Decrease in Skeletal Muscle Index After Definitive Chemoradiation Therapy for Stage III Non–small Cell Lung Cancer is Associated With Decreased Overall Survival

Abstract

Decrease in skeletal muscle mass (sarcopenia) is included as a criterion for diagnosis of cancer cachexia. Computed tomography (CT)-derived cross sectional muscle area (SMA) can be used as a surrogate to define sarcopenia. A decrease in SMA has been shown to correlate with decreased survival in patients with non-malignant pulmonary disorders. To our knowledge, no one has evaluated the prognostic implications of CT-defined sarcopenia during and after definitive chemoradiotherapy for stage III non-small cell lung cancer. This IRB-approved retrospective study queried patients with stage III NSCLC treated with definitive chemoradiotherapy from 2012-2016. Patients missing baseline weight at time of staging CT or accessible axial CT images from diagnosis and immediate post-treatment surveillance were excluded. SMA (cm2) was calculated based on manual segmentation (facilitated by standardized commercially available software) of abdominal wall and paravertebral musculature on two contiguous slices at the center of the L1 vertebral body for each patient using axial CT images from date of diagnosis and at immediately post-treatment. Skeletal muscle index (SMI) for each CT was calculated as the average of the SMA divided by height (m). Demographic and clinical information were obtained from chart review. A two sided paired t-test was used to compare changes in weight with change in SMI after treatment. The Kaplan-Meier method was used to estimate survival after treatment. The log rank test was used to compare survival of patients according to change in SMI. 27 patients were included in this analysis. 19 (70.4%) are alive with median follow up of 23 months for survivors (range 6 to 54 months). Mean age at diagnosis was 66 (range 51-86), 11 men and 16 women. 11 (40.7%) had squamous cell histology and 16 (59.3%) had adenocarcinoma. 17 (63%) had stage IIIA disease and 10 had IIIB disease (37%). Concurrent chemotherapy regimens included carboplatin/etoposide, carboplatin/paclitaxel, and carboplatin/pemetrexed. Mean SMI at staging was 60.53 (range 31.00-87.67) with a mean change of +2.60% after treatment (range -12.24 to +23.38%). 15 patients had an increase in SMI and 14 patients had an increase in weight. Mean change in weight was +0.3% (range –11.50 to +14.1%). Seven patients had an inverse change in weight vs. SMI (ie. increase in weight with decrease in SMI or vice versa). For the entire cohort, there was no statistical correlation between change in weight and change in SMI (p = .254). Decrease in SMI greater than -3% was correlated with decreased 2 year overall survival (2 year OS with decrease in SMI >= -3% was 57.1% vs. 80.1%, p = 0.048). Patients with a decrease in SMI after definitive chemoradiotherapy have a poor prognosis. This data may allow for the selection of patients who may benefit from the integration of additional systemic therapy, closer surveillance, or nutritional optimization after definitive chemoradiotherapy.