The prognostic value of early onset, CT derived loss of muscle and adipose tissue during chemotherapy in metastatic non-small cell lung cancer

Objectives: To evaluate the relationship between early changes in muscle and adipose tissue during chemotherapy and overall survival (OS) in stage IV non-small cell lung cancer (NSCLC).

Materials and methods: In this post-hoc analysis of the first line NVALT12 trial (NCT01171170) in stage IV NSCLC, skeletal muscle (SM), radiation attenuation (RA), subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were assessed at the third lumbar level on CT-images obtained before initiation of chemotherapy and shortly after administration of the second cycle. The contribution of changes in different body compartments to overall survival was assessed.

Results: CT scans of 111 patients were included. Analysis of body composition changes between the baseline and the follow-up scan, revealed that overall SM cross sectional area (CSA), radiation attenuation and SAT CSA decreased respectively by -1.2 +/- 2.9 cm(2)/m(2) (p <0.001), -0.7 +/- 3.3 HU (p = 0.026) and -1.9 +/- 8.7 cm(2)/m(2) (p = 0.026), while no significant changes in VAT tissue were observed. Longitudinally, median OS was significantly shorter among patients losing SM compared to patients with preserved SM (9.4 versus 14.2 months; HR 1.9, 95% CI: 1.23, 2.79, p = 0.003). Multivariate analyses showed that proportional loss of muscle mass was associated with poor OS (HR 0.949, 95% CI: 0.915, 0.985, p = 0.006) independent from important clinical prognostic factors including WHO-PS, gender, age and Charlson comorbidity index.

Conclusion: Early loss of SM during first line chemotherapy is a poor prognostic factor in stage IV NSCLC patients. Future studies have to reveal whether early supportive intervention guided by initial CT muscle response to chemotherapy can influence the wasting process and related mortality risk.