bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolving trends in non-clear cell renal cell cancer (RCC) epidemiology: A large registry analysis of 4,483 patients.
Authors: Pai Ashok P. , Brown Monica , Pan Chong-xian , Lara Primo 
Published: March 2020

4607 Background: Non-clear cell (ncc) RCC is uncommon but includes a heterogeneous group of histologic subtypes such as papillary, chromophobe (Chr), medullary (Med), and collecting duct (CD) cancers. We used a large cancer registry to define nccRCC clinical features and outcomes, identify prognostic variables, and to generate hypotheses for further study. Methods: Invasive RCC tumors in the California Cancer Registry from 1998-2009 among adults > 18 years of age (n=38,251) were analyzed. Baseline clinical and tumor variables were collected. Primary outcome measures were 3-year cause-specific (CSS) and overall survival (OS). Uni- and multivariate survival analysis were used to identify predictors of CSS and OS. Results: Of 38,251 RCC cases, 19,149 (50%) were of clear cell type; 14,619 (38.2%) were “unclassified.” Thus, 4,483 (11.7%) nccRCC cases were identified and included in this analysis. Of these, 3,304 (73.7%) were diagnosed in 2004-09, suggesting a shift to more precise coding of histologic subtypes starting in the early 2000s. Histology distribution (n, %): papillary - 2,863 (63.9%); Chr - 1,507 (33.6%); and other including Med and CD - 113 (2.5%). Variables associated with significantly better OS and CSS (univariate analysis) were Chr histology, female sex, and higher socioeconomic status (SES). Significantly worse OS and CSS were seen in Med+CD, age > 65 yrs, no nephrectomy (Nx), and higher stage. Non-hispanic blacks had significantly worse OS and CSS, while the “targeted therapy era” (2004-2009) was associated with better OS. Multivariate analysis showed the following to be independently associated with outcomes (all p <0.001; Hazard Ratios [HR] shown for CSS and OS): Chr histology (0.48, 0.56), Med+CD histology (2.99, 2.42), no Nx (2.84, 3.18), regional stage (5.84, 1.98), distant stage (25.7, 7.67); and non-hispanic blacks (1.5,2 p=0.006; 1.25, p=0.03). Age > 65 yrs (HR 1.78, p<0.001) and high SES (HR 0.88, p=0.001) were associated with OS but not CSS. Conclusions: This is among the largest registry analyses of nccRCC ever performed, showing emerging trends in this uncommon RCC subset. Clinical variables associated with CSS and OS were identified that can inform the design of future clinical trials in nccRCC.
Incidence and severity of cardiotoxicity in metastatic renal cell carcinoma (RCC) patients treated with targeted therapies.
Authors: Hall Philip S , Witteles Ronald , Srinivas Sandy , Harshman Lauren Christine 
Published: March 2020

4610 Background: Almost all patients with advanced RCC are treated with therapies targeting the hypoxia inducible factor axis. The potential for these agents to cause cardiovascular (CV) toxicity has been increasingly recognized but the overall incidence and extent have not been well described. We sought to identify and characterize the incidence and severity of CV toxicity among RCC patients treated with targeted therapies. Methods: Between 2004 and 2011, all RCC patients treated with targeted therapies directed against the VEGF or mTOR axes were identified at our institution. The incidence of hypertension, left ventricular (LV) dysfunction, changes in serum markers of CV toxicity (e.g., troponin I, NT-proBNP) and heart failure were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE v.4.0). Results: Cardiovascular toxicity developed in 116 of 159 patients (73%). Excluding hypertension, 52 of 159 (33%) developed cardiovascular toxicity. Cardiac toxicity ranged from asymptomatic drops in LV ejection fraction (LVEF) to rises in NT-proBNP to severe heart failure. Asymptomatic cardiotoxicity as defined by decrease in LVEF or increase in NT-proBNP occurred in 43 patients (27%). Symptomatic heart failure (grade 2-3) and grade 3-4 decrease in LVEF each occurred in 4%. Sunitinib was the most frequently used and most common offending agent, with 66 of 101 sunitinib-treated patients (65%) developing a form of CV toxicity, or 32 of 101 (32%) excluding hypertension. However, it was notable that CV toxicity was observed in 68%, 66%, and 51% of patients treated with bevacizumab, sorafenib, and pazopanib as well. The mTOR inhibitors elicited significantly less CV toxicity, but sample sizes were small. Conclusions: Cardiovascular toxicity is an important adverse event related to targeted therapy administration. Close monitoring for the development of CV toxicity with the use of these agents should become standard of care as early detection of asymptomatic patients could preempt symptomatic toxicity and reduce treatment-related morbidity and mortality.
Circulating mir-21 and mir-378 are predictive of progression-free survival (PFS) in patients treated with everolimus in metastatic renal cell cancer (mRCC).
Authors: Chen James Lin , Rathmell Kimryn , McDermott David F. , Stadler Walter Michael 
Published: March 2020

4617 Background: The oral mTOR inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and modestly delays RCC progression. We hypothesized that circulating microRNAs, which have been associated with renal cancer and inflammation, may serve as predictive biomarkers to help better define a population more sensitive to treatment. Methods: Plasma from mRCC pts refractory to VEGF inhibition were obtained prior to treatment with standard dose everolimus as part of a clinical trial examining FDG-PET as a potential predictive biomarker. As we were specifically interested in tumor response to drug, only pts who died, remained on trial, or had radiographic progression by RECIST criteria were profiled. Pts who were unable to tolerate drug were excluded. MicroRNAs were extracted and profiled without pre-amplification using Exiqon LNA PCR panels. Crossing point (Cp) values within 5 of the negative control were removed. MicroRNAs must have been present in >90% of samples and varied at least p > 0.10 from mean to be further analyzed. Cox-proportional hazards model and Kaplan-Meier analyses were performed. Results: 28 patients had available plasma and met criteria for profiling. Pt characteristics included: 20 (71%) clear cell histology, median age 57.7 (43 – 76), median number of prior systemic therapies 2 (1 – 3). 103 microRNAs were expressed in at least 90% of all samples. Mir-21 and mir-378 were independently correlated with PFS (FDR: 0.02 and 0.06, respectively). Low circulating plasma mir-21 and mir-378 levels resulted in a median PFS prolongation of 370d vs. 101d (p=0.027) and 368d vs. 106d (p=0.001). Analysis of the clear cell cohort for mir-21 and mir-378 also demonstrated a significant median PFS difference of 350d vs. 173d (p=0.045) and 345d vs. 147d (p=0.004). Conclusions: Elevated levels of circulating mir-21 and mir-378 have been associated with systemic inflammatory states, and in our study are correlated with decreased PFS in mRCC pts undergoing everolimus therapy. Further prospective studies will be required to validate these exploratory results for their potential role as prognostic or predictive biomarkers.
Evaluation with DCE-US of antiangiogenic treatments in 539 patients allowing the selection of one surrogate marker correlated to overall survival.
Authors: Lassau Nathalie , Vilgrain Valérie , Taieb Sophie , Lacroix Joëlle , Aziza Richard , Cuinet Marie , Soria Jean-Charles , Chapotot Louis , Koscielny Serge 
Published: March 2020

4618 Background: A prospective study of dynamic contrast-enhanced ultrasound (DCE-US) with quantification for the evaluation of antiangiogenic treatments was launched (19 centers), supported by the French National Cancer Institute. The objectives were the diffusion of the standardized method, a cost evaluation and the identification of perfusion parameters predicting tumor response. Methods: All patients had DCE-US at baseline, D7, D14, D30, D60 and every two months. Each examination included a bolus injection of sonovue (Bracco) and 3 minutes of raw linear data with an Aplio (Toshiba). Raw data were analyzed with a mathematical model (patent PCT/IB2006/003742) to evaluate 7 parameters characterizing the tumor perfusion curve. Response to treatment was evaluated every 2 months with RECIST criteria. In order to have sufficient follow-up data, the statistical analysis has to be performed more than 6 months after the inclusion of the last analyzed patient. Inclusions were closed in March 2010. Results: A total of 539 patients have been included (mainly RCC (157) and HCC (107)); more than 2 000 DCE-US and 1700 CT-scan were performed. A follow-up more than 12 months showed that 3 parameters have a strong significant difference (p<0.0003) according to the response at 6 months. The decrease of more than 40% of AUC at one month is correlated to the TTP (p< 001) and OS (p< 0.04). Conclusions: Final results confirm the usefulness of this tool to monitor anti-angiogenic treatments. The criteria: the decrease of more than 40% of AUC at one month is predictive of response.
Use of bisphosphonates (Bis) combined with sunitinib (Su) to improve the response rate (RR), progression-free survival (PFS), and overall survival (OS) of patients (pts) with bone metastases (mets) from renal cell carcinoma (RCC).
Authors: Peer Avivit , Ish-Shalom Maya , Hammers Hans J. , Eisenberger Mario A. , Sinibaldi Victoria J. , Pili Roberto , Maimon Natalie , Gottfried Maya , Hayat Henry , Kovel Svetlana , Sella Avishay , Neumann Avivit , Boursi Ben , Berger Raanan , Carducci Michael Anthony , Keizman Daniel 
Published: March 2020

4619 Background: Bis are used to prevent skeletal events of bone mets, and may exhibit anti tumor effects. We aimed to evaluate whether Bis can bring a RR, PFS, and OS benefit to pts with bone mets from RCC that are treated with Su. Methods: We performed an international multicenter retrospective study of pts with bone mets from RCC who were treated with Su. Pts were divided into Bis users (group 1) and nonusers (group 2). The effect of Bis on RR, PFS and OS, was tested with adjustment for known prognostic factors using a chisquare test from contingency table and partial likelihood test from Cox regression model. Results: Between 2004-2011, 244 pts with metastatic RCC were treated with Su. 92 pts had bone mets, 41 group 1 and 51 group 2. The groups were balanced regarding the following known prognostic factors: past nephrectomy, clear cell vs non clear cell histology, initial diagnosis to sunitinib treatment (tx) time, presence of ≥ 2 mets sites, presence of lung/liver mets, ECOG performance status, anemia, calcium level > 10 mg/dL, elevated alkaline phosphatase (AP), pre-tx neutrophil to lymphocyte ratio (NLR) >3, sunitinib induced HTN, and the use of angiotensin system inhibitors. They were also balanced with regard to past cytokines/targeted tx, and mean sunitinib dose/cycle. Objective response was partial response/stable disease 85% (n=35) vs 71% (n=36), and progressive disease 15% (n=6) vs 29% (n=15) (OR 3.287, p=0.07) in group 1 vs 2 respectively. Median PFS was 15 vs 5 months (HR 0.433, p=0.035), and median OS not reached with a median folloup time of 43 mos vs 12 months (HR 0.398, p=0.003), in favor of group 1. In multivariate analysis of the entire pt cohort (n=92), factors associated with PFS were Bis use (HR 0.433, p=0.035), pre-tx NLR ≤3 (HR 0.405, p=0.016), and elevated AP (HR=3.63, p=0.012). Factors associated with OS were Bis use (HR 0.32, p=0.003), elevated AP (HR 3.18, p=0.002), and Su induced HTN (HR 0.193, p< 0.001). Conclusions: Bis may improve the outcome of Su tx in RCC with bone mets. This should be investigated prospectively, and if validated applied in clinical practice and clinical trials.
Prognostic role of body composition parameters in renal cell carcinoma (RCC).
Authors: Lanoy Emilie , Antoun Sami , Iacovelli Roberto , Albiges Laurence , Loriot Yohann , Merad Mansouriah , Fizazi Karim , Di Palma Mario , Baracos Vickie E. , Escudier Bernard J. 
Published: March 2020

4621 Background: Previous studies have shown that body component i.e. muscle tissue (MT) and adipose tissue (AT) are linked to overall survival (OS) and progression free survival (PFS). The aim of our study is to analyze whether MT and AT have a prognostic role in metastatic RCC treated with targeted therapy. Methods: We investigated body mass index (BMI), MT and AT in RCC pts. Analysis of CT image was used to evaluate cross-sectional areas (cm2) of total AT (TAT), MT, and the grey level image (GLI) of MT, reflecting physical properties of the scanned tissue and used as a proxy to describe the quality of muscle. The 3rd lumbar vertebra (L3) was chosen as a landmark since L3 and whole-body measurements are linearly related. Images were analyzed using Slice-O-Matic software V4.3 (Tomovision). Indexed on height MT (cm2/m2), indexed on height TAT (cm2/m2) and mean GLI of MT were computed and described stratified on sex. For each measurement, population was divided in two groups: patients with values < or >= median observed in patient of the same gender and OS and PFS were estimated using Kaplan-Meier method and compared with the log-rank test. Multivariable Cox proportional hazards model were adjusted for modified MSKCC risk group and treatment (active versus placebo). Results: There were 113 men aged of 60 (interquartile range=52-56) years with BMI of 26 (24-29) kg2/m2 and 36 women aged of 58 (54-65) years with BMI of 23 (20-26) kg2/m2. After adjustment for MSKCC (OS and PFS) and active treatment (PFS), GLI of MT over the median was associated with longer OS (HR=1.85, 95%CI=[1.22;2.82], p=.004) and PFS (HR=1.81, 95%CI=[1.22;2.65], p=.002) Conclusions: Quality of muscular tissue is independently associated with better outcome in RCC. Surprisingly, adipose tissue as well as BMI is not associated with survival in this study. [Table: see text]
Impact of maximum standardized uptake value (SUVmax) evaluated by 18-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG PET/CT) on survival for patients with advanced renal cell carcinoma.
Authors: Nakaigawa Noboru , Yao Masahiro , Tateishi Ukihide , Minamimoto Ryogo , Uemura Hiroji , Inoue Tomio , Kubota Yoshinobu 
Published: March 2020

4626 Background: In this era of molecular targeting therapy when various systematic treatments can be selected, prognostic biomarkers are required for the purpose of risk-directed therapy selection. Numerous reports of various malignancies have revealed that 18-Fluoro-2-deoxy-D-glucose (18F-FDG) accumulation, as evaluated by positron emission tomography, can be used to predict the prognosis of patients. The purpose of this study was to evaluate the impact of the maximum standardized uptake value (SUVmax) from 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET/CT) on survival for patients with advanced renal cell carcinoma (RCC). Methods: A total of 67 patients with advanced or metastatic RCC were enrolled in this study. The FDG uptake of all RCC lesions diagnosed by conventional CT was evaluated by FDG PET/CT. The impact of SUVmax on patient survival was analyzed prospectively. Results: The mean duration of observation was 461 days (range, 7-1229 days). The SUVmax before treatment of 67 patients ranged between undetectable level and 16.6 (mean 7.6±3.6). The patients with RCC tumors showing high SUVmax before treatment demonstrated poor prognosis (p<0.001 hazard ratio 1.289, 95% CI 1.161-1.430). The median survival time of 36 patients with RCC showing SUVmax less or 7.0 was 1229±991 days, that of 21 patients with RCC showing SUVmax between 7.0 and 12.0 was 446±202 days, and that of 10 patients RCC showing SUVmax higher than 12.0 was 95±43 days (≤7.0 vs. 7.0< ≤12.0 p=0.0052, 7.0< ≤12.0 vs. 12.0<:p=0.0169, log-rank test). SUVmax demonstrated a tendency to predict the survival compared with the Memorial Sloan-Kettering Cancer Center classification (p =0.015 vs 0.315, multivariate Cox analyses). Conclusions: The survival of patients with advanced RCC can be predicted by evaluating their SUVmax using FDG PET/CT. FDG PET/CT has potency as an “imaging biomarker” to provide helpful information for the clinical decision-making.
Efficacy and safety of cancer vaccine with 4-fold gene-modified allogeneic tumor cells: Results of the phase I/II ASET study in patients with advanced renal cell carcinoma.
Authors: Weikert Steffen , Grünwald Viktor , Schmidt-Wolf Ingo GH , Hauser Stefan , Kapp Kerstin , Schmidt Manuel , Schroff Matthias , Weith Ekaterina , Tschaika Marina , Wittig Burghardt 
Published: March 2020

4636 Background: MGN1601 was tested in the first-in-man phase I-II clinical study in patients with advanced renal cell carcinoma (RCC) who failed several previous therapy lines and had no further standard therapy available. MGN1601 consists of two active pharmaceutical ingredients in fixed combination: fourfold gene-modified allogeneic tumor cells expressing IL-7, GM-CSF, CD80 and CD154 through MIDGE vectors and a TLR-9 agonist, the immunomodulator dSLIM. Methods: The ASET study is a multicentric, single-arm phase I-II clinical trial. Clinical response was evaluated using CT scans (RECIST 1.1 or immune related Response Criteria, irRC). Efficacy data were evaluated in terms of PFS and OS for the intended to treat and the treated per protocol (TPP) populations, clinical parameters and quality of life. Immune response was determined using DTH to MGN1601, LTT assay, frequency and activation of blood cells, and mRNA, chemokine and cytotoxic T cells analysis as well as tumor tissue evaluation. Results: Nine of 19 included patients completed the TPP, the others discontinued the study earlier due to PD. Median PFS in the TPP group was 12 wks (3 months) and OS (not reached yet) 46 wks (11 months). Three patients achieved disease control (1 PR, 2 SD) after 12 wks. Two patients are continuing treatment in the extension phase and are progression free since 37 and 46 wks, respectively. Re-evaluation of tumor response data using irRC revealed 1 additional patient with a delayed tumor response 4 wks after treatment stop. Herewith, 4 out of 9 TPP patients (45%) achieved disease control. Of 7 patients receiving targeted therapy upon stop of study treatment, 4 had substantial objective responses, providing evidence that the study drug is able to render their tumors more vulnerable to subsequent therapies. Immune analysis showed trends towards increases of T-, NKT-cell and pDC frequencies and other immune parameters in those patients with clinical responses, indicating anti-tumor immunity of study treatment. Conclusions: The therapeutic cancer vaccine MGN1601 shows promising efficacy in late stage mRCC patients. Results warrant further clinical studies with MGN1601.
Adjuvant radiotherapy after primary surgical resection in patients with adrenocortical carcinoma: Retrospective cohort analysis.
Authors: Habra Mouhammed Amir , Ejaz Shamim , Feng Lei , Das Prajnan , Deniz Ferhat , Grubbs Elizabeth Gardner , Phan Alexandria T. , Waguespack Steven , Ayala-Ramirez Montserrat , Jimenez Camilo , Vassilopoulou-Sellin Rena 
Published: March 2020

4641 Background: Adrenocortical carcinoma (ACC) is a rare malignancy with high recurrence and mortality rates. The role of adjuvant radiotherapy (RT) to improve outcome remains unclear. Considering the rarity of ACC, we conducted a historical cohort study to ascertain the effect of adjuvant RT on overall survival and recurrence rates. Methods: Patients were selected from the MD Anderson Cancer Center (MDACC) ACC registry (1998- 2011) who had primary tumor resection with no evidence of distant metastasis at the time of initial diagnosis and a minimum follow-up of 6-months. The adjuvant RT group included patients who received adjuvant RT within 3 months of diagnosis. Control group included patients who did not receive RT and matched based on resection margin status and stage at diagnosis. Results: There were no significant differences between the adjuvant RT group (n=15) and comparison group (n =45) in gender distribution, age, tumor size, functional status, and use of adjuvant mitotane therapy. On multivariate Cox proportional hazard model for overall survival, the adjuvant RT group had hazard ratio of 1.981(95% confidence interval [CI] 0.894-4.391, p=0.0922) compared to the control group. The differences in median time to local recurrence, distant recurrence and of recurrence free survival were not significant between the two groups. In subgroup analysis including only the patients whose initial treatments were from outside of MDACC, RT group (n=15) had hazard ratio of overall survival of 1.604 (95% CI 0.712- 3.613, p=0.2543) compared to group without adjuvant RT (n= 32). Median times to local recurrence, distant recurrence, or of recurrence free survival were also not significantly different between the two groups. Conclusions: To our knowledge, this is the largest single institution report about adjuvant RT use in ACC. In our study, RT did not appear to cause a significant difference in overall survival, recurrence rate, or time to recurrence. However, it is still possible that patients offered adjuvant RT and control groups may have been inherently different. Hence, a prospective study is needed to clarify the role of adjuvant RT in patients with resectable ACC.
Polymorphisms in fragile histidine triad gene (FHIT) associated with aggressive prostate cancer and cancer specific mortality.
Authors: Ding Yan , Black Amanda , Hsing Ann W , Andriole Gerald L. 
Published: March 2020

4646 Background: FHIT is a 1.5 Mb gene encoding a 16.8 kD triphosphatase known to promote apoptosis responding to DNA damage in epithelial cells. It resides in the most frequently observed fragile site in the human genome, FRA3B, and is frequently deleted in early development of multiple cancer types. More importantly, down regulation of FHIT protein has been associated with clinical features of tumors, such as the presence of extraprostatic extension and Gleason Score > 8 in prostate cancer (CaP), advanced diseases in breast cancer, and shorter survival after platinum-based treatment for advanced non-small cell lung cancer. Previously, a genetic locus for CaP has been reported in FHIT. Here we evaluated association of aggressive CaP and death due to CaP with Single nucleotide polymorphisms (SNPs) in FHIT using cases and controls of European origin nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening trial with 13 years of follow-up. Methods: We analyzed 659 SNPs on FHIT in 1,164 CaP patients (476 with nonaggressive CaP, Gleason < 7 and stage < III; 688 with aggressive CaP, Gleason >= 7 and/or stage III/IV; 63 with death due to CaP) and 1,167 controls using an incidence density sampling strategy. Stratified Cochran-Mantel-Haenszel test and logistic regression were performed to test association. Results: We detected significant association (p < 0.05) of incident CaP to 48 SNPs and aggressive CaP to 52 SNPs. After 50,000 permutations, two SNPs within a 7 kb region, one for incident CaP and the other for aggressive CaP, remained marginally significant (corrected p = 0.053 and 0.093, respectively). The same risk allele for aggressive CaP was also associated with CaP-specific mortality (OR = 1.50, p = 0.027). The association was stronger after adjusting for Gleason, stage, and PSA at diagnosis, treatment options after diagnosis. Test on imputed SNPs within the 7 kb intronic region identified 7 additional SNPs in 2 linkage disequilibrium groups at higher risk to CaP-specific death (OR = 1.98, p = 0.00015 and OR = 2.51, p = 0.0027). Conclusions: Risk SNPs in FHIT were implicated for aggressive disease and CaP specific death. Replication of these SNPs in other populations is warranted.