Deterioration in Muscle Mass and Physical Function Differs According to Weight Loss History in Cancer Cachexia

Abstract

Background: Muscle mass and physical function (PF) are common co-primary endpoints in cancer cachexia trials, but there is a lack of data on how these outcomes interact over time. The aim of this secondary analysis of data from a trial investigating multimodal intervention for cancer cachexia (ClinicalTrials.gov: NCT01419145) is to explore whether changes in muscle mass and PF are associated with weight loss and cachexia status at baseline. Methods: Secondary analysis was conducted using data from a phase II randomized controlled trial including 46 patients with stage III–IV non-small cell lung cancer (n = 26) or inoperable pancreatic cancer (n = 20) due to commence chemotherapy. Cachexia status at baseline was classified according to international consensus. Muscle mass (assessed using computed tomography (CT)) and PF outcomes, i.e., Karnofsky performance status (KPS), self-reported PF (self-PF), handgrip strength (HGS), 6-minute walk test (6MWT), and physical activity (PA), were measured at baseline and after six weeks. Results: When compared according to cachexia status at baseline, patients with no/pre-cachexia had a mean loss of muscle mass (−5.3 cm2, p = 0.020) but no statistically significant change in PF outcomes. Patients with cachexia also lost muscle mass but to a lesser extent (−2.8 cm2, p = 0.146), but demonstrated a statistically significant decline in PF; KPS (−3.8 points, p = 0.030), self-PF (−8.8 points, p = 0.027), and HGS (−2.7 kg, p = 0.026). Conclusions: Weight loss history and cachexia status at baseline are of importance if one aims to detect changes in PF outcomes in cancer cachexia trials. To improve the use of co-primary endpoints that include PF in future trials, outcomes that have the potential to detect change relative to weight loss should be investigated further.

Associations of low handgrip strength with cancer mortality: a multicentre observational study

“…Cancer accelerates the decline process owing to its chronic consumptive characteristics for resulting syndromes or diseases such as fatigue, cancer cachexia, and sarcopenia. [4][5][6] Recently, HGS was recommended to be a criterion in the definition of cancer cachexia. 7 More strikingly, HGS replaced the muscle mass as the primary criterion to define sarcopenia.…”

“…The HGS of cancer patients was different from that of the healthy populations. Cancer accelerates the decline process owing to its chronic consumptive characteristics for resulting syndromes or diseases such as fatigue, cancer cachexia, and sarcopenia 4–6 . Recently, HGS was recommended to be a criterion in the definition of cancer cachexia 7 .…”

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

“…The magnitude of muscle mass loss in the control arm in this study does not evoke a corresponding reduction in HGS. Low muscle mass is associated with reduced physical function; however, the relationship is nonlinear and, likely, there is a variable impact on physical function outcomes depending on the magnitude of changes in muscle mass ( 14 ). The potential of physical function outcomes such as HGS (and other performance testing) to detect change relative to muscle/weight changes in cancer cachexia remains unclear.…”

“…Handgrip strength (HGS) (kg) was collected at baseline and after 6 weeks and measured with a hydraulic handheld dynamometer (JAMAR). The test was performed using the dominant hand, and three test trials were performed ( 7 , 14 ).…”

The Impact of Protein Supplementation Targeted at Improving Muscle Mass on Strength in Cancer Patients: A Scoping Review

“…In spite of a linear correlation between the two reported by some authors [ 26 ], others failed to demonstrate it. Results from the latter studies instead showed preserved muscle function in the early stages of the disease, in spite of significant muscle loss and a prevalent decline during the late stage of cachexia prior to minor loss of muscle mass [ 62 ]. Thus, the heterogeneity of study populations in terms of cancer type and stage and baseline nutritional status could hamper conclusions when comparing the results of different trials.…”