Rehabilitation for Patients with Cancer Diagnoses

Mary M. Vargo

Justin C. Riutta

Deborah J. Franklin

GENERAL ASPECTS OF REHABILITATION FOR CANCER PATIENTS

Historical Background

Patients with cancer diagnoses are living longer because of a combination of early detection, a broader selection of cancer treatment options, and better general medical management. While the treatment of cancer has moved toward less invasive and more preservation-oriented techniques, there remains a high incidence of disability in individuals with cancer and survivors (1, 2, 3). Census data indicates cancer as the 13th most common cause of self-reported disability (4).

Rehabilitation Expectations in the Cancer Population

While rehabilitation goals for cancer patients have historically been organized into restorative, supportive, preventative, and palliative categories (5), another important concept is that the clinical course can be both chronic and dynamic (6), resulting in need for rehabilitation at various points in the disease trajectory. The heterogeneity of cancer types creates very diverse rehabilitation needs in this population. The more common issues are highlighted here.

Demographics of Cancer and Its Relevance to Rehabilitation

Cancer is the second leading cause of death in the United States, accounting for approximately one in every four deaths among both children and adults (7). Nearly 60% of all cancers occur in individuals age 65 and older, and age-adjusted incidence is ten times greater in individuals over age 65 than younger age groups (8). The overall 5-year relative survival rate for 1996 to 2002 was 66% (Table 44-1), up from 51% in 1975 to 1977, and 35% in the 1950s (9). Five-year survival for childhood cancers has improved from less than 50% prior to the 1970s to about 80% today, though there is variability by site (7). The lifetime risk of being diagnosed with cancer is approximately 40%, and there are greater than 10.7 million individuals alive in the United States with a history of cancer diagnosis (2004 estimate) (9).

Historically, knowledge of survival statistics has been important for rehabilitation decision making, because aggressive restorative services may not be appropriate for those with a markedly reduced life expectancy. However, survival often varies markedly within a given tumor type because of factors such as stage of disease and histology, so each case must be approached individually. Radically improved survival rates now compel rehabilitation professionals to examine the needs of long-term survivors. Of particular interest are the more common cancers with large survivorship populations, such as breast and prostate cancer (7), and cancers known to have a high incidence of disabling complications (see next section) (10). Since cancer is most common in older age groups, the impact of cancer within the geriatric population is receiving increasing attention. In general, cancer in the elderly may not be more disabling than other common medical conditions such as diabetes or congestive heart failure (11), but more severe symptoms or extensive treatment is associated with greater loss of function (12).

CANCER REHABILITATION SERVICE DELIVERY

One seminal study of the rehabilitation needs of individuals with cancer identified that 54% had physical medicine problems (10), with very high incidence (70% or greater) among those with central nervous system (CNS), breast, lung, or head and neck tumors. There was a large gap between the identified rehabilitation needs and the services actually delivered, which improved dramatically with a program for patient education, automatic screening of patients for rehabilitation needs, and introducing a physiatrist into the clinical oncology team. Organized cancer rehabilitation programs, while not widespread, have been described (13). Core components include a committed administration, physiatrist as medical director, and effective marketing, as well as practical considerations including accessibility.

Because of the heterogeneity of rehabilitation needs across the cancer spectrum, as well as the complexity of care in individual cases, screening and surveillance tools should be employed which are both systematic and clinically practical. Issues may be present at symptom, impairment and function levels. Visual analog scores have been described for pain, fatigue, appetite, mood, and sleep (14). Office-based tests that have been applied
to assess impairments and basic function include manual muscle testing, grip dynamometry, range of motion, limb girths, up and go test (15), timed walking, single foot balance, tandem walking (16), modified sit-and-reach test (for flexibility), and stand and sit test (for strength) (17). Karnofsky (Table 44-2) and Eastern Cooperative Oncology Group (ECOG) scales have been employed by oncologists as a measure of performance status, less so for functional outcome; hence, these measures are of uncertain value in rehabilitation. Some questionnairebased tools developed for oncology patients incorporate both functional and quality-of-life measures. Examples include the Functional Assessment of Cancer Therapy (FACT), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTCQ), Cancer Rehabilitation Evaluation System (CARES), and Functional Living Index-Cancer (FLIC). The 36-Item Short Form Health Survey (SF-36), a health status instrument, has also been applied to the cancer population (18, 19, 20).

TABLE 44.1 Estimated New Cancer Cases and Deaths by Sex, United States, 2008

		Estimated New Cases			Estimated Deaths
		Both Sexes	Male	Female	Both Sexes	Male	Female
All sites		1,437,180	745,180	692,000	565,650	294,120	271,530
Oral cavity and pharynx		35,310	25,310	10,000	7,590	5,210	2,380
	Tongue	10,140	7,280	2,860	1,880	1,210	670
	Mouth	10,820	6,590	4,230	1,840	1,120	720
	Pharynx	12,410	10,060	2,350	2,200	1,620	580
	Other oral cavities	1,940	1,380	560	1,670	1,260	410
Digestive system		271,290	148,560	122,730	135,130	74,850	60,280
	Esophagus	16,470	12,970	3,500	14,280	11,250	3,030
	Stomach	21,500	13,190	8,310	10,880	6,450	4,430
	Small intestine	6,110	3,200	2,910	1,110	580	530
	Colon	108,070	53,760	54,310	49,960	24,260	25,700
	Rectum (deaths included with colon)	40,740	23,490	17,250
	Anus, anal canal, and anorectum	5,070	2,020	3,050	680	250	430
Liver and intrahepatic bile duct		21,370	15,190	6,180	18,410	12,570	5,840
	Gallbladder and other biliary	9,520	4,500	5,020	3,340	1,250	2,090
	Pancreas	37,680	18,770	18,910	34,290	17,500	16,790
	Other digestive organs	4,760	1,470	3,290	2,180	740	1,440
Respiratory system		232,270	127,880	104,390	166,280	94,210	72,070
	Larynx	12,250	9,680	2,570	3,670	2,910	760
	Lung and bronchus	215,020	114,690	100,330	161,840	90,810	71,030
	Other respiratory organs	5,000	3,510	1,490	770	490	280
Bones and joints		2,380	1,270	1,110	1,470	820	650
Soft tissue (including heart)		10,390	5,720	4,670	3,680	1,880	1,800
Skin (ex-basal and squamous)		67,720	38,150	29,570	11,200	7,360	3,840
	Melanoma of the skin	62,480	34,950	27,530	8,420	5,400	3,020
	Other nonepithelial skin	5,240	3,200	2,040	2,780	1,960	820
Breast		184,450	1,990	182,460	40,930	450	40,480
Genital system		274,150	195,660	78,490	57,820	29,330	28,490
	Uterine cervix	11,070		11,070	3,870		3,870
	Uterine corpus	40,100		40,100	7,470		7,470
	Ovary	21,650		21,650	15,520		15,520
	Vulva	3,460		3,460	870		870
	Vagina and other genital, female	2,210		2,210	760		760
	Prostate	186,320	186,320		28,660	28,660
	Testis	8,090	8,090		380	380
	Penis and other genital organs, male	1,250	1,250		290	290
Urinary system		125,490	85,870	39,620	27,810	18,430	9,380
	Urinary bladder	68,810	51,230	17,580	14,100	9,950	4,150
	Kidney and renal pelvis	54,390	33,130	21,260	13,010	8,100	4,910
	Ureter and other urinary organs	2,290	1,510	780	700	380	320
Eye and orbit		2,390	1,340	1,050	240	130	110
Brain and other nervous system		21,810	11,780	10,030	13,070	7,420	5,650
Endocrine system		39,510	10,030	29,480	2,430	1,110	1,320
	Thyroid	37,340	8,930	28,410	1,590	680	910
	Other endocrine	2,170	1,100	1,070	840	430	410
Lymphoma		74,340	39,850	34,490	20,510	10,490	10,020
	Hodgkin’s lymphoma	8,220	4,400	3,820	1,350	700	650
	Non-Hodgkin’s lymphoma	66,120	34,450	30,670	19,160	9,790	9,370
Myeloma		19,920	11,190	8,730	10,690	5,640	5,050
Leukemia		44,270	25,180	19,090	21,710	12,460	9,250
	Acute lymphocytic leukemia	5,430	3,220	2,210	1,460	800	660
	Chronic lymphocytic leukemia	15,110	8,750	6,360	4,390	2,600	1,790
	Acute myeloid leukemia	13,290	7,200	6,090	8,820	5,100	3,720
	Chronic myeloid leukemia	4,830	2,800	2,030	450	200	250
	Other leukemia	5,610	3,210	2,400	6,590	3,760	2,830
Other and unspecified primary sites		31,490	15,400	16,090	45,090	24,330	20,760
Excludes in situ carcinomas except urinary bladder. About 67,770 female carcinomas in situ of the breast and 54,020 melanomas in situ will be newly diagnosed in 2008. National Center for Health Statistics, Centers for Disease Control and Prevention, 2008. ©2008, American Cancer Society, Inc., Surveillance Research.

TABLE 44.2 Karnofsky Scale

Able to carry on normal activity; no special care is needed.

10 Normal; no complaints, no evidence of disease

9 Able to carry on normal activity; minor signs or symptoms of disease

8 Normal activity with effort; some signs or symptoms of disease

Unable to work; able to live at home; cares for most personal needs; varying amounts of assistance is needed.

7 Cares for self; unable to carry on normal activity or do active work

6 Requires occasional assistance, but is able to care for most of own needs

5 Requires considerable assistance and frequent medical care

Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly.

4 Disabled; requires special care and assistance

3 Severely disabled; hospitalization is indicated, although death is not imminent

2 Very sick; hospitalization necessary; active supportive treatment necessary

1 Moribund, fatal process progressing rapidly

0 Dead

Inpatient Rehabilitation

Several studies have shown that cancer patients and noncancer patients achieve comparable functional gains from inpatient rehabilitation programs, as measured by the Functional Independence Measure (FIM). Patients with neoplastic spinal cord injury (SCI) (21) and brain tumors (22,23) have been shown to have shorter rehabilitation lengths of stay but similar discharge rates to home when compared to age matched controls. Reasons may include higher initial FIM score (seen in some studies), and possibly fewer behavioral sequelae, better social support, and expedited discharge planning due to poor long-term prognosis in some cases (24). Functional improvements made during acute rehabilitation are maintained 3 months after discharge (25). Chemotherapy, radiation therapy, and specific tumor type have not been shown to adversely affect rehabilitation outcome (26,29).

The incidence of transfer back to acute care from rehabilitation is higher than noncancer patients in most (26, 27, 28) but not all (29) series. One study that examined reasons for transfer found that infection was more common in cancer patients than in controls (28). Low albumin, elevated creatinine, and use of feeding tube or indwelling bladder catheter have been reported to be risk factors for transfer (30). Prognosis and the patient’s general tolerance of rehabilitation therapies must be weighed in the decision for inpatient rehabilitation. However, poor expected long-term survival is not a contraindication if substantial functional gains are likely to be made in the short or intermediate term. Functional gains for patients with advanced disease should be defined broadly enough to include family/caregiver training that will allow terminally ill patients to remain home with hospice services if that is their choice.

Outpatient Rehabilitation

Outpatient care, typically, addresses specific musculoskeletal or soft-tissue problems, such as lymphedema, contracture, and pain, as well as mobility and self-care issues. Often there is need
for surveillance of symptoms and function, both at critical points in care (e.g., in association with surgery) and over an extended period of time. One study of individuals with advanced breast cancer and remediable disabling impairments found that outpatients were markedly less likely than inpatients to receive rehabilitation services (31). This suggests the need for improved rehabilitation systems for outpatients and perhaps especially for those with advanced disease. Home health care may be needed if mobility is a significant obstacle to treatment.

Increasing attention is being paid to appropriate models for outpatient care, especially survivorship care. The Institute of Medicine has recommended that all cancer patients receive a care plan at the end of treatment summarizing care and also detailing future concerns. While many of the issues such as surveillance for recurrence or new cancers, medical late effects, reproductive issues, genetic testing, and economic factors, are beyond the typical rehabilitation scope, other surveillance issues may be highly relevant for good functional outcomes and clearly do pertain to rehabilitation care. For example, some physical impairments, such as contracture or lymphedema, can occur as late effects that warrant ongoing physiatrist’s assessment and management. In addition, the beneficial effects of physical activity are becoming increasingly convincing, both for cancer survival and reducing disability from comorbidities (32). The clinical focus and program structure of rehabilitation services for survivors vary widely but they tend to be most readily found, either as part of a comprehensive multidisciplinary outpatient cancer clinic or through referrals for outpatient consultations by physiatrists specializing in cancer care (33).

Consultation During Acute Care

In the acute care setting, consultation is most frequently requested for evaluation and treatment of mobility and self-care needs, as well as for the assessment of cognitive status, communication, and swallowing. The physiatrist will be asked to participate in decision making about the setting for future rehabilitation efforts. Services for pain control or the provision of orthotic/prosthetic devices may also be indicated. One study administering the FIM instrument to acute oncology inpatients found that 87% of patients had rehabilitation needs on admission and 84% still had needs upon discharge (16). Another study applying organized interdisciplinary rehabilitation care to oncology inpatients reported significant functional improvement per Barthel Mobility Index and Karnofsky Performance Scale (34).

Precautions

The physiatrist should routinely check for the following conditions, some a result of treatment such as chemotherapy, which empirically have an impact on the ability of the patient to safely tolerate some rehabilitation services, such as exercise or therapeutic heat.

Hematologic profile: hemoglobin less than 7.5 g, platelets less than 20,000, white blood cell count less than 3,000
Metastatic bone disease (see the section “Bony Metastatic Disease”)
Compression of a hollow viscous (bowel, bladder, or ureter), vessel, or spinal cord
Fluid accumulation in the pleura, pericardium, abdomen, or retroperitoneum associated with persistent pain, dyspnea, or problems with mobility
CNS depression or coma, or increased intracranial pressure
Hypokalemia/hyperkalemia, hyponatremia, or hypocalcemia/hypercalcemia
Orthostatic hypotension
Heart rate in excess of 110 beats/min or ventricular arrhythmia
Fever greater than 101°F

CANCER-RELATED PAIN

General Approach to Assessment and Treatment

An estimated 60% of patients with cancer experience pain, with 25% to 30% having severe pain (35). Presence of pain, as well as other symptoms such as fatigue and insomnia, is associated with decrease in functional status, particularly in elderly cancer patients (12).

The World Health Organization (WHO) analgesic ladder, which has been validated and is considered the cornerstone of cancer pain management, matches treatment to the pain intensity. The first line of treatment is the nonopioid analgesics (aspirin, acetaminophen, and nonsteroidal anti-inflammatories, etc.). If insufficient, an opioid (codeine, oxycodone, morphine, fentanyl, methadone, etc.) should be added. In addition to intensity, one must consider multiple other factors, including acuity (acute, crescendo, chronic), pathophysiology (somatic, visceral, neuropathic), and temporal (continuous, intermittent, breakthrough) (35,36). Visceral pain is typically poorly localized, cramping, or deep aching. Somatic pain is well localized to discrete anatomic areas, often sharp or stabbing, and neuropathic pain has a burning, tingling, or throbbing quality. While the WHO ladder remains fundamental, increasing attention is being paid to other treatments, such as early use of interventional procedures when clinical assessment suggests a high chance of success, not just when all other measures have failed. Medication regimens should be tailored to specific pathophysiologic pathways. For example, when pain is due to direct tumor spread, antitumor therapy is most likely to be effective. Edema or antibody-mediated neurologic compromise is often managed with corticosteroids, inflammatory pain with nonsteroidal anti-inflammatory medication or corticosteroids, and neuropathic pain with antidepressants, anticonvulsants, and topical preparations (36).

Pain intensity can be measured by numerical (1 to 10 rating), categorical (none, mild, moderate, severe), or pictoral (Wong-Baker FACES) methods (36). Historically, complete pain relief has been the goal, and even described as a “patient right,” but there is increasing recognition that it may not
always be possible, and that in most cases 33% to 50% pain reduction is clinically meaningful (37). Factors associated with difficulty attaining adequate pain control include neuropathic quality, psychologic distress, history of addiction, and impaired cognition (35).

Patient wishes should be included in the treatment plan, and use of a pain dairy can assist in optimizing treatment (37). Technological innovations such as an interactive computer program for education about pain and other symptoms have also been developed (38).

Opioid Strategies

Opioid agents that are commonly prescribed in the setting of cancer include oxycodone, morphine, hydromorphone, and fentanyl (Table 44-3). Meperidine and propoxyphene should be avoided due to toxic metabolites that can lead to seizures or cardiac arrhythmias, especially in the setting of dehydration or renal dysfunction (36). Methadone may be desirable in the setting of renal failure; however, because of its high potential for interaction with other medications and marked individual variation in pharmacokinetics, it should only be prescribed by physicians highly experienced with this drug (35). While oral administration predominates in most physiatric settings, increasing options have become available including parenteral routes such as transdermal, epidural, and intrathecal administration (39). In general, dosing is advanced to the level at which pain is controlled or at which toxicities preclude higher dosing. Daily effective dose can be established with short-acting preparations, and then converted to longer-acting forms. There should be additional dosing available for breakthrough, intermittent, or incident pain (including that associated with rehabilitation therapies) consisting of the equivalent of a patient’s 4 hours dosing needs, 25% to 50% of that dose, or 5% to 10% of the total daily opioid dose (35).

TABLE 44.3 Pharmacologic Management of Pain

Analgesic	Route	Duration of Analgesic	Dosage	Side Effects
Aspirin	Oral	4-6 h	650 mg every 4 h	Gastritis, tinnitus
Acetaminophen	Oral	4-6 h	650 mg every 4 h	Hepatotoxicity
NSAIDs^a	Oral	Varies by agent	Varies by agent	Gastritis
Tramadol	Oral	6-8 h	50-100 mg every 6 h	Sedation, nausea, constipation
Morphine^b	Intravenous	1.5-2 h	2-10 mg	Sedation, respiratory depression, constipation, confusion, pruritus
	Epidural/intrathecal	Up to 24 h	5 mg
	Oral	2-4 h	15-60 mg
Delayed release MS Contin, Roxanol	Oral	8-12 h	15-60 mg	Sedation, respiratory depression, constipation, confusion, pruritus
Methadone	Oral	24 h	Varies	Sedation, respiratory depression, constipation, confusion; variable dosing efficacy
Oxycodone	Oral	3-6 h (standard)	5-10 mg every 4-6 h	Sedation, respiratory depression, constipation, confusion
		12 h (sustained release)
Hydromorphone	Oral	2-4 h	7.5 mg	Sedation, respiratory depression, constipation, confusion
	Parenteral	2-4 h	1.5 mg
	Rectal	6-8 h	3 mg
Hydrocodone	Oral	3-5 h	30 mg	Sedation, respiratory depression, constipation (often more severe than with other opioids), confusion
Fentanyl	Transdermal	72 h	50 µg/h	Sedation, respiratory depression, constipation, confusion. Use transmucosal form only in opioid tolerant patients, for breakthrough; only for cancer patients
	Transmucosal (buccal)	4 h (variable)	200 µg
^aNSAIDs, nonsteroidal anti-inflammatory drugs. Numerous options, including COX-2 inhibitors (rofecoxib, celecoxib) with reduced incidence of gastritis. ^bDosing of this agent and other opioids will be highly variable, depending on degree of opioid tolerance. Dosing can be advanced.

Management of side effects is crucial. An effective bowel program, including stool softeners and laxatives should be prescribed. Sedation is often transient, but if persisting greater that 1 week, measures such as caffeine intake or use of a stimulant such as methylphenidate can be helpful (36). However, in the setting of delirium, a neuroleptic may be necessary after other
metabolic causes have been excluded. Myoclonus related to opioid use may respond to baclofen, benzodiazepines, dantrolene, or valproate (35). While tolerance of a particular opioid may develop, reduced cross tolerance between different agents makes rotation of opioid drugs an effective way of avoiding escalating dosage requirements and the resulting side effects (35).

Nonpharmacologic Pain Management Approaches

Physical modalities such as cryotherapy, biofeedback, iontophoresis, transcutaneous electrical nerve stimulation, and massage are well tolerated and believed to be safe, though the latter two are not performed directly over areas with known tumor (39). Deep heat such as ultrasound is contraindicated directly over an area of tumor. Data are limited, but one study in mice showed increase in tumor size (but no increase in rate of metastasis) with application of ultrasound (40). Routine physiatric procedures such as trigger point injections may be helpful. Psychologic techniques including imagery, distraction training, relaxation techniques, and coping strategies are encouraged (36). Interventional options can include nerve blocks, vertebroplasty, spinal analgesia (including long-term catheter systems), dorsal column stimulators, and neuroablative procedures (neurectomy, rhizotomy, cordotomy). Complementary and alternative medicine strategies are widely used, with increasing acceptance of massage and acupuncture, especially when other modalities have failed to achieve adequate pain relief (39).

BONY METASTATIC DISEASE

Metastatic disease to the skeleton is one of the most problematic situations for clinicians managing musculoskeletal disorders. The skeleton is the third most common location for systemic metastatic disease (41) (Fig. 44-1). Breast, lung, prostate, kidney, and thyroid cancers account for 80% of malignancies to bone (42). The biology of bone metastasis is thought to involve the interaction of cellular adhesion molecules with the architecture and circulatory supply of the bony apparatus (43). Bone metastases are osteolytic (primarily osteoclastic activity), osteoblastic (primarily osteoblastic activity), or mixed (43). Lymphoma, multiple myeloma, thyroid and renal cell malignancies have the highest rates of osteoclastic activity and therefore high levels of structural damage to bone and fracture risk. However, even in conditions where osteoblastic changes predominate, such as prostate cancer, pathologic fractures can occur. Early and aggressive management is imperative in maintaining function (44).

FIGURE 44-1. Extensive lumbar spinal metastasis, mixed lytic, and blastic lesions.

Pain is the most common clinical presentation of bone metastases (45). The pain is insidious, unrelenting, not associated with trauma or activity, and may be present or intensify at rest (46). The pain is frequently located in less common locations such as the thoracic spine or femoral shaft. Although pain is a common presentation, more than 25% of bone metastases are asymptomatic and found on routine imaging. Classic findings on physical examination include weight loss, exquisite point tenderness over the involved bone, and possibly neurological impairment. Failure to respond to initial treatment and progressive symptoms are “red flags” that require further scrutiny (47).

The assessment of patients with suspected bone metastasis requires an efficient structured approach, including a detailed history and physical examination. Functional assessment and social history are imperative for establishing rehabilitation goals and the need for family support. Initial laboratory evaluation in those with suspected metastatic disease should include a complete blood count, serum protein electrophoresis, urinalysis, C-reactive protein, and a comprehensive metabolic panel including calcium and alkaline phosphatase (47). Plain radiographs, though inexpensive and easily accessible, have limited utility in identifying metastatic bone disease because greater than 50% of the cortex needs to be involved before metastatic disease will be identified (47). The most sensitive imaging study for the identification of bone metastases is the triple phase bone scan, as only 5% to 10% of cortical involvement is required to identify abnormalities (48). Bone scans identify osteoblastic activity in bone and therefore may produce normal results (false negatives) in patients with primarily osteolytic disease such as myeloma or lymphoma. In addition, bone scans have poor specificity. For those patients with localized bone pain, equivocal bone scans, or neurological impairment, magnetic resonance imaging (MRI) with gadolinium is the most appropriate test, particularly for suspected spinal lesions (49). The recent advent of PET scanning has helped to detect tumor activity in cases when the above imaging studies are equivocal or when the primary lesion is osteolytic (50). In some cases, biopsy may be indicated to guide treatment (46).

The median survival for patients with isolated bone disease from cancer of the breast, prostate, or from multiple myeloma is 21 to 33 months (51). During this time, the appropriate use of supportive measures to decrease morbidity and pain, and improve function should be employed. Multidisciplinary
management involves collaboration among physiatry, orthopedic surgery, medical and radiation oncology, with care goals that encompass systemic disease management, pain control, skeletal stabilization, and rehabilitation.

Systemic management options, usually prescribed by a medical oncologist, include chemotherapy, hormonal therapy, monoclonal antibodies, and anti-angiogenesis agents. The administration of bisphosphonates is usually initiated when bone metastases are first detected, although in some cases they may be administered prophylactically. Intravenous bisphosphonates decrease skeletal morbidity, fracture rate, and pain through the inhibition of osteoclastic activity and suspected modulation of local tumor activity (52,53). Radiation therapy, including direct beam and radiopharmaceutical options, frequently can be effective in decreasing local tumor burden and controlling pain (54).

Multimodal pain control begins with the management of systemic malignancy as described above. Nonsteroidal antiinflammatory agents are employed to decrease periosteal bone reaction, and opioids are used for general pain control (48). In some cases, more aggressive interventional measures may be necessary.

Stabilization of the skeleton is imperative for pain control and function. No system for predicting stability of long bone has been universally accepted. Generally, the greater the amount of cortex involved with metastatic disease the greater the risk of fracture (55). Size criteria for pathologic fracture risk in lower limb long bone include lesions measuring more than 2.5 cm, involvement of more than 50% of the bony cortex, and the Mirels scoring system incorporating pain, size, location, and radiographic appearance (49) (Table 44-4). A recent study comparing various methods found only axial cortical involvement of greater than 30 mm and circumferential cortical involvement predictive of fracture; the former measure has the advantage of being accessible with x-rays alone (56). In practice, it is often difficult to gauge the size of bony lesions, especially lytic ones, which may be irregular, permeative, and difficult to distinguish from surrounding osteopenia. Apart from radiographic assessment, pain that increases with weight bearing may be an indication of an unstable bony structure (46), warranting early surgical assessment. Fracture risk may actually increase during the first 6 to 8 weeks after radiation as a result of tumor necrosis and softening of bone. Therefore, surgical stabilization is typically done prior to radiation of unstable lesions.

TABLE 44.4 Fracture Risk (>8 Points High Risk)

	Points Assigned
	1	2	3
Anatomic site	Upper extremity	Lower extremity	Trochanter
Lesion type	Blastic	Blastic/lytic	Lytic
Lesion size	<1/3 diameter	>1/3, <2/3 diameter	>2/3 diameter
Intensity of pain	Mild	Moderate	Severe

In the spine, the stability of the bone and the presence of neurological impairment guide the assessment in Harrington’s classification of vertebral metastases:

No significant neurological involvement
Involvement of bone without collapse or instability
Major neurological impairment without significant bone involvement
Vertebral collapse without neurologic impairment
Vertebral collapse with neurologic impairment

For class III to V involvement, surgical intervention is warranted (54). Surgical management of the unstable skeleton is very effective in reducing pain and increasing function. Harrington found good or excellent pain relief in 96% of long bone and 88% of spinal fractures (57), and improved function in 82% of spine stabilization cases (57). A recent advance has been the NOMS algorithm, incorporating neurologic (cord compression), oncologic (radiosensitive or not), mechanical (movement-related pain; fracture/subluxation >5 mm, or angulation >11 degrees with subluxation >3.5 mm), and systemic factors (medical risks of surgery) into decision-making for surgery (58). In refractory cases or nonsurgical candidates, bracing can be considered, but wearing tolerance remains a significant barrier.

The rehabilitation of patients with bone metastasis is based on protection, pain control, energy conservation, and maintenance of function. Protection and pain control can be obtained through the use of bracing, mobility aids, and activity precautions. Some patients with exclusively lower extremity disease may be able to maintain mobility with the use of a cane or walker. Those with more diffuse (including upper limb), or bilateral disease may require a wheelchair or power mobility. Neutral spine techniques preserve function and minimize pain in patients with spinal metastases. It is essential to assess the weight-bearing status of all limbs when prescribing assistive devices for patients with known or suspected bone metastases as bony metastases usually occur at multiple sites, with 20% of metastases present in the upper limbs, especially the humerus (49). Exercise prescriptions should focus on increasing strength, endurance, and function with minimal loading or torsion of the affected bone. A typical exercise program may include aquatic therapy, non-weight-bearing exercise such as cycling and isometric exercise for strength maintenance. Compensatory techniques can decrease the biomechanical load on affected bones and maximize function. These include the use of reachers for activities of daily living, neutral spine techniques, and a step-to-gait pattern when climbing stairs. When metastatic disease limits independence, family training and education are beneficial to reduce the risk of injury to both caregiver and patient, and to identify needs for durable medical equipment.

CANCER-RELATED FATIGUE (CRF)

Fatigue is a normal physiological response to exertion. It becomes pathological when it persists, occurs during routine activities, and does not respond to rest (59,60). Stringent clinical studies routinely find that the majority of cancer patients will meet criteria for CRF at more than one time during their disease continuum (61). High prevalence, impact on function and quality of life, and caregiver burden make the assessment and treatment of CRF a central goal of almost every cancer rehabilitation program (62,63).

Numerous fatigue assessment tools have been validated for oncology patients (64). Busy clinicians, however, may find it easiest to screen their patients using a mild/moderate/severe designation based on a 0 to 10 Likert type scale. Patients reporting fatigue intensity of 1 to 3 are considered as having mild CRF, 4 to 6 as moderate, and 7 to 10 as severe. The National Comprehensive Cancer Network (NCCN) recommends screening for fatigue at the time of diagnosis, consistently during treatment, and as part of the long-term follow-up care (65), even after the completion of successful oncologic treatment.

It is not yet clear whether CRF is a specific physiologic process or “a final common pathway to which many predisposing or etiologic factors contribute” (66,67). Nonetheless, clinical studies have been able to recognize specific factors that are consistently associated with CRF and are therefore thought to precipitate it or intensify its impact. The most common associated factors are pain, emotional distress, sleep disturbance, anemia, nutritional deficiencies, deconditioning, and medical comorbidities (65) (Table 44-5). Identification of lead factors guides the treatment process.

Successful management of CRF requires the coordinated collaboration between clinicians who can address etiologic factors affecting a specific patient. The NCCN guidelines recommend four types of treatment interventions: (a) education and counseling, (b) general strategies, (c) nonpharmacologic, and (d) pharmacologic (65). Since CRF affects patients throughout the cancer continuum, the NCCN provides guidelines for three types of patients: (a) patients on active treatment, (b) patients on long-term follow-up, and (c) patients at the end of life (65).

General education about the nature and management of CRF provides reassurance and leads to earlier recognition and mitigation of its effects. General strategies, as opposed to causespecific interventions, are intended to minimize the impact and intensity of existing CRF after reversible causes have been addressed. Energy conservation strategies developed for cardiac and pulmonary patients are equally effective for patients with CRF (68). Beneficial interventions include strengthening and endurance programs, psychosocial interventions, nutritional management, and sleep optimization.

The prevalence of disrupted sleep among persons with cancer diagnoses makes it one of the most common and intuitively obvious factors in CRF (69). Many cognitive and behavioral strategies exist for promoting restorative night time sleep and minimizing daytime sleepiness (69). Addressing the underlying anxiety and depression often improves sleep as does increasing physical activity. Sleep can also be addressed with judicious use of pharmacological agents.

TABLE 44.5 Interventions for Fatigue

Strategy	Examples
Restore energy balance	Correct anemia
	Nutritional and vitamin supplementation
	Correct endocrine dysfunction (thyroid)
Medications	Stimulants (methylphenidate, D-amphetamine)
	Analgesics
	Antidepressants (bupropion, SSRIs, TCAs)
	Regulate sleep/wake
	Glucocorticoids
	Investigational—cytokine-targeted therapy (including NSAIDs)
Exercise	Aerobic exercise is best-studied form.
	Individualized
	Attention to precautions
	Cachectic patients may not tolerate.
Energy conservation	Education
	Adaptive equipment
Psychologic/coping	Recreational activities
	Relaxation techniques
	Support groups
	Spiritual supports, participation
SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic antidepressant agents; NSAIDs, nonsteroidal anti-inflammatory drugs.

Anemia is a common cause of CRF that responds to medical management. Blood transfusions may be useful for more rapid correction of profound anemia, particularly after tumor resection or myeloablative chemotherapy. Several large scale studies demonstrated the utility of erythropoietin for both increasing hemoglobin and reducing fatigue scores in patients with anemia associated with chemotherapy (70). However, the use of erythropoietin in cancer patients was reassessed in light of data concerning increased risk of thrombotic events in dialysis patients receiving erythropoietin (71). Some studies have also shown a decreased survival rate in cancer patients treated with erythropoietin that was not associated with thrombotic events (72). Recent data suggest that target hemoglobin levels of 12 g/dL can confer symptomatic benefit without increasing risk (65).

In addition to medical management of factors contributing to CRF, physicians may use a range of prescription medications to treat CRF directly. Psychostimulants such as methylphenidate and modafinil have been used to treat CRF but their efficacy has not been definitively established (73, 74, 75, 76). Corticosteroids are used for numerous purposes in cancer patients and may modulate CRF (77).

Numerous studies have explored the safety and efficacy of exercise interventions for patients with CRF. A meta-analysis
identified the greatest statistically significant impact in studies limited to a specific disease population such as breast cancer with less effect demonstrated when patients with heterogeneous diagnoses were recruited (78). Even when exercise interventions do not directly reduce fatigue scores, they nonetheless play an important role in the management of CRF by stemming the cycle of deconditioning that occurs as patients with CRF reduce their activity.

Cancer patients should be screened by a physician prior to the prescription of a moderate intensity exercise program. Clinical literature supports the use of therapeutic exercise for CRF in patients with stage I to III disease but fewer guidelines exist for patients with advanced disease, particularly bony metastases. Walking has been the most frequently used mode of exercise in studies assessing the effect of physical activity on CRF although a recent investigation studied the effect of higher intensity training utilizing cycle ergometry (79). None of the studies reviewed reported any serious adverse events related to the prescribed exercise program. Strength training has been less well studied than aerobic exercise in oncology populations. One randomized prospective study of 155 men with prostate cancer receiving androgen deprivation therapy demonstrated significant reduction in fatigue as measured with the FACT-F scale after participation in a 12-week resistance exercise program (80).

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