Inactivity/disuse syndrome

The effects of immobility are evident in many cancer patients after debilitating treatment protocols, often in the context of prolonged hospitalizations. Joint contractures, orthostatic hypotension, muscle atrophy , skin breakdown, osteoporosis , and reduced endurance occur in the absence of concomitant restorative or mobilization programs—preferably supervised by a physical therapist. When possible, active ambulation twice daily for hospitalized patients—or at least a bedside exercise program using antigravity resistance and progressing to elastic bands as tolerated to preserve strength and range of motion—should be encouraged. Skin integrity must be protected with frequent repositioning and off-loading of bony prominences through the use of air-cushioned beds or padded pressure relief orthoses and attention to nutritional parameters. Many cancers are associated with a hypercoagulable state, and patients require vigilant prophylaxis to minimize the risk of deep venous thrombosis and subsequent postphlebitic syndrome or pulmonary embolism .

Meta-analyses of research studies examining the effects of exercise in cancer patients throughout the disease continuum continue to demonstrate the safety and benefit of exercise interventions . Initial work on aerobic activity is being supplemented by increased attention to strength training in different populations .

Radiation effects

Radiation therapy is an integral component of treatment for many types of cancer. It may be intended as curative or palliative, the latter including symptom relief from bone pain in metastatic disease or temporizing tumor growth in brain or soft tissue. Physiatrists should be able to anticipate, recognize, and accommodate the side effects of radiation treatment. Establishing the duration of treatment is essential, particularly when considering an inpatient rehabilitation program or the timing of outpatient interventions. It should be assumed that radiation will be started and completed at the same facility. Transportation to and from the site is an important consideration for patients debilitated by advanced disease who may be ready for discharge from an acute rehabilitation unit before completion of their radiation therapy. The toxic effects of radiation treatment are divided into acute, early delayed, and late. Technologic improvements and the technique of fractionation have reduced the amount of acute and late damage to normal tissue. Acute injury remains more prevalent in tissues with proliferating cells, such as skin and gastrointestinal organs, but they often have compensatory mechanisms that permit symptoms to subside fairly rapidly ( Table 2 ) .

Chemotherapy effects

Chemotherapy is an important component of many cancer treatment protocols. Tables of commonly used agents and their side effects are widely available . Many of the effects are dose related and resolve after treatment cessation. Effects that occur during active treatment are generally addressed by the medical oncology team but should be taken into account by physiatrists who provide exercise recommendations or other interventions during treatment. Bone marrow suppression that results in neutropenia creates an increased risk of infection that warrants thorough clinical and laboratory evaluation and hospitalization for fevers more than 38°C/101°F in patients with absolute neutrophil counts less than 1000/μL . There is no formal contraindication for exercise in asymptomatic patients with granulocytopenia or even low-grade fevers, but attention should be paid to their increased respiratory rate and fatigue and their risk of dehydration. The introduction of granulocyte colony stimulating factors, such as filagastrum, has helped reduce the frequency of neutropenia, and they are often used prophylactically despite their considerable cost. Granulocyte colony stimulating factors can cause diffuse bone pain and positive findings on bone scans for several weeks after administration. Thrombocytopenia is also a common occurrence, but there is little risk of spontaneous bleeding in patients with platelet counts more than 20,000/mm ³ . Low-impact aerobic exercise is permitted for patients with platelet counts between 30,000/mm ³ and 50,000/mm ³ , but resistance work is discouraged because of concern that isometric contractions can raise systemic pressures enough to increase the risk of intracranial hemorrhage in vulnerable patients.

Nausea and emesis are well-known side effects of many chemotherapeutic regimens and can be treated with a combination of 5HT-receptors, benzodiazepines, and dexamethasone and intravenous fluid repletion when indicated . A certain percentage of patients may develop anticipatory nausea, which is not as susceptible to pharmacologic management . Consulting nutritionists are often helpful for addressing the consequences of chemotherapy-related emesis, nausea, and anorexia. Unexpected weight gain, however, is an equally prevalent side effect of certain chemotherapy regimens. When combined with alopecia, mastectomy, or limb loss, it can affect mood and self-image and contribute to adjustment disorders that occur during and around cancer treatment.

Doxorubicin (adriamycin) induced cardiomyopathy does occur, but the autonomic neuropathy and more frequent peripheral sensory neuropathy from vincristine and cisplatin probably have the greatest impact on posttreatment functional performance and QOL. Chemotherapy-induced peripheral neuropathies tend to be distal, symmetric, and dose related; many resolve with discontinuation of treatment. Patients experience painful paresthesias and, in some cases, sensory loss and weakness. Vincristine and cis-platin cause axonal degeneration that resembles other toxic neuropathies . Stomatitis from cytoxan, fluorouracil, mercaptopurine, methotrexate, and other agents can interfere with nutritional intake and bear watching . Taxol also can be responsible for arthralgias, myalgias, and peripheral polyneuropathy, which may discourage activity during treatment. The longer term cognitive effects of adjuvant chemotherapy remain an issue of concern for many women and continue to be an area of active research .

Bone health

Although only a small number of cancers originate within the skeletal system, almost all patients with cancer diagnoses are at increased risk of bone-related pathologies that are known to affect survival and QOL parameters. Osteoporosis and the accompanying risk of long bone or vertebral fracture are serious concerns for patients with primary endocrine malignancies and multiple myeloma and for hormone-suppressed survivors of breast or prostate cancer. Corticosteroids are another common cause of iatrogenic osteoporosis in cancer patients that contribute to pathologic fractures and avascular necrosis of the femoral heads. In more acutely ill patients, the metabolic effect of immobilization may contribute to accelerated bone turnover. Bisphosphonates such as pamidronate have been used to control hypercalcemia associated with malignant disease and in lesser doses are used to treat osteoporosis in the general population. More recently they have been used to address demineralization in cancer patients . Concomitant oral calcium supplementation is particularly important for patients whose nutritional intake may be compromised by their disease or ongoing treatments.

Fracture risk

The risk of metastasis to bone varies depending on tumor type but reaches 70% in patients with breast or prostate cancer . Fractures at the site of bone metastases generally present with severe pain and often as part of life-threatening traumas with risk of fat emboli. Radiographic surveillance of cancer patients has expanded attention from the treatment of pathologic fractures to their prevention. Many lesions respond to radiation therapy, chemotherapy, and bisphosphonates . Prophylactic surgical repair is recommended for patients with persistent pain despite treatment and for patients at high risk for impending fracture. Unfortunately, reliable criteria for predicting fracture risk remain elusive . A combination of radiographic assessment, including degree of cortical involvement, tumor size, and type (lytic, blastic, or mixed), lesion location, pain, functional limitations, patient prognosis, and comorbidities, must be considered in each case .

Although the proximal femur is the most common site of bone metastases, malignant involvement of vertebral bone can be a cause of significant pain and may compromise the spinal cord. Pharmacologic management of bone pain should be supplemented by training in back-sparing transfer techniques and orthotic reinforcement . Oncologic myelopathy remains a medical emergency that requires the coordinated resources of a tertiary or quaternary care center .

Physiatric evaluation of patients at high risk for pathologic fractures initially should be limited to active range of motion as tolerated and should not include manual motor testing or passive range of motion on affected extremities . When bone lesions have been confirmed and a surgical or medical treatment is in place, every effort must be made to establish and achieve reasonable rehabilitation goals. In one study of 58 patients, 26 became independent with ambulation after surgical repair and inpatient rehabilitation, although only 38 of the patients in the study returned to their own home (some with hospice services). Poor outcome correlated with need for parenteral narcotics or hypercalcemia leads to the suggestion that hypercalcemia in the context of prophylactic bisphosphonate therapy may warrant a discharge to home with hospice . If inpatient rehabilitation is required after open reduction fixation in an upper or lower extremity, selection of a facility with oncologic experience is beneficial. Physical therapists should be familiar with fall and fracture precautions for this population and be comfortable with the concerns and anxieties that patients may have when metastases are discovered and treated.

Regardless of disposition, patients should be informed of the possible risk of injury versus the cost of immobility, including joint contractures, osteoporosis, atrophy, skin breakdown, and orthostatic hypotension. Selection of assistive devices for patients with restricted weight bearing of one extremity must take the possibility and extent of other metastatic lesions into account. Wheel chair propulsion in the presence of thoracic vertebral or sternal metastases or the use of a walker, even for transfers, by a patient with humeral and femoral lesions should be considered carefully. Upper extremity lesions can be treated with a fracture brace or sling during radiation therapy but frequently require occupational therapy services for adaptive one-handed strategies even before remobilization can be initiated.

Pain

A meta-analysis of 54 studies calculated the combined weighted mean prevalence of pain in cancer patients as 40% but noted the need to distinguish between early and late disease, with the latter group reaching a combined weighted mean prevalence of 74% (range, 53%–100%) . Specific pain syndromes, including postmastectomy syndrome, visceral and bone pain, leptomeningeal carcinomatosis, chemotherapy neuropathy, and superior vena cava syndrome, require a more tailored approach, but the general principles of pain management also continue to be applicable. Initial assessment, including severity, location, quality, and temporal pattern, is needed. Several cancer-specific assessment tools have been developed, including the Brief Pain Inventory and Memorial Pain Assessment Card , although the more general Visual Analog Scale or numerical rating scales also may be used. The role of concurrent symptoms, including fatigue, depression, and weakness, cannot be underestimated and must be incorporated into any pain management treatment plan.

Treatment of pain in cancer patients may include radiation or surgery and pharmacologic and nonpharmacologic interventions. The World Health Organization analgesic ladder provides a proven, effective means for organizing pharmacologic interventions . Although oral administration is preferable, familiarity with alternative routes and appropriate dosage adjustments, including parenteral, rectal, transdermal, and even intrathecal, is needed in many cases. In addition to opioids such as morphine, oxycodone, and fentanyl, methadone has become an important tool in the treatment of cancer pain. Good oral and rectal absorption, the absence of active metabolites, high potency, long dosing interval, low cost, and incomplete cross-tolerance with other μ-opioid receptor agonists make methadone a desirable option in many cases . Potential for delayed toxicity caused by variable interindividual pharmacokinetics, a long half-life, and inconsistent knowledge about equianalgesic conversion rates have limited its use in some settings. Adjuvant agents such as tricyclic antidepressants and anticonvulsants and gamma-aminobutyric acid analogs can be used to address neuropathic pain.

Nonpharmacologic modulation of pain plays a large role and may include relaxation techniques, massage, acupuncture, and modalities such as heat, cold, ultrasound, and transcutaneous electrical nerve stimulation. In the past, many therapists were discouraged during training from using modalities that enhance blood flow near tumor sites because of concern that it could promote metastatic spread, but no reliable research has proved or disproved these claims . More pertinent probably is the need to avoid heat or cold injury to irradiated skin or manual manipulative therapy in patients at risk for bone metastases.

Fatigue

Cancer-related fatigue is defined by the National Comprehensive Cancer Network as “an unusual persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual function” . Cancer-related fatigue is experienced by 70% to 100% of cancer patients and is often multifactorial . Anemia is a common and treatable cause of fatigue in patients with cancer. Itri’s review of several large-scale studies showed decreased fatigue and increased QOL scores when erythropoietin was used to raise hemoglobin to 12 g/dL or more in patients with chemotherapy-related anemia .

Undertreatment of chronic pain generally is associated with disrupted sleep and feelings of fatigue and energy depletion during the day in all patients, and the same is true for patients with malignant pain. Narcotics and adjuvant analgesics, including tricyclic antidepressants and anticonvulsants for neuropathic pain, may cause daytime sleepiness and disrupt restorative sleep-wake cycles. Because people develop a tolerance to the sedating side effects of these medications, however, they should not be implicated as an ongoing cause of daytime fatigue if they have been consistently used over a period of weeks or months. Sleep disturbances occur frequently among cancer patients and warrant a multimodal response, including patient education, treatment of associated anxiety and depression, behavior modification, and careful use of hypnotics and anxiolytics. The deconditioning that occurs in many patients undergoing treatment also can produce a sense of chronic fatigue as they try to return to their usual activities with reduced physiologic reserve.

Exercise plays an important role in fatigue because it elevates mood, improves endurance, decreases fatigue, and improves overall QOL. Studies that have demonstrated improvement in fatigue levels with exercise have relied on walking or biking several days a week at mild to moderate intensities. Lower intensities with more stringent precautions are appropriate for patients in active treatment, with higher intensities for patients who have completed treatment. Courneya’s review of published data on exercise in cancer survivors overwhelmingly demonstrated the safety and efficacy of tailored exercise programs for addressing fatigue, endurance, and QOL in patients who have cancer.

Nutrition, anorexia, and cachexia

Nutrition is an important parameter for maximizing rehabilitation outcomes in patients who have cancer throughout the disease trajectory. Decreased intake may begin early in the course of cancers; it may affect any part of the gastrointestinal system and impair chewing or swallowing. Patients with diseases that affect other organ systems may experience nausea and anorexia during treatment as a side effect of chemotherapy or narcotic analgesia. Radiation to the head or neck can alter taste and saliva production. Radiation changes that affect the stomach, large or small intestine, or rectum can lead to diarrhea. Lethargy, mental status changes, or hydrocephalus with central nervous system involvement can affect appetite and intake. Depression also may be an important cause of malnutrition in patients with local and advanced disease.

Guo and colleagues recently demonstrated a 50% prevalence of below-normal prealbumin (<18 mg/dL) in cancer patients admitted to an inpatient rehabilitation unit. Patients with compromised nutrition experience more serious complications, have prolonged hospital stays, and have reduced QOL . True cancer cachexia/anorexia syndrome is experienced by many patients with advanced disease. Once thought to reflect the increased metabolic demand of tumors themselves, cancer cachexia is currently understood as a group of metabolic abnormalities triggered by immune mediators (eg, tumor necrosis factor and interleukin-6) and tumor byproducts (eg, lipolytic hormone). These abnormalities promote lipolysis, weight loss, and depletion of skeletal and visceral proteins, which make patients more susceptible to skin breakdown and decreased performance status. Nutritional supplements, appetite stimulants, and anabolic steroids may be used to help modify the impact of these processes but are rarely able to reverse or avoid the syndrome altogether.

Nausea

Nausea is an important symptom for many cancer patients, with 70% to 80% of patients reporting nausea with or without vomiting with chemotherapy . Ten percent to 45% of patients have anticipatory nausea. Phenothiazines were once the mainstay of therapy. Newer antiemetics do better at controlling vomiting than eliminating nausea. Ten percent to 45% of patients develop anticipatory nausea, for which antiemetics are ineffective. Although difficult to predict, nausea may occur more frequently in younger patients and has been associated with higher rates of anxiety and depression .

Dyspnea

Subjective discomfort with breathing in the presence or absence of actual hypoxia occurs in many different cancers and becomes increasingly common in advanced diseases, particularly if there is direct involvement of the lung, chest, or upper airway. Because there is little correlation between subjective experience and actual respiratory function, efforts must focus on symptom relief and not just normalization of blood gas levels. In addition to supplemental oxygen, positioning and adaptive breathing techniques can be helpful . Inhaled or nebulized bronchodilators may be beneficial for patients with newly diagnosed lung cancer or underlying chronic obstructive pulmonary disease, but the reversible element of airway obstruction in advanced disease is less likely to be clinically significant. Research on the role of benzodiazepines remains equivocal, but many practitioners find that when used in low doses they are an effective means of reducing breathlessness while also modulating the cycle of respiratory panic in which breathlessness induces anxiety, which in turn aggravates breathlessness . Counseling in the form of relaxation techniques supplemented by modification of activity level and energy conservation strategies can help maximize the independence of patients with objective respiratory dysfunction and symptomatic dyspnea.

Lymphedema

The lymphatic system may be damaged by underlying oncologic disease and surgery or radiation, which impairs its ability to absorb fluid and cellular debris. Immune response is also diminished because bacteria can no longer be transported effectively through the lymphatics to lymphocytes in centralized lymph nodes. The use of circumferential measurement at standardized intervals remains the most common means of quantifying lymphedema . Other techniques, such as volume assessment, are available but generally are used for research purposes.

It is important to address lymphedema in at-risk patients, because once established, even minor cases can develop into progressively worsening cycles that culminate in significant dysfunction and risk of infection. Education is the primary and most important component of any program. Essential preventive measures include not interfering with lymphatic flow through constricting garments and protecting from infection, injury, and burns, including intense sun exposure. Instruction to seek medical attention promptly if new or worsening edema develops is equally important. Historically at-risk patients were counseled to avoid vasodilation and repetitive activity or even carrying a handbag on the affected side. This approach has been challenged most dramatically by the active participation of many breast cancer survivors in dragonboat racing, a demanding upper-extremity sport characterized by repetitive motion against resistance . Although it is probably safe to permit at-risk patients to begin or return to more vigorous activity, including gardening, tennis, or dragonboat racing, this should be done only under close supervision and after extensive counseling about a gradual program of increased activity, the need for close self-monitoring, and the early signs of lymphedema.

Once established, lymphedema can be managed effectively although not eradicated. Compression therapy is most useful, although the use of external intermittent pumps remains controversial . Manual lymph drainage combined with compression bandages and a series of exercises is the current standard of care and is often referred to as complete decongestive physiotherapy. Manual drainage is begun in an edema-free area bordering on the lymphostatic region and progresses centrifugally (proximally to distally) rather than by trying to propel fluid through a congested area by beginning distally. In most settings, treatment is provided 5 days a week for 4 to 6 weeks by occupational therapists, physical therapists, and occasionally physicians who have completed formal training and certification through one of the programs recognized by the National Lymphedema Network ( www.lymphnet.org ). When the affected area (ie, limb, truncal quadrant, breast, face) has been reduced maximally over time, a low-stretch, custom-fitted compression garment (ideally 40–60 mmHg) is worn during the day to maintain optimal limb volume. Despite rigorous compliance, patients occasionally develop recurrence, which warrants another course of complete decongestive physiotherapy after infection or tumor recurrence has been ruled out. The use of benzopyrones or surgical interventions for lymphedema has not been well established.

Sexual function

Sexuality is a frequently neglected component of cancer care but may be of considerable importance to many patients. Discussing sexual function is an essential component of evaluation and treatment during every phase of the disease continuum. Reproductive concerns must be addressed when either the affected organs or a patient’s age make this a matter of concern. Specific treatment, including antiestrogen therapy in breast cancer, surgical menopause after ovarian cancer, radical prostatectomy with radiation and antiandrogen treatment, or other cancers that require pelvic surgery or radiation may require targeted interventions to restore lubrication or erectile function or prevent dyspareunia. In other cases, patients and their partners avoid sexual activity for fear of causing injury, feelings of bodily dysmorphism, or negative emotional patterns that developed during diagnosis and treatment. Although physiatrists may not directly treat these conditions, they play an important role in identifying the difficulties and empowering and directing their patients to seek specific solutions from gynecologists, urologists, and, in some cases, specially trained psychotherapists and counselors.