bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective phase II trial of gemcitabine plus axitinib in patients with sarcomatoid type renal carcinoma.
Authors: Park Inkeun , Lee Hyo Jin , Bae Woo Kyun , Yoon Shinkyo , Lee Jae-Lyun 
Published: March 2019

616 Background: Sarcomatoid renal cell carcinoma (SRCC) is a rare but very aggressive type of RCC. The treatment option for SRCC is very limited, and there have been anecdotal reports of very good responders to gemcitabine or vascular endothelial growth factor receptor tyrosine kinaase inhibitors (VEGFR TKI). We conducted multicenter phase 2 trial of gemcitabine plus axitinib (GX) in patients (pts) with recurrent or metastatic SRCC to evaluate its efficacy and safety. Methods: Eligibility criteria included histologically confirmed metastatic or recurrent RCC with sarcomatoid component of 25% or more on resected kidney or exclusive sarcomatoid carcinoma on needle biopsy, ECOG PS 0-2, measurable lesion by RECIST v1.1, and adequate cardiac, hepatic, renal and bone marrow function. Pts with uncontrolled hypertension, prior exposure to gemcitabine or VEGFR TKI were exclude. Pts received gemcitabine 1,000 mg/m2 intravenously on days 1 and 8 by 3-week cycle and axitinib 5 mg twice daily. The primary endpoint was objective response rate (ORR) according to RECIST v1.1, and secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. Results: Twenty-five pts were enrolled between Oct 2014 and Aug 2018. Median age was 61 (range 33-80), and 84% was male. ECOG PS were 1 (92%) and 2 (8%), and 52% had prior nephrectomy. Clear cell carcinoma was the most common histology of carcinoma component, and median percentage of sarcomatoid component was 90% (25-100%). Pts belonged to intermediate (28%) and poor (72%) risk group according to IMDC risk stratification. Median 6 cycles of GX were administered, and 56%, 28%, and 12% of pts achieved PR, SD, and PD, respectively, with an ORR of 56% and median duration of response of 2.5 months. With a median follow-up duration of 21.4 mo, median PFS was 4.9 mo (95% CI, 3.5-13.3), and median OS was 8.4 months (95% CI 3.5-13.3 months). Most adverse events were manageable, and no unexpected toxicities were found. One pt died of grade 5 pneumonia. Conclusions: GX showed promising efficacy in pts with SRCC. GX might be considered as one of treatment options for pts with SRCC, although efficacy of GX should be confirmed in larger trial.
Proposal for tripartite re-classification of T1 renal cell carcinoma into cT1a (very low risk), cT1b (low risk), and cT1c (intermediate risk) substages.
Authors: Bradshaw Aaron , Uzzo Robert , Larcher Alessandro , Eldefrawy Ahmed , Capitanio Umberto , Joshi Shreyas , Ryan Stephen , Meagher Margaret Frances , Cotta Brittney , Yee Addison , Wan Fang , Montorsi Francesco , Derweesh Ithaar 
Published: March 2019

618 Background: Criteria for staging of T1 renal tumors into T1a (≤4cm) and T1b (4cm< and ≤7cm) have remained unchanged since 1997. Advancements in tumor biology have noted the heterogeneous potential of T1 renal tumors. We hypothesized that a three-tier classification may more rationally risk stratify T1 renal masses than the current T1a/T1b system. Methods: Multicenter (UCSD, Fox Chase Cancer Center, Ospadele San Raffaele) retrospective analysis of patients with cT1 renal cell carcinoma treated between 1987 and 2018. Patients were stratified into three groups: cT1a (≤2cm, very low risk), cT1b (2cm< and ≤5cm, low risk), and cT1c (5cm< and ≤7cm, intermediate risk). Primary outcome was recurrence free survival (RFS). Secondary outcome was overall survival (OS). Multivariable Cox Regression analysis (MVA) and Kaplan-Meier analyses (KMA) were utilized. Results: 3,324 patients were stratified into proposed T1 groups (T1a=578, T1b=2111, T1c=635; median follow-up 50 months). For cT1a, cT1b and cT1c, KMA revealed 5 year RFS of 96.9%, 91.6%, and 80.6% (p<0.001), and 5 year OS of 91.9%, 86.3%, and 76.2% (p<0.001). MVA for RFS revealed increasing age (HR=1.02, p<0.001), diabetes mellitus (HR=1.36, p=0.04), high tumor grade (HR=2.22, p<0.001) and tumor stage (Referent T1a; cT1b HR=2.18 p=0.001, cT1c HR=5.01 p<0.001) as independent risk factors. MVA for OS revealed increasing age (HR=1.05, p<0.001), diabetes mellitus (HR=1.57, p<0.001), high tumor grade (HR=1.34, p=0.002) and tumor stage (Referent T1a; cT1b HR=1.26 p=0.1, cT1c HR=2.050 p<0.001) as risk factors. Conclusions: Subclassification of cT1 renal cell carcinoma into three clinical stage categories corresponds to distinctive tumor groups whose biological potential varies significantly. Division into three distinct categories may enhance risk stratification, refine preoperative counseling, and augment postoperative follow-up protocols by delineating a very low risk and intermediate risk subset of renal tumors. [Table: see text]
The role of radiomics in the preoperative diagnosis of renal cell carcinoma with sarcomatoid dedifferentiation (sRCC).
Authors: Suk-Ouichai Chalairat , Kotrotsou Aikaterini , Idris Tagwa , Abrol Srishti , Umbreit Eric , McIntosh Andrew G. , Wood Christopher G. , Colen Rivka R. , Karam Jose A. 
Published: March 2019

621 Background: sRCC is an aggressive renal malignancy, with poor survival and limited response to therapy. Preoperative identification of sRCC would be helpful for counselling patients, and clinical trial enrollment. This study aims at assessing the potential of radiomics to discriminate clear cell sRCC from non-sarcomatoid clear cell RCC (nsRCC). Methods: The study included 49 sRCC and 41 nsRCC patients treated with surgery between 2007-2016, who had contrast-enhanced CT available. An experienced radiologist delineated the entire tumor using 3D Slicer ( http://www.slicer.org ). The extracted 3D region of interest was imported in our in-house radiomic pipeline. A total of 310 features (10 histogram-based and 300 second-order features) were calculated. Second-order radiomic features were calculated using the Grey Level Cooccurrence Matrix (GLCM) and 20 Haralick features were obtained from the GLCM. To account for directionality, the mean, variance and range of the features across different directions were calculated. Finally, different number of gray levels were also considered in the analysis (N = 8, 16, 32, 64, 256). Core features were obtained using a feature selection based on Least Absolute Shrinkage and Selection Operator (LASSO). Selected features were used to build a classification model for prediction of sRCC versus nsRCC (XGboost). To evaluate the robustness of the estimates, Leave One Out Cross-Validation (LOOCV) was conducted on the patient set. Results: Overall, median tumor size was 10.0 cm and most patients had pT3a (68%). There was no significant difference of age, gender, race, tumor size and stages between sRCC and nsRCC cohorts. The prediction of sRCC using LOOCV was significant with p-value < 0.0001. Area under the curve, sensitivity, and specificity for identification of sRCC were 96.8%, 92.6% and 93.8% respectively. Conclusions: This study demonstrates that CT radiomic features can accurately discriminate between sRCC and nsRCC. The proposed tool has the potential to advance clinical management strategies. In addition to being noninvasive, this methodology can be applied to scans obtained during routine clinical care. Further external validation is warranted.
Radiomic correlates of molecular and clinicopathological characteristics in clear cell renal cell carcinoma.
Authors: Coy Heidi , Young Jonathan R , Pantuck Allan J. , Douek Michael , Sisk Anthony , Magyar Clara , Brown Matthew S. , Sayre James , Raman Steven 
Published: March 2019

625 Background: Clear cell renal cell carcinoma (ccRCC) is a highly vascularized tumor and has a heterogeneous molecular profile, but the correlation between its tumor biology and radiomic features have only recently been investigated. As 70% of ccRCCs are detected incidentally at imaging, and tumor phenotypes are only available after surgery, a non-invasive biomarker to predict ccRCC phenotypes and aggressiveness on imaging may be clinically valuable, as low grade lesions may undergo active surveillance. Methods: With IRB approval and HIPAA compliance, our study cohort comprised 92 consecutive patients with 102 ccRCCs (mean age, 62 years (SD ± 14.2) with histopathology and molecular endpoints imaged preoperatively on CT with a four-phase renal protocol [unenhanced (U), corticomedullary (C), nephrographic (N), excretory (E)]. Radiomic data was obtained by contouring the entire ccRCC in each phase to obtain a 3D tumor volume of interest (VOI). The mean enhancement in each phase the and wash-in and wash-out of enhancement was calculated for each ccRCC. Molecular data was obtained through immunohistochemistry of resected ccRCCs to assess carbonic anhydrase-IX (CAIX), microvessel density (MVD), phosphatase and tension homolog (PTEN), and tumor grade (TG). Categorical variables were analyzed with logistic regression and odds ratio (OR) was reported. Continuous variables were analyzed with linear regression and Pearson correlation coefficient (r2) was reported. P-values < .05 were considered significant. Results: Significant radiomic associations included TG and 3D tumor enhancement in the C (OR = 4.72, p = .030), N (OR = 17.71, p < .0001), and E phases (OR = 17.10, p < .0001), and wash-in from U to C (OR = 8.27, p = .004). MVD had a significant positive association with 3D tumor enhancement in the C phase (r2= 0.410, p < .0001), wash-in from U to C (r2= 0.435, p < .0001) and wash-out from the C to N (r2= 0.435, p = .001). There were no significant radiomic correlates with CAIX or PTEN expression. Conclusions: A 3D ccRCC VOI on multiphasic CT had significant correlations with TG and MVD, independent of clinical features, potentially becoming a predictive imaging biomarker of ccRCC aggressiveness and clinical outcome.
Improving the definition of high-risk patients for tumor recurrence from clear cell renal cell carcinoma: The U-CISS classification.
Authors: Lebacle Cedric Michel , Kroeger Nils , Pooli Aydin , Liu Sandy , Chamie Karim , Belldegrun Arie S. , Shuch Brian , Drakaki Alexandra , Pantuck Allan J. 
Published: March 2019

629 Background: Thirty percent of patients with localized clear cell renal cell carcinoma (ccRCC) will ultimately develop recurrence (local or metastatic) after nephrectomy. Current risk stratification systems still misclassify patients. A better stratification is needed to select high-risk patients who may benefit from adjuvant therapy. We sought to improve the existing UISS by the addition of genetic information in a new UCLA cytogenetic integrated staging system (U-CISS). Methods: A total of 240 patients from UCLA with localized ccRCC and cytogenetic analysis on tumor specimen were included in the study. In a continuation of our previous research, cytogenetic (combined loss 3p-14q) and a pathological high-risk feature, microvascular invasion (MVI) were implemented in the UISS. Association with recurrence free survival (RFS) was analyzed in a uni- and multivariable fashion; prognostic accuracy was tested with the c-index. All tumors that had either MVI, combined loss 3p/14q or both in the UISS low-risk group were placed into the U-CISS intermediate group. Tumors with one or both risk factors in the UISS intermediate group were placed into the new U-CISS high-risk group. Results: Fifty patients developed tumor recurrence. On multivariate analysis, combined loss 3p-14q, and MVI were independent prognostic factors. The U-CISS placed significantly better prognosticated RFS in the high-risk group (7/50 (14%) with UISS vs. 23/50 (46%) with U-CISS) and thus, was more accurate in prognosticating RFS. The c-index for recurrence prognostication was improved in the U-CISS (0.70 vs. 0.65 for the UISS). Furthermore, the U-CISS was a better prognostication tool when the intermediate and high-risk group were combined (prognostication of 74% with U-CISS vs. 68% UISS). Conclusions: The use of U-CISS, which integrates genomic alterations with clinical and pathologic features, allowed a re-allocation of patients to create a better stratification of recurrence risk. This new definition of high-risk of recurrence could significantly improve selection of patients who are in greatest need of closer surveillance and/or adjuvant treatment. C.L. and N.K. contributed equally to first authorship.
The role of architectural patterns and cytologic features in the prognosis of clear cell renal cell carcinoma.
Authors: Cai Qi , Christie Alana , Zhou Qinbo , Araj Ellen , Cadeddu Jeffrey A , Margulis Vitaly , Singla Nirmish , Rajaram Satwik , Pedrosa Ivan , Rakheja Dinesh , McKay Renee , Brugarolas James , Kapur Payal 
Published: March 2019

632 Background: Clear cell renal cell carcinoma (ccRCC) exhibits a spectrum of clinical behavior and intratumoral heterogeneity histologically. Pathologic grading for ccRCC is primarily based on nucleolar size. Sarcomatoid and rhabdoid changes are known to be associated with aggressive behavior, the significance of the histopathologic heterogeneity occurring in ccRCC remains largely unknown. We evaluated the prognostic role of architectural patterns and cytologic features in ccRCC. Methods: We identified sequential ccRCC cases at our institution between 2006 and 2015 for which follow-up information was available beyond 1.5 years, excepting those who died sooner. Architectural patterns and cytologic features were predefined and quantitated in nephrectomy specimen slides, which were reviewed by an experienced GU pathologist. Nine novel architectural patterns and ten cytologic features were correlated with disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves were generated to visualize survival distributions. Results: 549 cases met selection criteria and were comprehensively reviewed including 16 grade 1 (2.9%), 278 grade 2 (50.6%), 201 grade 3 (36.6%) and 54 grade 4 (9.8%). Pathologic tumor stage distribution included 63.9% pT1 (n = 351), 6.0% pT2 (n = 33), 27.5% pT3 (n = 151), and 2.6% pT4 (n = 14). Microcystic, tubular, bleeding follicles, and small compact nest patterns (n = 309), were associated with better DFS and OS. In contrast, large nests, thick trabecular, solid sheet, alveolar or papillary/pseudopapillary patterns (n = 240) were associated with worse DFS and OS (p < 0.0001). In addition to multinucleated giant cells, and sarcomatoid and rhabdoid changes, cytologic features including large intracytoplasmic eosinophilic inclusions, voluminous cytoplasm, cytoplasmic spindling, a giant nucleus with perinuclear halo, and a wrinkled nucleus with perinuclear halo were associated with worse DFS and OS (p < 0.0004). Conclusions: Architectural patterns and cytologic features observed in ccRCC predict tumor behavior and are associated with clinical prognosis. Evaluation of histopathologic heterogeneity may shed light on tumor biology and complement prognostic models.
Predictors of prostate cancer-specific anxiety following stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer.
Authors: Salari Kamran , Aghdam Nima , Gersony Luara , Danner Malika , Ayoob Marilyn , Yung Thomas M. , Kataria Shaan , Lei Siyuan , Collins Brian Timothy , Kumar Deepak , Lischalk Jonathan W. , Dritschilo Anatoly , Suy Simeng , Lynch John J. , Collins Sean P. 
Published: March 2019

64 Background: Prostate Cancer (PCa) related anxiety varies widely based on management option. SBRT offers a safe and effective treatment for localized PCa. However, there is a paucity of data regarding PCa specific anxiety following SBRT and its relationship with PSA kinetics. In this report we present the results of a mail-in survey conducted amongst the participants of our prospective institutional quality of life (QOL) trial and identify sociodemographic and disease specific predictors of anxiety. Methods: Patients with localized PCa treated with SBRT at a single institution from 2007-2018 were eligible for inclusion in this study. The Memorial Anxiety Scale for PCa (MAX-PC) survey, was mailed to 450 patients on July of 2018. Patient’s total MAX-PC score (scale 0-54) was recorded. A score of ≥ 27 was defined as significant anxiety. Disease specific as well as demographic features were analyzed for possible correlation with self-reported anxiety. Results: By August 31, 2018, 227 patients had responded to the survey . The median score at all time points was 5 (1-41). Stratified by risk grouping; Low, Intermediate, and High Risk patients’ median scores were 7, 4.5 and 6. Six patients had a MAX-PC score≥27. Patients who were at least 2 years out from SBRT treatment had lower mean MAX-PC scores than those who were still within 2 years (6.3 versus 8.1, p = 0.045). Stratified by age, patients > 80 years old had a median score of 2 versus those < 70 with a median score of 6. Caucasian patients had lower mean MAX-PC scores than non-Caucasian patients (6.6 versus 9.1, p = 0.021). Patients who had at least a 0.5 ng/mL increase in PSA in their last 3 measurements had higher mean MAX-PC scores than those who did not (13.0 versus 7.0, p = 0.040). Conclusions: Patients with clinically localized PCa treated with SBRT experience minimal PCa specific anxiety. Anxiety surrounding PCa decreases with time. Non-Caucasian patients tended to have more anxiety than Caucasian patients. Patients who had recent PSA bounces tend to have higher levels of anxiety about their disease. Further follow-up of these patients over time would aid in assessing the progression of PCa specific anxiety as their lives progress.
The mutational burden of targeted genes significantly correlated with overall survival after targeted therapy in metastatic renal cell carcinoma.
Authors: Joung Jae Young , Kim Taek Sang , Park Sang Hyun , Kim Sung Han , Park Weon Seo , Chung Jinsoo 
Published: March 2019

643 Background: This study aimed to find the correlation between tumor mutation burden and systemic first line therapeutic response in metastatic tissue samples from patients with metastatic renal cell carcinoma (mRCC). Methods: Between 2005 and 2017, 168 triplet-tissue block samples from 56 mRCC patients were selected for targeted gene sequencing (TGS) using the 88 targeted genes from the National Cancer Center, Korea (NCC) kidney cancer panel. The patients’ medical records, including therapeutic responsive profiles with overall survival (OS) to first-line targeted therapy, were evaluated with the mutational burden of triplet tissue samples using 88 TGS. A few significant target genes associated with therapeutic response towards targeted therapy were identified after comparing the mutational burden of positive for all three blocks and one or two positive blocks (p-value < 0.05). Results: The median PFS for the first-line targeted therapy and OS were 8.7 and 42 months, respectively. MSKCC and Heng risk criteria showed 28.9/65.8/5.3% and 26,3/57.9/15.8% for favorable, intermediate, and poor risk groups, respectively. Also, 55.3% and 52.6% patients received metastatectomy and nephrectomy, respectively. Eighteen (32.1%) patients had all triplet blocks passed for quality check, whereas 21 (37.5%) and 17 (30.4%) patients had two or one passed tissue blocks, respectively. Among the 18 patients with triplet-block, TP53, URB4, PTK2, and SGO2 genes had significant discrimination power for OS on comparing their mutational burden in the three blocks positive group (N = 7) and two or fewer blocks positive groups (N = 11) (p < 0.05). Among the 39 patients with either doublet or triplet blocks passed for quality check, TP53, URB1, PTK2, SGO2, BRAF, NEDD4, PDXDC1, CDH1, FGFR2, RET, RUNX1, and SDHB genes had significant discrimination power for DFS when comparing their mutational burden in the three blocks positive group (N = 7) and two or fewer blocks positive groups (N = 14) (p < 0.01). Conclusions: The study showed the tumor mutational burden of many vital targeted genes to be significantly correlated with OS from metastatic tissues in mRCC.
Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients.
Authors: Elias Roy , Yan Flora , Singla Nirmish , Levonyack Nicholas , Formella Joseph , Christie Alana , Kapur Payal , Bowman Alex Isaac , Hammers Hans J. , Hannan Raquibul , Brugarolas James 
Published: March 2019

645 Background: With the approval of immune-checkpoint inhibitors (ICI) as first and second line agents for treating metastatic renal cell carcinoma (RCC), immune-related adverse events (irAE) are a growing concern. In this study, we present the safety profile and outcomes of 90 patients with RCC treated at two centers, including a university (UT Southwestern/Clements University Hospital) and a county hospital (UT Southwestern/Parkland). Methods: All patients with RCC treated with ICI were identified from 2013 to January 31, 2018. We examined the incidence of any treatment-related adverse events and “select” irAEs and evaluated their impact on patient outcomes and therapeutic decisions. Kaplan-Meier methods and Cox proportional hazards regression models were used to compare overall survival (OS) and time to next therapy (TTNT) by the presence of irAEs. Results: Of 90 patients treated with ICI, 65 (72.2%) patients experienced adverse events, most commonly fatigue (37.8%), nausea (14%), and decreased appetite (12.2%). Select irAEs were seen in 38 (42.2%) with the most common irAEs involving the skin (15.6%), gastrointestinal tract (14%), endocrine organs (11%), and lungs (7.8%). There were 15 (16.7%) grade III/IV irAEs resulting in cessation of therapy for 12 (13.3%) patients. The median OS was 35.9 (95% CI: 24.3-not reached) and 26.5 months (95% CI: 10.2-28.8; p = 0.002) for patients with and without irAEs, respectively. The median TTNT was 17.8 (95% CI: 11.3-29.3) and 6.6 months (95% CI: 4.5-9.6; p = 0.002) for patients with and without irAEs, respectively. In multivariate analysis of irAE status and Heng prognostic score, irAEs were associated with improved OS, HR 0.376 (95% CI 0.179–0.792; p = 0.010) and TTNT, HR 0.482 (95% CI 0.280–0.829; p = 0.008). Conclusions: ICI in RCC is well tolerated with only 16.7% of patients experiencing an adverse event resulting in cessation of therapy. The development of an irAE correlated with both an improved median OS as well as median TTNT, a benefit that persisted after multivariate analysis including Heng prognostic scoring. These findings suggest that the development of irAEs may be an independent positive prognostic factor in patients with RCC treated with ICI.