Τίτλος:
Body mass index and metastatic renal cell carcinoma: Clinical and biological correlations
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose: Obesity is an established risk factor for clear cell renal cell carcinoma (RCC); however, some reports suggest that RCC developing in obese patients may be more indolent. We investigated the clinical and biologic effect of body mass index (BMI) on treatment outcomes in patients with metastatic RCC. Methods: The impact of BMI (high BMI: ≥ 25 kg/m2 v low BMI:, 25 kg/m2) on overall survival (OS) and treatment outcome with targeted therapy was investigated in 1,975 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and in an external validation cohort of 4,657 patients. Gene expression profiling focusing on fatty acid metabolism pathway, in The Cancer Genome Atlas data set, and immunohistochemistry staining for fatty acid synthase (FASN) were also investigated. Cox regression was undertaken to estimate the association of BMI with OS, adjusted for the IMDC prognostic factors. Results: In the IMDC cohort, median OS was 25.6 months (95% CI, 23.2 to 28.6) in patients with high BMI versus 17.1 months (95% CI, 15.5 to 18.5) in patients with low BMI (adjusted hazard ratio, 0.84; 95% CI, 0.73 to 0.95). In the validation cohort, high BMI was associated with improved OS (adjusted hazard ratio, 0.83; 95% CI, 0.74 to 0.93; medians: 23.4 months [95% CI, 21.9 to 25.3 months] v 14.5 months [95% CI, 13.8 to 15.9 months], respectively). In The Cancer Genome Atlas data set (n = 61), FASN gene expression inversely correlated with BMI (P =.034), and OS was longer in the low FASN expression group (medians: 36.8 v 15.0 months; P =.002). FASN immunohistochemistry positivity was more frequently detected in IMDC poor (48%) and intermediate (34%) risk groups than in the favorable risk group (17%; P-trend =.015). Conclusion: High BMI is a prognostic factor for improved survival and progression-free survival in patients with metastatic RCC treated with targeted therapy. Underlying biology suggests a role for the FASN pathway. © 2016 by American Society of Clinical Oncology.
Συγγραφείς:
Albiges, L.
Ari Hakimi, A.
Xie, W.
McKay, R.R.
Simantov, R.
Lin, X.
Lee, J.-L.
Rini, B.I.
Srinivas, S.
Bjarnason, G.A.
Ernst, S.
Wood, L.A.
Vaishamayan, U.N.
Rha, S.-Y.
Agarwal, N.
Yuasa, T.
Pal, S.K.
Bamias, A.
Zabor, E.C.
Skanderup, A.J.
Furberg, H.
Fay, A.P.
De Velasco, G.
Preston, M.A.
Wilson, K.M.
Cho, E.
McDermott, D.F.
Signoretti, S.
Heng, D.Y.C.
Choueiri, T.K.
Περιοδικό:
Journal of Clinical Oncology
Εκδότης:
American Society of Clinical Oncology
Λέξεις-κλειδιά:
alpha interferon; axitinib; bevacizumab; cabozantinib; everolimus; pazopanib; sorafenib; sunitinib; temsirolimus; tivozanib, adult; aged; Article; body mass; cancer chemotherapy; cancer patient; cancer prognosis; FASN gene; female; gene; gene expression; human; human tissue; immunohistochemistry; kidney metastasis; major clinical study; male; molecularly targeted therapy; obesity; overall survival; phase 2 clinical trial (topic); phase 3 clinical trial (topic); post treatment survival; priority journal; treatment outcome; very elderly
DOI:
10.1200/JCO.2016.66.7311
