Power Comparisons and Clinical Meaning of Outcome Measures in Assessing Treatment Effect in Cancer Cachexia: Secondary Analysis From a Randomized Pilot Multimodal Intervention Trial

Abstract

Background: New clinical trials in cancer cachexia are essential, and outcome measures with high responsiveness to detect meaningful changes are crucial. This secondary analysis from a multimodal intervention trial estimates sensitivity to change and between treatment effect sizes (ESs) of outcome measures associated with body composition, physical function, metabolism, and trial intervention. Methods: The study was a multicenter, open-label, randomized pilot study investigating the feasibility of a 6-week multimodal intervention [exercise, non-steroidal anti-inflammatory drugs, and oral nutritional supplements containing polyunsaturated fatty acids (n-3 PUFAs)] vs. standard cancer care in non-operable non-small-cell lung cancer and advanced pancreatic cancer. Body composition measures from computerized tomography scans and circulating biomarkers were analyzed. Results: Forty-six patients were randomized, and the analysis included 22 and 18 patients in the treatment and control groups, respectively. The between-group ESs were high for body weight (ES = 1.2, p < 0.001), small for body composition and physical function [handgrip strength (HGS)] measures (ES < 0.25), moderate to high for n-3 PUFAs and 25-hydroxyvitamin D (25-OH vitamin D) (ES range 0.64-1.37, p < 0.05 for all), and moderate for serum C-reactive protein (ES = 0.53, p = 0.12). Analysis within the multimodal treatment group showed high sensitivity to change for adiponectin (ES = 0.86, p = 0.001) and n-3 PUFAs (ES > 0.8, p < 0.05 for all) and moderate for 25-OH vitamin D (ES = 0.49, p = 0.03). In the control group, a moderate sensitivity to change for body weight (ES = -0.84, p = 0.002) and muscle mass (ES = -0.67, p = 0.016) and a high sensitivity to change for plasma levels of 25-OH vitamin D (ES = -0.88, p = 0.002) were found. Conclusion: Demonstrating high sensitivity to change and between treatment ES and body composition measures, body weight still stands out as a clinical and relevant outcome measure in cancer cachexia. Body composition and physical function measures clearly are important to address but demand large sample sizes to detect treatment group differences. Trial registration: ClinicalTrials.gov identifier: NCT01419145.

Keywords: biomarkers; body composition; cachexia; effect size; multimodal management; outcome measures; sample size (n).

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Balstad, Brunelli, Pettersen, Schønberg, Skorpen, Fallon, Kaasa, Bye, Laird, Stene and Solheim.

Figures

Figure 1

Sample size per treatment arm by effect size values. Sample size by treatment arm by effect size (ES) values (black curve). Dashed vertical lines indicate reference value for small (0.8) ESs (17). Colored vertical lines indicate ESBG for each outcome measure: body weight (orange, n = 1), body composition (blue, n = 6, two overlap, one overlaps with metabolism outcome), physical function (black, n = 1), metabolic mediators (pink, n = 6, two overlap), and nutrient components (green, n = 4) (exact values are reported in Table 2). Sample size values for ES < 0.2 are higher than 1,000 and not shown in the figure.