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. 2020 Mar 5;12(3):595.
doi: 10.3390/cancers12030595.

Muscle Loss after Chemoradiotherapy as a Biomarker of Distant Failures in Locally Advanced Cervical Cancer

Jie Lee  1   2 , Jhen-Bin Lin  3 , Meng-Hao Wu  1 , Chih-Long Chang  2   4 , Ya-Ting Jan  5 , Yu-Jen Chen  1
Affiliations

Muscle Loss after Chemoradiotherapy as a Biomarker of Distant Failures in Locally Advanced Cervical Cancer

Jie Lee et al. Cancers (Basel). .

Abstract

This study aimed to evaluate whether computed tomography (CT)-based muscle measurement predicts distant failure in patients with locally advanced cervical cancer (LACC). Data from 278 patients with LACC who underwent chemoradiation therapy (CCRT) between 2004 and 2017 were analysed. Changes in the skeletal muscle index (SMI), skeletal muscle density, and total adipose tissue index during CCRT were calculated from CT images taken at the baseline and after CCRT. The predictive capability of CT-based muscle measurement for distant failure was evaluated using Cox proportional hazards regression, Harrell's concordance index (C-index), and time-dependent receiver operating characteristic curves. SMI loss ≥ 5% was independently associated with worse distant recurrence-free survival (DRFS) (HR: 6.31, 95% CI: 3.18-12.53; p < 0.001). The addition of muscle change to clinical models, including International Federation of Gynaecology and Obstetrics (FIGO) stage, lymph nodes, pathology, and squamous cell carcinoma-antigen, achieved higher C-indices (0.824 vs. 0.756; p < 0.001). Models including muscle change had superior C-indices than those including weight change (0.824 vs. 0.758; p < 0.001). The area under the curve for predicting 3-year DRFS was the highest for the muscle-loss model (0.802, muscle-loss model; 0.635, clinical model; and 0.646, weight-loss model). Our study demonstrated that muscle loss after CCRT was independently associated with worse DRFS and that integrating muscle loss into models including classical prognostic factors improved the prediction of distant failure.

Keywords: cervical cancer; chemoradiotherapy; computed tomography; distant failures; skeletal muscle loss.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The change of skeletal muscle area (outlined in blue) on computed tomography (CT) images at the L3 vertebral level at the baseline (A) and after chemoradiation therapy (B) from one patient. Images were taken 5 months apart. At the time point of pre-treatment CT, the body mass index (BMI) and skeletal muscle index (SMI) were 24.1 kg/m2 and 51.8 cm2/m2, respectively. At the time point of post-treatment CT, the BMI and SMI were 25.4 kg/m2 and 47.3 cm2/m2, respectively.
Figure 2
Figure 2
Scatter plots showing correlations between the changes in BMI, SMI, skeletal muscle density (SMD), and total adipose tissue index (TATI): (A) SMI vs. BMI, (B) SMD vs. BMI, (C) TATI vs. BMI, (D) SMD vs. SMI, (E) TATI vs. SMI, and (F) TATI vs. SMD. Spearman’s rank correlation coefficient (rho) was used to assess correlations between body composition parameters. Slopes (m) for the correlations are shown on each graph.
Figure 3
Figure 3
Pre-treatment (A) BMI, (B) SMI, (C) SMD, and (D) TATI according to SMI change groups.
Figure 4
Figure 4
Kaplan–Meier curve demonstrating distant recurrence-free survival according to (A) weight change, (B) SMI change, (C) SMD change, and (D) TATI change groups. DRFS, distant recurrence-free survival; SMD, skeletal muscle density; SMI, skeletal muscle index; TATI, total adipose tissue index.
Figure 5
Figure 5
Kaplan–Meier curve demonstrating distant recurrence-free survival in patients with “No SMI loss”, “Only SMI loss”, and “SMI and TATI losses”.
Figure 6
Figure 6
Receiver operating characteristic curves for 3-year distant recurrence-free survival in overall patients (n = 278).
See this image and copyright information in PMC

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