In a study investigating the clinical and biologic effects of body mass index on treatment outcomes in patients with metastatic renal cell carcinoma, Albiges et al found that obese patients treated with targeted therapy had improved survival and progression-free survival compared with patients with a low body mass index. The results, which were reported in the Journal of Clinical Oncology, suggest that inhibiting the expression of fatty acid synthase (FASN) may improve outcomes in patients with kidney cancer.
Although obesity is an established risk factor for clear cell renal cell carcinoma, some studies have suggested that the cancer developing in obese people may be more indolent.
The researchers investigated the impact of body mass index (high body mass index: ≥ 25 kg/m2 vs low body mass index: < 25 kg/m2 ) on overall survival and treatment outcome with targeted therapy in patients with metastatic renal cell carcinoma. They analyzed data from 1,975 patients in the International Metastatic Renal Cell Carcinoma Database (IMDC) and in an external validation cohort of 4,657 patients.
To investigate biologic differences associated with different body mass index groups, the researchers used genomic data of mRNA expression from 324 patients in The Cancer Genome Atlas (TCGA) consortium. Tissue samples from the pretreatment primary tumors and/or metastatic lesions from 146 patients in the IMDC biospecimen repository were also analyzed. Gene-expression profiling focusing on the fatty acid metabolism pathway, in the TCGA data set, and immunohistochemistry staining for fatty acid synthase were also investigated.
Cox regression was undertaken to estimate the association of body mass index with overall survival, adjusted for the IMDC prognostic factors.
In the IMDC cohort, median overall survival was 25.6 months (95% confidence interval [CI] = 23.2–28.6 months) in patients with a high body mass index vs 17.1 months (95% CI = 15.5–18.5 months) in patients with a low body mass index (adjusted hazard ratio = 0.84; 95% CI = 0.73–0.95). In the validation cohort, a high body mass index was associated with improved overall survival (adjusted hazard ratio = 0.83; 95% CI = 0.74–0.93; medians: 23.4 months [95% CI = 21.9–25.3 months] vs 14.5 months [95% CI = 13.8–15.9 months], respectively). In the TCGA data set (n = 61), FASN gene expression inversely correlated with body mass index (P = .034), and overall survival was longer in the low Q:7 FASN expression group (medians, 36.8 vs 15.0 months; P = .002). FASN immunohistochemistry positivity was more frequently detected in IMDC poor-risk (48%) and intermediate-risk (34%) groups than in the favorable-risk group (17%; P trend = .015).
Targeting the FASN Pathway
“We demonstrate that [body mass index] affects [metastatic renal cell carcinoma] clinical outcomes even after adjustment for known prognostic factors. Biologically, we used tumors from patients with [metastatic renal cell carcinoma] from the [clear cell renal cell carcinoma] TCGA and from the IMDC data sets and showed that FASN pathway activation (FASN gene expression and [immunohistochemistry] staining) is associated with [body mass index] and survival. This suggests an integral role for [fatty acid] metabolism in the prognosis of patients with [metastatic renal cell carcinoma] and lays the groundwork for future therapeutic interventions that target the FASN pathway,” concluded the researchers.
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