Skeletal muscle depletion during chemotherapy has a large impact on physical function in elderly Japanese patients with advanced non-small-cell lung cancer

Abstract

Background: Elderly patient with advanced cancer is one of the most vulnerable populations. Skeletal muscle depletion during chemotherapy may have substantial impact on their physical function. However, there is little information about a direct relationship between quantity of muscle and physical function. We sought to explore the quantitative association between skeletal muscle depletion, and muscle strength and walking capacity in elderly patients with advanced non-small cell lung cancer (NSCLC).

Methods: Thirty patients aged ≥70 years with advanced NSCLC (stage III-IV) scheduled to initiate first-line chemotherapy were prospectively enrolled between January 2013 and November 2014. Lumbar skeletal muscle index (LSMI, cm²/m²), incremental shuttle walking distance (ISWD, m), and hand-grip strength (HGS, kg) were assessed at baseline, and 6 ± 2 weeks (T2) and 12 ± 4 weeks (T3) after study enrollment. Associations were analyzed using linear regression.

Results: Altogether, 11 women and 19 men with a median age of 74 (range, 70-82) years were included in the study; 24 received cytotoxic chemotherapy and 6, gefitinib. Mean ± standard deviation of LSMI, ISWD and HGS were 41.2 ± 7.8 cm²/m², 326.0 ± 127.9 m, and 29.3 ± 8.5 kg, respectively. LSMI and ISWD significantly declined from baseline to T2 and T3. HGS significantly declined from baseline to T2 and T3 only in men. Change in LSMI was significantly associated with change in HGS (β = 0.3 ± 0.1, p = 0.0127) and ISWD (β = 8.8 ± 2.4, p = 0.0005).

Conclusions: Skeletal muscle depletion accompanied with physical functional decline started in the early phase of the chemotherapy in elderly patients with advanced NSCLC. Our results suggest that there may be a need for early supportive care in these patients to prevent functional decline during chemotherapy.

Trial registration: Trial registration number: UMIN000009768 Name of registry: UMIN (University hospital Medical Information Network). URL of registry: Date of registration: 14 January 2013. Date of enrolment of the first participant to the trial: 23 January 2013.

Keywords: Cancer cachexia; Hand-grip strength; Incremental shuttle walking distance; Non–small cell lung cancer; Sarcopenia; Skeletal muscle mass.

Fig. 1

Flow diagram. The number of patients and evaluable data at the T1 (baseline), T2 (6 ± 2 weeks), and T3 (12 ± 2 weeks) point is shown. The number of evaluable data for each variable is described in the box. The reasons for a missing value are described in the right side of each box. HGS, hand-grip strength; ISWD, incremental shuttle walking distance; LSMI, lumbar skeletal muscle index

Fig. 2

Longitudinal changes in body-mass, muscle mass, and physical function. Mean changes ± standard error of physical parameters from baseline value is shown. P-value of Wilcoxon signed-rank test was shown

Fig. 3

Association between changes in skeletal muscle mass and physical function. The association between change in muscle mass, and hang-grip strength (a) and shuttle walking distance (b) at all time points are plotted. Dotted line indicates the 95% confidence interval. Circle, triangle, and square mark represents change at T2 from baseline, T3 from baseline, and T3 from T2, respectively

Fig. 4

Subset analysis for change in skeletal muscle mass at T2 point. Median change of skeletal muscle mass at T2 point in each subset was shown. The number of patients in each subset is indicated in parenthesis. White line indicates the median. The top and bottom of each box represent the upper and lower quartiles of the values for the sample. Bars extend above and below each box to the maximal and minimal values in the sample. P-value of Wilcoxon rank-sum test was shown. PS, Eastern Cooperative Oncology Group performance status; PD, progressive disease assessed by the Response Evaluation Criteria in Solid Tumors at T2 point