Control 1 Cancer en Adulto Mayor

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Rehabilitation in older cancer patients

Elisabetta Morello, Geremia Giordano, Cristina Falci & Silvio Monfardini
Cancer treatment has meant an increasingly prolonged survival of older cancer patients, often associated with a functional decline. Rehabilitation focuses on facilitating recovery of the ability to perform activities of daily living and on enhancing a patients quality of life. The rehabilitative program should be tailored to single-out elderly patients after an attentive evaluation of their needs and the assessment of clinical, psychological and social conditions through a comprehensive geriatric assessment. The evaluation of fatigue, pain, malnutrition, depression and cognitive impairment is essential in order to establish supportive therapies and improve compliance and outcomes. Rehabilitation care is performed with a multidisciplinary approach. Management consists of physical exercises and occupational therapy associated with specific organ rehabilitation, and is also related to the sequelae of treatments such as surgery, hormonotherapy and radiotherapy.
The WHO underlines that the goals of cancer treatment programs are not only to cure or pro long the life of cancer patients but also to ensure the best possible quality of life to cancer survivors. Therefore, treatment involves also the psychological and rehabilitation needs of the patients and their family [1] . At present, approximately 60% of new cancer cases in European Countries and North America occur in people older than 65years, and approximately 40% occur in persons older than 70years; however, the dimension of the epidemiological problem is increasing, leading to a progressively higher assistant burden (mainly care givers). While fit elderly patients can gener ally receive the same treatment as younger adults, cases with associated comorbidity may require reduced dosages of chemotherapy or the use of less toxic anticancer drugs, as well as supportive therapy and rehabilitation. Rehabilitation is the process of restoring the skills of a person who has had an illness or injury that has impaired his/her functioning. It plays an essential role in enhancing the quality of life for people with dis abilities or impairments [24,201] , in facilitating the recovery of their ability to perform everyday activities in order to live as independently as pos sible or in enhancing residual capability. While in younger patients disability is often strictly related to a single organ impairment due to a specific c ancer, in older patients, disability results from multi ple associated causes. These disabili ties can be related to cancer itself (i.e.,local or distant spread), to cancer treatment (i.e.,conse quences of surgery, hormonal therapy, chemo therapy and radiotherapy [RT]), to previous general conditions (i.e., comorbidities involving disability, for example prior stroke) or functional decline related to aging. Therefore, an attentive assessment of the individual patient is essential to identify their needs, set appropriates goals and
10.2217/AHE.09.32 2009 Future Medicine Ltd
define an individualized rehabilitative plan. In the rehabilitative context, comprehensive geri atric assessment (CGA) becomes a useful tool. This evaluation demonstrates the characteristics of the older cancer patient owing to concomitant illnesses (i.e., comorbid conditions), geriatric syndromes, impairment related to cancer itself and the consequences of the treatment [5,6] . This review aims to present the available knowledge regarding rehabilitation in the older cancer patient as well as the need for a specificapproach.
Assessment of older cancer patients before rehabilitation Comprehensive geriatric assessment
There is growing evidence of CGAs useful ness in the assessment of older cancer patients. Therefore, there are no substantial reasons not to apply CGA to rehabilitation, despite the lack of study in this field. CGA consists of a multi disciplinary evaluation of an older individuals functional status, comorbidity, cognition, nutrition, psychological state and social condi tion[710] . Evidence suggests that CGA, associ ated with a long-term management, is effective in improving functions (e.g., prevention of dis ability progression, reduction of risk of falls), uncovering unrecognized problems and predict ing mortality [11] . The use of objective measures should be employed, utilizing some specific tools, such as evaluation scales, widely used in geriatrics and physiatric practice that can help to ensure a correct and reproducible evaluation (Table1) [5] .
Functional assessment
Author for correspondence Istituto Oncologico Veneto, IOV, IRCCS, Via Gattamelata 64, 35128, Padova, Italy Tel.: +39 0498 215 931 Fax: +39 0498 25 932 silvio.monfardini@unipd.it
Keywords
cancer comprehensive geriatric assessment elderly palliation rehabilitation
Aging is associated with increasing functional decline and several comorbidities; in addition, cancer patients are even more vulnerable to physical impairment [12] . Performance status
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Table1. Comprehensive geriatric assessment measures of older cancer patients.
Domains
Function
Measure
Activities of daily living Instrumental activities of dailyliving Barthel Index Functional Independence Measurement
Administration
Self or interviewer Self or interviewer Interviewer Interviewer Interviewer Interviewer Interviewer Interviewer Self Interviewer Interviewer Interviewer Interviewer
Score range
016 014 0100 18126 028 14 categories 19 categories 030 030 038 012 520 623
Cut-off point for adverse outcomes*

<14 <12 <60
Ref.
[18] [19] [14] [15]
Physical performance Comorbidity
Tinetti Scale Cumulative Illness Rating Scale Geriatrics Charlson Comorbidity Index
<19 Number of categories at level 3 or 4 severity Four categories: 0, 12, 34, >4 <24 >9 >8 <11 <15 <16
[17] [24] [23] [28] [34] [35] [56] [59] [60]
Cognition Depression Nutrition Risk of pressure ulcer
Folstein Mini Mental StateExamination Geriatric Depression Scale Cornell Scale Mini Nutritional Assessment Norton Scale Braden Scale
*Prospectively associated with an increase in disability, mortality or adverse outcomes in previous studies.
in oncology is traditionally assessed using two main methods: the Karnofsky and the Easter Cooperative Oncology Group (ECOG) perfor mance status scales [13] . The Barthel Index [14] and the Functional Independence Measurement instrument [15,16] are commonly used in rehabili tation for functional assessment. They explore different domains such as mobility, locomotion, self-care and sphincter control; the Functional Independence Measurement also considers com munication and social cognition. The Barthel Index is easy to administer but is not particularly responsive to change if carried out to assess per formance before admission and after discharge from a rehabilitation program. Physical perfor mance is also well evaluated by the Tinetti Scale, which assesses different phases of walking and balance[17] . The scales of the activities of daily liv ing (ADL) [18] and instrumental ADL (IADL)[19] are widely used and are very important for avoid ing the under estimation of the extent of disability in terms of performing everyday activities.
Comorbidity
An attentive evaluation of comorbidities (e.g., cardiovascular, respiratory, neurological dis eases, diabetes, renal failure, vision/hearing problems, arthritis and fracture history) and geriatric syndromes (e.g., delirium, urinary and
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bowel incontinence and falls) is important in order to determine a tailored individual reha bilitative program. Patients with comorbidities and geriatric syndromes (i.e., vulnerable and frail patients) have more complex healthcare needs. Even if comorbidity is independent from functional status [2022] , it is an etiologic risk factor for frailty[8] . The Charlson Comorbidity Index (CCI) and the Cumulative Illness Rating Scale Geriatrics (CIRSG) are validated and reproducible scales predicting end points, such as mortality [23,24] . They accurately provide a summary score of burden of illnesses and are widely used in geriatrics and oncology; however, they are often not applied in rehabilitation [25] . In rehabilitation, frail elderly people often have active medical problems and comorbidities that require close medical management, concomitant treatment and leave the goals of rehabilitation to be reviewed. An attentive evaluation of hearing and visual impairment is also important in order to determine its influence on balance and walk ing as well as level of comprehension of simple and complex rehabilitative tasks. Presbyacusis, the common hearing loss in the elderly, is easily screened for and can benefit from a rehabilita tion approach, such as communication courtesy, environmental manipulation, assistive devices or cochlear implants [26] .
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Cognition
Cognitive screening is important in assessing rehabilitation potential. Inability to understand instructions or remember information may hin der therapy. Moreover, cognitive impairment can impact a patients collaboration, as well as his/her ability to correctly take drugs or make conscious treatment decisions. Nevertheless, mild-to-moderate dementia should not be a criterion for exclusion from rehabilitation [6,27] . The Mini-Mental State Examination is a screen ing tool that detects alteration in cognition. It is easy to administer but it lacks sensitivity to detect mild cognitive impairment or longitudi nal changes in cognitive function [28] . In these cases, a further evaluation by neuropsychological test is needed. Focal cognitive dysfunction or dementia can be the consequence of cancer itself, such as CNS neoplasm or cerebral metastasis; various other etiologies that are frequent in the elderly, such as Alzheimers disease or vascular encephalopathy, or related to cancer treatment. Some studies have outlined that cancer treatment, such as chemotherapy [29] , andro gen-deprivation therapy (ADT) in prostate cancer [30] , endocrine therapy (e.g., aromatase inhibitors) in breast cancer [31] and RT can compromise different cognitive domains with an impact on quality of life and occupational pursuit. For these reasons, more attention must be given in this field for therapeutic choices, follow-up and adequate rehabilitative plans.
Depression
potential drug interactions) and adverse effect profiles should be considered in the choice of pharmacological treatment [36,37] .
Polypharmacy
Older cancer patients experience higher rates of depression compared with younger patients[32] . This can be attributed to the high prevalence of disease in the elderly, cancer-related health wor ries and some treatments that can cause these symptoms (e.g., steroids and brain RT) [33] . In a rehabilitative context, these patients are often less motivated to participate in therapy. Therefore, all frail and older patients should be screened for depression and treatment should be initiated, including pharmacological or nonpharmacologi cal, such as psychotherapy or cognitive behavioral therapy [6] . Moreover, improvement of mood is associated not only with better quality of life, but also with progress in physical functioning. Screening scales, such as the Geriatric Depres sion Scale or Cornell Scale for cognitive impaired patients are used to detect depressive disorders and accompanying symptoms [34,35] . Many comor bid conditions, such as sexual dysfunction and malnutrition, accompanying symptoms, such as insomnia, anxiety and pain, polypharmacy (i.e.,
The physiological age-related changes of hepatic metabolism, renal function, body flu ids and muscle/fat repartition induce different pharmacokinetics and dynamics. These modi fications associated with the polypharmacy can contribute to adverse drug events, particularly in older cancer patients undergoing chemo therapy and related supportive cares. In par ticular, aging is associated with a progressive decrease of kidney functional reserves [38,39] . Assessment of glomerular filtration rate (GFR) and hydratation status involves an adequate dose reduction and a decrease in drug toxic ity. The GFR may be evaluated by estimating creatinine clearance (CrCl) even when serum creatinin is within the normal range. The CrCl can be easily estimated in clinical practice by the formulae of Cockroft-Gault (using data such as age, sex, weight and serum creatinine level) or Wright [40,41] . An attentive assessment of a patients medica tion therapy, drug interaction and discontinua tion of nonessential medications is crucial for reducing adverse effects and complications in the elderly. Careful attention must be paid in detect ing drug consumption not mentioned by the patients (e.g., laxatives, sleeping tablets, analge sics and sedative pharmacotherapy). Compliance of the patient, correct assumption of drugs and presence of a caregiver should also be considered. Moreover, the role of the pharmacist, if pres ent in the team, can help decrease the risk of p olypharmacy [5] .
Social evaluation
An accurate evaluation of the social condition is an essential step in geriatric rehabilitation, high lighting the presence of social isolation and care giver support. A social worker is part of the team and works in close relation with the clinicians. He/she has a crucial role in the management of social and financial issues. Interviews with the caregiver are essential in order to obtain anam nestic information, particularly if a patient has some cognitive impairment. Involvement by the caregiver is important for ensuring participation in the rehabilitation project, continuity of care and correct discharge planning. Providing care for an older cancer patient at any stage of their disease may engender nega tive physical and psychosocial consequences;
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therefore, caregivers often need support and, in some cases, intervention aimed at reducing the emotional consequences [42] . The interview with the caregiver is also use ful to identify structural home limits that may be critical for a home discharge. An effective rehabilitative step consists of planning and sup plying restorative equipment, as well as making home modifications that enhance the reinstate ment of the survivor who has regained previous capacities, avoiding social isolation and mobil ity limits, and to maintain the functional gains of the patient acquired during rehabilitation. In both cases, the intervention consists of bringing environmental adaptations and providing equip ment, such as ramps for wheelchairs to provide independent access to home, stair glides, grab bars, tub seats, commodes and hoyer lifts [4] . Those measures associated with teaching of compensatory strategies also supply help to the caretaker at home after discharge facilitating the management of ADL andcare.
General conditions related to the neoplastic disease and/or treatment Fatigue
exercise programs appear to be effective even in older cancer patients for reducing fatigue and improving quality of life[4651] . Hence, fatigue in the elderly is an often unrecognized complaint that is not related to age and that should be considered.
Malnutrition
Fatigue is the most common adverse experience of cancer patients, affecting almost 70% of can cer patients during the course of disease, and is responsible for deterioration of quality of life and disabilities. It is a subjective feeling of tiredness, weakness or lack of energy [43] . Cancer-related fatigue may involve many aspects: physical (feeling of lack of energy); emotional (uneasi ness); cognitive (difficulty concentrating and in short-term memory); and behavioral (inability performing ADL). A study from Balducci etal. evaluated a group of older cancer patients (mean age: 71years) undergoing medical treatment[44] . A total of 72.7% of patients experienced fatigue, and for 84% of patients it interfered with ADL. Anemia and depression were correlated with fatigue severity and fatigue disruptiveness, but not with cognitive status. In a more recent study, it was found that fatigue was significantly associated with ADL and IADL dependencies, which may represent a major cause of functional d ependence [45] . Many factors influence fatigue, such as pain, anemia, psychological problems (e.g., depression and anxiety), nutritional problems and comor bidities. Often, specific treatments of these symp toms are not satisfactory to resolve the fatigue, and additional evidence suggests that physical activity may play a positive role. At present, there are no specific protocols, but rehabilitative aerobic
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Nutritional deficiency is diffuse in the elderly population, frequent in rehabilitation wards [6] and is worsened by cancer [5254] . The high preva lence of malnutrition in older subjects is caused by inadequate food intake owing to anorexia, depression, disorders of mastication, alteration of smell and taste or simply for socioeconomical reasons that may be solved by the social worker of the team. With this background there is a greater susceptibility for adverse effects or consequences of cancer treatment, such as xerostomia, muco sal integrity alteration, fungal infection, malab sorption following chemotherapy or RT. In the elderly, assessment of those factors interfering with adequate oral intake is crucial, as is con trol of adequate dentition and dental prostheses. Moreover, patients may be affected by dysphagia, requiring enteral feeding because of cancer exten sion (causing obstruction or neurological deficit) or because of surgical treatments involving nerve injuries. If enteral nutrition is delivered to an older patient for long periods of time, the rehabilitative approach consists of training the patients care giver for home management [55] . In geriatrics, the Mini-Nutritional Assessment is a widely used screening tool for risk assessment of inadequate nutrition, taking into account anamnestic data, dietary habits, anthropometric measurements and bodyweight changes [56] . Serum albumin is an independent risk factor for all-cause mortality [57] and it is an easy and relatively inexpensive biologi cal marker of malnutrition, such as lymphocyte counts, pre-albumin and transferrin. Oral nutrition, representing the most physi ological nutritional option, should be continued for as long as possible; this can be improved by nutritional supplementation to support increas ing protein intake and pharmacological interven tions enhancing appetite, such as megestol and mirtazapine. In rehabilitation, management of overweight individuals and obesity should also be considered in order to favor mobility and reduce cardiovascular risks; despite this, no specific s tudies on older cancer patients are available [58] .
Pressure ulcers
Pressure ulcers are localized areas of tissue dam age caused by excessive pressure, shearing or friction forces. They mainly occur in conditions
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of limited mobility. Elderly patients are particu larly vulnerable to this tissue damage owing to the high prevalence of malnutrition, dehydra tion, fecal and urinary incontinence, inducing soaking of the skin, and other comorbidities, such as diabetes, nerve injuries and artery dis ease. In a rehabilitation ward, the nursing team should be trained to conduct a regular atten tive assessment of the skin of the patient as well as to recognize the risk of pressure ulcers. Assessment tools, such as the Norton Scale [59] and the Braden Scale [60] , may be useful for this purpose. They provide a risk score based on the evaluation of physical condition, mental condi tion/sensory perception, incontinence/moisture, activity, mobility and nutrition. Prevention con sists of avoiding the aforementioned risk fac tors [61] and in using pressure-relieving beds, mattresses and seat cushions [62] . The treatment consists of avoiding immobilization, changing position every 2hours using turning and trans ferring schedules, optimizing local wound care, even if there is no evidence of superiority of one dressing over others, and managing c ontributing factors [63] .
Pain
Cancer-related pain is a frequent symptom that is often associated in elderly patients with non oncologic chronic pain due to arthritis, neural gias and other chronic diseases. Undertreatment is still common in older patients and causes impairment of functional autonomy and qual ity of life. Thus, adequate pain management is crucial for successful rehabilitation [64] . In older patients, pain sensitivity is not reduced but the capacity to communicate this discomfort is often compromised. Pain may be expressed by behav ioral changes, such as aggressiveness, restless ness, decreased socialization, sleep disturbance or lack of appetite. The tools commonly used for self-reported pain assessment (e.g., visual analog scale and numeric scale) are often inadequate for elderly patients owing to difficulty with compre hension, low educational level, difficulty hearing and visual impairment. Multidimensional mea sures with observational pain scales, completed by the nursing team, appear to be more satisfac tory for assessing pain in cognitively impaired or noncommunicative older adults because they consider facial expression, body posture, changes in activity patterns and interpersonal inter actions. For example, the Doloplus scale includes somatic items (e.g., somatic complaints, protective body posture at rest, protection of sore area, facial expression and gaze, and sleep
pattern), psychomotor items (e.g., observation of washing, dressing and mobility) and psycho social items (e.g., communication, social inter ation and behavior)[65] . Nevertheless, informa tion from family and other caregivers should also be included in the assessment. A precise diagno sis of etiology and type of pain is necessary to decide the treatment in both younger and older patients [55] . Many analgesics are available and can be safely used in the elderly as long as caution is employed starting with a low dose followed by gradual dose escalation reaching a favorable balance between analgesia and adverse effects. Elderly patients may require a lower dose per day as compared with younger subjects owing to the physiological age-related changes with pharmacokinetic implications. Considering the adverse effect profiles in the elderly, it is better to administer acetaminophen rather than NSAIDs, to avoid cortico steroids or, if necessary, prefer ring dexametasone (because of low mineral corticoid and glucocorticoid effect), to use opi oid analgesics with an attentive titration and the most adapted route for the particular individual (e.g., transdermal patches for dysphagic patients or noncontinual presence of a caregiver) [6669] . In frail elderly patients with chronic constipa tion, prostatic hypertrophy, dementia or coad ministration of sedating medication, an atten tive assessment of the known adverse effects of opioids is crucial to avoid worsening of symp toms (i.e., bowel occlusion, urinary retention, c onfusion and delerium).
Rehabilitation
Since the provision of effective rehabilitation requires the formulation of appropriate goals, the prior assessment of the individual patient is essential in order to tailor the rehabilitation pro gram. It also relies on the pre-existing functional status information, which is obtained from the interview with the caregiver. Moreover, the program should be regularly reviewed on the basis of the evolving clinical situations that may impact its course. There are no clear guidelines for the management of the older cancer patient experiencing an acute disease during the reha bilitation period. Frequently, an acute situation, such as heart failure, pneumonia or other infec tions, may be treated in the rehabilitation ward and require close medical supervision, resulting in the interruption of the rehabilitative program, which is regained after the resolution of the event. Sometimes intense illnesses may neces sitate a transfer to a specialized ward (such as for a myocardial infarction or for an accidental
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femur fracture). However, if the recent event has a functional impact and involves a new functional impairment, the rehabilitation plan should be reviewed, including new approaches addressed to the new deficit; on the other hand, if the impairment induces a severe prognosis it could also be necessary to address the patient to palliative care. Oncological rehabilitation provides an opportunity for those living with cancer to improve the quality of their lives by rebuilding their strength and re-establishing mobility and independence. Patient prognosis can vary widely and is not a consideration for admission, providing the person has achievable rehabilitation goals; particularly because, in the elderly, small gains in several areas may result in improved functional status and quality of life. At present, there are no specific criteria or guidelines for enrolment of older cancer patients in rehabilitative programs, and they are often excluded because of their frailty; moreover there is a lack of studies regarding the outcomes of rehabilitative approaches. Enhanced mobility and self-care can be achieved through interven tions provided by most standard rehabilitation facilities. Given that the elderly can often have a precipitous functional decline, rehabilitation could also hold a preventive role. Rehabilitation for the elderly should be performed in an inward setting with a multidisciplinary team skilled in geriatrics or it may be carried out for outpatients if there are collaborative caregivers and adequate social conditions.
Team applied to the old cancer patient General interventions in all old cancerpatients Physical therapy
In the rehabilitation of older cancer patients, programs should rely on an interdisciplinary team. The multidisciplinary approach consists of joint decision making and common defined goals. Health professionals work together with this aim, even if elderly patients sometimes pre fer to relate to a limited number of people. The team should be composed of a geriatrician, phys iatrist, oncologist, nurse, physiotherapist, speech therapist, occupational therapist, psychologist, social worker, pharmacist and dietitian, when available. Moreover, advice from specialist con sultants, such as orthopedic surgeons, neurolo gists, nose and throat specialists, gynecologists, urologists, cardiologists and pneumologists is essential [5,7072] . Currently, geriatric rehabilita tion in oncology is a new field and the team often faces new situations owing to clinical instabil ity of the patient and uncertain prognosis that may lead to terminal situations with ethical concern[73] .
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Medical oncologists should be aware that, in the elderly, prolonged bed rest and restricted mobil ity can often cause severe consequences, such as muscle retraction or atrophy, bone loss, effects on cardiovascular system and respiratory prob lems. It may be worth recalling that this decon ditioning benefits from physical therapy. The main form of prevention of hypotonia or atro phy of muscles is active exercises or static iso metric work. Muscle retraction owing to short ening of muscles, tendons and ligaments (which may also be a result of pain) can be avoided with physical therapy, such as stretching exer cises, maintaining joint motion, or, if patient collaboration is scarce, they may also benefit from adjunctive therapy, such as ultrasound and low-level laser therapy. Moreover, osteope nia owing to immobilization can benefit from frequent mobilization and bisphosphonates. Respiratory problems are related to reduced thoracic expansion, which may result after sur gery for fear of pain or due to severe fatigue, weakness in breathing and coughing causing retained secretions. Deep breathing exercises and effective coughing should be performed; however, in the elderly the correct execution of these tasks is often strictly related to the com prehension capacity of the patient. Prevention of deep vein thrombosis should be set out using anti coagulant therapy and compression devices, for example elastic bandages [4] . Exercise for cardiovascular conditioning and resistance training enhances the strength of preserved muscle groups reducing the functional impact of deconditioning, which is a frequent symptom often unmet in cancer patients [74,75] . In cases of deconditioning or sensorimotory injuries, instruction of compensatory strategies is essen tial in order to ameliorate mobility and perform ADL. These strategies enhance transfers (e.g., from supine to sitting or standing position) or ambulation relying, for example, on visual cues rather than proprioceptives if this sense is impaired. Prescription of appropriate assistive devices is a crucial part of the rehabilitation program in the elderly. Canes, crutches and walkers are used to enhance mobility and bracing strategies are used for joint instability and lower extremity orthoses. Other devices can help with perform ing ADL, such as dressing and bathing, par ticularly in patients with a neurologic deficit. In some cases, mobility is restored through the
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use of an adequate wheelchair and strategies to maintain correct posture and transfer techniques should be taught. Few researchers have evaluated the effect of rehabilitation on cancer patients; more fre quently, studies are conducted in samples of young patients that do not demonstrate all the comorbidities typical of older patients. In a retrospective study of 200 cancer patients with an impairment related to cancer or its treat ment (mean age: 71years), rehabilitation had improved motor and cognitive function in all cases except for cognitive gains in patients with intracranial neoplasm or CNS dysfunction [76] . In another retrospective study of cancer patient with a lower mean age ( ~56years) significant functional gains were obtained from rehabilita tion, even in the presence of metastatic disease or in patients receiving ongoing radiation treat ment [77] . Despite limited studies on the benefit of exercise in older cancer survivors, there is evidence for its advantage in other older popu lations [78] . Moreover, exercise seems to improve functional capacity, muscular strength [79] , flex ibility, fatigue, depressive symptoms, insomnia and quality of life [80,81] . All rehabilitative pro cedures and plans should be proposed to the older patient with respect for his/her wishes andmotivation.
Occupational therapy
Problems of specific organ rehabilitation Breast cancer
Occupational therapy is the part of rehabilita tion oriented to the restoration or the mainte nance of independence in the ADL. It focuses on the recovery to perform activities such as dressing, grooming, making a meal, toileting and bathing, as well as IADL, such as handling finances, managing medications and using a telephone[82] . Occupational therapists are also concerned with the mental health, insight and acceptance of diagnosis; they also consider the needs and the desires of the patient, enabling realistic expectation, re-establishing his/her sense of control, encouraging the patient to live within their limitations and teaching compen satory strategies. This approach improves qual ity of life and facilitates home reintegration. Occupational therapy has still not been well assessed in oncological rehabilitation, despite the known effectiveness in improving abilities for ADL in other populations, such as post-stroke patients [8385] . Further research is necessary to establish the costeffectiveness of occupational therapy and to define those individuals who are most likely to benefit fromtherapy.
The current management of breast cancer in older women has brought about a reduction of radical mastectomy and increased medical treatment in Europe, but radical mastectomy is still preferred to lumpectomy, followed by RT in other countries [86,87] . The rehabilitation mainly consists of the prevention and attenua tion of the sequelae of surgical treatment, but also of RT and the management of the conse quences of local extension of disease. Hormonal therapy and chemotherapy have several known side effects that the clinician must be aware of when planning rehabilitative project (see next section). A recent study evaluating the reha bilitative needs of 163 community-dwelling patients (mean age: 56 years; fewer comor bidities compared with older patients) with metastatic breast cancer undergoing chemo therapy highlights a high prevalence of physi cal impairment (92%) with unmet and unad dressed rehabilitation needs, with fewer than 30% receiving a rehabilitative treatment [88] . The rehabilitation after surgical treatment in the elderly does not differ significantly from younger patients; nevertheless, the compliance of the older patient and their motivation play a crucial role. The main problems are shoulder pain due to inflammation, muscular retraction and wounds, joint and myofascial dysfunction, all of which may benefit from physical therapy (active or passive), laser therapy and result from breast reconstruction or neuropathies (due to surgical techniques or RT). Another well-known surgical complication after lymph nodes removal, inducing several impairments and causing an emotional and psychological impact with worsening of quality of life, is lymphedema. Lymphedema triggers severe pain related to stretching of soft tissues and interferes with basic ADL. Early initiation of treatment is crucial for the prognosis. Treatment consists of pressotherapy, electrical drainage, compressive pumps, manual lymph drainage and use of gar ments (e.g., elastic bandages and sleeves) [89] . Education of older patients and their caregiver is an important aspect of lymphedema man agement. It consists of skin care and use of protection, such as gloves, in order to prevent infections due to small breaks in the skin (e.g., cracks in dry skin, cat scratches, insect bites, burns and injuries during manicure, gardening or cleaning) and avoiding exposure to heat and tight clothing.
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Lung cancer
Physiotherapy is performed before and after sur gery in order to prevent complications such as atelectasis, postoperative pneumonia and aspira tion pneumonia; moreover, rehabilitation may be focused on complications of radiotherpy and chemo therapy or tumor metastases. Apart from the evaluation of general conditions, cardio vascular conditions and comorbidities, in the elderly, an attentive assessment of other pulmo nary disease (e.g., chronic obstructive pulmonary disease and emphysema) or pathologies affect ing the chest wall (e.g., kyphoscoliosis from osteoporotic vertebral fractures) or respiratory muscles (e.g., Parkinson disease) is fundamental for establishing the rehabilitative program [90] . In this field, motivation, degree of comprehension and adherence of the older patient, as well as family support, strongly influence the outcomes. Rehabilitation in the context of chest sur gery[9193] consists of teaching controlled breath ing and cough techniques in order to remove secretions, management of shoulder pain, motion and surgical wounds, correction of wrong pos ture associated with trunk muscle conditioning and aerobic work with peripheral muscle train ing (e.g., leg cycle ergometer, walking exercice and muscle electric stimulation). These activities improve respiratory function, exercise capacity, fatigue and quality of life. In the case of patients undergoing primary RT or combined radioche motherapy [86] owing to locally advanced nonsmall-cell lung cancer, contraindication/refusal of surgery or vulnerable conditions [94] , manage ment focuses instead on collateral effects, such as neuropathies. Advanced cancer with brain metastases [4] may cause motor deficits with spastic hemiparesis. In these cases, rehabilitation consists of improving strength in paretic muscles through incremental resistance training, teaching compensatory strategies and prescribing assistive devices and orthotic devices (e.g., use of sling to prevent trauma to the plegic arm and splint for the extremities).
Head & neck cancer
Head and neck cancer is not a rare event in patients older than 60years. Radical treatment is often less frequent in the elderly; however, older patients can undergo radical or conservative surgery, radiation therapy or chemotherapy[95] . The cancer itself or the treatments involve many sequelae, such as dif ficulty in swallowing or speech, alteration of oral secretion, scars, pain and impairment of shoulder motion. Rehabilitation techniques taught to the patient and his/her caregiver may improve quality
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of life. Dysphagia, depending on the type of swal lowing dysfunction (i.e., neurological or anatomi cal/mechanical), may benefit from strategies of speech therapists to avoid aspiration pneumonia, such as neck flection, turning the head towards the weak side, glottis adduction exercise or breath holding and postural adjustments or coughing techniques [4] . Artificial nutrition by gastrostomy tube is often necessary in order to maintain a cor rect hydration and caloric intake; alternatively, prosecution of oral feeding with adequate food consistencies and nutritional supplements can be carried out. Speech therapists rehabilitate dysar thria and dysphonia with voice exercises, alter nate speaking techniques and use of assistive and amplifying devices. Obviously ,these approaches require a good comprehension and collaboration that is not always provided by elderly patients. In older cancer patients, in cases of tracheostomy respiratory rehabilitation, use of filters and family support is essential. Radiotherapy and chemotherapy involve many other adverse and strongly compromising effects, such as hearing or vestibular impairment, that may worsen a pre-existing balance dysfunction and create an increased risk of fall, as well as mucositis, mouth pain, alteration in oral secretion, loss of taste and sense of smell involving aggrava tion of malnutrition [96,97] . Some drugs used in young patients, such as pilocarpine for xerosto mia or anticholinergic medications for scialorrea, should be avoided in the elderly owing to their frequent adverse effects, whereas it is important to promote the use of certain formulations of medi cations that facilitate swallowing or those that can be administered via gastrostomy tube (liquid) or via other forms of administration (e.g., patchs). In this field, dentists may play an important role cre ating adequate prostheses [98] . After neck surgery or RT, patients undergoing muscular retraction, shoulder pain and motion impairment, such as winged scapula due to spinal nerve injury, may benefit from stretching and active exercises, pos tural adjustments, massage and therapies such as laser therapy, ultrasound therapy, transcutaneous electrical nerve stimulation to prevent scar retrac tion, fibrosis and pain. The management of head and neck cancer often induces changes in body image and disfigurement that may worsen depres sion and social isolation and, therefore, should be supported by apsychologist.
Bone metastatic disease
Skeletal involvement results from many types of solid tumors and myeloma, although primary bone neoplasm are rare in the elderly. Bone
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metastasis causes severe pain and disability and, in older cancer patients, the risk of bone fractures is increased owing to coexistent osteo porosis. Management involves several treatments, such as surgical stabilization of pathological fractures, RT, chemotherapy, analgesic therapy and phar macological adjuvants [99] . Rehabilitation focuses on patients who underwent surgical repair of pathological or impending fractures, on vertebral disease with spinal cord compression needing a neurological rehabilitation and on patients with bone metastasis who are noncandidates for surgi cal treatment[4,100] . After surgical treatment (e.g., insertion of rod or joint prosthesis) the approach does not significantly differ from standard proto col in elderly patients not suffering from cancer. Aimed at early mobilization, full weight bear ing is associated with the use of assistive devices (e.g., cane or walker) to relieve pain, ameliorate balance and reduce fear of falling. Bony lesions of upper extremities may undergo conservative treatment, which necessitates occupational ther apy to improve ability to conduct one-handed activities. Vertebral metastases with spinal cord compression may cause sensory-motor deficit, which can be approached with resistance train ing to enhance muscle strength, instruction in back-sparing transfers, compensatory strategies to carry out ADL, and training in the use of assistive devices. Use of orthotic devices (e.g., truncal orthotics and collars) is important to reduce risk of bone fractures and vertebral col lapse, unloading the affected bone, maintaining mobility and safety of the skeletal system dur ing daily routines. In cases of nonsurgical bony lesions, the use of standard or rolling walkers is encouraged in order to maintain ambulation at least within the home. In some circumstances, prescription of a wheelchair may be necessary for permanent use or to facilitate transportation outside the home. These approaches are supported by the use of pharmacological treatment, such as bisphospho nates and analgesic (opioids), aimed at reducing pain [101] . In the elderly, the potential side effect of bisphosphonates on nephrotoxicity should be carefully assessed since baseline bisphospho nate dosage decreases kidney functional reserve. Corticosteroid and NSAIDs are not the first-line choice in the elderly owing to the known adverse effects in this population.
Gastrointestinal cancer
also of deconditioning related to being bedrid den. A small study of elderly patients (mean age: 80years) undergoing elective surgery for gastric and colorectal cancer [102] has demonstrated a transient decrease in ADL at the first postoperative month with a recovery at 6months, and with only 3% demonstrating a persistent decline. Moreover, surgical treatment improved quality of life in all patients. In order to reduce impairment after sur gery it is important to decrease surgical complica tions with a pre operative attentive assessment [103] and to establish a direct rehabilitation program for preventing protracted disability, first of all provid ing early mobilization after surgery. Moreover, all the patients undergoing abdominal surgery may benefit from preoperative breathing exercises with a reduction of postoperative pulmonary complications [104] . To maintain the quality of life of vulnerable older patients with colorectal cancer after pal liative or radical surgery, the problem of care of the stoma and fecal incontinence should be considered [105] . All patients treated with a combined modality (e.g., chemotherapy, RT and surgery) might require attention regarding the problem of the possible decreased rectal conti nence. Patients with ostomy require a physical and psychological rehabilitation that consists of teaching management of the pouching system, and peristomal and stomal complications. With elderly patients, the involvement of family mem bers is often essential since impairment can com promise self-care learning [106] . Management of fecal incontinence requires a multidisciplinary assessment with specialized investigation and an individualized approach. The interventions include lifestyle and dietary modifications and pharmacotherapy [107] . Rehabilitation consists of different approaches, such as pelvic floor muscle training, biofeedback, volumetric rehabilita tion and anal electric stimulation. However, the effectiveness of these techniques remains u ncertain [108110] . There is widespread agreement on the cru cial role of patient motivation and compliance; therefore, some of these treatments are often not appropriate for frail older patients who cannot understand or comply with instructions owing to cognitive or perception impairment.
Gynecologic & urologic cancer
In older patients, rehabilitation after colorectal and gastric cancer treatment does not only consist of management of ostomy or incontinence but
Rehabilitation of gynecologic and urologic can cer consists of the management of the conse quences of surgical, pharmacological treatments and RT, such as urinary incontinence and sexual dysfunctions. However, specific rehabilitation
377

practices are rarely adopted for unfit frail elderly patients since their compliance and cognitive function are inadequate. In prostate cancer patients, the approach for conservative management of urinary inconti nence includes pelvic floor muscle training with or without biofeedback, electrical stimulation, external compression devices (e.g., penile clamps) associated with lifestyle adjustments and eventual pharmacological treatment. The value of this approach, however, remains uncertain [111113] . The management of erectile dysfunction due to surgery, radiation or ADT is mainly pharmaco logical (e.g., PDE5-inhibitors and intracavernous injections of vasoactive drugs) and surgical (e.g., penile prosthetic surgery) [114116] . An attentive baseline assessment of libido and erectile dys function should be performed because many older man have sexual dysfunction at baseline prior to ADT initiation. Moreover, in the elderly, PDE5-inhibitors should be used with caution because of severe cardiovascularcomorbidities. Rehabilitation of gynecologic cancer focuses on urinary incontinence, consequences of lumbo sacral plexopathies for direct extension of disease [117] , limb lymphedema occurring after radiation therapy or for lymphatic flow obstruc tion owing to local extension of malignancy [4] . The approach does not differ significantly with regard to other body sites (e.g., brachial plexo pathy, lymphedema or incontinence for prostate cancer). In both gynecologic and urologic can cer rehabilitation, psychological support and c ounseling play an important role.
Radiotherapy-related damage
complaint that need an attentive assessment in order to be treated and rehabilitated (e.g., isch emic claudication on the iliac district reflecting a lumbosacral radiculo pathy) [118] . The manage ment of late complications is similar for young and old patients and includes segmental physio therapy for muscular strength, exercises for bal ance and ambulation, use of devices for para lyzed limbs, occupational therapy for brachial plexopathy[119] , pulmonary physiotherapy, laser therapy, ultrasound therapy and t ranscutaneous electrical nerve stimulation.
Chemotherapy-related damage
Side effects of RT depend on the area of irradia tion and can appear immediately or at a later date. Acute complications, such as dermatitis and mucositis, can be reversible but interfere with quality of life owing to discomfort, and worsen pre-existing nutritional problems and weight loss in vulnerable older patients. Late sequelae have more rehabilitative implications, such as the effect of RT on irradiated bone, including osteonecrosis, osteoporosis, increased susceptibility to fractures and functional limita tions with joint and muscle contractures, tissues fibrosis and lymphedema, as well as plexopathies and myelitis[117] . Irradiation of thorax provokes lung fibrosis, while whole-brain radiation may cause cerebellar toxicity, with related ataxia, as well as depression, cognitive decline and demen tia in the elderly [33] . In addition, alteration of vessel structure (e.g., endarteritis obliterans) may induce symptoms similar to neurologic
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Susceptibility to complications of chemo therapy increases with age and involves many systems [33,120,121] . The sequelae that mainly concern rehabilitation in the elderly are related to the peripheral nervous system and the CNS [117] . Certain chemotherapeutic agents (e.g., platinum- based agents, vincristine and the taxanes) are primarily associated with sen sory neuropathy arising with paresthesia, loss of deep tendinous reflex and tactile sensitivity, which leads to muscular weakness and may hinder mobility. Management consists (also in the elderly if possible) in exercises improv ing balance and teaching compensatory strat egies. The use of a sling or assistive devices could be useful in reducing the functional impact of neuro pathy [4] . Chemotherapy may cause contractures in case of accidental drug extra vasation. In addition, the potential cog nitive adverse effects should be considered. As reported in a review of studies evaluating cogni tive function in cancer adults (with the exclusion of primary brain tumors or CNS involvement) undergoing chemotherapy, over 15% of patients presented a cognitive impairment, mainly with respect to attention and concentration, verbal and visual memory and speed process ing[122] . The drugs that are principally involved appear to be c yclophosphamide, methotrexate and5-fluorouracil.
Hormonal therapy-related damage
Many well-known side effects can occur after hormonal therapy and may cause greater concern among the elderly owing to underlyingconditions. Aromatase inhibitors used for the treatment of breast cancer may cause arthralgias and increase bone turnover, leading to osteoporosis and frac tures. Rehabilitation focuses on exercise pro grams of resistance training and weight-bearing exercises. Moreover, these bone complications
REVIEW
could be reduced by an attentive risk-factor assessment of osteoporosis, and an appropriate calcium and vitamin D intake. In addition, the use of bisphosphonates can reduce complications further, even though it is not clear which type to prescribe, how long they should be used for and until what age they are most appropriate [123,124] . Androgen deprivation therapy for prostate cancer results in many complications that impact the physical performance of older men [125127] and may accelerate development of frailty in vulnerable patients[128] . ADT increases body fat mass and reduces lean body tissue, decreasing muscle strength and the ability to accomplish physical tasks, such as climbing stairs or walk ing distances. A study investigating functional and physical assessment of men aged 70years and older receiving ADT has demonstrated sig nificant impairment and greater risk of fall com pared with a similar-aged cohort [128] . Moreover, ADT causes bone loss and osteoporosis, which increases risk of fracture [129132] . Therefore, muscle-strengthening exercises and weight and balance training should be encouraged, as should the use of bisphosphonates [123] to reduce bone loss. Anemia can impact functional status caus ing fatigue and reduces exercise resistance. Hot flashes may worsen quality of life. Impairment of erectile function and reduction of libido may require a specific rehabilitation treatment, as mentioned previously, for prostate cancer. This endocrine therapy can also impair cogni tive functions, such as verbal memory, spatial ability and executive functioning with further potential d ifficulties in performing ADL in older patients[133] . Adrenocorticosteroids are also frequently pre scribed in patients with brain and spinal cord edema for neuropathic pain, for the control of chemotherapy-induced nausea and as adjuvant analgesic therapy. These drugs may induce many complications that worsen pre-existing frailty in the elderly. They cause myopathy, weakness in the proximal muscles of the extremity and neck flexors, and body composition changes with centripetal obesity. Muscle weakness can lead to a decline in respiratory function and a development of dyspnea. Moreover, they cause osteopenia and, in some rare cases, avascular necrosis of the hips [134] . Adrenocorticosteroids may worsen cataract and exacerbate depressive symptoms, determining a worst adherence of the older patient to rehabilitative projects. Therefore, steroid treatment should be avoided in the elderly when possible, or discontinued as soon as p ossible since myopathy may be reversible.
Palliative rehabilitation
Rehabilitation in older patients with advanced cancer is an emerging approach aimed at improving comfort and function related to consequences of bed rest and deconditioning. Rehabilitative and palliative care share common aspects aimed at problem-solving and improv ing quality of life, with an individualized, tai lored and multidisciplinary approach [135,136] . Palliative rehabilitation shares similarities with geriatric care since the goal of the treatment often cannot include the recovery of dysfunction, but rather the symptom control and maintenance of the best possible autonomy [202] . Moreover, all of these disciplines empower families to play an active role. The goals of rehabilitation in this context should be re-evaluated at critical points along the disease course, always with respect to the patients wishes. In older patients with a good decision-making capacity, discussing care issues with the patient alone should be encour aged since family members with unrealistic goals can often influence the decision-making in an unwanted way. Rehabilitation consists of preventing and reducing complications of immobility, such as dyspnea with a respiratory program and ankylosis or muscle retraction with passive or active exercises, aimed at maxi mizing the range of motion, muscle strength and endurance. Palliative rehabilitation also provides a comprehensive approach avoiding pressure sores. Furthermore, a rehabilitative program in the elderly is aimed at teaching care givers the correct and safe sitting positions and transfer techniques, as well as providing mobil ity devices, such as wheelchairs, if necessary. However, today, this rehabilitative approach is mainly performed in specialized settings, such as hospice services or in the context of home palliative programs, but patients could benefit if this approach is improved in other settings, such as in nursing homes.
Conclusion & future perspective
Rehabilitation in older cancer patients is an emerging discipline aimed at improving func tional recovery and quality of life during the course of disease and its treatment. A multi disciplinary approach is essential, as well as a continued re-evaluation of the goals of reha bilitation. The diversity of neoplasms and their clinical picture, psychological factors, expecta tions and disease acceptance make it difficult to formulate definitive guidelines regarding the location and techniques for rehabilitating the older patient with advanced cancer. It seems
379

advisable to use measurement tools not only for the assessment of the elderly patients (as known in CGA) but also to help to determine whether our interventions are effective in ameliorating functional limitations and in improving quality of life [137,138] . In clinical practice, a CGA should be performed to define the needs of elderly can cer patients and determine tailored rehabilita tive plans. More research should be addressed to this field in order to objectively demonstrate the efficacy of rehabilitative interventions and to define criteria of management. Moreover, there is a call for a widespread education of all profes sionals to be aware of the rehabilitative needs of the elderly, to offer all patients the opportunity
Executive summary
Rationale for rehabilitation in older cancer patients Elderly cancer patients present functional decline and disability, compromising activities of daily living and quality of life. Rehabilitation is considered part of the treatment to restore physical function and improve quality of life. In elderly patients with any stage of cancer with associated comorbidities, small gains in several functional areas may result in an improved functional status. Rehabilitative approach The rehabilitative approach consists of a multidisciplinary approach with an interdisciplinary team focused on defined goals. Definition of the rehabilitative plan relies on a comprehensive geriatric assessment of the general conditions (e.g., stage of cancer, comorbidities and complication of treatment) and the rehabilitative needs of the patient. Evaluation tools may help to define an individualized approach. Future perspective Future trials of elderly patients are necessary in order to define the selective criteria to address rehabilitation and to establish the effectiveness of rehabilitative intervention. In clinical practice, comprehensive geriatric assessment should be widely performed and health professionals should be educated to be aware of the rehabilitative needs of elderly cancer patients.
to ameliorate function or receive adequate pal liation of symptoms, in order to sustain improve ments of rehabilitative care practice through healthcare systems [139141] .
Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or p ending, or royalties. No writing assistance was utilized in the p roduction of this manuscript.
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Elisabetta Morello Servizio di Riabilitazione Generale e Geriatrica, Fondazione Don Carlo Gnocchi, Istituto Palazzolo, ViaPalazzolo 21, 20149, Milano, Italy Tel.: +39 023 9701 Fax: +39 023 3007 193 emorello@dongnocchi.it Geremia Giordano Servizio di Riabilitazione Generale e Geriatrica, Fondazione Don Carlo Gnocchi, Istituto Palazzolo, ViaPalazzolo 21, 20149, Milano, Italy Tel.: +39 0239 701 Fax: +39 023 3007 193 ggiordano@dongnocchi.it
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Rehabilitation in older cancer patients

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Rehabilitation in older cancer patients

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Rehabilitation in older cancer patients

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