Systemic cancer therapy-associated skeletal muscle wasting is emerging as a powerful impetus to the overall loss of skeletal muscle experienced by patients with cancer. This review explores the clinical magnitude and biological mechanisms of muscle wasting during systemic cancer therapy to illuminate this adverse effect. Emerging strategies for mitigation are also discussed.Clinical findings include precise, specific measures of muscle loss over the course of chemotherapy, targeted therapy and immunotherapy. All these therapeutic classes associate with quantitatively important muscle loss, independent of tumor response. Parallel experimental studies provide understanding of the specific molecular basis of wasting, which can include inhibition of protein synthesis, proliferation and differentiation, and activation of inflammation, reactive oxygen species, autophagy, mitophagy, apoptosis, protein catabolism, fibrosis and steatosis in muscle. Strategies to mitigate these muscle-specific adverse effects of cancer therapy remain in the earliest stages of development.The adverse side effect of cancer therapy on skeletal muscle has been largely ignored in the development of cancer therapeutics. Given the extent to which loss of muscle mass and function can bear on patients' function and quality of life, protection/mitigation of these side effects is a research priority. 

Adverse effects of systemic cancer therapy on skeletal muscle: myotoxicity comes out of the closet

Purpose of review Systemic cancer therapy-associated skeletal muscle wasting is emerging as a powerful impetus to the overall loss of skeletal muscle experienced by patients with cancer. This review explores the clinical magnitude and biological mechanisms of muscle wasting during systemic cancer therapy to illuminate this adverse effect. Emerging strategies for mitigation are also discussed. Recent findings Clinical findings include precise, specific measures of muscle loss over the course of chemotherapy, targeted therapy and immunotherapy. All these therapeutic classes associate with quantitatively important muscle loss, independent of tumor response. Parallel experimental studies provide understanding of the specific molecular basis of wasting, which can include inhibition of protein synthesis, proliferation and differentiation, and activation of inflammation, reactive oxygen species, autophagy, mitophagy, apoptosis, protein catabolism, fibrosis and steatosis in muscle. Strategies to mitigate these muscle-specific adverse effects of cancer therapy remain in the earliest stages of development. Summary The adverse side effect of cancer therapy on skeletal muscle has been largely ignored in the development of cancer therapeutics. Given the extent to which loss of muscle mass and function can bear on patients’ function and quality of life, protection/mitigation of these side effects is a research priority.

Objective Skeletal muscle mass (SMM) is an important biomarker for prognosis and health in older patients with cancer. Limited information is available on the recovery course of SMM after oesophagectomy following neoadjuvant chemotherapy (NAC) in older patients. This study was performed to investigate the recovery course of SMM after oesophagectomy following NAC and the preoperative predictors of delayed recovery in older patients with locally advanced oesophageal cancer (LAEC). Methods This single-centre retrospective cohort study involved older (≥65 years) and non-older (<65 years) patients with LAEC who underwent oesophagectomy following NAC. The SMM index (SMI) was calculated using CT images. One-way analysis of variance and multivariate logistic regression analysis were performed. Results In total, 110 older patients and 57 non-older patients were analysed. Loss of the SMI after NAC to 12 months postoperatively was significantly greater in older patients than in non-older patients (p<0.01). The significant preoperative predictor of delayed recovery of the SMI 12 months after surgery was loss of the SMI during NAC in older patients (per 1%: adjusted OR 1.249; 95% CI 1.131 to 1.403; p<0.001), but not in non-older patients (per 1%: OR 1.074; 95% CI 0.988 to 1.179; p=0.108). Conclusions There is an especially large unmet need for preventing the long-term sequelae of SMM loss in older patients with LAEC after oesophagectomy following NAC. In older patients, loss of SMM during NAC is an especially useful biomarker for prescribing postoperative rehabilitation to prevent postoperative loss of SMM.

Skeletal muscle mass recovery after oesophagectomy and neoadjuvant chemotherapy in oesophageal cancer: retrospective cohort study

ASO Author Reflections: Significance of Loss of Skeletal Muscle Mass During Neoadjuvant Chemotherapy in Older Patients with Esophageal Cancer

This study aimed to determine how behavioral restrictions due to the emergency declaration following the coronavirus disease 2019 (COVID-19) pandemic affect exercise tolerance and its outcomes in patients in the phase III cardiac rehabilitation program. This is a multicenter retrospective cohort study. Participants in outpatient cardiac rehabilitation programs and cardiopulmonary exercise testing before and after the emergency declarations were included. A total of 90 participants were included (median age 75.0 years, 69% male), and the changes in physical function and exercise tolerance were compared before and after the emergency declaration. Patients were divided into a decline-in-peak oxygen uptake (VO2 ) group and a nondecline-in-peak VO2 group. Comparison before and after the emergency declaration showed that the anaerobic threshold declined significantly and peak VO2 exhibited a downward trend. The decline-in-peak VO2 group consisted of 16 patients (17%) with better exercise tolerance, multiple comorbidities, and declined lower extremity muscle strength. These patients also had a higher rate of subsequent composite events (HR, 5.2; 95% confidence interval, 1.4-18.8, p = 0.01). Before and after the emergency declaration, the patient's exercise tolerance may decline, leading to a poor prognosis. This study suggests the importance of maintaining exercise tolerance during the COVID-19 pandemic. This article is protected by copyright. All rights reserved.

Impact of the COVID-19 pandemic on exercise tolerance and patient outcomes with phase III cardiac rehabilitation in Japan: A multicenter study.

Prognostic Impact of the Loss of Skeletal Muscle Mass During Neoadjuvant Chemotherapy on Older Patients with Esophageal Cancer

Abstract If physical functions are impaired in patients with cancer owing to the progression of the disease and the treatment processes, their activities of daily living (ADLs) decline; thus, the quality of life is impacted. Elderly patients with cancer constitute a group with diverse basic physical, mental and social skill levels owing to aging. Given that there are potential risks of frailty and sarcopenia, their physical functions and ADL are prone to decline. Furthermore, there are many cases in which patients live alone, isolated from the society or face social problems. Therefore, in the treatment of elderly patients with cancer, geriatric assessment is used to comprehensively assess comorbidity, physical functions and psychophysiological/social/environmental situations and a system that provides supportive care is required. As part of this process, cancer rehabilitation plays an important role in prevention of complications, functional recovery and maintenance and improvement of physical functions and ADL until the time of palliative care. To provide rehabilitation, utmost attention must be paid to issues unique to elderly people, such as frailty, sarcopenia, dementia, delirium, pain management, depression and undernutrition/dysphagia.

/pdf/rehabilitation-for-elderly-patients-with-cancer-1i522q52.pdf

Rehabilitation for elderly patients with cancer

https://link.springer.com/content/pdf/10.1007/s41999-022-00735-0.pdf

Impact of early postoperative factors on changes in skeletal muscle mass after esophagectomy in older patients with esophageal cancer

In 2020, COVID-19 spread throughout the world, and international measures such as travel bans, quarantines, and increased social distancing were implemented. In Japan, the number of infected people increased, and a state of emergency was declared from 16 April to 25 May 2020. Such a change in physical activity could lead to a decline in physical function in people with disabilities. A retrospective study was conducted to determine the impact of the pandemic on the physical function of disabled persons living in the community. Data were collected at four points in time: two points before the declaration of the state of emergency was issued and two points after the declaration period had ended. Time series data of physical function at four points in time were compared for 241 people with disabilities. The mean age was 72.39 years; 157 had stroke, 59 musculoskeletal disease, and 26 other diseases. Overall, there was a long-term decrease in walking speed (p < 0.001) and a worsening of the Timed Up-and-Go (TUG) score (p < 0.001) after the period of the state of emergency. The TUG score worsened only in the group with a walking speed of 1.0 m/s or less before the state of emergency (p = 0.064), suggesting that this group was more susceptible.

https://www.mdpi.com/1660-4601/19/19/12599/pdf?version=1665462697

Tetsuya Tsuji

Papers

Prognostic Impact of the Loss of Skeletal Muscle Mass During Neoadjuvant Chemotherapy on Older Patients with Esophageal Cancer

Rehabilitation for elderly patients with cancer

Impact of early postoperative factors on changes in skeletal muscle mass after esophagectomy in older patients with esophageal cancer

Skeletal muscle mass recovery after oesophagectomy and neoadjuvant chemotherapy in oesophageal cancer: retrospective cohort study

Effects of the COVID-19 Pandemic on Physical Function of Community-Dwelling People with Disabilities in Japan