Effects of Exercise Training during Concomitant Chemoradiation Therapy in Head-and-Neck Cancer Patients: A Systematic Review

INTRODUCTION

Head-and-neck carcinoma is a heterogeneous disease, encompassing a variety of tumors that originate in the hypopharynx, oropharynx, lip, oral cavity, nasopharynx, or larynx. It is considered as the sixth most common cancer worldwide.[1] Head-and-neck cancer is predominantly seen in 25%–30% of the Indian population, whereas 60%–80% presenting with the advanced stage of the disease.[2]

Treatment of head and neck cancer depends on the extensiveness or the stage of the tumor. In the early stages (Stage I and II), surgery has always been the treatment of choice, whereas in the advanced stages of the disease (III and IV, IVa, IVb, and IVc), multimodality treatment (surgery with radiotherapy [RT] and/or chemotherapy, chemoradiation therapy [CRT]) is used.[3]

CRT along with its benefits also results in substantial number of treatment-related adverse effects.[1] Primarily, due to the anatomic location of the tumor, CRT affects the speech, swallowing, and respiratory functions.[4] Adverse effects also extending to fatigue, generalized peripheral muscle weakness that includes muscle wasting, cachexia, and disuse muscle atrophy; and depression often lead to physical inactivity in these patients.[56]

Hence, all of these above factors impair the quality of life (QOL) and daily functional capacity in head and neck cancer patients, facilitating the need for an exercise rehabilitation program.[5] Exercise being an acute intervention shows many effects on the cardiovascular system and lean body mass (LBM) and also reduces the risk of metabolic disorders, when incorporated as an adjunct with chemoradiotherapy.[7] Hence, physical activity in the form of exercise is a possible and effective treatment that may positively impact head and neck cancer patients' body composition, physical functioning capacity, and overall QOL.[8] Thus, this review aims to investigate the current state of exercise-based research in this population.

METHODS/SEARCH STRATEGY

An all-encompassing search was conducted in CINAHL, Cochrane Library, EBSCO, and PubMed Central using keywords – Neoplasms, Head and Neck, Head, Neck Neoplasms, Cancer of Head and Neck, Head and Neck Cancer, Upper Aerodigestive Tract Neoplasms, Training, Resistance, Strength Training, Training, Strength, Strengthening program, Aerobic Exercises, and Aerobic training. Keywords were identified using Medical Subject Heading, synonyms of the words in the title, and keywords from the articles. Boolean operator “AND” and reference list of articles found were used to search articles for the review. Studies that evaluated exercise interventions in head and neck cancer patients on concomitant CRT and the studies published in English-language journals were included for the review. Any of the studies that evaluated cancer survivors admitted to an intensive care unit and yoga intervention were excluded. Furthermore, any studies that included interventions addressing complications such as amputations and nervous system impairment following cancer were excluded. Only randomized controlled trials (RCTs) were included in our review. The protocol for the review was constructed by SRS and MD. Two investigators (MD and SRS) independently conducted data search in the above mentioned search engines, and the search results from all the databases were screened independently for eligibility by the two investigators.

All the retrieved data used in this systematic review underwent a qualitative methodological rating given by authors MD and SRS using the PEDro scale. Any differences in the opinion were resolved by discussions between MD and SRS. A data extraction sheet was made to cover all the data regarding the objectives of the study, type of exercise intervention, primary and secondary outcome measures, study design, sample size, participant selection, details of exercise intervention, and adverse events as reported by the study. Data were briefed to highlight the study characteristics, methodological rating score, type of exercise interventions, and outcomes reported from each study.

RESULTS

The following PRISMA flow diagram shown in Figure 1 summarizes the, identification, screening, eligibility, and inclusion of the clinical trials. All the retrieved trials that were eligible for the systematic review underwent a quality rating following which a methodological rating was given to each using the PEDro scale [Table 1] for RCTs. The scores ranged from 6 to 10 out of 11, and therefore, the trials were categorized as high quality (6–10). All the studies were reasonably reliable to assess the effect of the intervention on their principle outcome measures.

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Figure 1

PRISMA flow diagram

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All the studies characterized in this review were RCTs. Three types of exercise interventions were noted: strength training, aerobic training, and home-based walking program. All details regarding the study design, sample size, cancer management, and type of exercise intervention and outcome measures assessed are summarized in Table 2, and detailed explanation of exercise intervention and their respective results are mentioned in Table 1.

DISCUSSION

The present study is the first comprehensive systematic review on exercise interventions for head and neck cancer survivors from India. Cancer survivors are known to be at an increased risk of developing chronic diseases and are more likely to die from non-cancer causes. Indians are considered to have a lower threshold for developing chronic diseases, and therefore, India currently has a high burden of chronic diseases. Hence, this could be a potential area for research. Physiotherapy-based interventions have been shown to reduce the recurrence of cancer, anxiety, depression, pain, and body mass index and improve survival, cardiorespiratory fitness, strength, fatigue, range of motion, appetite, and QOL.[9] The present review showed three different types of exercise protocol and intervention to note its effect on strength, aerobic functional capacity, and QOL in head and neck cancer patients undergoing CRT. Exercise for this review is operationally defined as exercise intervention in the form of aerobic and resistance training administered to head and neck cancer survivors on concomitant chemoradiotherapy. A study conducted by Samuel et al. in 2013 evaluated the effect of exercise training on the functional capacity and QOL in head and neck cancer patients. In this study, the author justified that low functional capacity in these patients due to the harmful concomitant side effects of CRT could be counteracted by a structured exercise training program. Thus, the study showed positive results and improvement in the functional capacity through exercise training evaluated by 6-min walk distance and Short Form-36 (SF-36) questionnaires. The authors hypothesized that exercise positively influences the oxygen transport thus increasing the oxygen uptake by the tissues and prevents the peripheral muscle fatigue, thereby restoring the energy, improving strength, and maintaining cardiorespiratory endurance.[10] Another study conducted by Zhao et al. aimed at studying the impact of resistance training and walking program on different components in head and neck cancer patients. These components involved strength, mobility, physical activity, diet, and QOL that were assessed using dynamometers, self-reported physical activity questionnaires, 6-min walk tests, BMI, SF-36 questionnaire, respectively. This study showed gradual changes and improvement in the above outcomes from 7^th to 14^th weeks of the study. One of the important study limitations was a small sample size which limited the statistical power, but the assessment and intervention showed feasible results.[11] A similar randomized trial study by Lonkvist et al. in 2017 was conducted to evaluate the changes and effect of progressive resistance training (PRT) in LBM, physical function, and mobility after 12 weeks of training. These were evaluated using dual-energy X-ray absorptiometry, muscle biopsies to evaluate the muscle fiber change. A twelve-week period was chosen as it was considered a sufficient period of PRT to affect LBM. Although this study found that PRT is feasible and safe during CRT for head and neck cancer, it pointed the need for a randomized trial to reveal the potential effect of PRT during CRT in HNC.[12] In 2019, Samuel et al. published an RCT to evaluate the effect of exercise training on strength, functional capacity, and QOL. Results showed beneficial improvements in the above outcomes and that aerobic and resistance training are both safe and feasible during chemoradiation for head and neck cancer.[13] The studies retrieved by this review help us to understand that exercise is feasible during the course of CRT in patients with head and neck cancer. To summarize, the following outcome measures, i.e., muscle strength, mobility, functional capacity, and QOL, have been studied and the following exercise interventions in the domain of aerobic and resistance training have been studied.

We further suggest that future studies should use the above outcomes and following types of training such as interval training can be studied in the domain of aerobic, e.g., brisk walking, deep breathing exercises, cycling, and resistance training involving theraband exercises, and weights for major muscle groups such as the biceps, triceps, pectorals, hip abductors, extensors, quadriceps, and gastrocnemius muscles. We also recommend more studies in this area to strengthen the current body of evidence in this field of exercise oncology.

CONCLUSION

All these data, therefore, conclude that exercise-based intervention is safe, feasible, and beneficial in patients with head and neck cancer receiving CRT.