Cachexia and efficiency of trifluridine/thymidine phosphorylase inhibitor + bevacizumab in metastatic colorectal cancer

Abstract

In later-line treatment of metastatic colorectal cancer (mCRC), there may be large differences in treatment efficacy depending on cancer cachexia. Recently, the cachexia index (CXI), which was calculated from the skeletal muscle mass index (SMI), serum albumin concentration, and neutrophil-to-lymphocyte ratio, was developed to evaluate cancer cachexia. We retrospectively examined the CXI of 80 patients who were treated with trifluridine/thymidine phosphorylase inhibitor (FTD/TPI) + bevacizumab (Bmab) therapy as a later-line treatment for mCRC, and assessed the impact of cancer cachexia on chemotherapeutic efficacy using CXI. Progression-free and overall survival rates were significantly worse in the low CXI group than in the high CXI group, although there were no marked differences in tumor factors, such as the number of metastatic organs or gene mutations, between the two groups. As the cross-sectional area of the iliopsoas muscle was significantly associated with that of the skeletal muscle, the accuracy of the CXI based on the psoas mass index (P-CXI), which is easier to calculate than the SMI, in predicting treatment outcomes was equivalent to that of the CXI based on the SMI (S-CXI). Cancer cachexia is an important factor related to treatment efficacy in later-line treatments, such as FTD/TPI + Bmab therapy.

Keywords: Bevacizumab; CXI; Cachexia; Colorectal cancer; FTD/TPI.

Fig. 1

Representative images of body composition components were reconstructed using the SYNAPSE VINCENT 3-dimensional medical image analysis system. (a) Cross-sectional computed tomography image at the level of the umbilicus. Areas colored in yellow and orange indicate the skeletal muscle area, and those colored green indicate the psoas muscle area. (b) Three-dimensional image construction. Green areas indicate the total volume of the psoas muscle.

Fig. 2

A receiver operating characteristic curve analysis of the cachexia index. (a) The cachexia index based on the skeletal muscle mass index (S-CXI) in men. Area under curve = 0.579, 95% confidence interval = 0.398–0.759, p = 0.389. (b) The cachexia index based on the psoas muscle mass index (P-CXI) in men. Area under curve = 0.590, 95% confidence interval = 0.409–0.772, p = 0.322. (c) S-CXI in women. Area under curve = 0.555, 95% confidence interval = 0.370–0.740, p = 0.535. (d) P-CXI in women. Area under curve = 0.574, 95% confidence interval = 0.392–0.756, p = 0.431.

Fig. 2

A receiver operating characteristic curve analysis of the cachexia index. (a) The cachexia index based on the skeletal muscle mass index (S-CXI) in men. Area under curve = 0.579, 95% confidence interval = 0.398–0.759, p = 0.389. (b) The cachexia index based on the psoas muscle mass index (P-CXI) in men. Area under curve = 0.590, 95% confidence interval = 0.409–0.772, p = 0.322. (c) S-CXI in women. Area under curve = 0.555, 95% confidence interval = 0.370–0.740, p = 0.535. (d) P-CXI in women. Area under curve = 0.574, 95% confidence interval = 0.392–0.756, p = 0.431.

Fig. 3

Kaplan-Meier survival curves for the progression-free (a) and overall survival (b) according to the cachexia index based on the skeletal muscle mass index (S-CXI). The low-S-CXI group showed a poorer prognosis in comparison to the high-S-CXI group with regard to progression-free and overall survival (p = 0.012, p = 0.015, respectively).

Fig. 4

The Kaplan-Meier survival curves for the progression-free (a) and overall survival (b) according to the cachexia index based on the psoas muscle index (P-CXI). The low-P-CXI group showed a poorer prognosis in comparison to the high-P-CXI group with regard to progression-free and overall survival (p = 0.022, p = 0.006, respectively).

Fig. 5

Correlation between the cross-sectional area of the iliopsoas muscle at the level of the umbilicus and other indicator of muscle mass. (a) Correlation between the cross-sectional area of the iliopsoas muscle at the level of the umbilicus and the total volume of the psoas muscle calculated by a 3-dimensional analysis. (b) Correlation between the cross-sectional area of the iliopsoas muscle at the level of the umbilicus and that of the skeletal muscle at the level of the umbilicus.