bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receipt of systemic therapy in older versus younger patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Hahn Andrew W , Haaland Ben , Rathi Nityam , Dizman Nazli , Maughan Benjamin Louis , Pal Sumanta K. , Agarwal Neeraj 
Published: March 2019

580 Background: More than half of pts diagnosed with mRCC are age 65 or older. However, older pts are often under-accrued/under-represented in clinical trials, partly due to concerns about their ability to tolerate systemic therapy (Rx). Given this, efficacy data from the registration trials may not apply to older pts. Herein, we investigate whether older patients with mRCC are less likely to receive various lines of systemic Rx than their younger counterparts. Methods: Clinical data was obtained from a prospectively maintained mRCC registry at the Huntsman Cancer Institute, University of Utah. Older pts were defined as ≥65 yrs at initiation of first-line systemic Rx for mRCC. Univariate analyses of the lines of systemic Rx received were performed using the Chi-squared test. Comparison of ordered categorical variables was made with the Wilcoxon rank sum test. Results: 264 pts who received first-line Rx for mRCC between 2004-2018 were included, and 108 of them were older pts. For older pts, median age at first-line Rx was 71.1 years and 78.7% had clear cell histology, whereas, the median age for younger pts was 53.4 years and 75.6% had clear cell histology. There was no difference in the baseline IMDC risk categories in older vs. younger pts (p = 0.907). A similar proportion of older and younger pts received at least two lines of systemic Rx (66.9% vs. 62.4%, p = 0.532). Furthermore, when analyzed across all lines of treatment, there was no difference in the number of systemic Rx between older and younger pts (p = 0.593). The median OS was similar in both groups: older 30 months (95% CI 21-44 months) vs. younger 34 months (95% CI 30-46 months) (p = 0.639). Conclusions: Older pts with mRCC receive a similar number of systemic Rx as their younger counterparts, and have similar survival outcomes. These findings can inform clinicians when selecting first and salvage-line treatment for older pts, and warrant proportionate accrual and representation of older pts in clinical trials.
Investigation of IMPDH2 overexpression in renal cell carcinoma (RCC) & its association with oncologic outcomes.
Authors: Sendilnathan Arun , Velagapudi Ramya Krishna , Marinos Velarde Alejandro , Jandarov Roman , Zhu Zheng , Randhawa Jaskirat Singh , Dillehay McKillip Kelsey , Yoshino Hirofumi , Kofuji Satoshi , Okumura Koichi , Naffouje Rand , Koch Matthew , Ao Xiang , Finley Kara , Sasaki Atsuo 
Published: March 2019

594 Background: Approximately 40% of locoregional RCC patients relapse after nephrectomy leading to lower 5 year survival rates of 53% (stage III) & 8% (metastatic). No biomarkers of prognostic significance are in clinical use at this time. It is important to identify biomarkers that can better inform clinicians the nature of disease & personalize treatment. It is even better if the biomarkers are targetable with drugs. Inosine 5”-mono-phosphate dehydrogenase type II (IMPDH2), a rate limiting enzyme in the de novo guanine nucleotide biosynthesis is upregulated in many tumor types. Work by Sasaki laboratory showed increased GTP synthesis by IMPDH2 upregulation is important for cell growth, metastasis & cell maintenance in Gliobastoma Multiforme cell lines. Hypothesis: We are investigating the feasibility of using IMPDH2 expression in RCC as a diagnostic & prognostic biomarker. Methods: 45 cases of clear cell RCC (all stages) were identified by chart review. Slides reviewed to identify blocks with carcinoma, normal tissue & interface. Tissue microarray (TMA) was constructed using the fully automated TMA Master. TMA sectioned and stained with H &E & IMPDH2 antibody. Staining interpretation: TMA stained with IMPDH2 were reviewed based on IRS scoring system (PP x SI) - percentage positive(PP) cells (Negative-0, ≤ 10% -1, ≥ 11%- ≤ 50%- 2, ≥ 51%-≤ 80% -3, and ≥ 81%-4) & staining intensity (SI) (Negative-0, Weak-1, Moderate-2, and Strong-3). The scoring pathologist was blinded to the clinical data & outcomes of patients. Results: Preliminary results show IMPDH2 is overexpressed in RCC and tumor-normal interface compared to normal kidney. Further analyses are ongoing if IMPDH2 overexpression correlates with pertinent clinical & pathological variables including TNM stage, histologic grade (Fuhrman Grade) & oncologic outcomes including overall survival (OS) & risk of relapse. Conclusions: In the era of Sunitinib being approved as an adjuvant therapy (but not widely used due to lack of OS data), the above data will be important to verify if IMPDH2 can be used as a clinically useful test & may give insight to future personalized & targeted treatment strategies (IMPDH2 inhibitors like mycophenolate) for RCC.
Association of elevated C-reactive protein with oncologic outcomes in renal CELL carcinoma: A multicenter analysis.
Authors: Patel Sunil Hemant , Meagher Margaret Frances , Saito Kazutaka , Patil Dattatraya , Bindayi Ahmet , Eldefrawy Ahmed , Ryan Stephen , Cotta Brittney , Yim Kendrick , Nasseri Ryan , Hamilton Zachary , Yasuda Yosuke , Fujii Yasuhisa , Master Viraj A. , Derweesh Ithaar 
Published: March 2019

596 Background: C-reactive protein (CRP) is a systemic inflammatory marker which has been associated with overall survival (OS) in Renal Cell Carcinoma (RCC) patients in Asia. Data supporting utility of CRP as a predictive marker in non-Asian populations are sparse and controversial. We analyzed utility of pre-treatment CRP as a predictor of survival and oncological outcomes in a multicenter cohort of RCC patients. Methods: Retrospective international 3 center analysis of patients of patients with RCC with pretreatment CRP values from 2006-2017. CRP > 0.5mg/dl was used as threshold for elevation and the cohort was subdivided into two groups for descriptive analysis (normal-CRP ≤0.5 and elevated-CRP > 0.5). Primary outcome was recurrence-free survival (RFS). Secondary outcome was overall survival (OS). Kaplan-Meier (KMA) and multivariable analyses (MVA) were utilized to delineate survival outcomes and their predictors. Results: Overall 2695 patients were analyzed (1791 Male/904 female, CRP≤0.5 1198/CRP > 0.5 1496; mean follow-up 36 months). Patients with elevated CRP had higher incidence of hypertension (p = 0.001), BMI (p < 0.001), and tumor size (3.91 cm vs. 6.05 cm, p < 0.001). MVA for RFS demonstrated elevated CRP (OR = 0.542, p = 0.005), increasing tumor size (OR = 0.915, p < 0.001), and high tumor grade (OR = 0.322 p < 0.001) to be independent risk factors. MVA for all-cause mortality demonstrated elevated CRP (OR = 12.396, p = 0.005), increasing tumor size (OR = 1.126, p < 0.001), high tumor grade (OR = 2.474, p < 0.001), and receipt of PN (OR = 1.826, p = 0.001) to be independent risk factors. For normal vs. elevated CRP, KMA revealed 5-year RFS of 90% vs. 85% (p = 0.001), 95% vs 85% (p = 0.163), 85% vs 62% (p = 0.001), 50% vs 60% (p = 0.513) for Stages 1, 2, 3, and 4, respectively. KMA revealed 5-year OS of 98% vs 80% (p = 0.001), 95% vs 80% (p = 0.103), 95% vs 65% (p = 0.001), 99% vs 40% (p < 0.001) for Stages 1, 2, 3, and 4, respectively. Conclusions: Pre-treatment CRP was an independent predictor of recurrence free survival and overall survival in a multicenter cohort of RCC patients. While further confirmation is requisite, our findings suggest incorporation of CRP into nomographic and risk stratification protocols.
Real-world experience with sunitinib treatment in patients with metastatic renal cell carcinoma: Clinical outcome according to risk score.
Authors: Schmidinger Manuela , Porta Camillo , Oudard Stephane , Dénéchère Gwénaël , Brault Yves , Serfass Lucile , Costa Nuno Matos , Larkin James M. G. 
Published: March 2019

606 Background: ADONIS, an ongoing, observational study in 9 EU countries, evaluates treatment patterns/outcomes in patients (pts) with metastatic renal cell carcinoma treated with 1st-line (1L) sunitinib (SU) and/or 2nd-line (2L) axitinib (AX) post SU. Analysis of the data is planned in 4 parts, to occur stepwise as data matures; evaluation of SU efficacy in intermediate (INT) risk pts is presented here. Future analyses include sequencing data, SU followed by AX and other treatments (cabozantinib, nivolumab and others); SU and AX therapy management strategies, and quality of life. Methods: Pts enroll at start of 1L SU or 2L AX post SU. Data cutoff: May 31, 2018. Analysis focused on 1L SU. Results: 467 pts, median age 64 y (range 31–90), 77.7% were male, with ECOG PS < 2 = 90.2% and ECOG PS ≥ 2 = 9.8% at SU initiation. Overall median progression-free survival (mPFS) was 10.4 mo (95% CI 9.3–12.5), and median overall survival (mOS) 34.0 mo (95% CI 28.3–46.6). Data on individual risk factors (RF) were available for 120 pts, allowing analysis by INT 1RF and INT 2RF groups for this subset. Clinical trial information: NCT02184416. Conclusions: For pts overall and by risk group stratification, survival estimates were aligned with improvements in clinical practice over the past decade. In pts with INT risk with 1RF, OS was very similar to pts with good risk. However further exploration is needed to confirm these observations.[Table: see text]
The association between hospitals’ risk-adjusted emergency department visits and survival and costs in kidney cancer patients.
Authors: Segel Joel E , Schaefer Eric W. , Raman Jay D. , Hollenbeak Christopher S. 
Published: March 2019

609 Background: As payers turn to alternative payment models, including the CMS Oncology Care Model, risk-adjusted emergency department (ED) visits are being incorporated as a quality. Yet little is know about this metric compares to existing metrics such as risk-adjusted mortality rates and costs. Methods: Using 2007-2012 SEER-Medicare data, we used logistic regression to model occurrence of an ED visit within 30 and 365 days for all kidney cancer patients receiving initial surgery. Our model controlled for demographics, stage, histology, systemic targeted therapy, and comorbidities. Based on model predictions, we created a ratio of actual versus predicted ED visits for hospitals to identify hospitals with higher and lower than predicted ED visit rates. We estimated the association between the hospitals’ ED visit ratio and hospitals’ risk-adjusted 365-day mortality rates, and 6- and 12-month total costs and total costs (less ED visits). Results: In our sample of 6,078 patients, 15.5% had an ED visit within 30 days of surgery and 43.5% within 365 days. For hospitals with ≥10 patients, we found no statistically significant association between 30-day or 365-day risk-adjusted ED visit rate and their 365-day risk-adjusted mortality rate. While hospitals’ 30-day ED visit rates were significantly associated with 6- and 12-month costs, the association was largely driven by the cost of the ED visit itself. Conversely, hospitals’ 365-day ED visit rates were significantly associated with 12-month costs after excluding the cost of the ED visit. Conclusions: Our results suggest hospitals’ risk-adjusted ED visit rates capture a qualitatively different measure of quality than the more commonly reported mortality rates and is significantly associated with patient cost.
Real-world assessment of clinical outcomes among first-line (1L) sunitinib (SUN) patients (pts) with metastatic renal cell carcinoma (mRCC) by the international mRCC database consortium (IMDC) risk group.
Authors: Savard Marie-France , Wells J Connor , Graham Jeffrey , Steinharter John A. , McGregor Bradley Alexander , Donskov Frede , Bjarnason Georg A. , Vaishampayan Ulka N. , Hansen Aaron Richard , Iafolla Marco Adelmo James , Zanotti Giovanni , Huynh Lynn , Duh Mei Sheng , Heng Daniel Yick Chin 
Published: March 2019

610 Background: Prognostic factors such as the IMDC criteria have included all types of targeted therapy. This study assesses clinical outcomes and provide benchmarks for mRCC pts treated specifically with 1L SUN in the real world to provide contemporary benchmarks for outcomes and survival. Methods: Clear cell mRCC pts initiating SUN as 1L therapy between 2010-2018 were included in a retrospective database study. Kaplan Meier analysis was used to estimate median time to treatment discontinuation (TTD) and overall survival (OS: time to death) by IMDC risk groups based on Karnofsky Performance Status < 80%, diagnosis to treatment interval < 1 year, anemia, neutrophilia, hypercalcemia and thrombocytosis. Results: Among 1,769 1L SUN pts with clear cell in the RW clinical database, 318 (18%) had favorable, 1,031 (58%) had intermediate and 420 (24%) had poor IMDC risk. Across the favorable, intermediate, and poor risk groups, pts had similar mean age in years, gender distribution, and year of SUN initiation (age: 63.8, 62.9 and 62.6; male: 74%, 75%, and 72%; SUN initiation year of 2010-2013: all 71%). In the favorable risk group, 99% received nephrectomy vs 88% in intermediate and 66% in poor risk group. Median TTD was 15.0, 8.5, and 4.2 months (mos) in the favorable, intermediate, and poor risk groups, respectively, and was 7.1 mos in the combined intermediate/poor risk groups. Median OS was 52.1, 31.5, and 9.8 mos in the favorable, intermediate, and poor risk groups, respectively, and was 23.2 mos in the combined intermediate/poor risk groups. Conclusions: This real world study based on a contemporary cohort of 1L SUN mRCC pts found a median OS of 52 mos which sets a new benchmark for clear cell mRCC in the favorable risk group. OS in the intermediate and poor risk groups are similar to previous reports. This affects pt counselling and clinical trial design.
Safety and feasibility of nephrectomy after receipt of immune checkpoint inhibitors for renal cell carcinoma.
Authors: Singla Nirmish , Elias Roy , Ghandour Rashed , Freifeld Yuval N , Bowman Alex Isaac , Woldu Solomon L. , Gahan Jeffrey , Bagrodia Aditya , Brugarolas James , Hammers Hans J. , Margulis Vitaly 
Published: March 2019

619 Background: With the approval of immune checkpoint inhibitors (ICI) for metastatic renal cell carcinoma (RCC), the role, timing, and safety of surgically excising the primary tumor remain unclear. We sought to evaluate the safety and feasibility of nephrectomy following receipt of ICI for RCC. Methods: We reviewed our experience of RCC patients who underwent nephrectomy from 2016-2018 following exposure to nivolumab or combination ipilimumab/nivolumab. Demographics, IMDC risk score, and pathology were collected. Surgical outcomes including operative time (OT), estimated blood loss (EBL), hospital length of stay (LOS), readmission rates, and 30- and 90-day complication rates were analyzed using descriptive statistics. Results: 11 nephrectomies (10 radical, 1 partial) were performed in 10 patients after ICI with median postoperative follow-up 98 days. 6 patients received 1-4 cycles of ipilimumab/nivolumab, while 5 received 2-12 infusions of nivolumab preoperatively. One patient with non-metastatic, synchronous bilateral renal masses underwent staged left radical nephrectomy and right partial nephrectomy. 5 surgeries were performed laparoscopically, and 4 patients underwent thrombectomy. IMDC score for metastatic patients was intermediate (7/9) or poor (2/9). One patient exhibited complete response (pT0) to ICI, and 3/4 patients who underwent metastasectomy for hepatic, pulmonary, or adrenal lesions exhibited no malignancy in any of the metastases resected. No patients experienced any major intraoperative complications, and all surgical margins were negative. Median OT, EBL, and LOS were 180 minutes, 100 mL, and 4 days, respectively. One patient died of progressive disease > 3 months after surgery; one patient required thoracentesis and another required paracentesis of a sterile fluid collection in the hepatic resection bed. No complications were noted in the remaining 7 patients, none of whom required readmission. Conclusions: Nephrectomy following ICI for RCC is safe and technically feasible with favorable surgical outcomes and pathologic response. As multimodal management in the era of ICI continues to evolve, use of neoadjuvant ICI for selected patients may warrant attention.
Prognostic value of gain of chromosome 5q in localized renal cell carcinoma.
Authors: Lebacle Cedric Michel , Pooli Aydin , Rao Nagesh , Wood Erika Louise , Kroeger Nils , Liu Sandy , Faiena Izak , Chamie Karim , Belldegrun Arie S. , Shuch Brian , Drakaki Alexandra , Pantuck Allan J. 
Published: March 2019

623 Background: While gain of chromosome 5q is a frequently seen cytogenetic abnormality noted to occur in patients with renal cell carcinoma (RCC), little is known about its prognostic significance. We investigated the association of gain of 5q with disease-free survival (DFS) in patients with localized (non-metastatic T1-2) RCC. Methods: All patients from UCLA with primary tumor stage T1-2 RCC who had tumor cytogenetic analysis on tumor specimen were included. Alterations in chromosome 5q was specifically reviewed in this study. Logistic regression analyses were used to assess association of gain of 5q with final histopathology, ISUP grading, and T-stage. Cox proportional hazard modeling and Kaplan-Meier analyses were used to assess the impact of gain of 5q on DFS. Recurrence was defined as any local recurrence or development of new metastasis. Results: A total of 676 patients were included in this study. Gain of 5q occurred in 108 (16%) patients and was more commonly seen in clear cell versus non-clear cell tumors (19% vs. 9%, p = .002). Gain of 5q was associated with low grade ISUP (1 or 2) of clear-cell RCC (p = 0.011). On survival analysis, there was a 67% decreased risk of RCC recurrence for patients with gain of 5q (HR = 0.33, p = 0.018). The 5- and 10-year risk of recurrence was 2% vs. 16% and 14% vs. 28% for patients with and without gain of 5q, respectively (p = 0.013). In multivariable Cox analysis, the gain of 5q was an independent prognostic factor (p = .026 with ISUP grade and p = .025 with T-stage). These findings were confirmed among clear-cell RCC subgroup. Conclusions: Gain of chromosome 5q is an independent prognostic factor associated with decreased risk of recurrence in patients with localized T1-2 renal cell carcinoma. Identifying patients with a gain of 5q will improve the stratification of the risk of recurrence, could allow to adapt the follow-up protocols and avoid adjuvant treatment.
Combination anti-angiogenic tyrosine kinase inhibition and anti-PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes.
Authors: Laccetti Andrew L. , Economides Minas P. , Venkatesan Aradhana M. , Gao Jianjun , Jonasch Eric , Corn Paul Gettys , Zurita Amado J. , Tannir Nizar M. , Msaouel Pavlos , Shah Amishi Yogesh , Campbell Matthew T 
Published: March 2019

630 Background: Emerging phase III data support combination antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) as front line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off-protocol experience and later line treatment with this therapeutic approach including tolerance, response and survival. Methods: We conducted a retrospective analysis of mRCC patients (pts) who received combination TKI-IO between 11/2015 and 05/2018 at MD Anderson Cancer Center. Chart review detailed baseline characteristics, TKI-IO treatment, toxicity and survival. An independent radiologist, blinded to pts history and clinical data, assessed radiographic response using RECIST v1.1. Results: 36 mRCC pts were identified for study inclusion: median (med) age 63.5 years, 72% clear cell histology, 53% intermediate risk (19% good, 28% poor) by IMDC, med metastatic sites 2, med prior therapies 2, previous TKI 94% and previous IO 47%. Combinations included nivolumab (nivo)-cabozantinib (15), nivo-low dose pazopanib(ldP) (13), nivo-axitinib (5), nivo-lenvatinib (2) and pembrolizumab-axitinib (1). Median time on TKI-IO was 5.6 months (m) (95% CI: 5.2 - 7.7). 56% of pts initiated TKI prior to IO addition at progression and 36% of pts initiated IO prior to TKI addition. ORR was 35% (29% PR and 6% CR); disease control rate was 78% (43% stable disease). With med follow-up of 8.0 m (95% CI: 6.4 – 9.4), med PFS was 7.7 m (95%CI: 5.8 - 9.5), med OS was not reached. Med PFS for pts receiving nivo-ldP was not reached. TKI-IO therapy was well tolerated with only 1 pt demonstrating grade 3 or 4 immune related toxicity (nephritis). 92% of pts experienced any grade of adverse events (ADE) with ADE of interest as follows: diarrhea (25%), hypothyroidism (17%), and pneumonitis (8%). Conclusions: To our knowledge, this is the first case series of off-label combinations of TKI-IO for mRCC. TKI-IO, particularly nivo-ldP, is safe, well tolerated and efficacious. Although further prospective research is essential, TKI-IO could be considered for select mRCC patients, particularly in the setting of TKI or IO refractory disease.
Identifying predictive biomarkers for metastatic progression in stage I and II clear cell renal cell carcinoma.
Authors: Murphy Neal J , Shih Andrew , Kozel Zachary , Shah Paras , Yaskiv Oksana , Khalili Houman , Liew Anthony , Kavoussi Louis R , Hall Simon , Vira Manish Arvind , Lee Annette , Zhu Xinhua 
Published: March 2019

631 Background: For most clear cell renal cell carcinoma (ccRCC) patients with early stage disease, surgical resection offers definitive cure. However, for the small percentage of tumors that metastasize, analyzing gene expression profiles from the primary site at the time of nephrectomy can serve as a model to understand the molecular aberrations behind a metastatic phenotype. Differences in gene expression profiles between patients with Stage I and II ccRCC who experience metastasis versus patients who maintain cure after surgery may help elucidate significant molecular targets and stratify patients at higher risk for metastasis. Methods: Nineteen Stage I and twenty Stage II ccRCC tumors preserved in FFPE blocks after nephrectomy were included in this study. Patients were matched for age, gender, tumor size and grade. In both stages, approximately half the patients that experienced metastasis within 5 years of surgery were part of the experimental group, whereas the control group had > 5 years of follow-up without evidence of disease. Extracted RNA for Stage I patients was sequenced using Illumina TruSeq RNA Access Library. Gene counts were assessed by ht-seq counts and differential expression using DESeq2. Significant genes found were validated in the Stage II group using RT-qPCR. Results: In the Stage I experimental group, statistically significant upregulation of several genes associated with unfavorable prognosis in RCC were found: COL1A1, NUMBL, and STEAP3. Random forest classification accurately separated Stage I control versus experimental patients based on expression of COL1A1. Affected genes were consistent with molecular changes seen in TCGA analysis. In the Stage II group, a double-blinded analysis correctly identified the clinical outcome for the majority of the patients using qPCR expression of COL1A1, NUMBL, and STEAP3. Conclusions: Differences in gene expression profiles harbored in the primary site of early stage ccRCC may be employed to predict patients at high risk for developing metastasis. Validating these findings in a larger study carries the potential to better understand mechanisms of metastasis and identify an at risk cohort of patients with early stage disease.