Physical Exercise Protocol as a clinical biomarker for improvement in functional capacity and activity performance in hospitalized cancer survivors- An Experimental Study.

INTRODUCTION

The number of cancer cases is increasing making cancer the second most common disease responsible for mortality with about 0.3 million deaths per year.¹ The advancement in branch of oncology, improved cancer treatment and their screening methods has led to increasing survivorship.² Literature suggests that patients express to carry out their functional tasks by themself as long as possible.³ Reduced physical functioning has also been attributed as a main reason for increasing the chances of mortality.⁴ The various cancer treatments such as surgery, chemotherapy, radiation therapy, hormone replacement therapy and/or a combination of these treatments lead to multitude of adverse effects which later in the course tend to impede performance of activities of daily living and thus, negatively affecting survivorship.

There is a growing body of supporting literature regarding safety of exercise its effectiveness as a non-pharmacological therapy for restoring and maintaining patient’s strength, endurance, physical activity status, chronic and late side effects and improving quality of life during the cancer continuum.⁵ Studies published to date highlight that cancer patients suffer from various post treatment physical complications, many of which can be effectively treated with physical therapy intervention. But there is dearth in literature regarding the role of physical therapy exercises in managing the immediate post-operative complications, side effects experienced during chemo-radiation therapy and effectiveness of physical therapy exercise interventions during that period of hospitalization stay stating a lack of standardized physical exercise protocol for hospitalized setting. The purpose of this study was to evaluate effectiveness of physical exercise protocol as a clinical biomarker for improvement in functional capacity and activity performance in hospitalised cancer survivors in an Indian clinical set-up.

MATERIALS AND METHODS

The present single arm clinical trial study was conducted in a tertiary care hospital for cancer subjects who underwent surgery and/or radiation therapy and/or chemotherapy or a combination of these. Ethical clearance for the study was obtained by the Institutional Ethical Review Committee. Prior to commencement of the study a written consent in their vernacular language was obtained. All study subjects were screened for inclusion and exclusion criteria prior to their enrolment in the study. All 33 adults, male and female hospitalised subjects within age group of 18-65 years, willing to participate in the study with a primary diagnosis of cancer having no contraindication prohibiting participation in low to moderate exercise regimen assessed by the medical oncologist, capable of verbal communication without any psychiatric illness as diagnosed by the clinical psychiatrist were included in the study. CNS malignancies, bone tumours and haematological malignancy were excluded from the study (Fig.1). The sample size was calculated using the formula n=2(𝑍�+ 𝑍𝛃)² * 𝛔2/𝒅2. With 5% level of significance and 90% power, the sample size was calculated as n= 2(1.96+1.2816)2* 102/82 thus gaining a total sample size, n=33.

A brief demographic data of each subject was noted after which each subject was assessed for functional capacity using six-minute walk test and were then administered the Karnofsky Performance Status Scale for noting the activity status and documentation of Functional Assessment of Cancer Therapy General questionnaire for quality of life was done.

All the exercises were performed under physical therapist’s supervision once daily in the morning hours between 09-11am. Subject was asked to repeat the same protocol for 2nd time in the evening between 3:30-5:30pm. Apart from these exercises, subjects were made to ambulate, once by the therapist and twice by the relative or instructed to carry out self-ambulation. A total of 33 (thirtythree) subjects completed the protocol.

After 01 week of intervention the pre-post data analysis was assessed for six minute walk distance, Karnofsky Performance Status scale and Functional Assessment of Cancer Therapy General scale scores.

The following outcome measure were used:

1. 6 Minute Walk Distance (6MWD):⁶ The 6 MWD is a self-paced walk test that assesses submaximal level of functional capacity. It requires subject to walk a 100ft hall way. This test measures distance that the patient can quickly walk on hard surface in a period of 6 minutes. It evaluates the global and integrated responses of all systems involved during exercise including pulmonary and cardiovascular systems, systemic circulation, peripheral circulation blood, neuromuscular units and muscle metabolism.

2. Karnofsky Performance Status Scale (KPS):^7,15 The KPS is used as a prognostic factor when deciding antineoplastic treatment based on the functional status of the patient, with regard to the ability to undertake daily activities, with or without help. There are 7 behaviour based questions. Each of the items in the Karnofsky score for performance status is awarded a number of points, from 0 to 100, in 10 point increments, where 100 indicates a patient with normal condition and 0 indicates condition incompatible with life.^11,12

3.Functional Assessment of Cancer Therapy General (FACT-G): This questionnaire assesses quality of life in subjects suffering from cancer. This self-assessing questionnaire consists of 33 questions under 4 sub- domains i.e. physical, social, emotional and functional well-being. The FACT- G Questionnaire demonstrates high coefficients of reliability and validity with the Cronbach’s alpha of the total scale is 0.89 and subscales range from 0.82 to 0.69.

RESULTS

Analysis for the present study was done using SPSS version 22. Various statistical measures such as mean, standard deviation was used to assess demographic data of all subjects participated in the study. Normality of all the parameters was determined by Kolmogorov Smirnov test. The differences (pre-test to post-test) scores of few parameters in the study that did not follow normal distribution. Non-parametric test i.e. Wilcoxon matched paired test was applied for KPS, PWB and EWB components of FACT-G. For 6MWD, SWB and FWB components of FACT-G paired t-test was applied. Probability values of p≤0.05 were considered statistically significant.

The present study included thirty-three subjects who received an intervention comprising of cancer specific exercise protocol administered twice daily for a period of 01 (one) week.

Out of a total of 33 subjects 42.42% were males and 57.58% were females respectively. The age group of both the male and female subjects were in the mean age group of 52.12±10.18 years. Amongst the type of cancer, Head and Neck Cancer dominated the group with 39.39%, followed by 24.24% pelvic cancer, 21.21% breast cancer and 15.15% abdominal cancers respectively. However, differentiation amongst the gender and type of cancer was not done. Highest number of cases of cancer recorded were in stage II as per the AJCC staging criteria (n=10) with the highest number of cancer treatment in the form of surgery (n=19) (Table1). All the outcome variables have demonstrated statistical significance with p≤0.05 respectively (Table 2).

DISCUSSION

Results of the present study demonstrated improvement in the functional capacity, physical activity performance and overall quality of life of the head and neck cancer, breast cancer, abdominal cancer and pelvic cancer subjects with the therapist designed exercise protocol on basis of Six Minute Walk Distance to know improvement in functional capacity, Karnofsky Performance Status scale for activity performance and FACT- G to determine changes in quality of life in hospitalized cancer survivors pre and post intervention. The formulated therapist designed exercise protocol included general and cancer-wise specific exercises.

The therapist designed exercise protocol included different breathing exercises and ambulation irrespective of the cancer or treatment type. For treatment related impairment, specific exercises such as soft tissue stretching techniques, range of motion exercises and gentle strengthening exercises for weakened musculature were studied. The combination of these exercises resulted in significant improvement (p≤0.05) in functional capacity indicating reduction in level of cancer related fatigue which usually sets in due to the cancer and the cancer treatment hindering patient’s ability to perform activities of daily living hence reducing their quality of life.

The effect of exercise on cancer related fatigue on diagnosed cancer patients who were in active treatment or follow up have demonstrated exercise are not only effective in managing the cancer related fatigue but also have shown to improve depression and quality of sleep. However, the type of exercise specified may not significantly influence the effect on fatigue, depression, or sleep disturbance.⁸ Similar results were obtained in the present study wherein the improved levels of functional capacity and quality of life was noted during the active treatment indirectly indicative of effective management of the element of cancer related fatigue in the acute phase of the treatment.

There is documented evidence to suggest the beneficial effect of 11 week structured combined aerobic and resistance training in managing fatigue, decreased functionality, and impaired quality of life for head and neck cancer patients which are some of the most common adverse outcomes of chemoradiotherapy.⁹ The authors intended to manage the initial effects of the chemoradiation treatment with a one week intervention with a view of maintaining their levels of activity performance as well as their functional capacity which exhibited marked improvement in the levels of fatigue, overall functionality and quality of life which were consistent with the results of present study. However, there was a difference in the duration of intervention, cancer wise specificity and the hospital set-up.

Research on relaxation training along with aerobic training for post-operative lung and gastrointestinal cancer patients have observed to be effective in improving physical performance in an out-patient basis.¹¹ However, contradictory to the present study effectively demonstrated the importance and beneficence of post-operative early mobilization and relaxation training for better long-term results of physical performance in the hospitalized cancer patients.

There is evidence stating early mobilization is effective in improvement of functional capacity of abdominal cancer surgery subjects with the exercise as intervention from post- operative day 1 till the day of discharge focusing on core stability, orthostatic training, gait training, aerobic and resistance training similar to results of the present study.¹⁶

In conclusion, the present study of hospitalised cancer survivors who were subjected to various cancer treatments such as surgery, radiation therapy and chemotherapy singly or in combination has demonstrated that the therapist designed exercise protocol including the impairment specific as well as the aerobic exercise when introduced early during the oncological intervention is supportive in terms of improvements in functional capacity, activity performance and quality of life in this small sample of hospitalized cancer subjects undergoing some form of cancer treatment. Further study in the form of larger clinical trials with a homogenous population of hospitalized cancer patients using this therapist designed protocol is suggested to confirm these therapeutically beneficial findings within this study population.

Conflict of interest: Nil