.769-1.438, p = 0.754). Similarly, PFS (5.5 vs. 8.0 months, aHR 1.016, 95% CI 0.793-1.301, p = 0.902) and ORR (23.3% versus 27.4%, p = 0.344) were not different between PPI users and non-users. These findings were consistent across International mRCC Database Consortium risk groups and by line of therapy. Adverse events were also similar between both groups. Conclusions: In this analysis, we demonstrate that PPI use does not appear to negatively impact the efficacy of VEGF-TKIs in mRCC patients treated in the targeted therapy era. Given the current landscape expanding to include more self-administered treatments, documentation of concomitant medications, and patient education on potential drug interactions are critical for optimizing the utilization of oral cancer targeting therapy.
Correlations between tumor-infiltrating and circulating lymphocyte subpopulations in mRCC patients treated with immune-checkpoint inhibitors.
Authors: Bersanelli Melissa , Gnetti Letizia , Vaglio Augusto , Sverzellati Nicola , Campanini Nicoletta , Galetti Maricla , Incerti Monia , Varotti Elena , Parziale Raffaele , Corrado Michele , Bottarelli Lorena , Azzoni Cinzia , Rapacchi Elena , Caruso Giuseppe , Cosenza Agnese , Ferri Leonarda , Silini Enrico Maria , Leonardi Francesco , Buti Sebastiano 
Published: March 2017

494 Background: In clinical trials with immune-checkpoint inhibitors (CKI), histological features such as tumor-infiltrating lymphocites (TILs) are investigated as potential predictive biomarkers, with the possible limit of an outdated parameter for a typically dynamic element. Methods: This explorative study compared, in metastatic renal cell carcinoma (mRCC) patients, basal pathological data about TILs on diagnostic histological specimens with circulating lymphocyte subpopulations measured before and during therapy with nivolumab, with the primary aim to assess their concordance. Secondarily, with the limit of a small sample size, a possible relation with treatment outcome was explored. Results: Of 11 mRCC patients, 5 had low presence of TILs (L-TILs), 3 moderate amount (M-TILs), and 3 high number (H-TILs). Overall, 8 patients had low intratumoral pathological CD4+/CD8+ ratio (LIPR) ≤ 1 and 3 cases high intratumoral pathological ratio (HIPR) ≥ 2. Of 8 patients with LIPR, only 2 cases matched with low circulating CD4+/CD8+ ratio (LCR) ≤1, whilst 5 cases had high circulating ratio (HCR) ≥ 2 (1 undetermined). All 3 cases with HIPR (≥ 2) conversely had LCR (≤ 1). Unexpectedly, independently from the clinical outcome, circulating CD4+/CD8+ ratio remained unchanged during therapy with CKI in each patient, maintaining the same value after 8 weeks (mean -0.12). The respective percentage values of CD4+ and CD8+ circulating T cells also remained stable during treatment (mean variation 0%); the absolute value of CD4+ was more likely to increase (mean +46.3/mm3); the level of CD8+ tended to slightly decrease (mean -6.5/mm3). No correlation of lymphocyte subpopulations with treatment outcome was found. Conclusions: Of note, this study did not evidence any correspondence between histopathological and circulating findings in terms of T-lymphocyte subpopulations in mRCC patients undergoing treatment with CKI, also suggesting the inconsistency of circulating data in terms of relative variations. Considering the likely high dynamism of TILs, rebiopsy before CKI therapy might be the most reliable way to assess the utility of TILs characterization for predictive purpose.
Second line axitinib in metastatic renal cell carcinoma: Evaluation of prognostic factors influencing outcome.
Authors: Brooks Helen , Challapalli Amarnath , Reed Hannah , Masson Susan , Hilman Serena , Bahl Amit 
Published: March 2017

495 Background: Axitinib has been approved for 2nd line treatment in the UK for patients with advanced renal cell carcinoma on the basis of the AXIS study, which showed improved progression free survival (PFS) and a trend towards overall survival (OS) benefit. There is no randomised data to support the use of Axitinib after first line Pazopanib. Hence, we compared the efficacy of Axitinib after first line Pazopanib or Sunitinib. The influence of Heng prognostic risk score (HPRS) at initiation of Axitinib, previous nephrectomy, and haemoglobin (Hb) rise during Axitinib treatment on outcome was also evaluated. Methods: Thirty one patients were commenced on Axitinib between May 2013-May 2016. Patient demographics, laboratory parameters, and survival data were collected retrospectively. Data were analysed in October 2016, which served as a censor date for patients who were alive. Analysis of PFS and OS was performed by Kaplan-Meier estimates and log-rank test. Results: All 31 patients received axitinib as 2nd line treatment. At the time of analysis, 14 patients were alive and 7 remained on axitinib. The prognostic factors influencing outcome are shown in the table. Conclusions: There was no significant difference in PFS or OS regardless of first line treatment, supporting the use of axitinib post pazopanib or sunitinib. Prior nephrectomy, and favourable HPRS significantly predict better PFS and OS. The impact of Hb rise needs further validation in a larger cohort.[Table: see text]
Perinephric white adipose tissue inflammation in clear cell renal cell carcinoma (ccRCC).
Authors: Furberg Helena , Hakimi A. Ari , Gucalp Ayca , Iyengar Neil M. , Williams Samantha , Petruzella Stacey , Tennenbaum Daniel M. , Samson Marguerite , Mannino Nicole , Giri Dilip D. , Zhou Xi K. , Russo Paul , Dannenberg Andrew J. 
Published: March 2017

507 Background: High body mass index (BMI) is an established risk factor for developing ccRCC but is associated with better survival in clinical studies. The obesity paradox may be influenced by metabolically healthy patients classified as obese, and metabolically unhealthy patients classified as normal weight. We evaluated white adipose tissue inflammation (WATi) in perinephric fat as a new marker of metabolic dysregulation and examined its association with clinicopathological characteristics. Methods: In July 2015, we established a prospective cohort study at Memorial Sloan Kettering Cancer Center to investigate the prognostic significance of perinephric WATi among patients undergoing nephrectomy. Perinephric WAT is collected during surgery and patients are followed for clinical outcomes. WATi is defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS) and detected through immunohistochemistry. Clinicopathological data are abstracted from the electronic medical record. Wilcoxon rank-sum, Chi-square, or Fisher’s exact tests describe the relationship between CLS status and clinicopathological characteristics on the first 38 ccRCC patients. Results: The study cohort had a median age of 56 years (range 47-64 years) and was predominantly male (71%). CLS were detected in 50% of patients, did not differ by age or sex, and were present in all BMI levels; 59% of obese, 38.5% of overweight, and 33% of normal weight patients (p = 0.47). CLS was significantly associated with advanced disease characteristics including higher stage (p = 0.03) and local invasion (p = 0.02). Median tumor size was larger in patients who were CLS+ (3.5 cm, range 2.65-5.75) than CLS- (2.2 cm, range 1.55-3.00; p = 0.02). Conclusions: Perinephric WATi was found in ccRCC patients of all BMI levels and associated with factors related to poor prognosis. Patients with occult inflammation may be at higher mortality risk, regardless of their BMI. Recruitment of additional cases and analyses to examine how CLS influences ccRCC survival are on-going.
Predictors of mortality in metastatic papillary renal cell cancer.
Authors: Sidana Abhinav , Jain Amit L , Kadakia Meet , Krane Spencer , Friend Julia C. , Muthigi Akhil , Ninos Martha , Shih Joanna H. , Srinivasan Ramaprasad 
Published: March 2017

509 Background: While studies have established several prognostic factors determining mortality in metastatic clear cell renal cell cancer patient, similar analysis has been lacking in metastatic papillary renal cell cancer (pRCC) patients. We aim to determine the predictors of mortality in metastatic pRCC patients. Methods: Retrospective evaluation of the medical records of patients with metastatic pRCC seen at National Cancer Institute (2000-2014) was undertaken. Patient demographics, tumor characteristics, and outcomes were studied. Kaplan-Meier Survival analysis was done to estimate overall survival (OS). Cox proportional-hazards regression analysis was done to identify predictors of All cause mortality (ACM) in this population. Results: 106 consecutive patients with metastatic pRCC were identified. The median age and follow up time after the diagnosis of metastases was 50 years (11-80) and 33.8 mon (2.3-246.7) respectively. Twenty one (19.8%) and 42 (39.6%) patients had papillary type 1 and papillary type 2 renal cancers respectively; in 43 (40.5%) patients, tumors were classified as papillary, not otherwise specified. Half (53) of patients had hereditary origin of pRCC. Median estimated OS of entire cohort was 37.5 mon. There was no difference in survival between patients with hereditary or sporadic pRCC (p = 0.80) or among patients with different subtypes of pRCC (p = 0.79). On univariate analysis, elevated serum corrected calcium elevated lactate dehydrogenase, Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and presence of malignant ascites significantly affected the patients’ prognosis. Corrected Calcium (p = 0.03) and NLR (p = 0.004) were found to be independent predictors of ACM on multivariate analysis. Conclusions: To our knowledge, this is the largest single center series evaluating survival and predictors of survival in metastatic pRCC. Metastatic pRCC patients with elevated NLR and serum corrected calcium are significantly associated with relatively poor OS when compared to patients without these findings. If validated in larger multi-institutional cohorts, it might be reasonable to incorporate corrected calcium and NLR in nomograms predicting ACM in metastatic pRCC.
Immune cell phenotyping of clear cell renal cell carcinoma.
Authors: Ghanaat Mazyar , Liu Ming , Manley Brandon , Kashan Mahyar , Becerra Maria , Redzematovic Almedina , Coleman Jonathan , Russo Paul , Hsieh James , Li Ming , Hakimi A. Ari 
Published: March 2017

511 Background: Clear cell renal cell carcinoma (ccRCC) tumors develop mechanisms that impair function and/or prevent entry of the host infiltrating immune cells (immune exclusion) within the tumor microenvironment. The goal of immunotherapy is to overcome this immune resistance. We aim to characterize the T−cell populations in a cohort of largely untreated high risk patients with ccRCC. Methods: We prospectively collected ccRCC tumor and adjacent normal kidney (NK) from patients undergoing surgical resection at our institution from 6/2015-8/2016. Immune cell phenotyping was performed by immune cell staining of single cell suspensions. Analysis of immune cell populations were determined by CD45+ staining and corresponding proportions of different T−cell populations (CD3+, CD4+, CD4+Treg, and CD8+ T cells). Staining for CD4+Treg was not available for two patients. Student t−test was utilized to compare the immune populations between tumor and adjacent NK tissue. Analysis was also conducted by stratifying patients who presented with localized versus metastatic disease. Results: A total of 31 tumor and adjacent NK were analyzed. Median tumor pathological size was 8.5cm (2.9cm−18cm), 27(87%) had pT3a−pT3b and 13(42%) presented with metastatic disease. Overall 84% of tumors had higher immune infiltrate with an average ratio of four-fold increase compared to adjacent NK as determined by CD45+ cells. Intriguingly, the other 16% presented with metastatic (4) or rapidly metastatic disease (1). Orthogonal validation with inferred immune populations using RNAseq data from the The Cancer Genome Atlas (TCGA) demonstrated similar aggressive behavior in tumors with lower immune infiltrate compared to NK. Comparison of immune cell populations of tumor and NK tissue is shown in table 1. No specific T-cell subtype was associated with specific clinical outcomes in this cohort. Conclusions: Our data shows a general trend of immune infiltration in ccRCC when compared to adjacent NK with a diversity of T-cell subsets and possible evidence of immune exclusion. Further genomic characterization of these tumors is currently underway. [Table: see text]
Does dose modification affect efficacy of first-line pazopanib in metastatic renal cell carcinoma?
Authors: Grassi Paolo , Procopio Giuseppe , Ratta Raffaele , Porcu Luca , Martinetti Antonia , Mennitto Alessia , Verzoni Elena 
Published: March 2017

512 Background: Pazopanib is a standard treatment for metastatic renal cell carcinoma (mRCC) and 800 mg/day is considered the optimal dose for mRCC patients (pts). However, some pts require a dose reduction due to toxicity. It remains unclear whether reduced-dose pazopanib is as effective as the standard dose in achieving a response. Methods: We retrospectively evaluated treatment duration, objective response rate (ORR), progression-free survival (PFS), and discontinuation rate in consecutive pts with mRCC treated with first-line pazopanib between 2011 and 2016 at the Istituto Nazionale Tumori of Milano, Italy. Three patient groups were compared: group 1 received the standard starting dose of 800 mg/day continously, group 2 received a dose reduced to 400 or 600 mg/day after starting with 800 mg/day, and group 3 received a reduced starting dose of 400 or 600 mg/day because of ECOG performance status = 2-3 and/or comorbidities. Results: We included 69 pts, with 34 in group 1, 19 in group 2, and 16 in group 3. Median age at diagnosis was 62 years, and 64% were male. Overall 13% and 87% of pts were classified as Heng good and intermediate-risk respectively. In 10 and 9 pts of the group 2, the dose was reduced to 600 and 400 mg/day respectively while 12 and 4 pts in the group 3 received a reduced initial dose of 400 and 600 mg/day respectively. After a median follow-up of 13.9 months (range 0.3-43.8), 27 (39.1%) pts showed progressive disease (PD) and 3 (4.3%) pts were dead. Incidence rate of PD or death was 2.5 (95% CI: 0.6-4.4; Hazard ratio [HR]:1) per 100 person-months in group 1; 4.0 (95% CI: 0-11.4; HR: 1.45) per 100 person-months in group 2 and 3.3 (95% CI: 0-6.8; HR: 1.19) per 100 person-months in group 3. Rates of discontinuation due to PD were 28% in group 1, 42% in group 2, and 44% in group 3. ORR was 44%, 11% and 19% in group 1, group 2, and group 3 respectively. Conclusions: Our results suggest that mRCC pts receiving a lower dose of first-line pazopanib might not have a meaningful PFS advantage compared with those receiving standard dose. These data highlight the importance of management of the treatment-related side effects that may eventually lead to optimal drug exposure.