Abstract
BackgroundLow skeletal muscle index (SMI) in metastatic colorectal cancer (mCRC) patients is associated with poor outcomes. The prognostic impact of SMI changes during consecutive palliative systemic treatments is unknown.MethodsThis is a retrospective analysis of the phase 3 CAIRO3 study. The CAIRO3 study randomized 557 patients between maintenance capecitabine + bevacizumab (CAP‐B) or observation, after six cycles capecitabine + oxaliplatin + bevacizumab (CAPOX‐B). Upon first disease progression (PD1), CAPOX‐B was reintroduced until second progression (PD2). SMI was assessed by computed tomography (CT) (total 1355 scans). SMI and body mass index (BMI) changes were analyzed for three time‐periods; p1: during initial CAPOX‐B, p2: randomization to PD1, and p3: PD1 to PD2. The association between absolute and change in SMI and BMI (both per 1 standard deviation) during p1‐p3, with PD1, PD2, and survival was studied by Cox regression models.ResultsThis analysis included 450 of the 557 patients randomized in the CAIRO3 study. Mean SMI decreased during p1: mean −0.6 SMI units [95% CI −1.07;‐0.26] and p3: −2.2 units [−2.7;‐1.8], whereas during p2, SMI increased + 1.2 units [0.8‐1.6]. BMI changes did not reflect changes in SMI. SMI loss during p2 and p3 was significantly associated with shorter survival (HR 1.19 [1.09‐1.35]; 1.54 [1.31‐1.79], respectively). Sarcopenia at PD1 was significantly associated with early PD2 (HR 1.40 [1.10‐1.70]). BMI loss independent of SMI loss was only associated with shorter overall survival during p3 (HR 1.35 [1.14‐1.63]).ConclusionsIn mCRC patients, SMI loss during palliative systemic treatment was related with early disease progression and reduced survival. BMI did not reflect changes in SMI and could not identify patients at risk of poor outcome during early treatment lines.
Highlights
In metastatic colorectal cancer patients, the identification of predictive and potentially modifiable characteristics that predispose to poor treatment outcomes is important to improve outcomes, quality of care, and reduce health-care costs.[1]An interesting novel prognosticator is the loss of skeletal muscle mass, as muscle mass loss in cancer patients can be evaluated using computed tomography (CT) scans.[2,3] During advanced cancer, muscle mass loss is the result of a multifactorial syndrome in which a reduced nutritional intake, metabolic changes, often combined with low physical activity levels, lead to alterations in body composition and eventually to cancer cachexia.[4]
In this large longitudinal study in metastatic colorectal cancer (mCRC) patients, we provide a unique insight into skeletal muscle index (SMI) and body mass index (BMI) changes during various palliative systemic treatments, starting from firstline treatment, and show how these changes relate to time to progression and survival
Absolute BMI or BMI loss independent of SMI loss was not associated with early progression or death, except for BMI loss independent of SMI loss during capecitabine + oxaliplatin + bevacizumab (CAPOX-B) reintroduction treatment and overall survival
Summary
In metastatic colorectal cancer (mCRC) patients, the identification of predictive and potentially modifiable characteristics that predispose to poor treatment outcomes is important to improve outcomes, quality of care, and reduce health-care costs.[1]. No studies have investigated the evolution of muscle mass on multiple time points, during consecutive treatment regimens, and how, within each regimen, these changes relate to (progression free) survival. This is of particular relevance shortly after the mCRC diagnosis, when an anabolic response is more likely to occur and change in muscle mass is potentially modifiable by interventions that aim to improve muscle mass.[7,14]. In advanced cancer patients, including CAIRO3 patients, body weight changes over time may not correlate with muscle mass changes.[11,14] muscle mass and fat mass have been found to respond differently to tumor and treatment, and are differently associated with cancer patients' outcome.[3,14,16] as a secondary aim, we investigated longitudinal body mass index (BMI) changes, including BMI changes adjusted for KURK et al muscle mass changes (ie, as a surrogate for fat mass), to study their relation with survival outcomes
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