Abstract
Skeletal muscle depletion is common in patients with advanced cancer and may be associated with a poor outcome. To investigate whether the changes in skeletal muscle in metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy are associated with clinical outcome, we undertook an observational cohort study using data from a number of randomized clinical trials previously conducted at the Fudan University Shanghai Cancer Center. The muscle mass was evaluated by comparing computed tomography images obtained at baseline with those obtained after 3–4 months of treatment. A total 101 patients were included in the study. The mean skeletal muscle area reduced from 41.6 cm2/m2 to 39.9 cm2/m2 after 3–4 months of targeted therapy. In multivariable analyses adjusted for the number of baseline covariates, muscle loss ≥5% was shown to be a significant prognostic factor for both progression-free (hazard ratio [HR]: 1.744, 95% confidence interval [CI]: 1.077–2.826, P = 0.024) and overall survival (HR: 2.367, 95%CI: 1.253–4.469, P = 0.008). The addition of muscle loss to the Heng model significantly improved its discriminative ability. In summary, early skeletal muscle loss is frequently observed in mRCC patients and can add prognostic information to current clinical risk scores.
Highlights
Cachexia is a complex metabolic syndrome that typically occurs in cancer and other chronic diseases[1]
In multivariable analyses adjusted for the number of baseline covariates, multivariate Cox survival analysis indicated that skeletal muscle loss ≥5% remained a significant prognostic factor for poor Progression-free survival (PFS) (HR: 1.744, 95% CI: 1.077–2.826, P = 0.024) and Overall survival (OS) (HR: 2.367, 95% CI: 1.253–4.469, P = 0.008; Table 3)
We observed a mean reduction in muscle area and muscle density of 1.71 cm2/m2 and 5.6 Hounsfield unit (Hu) after [3,4] months of targeted therapy
Summary
Cachexia is a complex metabolic syndrome that typically occurs in cancer and other chronic diseases[1]. Cachexia is commonly identified in advanced and metastatic renal cell carcinoma (RCC) patients, and it can indicate a paraneoplastic syndrome[3]. Cachexia-like symptoms have been shown to be an independent biomarker of a worse prognosis in patients with early stage RCC4. It is generally accepted that the weight loss associated with advanced malignant diseases involves the loss of fat and lean body mass, especially skeletal muscle. Cross-sectional studies in metastatic RCC patients have shown that weight and tissue loss is specific to anti-angiogenic therapies[12], few studies have investigated the prognostic value of longitudinal changes of body composition over time in metastatic RCC patients receiving targeted therapy. Very recently have we appreciated that the change of muscle mass over time is highly important[13], but we did not know this for renal cell carcinoma. Patients after [3,4] months of treatment, and to investigate any correlations with survival or treatment toxicity, using computed tomography (CT) images obtained during a number of previous phase II and III clinical trials
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