1. Introduction
Renal cell carcinoma (RCC) constituting 4 % of all cancers is the sixth and the tenth most frequently diagnosed cancer type in men and women worldwide, respectively [1]. Although most of the lesions detected incidentally via developed imaging techniques were small and low-grade tumors, 17% of all RCC cases present with distant metastasis at diagnosis [2]. Due to recent advances, the first-line treatment for metastatic renal cell carcinoma (mRCC) has evolved from cytokine-based treatment to vascular endothelial growth factor (VEGF) pathway inhibitors, immune checkpoint blockers, and their combination. To define the prognosis of mRCC patients, two models named “International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)” and “The Memorial Sloan-Kettering Cancer Center (MSKCC) Criteria” were established, and mRCC patients were classified in terms of risk levels as favorable, intermediate and poor [3, 4].
Although obesity is linked to increased risk of developing RCC, underlying mechanisms of this link is poorly understood [5]. It has been demonstrated that the biological mechanisms of obesity leads to development of RCC including chronic tissue hypoxia, change of the hormonal environment in the fat tissue, and immune dysfunction [6, 7]. Interestingly, some studies showed that obese mRCC patients have a better response to treatment and thereby a better prognosis as it has been named as the ‘obesity paradox’ in the literature [8, 9]. This ‘risk factor’ paradox may be due to the time gap between two detrimental risk factors that overnutrition is a well known long-term killer but can be a protective factor in the short term, while malnutrition is a short-term killer [10]. Additionally, the decline of skeletal muscle, called sarcopenia, has been reported as a predictor of prognosis in various tumors including RCC [11-13]. Also, it has been shown that the decline in skeletal muscle mass is related to increased side effects in cancer treatment and worsened survival outcomes [14, 15].
Body Mass Index (BMI) is a rough sketch of the distribution of fat in the body. Hence, BMI alone is not sufficient to detect the exact body composition parameters and the sarcopenia, which is characterized by the loss of body fat composition and skeletal muscle tissue. Computerized tomography (CT) is routinely used to determine staging and treatment response evaluation of RCC. This technique allows for the better categorization of fat and skeletal muscle tissue. Additionally, CT can be used in the relative classification of the fat tissue in visceral and subcutaneous compartments [visceral adipose tissue (VAT) and superficial adipose tissue (SAT)]. The studies on the effects of these parameters on the prognosis of mRCC delivered different results. Steffens et al. [8] and Gu et al. [16] demonstrated that the higher VAT and SAT were correlated with prolonged OS in mRCC patients. Contrary to these findings, increased VAT was found to be correlated with poor outcomes in the Ladoire’s cohort [17]. A study by Antoun et al. demoonstrated no correlation between VAT or SAT and survival outcomes in patients with mRCC [18]. It has been shown that body weight and tissue loss can contribute to predicting the prognosis of mRCC patients treated with targeted therapy [19]. However, few studies have evaluated the prognostic value of longitudinal changes in parameters of body composition over time in mRCC patients treated with targeted therapy. The current study aimed to investigate whether or not obesity and volumetric body composition (VBC) parameters can predict the outcomes in mRCC patients treated with targeted therapy (pazopanib or sunitinib) in terms of VAT, subcutaneous SAT, BMI, skeletal muscle area (SMA) measurements and their changes after 3-4 months after initial CT.