The association between changes in muscle mass and quality of life in patients with metastatic colorectal cancer

Abstract

Background: Skeletal muscle mass (SMM) loss is common in metastatic colorectal cancer (mCRC) patients and associated with poor clinical outcomes, including increased treatment-related toxicities and reduced survival. Muscle loss may contribute to reduced health-related quality of life (HRQoL), including fatigue. Our aim was to study associations between changes in SMM and concomitant changes in patient-reported HRQoL.

Methods: This was a secondary analysis of mCRC patients in the CAIRO3 randomized clinical trial who were-after initial treatment-randomized between maintenance treatment with capecitabine plus bevacizumab (CAP-B) and observation until first disease progression (PD1). Included patients had computed tomography images for SMM quantification, together with HRQoL assessments available at randomization and PD1. Changes in SMM (categorized as >2% loss, stable, and >2% gain) and HRQoL were computed between randomization and PD1. Changes in HRQoL score >10 points were considered clinically relevant. Associations between SMM and HRQoL changes were studied by multiple linear regression models. We also investigated whether associations differed by treatment arm for global health and the 13 other HRQoL subscales.

Results: Of 221 patients included (mean age 63.5 ± 8.4 years), 24% lost, 27% remained stable, and 49% gained SMM. At randomization, mean global health status was 73.5 ± 15.9 in the CAP-B arm and 75.1 ± 17.5 in the observation arm (P = 0.48). A stable or gain in SMM was significantly associated with a clinically relevant improvement in global health status (9.9 and 14.7 points, respectively), compared with patients who lost SMM. From the subscales that did not show significant differences between the two treatment arms, we found significant and clinically relevant associations for stable or gain in SMM with improved role functioning (12.0 and 17.9, respectively) and with less fatigue (-10.0 and -15.0, respectively) and pain (-16.3 for SMM gain). From the subscales that did show significantly different associations with SMM between the two treatment arms, we only found significant results in the observation arm. Here, associations were found for stable or gain in SMM with clinically relevant improved physical (12.4 for SMM gain), cognitive (10.7 and 9.7, respectively), and social functioning (15.5 and 15.6, respectively) as well as reduced appetite loss (-28.5 and -30.7, respectively).

Conclusions: In mCRC, SMM preservation during CAP-B and observation treatment is associated with significant and clinically relevant improvements in global health status and multiple functional and symptom scales. Studies are warranted to investigate whether interventions targeting SMM lead to improved HRQoL, fewer symptoms, and better functioning.

Keywords: Metastatic colorectal cancer; Quality of life; Skeletal muscle mass; Supportive care.

Figure 1

Flow diagram of the selection of individuals for the current analyses. ^aOne participating patient revoked informed consent. ^bNo CT scans available from nine participating hospitals, due to logistic reasons. ^cNo CT scan at randomization and/or PD1 {reasons: non‐evaluable, i.e. incomplete depiction of skeletal muscle at L3, stoma through muscle layer at L3, scan of insufficient quality [n = 114 (89%)] or patient did not reach PD1 yet [n = 10 (8%)] or patient deceased before CT was made [n = 4 (3%)]}. ^dReason: questionnaires not sufficiently completed. ^eReasons for no data at PD1: no more questionnaires returned after baseline, patient did not reach PD1 yet, or unknown. ^fThe final dataset is based on combined SMM and HRQoL data (n = 322 and n = 370, respectively) and contains data from 221 patients, as the available SMM and HRQoL data do not necessarily include the same patients. CT, computed tomography; HRQoL, health‐related quality of life; L3, third lumbar vertebra; PD1, first progression of disease; SMM, skeletal muscle mass.

Figure 2

Associations between stable (solid circles) or gain in SMM (open circles) vs. loss of SMM (reference) and change in global health status and functional subscales of HRQoL, for both CAIRO3 arms combined or stratified by treatment arm in case of a significant interaction (n = 221). Results from a multivariable linear regression analysis, which highlight the change in HRQoL scores for patients with stable SMM and patients who gained SMM. Grey zones show the cut‐off for clinically relevant (i.e. ≥10 points) changes. Models were adjusted for age, sex, treatment arm, World Health Organization performance status, time to PD1, LDH at randomization, previous adjuvant chemotherapy, response to induction treatment, and hospital. Treatment arm was taken out of the model when stratified on treatment arm. This stratification is based on the relative goodness of fit (AICc) of the model with vs. without the interaction terms. Change scores are shown as means with 95% confidence interval. Confidence intervals not including 0 (P < .05) are considered statistically significant. HRQoL, health‐related quality of life; LDH, lactate dehydrogenase; PD1, first progression of disease; SMM, skeletal muscle mass.

Figure 3

Associations between stable (solid circles) or gain in SMM (open circles) vs. loss of SMM (reference) and change in symptomatic aspects of HRQoL, for both CAIRO3 arms combined or stratified by treatment arm in case of a significant interaction (n = 221). Results from a multivariable linear regression analysis, which highlight the change in HRQoL scores for patients with stable SMM and patients who gained SMM. Grey zones show the cut‐off for clinically relevant (i.e. ≥10 points) changes. Models were adjusted for age, sex, treatment arm, World Health Organization performance status, time to PD1, LDH at randomization, previous adjuvant chemotherapy, response to induction treatment, and hospital. Treatment arm was taken out of the model when stratified on treatment arm. This stratification is based on the relative goodness of fit (AICc) of the model with vs. without the interaction terms. Change scores are shown as means with 95% confidence interval. Confidence intervals not including 0 (P < .05) are considered statistically significant. HRQoL, health‐related quality of life; LDH, lactate dehydrogenase; PD1, first progression of disease; SMM, skeletal muscle mass.