DP crm tor upton Review Article ‘Aner Jura of Howie Palas Matcn™ 2, Vol 366) 502511 {8 The Author) 2020 (SAGE Role of Physiotherapy in Hospice Care of Patients with Advanced Cancer: A Systematic Review Prina Vira, BPT', Stephen Rajan Samuel, MPT, PhD?0, Sampath Kumar Amaravadi, MPT, PhD?, PU Prakash Saxena, MBBS, MD, FAGE”, Santosh Rai PV, MBBS, MD, DNB, FRCR‘6, Jestina Rachel Kurian, MPH?, and Rachita Gururaj, BPT' Abstract ‘Objective: To review the role of physiotherapy and its effects in hospice care of patients with advanced cancer. Methods: A. ‘comprehensive literature search was performed in PubMed, Scopus, Web of Science, CINAHL and PEDro. The search strategy was devised, articles were screened, and 2 independent reviewers conducted data extraction. Eligible studies were ‘methodologically assessed for quality rating using modified Downs and Black's checklist. The extracted data was summarized according to sitelstage of cancer, details of intervention, outcome measures and the results. Result: The total number of screened articles were 2102, out of which 9 were identified as suitable for the purposes of comprehensive review. The studies included exercise therapy, massage therapy, relaxation therapy, compression bandaging and use of TENS as the various physiotherapy interventions under consideration. Studies were generally of low to moderate quality. A broad range of ‘outcomes were employed including physical symptoms like loss of function, pain, fatigue, edema, sleep disturbances and quality of life, The findings of the studies supported the benefits of the interventions. Conclusion: A structured exercise protocol, massage therapy, TENS and compression bandaging are useful in alleviating the symptoms experienced by patients with advanced cancer in hospice care. The reduced symptom burden has reflected as an improvement in their quality of life. However, there is a further need for high quality studies to strengthen the findings of this review. Keywords physiotherapy, hospice care, physical therapy, palliative care, advanced cancer, rehabilitation Introduction According to American Society of Clinical Oncology, hospice care is a part of palliative care that provides a comprehensive approach to the patients with advanced or terminal illnesses having life expectancy of 6 months or less. Hospice care aims to prevent, manage, and/or relieve discomfort and symptoms ccaused by cancer and its treatment by following a multidisei- plinary approach," Patients with advanced cancer suffer from distressing symptoms such as pain, weakness, fatigue, breath- lessness, nausea, vomiting, constipation, sleeping disorders, lymphedema, venous thrombosis and so on.” These symptoms impair their physical functioning eteating dependency, which ccan often lead to limitations in their ability to perform activities of daily living." Hence, it is imperative to address the symp- toms in patients with advanced cancer to maintain their inde pendence and improve overall quality of life [QoL.}. According to American Physical Therapy Association, the goal of phy- siotherapy is to optimize movement and function ofall people.” This, if applied in hospice care, may have potential to improve the function and QoL. of patients with advanced cancer. Phy- siotherapy in hospice care focuses on control of localised pain, reduction of limb edema, relief of respiratory symptoms, restoration and maintenance of mobility.’ Jane Toot in 1982, ‘was the first physical therapist to describe the significance of physiotherapy in palliative and hospice care, Her work high- lighted the role of the physiotherapist as a clinician, educator, counsellor and team member.° This paved way for further " Department of Physiotherapy, Kasturba Medical College, Mangalore, Manipal Academy of Hier Education, Karnataka, nda * Deparment of Physiotherapy, Kasturba Mecial College, Manipal Academy of Higher Education, Mangalore, Karat, nat "Department of Radiation Oncology, Kascurba Medical College, Manipal Academy of Higher Education, Manglors, Karnataka, Inia “Department of Radoigy, Kesurba Medel Calege, Manipal Academy of Higher Education, Mangalore, Karnacaa, Inia 5 Prasanna School of Pubic Heakh, Manipal Academy of Higher Education Manbl, Karmal, Inda Corresponding Author: ‘Stephan Rajan Samus MPT, PHD, Department of Physiotherapy, Kastorba Medial College, Manglor, Manipal Aademy of Hier Educauon, Kernaaka 575001, ini Era stephen sarvel@manipaeds504 “American Journal of Hospice & Palliative Medicine” 38(5) research, However, there are no studies systematically sum- marizing the evidence of physiotherapy interventions in hospice care of patients with advanced cancer unlike that of long-standing cardiac or pulmonary diseases.” This systematic review was developed with an aim to answer the following rescarch questions: (1) What are the var- ious physiotherapy interventions addressing the symptoms of patients with advanced cancer in hospice care? (2) What are the characteristics (dose, duration, type and intensity) and effects of physiotherapy interventions in hospice care of patients with advanced cancer? Methods Search Strategy and Selection Criteria ‘Studies were identified from databases such as PubMed, Sc pus, Web of Science, CINAHL and PEDro from inception until April 2020, The identification ofthe articles was done using the search terms advanced cancer; carcinoma; neoplasm; hospice; palliative care; terminal care; end-of-life care; physiotherapy: physical therapy; exercise therapy; electrotherapy; electrical stimulation therapy; exercise interventions; aerobic exercises; massage; manual lymphatic drainage; breathing exercises; chest physiotherapy; Transcutaneous electrical stimulation(- TENS); low-level light therapy; relaxation therapy and com- session bandages by adding the Boolean operators “AND” and ‘OR”. We included only experimental studies (Randomised Controlled Trials (RCTS), non-Randomised Controlled Trials (non-RCTs), case reports & case series) in our review. The search was restricted to studies done on human population Only articles published in English were included. . Initially a scoping search was conducted in January-February 2020 witha detailed structured search conducted in March & April 2020. ‘Two investigators (PV and SRS) conducted the search in the databases mentioned above. Studies retrieved after the search ‘were independently screened for eligibility criteria by PV and SRS. Differences in opinion were addressed by discussions between PV and SRS. Inclusion and Exclusion Criteria ‘Studies that met the following criteria were included 1) Type of participants: Participants with age >18 years, diagnosed with advanced cancer, receiving hospice care, Advanced cancer was defined as “cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment” 2) Type of design: RCTs, non-RCTs, case reports, case ‘Studies that do not include physical therapy as interventions such as all the complementary and alternative medicine thera- pies, yoga, speech therapy, ete. were excluded, Quality Assessment and Methodological Rating Studies eligible for the systematic review were methodologi- cally assessed and rated by PV and RG for the quality of study using modified Downs and Black’s checklist.® Data was ‘extracted into an excel shect that included the objectives of the study, site and stage of cancer, participant selection, adjuvant treatment, type and details of intervention, comparator agent, ‘outcome measures, study design, sample size and adverse ‘events as reported by the study. Data from each selected study were organized into a table to highlight the scores of methodo- logical assessment, site and stage of cancer, study design, sam- ple size, details of interventions, outcome measures and results Results A total of 2102 articles were obtained after searching the databases. After merging the duplicates, 1784 articles ‘were screened through title and abstract, out of which 19 arti- cles were found eligible for fulltext reading. Of these, 9 articles ‘were found to be eligible for inclusion. Figure | summarizes the identification, screening, eligibility, and inclusion of the studies, All the included studies underwent quality assessment using, modified Downs and Black’s check list. The studies were of low to moderate quality due to factors such as poor study designs, small sample size, high drop-out rates and missing data, Details ofthe methodological quality assessment are sum- ‘marized in Table 1. Among the 9 studies, 4 were single arm re-post intervention design; 3 were RCTS; one was a non-RCT and another, a case series. Al studies, except one” had mentioned the cancer stage oF sites. All the studies had patients with advanced or incurable cancer, Most of the patients included in the studies had a life expectancy of 6 months or less or were in the terminal stage, ‘The outcome measures were symptom-based including physi- cal function, fatigue, pain, lymphedema & sleep disturbances and QoL. Exercise therapy," electrotherapy,'* massage therapy, relaxation therapy'® and compression bandaging!” were the interventions included in this review. Five out of 9 studies evaluated the effect of various exercise interventions such as individualized exercise supervised by physiotherapist”; group circuit training program comprising of 6 different exercises"; « home-based functional walking program’'; cardiovascular and resistance exercises’? and Duke Energizing Exercise plan (DEEP). Details regarding the cancer site/stage, study design, sample size, adjuvant treatment, comparator agent and outcome mea- sures assessed in these studies are summarized in Table 2, and the details of intervention and results are given in Table 3 Discussion World Health Organization in 2018, reported rise in cancer incidence to 18 million with further increase in the numberVira et al 505, of cases expected every year." 34% of worldwide burden of hospice care requirement is generated by cancer patients, when compared to all other conditions, making this disease a prior- ity.!” Hence, this review was developed to compile and analyze evidences, evaluating the effect of physiotherapy interventions in hospice care of patients with advanced cancer. The evidence retrieved from the search promotes the use of exercise therapy, electrotherapy, massage techniques and compression banda ging for the management of specific symptoms presented in the patients with advanced cancer. The effect of each interven- tion has been discussed in detail under each symptom. Physical Function Patients in the advanced stage of cancer suffer from symptoms due to cancer and treatment, that leads to loss or diminished physical funetion, This causes reduced muscular strength and ‘endurance, affecting their level of independence.”” A study by 5 Records identified through 3 database searching 3 (n= 2102) 3 — Records after duplicates removed (n= 1784) z ¥ a Records soreened Records excluded (n= 1784) *] a= 1765) Fulltext articles Fulltext atc zg assessed for eligibility excluded, 3 (a= 19) (n=10) = Qualitative study LJ | Population not defineda-3) Swudies included in Participants with life ‘qualitative synthesis expectancy more than z (n=9) ‘émonths(n=4) 2 Individuals with primary ‘Oldervoll et al, evaluated the effect of a 6-week structured ‘exercise program focusing on improving strength and mobility inpatients with advanced cancer. It was effective in improving the physical function ofthese patients and was feasible in this, setting despite the heterogeneity of the population." A study conducted by Liteinni eta, revealed that both resistance and cardiovascular training ean be beneficial for improved mobility in patients with advanced cancer with no statistical inter group difference." The effect of a home-based functional walking program that included strength and balance training studied by Lowe et al, showed that even a minimal amount of physical activity tolerated by patients was beneficial than no activity at all" In summary, a structured exercise intervention showed beneficial effect on the physical function of patients with advanced cancer but there is lack of evidence regarding the ‘optimal mode of exercise. However, the prescribed exercises should be tailor made and aimed at maintenance rather than progression in hospice care.506. “American Journal of Hospice & Palliative Medicine” 38(5) Table 1. Quality Assessment Using Modified Downs and Black's Checklist. Ineernal valdity-confounding Swudy Reporting (11) External validity (3) _validiy-bias (7) (selection bas) (6) Power (I) Total score (28), Porock eta, 2000 0 3 6 5 ° 24 Wikie et al, 2000 10 2 6 5 1 25 Oldervol et al, 2006 0 3 5 2 ° 20 Buss et al, 2009 4 3 4 3 ° 14 Duclows et a 2012 10 3 3 4 ° 20 Lceerini et al, 2013 0 3 5 4 1 2 Lowe et al, 2013 7 3 2 2 ° 4 Gradalsi, 2019 3 3 2 3 ° 7 Siemens etal, 2020 10 3 6 6 0 25 Fatigue Many physiological and psychological factors such as insom- nia, inactivity, anemia, prolonged inflammation due o cancer, influence fatigue?! Fatigue causes loss of energy and extreme. exhaustion in the terminal phase of the illness“? Among the studies included, 2 studies"? measured fatigue as the primary ‘outcome and 3 other studics'®'? evaluated fatigue as a second ary outcome, The subscales ofthe patient-reported outcome measures that evaluated fatigue showed improvement after administering DEEP" and group exercise program.'? Buss et al showed reduced intensity of fatigue (p = 0.001) experi= enced by patients with advanced cancer following a 3-week Kinesiotherapy intervention.’ An RCT evaluating the effect of cardiovascular and resistance training showed a slight decrease in the intensity of fatigue (p = 0.05)'? whereas, a case series evaluating a walking based exercise programme showed no improvement in the patient-reported fatigue scale''. Although studies (pre-pst intervention and non RCT) showed significant improvement in the level of fatigue," an RCT showed some improvement which could not be reflected statistically.” Hence, an individualized exercise protocol depending on the patents tolerance level can be administered to improve fatigue in hospice care. This can reduce symptom burden and better their quality of ie Cancer Pain About 66.4% patients with advanced cancer experience can- cer pain in their terminal stage?* The high prevalence of cancer pain in the advanced stage compared to initial stage?? and the disparity in the availability of opioids espe- cially in the low & middle-income countries implies the ced for use of non-pharmacological measures to address cancer pain in hospice care.’* An RCT conducted by Sie~ ‘mens et al, evaluated the effect of TENS on cancer pain in patients with advanced cancer. Although there was no sig- nificant difference in the intensity modulated TENS and placebo TENS, both showed efficacy, feasibility and were safe to use," Another RCT conducted by Wilkie et al showed that administering therapeutic massage reduced the intensity of pain and decreased the dosage of analgesics in hospice care of patients with advanced cancer.'* In a study conducted by Litterini et al, the effect of exercise showed ‘minimal reduction in pain level post intervention. The min- imal reduction could be attributed to low level of pain at the baseline. Hence, the evidences currently suggest the use of physiotherapy interventions as an adjunct to the primary line of treatment for pain, lymphedema Lymphedema at the end of life is a detrimental symptom often ‘hampering the physical functioning of an individual. Complex decongestive therapy (CDT) is commonly used to treat lym- phedema. A study conducted by Gradalski in 2019 shows that short-stretch compression bandaging (a component of CDT) along with pharmacotherapy significantly reduce the limb vol- ‘ume and was tolerable among the patients with advanced Sleep Disturbances Sleep disturbances in patients with advance cancer may further aggravate their symptoms and indirectly impair their health-related quality of life. Sleep disturbances may be attributed to the increased stress duc to hospital environ- ‘ment or cancer diagnosis, existing chronic insomnia or asso- ciated psychological disturbances. A study showed that relaxation training had no significant short-term effect on sleep satisfaction of the hospitalized patients with advanced cancer.'® In summary, physiotherapy interventions have shown to be safe in hospice care for patients with advanced cancer with no adverse effects reported in any of the stud- ies. However, the cancer stage and type, previous physical activity levels, current status of the patient and relative contraindications should be considered while prescribing interventions. A tailor-made approach can help in applying the same in a clinical setting. 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Study Interventions and their Results, Authors Porock etal, 2000 Wikie eal, 2000 Oldervoll fe al, 2006 2009 Ducloux cet al, 2012 Lccerni etal, 2013, Lowe etal, 2013, Intervention Duration of intervention Duke Energizing Exercise plan (DEEP) weeks Standardized hospice massage ‘therapy study protocol consisting of effleurage, light petrssage, nerve stroke ight compression, vibration and ‘apotement along with usual hospice care, 30-45 minutes per session twice ‘weekly for 2 weeks, ‘50 minutes each session cwice ‘weekly for a 6-week period Individualized circuit training program Scheduled exercise pattern Individually supervised by a physiotherapist 20-30 mins, thrice weekly for 3 4 weeks Deep breathing exercises, somatic tension release, muscle relaxation training. {An audio recording of the tralning program given to lsten during the night before faling asleep or as needed during the night. Individualized resistance IG had ineervention from day 3 10 6, DIG had intervention from day 6 t0 9. Twice weekly for 10 weeks. Each session lasted 30 to 60 Modified home-based functional ‘walking program along with set of strengthening ‘Thrice weekly on non- ‘consecutive days for 6 weeks Results Significant decrease in MFI scores, and HADS scores. The evel of symptom distress was low to moderate on the SDS. Quay of Life Scores Quality of He scores improved from Days Oto 14 Pulte rates and respiratory rates reduced stascaly after ‘each session. Pain intensity in experimental group decreased by 42% compared to 225% reduction in the control group bue this ference was not stausaly figifcan(p > 05).Thediflerence in morphine tuvalencs from beginning to end of study was not SEatistialysignfean p> 16) QoL baseline scores were Higher inthe experimenca group than inthe usual hospice care group, but only Current QoL wa sattlaly signiant(p < 0 .03)% ‘There was a sgncanc improvement in emotional functioning (P = 0.002) and decrease in figue(p = 006) component of EORTC QLO.C30. Improvement ‘was seen in total fatigue (TF) (p ~ 0.006)* and physical {sigue (PF) (p — 0.004)" component ofthe Fatigue Questionaire (FQ). There was a sgifcan increase in walking length (P — 0.007)* for &-MWT. A sgnfiant ‘ecreat in ined “sto stand” ( — 0.001)" was assessed. No significant improvement was seen in Functional reach test(P ~ 0.07) Group A wth Knestherapy) showed signfeane decrease in incensicy of fatigue (P < 0.001)" after 3 weeks of incervention, showed improved physical symptoms on RSCL (p < 0.05)" ar 2 weeks of mtervention and stable ual oflife on RSCL (005 < p< 01!) s compared to group 8 (without kinesitherapy) ‘There was no significant difference berween both the ‘groups (P > 0.05). Increase in SPPB total score (P < 0.001)* increase in gait speed (P ~ .001)*, and reduction in fatigue (P ~ 005). Cardiovascular exercise participants had a modestly greater improvement in SPPB total scare than resistance ‘taining partiipanes (P = 0.045) No differential effect of cardiovascular and resistance ‘exercise on fatigue level (P = 0.37) or pain level (P 052). Physical activity decreased significantly aver the course of 6 ‘weeks, Improvements were noted in total MQOL scores In ofthe 3 cases presented. Two ofthe 3 cases showed 1 decline in physical functioning, as demonstrated by the total LLFDI scores, All 3 participants shared an overall trend towards worsening ESAS symptom scores, and worsening total BF global fatigue scores post- Intervention whereas no significant changes were seen in HDI scores. (cominued)510. “American Journal of Hospice & Palliative Medicine” 38(5) Table 3. (continued) ‘Authors Ineerveneion Duration of incervention Results Gradalski, 2-3 layers of shore-stretch 5-7 days Significant improvement was seen inthe limb volumes of 2019 bandage compression applied ‘subjects post intervention(p < 0.001)* The inensiy of lover the edematous limbs ‘commonly seen edeina symptoms and overall well-being, uniformly daly. impairment improved in a short time within the whole sroup of patent: imb pan (<0.001)*, sweling (p < 0.001)*, heaviness (p < 0.001)", weakness (p 0.003)*, paresthesia (p = 0.004), funtion (p < 0.001)* and quality of Ife (p < 0,001), The sutn of ‘edema sensations severity in all those treated decreased {p < 0.001).The median total ESAS-C score decreased {p = 0.002), improving Qualy of fe. Siemens etal, intensiqy-modulated TENS Patients used the frst TENS The primary outcome didnot differ between groups 2020 (IMT) with 100 He: intensity mode during the first 24+h However responder rates were higher in IMT (P ‘was modulated automaticaly phase. After the 24 h 0.0428)" swith a decrease of 40% every washout phase, crossover to 05 s inorder to prevent the other TENS mode for habitation another 24 Strengths and Limitations References This review, to the best of our knowledge is the first ofits kind addressing the role of physiotherapy in hospice care of patients with advanced cancer. A comprehensive data search was per- formed in 5 databases including all the experimental study designs ensuring the inclusion of all the potential evidence. ‘The limitations of this review are inclusion of studies published only in English and exclusion of the grey literature. Conclusion This review throws light on the scope of physiotherapy in hospice care and it's benefits in addressing the symptoms of patients with advanced cancer. Despite the limitations of the identified studies, the positive outcomes were significant in ceach case. The results of the studies evaluating the effect of structured exercise program, therapeutic massage, TENS and compression bandaging are encouraging and can be translated to clinical practice. However, relaxation therapy lacks staisti- cally significant evidence to improve sleep disturbances in these patients. The reduction in symptom burden improved QoL. as shown by patient-reported outcome scales, Fusther- more, high quality studies are required to the strengthen the findings of this review. Declarat n of Conflicting Interests ‘The authors declared no potential conflets of interest wit the research, authorship, andor publication ofthis article Funding ‘The authors received no financial support for the research, authorship, andor publication of tis article ORCID iDs Stephen Rajan Samuel ® hnipsi/oreid.orB/0000-0002-5636-2620 Santosh Rai PV © hitps/orcid.org/0000-0002-7750-7147 1 Hospice Care| Cancer Net, Published September, 2019, Accessed July 26, 2020, husps:/www.cancer.neVnavigating-cancer-care! advanced-cancer/bospice-care Jensen W, Bisly L, Ketels G, Baumann FT, Bokemeyer C, Occhle K. Physical exercise and therapy in terminally ill cance patients: a retrospective feasibility analysis. Support Care Can- cer. 2014:22(5): 1261-1268 Gray R. The role of physiotherapy in hospice care. Physiother Theory Pract, 198935(1)9-16, Dahlin Y, Heiwe S, Patients’ experiences of physical therapy ‘within palliative eancer care. 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