scholarly journals MP16-19 MECHANISMS UNDERLYING THE ASSOCIATION BETWEEN SARCOPENIA AND POOR ONCOLOGIC OUTCOMES IN CLEAR CELL RENAL CELL CARCINOMA

2019 ◽  
Vol 201 (Supplement 4) ◽  
Author(s):  
Alejandro Sanchez* ◽  
Fengshen Kuo ◽  
Stacey Petruzella ◽  
Oguz Akin ◽  
Michael Paris ◽  
...  
2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16096-e16096
Author(s):  
Nirmish Singla ◽  
Oreoluwa Onabolu ◽  
Layton Woolford ◽  
Christina Stevens ◽  
Vanina Tcheuyap ◽  
...  

e16096 Background: The tropism of cancer metastases is poorly understood yet holds prognostic value. Clear cell renal cell carcinoma (ccRCC) exhibits a broad pattern of metastases, making it an optimal model to study organotropism. Notably, when ccRCC metastasizes to the pancreas (PM) independently of other sites, it is associated with favorable outcomes in patients for unclear reasons. Here, we comprehensively analyzed the clinical and molecular profile of patients with PM. Methods: RCC patients with PM from UTSW and Cleveland Clinic were identified. Clinicopathologic data and oncologic outcomes were analyzed. Whole exome sequencing (WES), RNAseq, and histologic assessment of primary and metastatic tumors from PM patients were conducted. Results: 31 RCC patients with PM were identified. We observed remarkably favorable outcomes in our PM cohort, with a median overall survival (OS) of 10.7 years from metastatic diagnosis and a long latency between initial diagnosis and development of metastasis (median 69 months in patients who were non-metastatic at diagnosis). OS was independent of both metastatic tumor burden and known IMDC prognostic factors. We discovered that tumors from PM patients were markedly uniform and clustered together by gene expression analysis. WES and DNA copy number analyses revealed a high frequency of VHL and PBRM1 mutations, 3p loss, and 5q amplification, along with a lower frequency of 9p, 14q and 4q losses and BAP1 mutations, characteristic of indolent ccRCC. Furthermore, the genomic and histologic features of tumors from patients with PM can be recapitulated in patient-derived xenograft models. Conclusions: To our knowledge, this is the first report to unravel molecular determinants of organotropism, and we highlight that organotropism can be an independent prognostic factor. Understanding tumor heterogeneity may help refine prognostic models for metastatic RCC and hold implications for improved personalization of therapy.


2016 ◽  
Vol 34 (10) ◽  
pp. 1429-1436 ◽  
Author(s):  
Vincent Trudeau ◽  
Alessandro Larcher ◽  
Maxine Sun ◽  
Katharina Boehm ◽  
Paolo Dell’Oglio ◽  
...  

2014 ◽  
Vol 191 (6) ◽  
pp. 1671-1677 ◽  
Author(s):  
Laura-Maria Krabbe ◽  
Mary E. Westerman ◽  
Aditya Bagrodia ◽  
Bishoy A. Gayed ◽  
Oussama M. Darwish ◽  
...  

2022 ◽  
Vol 11 ◽  
Author(s):  
Josiah An ◽  
Vignesh T. Packiam ◽  
Adithya Chennamadhavuni ◽  
Jordan Richards ◽  
Jayanshu Jain ◽  
...  

BackgroundNon-clear cell renal cell carcinoma (ccRCC) includes histologically and molecularly distinct subtypes such as papillary, chromophobe, collecting duct, and sarcomatoid RCC, with an incidence ranging from 20% to 25%. Oncologic outcomes and the role of adjuvant systemic therapy [vascular endothelial growth factor inhibitor (VEGFi) or immunotherapy] for non-ccRCC are not well-described.ObjectiveTo assess the incidence and survival outcomes of non-ccRCC subtypes in comparison to ccRCC.MethodsThe National Cancer Database was utilized to identify patients with non-metastatic RCC (T1–T4, N0–N1) between 2004 and 2015. The non-ccRCC cohort was further stratified by histologic subtype: papillary, chromophobe, sarcomatoid, and collecting duct RCC. Multivariable Cox regression models were used to compare overall survival (OS).ResultsThe 5-year OS for chromophobe, papillary, clear cell, collecting duct, and sarcomatoid RCC was 91%, 82%, 81%, 44%, and 40%, respectively. After adjusting for clinicopathologic and treatment characteristics, there was no significant difference in OS between papillary RCC and ccRCC (p = 0.17). Patients with collecting duct and sarcomatoid subtypes were at over two times increased risk of death compared to patients with clear cell (p < 0.01 and p < 0.01, respectively). Conversely, patients with chromophobe RCC were at 36% decreased risk of death compared to ccRCC (p < 0.01).ConclusionsThis hospital-based analysis confirms that collecting duct and sarcomatoid histologic subtypes are uncommon and associated with poor survival after surgery when compared to the other RCC subtypes. Further studies are needed to evaluate the role of neoadjuvant and adjuvant systemic therapies in these subtypes to improve oncologic outcomes.


2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
Heinric Williams ◽  
Anup Vora ◽  
Angelo Baccala ◽  
Peter Pinto ◽  
W. Marston Linehan ◽  
...  

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