Muscle Loss Is Associated with Overall Survival in Patients with Metastatic Colorectal Cancer Independent of Tumor Mutational Status and Weight Loss

Abstract

Background Survival in patients with metastatic colorectal cancer (mCRC) has been associated with tumor mutational status, muscle loss, and weight loss. We sought to explore the combined effects of these variables on overall survival. Materials and Methods We performed an observational cohort study, prospectively enrolling patients receiving chemotherapy for mCRC. We retrospectively assessed changes in muscle (using computed tomography) and weight, each dichotomized as >5% or ≤5% loss, at 3, 6, and 12 months after diagnosis of mCRC. We used regression models to assess relationships between tumor mutational status, muscle loss, weight loss, and overall survival. Additionally, we evaluated associations between muscle loss, weight loss, and tumor mutational status. Results We included 226 patients (mean age 59 ± 13 years, 53% male). Tumor mutational status included 44% wild type, 42% RAS‐mutant, and 14% BRAF‐mutant. Patients with >5% muscle loss at 3 and 12 months experienced worse survival controlling for mutational status and weight (3 months hazard ratio, 2.66; p < .001; 12 months hazard ratio, 2.10; p = .031). We found an association of >5% muscle loss with BRAF‐mutational status at 6 and 12 months. Weight loss was not associated with survival nor mutational status. Conclusion Increased muscle loss at 3 and 12 months may identify patients with mCRC at risk for decreased overall survival, independent of tumor mutational status. Specifically, >5% muscle loss identifies patients within each category of tumor mutational status with decreased overall survival in our sample. Our findings suggest that quantifying muscle loss on serial computed tomography scans may refine survival estimates in patients with mCRC. Implications for Practice In this study of 226 patients with metastatic colorectal cancer, it was found that losing >5% skeletal muscle at 3 and 12 months after the diagnosis of metastatic disease was associated with worse overall survival, independent of tumor mutational status and weight loss. Interestingly, results did not show a significant association between weight loss and overall survival. These findings suggest that muscle quantification on serial computed tomography may refine survival estimates in patients with metastatic colorectal cancer beyond mutational status.

Deep learning‐based assessment of body composition and liver tumour burden for survival modelling in advanced colorectal cancer

“…In particular, the presence of RAS mutations in association with the primary tumour sidedness is of major importance for the selection of antibody therapies. In our study, we saw no correlation between the KRAS mutational status and body composition parameters, which is in line with previous studies 27 . Because MBR was a predictor of overall survival independent of KRAS mutational status and the primary tumour sidedness, this suggests high generalizability.…”

“…In our study, we saw no correlation between the KRAS mutational status and body composition parameters, which is in line with previous studies. 27 Because MBR was a predictor of overall survival independent of KRAS mutational status and the primary tumour sidedness, this suggests high generalizability. In a subgroup with available information at baseline, we could demonstrate that BMI, unlike MBR, did not serve as predictor of overall survival.…”

Sarcopenia, adiposity, and discrepancies in cystatin C versus creatinine-based eGFR in patients with cancer: a cross-sectional study

“…[18][19][20][21][22] In addition, imagingdefined sarcopenia has been shown to have a strong association with adverse clinical outcomes in patients with cancer. [23][24][25] Given that patients with active cancer undergo frequent CT scans for diagnosis and monitoring of disease progression, CT is a convenient tool to evaluate body composition and detect sarcopenia, and may aid in the accurate interpretation of SCr or cystatin C-based eGFR.…”

“…18-22 In addition, imaging-defined sarcopenia has been shown to have a strong association with adverse clinical outcomes in patients with cancer. 23-25…”

Muscle Mass Matters in Patients with Renal Cell Carcinoma, but That Is Only the Beginning…

“…We also need a better understanding of how dynamic changes in lean muscularity may influence a patient's ability to tolerate antineoplastic therapy, and ultimately, the patient's survival. 15 Second, the relationships between observations of muscle loss and potentially additive risk factors such as malnutrition, low activity, and multimorbidity remain to be fully characterized, as well as key outcomes beyond survival such as physical function, independence, cognition, and quality of life. 11,16,17 Finally, numerous outstanding methodologic questions are saliant for the continued pursuit of high-quality body composition research.…”