Acute Pain

Acute pain after surgery or radiation therapy can be successfully treated using conventional algorithms for acute postoperative pain.³ Nerves are frequently severed, compressed, or stretched during tumor resection, making it possible for neuropathic pain to be a major factor during the postoperative period. Neural compromise contributes significantly to postmastectomy and postthoracotomy pain syndromes. Adjuvant analgesics (e.g., gabapentin) should be initiated when a neurogenic contribution to the pain is suspected. As with all postoperative pain that impedes function, aggressive opioid-based and antiinflammatory analgesia should be considered. Acute pain control allows movement and limits immobility. This is particularly important in cancer patients who face the debilitating effects of chemotherapy or radiation therapy shortly after surgery.

To allow patients whose cancers eventually recur or progress to benefit from opioid rotation, opioid use should be confined to the “immediate-” and “sustained-” or “continuous-release” formulations of a single drug. The dose threshold for switching opioids because of lack of efficacy in patients with poor prognoses should be high. In this way, patients’ exposure can be restricted to a limited number of opioids, allowing them to benefit from opioid rotation in the late stages of disease.^112,166

Acute pain can also complicate the administration of chemotherapy, hormonal therapy, and irradiation. Most of the associated pain syndromes are transient but can produce intense discomfort that warrants aggressive analgesia. Acute pain syndromes associated with cancer therapy include paclitaxel-related arthralgias and myalgias,²¹⁷ bisphosphonate-related bone pain,¹⁰⁴ radiation mucositis,²¹¹ steroid pseudorheumatism (after withdrawal of corticosteroids),²¹⁶ intravesicular Bacillus Calmette Guerin (BCG–induced cystitis, hepatic artery infusion pain,¹²⁴ bone pain associated with colony-stimulating factor (CSF) and granulocyte macrophage CSF administration,²⁶⁶ and radiopharmaceutical-induced pain.

Chronic Pain

Chronic cancer-related pain can arise from visceral or neural structures but is most commonly associated with bone metastases.¹⁴⁵ Bone metastases occur in 60% to 84% of patients with solid tumors. Pain intensity does not correlate with the number, size, or location of bone metastases. Pain intensity also does not correlate with tumor type because 25% of patients with bone metastases report no pain.²¹⁰ Bone pain is particularly relevant to physiatrists because recruiting muscles that act on or loading affected structures can precipitate severe pain. Too often the excellent pain control achieved while patients remain in bed proves inadequate when they begin to transfer and ambulate. As mentioned above, bone pain responds well to local irradiation.²⁷⁷

Nonsteroidal Antiinflammatory Drugs for Bone Pain

Pharmacologic interventions reduce the intensity of bone pain. Prostaglandins have been implicated in pain associated with lytic bone metastases.¹⁶⁷ Blockade of prostaglandin synthesis is likely the principal mechanism by which nonsteroidal antiinflammatory drugs (NSAIDs) alleviate bone pain.²²¹ NSAIDs are considered first-line therapy for bone pain, and a trial is warranted unless contraindicated. Patients’ limited prognoses and the intensity of their suffering might eclipse cyclooxygenase (COX)-2 inhibitors’ worrisome cardiovascular risk profile. Although caution should be exercised, the significant potential benefits of COX-2 inhibitors outweigh their risks in many cancer patients with thrombocytopenia and/or gastropathy. Currently celecoxib is the only COX-2 inhibitor for oral use that remains available on the U.S. market.

COX nonselective inhibitors offer comparable or greater pain relief but a less desirable toxicity profile.²²³ Choline magnesium trisalicylate causes less inhibition of platelet aggregation than other COX nonselective inhibitors, but did not statistically outperform placebo when trialed in cancer-related bone pain.¹²¹ COX nonselective inhibitors with less desirable toxicity profiles have proven more effective. Several placebo-controlled, randomized trials found that ketoprofen reduced cancer pain to a greater extent than either codeine or morphine.²⁴⁹ Dosing NSAIDs for bone pain is no different from using them at antiinflammatory doses for pain of other etiologies.

Adjuvant for Bone Pain

Adjuvant and opioid analgesics can augment NSAID-related control of bone pain. A study found corticosteroids to be beneficial in relieving cancer pain,²⁴ and extensive anecdotal experience supports their use. The toxicity profile of corticosteroids includes edema, bone demineralization, immunosuppression, and myopathies. This mandates that they be used transiently and rapidly tapered, except for patients in whom sustained analgesic benefit justifies the associated toxicity risk.

Use of calcitonin for bone pain is discouraged because of the weak supportive evidence and rapid tachyphylaxis.^158,167 Evidence supporting the use of parenteral bisphosphonates in the management of bone pain is more robust.^54,167,267 Aminobisphosphonates appear to have greater effectiveness in reducing bone pain than nonaminobisphosphonates (such as clodronate), and are preferred for patients with high pain scores. Effective doses include 30 to 90 mg of intravenous pamidronate every 4 weeks, 4 mg of intravenous zoledronic acid every 3 weeks, and 1600 mg of oral clodronate daily. Opioids enhance analgesia afforded by NSAIDs and can reduce the doses required for adequate pain relief.²⁴²

Opioids

As previously mentioned, opioid-based pharmacotherapy is the current standard of care for the management of moderate to severe cancer pain, irrespective of its etiology.^{12,64,168,185} Opioid use should be restricted to pure μ-receptor agonists. Many μ-receptor agonists are commercially available in the United States. Those most commonly used in cancer pain management include morphine, hydromorphone, oxycodone, oxymorphone, fentanyl, and methadone. Opioid analgesic requirements change over time depending on whether a patient’s cancer progresses or responds to treatment. Ongoing dose adjustment maximizes pain control while reducing the incidence of side effects. The dominant paradigm for opioid administration has a well-established track record and has been reiterated by many experts in the field with few changes over the past.^72,115,145

Recognizing that most patients experience constant, baseline pain punctuated by potentially severe incident pain, combined use of immediate and sustained-or continuous-release opioid preparations is recommended. Providing patients with liberal access to an immediate-release opioid formulation (generally through use of a patient-controlled analgesia pump or enteral route) allows rapid estimation of initial dose requirements. Once use has stabilized, mean daily or hourly consumption can be calculated, and an oral or transdermal sustained-release preparation can be initiated. For enteral or transdermal routes, the mean daily opioid dose is divided by the dosing interval of the sustained-release preparation. Use of a patient-controlled analgesia pump accelerates the dose estimation process, and an appropriate starting basal infusion rate can be estimated after only 6 to 12 hours of monitored patient-initiated dosing. Initial rates and doses provide a crude estimate of true opioid requirements. The ongoing dose titration should be driven by patients’ use of supplemental immediate-release or “rescue” opioid doses. Rescue doses are typically 10% to 15% of the total daily dose.

Several practices can increase the likelihood of a successful opioid trial. First, anticipate side effects (particularly constipation and nausea), and address them proactively. Second, in the absence of dose-limiting side effects, resist the urge to switch or to add additional opioids when a single μ-receptor agonist initially fails to control pain. Current recommendations urge dosing a single agent to effect or side effect and each agent should be adequately trialed. Third, remain vigilant for opioid-induced hyperalgesia and alterations in patients’ capacity to absorb, metabolize, or eliminate opioids in the face of progressive cancer.

Opioid Conversion

Significant intraindividual variations in response to different opioids have long been recognized and are now presumed to result from genetically determined differences in pharmacokinetics and pharmacodynamics.^75,214 An alternative opioid should be considered when an “adequate” trial of a particular agent has failed to achieve an acceptable decrement in pain intensity or has engendered refractory and untenable side effects. An adequate opioid trial in the cancer patient can entail use of high doses (e.g., >1 g/day intravenous morphine sulfate). Opioid dose conversion requires calculation of the equianalgesic dose of the novel agent (Table 57-2) and reduction by 50% for incomplete cross-tolerance. Incomplete cross-tolerance describes the property of opioids to induce analgesic tolerance with sustained high-dose opioid exposure. Tolerance is usually considerably lower to a novel agent. For this reason, patients often experience greater sedation and needless side effects when exposed to 100% of the equianalgesic dose. Reductions of 50% provide better estimates of the minimal effective opioid dose. If patients are being converted from methadone, reductions of 80% to 90% of the equianalgesic dose have been recommended because of methadone’s long half-life.²⁷⁴ Opioid conversions are based on imperfect dose equivalencies. Providing patients with liberal access to rescue doses is critical during the conversion period to avoid precipitation of pain crises.

Invasive and Intraspinal Analgesic Approaches

As mentioned previously, permanent ablation of central afferent tracts becomes tenable in the context of advanced cancer, and has been used with considerable success.^{36,88,255,272} More discrete neural blockade can effectively reduce pain transmitted by one or several adjacent peripheral nerves. Intercostal, paravertebral, genitofemoral, ilioinguinal, and trigeminal nerve blocks can afford dramatic relief and reduce analgesic requirements. Nociceptive impulses of visceral origin can be blocked by ablation of sympathetic ganglia. Celiac plexus blockade affords excellent relief of visceral cancer pain.⁶⁷ Intraspinal opioid administration can reduce dose requirements and associated side effects.²⁴³ The potential benefits, however, must be weighed against the added cost, required maintenance, and risk of infection. Despite efforts to demonstrate cost savings through the use of implantable intrathecal opioid delivery systems,⁹⁵ these devices are not widely used.

Bone Metastases

Bone metastases are an important source of cancer-related impairment and a critical consideration in rehabilitation.⁴³ Surgical stabilization of acute or impending fractures produces impairments that warrant physiatric attention. Greater challenges arise when bone metastases produce severe, function-limiting pain or pose an uncertain fracture risk during therapeutic exercise. Bone metastases are highly prevalent because bone is the most common site of metastatic spread, and osseous lesions complicate the most frequently occurring cancers: lung, breast, and prostate. Thyroid cancer, lymphoma, renal cell carcinoma, myeloma, and melanoma also commonly spread to bone. Between 60% and 84% of patients with solid tumors will develop bone metastases.^146,210 Management of bony metastatic pain is discussed in the preceding section on chronic pain. Of greatest physiatric concern are lesions involving the spine and long bones. These structures are critical for weight-bearing and mobility, and are the most prone to fracture. Bone metastases are managed with medications, radiopharmaceuticals, orthoses, radiation therapy, and/or surgical stabilization. The choice of intervention(s) will depend on lesion location, degree of associated pain, presence or risk for fracture, radiation responsiveness, and related neurologic compromise. The overall clinical context (e.g., prognosis, severity of medical comorbidities, and operative risk) must also be taken into consideration. Most patients with unfractured bony lesions can be treated nonoperatively with systemic therapy and radiation.

Bisphosphonates are the primary medications used to manage bone metastases. Use of these agents relieves pain and mitigates the spread and progression of bone metastases. Bisphosphonates are generally delivered parenterally. Bisphosphonates can reduce the risk of vertebral fracture (odds ratio, 0.69), nonvertebral fracture (odds ratio, 0.65), and hypercalcemia (odds ratio, 0.54).²¹⁵ Bisphosphonates also significantly increase the time to first skeletal event after the initial detection of osseous metastases. Current evidence supports the empiric initiation of bisphosphonates in patients with bone metastases. Radiopharmaceuticals such as strontium-99 are predominantly used to manage severe, refractory pain associated with widely disseminated bone metastases. Drawbacks to radiopharmaceuticals include prolonged bone marrow suppression and potentially severe pain flares after administration.

Radiation delivered to bone metastasis offers an effective means of rapidly achieving local control of pain and tumor growth. Palliative radiation was formerly delivered in 10 fractions of 300 cGy. However, single fractions of 8 Gy also effectively alleviate pain.²⁷⁷ At present the protocols in use range between these extremes, with the choice of dose and schedule being heavily influenced by individual patient factors and institutional culture. Radiation can be delayed after surgical stabilization. It is an important adjunctive treatment, however, because it suppresses tumor growth in areas where surgical management could have distributed microscopic emboli.

Painful osteolytic lesions are predominantly responsible for pathologic fractures. The incidence of pathologic fracture among all cancer types is 8%.²²⁰ Breast carcinoma is responsible for roughly 53% of these. Other solid tumors associated with pathologic fractures are kidney, lung, thyroid cancer, and lymphoma. Sixty percent of all long bone fractures involve the femur, with 80% of these located in the proximal portion.²¹⁰

Management of osseous metastases that present a risk of fracture remains a source of clinical uncertainty. Precise quantification of fracture risk has been a persistent challenge in orthopedic oncology. Table 57-3 outlines Mirels’s proposed rating system for calculating fracture risk, whereby specific attributes are ascribed points.¹⁷⁰ Neither this nor any other approach based on retrospective review has been adequately validated in clinical practice.

Pathologic fractures are generally managed through well-established surgical algorithms. Four main goals direct surgical management of pathologic fractures: pain relief, preservation or restoration of function, skeletal stabilization, and local tumor control.⁹⁸ The general indications for surgery are life expectancy of more than 1 month with fracture of a weight-bearing bone, and more than 3 months for fracture of a non–weight-bearing bone. Internal fixation and prosthetic replacements with polymethylmethacrylate are the most effective ways of relieving pain and restoring function in patients with pathologic fractures.⁹⁸ These procedures allow immediate weight-bearing. Intraoperative resection removes residual tumor that would impede bony healing, but healing rates are low after pathologic fractures. One review of 123 patients reported a 35% incidence of fracture healing.⁷⁴

Fractures of the pelvis are generally treated conservatively, unless pain persists after radiation or they involve the acetabulum. In the latter case, patients are generally surgically reconstructed with screws or pins, and with an acetabular component. Vertebral fractures that are not associated with neurologic compromise are generally treated conservatively with radiation and bracing. Operative decompression and stabilization might be indicated for persistent pain refractory to aggressive analgesic therapy. Vertebroplasty can be considered for patients who are not at risk of tumor displacement into the spinal canal and associated myelopathy. Two large, recent randomized trials, however, have failed to demonstrate benefit in compression fractures related to osteoporosis.^26,123 These results have raised skepticism regarding vertebroplasty’s benefit in cancer.

Brain Tumors: Primary and Metastases

Brain metastases occur in 15% to 40% of cancer patients, accounting for 200,000 new cases per year in the United States.⁷⁸ They are the most common intracranial tumors.¹⁹³ The incidence has increased in recent years, presumably as a result of prolonged patient survival and better early detection of small tumors through superior imaging modalities.⁶⁶ Lung cancer is the most common primary source of brain metastases. As many as 64% of patients with stage IV lung cancer develop metastases.²²⁷ Breast cancer is the second most common source, followed by melanoma, with 2% to 25% and 4% to 20% of patients developing brain metastases, respectively.²²⁷ Brain metastases from colorectal cancers, genitourinary cancers, and sarcomas occur with considerably less frequency (1%).²⁶³ The distribution of metastases reflects cerebral blood flow, with 90% situated in the supratentorial region and 10% in the posterior fossa.²⁶³ Brain metastases are multiple in approximately 50% to 75% of cases.

Epidural Spinal Cord Compression

Malignant spinal cord compression (SCC) occurs in up to 5% of patients.⁴² In contrast to brain metastases, which involve the brain parenchyma, most symptomatic tumors compress the spinal cord or cauda equina from the epidural space.²⁰⁰ Epidural lesions generally arise from vertebral metastases and rarely breach the dura.⁹⁴ Invasion of the dural space accounts for only 5% of neoplastic SCC, and is due to either growth of tumor along the spinal roots or hematogenous spread to the cord.^44,209 The cancers that most commonly cause SCC are those that produce vertebral metastases (e.g., breast, lung, myeloma, and prostate).^17,276

Cancer Involving Cranial and Peripheral Nerves

Compromise of cranial and peripheral nerves is a common source of cancer-related pain and impairment. Cancer can affect nerves through local extension of primary tumors (e.g., brachial plexopathy associated with Pancoast tumors) or through metastatic spread.

Cranial Nerves

Cranial nerve palsies are caused by tumors that either originate near the base of the skull or metastasize there. Cancer can directly invade cranial nerves or exogenously compress them. Tumors often invade the neural foramina, which is seen in 15% to 35% of patients with nasopharyngeal carcinoma (a highly neurotrophic cancer).²⁶⁴ Bone metastases from lung, breast, and prostate cancers involving the base of the skull are also common sources of cranial nerve compromise.²⁰⁹ The incidence with which different cranial nerves are affected by cancer remains poorly quantified. One series of breast cancer patients reported a 13% incidence of cranial nerve dysfunction.⁹⁰ The trigeminal and facial nerves were most frequently involved.

Clinical presentations vary depending on the cranial nerve being compressed. Evaluation should include MRI, which is the diagnostic test of choice.²⁰⁶ If patients have a bone-avid tumor (e.g., lung, breast, or prostate), a CT scan should be considered because bone destruction is more easily observed on CT scan.¹⁸⁹ Positron emission tomography (PET) scanning, particularly in conjunction with CT scanning, can help to discretely localize tumor if extensive postradiation change or surgical alteration of the bony architecture has occurred. Acute management should include oral steroids, unless contraindicated, to preserve neurologic function until definitive treatment is delivered. Treatment generally involves chemotherapy and radiation.²⁰²

Spinal Roots

Malignant radiculopathies arise through direct hematogenous spread to the nerve roots or dorsal root ganglia, or more commonly by invasion from the paravertebral space. When the latter occurs, tumor can grow longitudinally in the paravertebral space and concurrently invade multiple foramina to produce a polyradiculopathy.²⁰² Most cancer-related radiculopathies initially produce dysesthetic, aching, or burning pain in the affected dermatome, which can be associated with lancinations. Sympathetic hyperactivity or hypoactivity can be present.⁵⁰ Involvement of the lower cervical or upper thoracic roots can produce Horner syndrome. In patients with a history of cancer, a new case of Horner syndrome should be attributed to malignancy until proven otherwise. Patients can complain of muscle cramps in affected myotomes.²⁴⁴

Nerve Plexuses

The brachial and lumbosacral plexi are commonly compressed or invaded by tumor. The frequency of neoplastic brachial plexopathy is 0.43%, and lumbosacral plexopathy 0.71%, based on retrospective case series.^117,132 The most common sources of brachial plexopathy are tumors at the lung apex and regional spread of breast cancer.¹³² Because cancer generally grows superiorly to invade the lower brachial plexus, the inferior trunk and medial cord are most commonly involved. Occasionally head and neck neoplasms grow inferiorly to invade the upper trunk.¹¹⁶

Pain in the shoulder region and proximal arm occurs in 89% of patients with malignant brachial plexopathy and is the most common presenting symptom.¹³³ The presence of pain helps to distinguish malignant from radiation-induced plexopathy. Only 18% of patients with radiation-induced plexopathy develop pain.¹³³ Radiation plexopathies also differ in their propensity to cause progressive weakness in the C5–C6 myotomes as opposed to the lower cervical levels.¹³³ Horner syndrome occurs in 23% of cancer patients with malignant brachial plexopathies.¹¹⁶ The presence of Horner syndrome suggests potential neuroforaminal encroachment and SCC. Numbness and paresthesias associated with malignant plexopathies typically are perceived in the C8 dermatome, especially digits 4 and 5.²⁰² Loss of hand dexterity and power can be the initial motor complaint. Weakness subsequently extends proximally to involve the finger flexors, wrist extensors and flexors, and elbow extensors.²⁰²

Malignancies responsible for lumbosacral plexopathies include colorectal carcinomas; retroperitoneal sarcomas; or metastatic tumors from breast, lymphoma, uterus, cervix, bladder, melanoma, or prostate.¹¹⁷ When primary intrapelvic neoplasms are not responsible, the lumbosacral plexus is generally invaded from lymphatic and osseous metastases.¹¹⁶ Sacral plexopathies are more common than those in the lumbar region. Lumbar and sacral plexopathies can also occur concurrently.²⁰² Lumbosacral plexopathies are bilateral in 25% of patients, particularly when the sacral plexus is more extensively involved.^116,202 Incontinence and impotence strongly suggest bilateral involvement.¹¹⁷ Back, buttock, and/or leg pain is present in 98% of patients with malignant lumbosacral plexopathies. Among the 60% of patients who eventually develop neurologic deficits, 86% have leg weakness and 73% sensory loss.¹¹⁶ Positive straight leg raise is present in more than 50% of patients.¹¹⁷ As many as 33% of patients complain of a “hot dry foot” resulting from involvement of sympathetic components of the plexus.⁵⁰

Peripheral Nerves

Peripheral nerves are affected most often by cancer when extension of a bone metastasis produces a mononeuropathy.²¹³ Rare polyneuropathy or mononeuritis multiplex resulting from myeloma, lymphoma, or leukemia has been reported.^118,162 More commonly, nerves are compressed where they pass directly over an involved bone or through a bony canal.²¹³ Common sites of nerve compression include the radial nerve at the humerus, obturator nerve at the obturator canal, ulnar nerve at the elbow and axilla, sciatic nerve in the pelvis, intercostal nerves, and peroneal nerve at the fibular head. Pain generally precedes motor and sensory loss.²⁰²

Paraneoplastic Syndromes

Paraneoplastic syndromes are pertinent to rehabilitation because they produce refractory neurologic deficits and severe disability.⁵⁸ The incidence of paraneoplastic neurologic disorders (PNDs) is low, occurring in less than 1% of all cancer patients.¹⁰⁶ PNDs can affect any level of the nervous system. Classic PNDs are listed in Table 57-4. These syndromes are produced when antibodies are made against tumors that express nervous system proteins. Discrete or multifocal neural degeneration produces diverse symptoms and deficits. Most PNDs are triggered during the early stages of cancer, when primary tumors and metastases might be undetectable by conventional imaging techniques. The emergence of a PND in a patient with known cancer should trigger workup for recurrent or progressive disease. PNDs are characterized by symptoms that develop and progress rapidly in days to weeks, and then stabilize. Spontaneous improvement is rare. Diagnostic workup can include serum and cerebrospinal fluid studies, brain MRI, and PET.^5,47 Screening patients’ serum or cerebrospinal fluid for antineuronal antibodies known to be associated with particular cancers can direct the search for an occult malignancy. Timely diagnosis and treatment of the tumor offer the greatest chance of success in managing PNDs.^11,35 PNDs do not generally respond solely to immunotherapies, including intravenous immunoglobulin, corticosteroids, and immunosuppressants. However, these can be useful adjuvant treatments.

Rehabilitation of patients with PNDs is determined by the type, distribution, and severity of the associated neurologic deficits. Potential improvement with planned antineoplastic therapy should be taken into consideration. Supportive and preventive measures to protect the integrity of the skin, affected joints, and genitourinary symptoms are critical while awaiting stabilization of neurologic deficits. Communication, respiratory, and nutritional issues should be addressed in patients with bulbar involvement.

Skin Metastases

Dermal metastases occur in 5.3% of patients and are most common in breast cancer.¹³⁴ Skin metastases can be a source of pain and an entry point for infectious pathogens. Because the associated wounds seldom heal, chronic wound care is necessary and becomes an integral part of patients’ rehabilitation needs. Figure 57-1 shows a breast cancer patient with dermal metastases involving the breast and proximal arm. Dermal metastases often engender or aggravate lymphedema. Use of compression is limited only by patient tolerance. Malignant wounds should be managed with nonadherent, bacteriostatic, hyperabsorbent dressings (e.g., SilvaSorb or Aquacel Ag). Associated pain must be managed aggressively to minimize adverse functional consequences. Proactive range of motion (ROM) activities can prevent the formation of contractures in joints adjacent to malignant wounds, facilitating hygiene and autonomous self-care.

FIGURE 57-1 Skin metastases producing unhealing wounds in a breast cancer patient.

Cardiopulmonary Metastases

Lung, pleural, and pericardial metastases involving the heart and lungs can produce dramatic and abrupt reductions in patients’ stamina and functional status. Virtually all cancers have the potential to spread to the lungs and pleura. At autopsy, 25% to 30% of all cancer patients have lung metastases.⁴⁹ Pleural metastases occur in 12% of breast and 7% to 15% of lung cancers.^135,138 Metastases to the heart and pericardium are less common, although their functional impact can be similarly devastating. A series of 4769 autopsies revealed the presence of cardiac metastases in 8.4% of cancer patients.²³⁷ Melanoma, mesothelioma, lung tumors, and renal neoplasms had the highest prevalence of cardiac spread. The clinical diagnosis of heart or lung metastases can be generally made by CT scans. PET scans and plain radiographs can also be helpful, depending on the clinical context.

Treatment of lung, pleural, pericardial, or cardiac metastases varies considerably. The type and efficacy of anticancer treatment will depend on the primary tumor, number and location of metastases, previous antineoplastic therapies, overall medical condition of the patient, and degree of associated symptomatic distress. Surgical metastectomy has the potential to definitively eliminate disease in certain patients.²⁶⁰ Discrete metastases that are not resectable might be amenable to radiation therapy. Patients with extrathoracic metastases are commonly treated with systemic chemotherapy.

Malignant pleural effusions should be evacuated when patients become symptomatic. The associated dyspnea often arises from other causes as well, and reducing the effusion might fail to alleviate patients’ shortness of breath if the lung is trapped because of parenchymal or pleural disease. Reaccumulation of malignant effusions can be managed through intermittent thoracentesis or pleurodesis, or placement of an indwelling pleural catheter.³⁹ Chemical pleurodesis has an overall complete response rate of 64% when all sclerotic agents are considered.¹³⁸ Talc appears the most effective, with a complete response rate of 91%.

The functional relevance of heart and lung metastases stems from their deleterious effect on patients’ aerobic capacity. Small reductions in cardiopulmonary reserve can devastate patients who are deconditioned or have other impairments. For this reason, all potentially treatable causes should be definitively addressed. Supplemental oxygen should be initiated as soon as dyspnea becomes function-limiting. In this way, patients can remain independent and ambulatory. If tolerated, gradual, progressive aerobic conditioning will optimize peripheral conditioning, reducing the percentage of maximal volume of oxygen consumption (VO_2max) required for activities. Referral for outpatient aerobic training should be considered when cancer patients with cardiopulmonary disease are hospitalized for other problems (e.g., neutropenic fever). These patients are prone to rapid functional decline that usually proves permanent in the absence of structured therapy.

Combined Modality Therapy

The push toward organ preservation in primary cancer care has led to widespread use of combined modality therapy. Clinical trials have consistently shown that concurrent or sequential administration of radiation and chemotherapy reduces the extent of tissue resection required to achieve local cancer control, without compromising 5-year survival rates. The trend toward use of combined modality therapy is relevant to rehabilitation because most cancer patients receive some combination of chemotherapy, radiation therapy, and surgery contingent on the type and stage of cancer. This makes patients vulnerable to cumulative normal tissue toxicities associated with each modality.

Surgery-Related Impairments

Primary impairments resulting from surgery depend on the extent, location, and type of tumor. Normal tissue is inevitably affected by surgical efforts to achieve local control of cancer. The principal reasons for resecting normal tissue, with the associated risk of adverse long-term consequences, include accurate staging (e.g., sampling of lymph nodes, and visceral and parietal peritoneum), definitive eradication of tumor, assurance of local disease control (e.g., removal of lymph nodes that might harbor cancer cells), and harvest for reconstructive purposes.

Cancer surgery has the greatest physiatric relevance when certain tissue types are affected. These tissues include bone, nerve, muscle, lung parenchyma, and lymphatics. Normal postoperative healing is often compromised by the previous administration or coadministration of additional anticancer treatment(s) (e.g., radiation and chemotherapy).

The list of established surgical approaches to eradicate tumor is vast, and readers are referred to Surgical Oncology: Contemporary Principles and Practice for more precise and extensive procedure-specific discussions. Operations that commonly warrant the immediate, postoperative attention of a physical medicine specialist include neck dissection for oropharyngeal carcinomas (spinal accessory nerve palsy), limb salvage or amputation for osteosarcoma (impairments vary by site), resection of truncal or limb myosarcoma (weakness, gait dysfunction, biomechanical imbalance), and pneumonectomy or lobectomy for lung neoplasms (aerobic insufficiency). Procedures such as nephrectomy, colectomy, mastectomy, and oophorectomy can involve the resection of muscles, nerves, and/or vessels to achieve clean margins resulting in acute functional loss. Muscles can also be transposed for coverage of bony prominences or to substitute for resected muscles. Review of patients’ surgical reports is essential to accurately identify all potential sources of impairment.

Neurosurgical resection of central and peripheral nervous system malignancies mandates physiatric evaluation, irrespective of the presence of gross deficits, given the potentially devastating effects of subtle impairments and the high likelihood of future recurrence and progression.

Secondary Impairments

Secondary surgery-associated impairments often emerge well after the responsible operations and can present as familiar musculoskeletal problems (e.g., tendinopathies and arthropathies). Patients’ compensatory attempts to negotiate impairments during mobility and ADL performance can produce maladaptive movement patterns that might, in turn, engender secondary pain sources and impairments. A common example is myofascial dysfunction of the scapular retractors and middle trapezius and rhomboid muscles as a result of pectoralis major and minor tightness after mastectomy or chest wall radiation and breast implant insertion. Secondary impairments are fortunately readily reversible through timely and comprehensive physiatric evaluation and treatment.

Donor Site Morbidity

Donor site morbidity associated with surgical tissue harvest for reconstructive purposes produces significant impairments less often than might be anticipated. Muscle, skin, bone, and fat are used to achieve adequate coverage of surgical defects and to optimize cosmesis. Radial forearm and fibular flaps are commonly harvested to eliminate defects produced by mandibular resection. Both are typically well tolerated and seldom produce functional deficits. Impairments associated with the harvest of myocutaneous flaps vary by extent and site, and are no different in cancer than in other rehabilitation cohorts. Partial transposition of the pectoralis major muscle from its insertion on the humerus has been used to repair soft tissue defects involving the anterolateral neck. This procedure can destabilize the shoulder in the absence of therapeutic intervention.

By virtue of the high incidence of breast cancer, significant donor site morbidity is most prevalent with autogenous tissue transposition for breast reconstruction. Transverse rectus abdominis muscle (TRAM), gluteus maximus, and latissimus myocutaneous flaps are used, with the former being more common. With a relatively low complication rate (25.3%) and potentially excellent cosmesis (Figure 57-2), the TRAM flap procedure is an increasingly common choice, given the potential to create a natural-looking breast with normal ptosis and an inframammary fold. More patients are electing to undergo immediate breast reconstruction to reduce the risk associated with repeat operations and the psychologic distress engendered by mastectomy.

FIGURE 57-2 Excellent cosmesis achieved with bilateral transverse rectus abdominis flap breast reconstructions.

The TRAM procedure involves the transposition of muscle and adipose tissue to match preoperative breast appearance (Figure 57-3). Other advantages of the TRAM procedure include relatively hidden scars and a satisfactory donor site resulting in a flat abdomen.¹⁸⁸ The TRAM flap can be divided into the pedicled or free flap procedures. These procedures differ in that the pedicled, or conventional, procedure uses the epigastric vessels supplying the rectus muscle to perfuse the subumbilical fat. Subumbilical adipose tissue is tunneled under the abdominal skin to repair the defect created by mastectomy. The inferior end of the contralateral rectus abdominis muscle is tunneled with the fat (see Figure 57-3). In contrast, the free flap procedure involves the creation of anastomoses with vessels in the chest, such as the thoracodorsal or internal mammary arteries. Although the free flap procedure requires increased operative time, it is associated with decreased incidence of partial flap loss resulting from fat necrosis.⁹

FIGURE 57-3 The transverse rectus abdominis flap procedure uses the superior epigastric artery to supply blood to the subumbilical fat, which is used to reconstruct the mastectomized breast. Both the fat and inferior end of the rectus muscle are tunneled under the abdominal wall into the defect caused by mastectomy.

Despite declining perioperative complication rates, the adverse musculoskeletal sequelae of TRAM flap breast reconstruction can be significant.¹⁷⁵ Fat necrosis within the reconstructed breast can significantly undermine cosmesis.³⁸ Donor site complications include abdominal wall bulge (2.9% to 3.8%), abdominal hernia (2.6% to 2.9%), and dehiscence (3.8%).^40,136 Patients experience abdominal weakness and reduced exertional tolerance, particularly those undergoing bilateral procedures.¹⁷¹ Because the TRAM procedure produces a defect in the abdominal wall, patients have difficulty stabilizing the trunk while transferring from supine and seated positions. Partial denervation of the abdominal wall also leads to deficits in proprioception and truncal balance. Weakness of the abdominal wall can lead to exaggerated lumbar lordosis and an increased incidence of back pain. An algorithm for treatment of patients post–TRAM flap reconstruction is presented in the “Rehabilitation of Specific Cancer Populations” section of this chapter.

Radiation Therapy–Related Impairments

Radiation therapy has become an integral part of combined modality and organ preservation therapy for many cancers. Approximately 50% of cancer patients undergo radiation therapy during the course of their disease. Although highly effective in eliminating radiosensitive tumors, controlling regional disease, and palliating symptomatic metastases, radiation therapy also injures normal tissue. The tolerance of normal tissues surrounding tumors is the most important radiation dose-limiting consideration.⁹⁶ Radiation injury is multiphasic, characterized by discrete acute and late phases mediated by distinct pathophysiologic processes. Acute injury is predominantly caused by inflammation and the death of rapidly proliferating cell types. Cell death occurs through the induction of apoptosis and free radical-mediated DNA damage. Patients can develop desquamation of the dermis and mucous membranes, visceral inflammation (e.g., colitis, cystitis, and enteritis), and muscle hypertonicity, among other symptoms. Biologic response modifiers released from injured tumor cells are thought to mediate systemic radiation effects such as fatigue and malaise.¹⁴³ The time course of acute radiation effects on normal tissue varies significantly by tissue type and radiation dose. Most patients return to their preradiation baseline by the second month after treatment. The distribution is highly skewed, however, and some patients remain symptomatic as many as 12 months after treatment.

The deleterious effects of late radiation injury are being subjected to increasing scrutiny. Adverse late effects can be attributed to tissue necrosis and fibrosis. The mechanisms underlying these end processes are being actively investigated. Microvascular injury predisposes to thrombus formation and produces a hypoxic interstitial environment.⁶⁸ Hypoxia is believed to favor the generation of free radical species that produce further damage, and ultimately a self-perpetuating cycle of tissue injury and fibrosis.²⁶⁸ In addition to compression from fibrosis, neural and microvascular injury can occur from occlusion of the vasonervorum, vasorum, and lymphorum with resultant infarction. Dysregulated transforming growth factor β (TGF-β)–mediated fibroblast activation has also been implicated, as has aberrant signaling of TGF-β–related pathways.¹⁹⁷

The adverse late effects of radiation therapy depend on the extent and location of the radiation field. Identifying the tattoos placed during radiation therapy simulation can help delineate the extent of the irradiated tissue. This is particularly helpful when clinical records are unavailable. Table 57-5 lists conditions caused by delayed radiation toxicity by system. Late radiation effects most relevant to rehabilitation medicine include those involving connective tissue, muscles, and nerves. Fibrosis occurs to some degree in all muscles and connective tissue within a radiation portal. In the absence of ongoing ROM, patients can develop contractures. Because free radical-mediated and TGF-β–mediated late radiation injury is an ongoing and potentially self-perpetuating process, ranging of affected muscles and fascia should continue indefinitely.

Table 57-5 Conditions Caused by Delayed Radiation Toxicity

The most devastating neural effects of radiation therapy include myelopathy, plexopathy, and encephalopathy. Delayed radiation myelopathy produces symptoms 12 to 50 months after radiation therapy, and progresses over weeks or months to paraparesis or quadriparesis.^62,228 Symptoms can worsen or stabilize, producing deficits ranging from mild to complete motor weakness. Although radiation hyperfractionation has reduced the incidence of myelopathy, it has been reported to affect 5% of patients who survive 18 months after receiving 5000 cGy (1 Gy = 100 rads, 1 cGy = 1 rad) to the mediastinum for lung cancer.²⁷¹ Risk factors include radiation therapy fraction size greater than 180 cGy and older age.²¹⁸ The presenting symptom is usually a Brown-Séquard syndrome, which begins distally and ascends to reach the irradiated level of the cord.²⁰³ MRI is useful in distinguishing radiation from malignant myelopathy. Hyperbaric oxygen might offer benefit if initiated soon after the onset of weakness; however, this remains controversial.

Radiation plexopathies occur in 1.8% to 4.9% of treated patients.^196,207 Risk is dose-related and seems to increase with radiation therapy exposure greater than 5000 cGy.¹²⁶ Concurrent administration of chemotherapy increases the risk.¹⁸⁵ Radiation therapy-induced brachial plexopathies develop between 3 months and 14 years (median, 1.5 years) after therapy.¹³² Lumbosacral plexopathies develop between 1 month and 31 years (generally 1 to 5 years) after radiation therapy.²⁵⁸ Characteristics of radiation therapy plexopathies that distinguish them from malignant plexopathies include lower incidence of pain (18%), pain that develops after weakness, and the presence of myokymia on electromyography.

Delayed radiation therapy encephalopathy resulting from necrosis of brain parenchyma occurs in 3% to 5% of patients receiving more than 5000 cGy, and in 5% to 15% of patients receiving 6000 cGy.¹⁵⁷ Symptoms generally develop 2 years after completion of radiation therapy. The clinical presentation often resembles that of the primary malignancy, raising the question of local recurrence. PET scanning is of greater usefulness in distinguishing tumor from radiation necrosis than either MRI or CT because radiation necrosis is hypometabolic.^21,57

Cerebral atrophy occurs more commonly than radiation therapy necrosis, being present invariably after whole brain radiation therapy of 3000 cGy in 10 fractions.²⁰³ Virtually all patients complain of memory loss, which can be sufficiently severe to compromise vocational viability.³⁷ Memory loss progresses in 10% to 20% of patients to involve other cognitive domains, potentially leading to dementia.⁵² Patients can also develop gait abnormalities and urinary urgency.⁵²

Medical treatment of radiation therapy-associated neural compromise can include short-term steroids, anticoagulation, and/or hyperbaric oxygen therapy.^82,208 Focal radiation necrosis of brain parenchyma can require surgical resection. Increasing use of bevacizumab to reverse radiation fibrosis is based on anecdotal successes and a tenuous but growing evidence base.^147,261 Pentoxifylline (800 mg/day) coadministered with tocopherol attenuates radiation fibrosis.^55,56 The benefits of pentoxifylline have yet to be assessed in radiation therapy-related neural compromise.

Chemotherapy

Chemotherapy is a mainstay of anticancer therapy. Chemotherapy drugs are used for different purposes and with varying efficacy in the management of cancer. Chemotherapy is used for four general purposes:

Induction chemotherapy is administered to patients with advanced disease for which no other treatment exists. Adjuvant chemotherapy is administered after local control is achieved through surgery or radiation when no obvious tumor is present to eliminate undetectable micrometastases and reduce the risk of recurrence. Neoadjuvant therapy can be used before surgery to reduce tumor size and thereby minimize the degree of anatomic disruption. Chemotherapy is increasingly being used serially to temporize the spread of incurable, stage IV cancer.

A staggering array of chemotherapeutic agents, or antineoplastics, is currently used in oncologic practice. Antineoplastic drugs can be mechanistically grouped into a manageable number of subclasses for the nononcologist, which include alkylating agents, platins and their analogs, antimetabolites, topoisomerase interactive agents, antimicrotubule agents, differentiation agents, and miscellaneous agents. Table 57-6 lists antineoplastics by class.

The type, dose, and duration of chemotherapy vary across different cancer types and stages, but common overarching strategies apply. To exploit complementary mechanisms of action, achieve synergy, and reduce normal tissue toxicity, different chemotherapeutic agents are generally coadministered or sequentially administered. Standardized combined chemotherapy regimens have given rise to a host of acronyms. Common examples include CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), ICE (ifosfamide, carboplatin, and etoposide), and MOPP (mechlorethamine, vincristine [Oncovin], procarbazine, and prednisone); there are many others. It is currently rare for a single chemotherapeutic agent to be administered as monotherapy.

Antineoplastics are distinguished by their capacity to preferentially injure rapidly dividing cancer cells while sparing normal cells, but all are associated with significant potential for normal tissue toxicity. The chemotherapeutic toxicities that most commonly produce functional impairments are peripheral neuropathy, cognitive dysfunction, cardiomyopathy, and pulmonary fibrosis. Fortunately, with proactive screening, the incidence of significant cardiopulmonary toxicity has been substantially reduced. Bleomycin produces pulmonary fibrosis in 10% of patients.¹⁹² The risk of doxorubicin-associated cardiac toxicity directly parallels increases in cumulative dose. With cumulative doses of 550, 600, and 700 mg/m², the incidence is 7%, 15%, and 30%, respectively.¹⁰¹ Cardiomyopathy becomes a real concern in stage IV breast cancer patients who resume doxorubicin treatment after having received it in the context of primary adjuvant therapy. Trastuzumab produces cardiac toxicity in 3% to 5% of patients receiving monotherapy and in 28% of patients who concurrently receive anthracyclines.¹²⁸

Chemotherapeutic neuropathy is a prevalent and functionally morbid complication of cancer treatment. The vinca alkaloids, cisplatin, ixabepilone, the taxanes, and thalidomide are among the most important drugs inducing peripheral neurotoxicity.²³⁸ These drugs are widely used for various malignancies, such as ovarian and breast cancer, and hematologic cancers. Chemotherapeutic neuropathy is related to cumulative dose or dose intensity.³⁰ Patients who already have neuropathic symptoms resulting from diabetes mellitus, hereditary neuropathies, or earlier treatment with neurotoxic chemotherapy are believed to be at higher risk.

All platin compounds (e.g., cisplatin, carboplatin, and oxaliplatin) have the potential to produce sensory neuropathy. Cisplatin is a more frequent source of neurotoxicity than the latter two compounds. Symptoms often occur after completion of treatment.^148,236 Large sensory fibers are preferentially affected, leading to proprioceptive deficits. Pinprick and temperature sensation, as well as motor function, are relatively spared.³⁰ Lower-limb muscle stretch reflexes often disappear. Autonomic nerves remain unaffected. Nerve conduction studies show decreased sensory nerve action potentials and prolonged sensory distal latencies, whereas nerve conduction velocities are minimally impaired.^148,236

Peripheral neuropathy related to vinca alkaloid treatment is observed most commonly with vincristine. Paresthesias in the distal extremities are the initial symptoms, and loss of lower-limb muscle stretch reflexes is the initial sign. Weakness of the wrist and digital extensors can occur. Autonomic neuropathy is common and might lead to paralytic ileus, orthostatic hypotension, and impotence.⁸⁹ Vibration sense generally remains intact.³⁰ Nerve conduction studies show decreased distal motor and sensory nerve action potentials, with only slight reduction in nerve conduction velocities, indicating an axonal rather than a demyelinating mechanism of injury.²⁰

Taxanes have become first-line therapy in the treatment of primary breast, ovarian, and lung cancers. Docetaxel is a more frequent and severe source of neuropathy. Signs and symptoms that characterize taxane neuropathy include paresthesias, loss of muscle stretch reflexes, and diminished vibration sense.²⁰⁵ Patients can develop mild proximal muscle weakness that resolves spontaneously.⁷³ Autonomic neuropathy occurs uncommonly.¹²⁰ Nerve conduction studies show reduction of sensory nerve action potentials in patients treated with taxanes.²²² Reduced motor nerve action potentials and diminished sensory and motor nerve conduction velocity have been reported.²²²

Novel targeted biopharmaceuticals are increasingly displacing established treatment standards. These include monoclonal antibodies to epidermal growth factor receptors (pertuzumab), small molecule tyrosine kinase inhibitors that targeted the various epidermal growth factor receptors (gefitinib, erlotinib), monoclonal antibodies directed at the vascular endothelial growth factor (bevacizumab), and the small tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor.²⁸ The risk profiles of many of these agents remain inadequately characterized, particularly when administered to elderly and infirm patients who differ considerably from the cohorts studied in trials. Thromboembolic events are of concern in patients receiving therapies targeting the vascular endothelial growth factor receptor.⁸⁵

Rehabilitation of Bone Metastases

Strategies to rehabilitate patients with bone metastases and pathologic fractures remain largely theoretic because of a lack of empiric data. An overarching mandate is the need to coordinate therapeutic efforts with oncologic orthopedists, radiation oncologists, and medical oncologists. Bone metastases occur in complex, highly individual, and dynamic settings. Developing an integrated cross-disciplinary, long-term management plan offers patients the best chance of preserved comfort and function. Physiatric approaches can be grouped into the use of orthoses, assistive devices, therapeutic exercise, and environmental modification. All essentially deweight or immobilize compromised bones. Orthoses can be fabricated to stabilize bones in positions that limit potentially damaging forces. A common example is the use of thoracolumbosacral or spinal extension orthoses, such as cruciform anterior spinal hyperextension or Jewett braces. These orthoses limit spinal flexion, thereby reducing loads on the anterior vertebrae to protect against compression fractures. Orthoses can also be used to protect and deweight sites of fracture or impending fracture. Thermoplast arm troughs allow patients with humeral metastases to immobilize the affected limb and reduce damaging forces. Extreme caution must be used in patients with diffuse bone metastases while redistributing weight and loading patterns. Careful radiologic evaluation of the bones to be loaded reduces the likelihood of complications. Bone metastases are rarely discrete. It can be challenging in widespread osseous disease to find sufficiently intact bone to unload weight-bearing structures.

Assistive devices and instruction in compensatory strategies might similarly unload compromised bones. Canes, crutches, and walkers are frequently used to minimize fracture risk. Identical caveats regarding the need to evaluate skeletal structures that will receive additional load via the assistive devices apply. Patients should be instructed to minimize forces by performing activities close to the body, which limits torque on long bones.

Although theoretically appealing, evidence is lacking for the usefulness of therapeutic exercise in the prevention of pathologic fractures. Regardless, patients at risk for vertebral fractures routinely tolerate exercise programs designed to strengthen the abdominal and spinal extensor muscles and to enhance their awareness of body positioning. A comprehensive exercise program should include postural and balance training, as well as truncal strengthening. Simple environmental modifications can significantly reduce patients’ fracture risk. Throw rugs and other hazards that increase fall risk should be removed. Railings can be added to stairwells and bathrooms as appropriate. Patients’ prognoses should obviously be considered in the zeal and expense with which such modifications are implemented.

Exercise

Comprehensive Inpatient Rehabilitation

The appropriateness and potential benefits of comprehensive inpatient rehabilitation must be assessed on a case-by-case basis. Cancer patients’ candidacy is generally deemed appropriate when their deficits conform to a neurologic or musculoskeletal syndrome familiar in the inpatient rehabilitation setting, that is, hemiparesis, paraplegia, or amputation. Several studies have reported equal functional independence measure (FIM) efficacies when patients with malignant SCC are compared with patients with similar but traumatically and ischemically induced impairments. Patients with malignant SCC achieve less functional improvement but, because of shorter lengths of stay, have comparable FIM efficiencies relative to patients with traumatic spinal cord injury.¹⁶¹ Home discharge rates are equal, 84% in a retrospective case series,¹⁶⁰ or higher among patients with malignant SCC.

Retrospective case series of patients transferred to rehabilitation after treatment for primary brain tumors and intracranial metastases describe substantial gains in cognitive ADL and mobility domains.^110,156 The functional gains achieved by brain tumor patients are similar to those of patients with acute stroke¹⁰⁸ and traumatic brain injury.^109,183 Patients with brain tumors are consistently discharged to the community more than 80% of the time¹⁰⁹ and have significantly shorter lengths of stay.^108,182 Studies have differed on the impact of concurrent radiation therapy. Some describe greater FIM mobility efficiencies with radiation, whereas others report the opposite.¹⁸³

A recent comparison of patients admitted for inpatient rehabilitation with wide-ranging cancer-related impairments noted no significant differences in FIM efficiencies or length of stay relative to noncancer patients. This suggests that inpatient admissions should be considered for cancer patients whose debilities arise from impairments other that intracranial or epidural metastases.²⁵⁶ That said, roughly 31% of cancer patients admitted for acute inpatient rehabilitation undergo unplanned transfer back to acute care units. The predictors for transfer are low albumin, elevated creatinine, and a requirement for tube feeding or a Foley catheter.⁸⁶

Lymphedema Management

Lymphedema is a chronic and currently incurable condition that frequently complicates cancer therapy. After resection or irradiation of lymph nodes and vessels, lymphatic congestion can develop in any region of the body drained by the affected structures. If congestion becomes sufficiently severe, swelling can result from accumulation of protein-rich fluid.²⁷³ Far from being a treatment-refractory and inexorably progressive condition, lymphedema is now amenable to highly effective and widely available therapy. Complete (or complex) decongestive therapy (CDT) represents the current international standard of care for lymphedema management.¹³ This was formalized in a white paper published by the International Society of Lymphology in 2001.¹³ CDT is an intensive integration of manual approaches and is able to achieve and maintain substantial volume reduction for the majority of lymphedema patients. Surgical, dietary, and pharmacologic approaches offer equivocal benefit at best but can be considered when appropriate manual and compression therapy fail to adequately reduce lymphedema.²⁵²

CDT is a two-phase, multimodal system that incorporates manual lymphatic drainage (MLD), short-stretch compressive bandaging, skin care, therapeutic exercise, and elastic compression garments. The initial phase, sometimes designated with a Roman numeral I or described by the term reductive, has as its primary goal decreasing lymphedema volume.⁷⁰ During daily phase I CDT sessions, patients receive approximately 45 minutes of MLD, followed by the application of compression bandages and performance of remedial exercises. Compressive bandages are left in place 21 to 24 hr/day. The efficacy of treatment delivered at this intensity has been demonstrated in numerous case series.^71,130,176 Figure 57-4 shows pre- and post-CDT images in a patient with bilateral stage 3 lymphedema. After maximal volume reduction, patients are gradually transitioned to a long-term maintenance program (phase II). In this phase, compressive garments are used during the day, with application of compressive bandages overnight. Patients perform remedial exercises daily while bandaged and receive MLD as needed.

FIGURE 57-4 Lower extremity lymphedema before (A) and after (B) complete decongestive therapy, which afforded dramatic volume reduction.

Compression forms the basis of virtually all successful lymphedema therapy. During both CDT phases I (day and night) and II (night-time only), compression is achieved through the use of short-stretch bandages. Short-stretch bandages have a high working pressure by virtue of contractions in the underlying muscles.^190,191,245 The bandages exert low pressure while the muscles are resting. A distal to proximal compression gradient is achieved by applying more layers of bandages distally, rather than varying the amount of tension used to apply the bandages. Compression garments are added to patients’ phase II regimens for daytime compression. Compression garments achieve the following:

MLD or “lymphatic massage” is a highly specialized technique designed to enhance the sequestration and transport of lymph. Specific stroke duration, orientation, pressure, and sequence characterize MLD. MLD stimulates the intrinsic contractility of the lymph vessels, leading to increased sequestration and transformation of macromolecules in the interstitium.³³ Through gentle and rhythmic skin distention, congested lymph is directed through residual lymph vessels into intact lymph node beds. MLD permits shifting of congested lymph to lymphotomes (anatomic regions drained by a specific lymph node bed with preserved drainage, as illustrated in Figure 57-5). The massage is light and superficial, limited to finger or hand pressures of around 30 to 45 mm Hg. MLD treatments are initiated proximally in lymphostatic regions adjacent to functioning lymphotomes. Lymph is constantly directed toward functional lymphotomes and lymph node beds with strategic hand movement. Treatments gradually progress distally to terminate in the regions farthest removed from intact lymphatics.

FIGURE 57-5 Manual lymphatic drainage sequence in the treatment of right lower limb lymphedema resulting from inguinal lymph node dissection: 1, stimulate intact lymph node beds where the stagnant lymph will be directed; 2, clear the pathways that will be used to redirect stagnant lymph into functioning lymphotomes; 3, direct stagnant lymph proximally along the cleared pathways, working backward into the congested territory; 4, complete treatment with proximal redirection of lymph from the most distal portions of the lymphedematous territory.

Remedial lymphedema exercises refer to repetitive movements designed to encourage rhythmic, serial muscle contractions in lymphedematous territories. Remedial exercises are always performed with external compression, most commonly compressive garments or bandages. Remedial exercises repeatedly compress the lymph vessels through sequential muscle contraction and relaxation, thereby triggering smooth muscle contraction in lymph vessel walls.¹⁸⁶ An internal pumping mechanism is established that encourages congested lymph to flow along the compression gradient created with bandages or garments.^141,142 Progressive strength training, when supervised and gradually progressed, was shown to reduce lymphedema flares in a large, randomized controlled trial. Based on this finding, strength training should be integrated into the routine management of breast cancer–related lymphedema.²²⁵

Skin care is stressed in manual approaches to lymphedema. The goals of skin care include controlling skin colonization with bacteria and fungi, eliminating overgrowth in skin crevices, and hydrating the skin to eliminate microfissuring. Daily cleansing with mineral oil-based soap will remove debris and bacteria while moisturizing the skin.³²

The current shortage of adequately trained and experienced lymphedema therapists in the United States is a consistent impediment to successful treatment. The Lymphology Association of North America (LANA) has developed a certification examination to identify therapists with the requisite knowledge and manual training. A list of certified therapists is available through the LANA website (http://www.cltlana.org). The National Lymphedema Network (http://www.lymphnet.org) offers an extensive list of lymphedema-related resources. Patients with lymphedema complicated by aggressive recurrent cancer, dermal metastases, chemotherapeutic neuropathies, or pain will require specialized care generally available only at tertiary medical and comprehensive cancer centers.

Augmentative and Compensatory Strategies

Cancer-related impairments often render necessary daily activities challenging or impossible. The adaptation of conventional rehabilitation programs for the development of alternative and compensatory strategies allows patients to remain functionally independent. Use of assistive devices for mobility and ADL performance might be necessary. Environmental modification and augmentative communication devices should be explored in appropriate cases. Pacing strategies become essential for fatigued patients receiving intensive anticancer therapy, or for those with advanced disease. The appropriateness and cost–benefit ratio of interventions must be determined on a case-by-case basis.

Breast Cancer

Functional impairments unique to breast cancer patients develop after surgical procedures for tumor removal and breast reconstruction. These procedures include modified radical mastectomy (MRM), lumpectomy, sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), and autogenous tissue transposition for reconstruction.

Persistent deficits in shoulder ROM occur in as many as 35% of patients after ALND¹⁴⁰ (Table 57-7). Even after SNLB, 16% of patients have self-reported limitations.¹⁴⁴ Lotze et al.¹⁴⁹ reported that vigorous shoulder mobilization in the immediate postoperative period led to an increase in seroma formation. The timeline for shoulder mobilization presented in Table 57-8 adequately restores shoulder mobility without increasing the incidence of postsurgical complications but has not been empirically evaluated. MRM and ALND are performed as same-day procedures at some institutions. In such cases, a gradual, supervised, and progressive ROM program is not possible. In such cases patients are often provided with illustrated exercise sheets covering “wall walking,” forward flexion assisted by the unaffected arm, shoulder rolls, etc. A growing literature suggests that physical therapy after surgery for breast cancer offers a number of compelling benefits, including reduced pain, shoulder limitations, and lymphedema, as well as enhanced psychologic well-being.^{15,19,139,262} This evidence is arguably strong enough to mandate the inclusion of physical therapy as standard care in postsurgical breast cancer management.

For patients who have undergone immediate breast reconstruction, particularly the TRAM flap procedure, shoulder mobilization should be reviewed with the plastic surgeon unless an institutional algorithm has been formulated.

Axillary web syndrome (Figure 57-6) refers to the presence of taut, palpable cords originating in the axilla and extending distally along the anterior surface of the arm, often below the elbow.¹⁷⁸ What precise tissues comprise the cords remains a source of speculation. In a limited case series resected cords were pathologically evaluated and contained either lymphatic vessels or veins and surrounding connective tissue.¹⁷⁸ The clinical relevance of axillary web syndrome arises from its potential for painful restrictions in shoulder ROM. In severe cases, the cords tether the humerus, preventing full shoulder flexion or abduction. Pain generally responds to NSAIDs, but opioid analgesics might be necessary during passive and active assisted ROM if the pain is severe. Therapy involves incremental ROM activities, topical heat, manipulation to soften and potentially “pop” the cords, as well as provision with a home exercise program. Heat should be used briefly, if at all, given the risk of lymphedema and the almost universal presence of intercostal brachial neuropathy in the axilla and upper arm.

FIGURE 57-6 Axillary web syndrome manifest by thick, fibrous cords tethering the arm.

The surgical community has increasingly recognized the need for rehabilitation after TRAM flap breast reconstruction. The procedure denervates and disrupts the integrity of the abdominal wall, producing significant deficits in truncal stability, particularly during functional transfers. The goals of post-TRAM rehabilitation are to prevent subdermal fibrosis and adhesions, restore truncal alignment, minimize stress on the lumbar spine, optimize proprioceptive acuity in residual abdominal muscles, and encourage normal muscle recruitment patterns. The algorithm for post-TRAM flap rehabilitation (Table 57-9) was well tolerated and eliminated lasting impairment in a cohort of 52 patients.²⁴⁷ No patients developed donor site herniation or wound dehiscence.

Table 57-9 Post-TRAM Procedure Rehabilitation Program

Head and Neck Cancer

Combined modality therapy for head and neck cancer has afforded improved cure rates and reduced normal tissue compromise. The type and sequence of therapies used to treat head and neck cancer vary by the location of the primary tumor, the extent of cervical lymph node involvement, and the pathologic characteristics of the tumor. Treatment approaches increasingly reflect a trend toward organ preservation. For example, the emphasis on “normal” tissue preservation has led to the substitution of supracrichoid partial laryngectomy for total laryngectomy, and of a functional neck dissection for radical neck dissection.

Treatment of head and neck cancer continues to produce some of the most challenging impairments within the scope of cancer rehabilitation. Many of the impairments directly undermine patients’ ability to socialize because of facial dysmorphism, loss of spontaneous or intelligible speech, and the inability to eat normally. Common rehabilitation problems include spinal accessory nerve palsy, radiation-induced xerostomia, soft tissue contracture of the neck and anterior chest wall soft tissues, dysphagia, dysphonia, and myofascial dysfunction. Impairments evolve over the course of head and neck cancer treatment and recovery. Rehabilitative interventions must be adjusted accordingly. This chapter addresses the common problems that occur uniquely in the context of head and neck cancer: spinal accessory nerve palsy, cervical soft tissue contracture, and dysphonia.

Spinal Accessory Nerve Palsy

The recognition that comparable cure rates can be achieved with more conservative surgical resection has spurred the shift from radical to functional neck dissections. The former procedure removes the sternocleidomastoid muscle, the spinal accessory nerve, and the external jugular vein. The nerve to the levator scapulae muscle was also frequently resected, producing severe ipsilateral shoulder dysfunction. Functional neck dissections, however, preserve all structures that can be safely left intact, producing dramatically lower rates of postoperative shoulder morbidity. Many head and neck cancer patients now emerge from surgery with largely spared spinal accessory nerve function. The integrity of the spinal accessory nerve can be easily assessed by side-to-side comparison of resisted end-range forward flexion of the shoulder. Some degree of weakness can be elicited in most patients on the side of the neck dissection.

The severity and distribution of trapezius weakness secondary to spinal accessory nerve palsy (Figure 57-7) are subject to great individual variability. The upper, middle, and lower trapezius muscles can be innervated solely by the spinal accessory nerve or receive partial or total innervation from the cervical plexus.²² When the spinal accessory nerve was routinely sacrificed during radical neck dissections, some patients developed little to no shoulder compromise, suggesting that innervation was predominantly derived from the cervical plexus. Baseline anatomic variability is compounded by inconsistency in the type and degree of intraoperative nerve injury. The spinal accessory nerve can be entirely spared or subject to neurapraxic, axonotmetic, or neurotmetic insult, all with different rates and degrees of recovery. Electrocautery of blood vessels can undermine blood supply to the vasonervorum, producing ischemic nerve injury.

FIGURE 57-7 A, Resting posture of a head and neck cancer patient with complete spinal accessory nerve palsy. B, Active shoulder abduction is limited to 90 degrees on the affected side because of middle trapezius muscle weakness.

The timing and intensity of rehabilitation should be guided by patients’ prognosis for recovery. Frequent reevaluation is essential. Spinal accessory nerve reinnervation can continue over 12 months after surgery. Important elements of spinal accessory nerve rehabilitation include:

Rehabilitative efforts should by constantly informed by the rate of reinnervation. Patients with complete, persistent spinal accessory nerve palsy can be fitted with an orthosis. To date, none of the braces designed to substitute for absent or weak trapezius muscles have enjoyed widespread success. The relevant literature does not extend beyond limited case reports. For patients plagued by levator scapulae fatigue and spasms, a “shelf” orthosis (Figure 57-8) designed to encircle the waist, and to provide a ledge on which patients can rest their affected arms when not in use, reduces symptoms.

FIGURE 57-8 “Shelf” orthosis fabricated to encircle the torso of patients with complete spinal accessory nerve palsies and to provide a ledge on which they can rest their affected extremities when not in use.

Cervical Contracture

Progressive fibrosis of the anterior and lateral cervical soft tissue can be highly problematic for head and neck cancer patients, particularly those who receive external beam radiation. A general approach to radiation-induced fibrosis was outlined previously in this chapter. Because of the high radiation doses delivered to some head and neck cancer patients, proactive ROM in all planes of neck motion should be initiated as soon as safely possible. Cervical ROM can continue throughout radiation therapy in the absence of significant skin breakdown. Ranging activities should ideally begin immediately after surgery and before radiation. The delicate balance between flexibility and postsurgical wound healing must be respected. Surgeons should be consulted regarding the length of the postoperative interval before ROM activity can begin. For an uncomplicated radical or functional neck dissection, 3 days is generally considered safe. Reconstruction with tissue transposition requires a longer recovery period. ROM activities should be delayed until all drains are removed to avoid seroma formation.

Irradiated patients should perform ROM activities twice daily during the first 2 years after cancer treatment and daily thereafter. As previously mentioned, radiation-induced fibrosis can be indefinitely progressive. Figure 57-9 demonstrates the head-forward posture and thoracic kyphosis characteristic of head and neck cancer patients with severe anterior cervical soft tissue fibrosis. For optimal results, patients should be taught to provide additional stretch during end-range lateral bending or rotation by exerting additional pressure with the contralateral hand. Stretches should be held for five deep breaths and repeated between 5 and 10 times per session. Isometric strengthening of the cervical extensors and postural modification with visual cuing are beneficial.

FIGURE 57-9 Head-forward posture and exaggerated thoracic kyphosis, associated with radiation-induced soft tissue contracture, in a head and neck cancer patient.

Manual fibrous release techniques are indicated when ROM is restricted by robust soft tissue fibrosis or tethering of the skin to subdermal tissues. Patients can be taught self-massage to augment the efficacy of ROM activities. Compression of severely fibrotic areas breaks down established scar tissue and inhibits re-formation. Compression garments, either off the shelf or customized, are a convenient means of applying compression. Custom-cut foam pieces that are strategically inserted can achieve greater focal pressure on stubborn areas. Constant vigilance must be maintained to ensure that friable, irradiated skin is not compromised. Botulinum toxin injection can be trialed in refractory cases.²⁴⁸

Aphonia and Dysphonia

Impaired vocal communication occurs in the majority of head and neck cancer patients at some point during treatment. Many conditions other than total laryngectomy can compromise phonation. These include radiation-induced laryngeal or pharyngeal swelling and fibrosis, tracheostomy, partial or total glossectomy, reduced oral excursion secondary to trismus, copious secretions, and neurogenic pharyngeal or laryngeal paralysis. Some patients are rendered acutely voiceless after surgery. Such acute loss occurs most dramatically after total laryngectomy but is also frequent after tracheostomy and glossectomy. Gradual compromise of vocal precision, endurance, and volume is more common with organ preservation therapies. Irrespective of the acuity of onset, loss of spontaneous, intelligible speech can be profoundly isolating. It renders patients dependent in communication and can be vocationally devastating.

Various approaches to restore communication can be used depending on the anticipated duration, severity, and nature of the deficit. The most common compensatory strategies used by acutely voiceless adults include mouthing words, gestures, writing, and head nods.^8,92 Patients rendered chronically aphonic by total laryngectomy can communicate through esophageal speech, tracheoesophageal speech, or use of an electrolarynx. The frequency with which these options are offered to and accepted by patients varies considerably across physician practices, institutions, and geographic regions.¹⁶⁵ The following frequencies for different types of alaryngeal speech have been reported: esophageal speech, 1% to 32%; tracheoesophageal speech, 20% to 45%; electrolarynx, 0% to 50%; and nonvocal, 17% to 26% (see Chapter 3).^{79,103,165,241}

Both esophageal and tracheoesophageal speech use the oropharynx, lips, and tongue to produce intelligible sound. Esophageal speech is time consuming and difficult to learn. Among a cohort of laryngectomized esophageal speakers, a subjectively “good enough” result was achieved by 41% in less than 6 months, by an additional 20% in 6 to 12 months, and by a further 10% in more than 12 months.²⁷⁸ Despite the challenges of mastery, tracheoesophageal puncture, or the TEP procedure, represents an increasingly common approach to voice restoration. The TEP procedure creates a stoma between the trachea and esophagus. A one-way valved prosthesis is inserted in the stoma, allowing pulmonary air to enter the esophageal reservoir when patients manually occlude their tracheostomies. Although guttural, the resultant speech can be exceedingly intelligible, with natural-sounding inflection. Compared with other types of alaryngeal speech, TEP speakers most closely approximate the frequency and intensity of the normal voice.¹⁰⁴ In two surveys, TEP speech received higher satisfaction ratings than alternative methods, particularly with telephone use.^41,278

For patients who elect not to undergo TEP, speech is most often accomplished through use of an electrolarynx. Many head and neck cancer patients who fail to achieve intelligible esophageal speech eventually opt for an artificial larynx. The currently marketed devices vary with respect to placement of the transducer. Some sense vibrations within the oral cavity, whereas others are placed on the submental or buccal skin. Training is essential to the achievement of acceptable voice quality. Various transducers should be trialed because patients’ preferences vary. A significant downside of electrolaryngeal speech is its mechanical and monotonic quality.

Additional Concerns

Head and neck cancer patients, by virtue of their treatment and premorbid risk profile, are prone to the development of osteoradionecrosis, dental caries, and recurrent substance abuse. Comprehensive rehabilitation involves proactive screening for these conditions. Because of the high radiation doses delivered in head and neck cancer treatment, 5% to 15% of these patients develop osteoradionecrosis, an extremely painful condition caused by radiation-induced bone death. The mandible is most often affected. Patients complain of relentless jaw pain aggravated by chewing and vocalization. Associated pain should be aggressively treated with combined opioids and NSAIDs. Referral for hyperbaric oxygen treatments should be considered.