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.

Days Spent at Home near the End of Life in Japanese Elderly Patients with Lung Cancer: Post hoc Analysis of A Prospective Study.

OBJECTIVE: Days spent at home (DASH) near the end of life is considered an important patient-centered goal and outcome because many patients want to stay at home toward the end of life. This study aimed to estimate the individual DASH near the end of life and identify its early predictors, including muscle mass and physical function, among elderly patients with advanced non-small-cell lung cancer (NSCLC). METHODS: We conducted a post hoc analysis of the prospective observational study (UMIN000009768) that recruited patients aged ≥ 70 years who were scheduled to undergo first-line chemotherapy because of advanced NSCLC. We measured the muscle mass by bioelectrical impedance analysis at baseline. DASH was calculated as 30 days minus the number of days spent in hospitals, palliative care facilities, or nursing homes during the last 30 days of life. We performed linear regression analyses to evaluate the predictors of DASH. RESULTS: Altogether, 16 women and 28 men with a median overall survival of 15.5 months (range: 2.9-58.9) were included. The median DASH in the last 30 days of life was 8 days (range: 0-30, interquartile range: 0-23). Men had longer DASH than women by 7.3 days. Patients who had good trunk muscle mass index and hand-grip strength had significantly longer DASH than those who did not (4.7 days per kg/m2 increase [P = 0.017] and 0.4 days per kg increase [P = 0.032], respectively). CONCLUSIONS: Most elderly patients with advanced NSCLC had a limited DASH near the end of life. The risk factors for reduced DASH were women, reduced muscle mass, and poor physical function at the time of diagnosis of advanced NSCLC. Our findings would encourage early discussions about end-of-life care for patients with advanced cancers with risk factors for short DASH at the time of diagnosis, and thus, improve the quality of end-of-life care.

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.

Promotion of Behavioral Change and the Impact on Quality of Life in Elderly Patients with Advanced Cancer: A Physical Activity Intervention of the Multimodal Nutrition and Exercise Treatment for Advanced Cancer Program.

OBJECTIVE: Physical activity (PA) may improve the quality of life (QOL) of cancer survivors. However, the impact on patients with advanced cancer with high cachectic potential is unknown. We analyzed the feasibility of PA intervention using the multimodal program Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) and the impact on QOL in elderly patients with advanced cancer. METHODS: We recruited 30 patients aged ≥70 years who were scheduled to receive the first-line chemotherapy for newly diagnosed advanced pancreatic or non-small-cell lung cancer. The QOL was assessed using the European Organization for Research and Treatment of Cancer QOL Questionnaire version 3.0, while the PA was measured using a pedometer/accelerometer. Instructors counseled patients to increase daily activity in an 8-week educational intervention. We assessed patient attendance, compliance, and intervention efficacy. RESULTS: The median patients' age was 75 years (range, 70-84 years). Twelve patients (40%) were cachectic at baseline. Twenty-eight (93%) patients attended all sessions. Six (21%) and 15 (52%) patients increased their indoor and outdoor activity, respectively. There were significant differences in measured PA, global QOL, and role and emotional functioning between the patients who increased outdoor activity and those who did not. CONCLUSIONS: The PA intervention of the NEXTAC program was feasible as the elderly patients with advanced cancer in this study were highly compliant. The majority of patients demonstrated behavioral changes that were associated with the improvement in global QOL. We conduct a randomized phase II study to measure the impact of the NEXTAC program on QOL and functional prognosis.

Impact of Cancer Cachexia on Hospitalization-associated Physical Inactivity in Elderly Patients with Advanced Non-small-cell Lung Cancer.

OBJECTIVE: New or worsening disability can develop in elderly patients in just 1 week of hospitalization for acute illness. Elderly patients with cancer, particularly those with cancer cachexia, are vulnerable to disability. This study aimed to explore the impact of hospitalization and cachexia on physical activity (PA) in elderly patients during chemotherapy. METHODS: We prospectively enrolled 18 patients aged ≥70 years with newly-diagnosed, advanced non-small-cell lung cancer scheduled to initiate first-line chemotherapy. PA was measured using an accelerometer (Lifecorder®, Suzuken Co., Ltd., Japan). Mean daily steps at baseline, during hospitalization, and subsequent weeks (1st, 2nd, and 3rd week after discharge) were compared. RESULTS: A total of 30 hospitalizations for chemotherapy were evaluated in 18 patients with a median age of 74.5 years. The median number of baseline daily steps was 3756. Fifteen cases (50%) showed fewer daily steps during hospitalization and no recovery to baseline level during the 1st week after discharge. Long hospitalizations (≥8 days) and the presence of cachexia were associated with persistent physical inactivity. One patient developed disability within 30 days after hospitalization. CONCLUSIONS: Physical inactivity was frequently seen after hospitalization for chemotherapy in elderly patients with advanced lung cancer. Longer in-hospital days and the presence of cancer cachexia caused slow recovery from physical inactivity. Individualized hospitalization planning based on careful consideration of patient age and the presence of cancer cachexia may be needed to prevent physical inactivity and disability.