Concurrent losses of skeletal muscle mass, adipose tissue and bone mineral density during bevacizumab / cytotoxic chemotherapy treatment for metastatic colorectal cancer

Summary

Background

Changes in skeletal muscle mass (SMM), total adipose tissue mass (TAT) or bone mineral density (BMD) have been described in patients with cancer undergoing various treatments; simultaneous variations of all 3 tissues has not been reported.

Methods

Data were prospectively collected in a clinical study (NCT00489697) including patients with liver metastases of colorectal cancer who received 4 cycles of bevacizumab in combination with cytotoxic chemotherapy. Computerized tomography (CT) at baseline and after chemotherapy was used to quantify skeletal muscle and adipose tissue cross-sectional areas, and mean lumbar spine BMD using validated approaches.

Results

After exclusion of patients lacking adequate CT images or missing data, 72 subjects were included. Patients were 63% male, aged 63.2 ± 10.3 years, 100% had liver metastases and 54%, 24% and 22% respectively has 0, 1 and ≥2 extrahepatic metastases. 100% tolerated 4 cycles of treatment and none showed progressive disease at the end of treatment. The scan interval was 70 days (95% CI, 62.3 to 80.5). Thresholds for loss of tissue were defined as loss ≥ measurement error. 10% of patients showed no loss of any tissue and a further 43% lost one tissue (SMM, TAT or BMD); 47% of patients lost 2 tissues (16.5% lost SMM + TAT, 8% lost SMM + BMD, 10% lost TAT + BMD) or all 3 tissues (12.5%). Catabolic behavior (2 or 3 tissue loss vs 0 or 1 tissue loss) associated with disease burden, including unresectable primary tumor (p = 0.010), presence of extrahepatic (EH) metastases (p = 0.039) and number of EH metastases (p = 0.004). No association was found between the number of tissues lost and treatment response, which was uniformly high, or treatment toxicity, which was uniformly low.

Conclusion

Multiple tissues can be measured in routine CT images and these show considerable inter-individual variation. Substantial losses in some individuals appear to associate with disease burden.