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

ABSTRACT: 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).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.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 (? = 0.3 ± 0.1, p = 0.0127) and ISWD (? = 8.8 ± 2.4, p = 0.0005).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 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.

SUBMITTER: Naito T

PROVIDER: S-EPMC5574084 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Naito Tateaki T Okayama Taro T Aoyama Takashi T Ohashi Takuya T Masuda Yoshiyuki Y Kimura Madoka M Shiozaki Hitomi H Murakami Haruyasu H Kenmotsu Hirotsugu H Taira Tetsuhiko T Ono Akira A Wakuda Kazushige K Imai Hisao H Oyakawa Takuya T Ishii Takeshi T Omori Shota S Nakashima Kazuhisa K Endo Masahiro M Omae Katsuhiro K Mori Keita K Yamamoto Nobuyuki N Tanuma Akira A Takahashi Toshiaki T

BMC cancer 20170825 1

<h4>Background</h4>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 canc ...[more]

PMID: 28841858

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Project description:BackgroundDecreased lean muscle mass in the lower extremity in diabetic peripheral neuropathy (DPN) is thought to contribute to altered joint loading, immobility, and disability. However, the mechanism behind this loss is unknown and could derive from a reduction in size of myofibers (atrophy), destruction of myofibers (degeneration), or both. Degenerative changes require participation of muscle stem (satellite) cells to regenerate lost myofibers and restore lean mass. Determining the degenerative state and residual regenerative capacity of DPN muscle will inform the utility of regeneration-targeted therapeutic strategies.MethodsBiopsies were acquired from 2 muscles in 12 individuals with and without diabetic neuropathy undergoing below-knee amputation surgery. Biopsies were subdivided for histological analysis, transcriptional profiling, and satellite cell isolation and culture.ResultsHistological analysis revealed evidence of ongoing degeneration and regeneration in DPN muscles. Transcriptional profiling supports these findings, indicating significant upregulation of regeneration-related pathways. However, regeneration appeared to be limited in samples exhibiting the most severe structural pathology as only extremely small, immature regenerated myofibers were found. Immunostaining for satellite cells revealed a significant decrease in their relative frequency only in the subset with severe pathology. Similarly, a reduction in fusion in cultured satellite cells in this group suggests impairment in regenerative capacity in severe DPN pathology.ConclusionDPN muscle exhibited features of degeneration with attempted regeneration. In the most severely pathological muscle samples, regeneration appeared to be stymied and our data suggest that this may be partly due to intrinsic dysfunction of the satellite cell pool in addition to extrinsic structural pathology (eg, nerve damage).Clinical relevanceRestoration of DPN muscle function for improved mobility and physical activity is a goal of surgical and rehabilitation clinicians. Identifying myofiber degeneration and compromised regeneration as contributors to dysfunction suggests that adjuvant cell-based therapies may improve clinical outcomes.

Project description:BackgroundSarcopenia has been confirmed as a poor prognostic indicator of lung cancer. However, the lack of abdominal computed tomography (CT) hindered the application to assess the status of sarcopenia. The purpose of this study was to assess the ability of chest CT radiomics combined with machine learning classifiers to identify sarcopenia in advanced non-small cell lung cancer (NSCLC) patients.MethodsThis study retrospectively analyzed CT images of 99 patients with NSCLC. Skeletal muscle radiomics were extracted from a single axial slice of the chest CT scan at the 12th thoracic vertebrae level. In total, 854 radiomic and clinical features were obtained from each patient. Feature selection was conducted with FeatureSelector module, optimal key features were fed into the lightGBM classifier for model construction, and Bayesian optimization was adopted to tune hyperparameters. The model's performance was evaluated by specificity, sensitivity, accuracy, precision, F1-score, Matthew's correlation coefficient (MCC), Cohen's kappa coefficient (Kappa), and AUC.ResultsA total of 40 patients were found to have sarcopenia. Five optimal features were selected. In the base lightGBM model, the specificity, sensitivity, accuracy, precision, F1-score, AUC, MCC, Kappa of validation set were 0.889, 0.750, 0.833, 0.818, 0.783, 0.819, 0.649, 0.648, respectively. After Bayesian hyperparameter tuning, the optimized lightGBM model achieved better prediction performance, and the corresponding values were 0.944, 0.833, 0.900, 0.909, 0.870, 0.889, 0.791, 0.789, respectively.ConclusionsChest CT-based radiomics has the potential to identify sarcopenia in NSCLC patients with the lightGBM classifier, and the optimal lightGBM model via Bayesian hyperparameter tuning demonstrated better performance.Key pointsSIGNIFICANT FINDINGS OF THE STUDY: Our study demonstrates that chest CT-based radiomics combined with lightGBM classifier has the ability to identify sarcopenia in NSCLC patients.What this study addsSkeletal muscle radiomics would be a potential biomarker for sarcopenia identity in NSCLC patients.

Dataset Information

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

Publications

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

Similar Datasets

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