Skeletal Muscle Depletion Predicts the Prognosis of Patients with Hepatocellular Carcinoma Treated with Radiation Therapy

Abstract

Sarcopenia is gaining attention, being identified as a poor prognostic factor for various types of malignancies. Particularly, sarcopenia occurs frequently in cases of hepatocellular carcinoma (HCC) after treatment. However, the clinical significances of sarcopenia in patients underwent radiotherapy (RT) for HCC is not yet been identified. The purpose of this study is to evaluate the association between sarcopenia and survival in HCC patients underwent RT to the primary site. Between January 2009 and November 2016, a total number of 156 patients with stage I-IVB primary HCC underwent RT to the liver. Among these, 64 patients received RT with definitive aim, 43 patients with palliative aim, and 49 patients with salvage aim. Eighty-one patients were treated with concurrent chemotherapy (CTx), and 75 patients were treated with RT only. The median RT dose was 50.4 Gy (30 Gy-70 Gy). The cross-sectional area of muscle at the level of 3rd lumbar vertebra was measured using baseline CT images (L3 skeletal muscle index; L3-SMI). Sarcopenia was defined as a L3-SMI of less than 49 for men and less than 41 for women as proposed by Korean-specific cut off value. The sarcopenia was identified at two-time points; pre- and post-RT. Pre-RT sarcopenia was diagnosed with data from the simulation CT prior to RT, while post-RT sarcopenia was diagnosed with data from the follow-up CT taken within 3 months from the end of RT. Overall survival (OS) and progression-free survival (PFS) were estimated from the start of RT, and the prognostic factors associated with the survival were analyzed. Among a total of 156 patients, 3 patients were stage I, 15 patients were stage II, 48 patients were stage III, and 90 patients were stage IV, respectively. According to Korean-specific cut off value, 99 patients (63.5%) had pre-RT sarcopenia, while 109 patients (69.9%) had post-RT sarcopenia. Pre-RT sarcopenia group had higher percentage of patients with previous CTx (14.1 % vs 1.8 %), compared with those without pre-RT sarcopenia. At a median follow up 9.3 months, median OS were significantly differed according to the presence of pre-RT sarcopenia (7.1 vs. 15.3 months, p < 0.001) and post-RT sarcopenia (7.5 vs. 16.8 months, p < 0.001), while median PFS differed according to pre-RT sarcopenia with borderline significance (3.3 vs. 5.6 months, p = 0.051). In univariate analysis, total dose, Child-Pugh classification, cancer stage at time of RT, AFP level, Neutrophil-Lymphocyte ratio, Platelet-Lymphocyte ratio, pre-RT and post-RT sarcopenia have shown to be significant prognostic factors for OS. In multivariate analysis, total dose and pre-RT sarcopenia were identified as independent prognostic factors for OS. In our study, pre-RT sarcopenia was associated with a poor prognosis for HCC patients underwent RT to liver. This result suggests the possibility that the identification of sarcopenia in HCC patients before RT might enable the early intervention to maintain muscle mass and improve prognosis.