Dongjin Seo ^{1 *},MD ; Han Sang Kim ^{2,3,4 *},MD, PhD ; Joong Bae Ahn ²,MD, PhD ; Yu Rang Park ^3,4,5, PhD

¹ Department of Medicine , Yonsei University College of Medicine , Seoul , KR
² Yonsei Cancer Center , Division of Medical Oncology, Department of Internal Medicine , Yonsei University College of Medicine , Seoul , KR
³ Brain Korea 21 FOUR Project , Graduate School of Medical Science , Yonsei University College of Medicine , Seoul , KR
⁴ Institute for Innovation in Digital Healthcare , Severance Hospital , Seoul , KR
⁵ Department of Biomedical Systems Informatics , Yonsei University College of Medicine , Seoul , KR

^*these authors contributed equally
Corresponding Author: Yu Rang Park, PhD

Background: Skeletal muscle and BMI are essential prognostic factors for survival in colorectal cancer (CRC). However, there is a lack of understanding due to scarce studies on the continuous aspects of these variables.

Objective: This study aimed to evaluate the prognostic impact of the initial status and trajectories of muscle and BMI on overall survival (OS) and assess whether these 4 profiles within 1 year can represent the profiles 6 years later.

Methods: We analyzed 4056 newly diagnosed patients with CRC between 2010 to 2020. The volume of the muscle with 5-mm thickness at the third lumbar spine level was measured using a pretrained deep learning algorithm. The skeletal muscle volume index (SMVI) was defined as the muscle volume divided by the square of the height. The correlation between BMI status at the first, third, and sixth years of diagnosis was analyzed and assessed similarly for muscle profiles. Prognostic significances of baseline BMI and SMVI and their 1-year trajectories for OS were evaluated by restricted cubic spline analysis and survival analysis. Patients were categorized based on these 4 dimensions, and prognostic risks were predicted and demonstrated using heat maps.

Results: Trajectories of SMVI were categorized as decreased (812/4056, 20%), steady (2014/4056, 49.7%), or increased (1230/4056, 30.3%). Similarly, BMI trajectories were categorized as decreased (792/4056, 19.5%), steady (2253/4056, 55.5%), or increased (1011/4056, 24.9%). BMI and SMVI values in the first year after diagnosis showed a statistically significant correlation with those in the third and sixth years (P<.001). Restricted cubic spline analysis showed a nonlinear relationship between baseline BMI and SMVI change ratio and OS; BMI, in particular, showed a U-shaped correlation. According to survival analysis, increased BMI (hazard ratio [HR] 0.83; P=.02), high baseline SMVI (HR 0.82; P=.04), and obesity stage 1 (HR 0.80; P=.02) showed a favorable impact, whereas decreased SMVI trajectory (HR 1.31; P=.001), decreased BMI (HR 1.23; P=.02), and initial underweight (HR 1.38; P=.02) or obesity stages 2-3 (HR 1.79; P=.01) were negative prognostic factors for OS. Considered simultaneously, BMI >30 kg/m2 with a low SMVI at the time of diagnosis resulted in the highest mortality risk. We observed improved survival in patients with increased muscle mass without BMI loss compared to those with steady muscle mass and BMI.

Conclusions: Profiles within 1 year of both BMI and muscle were surrogate indicators for predicting the later profiles. Continuous trajectories of body and muscle mass are independent prognostic factors of patients with CRC. An automatic algorithm provides a unique opportunity to conduct longitudinal evaluations of body compositions. Further studies to understand the complicated natural courses of muscularity and adiposity are necessary for clinical application.