Association of sarcopenia and treatment tolerability in older adults with advanced cancer: Secondary analysis of a nationwide NCI Community Oncology Research Program (NCORP) randomized clinical trial.
Authors: Dunne Richard Francis , Culakova Eva , Roeland Eric J , Williams Grant Richard , Arguello Joshua , Loh Kah Poh , Mohamed Mostafa Refaat , Tylock Rachael , Beg Mirza Faisal , Popuri Karteek , Goncalves Marcus D. , Hopkins Judith O. , Berenberg Jeffrey L. , Vinciguerra Vincent , Lin Po-Ju , Mustian Karen Michelle , Mohile Supriya Gupta 
Published: June 2023

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Background: Sarcopenia (sarc) is defined by reduced muscle function paired with low muscle mass or quality. Sarc is common in older adults, but the relationship between sarc and treatment tolerability in older patients (pts) with cancer has not been established. This secondary analysis of our nationwide University of Rochester NCORP Research Base randomized trial examines whether pre-treatment sarc was associated with treatment toxicity and survival in older pts with advanced cancers. Methods: Pts aged 70 and older with incurable solid tumors and lymphoma initiating a new high-risk systemic treatment were enrolled in GAP70+ (NCT02054741). GAP70+ was a cluster randomized trial evaluating whether a geriatric assessment intervention can reduce cancer treatment toxicity. This secondary analysis included 161 pts with baseline computed tomography (CT) scans and physical function testing. Sarc was defined as low muscle strength (5-time Chair Stand Test > 16.7 seconds) with reduced muscle mass (BMI and sex-specific cutoffs, cm/m2) or low muscle quality (Hounsfield units [HU] average radiodensity thresholds) utilizing validated cross-sectional CT imaging metrics. Sarc was defined as severe in presence of reduced physical performance (Timed-Up-And-Go > 13.5 seconds). We evaluated if the proportion of pts experiencing any grade 3-5 toxicity in the first 3 months of treatment using Common Terminology Criteria for Adverse Events (CTCAE) V4.0 was higher in those with sarc than those without sarc. Multivariate logistic regression was used to further explore this relationship. Multivariate Cox regression analysis was performed to evaluate the association of sarc and severe sarc with 1-year survival. Results: Mean age of the 161 participants included in this cohort was 76.6 years and 60.9% of were male; over half had gastrointestinal (34.8%) or lung cancer (23.6%). Sarc was found in 91 of 161 (56.5%) pts; 54 had severe sarc. Pts with sarc did not experience significantly more grade 3-5 toxicity compared to those without sarc (79.1% vs. 71.4%, p = 0.26). However, pts with sarc experienced more grade 3-5 non-hematologic toxicity (63.7% vs. 44.3%, p = 0.01) on univariate and multivariate analysis (OR 2.2, CI 1.1-4.5, p = 0.02). The association between sarc and worse survival at 1-year was not statistically significant (OR 1.5, CI 0.9-2.4, p = 0.13). Those with severe sarc did demonstrate significantly worse 1-year survival on multivariate analysis (HR 1.8, CI 1.1-2.9, p = 0.02). Conclusions: Older pts with cancer and sarc were more likely to suffer serious non-hematologic toxicity from cancer treatment. Furthermore, those with severe sarc had significantly worse survival. Evaluation for sarc before initiating treatment in older adults could help oncologists identify pts at higher risk of toxicity and poor survival. Clinical trial information: NCT02054741 .