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

Guro Birgitte Stene, Trude Rakel Balstad, Anne Silja M Leer, Asta Bye, Stein Kaasa, Marie Fallon, Barry Laird, Matthew Maddocks, Tora S Solheim, Guro Birgitte Stene, Trude Rakel Balstad, Anne Silja M Leer, Asta Bye, Stein Kaasa, Marie Fallon, Barry Laird, Matthew Maddocks, Tora S Solheim

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.

Keywords: cachexia; cancer; endpoints; grip strength; muscle mass; physical performance; weight loss.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scatterplots and Spearman’s Rho correlation coefficients (r) and p-values for skeletal muscle index (SMI) on the X- axis and the following physical function (PF) outcomes on the Y- axis 1. Karnofsky performance scale, 2. Self-reported PF, 3. Six-minute walk test, 4. Handgrip strenght and 5. PA, steps. Correlations are shown for all patients at (A) baseline (BL), (B) 6 weeks (WK 6) and (C) change from baseline to end of trial (∆ BL-WK 6). Statistically significant correlations are highlighted by bold types and the pre-fix * = correlation is significant at the 0.05 level, ** = correlation is significant at the 0.01 level. Sub-group analysis based on cachexia status at baseline are marked by blue dots=no/pre cachexia and red dots=cachexia in the scatter plots and correlation coefficients (r) and p-values are inserted below the plots for each sub-group.
Figure 1
Figure 1
Scatterplots and Spearman’s Rho correlation coefficients (r) and p-values for skeletal muscle index (SMI) on the X- axis and the following physical function (PF) outcomes on the Y- axis 1. Karnofsky performance scale, 2. Self-reported PF, 3. Six-minute walk test, 4. Handgrip strenght and 5. PA, steps. Correlations are shown for all patients at (A) baseline (BL), (B) 6 weeks (WK 6) and (C) change from baseline to end of trial (∆ BL-WK 6). Statistically significant correlations are highlighted by bold types and the pre-fix * = correlation is significant at the 0.05 level, ** = correlation is significant at the 0.01 level. Sub-group analysis based on cachexia status at baseline are marked by blue dots=no/pre cachexia and red dots=cachexia in the scatter plots and correlation coefficients (r) and p-values are inserted below the plots for each sub-group.
Figure 1
Figure 1
Scatterplots and Spearman’s Rho correlation coefficients (r) and p-values for skeletal muscle index (SMI) on the X- axis and the following physical function (PF) outcomes on the Y- axis 1. Karnofsky performance scale, 2. Self-reported PF, 3. Six-minute walk test, 4. Handgrip strenght and 5. PA, steps. Correlations are shown for all patients at (A) baseline (BL), (B) 6 weeks (WK 6) and (C) change from baseline to end of trial (∆ BL-WK 6). Statistically significant correlations are highlighted by bold types and the pre-fix * = correlation is significant at the 0.05 level, ** = correlation is significant at the 0.01 level. Sub-group analysis based on cachexia status at baseline are marked by blue dots=no/pre cachexia and red dots=cachexia in the scatter plots and correlation coefficients (r) and p-values are inserted below the plots for each sub-group.

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