Gain of visceral adipose tissue rather than low skeletal muscle mass is associated with overall survival in patients with colorectal liver metastases; results from the NewEPOC study.

Skeletal muscle index (SM-index) decreased significantly during neoadjuvant chemotherapy in both men and women.

• In men, SM-index decreased from 50.6 ± 8.7 to 47.6 ± 8.6 cm2/m2 (p < 0.001).
• In women, SM-index decreased from 40.5 ± 6.1 to 37.7 ± 5.9 cm2/m2 (p = 0.002).
• These changes occurred over the course of neoadjuvant treatment prior to resection of colorectal liver metastases.

Skeletal muscle radiation attenuation (SM-RA) decreased significantly during neoadjuvant chemotherapy in men.

• SM-RA decreased from 37.7 ± 7.8 to 36.0 ± 7.6 HU in men (p < 0.001).
• SM-RA is a measure of muscle quality, with lower values indicating greater intramuscular fat infiltration.
• The change in SM-RA was not associated with overall survival.

VAT-index and SAT-index did not change significantly during neoadjuvant treatment at the group level.

• Despite no statistically significant mean change in VAT or SAT indices during treatment, individual variation in VAT change had prognostic relevance.
• This finding underscores that mean group-level stability can mask clinically important individual-level changes.

Gaining more than 2% VAT-index over 12 weeks was independently associated with worse overall survival.

• HR 2.05, 95% CI 1.12–3.76, p = 0.025.
• This association was independent of other covariates in the multivariable model.
• The threshold used was >2% gain in VAT-index over the approximately 12-week neoadjuvant treatment period.

Sarcopenia, SM-loss, and SM-RA at baseline as well as change in SM-RA were not associated with overall survival.

• Neither baseline sarcopenia status nor loss of skeletal muscle mass during chemotherapy reached statistical significance as prognostic factors for overall survival.
• Both baseline SM-RA and change in SM-RA during treatment were similarly not associated with overall survival.
• These null findings contrast with a growing literature suggesting sarcopenia is prognostic in cancer patients.

Intervention arm assignment and undergoing resection of metastases were independently associated with overall survival.

• Intervention arm (addition of cetuximab): HR 1.96, 95% CI 1.21–3.19, p = 0.009, indicating worse overall survival in the cetuximab arm.
• Undergoing resection of metastases: HR 0.19, 95% CI 0.09–0.40, p < 0.001, indicating markedly better overall survival.
• These factors were identified in the multivariable analysis alongside VAT gain as independent prognostic factors.

This study was a subgroup analysis of the newEPOC randomized controlled trial examining body composition changes during neoadjuvant chemotherapy for colorectal liver metastases.

• The newEPOC RCT is registered as NCT00482222.
• Pre- and post-treatment CT scans were analyzed for total cross-sectional areas of skeletal muscle (SM), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intramuscular adipose tissue (IMAT), and skeletal muscle radiation attenuation (SM-RA).
• Body composition measurements were conducted at a single lumbar vertebral level as is standard in CT-based body composition analysis.