Impact of Physical Inactivity on the Risk of Disability and Hospitalization in Older Patients with Advanced Lung Cancer.

PURPOSE: This prospective observational study aimed to explore the influence of physical inactivity during initial chemotherapy on the risk of disability and hospitalization in later life among older patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients aged 70 or above who were scheduled to receive first-line chemotherapy for newly diagnosed advanced NSCLC were recruited for the study. An electronic pedometer was used to measure daily steps; based on the change rate (cutoff: -12.5%) from pretreatment to 12 ± 4 weeks after enrolment, patients were classified as active or inactive. The Barthel Index estimated activities of daily living. We compared disability-free survival time, mean cumulative functions of hospital stays, and medical costs, between the active and inactive groups. RESULTS: Among the 29 patients enrolled, 21 were evaluable. Compared with active patients (n = 11), inactive patients (n = 10) showed shorter disability-free survival (6.4 vs 19.9 months, p < 0.05) and tended to have longer hospital stays (23.7 vs 6.3 days/person) and higher inpatient care cost (¥1.6 vs ¥0.3 million/person [US$16,000 vs US$3000/person]) during the first year. CONCLUSION: Physical inactivity during initial chemotherapy may be a risk factor for developing disability and requiring hospitalization in later life for older patients with advanced NSCLC. Our findings may indicate the need for lifestyle interventions with multidisciplinary teams, which include physicians, nurses, and physiotherapists, for older patients with advanced lung cancer during an active cancer treatment. A large-sample-sized study is needed to validate our findings.

A randomized phase II study of nutritional and exercise treatment for elderly patients with advanced non-small cell lung or pancreatic cancer: the NEXTAC-TWO study protocol.

BACKGROUND: Most advanced elderly cancer patients experience fatigue, anorexia, and declining physical function due to cancer cachexia, for which effective interventions have not been established. We performed a phase I study of a new nonpharmacological multimodal intervention called the nutritional and exercise treatment for advanced cancer (NEXTAC) program and reported the excellent feasibility of and compliance with this program in elderly patients with advanced cancer who were at risk for cancer cachexia. We report here the background, hypothesis, and design of the next-step multicenter, randomized phase II study to evaluate the efficacy of the program, the NEXTAC-TWO study. METHODS: Patients with chemo-naïve advanced non-small cell lung cancer or pancreatic cancer, age ≥ 70 years, performance status ≤2, with adequate organ function and without disability according to the modified Katz index will be eligible. In total, 130 participants will be recruited from 15 Japanese institutions and will be randomized into either the intervention group or a control group. Computer-generated random numbers are allocated to each participant. Stratification factors include performance status (0 to 1 vs. 2), site of primary cancer (lung vs. pancreas), stage (III vs. IV), and type of chemotherapy (cytotoxic vs. others). Interventions and assessment will be performed 4 times every 4 ± 2 weeks from the date of randomization. Interventions will consist of nutritional counseling, nutritional supplements (rich in branched-chain amino acids), and a home-based exercise program. The exercise program will include low-intensity daily muscle training and lifestyle education to promote physical activity. The primary endpoint is disability-free survival. It is defined as the period from the date of randomization to the date of developing disability or death due to any cause. This trial also plans to evaluate the improvements in nutritional status, physical condition, quality of life, activities of daily living, overall survival, and safety as secondary endpoints. Enrollment began in August 2017. The study results will demonstrate the efficacy of multimodal interventions for elderly cancer patients and their application for the maintenance of physical and nutritional conditions in patients with cancer cachexia. This work is supported by a grant-in-aid from the Japan Agency for Medical Research and Development. DISCUSSION: This is the first randomized trial to evaluate the efficacy and safety of a multimodal intervention specific for elderly patients with advanced cancer. TRIAL REGISTRATION: Registered at August 23, 2017. Registry number: UMIN000028801 .

Feasibility of early multimodal interventions for elderly patients with advanced pancreatic and non-small-cell lung cancer.

BACKGROUND: Combinations of exercise and nutritional interventions might improve the functional prognosis for cachectic cancer patients. However, high attrition and poor compliance with interventions limit their efficacy. We aimed to test the feasibility of the early induction of new multimodal interventions specific for elderly patients with advanced cancer Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) programme. METHODS: This was a multicentre prospective single-arm study. We recruited 30 of 46 screened patients aged ≥70 years scheduled to receive first-line chemotherapy for newly diagnosed, advanced pancreatic, or non-small-cell lung cancer. Physical activity was measured using pedometers/accelerometer (Lifecorder® , Suzuken Co., Ltd., Japan). An 8 week educational intervention comprised three exercise and three nutritional sessions. The exercise interventions combined home-based low-intensity resistance training and counselling to promote physical activity. Nutritional interventions included standard nutritional counselling and instruction on how to manage symptoms that interfere with patient's appetite and oral intake. Supplements rich in branched-chain amino acids (Inner Power® , Otsuka Pharmaceutical Co., Ltd., Japan) were provided. The primary endpoint of the study was feasibility, which was defined as the proportion of patients attending ≥4 of six sessions. Secondary endpoints included compliance and safety. RESULTS: The median patient age was 75 years (range, 70-84). Twelve patients (40%) were cachectic at baseline. Twenty-nine patients attended ≥4 of the six planned sessions (96.7%, 95% confidence interval, 83.3 to 99.4). One patient dropped out due to deteriorating health status. The median proportion of days of compliance with supplement consumption and exercise performance were 99% and 91%, respectively. Adverse events possibly related to the NEXTAC programme were observed in five patients and included muscle pain (Grade 1 in two patients), arthralgia (Grade 1 in one patient), dyspnoea on exertion (Grade 1 in one patient), and plantar aponeurositis (Grade 1 in one patient). CONCLUSIONS: The early induction of multimodal interventions showed excellent compliance and safety in elderly patients with newly diagnosed pancreatic and non-small-cell lung cancer receiving concurrent chemotherapy. We are now conducting a randomized phase II study to measure the impact of these interventions on functional prognosis.

Long-Term Outcomes of Gastric Cancer Patients with Preoperative Sarcopenia.

BACKGROUND: There are few reports of long-term outcomes of gastric cancer patients with sarcopenia. The purpose of this study was to assess the impact of sarcopenia on long-term outcomes in gastric cancer patients who underwent curative resection. METHODS: A total of 951 patients aged 65 years or older who underwent R0 resection for gastric cancer were investigated. Sarcopenia was defined as a decreased arm muscle area < 38.05 cm2 in men and < 27.87 cm2 in women combined with a decline in grip strength to < 26 kgf in men and < 18 kgf in women. RESULTS: Of 951 patients, 111 (11.7%) were diagnosed with sarcopenia. Reduced surgery was performed significantly more frequently in patients with sarcopenia (p = 0.006). The incidence of eligible patients who received adjuvant chemotherapy was significantly lower in patients with sarcopenia than in those without sarcopenia (p = 0.030). Mortality due to gastric cancer and aging-associated multiple organ failure rates without obvious diseases were higher in patients with sarcopenia (p = 0.036 and p < 0.001, respectively). Overall survival (OS) and cause-specific survival (CSS) were significantly worse in patients with sarcopenia (p < 0.001 and p = 0.005, respectively). Multivariate analysis for OS and CSS revealed that sarcopenia was an independent prognostic factor in gastric cancer patients (p < 0.001 and p = 0.043, respectively). CONCLUSIONS: Sarcopenia is related to poor survival in gastric cancer patients and appears to be a significant negative prognostic factor in patients with gastric cancer who underwent curative resection.