Cardiopulmonary Rehabilitation and Cancer Rehabilitation. 3. Cancer Rehabilitation

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CARDIOPULMONARY REHABILITATION AND CANCER REHABILITATION

Cardiopulmonary Rehabilitation and Cancer Rehabilitation. 3. Cancer Rehabilitation Michael D. Stubblefield, MD, Christian M. Custodio, MD, Deborah Julie Franklin, PhD, MD ABSTRACT. Stubblefield MD, Custodio CM, Franklin DJ. Cardiopulmonary rehabilitation and cancer rehabilitation. 3. Cancer rehabilitation. Arch Phys Med Rehabil 2006; 87(3 Suppl 1):S65-71. This self-directed learning module highlights the treatment and rehabilitation of patients with cancer. It is part of the study guide on cardiac, pulmonary, and cancer rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article reviews medical and rehabilitation issues in patients with various types of cancer. Cases were selected to allow discussion of problems seen in both younger and older patient populations. Identification of common sequelae of cancer and cancer treatments, associated rehabilitation challenges, and appropriate interventions are included. Overall Article Objective: To summarize the medical and rehabilitation issues in patients with various types of cancer. Key Words: Chemotherapy; Electrodiagnosis; Neoplasms; Physical therapy techniques; Radiation; Rehabilitation. © 2006 by the American Academy of Physical Medicine and Rehabilitation 3.1

Clinical Activity: To develop a rehabilitation plan for a 15-year-old boy who has high-grade osteosarcoma of the distal left femur initially treated with high-dose methotrexate, doxorubicin, and cisplatin followed by limb-sparing total knee and distal femur replacements. He will be receiving 4 additional cycles of postoperative chemotherapy.

UCCESSFUL REHABILITATION STARTS early in the treatment process. At the time of diagnosis and during the S initiation of treatment, the boy and accompanying adults have a great deal of information to assimilate, and they will be making multiple visits to the oncologist, surgeon, and chemotherapy infusion center. Contemporary treatment protocols for lower-extremity osteosarcoma offer a 65% chance of eventfree survival at 5 years.1 Postoperatively the patient will require intensive physical therapy to achieve gait normalization and restore function of the quadriceps mechanism following en bloc resection of the tumor. Surgical preservation of the vastus medialis and training of compensatory muscles are essential to effective gait restoration.2 Rehabilitation programs instituted after limb-sparing surgery differ from protocols for total knee

From the Rehabilitation Medicine Service, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY (Stubblefield, Custodio); and Department of Physical Medicine and Rehabilitation, Magee Rehabilitation Hospital, Philadelphia, PA (Franklin). No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated. Reprint requests to Michael D. Stubblefield, MD, Rehabilitation Medicine Service, Dept of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, e-mail: [email protected]. 0003-9993/06/8703S-10546$32.00/0 doi:10.1016/j.apmr.2005.12.009

arthroplasty for patients with degenerative joint disease. Initial healing may be slower because of the extent of the surgery. Chemotherapy and radiation can delay wound healing. The risk of deep vein thrombosis is high and should be addressed in collaboration with the surgeon and oncologist. The rates of unintentional nerve injury or planned nerve sacrifice are higher because of the need to achieve adequate tumor-free surgical margins. The extent of motor and sensory injuries should be documented by clinical examination. Electrodiagnostic testing performed immediately after surgery and then again after 2 weeks can clarify prognosis and guide treatment such as bracing. Appropriate orthotic prescription and protective measures should be pursued when the patient has new motor or sensory deficits. In children and young adults, cancer treatment has a specific impact on educational achievement and emotional development. The involvement of social workers, psychotherapists, teachers, and family is imperative throughout the treatment process. Athletic adolescents may not be able to return to their previous performance levels and thus may experience loss of self-esteem as well as an important social and physical outlet. Age-appropriate peer support groups are often helpful at this time and may be more easily accessed if the child or teenager is treated at a pediatric facility rather than through an adult oncology center. Although the primary goal is the successful reintegration of an ambulatory, disease-free teenager into his peer group, physiatrists should anticipate the need for long-term musculoskeletal follow-up and the possibility of recurrence. Physiatrists continue to play an important role in cases of disease recurrence, because they treat the pain and dysfunction that occurs with disease progression. Modified rehabilitation goals can provide a hopeful focus for patients and their families while nonetheless recognizing the reality of disease progression. Consistent communication between members of the oncology or palliative care teams and rehabilitation services is essential during periods when the patient’s clinical status, prognosis, and treatment strategies are changing. 3.2

Clinical Activity: To evaluate a 65-year-old man who has prostate cancer metastatic to the lumbar spine, previously treated with lumbar spine radiation and who now presents with increased lateral hip pain.

Bone metastases are common in patients with prostate cancer. They occur in up to 70% of patients with advanced disease. Bone metastases are characterized as osteolytic, osteoblastic, or a mixture of both. Most prostate cancer metastases are osteoblastic. Osteoblastic lesions tend to be more structurally sound and less prone to fracture than osteolytic lesions. Bone metastases may cause severe pain, pathologic fractures, hypercalcemia, or compression of the spinal cord, cauda equina, nerve roots, plexus, or peripheral nerves.3 Patients with cancer may experience pain from the malignancy, its treatment, or unrelated disorders such as degenerative spinal disease. Multifactorial causes of pain are common in patients with cancer. Pain is generally classified as somatic, Arch Phys Med Rehabil Vol 87, Suppl 1, March 2006

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Fig 1. (A) Hip radiograph, (B) bone scan, and (C) lumbar spine magnetic resonance image from a patient with metastatic prostate cancer and left lateral hip pain. The left hip, although involved by tumor, was not the source of pain. External beam radiotherapy to the left hip provided no improvement. The patient’s lateral hip pain was attributable to a left L3 nerve root compression from the tumor (see arrow).

visceral, or neuropathic. Correct identification of the causes of a patient’s pain and its types (ie, somatic vs neuropathic) is instrumental in initiating proper therapy and minimizing side effects of treatment.4 The approach to the diagnosis of hip pain in a patient with metastatic prostate and other cancers can be particularly challenging. A careful history and physical examination may yield as much clinically useful information about the cause and type of pain as imaging and other diagnostic studies. The history should include details of pain location, quality, severity, timing, setting, aggravating and relieving factors, and associated symptoms. As a general rule, isolated lateral hip pain rarely, if ever, originates from the hip joint. Patients with hip pathology, regardless of etiology, usually experience a component of groin pain. Lateral hip pain may be caused by trochanteric bursitis or referred radicular pain. Although any lumbosacral radiculopathy may refer pain to the lateral hip, the upper lumbar nerve roots are most often implicated. Other relevant components of the history include a description of pain evoked by pressure on the lateral hip (suggestive of trochanteric bursitis), pain radiating to the groin that is worse with weight bearing or ambulation (a symptom of intrinsic hip joint pathology such as arthritis or metastasis), or pain worsened with spinal flexion, extension, or lateral bending (an indicator of neuroforaminal or central spinal stenosis). Pain described in neuropathic terms such as burning, tingling, or lancinating or associated with numbness and paresthesias generally indicates a neurogenic origin. Pain described as dull, aching, or gnawing may be more consistent with a somatic or musculoskeletal origin. Associated weakness may be neurogenic or from central inhibition because of pain. The musculoskeletal examination of patients with lateral hip pain should include palpation of the trochanteric bursa to illicit tenderness (as in trochanteric bursitis) and the FABER (Flexion, ABduction, External Rotation) maneuver. The FABER maneuver tests the intrinsic pathology of the hip joint and Arch Phys Med Rehabil Vol 87, Suppl 1, March 2006

capsule, and the result is considered positive if it reproduces groin pain.5 The neurologic evaluation of patients with lateral hip pain should include assessment of gait, strength, reflexes (including of the medial hamstrings and L5 reflex), and sensation (light touch, pin prick, proprioception). The radiologic evaluation of patients with lateral hip pain is important but may be misleading. Patients with obvious radiographically proven arthritis in 1 structure, such as the hip, are likely to have arthritis in other locations such as the spine. Moreover, patients with metastatic cancer are also likely to have lesions in both the hip and spine that confound diagnosing the primary source of pain (fig 1). It is important in both benign and malignant pathology to accurately determine the source of lateral hip pain, because treatment varies and outcomes may be adversely affected if an inappropriate treatment is instituted.6 Electrodiagnostic testing is often helpful in the evaluation of patients with lateral hip pain. It may show whether a lumbosacral radiculopathy is present, which level or levels are affected, how severe it is, and if it is acute, chronic, or both. It is important to perform needle electromyography on muscles innervated by upper-lumbar nerve roots, including the upperlumbar paraspinal muscles, because an upper-lumbar radiculopathy can easily be missed. Superficial peroneal and sural sensory nerve testing should be performed, because they help differentiate lumbar radiculopathy from plexopathy or neuropathy. 3.3

Clinical Activity: To identify the diagnostic and therapeutic challenges encountered during the assessment of a 65-year-old man who was treated with mantle field radiation 19 years ago and now presents with upper-extremity pain and weakness.

Mantle field radiation therapy, involving all lymph node groups from the angle of the jaw to the diaphragm, was routinely used, until recently, in the treatment of Hodgkin’s

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disease. Radiation-related nervous system injury can affect any level of the nervous system and can be classified as acute, subacute, or late. Acute complications occur during the course of treatment. Subacute complications occur 1 to 6 months after radiation. Late complications occur more than 6 months after radiation.7 Muscle atrophy in the neck and shoulder girdle is a common late finding after mantle field radiation therapy and indicates either a neuropathic or myopathic etiology. Radiation-induced brachial plexopathy with or without cervical root involvement usually begins with paresthesias and dysesthesias and is followed by progressive weakness. Neuropathic pain is unusual, but secondary musculoskeletal disorders related to weakness can occur. The brachial plexus, cervical nerve roots, and accessory cranial nerve can be affected by radiation injury. The presence of myokymic discharges on electromyography is highly suggestive of a radiation-induced etiology but does not exclude the possibility of tumor infiltration.8 Magnetic resonance imaging (MRI) should be performed on all patients to identify radiation-induced peripheral nerve tumors such as malignant peripheral nerve sheath tumors, malignant schwannomas, and neurofibrosarcomas. The myopathy associated with radiation-induced fibrosis is characterized by the pathologic finding of nemaline rods. This myopathy is a newly recognized late complication of mantle field radiation therapy and may contribute to the dropped-head syndrome.9 Electromyographic findings include decreased insertional activity and myopathic motor unit potentials in affected muscles. The usual kyphotic posture with associated cervical hyperlordosis can make the patient prone to secondary musculoskeletal disorders such as cervical facet arthropathy, painful cervical paraspinal spasms, myofascial pain, or shoulder impingement syndromes. Treatment is usually conservative with the goal of reducing pain, preventing further loss of function, and restoring function if possible. Physical therapy can improve posture and range of motion (ROM), decrease spasms, and increase strength. Pharmacologic pain management and therapeutic interventions such as trigger point and subacromial injections should be considered. Some evidence suggests a role for pentoxifylline in improving ROM.10 3.4

Clinical Activity: To design a diagnostic and therapeutic plan for a 75-year-old woman who was treated for breast cancer with surgery, chemotherapy, and radiation therapy 10 years ago and who now develops arm swelling and pain.

The incidence of postmastectomy lymphedema varies depending on the definition of lymphedema, but it has been reported to be as high as 80%.11 Risk is associated with axillary node dissection or radiation therapy alone, but it increases dramatically when patients undergo both treatments. It is estimated that 400,000 breast cancer survivors are currently living with lymphedema.12 Lymphedema can occur months to years posttreatment and onset is unpredictable. Any patient with new-onset limb pain and swelling must be evaluated for causes of swelling and pain other than lymphedema. Tumor recurrence should be excluded by MRI. An upperextremity ultrasound should be performed to detect the presence of a deep venous thrombosis (DVT). Cellulitis is diagnosed clinically and usually responds to oral antibiotics that have broad gram-positive coverage. Traumatic or pathologic humeral fractures can be evaluated using plain films, bone scans, or MRI. Acute infection, thrombosis, and fractures are all relative contraindications for complete decongestive

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therapy. Recurrent tumor is not a contraindication for this therapy, and it can be performed concomitantly with palliative chemotherapy or radiation therapy. Lymphedema can cause significant morbidity including reduced joint ROM, deconditioning, ongoing risk of DVT, infection, and cosmetic and psychologic impairments. Pharmacologic studies using benzopyrones and flavonoids in lymphedema management report conflicting results on the efficacy and hepatotoxicity of these agents.13 These medicines are currently not available for use in the United States. Virusmediated gene therapy using a mouse model that simulates congenital lymphedema shows the potential to develop new functional lymphatic vessels in affected limbs. The mainstay of lymphedema treatment is complete decongestive therapy, which consists of manual lymphatic drainage, graded compression using low-stretch bandages, exercise, and skin care. The goals of treatment are to provide education, reduce and prevent further swelling, prevent infection, and help patients cope with the psychologic sequelae of lymphedema.14 Once limb volume has stabilized, chronic lifetime maintenance using self-massage, self-bandaging, and graded compression garments is required. Multiple guidelines exist regarding avoidance of possible lymphedema triggers such as airline travel and strenuous exercise. These guidelines are often confusing, are not evidence based, and may negatively affect a patient’s overall quality of life. Reasonable precautions and allowing patients to make educated choices about lifestyle changes are recommended. 3.5

Clinical Activity: To differentiate the causes of diffuse pain, depression, and anxiety in a 36-year-old woman with previously treated breast cancer who now has an isolated L4 metastasis.

Not all pain in patients with cancer, even those with metastatic disease, is related to the primary oncology diagnosis or its treatment. Bone marrow is insensitive to pain and a metastasis that is confined to the marrow is usually painless (fig 2). A bone metastasis must breach the bony cortex to involve the periosteum, paravertebral soft tissues, or other pain-sensitive structures such as nerve roots before it is symptomatic.15 Other causes of pain common to both the general public and the cancer population should be considered. A careful clinical evaluation that includes a detailed history and physical examination are instrumental in determining the etiology of pain. Congruence between the patient’s history, physical examination, and diagnostic testing should be sought. When congruence is not present and all likely diagnoses have been excluded (appendix 1), chronic pain disorders, including the fibromyalgia syndrome, should be considered.16 Depression commonly affects about 6% of the general population and can therefore be expected to be present in at least 6% of patients with cancer. A premorbid affective disorder increases the risk that affective symptoms will manifest during the course of cancer. At least 25% of patients hospitalized with cancer will meet criteria for major depression or adjustment disorder with depressed mood.17 This increased risk for depression and anxiety may contribute to subjective worsening of all pain symptoms. The importance of diagnostic accuracy cannot be overstated. An incorrect diagnosis that pain is “cancer related” may prompt initiation of therapy with opioids when tricyclic antidepressants, gabapentin, cognitive-behavioral therapy, and aerobic exercise may be appropriate and effective. Arch Phys Med Rehabil Vol 87, Suppl 1, March 2006

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Fig 2. (A) An isolated L3 breast cancer metastasis in a patient with fibromyalgia. (B) The lesion is confined to the bone marrow and is unlikely to be symptomatic. Abbreviations: Ant, anterior; L, left; Post, posterior; R, right.

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Educational Activity: To describe the resources available to a physiatrist managing patients with complex functional deficits from cancer and its treatments.

The consolidation of cancer treatment at cancer centers has increased patients’ access to the many resources and providers needed for successful oncology rehabilitation. The high volume of patients treated at cancer centers creates rehabilitation team members who are comfortable and experienced with the care of cancer patients. Shared or adjacent treatment space facilitates interdisciplinary collaboration. The optimal cancer rehabilitation team includes all of the patient’s treating physicians, nursing and therapy providers, and a network of prosthetists, orthotists, and supportive services including home care agencies, nutritional counselors, social workers, hospice liaisons, support groups, and educational outreach programs.18 Close collaboration with palliative care physicians and advanced-practice nurses involved in pain and symptom management facilitates the rehabilitation management of this complex patient population.19 Psychologists who work with patients with cancer diagnoses provide supportive therapy but can also identify and treat some of the cognitive dysfunction that occurs in this population. Access to shared documentation such as computerized office notes and test results helps team members coordinate care with patients’ current medical and rehabilitation status. To encourage clinical communication, team members should be encouraged to attend or initiate team-wide conferences to discuss specific patients. Many institutions have tumor-specific clinical Arch Phys Med Rehabil Vol 87, Suppl 1, March 2006

team conferences that meet regularly. Palliative care services may also hold interdisciplinary rounds. These can provide an opportunity for better integrating the rehabilitation services available to cancer patients. Caring for oncology patients can be emotionally taxing, and team meetings can help dissipate some of the stress and sadness experienced by practitioners. Team members should also be encouraged to develop a shared database for frequently used resources, from contractors specializing in creating accessible homes to massage therapists. 3.7

Educational Activity: To discuss weight-bearing precautions in an 85-year-old man with colon cancer and a right proximal femoral metastasis.

Bone metastases occur in approximately 15% to 30% of patients with lung, colon, stomach, bladder, uterus, rectum, thyroid, or kidney carcinomas and in up to 70% of patients with breast or prostate cancer.3 The proximal femur is the most common appendicular site of bony metastases. Attempts to predict fracture risk in long bones based on radiographic assessment alone have been largely unsuccessful. Previous radiologic criteria based solely on tumor size and degree of cortical involvement apply to lytic osseous lesions in the subtrochanteric area of the femur only. Size, location, pain, and whether or not the lesion is lytic, blastic, or mixed are all factors that can help determine if prophylactic surgical fixation is warranted.20 It should be noted that in these earlier studies many patients who developed fracture did not receive further chemotherapy or radiation therapy. Metastatic lesions usually

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will progress to fracture if left untreated. Conversely, lesions can respond favorably both in size and symptom severity to palliative radiation therapy, chemotherapy, and bisphosphonates. Patients without fracture who have severe pain that is associated with functional activity and is not relieved with medical or radiation therapy should be referred for prophylactic surgical repair, provided each patient’s prognosis and underlying medical condition permit it.21 These patients should be non⫺weight bearing until surgically corrected. Patients responding to conservative management can bear weight as tolerated. Because of the risks of fracture, patients probably should avoid resistive exercises, passive or active-assisted ROM, and manual muscle testing of an involved limb until they are asymptomatic.22 When considering weight-bearing precautions in the lower extremity, it is important to evaluate for the presence of humeral and upper-extremity metastases that may preclude the use of assistive walking devices. Every attempt should be made to rehabilitate even those patients at high risk for pathologic fracture, to prevent complications associated with immobility.

may accelerate recovery by ensuring an adequate nutritional substrate. Neck dissection is often part of the initial surgical intervention and confers additional morbidity. A radical neck dissection removes the sternocleidomastoid, additional anterior neck muscles, the spinal accessory nerve (cranial nerve 11), the ansa hypoglossi, the superficial branches of the cervical plexus, and the internal jugular vein. Sacrifice of the spinal accessory nerve can create significant shoulder pathology, which leads to scapular depression, protraction, downward rotation with shortening of the pectoralis muscle, and possible glenohumeral subluxation. Twenty percent of patients, however, will have preserved trapezius function, presumably because of C3 to C4 innervation. Without appropriate exercise interventions, the remaining 80% are likely to develop adhesive capsulitis.23 A modified radical neck dissection can be performed. It will spare the spinal accessory nerve and sometimes the internal jugular vein or sternocleidomastoid muscle. Up to 50% of these patients will have spinal accessory neurapraxia at 3 months, with the number dropping to 8% at 12 months.24

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Clinical Activity: To design a comprehensive rehabilitation program for a patient with speech and swallowing deficits after surgical resection of a laryngeal cancer and radiation therapy.

Patients with laryngeal cancer risk developing communication, swallowing, and respiratory difficulties that influence both long-term survival and functional recovery. The extent of these difficulties is influenced by the oncology treatment, which may include radiation therapy, surgical procedures, and adjuvant chemotherapy. Other factors are the patient’s physiologic age and overall state of health. Treatment decisions are determined by the disease stage. Metastatic disease, for instance, may permit a voice-sparing surgical intervention, whereas more radical resection with the hope of definitive cure may be performed for local disease. Impaired communication may occur in patients who receive partial laryngectomy. Patients who undergo vertical hemilaryngectomies may experience vocal hoarseness but can usually return to oral intake 2 to 3 weeks after surgery. The risk of significant swallowing dysfunction is far more serious when supraglottic laryngectomies are performed, because these patients risk aspirating if the base of the tongue fails to meet the arytenoids, effectively closing off the reconstructed airway. Total laryngectomy removes all ability to produce a normal voice and requires immediate introduction of alternative communication aids for safety and psychologic well-being. The physician’s familiarity with available artificial larynxes and his/her close collaboration with knowledgeable speech-language pathologists is necessary if the patient’s ability to communicate is to be restored as rapidly as possible. An artificial larynx is usually introduced during the second postoperative week, with the initiation of esophageal voice therapy. Not all patients are able to achieve effective esophageal speech, although the option of a tracheoesophageal puncture has increased the number who will not have to rely on external devices. Concomitant radiation therapy creates additional speech and swallowing dysfunction, primarily through fibrosis of the residual larynx and pharynx. Reliably performed swallowing exercises may diminish these effects. Nutritional status is a very serious concern in patients with head and neck cancer. Treatment-induced dysphagia and comorbidities include depression, dyspnea in smokers, poor preillness nutritional habits, and alcoholism. Early gastrostomy

Clinical Activity: To justify the use of electrodiagnostic testing in a patient with multiple myeloma treated with chemotherapy who develops progressive paresthesias 1 year later.

Electrodiagnostic testing can be an extremely valuable diagnostic tool in the cancer population. A well-designed study can help clarify the etiology of symptoms, localize peripheral nervous system lesions, exclude competing diagnostic possibilities, predict neurologic prognosis, and assist in chemotherapeutic and radiotherapeutic decision making. The course of disease in many malignancies is replete with potential sources of damage to the central, peripheral, and/or autonomic nervous systems. Multiple myeloma, a common hematologic malignancy associated with monoclonal gammopathy, is a classic example.25 Multiple myeloma can compromise the peripheral nervous system at any level from the cauda equina to the small intraepidermal nerve fibers. The central and autonomic nervous systems may also be affected. Damage to the peripheral nervous system in multiple myeloma may result from direct compression of neural structures by tumor and rarely from paraneoplastic phenomena, amyloid deposition, and/or the effects of chemotherapies (ie, thalidomide, bortezomib). Electrodiagnostic testing in patients with multiple myeloma commonly demonstrates a distal symmetric axonal sensory or sensorimotor polyneuropathy. A demyelinating polyradiculoneuropathy resembling chronic inflammatory demyelinating polyradiculoneuropathy is also possible.26 A mononeuropathy multiplex pattern of neuropathy with conduction blocks at atypical sites may suggest amyloid deposition. Normal results from nerve conduction studies and electromyography in a patient with painful dysesthesias, diminished pain and temperature sensation, and normal reflexes and proprioception suggest small-fiber neuropathy, which may result from amyloid deposition.27 Both large- and small-fiber abnormalities may coexist. Radiculopathy from nerve root impingement attributable to a spinal compression fracture and central or neuroforaminal stenosis can mimic peripheral neuropathy clinically and can often be differentiated electrophysiologically. Arch Phys Med Rehabil Vol 87, Suppl 1, March 2006

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Clinical Activity: To assess the impact of wholebrain radiation on the cognitive functions of a 55year-old executive with a primary central nervous system lymphoma.

Primary central nervous system lymphoma is less common than metastatic involvement but presents similarly with headache, emesis, mental status changes, papilledema, or hemiparesis. Stereotactic biopsy is necessary for diagnosis but there is little role for extensive surgical resection, because the tumors have ill-defined margins and are often multifocal. For this reason, whole-brain radiation with doses as high as 5000cGy is an important component of treatment. More recently, systemic chemotherapy with high-dose methotrexate has been supplemented with intrathecal administration through a reservoir secured beneath the scalp. Radiation effects are conventionally divided into acute, subacute, and late. In theory, there should be little risk of acute injury using contemporary protocols, but coadministration of methotrexate or anticonvulsants has resulted in acute encephalopathies or toxic epidermal necrolysis. Because they are associated with a reduction in mass effect and concomitant symptom abatement, corticosteroids are often administered during radiation treatment. Treating physiatrists and therapists should be aware of the associated side effects, which include steroid psychosis, gastrointestinal bleeding, avascular necrosis, and proximal myopathy. The literature on inpatient rehabilitation for patients with intracranial neoplasms has shown a higher-than-average rate of medical transfers, but it has also shown meaningful gains in FIM instrument scores.28 More important, administering radiotherapy treatment during rehabilitation did not produce a statistically significant decrease in FIM scores.29 Subacute effects of whole-brain radiation may present as neurologic deterioration, with somnolence, headaches, and worsening of focal symptoms that may resolve over the following months. Comprehensive brain imaging and clinical and laboratory evaluations are needed to distinguish this deterioration from tumor recurrence or infection. The late effects of radiation, specifically radiation necrosis and cerebral atrophy, may begin to emerge after 4 to 6 months. Their mechanisms are poorly understood. Necrosis is often difficult to distinguish from recurrence and the patient may require evaluation by positron emission tomography. Diminished cognitive function after whole-brain radiation is multifactorial and may influence return to home and work. Comprehensive neuropsychologic assessment may be useful to identify specific areas of impairment. Depression and anxiety must be treated but care should be used when prescribing medications that may further affect cognition. Data collected from patients with gliomas have documented improvements in function after treatment with methylphenidate.30 3.11

Clinical Activity: To justify cancer screening in the evaluation of a 67-year-old woman who presents with weakness, falls, and fatigue.

Weakness, falls, and fatigue are common reasons for physiatric referral and can be seen in several neuromuscular processes, such as neuromuscular junction disorders, myopathies, and motoneuron diseases. All these disorders have been described as paraneoplastic syndromes.31 Although they are rare, it is important to recognize these syndromes. They often precede the diagnosis of cancer, and early recognition may increase survival. Treating the underlying malignancy, if present, usually results in improvement of symptoms. Arch Phys Med Rehabil Vol 87, Suppl 1, March 2006

Electrodiagnostic evaluation is an invaluable aid to guide further investigation. Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic disorder of neuromuscular transmission characterized clinically by proximal weakness, areflexia, and autonomic dysfunction. LEMS is associated with cancer in 50% to 70% of patients, with small-cell lung cancer being the most commonly implicated tumor.32 A history of smoking and weight loss in this clinical context should raise suspicion. Other malignancies, including lymphoma, breast, renal cell, ovarian, and pancreatic carcinoma have also been associated with LEMS. Electrodiagnostic studies show reduced compound muscle action potential (CMAP) amplitudes with a decremental response after low-frequency repetitive stimulation. After brief isometric exercise, facilitation occurs and CMAP amplitudes show at least a 100% increase. This finding is essentially pathognomonic for LEMS. Immunologic studies show antibodies against voltage-gated calcium channels. Findings of a symmetric, proximal myopathy on clinical examination and electrodiagnostic testing can likewise lead to the discovery of an undiagnosed cancer. Although their classification as paraneoplastic syndromes is controversial, polymyositis and especially dermatomyositis are associated with an increased risk of malignancy compared with the general population.33 Paraneoplastic necrotizing myopathy has been described as a distinct syndrome.34 Associated malignancies are usually identified within 2 years of presentation and include lung, colon, breast, and ovarian carcinoma. Serum creatinine kinase levels and erythrocyte sedimentation rates are typically elevated in these myopathies. Electromyography shows fibrillation potentials and rapid recruitment of small polyphasic motor unit potentials in proximal muscles. Muscle biopsy confirms the diagnosis. With regard to motoneuron disease syndromes, anti-Hu⫺ associated paraneoplastic encephalomyelitis/sensory neuronopathy has a strong link with small-cell lung cancer. Subacute motor neuronopathy and primary lateral sclerosis have been associated with lymphoma and breast cancer, respectively. There is no known association between cancer and classic amyotrophic lateral sclerosis.35 APPENDIX 1: DISORDERS ASSOCIATED WITH DIFFUSE PAIN Medication-related disorders Statins Antivirals Taxanes Polymyalgia rheumatica Hepatitis C Sleep apnea Parvovirus infection Cervical stenosis Systemic lupus erythematosus Rheumatoid arthritis Endocrine disorders Addison’s disease Cushing’s disease Hyperparathyroidism Hypothyroidism Lyme disease Eosinophilia-myalgia syndrome References 1. Goorin AM, Schwartzentruber DJ, Devidas M, et al. Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651. J Clin Oncol 2003;21:1574-80.

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2. Benedetti MG, Catani F, Donati D, Simoncini L, Giannini S. Muscle performance about the knee joint in patients who had distal femoral replacement after resection of a bone tumor. J Bone Joint Surg Am 2000;82:1619-25. *3. Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655-64. *4. Cheville AL. Pain management in cancer rehabilitation. Arch Phys Med Rehabil 2001;82(3 Suppl 1):S84-7. 5. Hoppenfeld S. Physical examination of the spine and extremities. New York: Appleton-Century-Crofts; 1976. p 262. 6. Bozic KJ, Rubash HE. The painful total hip replacement. Clin Orthop Relat Res 2004;Mar(420):18-25. 7. Cross NE, Glantz MJ. Neurologic complications of radiation therapy. Neurol Clin 2003;21:249-77. 8. Gillis TA, Garden FH. Principles of cancer rehabilitation. In: Braddom RL, editor. Physical medicine and rehabilitation. 2nd ed. Philadelphia: WB Saunders; 2000. p 1305-20. 9. Portlock CS, Boland P, Hays AP, Antonescu CR, Rosenblum MK. Nemaline myopathy: a possible late complication of Hodgkin’s disease therapy. Hum Pathol 2003;34:816-8. 10. Okunieff P, Augustine E, Hicks JE, et al. Pentoxifylline in the treatment of radiation-induced fibrosis. J Clin Oncol 2004;22: 2207-13. *11. Gillis TA, Cheville AL, Worsowicz GM. Cardiopulmonary rehabilitation and cancer rehabilitation. 4. Oncologic rehabilitation. Arch Phys Med Rehabil 2001;82(3 Suppl 1):S63-8. 12. Erickson VS, Pearson ML, Ganz PA, Adams J, Kahn KL. Arm edema in breast cancer patients. J Natl Cancer Inst 2001;93:96111. 13. Badger C, Preston N, Seers K, Mortimer P. Benzo-pyrones for reducing and controlling lymphoedema of the limbs. Cochrane Database Syst Rev 2004;(2):CD003140. *14. Cohen SR, Payne DK, Tunkel RS. Lymphedema: strategies for management. Cancer 2001;92(4 Suppl):980-7. *15. Posner JB. Neurologic complications of cancer. Philadelphia: FA Davis; 1995. p 111-42. 16. Clauw DJ. Fibromyalgia and diffuse pain syndromes. In: Klippel JH, editor. Primer on the rheumatic diseases. 12th ed. Atlanta: Arthritis Foundation; 2001. p 188-93. 17. Massie MJ, Holland JC. Depression and the cancer patient. J Clin Psychiatry 1990;51(Suppl):12-7. 18. Gaze MN, Wilson IM. Handbook of community cancer care. San Francisco: Greenwich Medical Media; 2003.

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Arch Phys Med Rehabil Vol 87, Suppl 1, March 2006