Factors Contributing to Cancer-Related Muscle Wasting During First-Line Systemic Treatment for Metastatic Colorectal Cancer

Abstract

Background: Increasing evidence indicates that loss of muscle mass is associated with adverse outcomes in metastatic colorectal cancer. Here, we investigate which demographic, lifestyle- (smoking), tumor-, and treatment-related factors are associated with muscle loss in patients with metastatic colorectal cancer during first-line palliative systemic treatment.

Methods: Data from 300 patients with computed tomography scans both at start and after six initial cycles of capecitabine plus oxaliplatin and bevacizumab was used (CAIRO3). From computed tomography, muscle mass normalized for stature (skeletal muscle index [SMI]) was calculated. A priori-selected variables were tested using multivariable linear regression models (P values ≤.05). Two models were developed: Model 1 contained variables measured at start and Model 2 contained variables assessed after initial therapy.

Results: In Model 1, loss of SMI was statistically significantly associated with a higher initial SMI (-0.32%, 95% confidence interval [CI] = -0.45% to -0.19% per unit increase in initial SMI), smoking status (-2.74%, 95% CI = -5.29% to -0.19% for smokers), and interval of metastases (-3.02%, 95% CI = -5.50% to -0.53%) for metachronous vs synchronous metastases), and primary tumor resection was statistically significantly associated with a gain in SMI (2.17%, 95% CI = 0.13% to 4.21% for resection vs no resection). In Model 2, loss of SMI was statistically significantly associated with response to capecitabine plus oxaliplatin and bevacizumab (-2.48%, 95% CI = -4.33% to -0.62% for stable disease vs partial/complete response).

Conclusions: Our results highlight, given the association of sarcopenia and survival, that patients with higher SMI should not be ignored. In addition, smoking is a potentially modifiable factor associated with muscle loss. The association between smoking and muscle loss might relate to worse clinical outcomes in smokers with metastatic colorectal cancer.

Figure 1.

Flowchart of the selection of patients for the current analyses. *One participating patient revoked informed consent. ^†No CT scans available from nine participating hospitals because of logistic reasons. ^‡CT scan at start of initial therapy nonevaluable. Reasons: no CT abdomen available, incomplete depiction of skeletal muscle at L3, stoma through muscle layer at L3, scan of insufficient quality. ^§CT scan at randomization nonevaluable. Reasons: no CT abdomen available, incomplete depiction of skeletal muscle at L3, stoma through muscle layer at L3, scan of insufficient quality. CAIRO3 = Maintenance Treatment Versus Observation After Induction in Advanced Colorectal Carcinoma; CT = computed tomography.