AUTHOR=Balstad Trude R. , Brunelli Cinzia , Pettersen Caroline H. , Schønberg Svanhild A. , Skorpen Frank , Fallon Marie , Kaasa Stein , Bye Asta , Laird Barry J. A. , Stene Guro B. , Solheim Tora S. 

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

JOURNAL=Frontiers in Nutrition

VOLUME=7

YEAR=2021

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2020.602775

DOI=10.3389/fnut.2020.602775

ISSN=2296-861X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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 (<italic>n</italic>−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.</p><p><bold>Results:</bold> 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, <italic>p</italic> &lt; 0.001), small for body composition and physical function [handgrip strength (HGS)] measures (ES &lt; 0.25), moderate to high for n-3 PUFAs and 25-hydroxyvitamin D (25-OH vitamin D) (ES range 0.64–1.37, <italic>p</italic> &lt; 0.05 for all), and moderate for serum C-reactive protein (ES = 0.53, <italic>p</italic> = 0.12). Analysis within the multimodal treatment group showed high sensitivity to change for adiponectin (ES = 0.86, <italic>p</italic> = 0.001) and n-3 PUFAs (ES &gt; 0.8, <italic>p</italic> &lt; 0.05 for all) and moderate for 25-OH vitamin D (ES = 0.49, <italic>p</italic> = 0.03). In the control group, a moderate sensitivity to change for body weight (ES = −0.84, <italic>p</italic> = 0.002) and muscle mass (ES = −0.67, <italic>p</italic> = 0.016) and a high sensitivity to change for plasma levels of 25-OH vitamin D (ES = −0.88, <italic>p</italic> = 0.002) were found.</p><p><bold>Conclusion:</bold> 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.</p><p><bold>Trial registration:</bold><ext-link ext-link-type="uri" xlink:href="https://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> identifier: NCT01419145.</p>