Safety

Cancer patients often face seeing multiple specialists across the whole spectrum of care from acute care hospitals to rehabilitation facilities and outpatient practices. Numerous handoffs and transitions may result in miscommunication and errors. Engaging family members and educating them regarding patient’s medications, precautions, and necessary follow-up will ensure patient safety through multiple transitions. In addition, patients may be engaged in learning proper techniques to assist cancer survivors with activities of daily living (ADLs) as they transition to home and community.

Brain Radiation

Acute complications of brain radiation occur during radiation therapy (RT) and up to 6 weeks after. These effects are often due to vasogenic edema and present as an acute encephalopathy with symptoms including headache, nausea, new onset or worsening of focal neurologic deficits and seizure. The acute side effects are most often seen on the inpatient rehabilitation unit and can present a safety concern, as patients may exhibit decreased safety awareness and increased risk of falls. Fortunately, RT encephalopathy is most often reversible, being easily treated or prevented with corticosteroids. Although often multifactorial, RT can contribute to the fatigue a patient experiences while undergoing treatment. Fatigue can hinder a patient’s performance in therapy and may also increase their risk for falls on the inpatient unit.

Early delayed side effects present from 6 weeks to 6 months post RT and most commonly include persistent fatigue and focal neurologic deficits or encephalopathy, thought to be caused by demyelination of the irradiated tissue. ^, Similar to the complications seen in the acute phase, early delayed side effects are most often reversible when treated with corticosteroids.

Late effects occur at least 6 months to a year after completion of RT and may present several years after. Unlike the acute or early delayed side effects, these effects are usually irreversible. Radiation necrosis develops with higher fractionation of radiation and is due to damage and necrosis of blood vessels, combined with demyelination of treated and surrounding brain tissue. This type of necrosis leads to new focal neurologic deficits, dementia, and ataxia, all of which present safety concerns for the patient. Incidence of long-term cognitive deficits varies with location of the tumor and fractionation and duration of RT, but may cause memory impairments, decreased concentration, and safety awareness. Distinguishing between radiation necrosis and recurrent tumor is often difficult, as the two have similar clinical presentations. MRI imaging of the brain without a clearly defined T2 mass as well as a higher ratio of edema to enhancing lesion are more suggestive of radiation necrosis than recurrent disease.

Radiation to the Spine

RT required for tumors of the spine may cause damage and fibrosis of the spinal cord itself, as well as the exiting roots and nerves and surrounding musculature. Damage to these structures may present as symptoms of myelopathy, radiculopathy, neuropathy, plexopathy, or myopathies. The rehabilitation team should be aware of structures included in the irradiated field during treatment in order to properly diagnose these potential side effects.

Side effects from RT to the spinal cord presenting a safety risk include transient myelopathy, chronic progressive myelopathy, and acute paralysis. Transient myelopathy, due to demyelination, occurs in the early delayed time frame and presents as Lhermitte symptom, a shock-like sensation down the spine induced by flexion of the neck. This myelopathy, although uncomfortable, resolves with time. Late radiation–induced myelopathy is most often irreversible and can be progressive in nature, leading to paralysis. Demyelination and necrosis of white matter, as well as vascular necrosis all contribute to chronic radiation myelopathy. Initial presentation is often with Brown-Sequard syndrome which then progresses with time to spastic paraplegia or quadriplegia with associated complications such as neurogenic bowel and bladder. Corticosteroids may be prescribed to slow the progression. This progressive myelopathy of course increases a patient’s risk for falls and skin breakdown. Lower motor neuron syndrome may occur with RT to the lower spinal cord and cauda equina, presenting as progressive lower extremity weakness. Sensory impairments are rare and bowel/bladder function is usually normal with the lower motor neuron syndrome. Weakness may progress very slowly, allowing patients to remain ambulatory for quite some time after initial presentation. Spinal cord hemorrhage is another late complication of RT. Radiation to the spine may lead to the development of vascular malformations such as telangiectasias and cavernomas, which may rupture and bleed. Patients present with acute onset of lower extremity weakness and back pain.

Safety in Exercise with Brain and Spinal Cord Tumors

The American College of Sports Medicine (ACSM) recommends all cancer patients participate in moderate to vigorous exercise as their condition allows. The ACSM also advises that a patient’s physical activity level and current medical status be assessed at the time of cancer diagnosis, during treatment, and at the time of completion. Assessing the patient at each interval will help to individualize exercise programs with the goal of improving overall health and function. Patients participating in a supervised exercise program have shown the most significant functional improvements and for this reason it is necessary for the treating team to be aware of the patient’s diagnosis, treatments, and both short- and long-term complications of the disease itself or the required treatment.

Participation in a rehabilitation program for patients with brain or spinal cord tumors has shown to improve functional outcomes. However, at present time there are no specific guidelines for the safety of exercise in patients with brain or spine cancer. Therefore, it is recommended the guidelines established by the ACSM for exercise in patients with cancer be followed. The ACSM recommends all cancer patients should avoid periods of inactivity, even when undergoing treatment, and should engage in regular aerobic, resistive, and flexibility exercises. The ACSM realizes modifications will need to be made for certain individuals, but emphasizes the goal of remaining as physically active as their condition allows. A recent study found there to be no adverse outcomes when patients with high-grade glioma participated in a daily exercise program consisting of walking and resistive and balance exercises.

While outlining a supervision of an individual’s rehabilitation and exercise program, the following complications of medical conditions should be taken into consideration. Modifications to individualized programs should be made as needed in order to maintain patient safety.

Introduction

Chemotherapy is an important part of the treatment regimen in most individuals with cancer. Temozolomide, bevacizumab, and irinotecan are commonly used in the treatment of primary brain tumors with good response rates. Spinal cord and brain tumors resulting from metastases are generally treated with chemotherapy agents for their primary cancers. The most common cancers that metastasize to the brain are from lung, breast, melanoma, renal, and colorectal, with the incidence of metastases to the brain increasing as the survivorship of the abovementioned malignancies continue to improve. All chemotherapeutic agents have short- and long-term adverse effects that can have effects on safety during rehabilitation.

Anemia

Anemia is a common complication experienced by patients undergoing chemotherapy as a part of their oncologic treatment regimen. Patients may commonly report symptoms of fatigue and dyspnea on exertion, both of which cannot only limit their activity tolerance but also affect their quality of life over time. The prevalence of anemia in adults with cancer is estimated to be as high as 39%, with numbers nearing 100% in those undergoing active chemotherapy. Studies have shown greater hemoglobin concentrations are linked to better physical and functional well-being, with direct correlation between uncorrected anemia and functional disability, even increased mortality. Most individuals will tolerate exercise despite having anemia, with no signs of tachycardia or dyspnea on exertion even with hemoglobin concentrations as low as 8 g/dL. Cardiopulmonary functional capacity and muscular performance can be influenced by anemia, with greater functional capacity decline occurring when there is an acute drop in hemoglobin concentration rather than a gradual drop. Therefore, monitoring the signs and symptoms of chemotherapy-induced anemia, as well as how rapidly the decline occurs in hemoglobin and hematocrit, is paramount to improving and maintaining a patient’s physical and functional performance, as well as increasing cancer treatment tolerance.

Neutropenia

Chemotherapy-induced neutropenia is a serious adverse effect experienced by some cancer patients, and it can be associated with severe localized and systemic infections and prolonged hospitalizations. The risk of serious infection increases with increasing grade and duration of neutropenia, especially neutropenia greater than 7 days’ duration with neutropenic fever being considered an oncologic emergency. It is important to note that these patients are most susceptible to infections that result from their own normal flora, especially those present in the gastrointestinal tract, than nosocomial infections. Therefore, it has been found that increased barrier protection, such as the use of gowns, gloves, and masks, is not useful in the prevention of infection; beneficial recommendations include proper hand hygiene among caregivers, grouping infected patients together, placing neutropenic patients in private rooms, and assigning caregivers to neutropenic patients so that their exposure to other infected patients is low. In an inpatient rehabilitation setting, safety consideration should be given as to whether neutropenic patients should perform their therapies in a commonly used space or their own private rooms.

Thrombocytopenia

Thrombocytopenia is the most common hematologic toxicity seen as a result of chemotherapy use and can lead to serious consequences, such as bleeding complications. It usually results from cumulative toxicity that is dose dependent and is observed 6–14 days after a treatment cycle. The predominant cause of low platelet counts secondary to chemotherapy results from decreased platelet production. Temozolomide was found to be associated with the development of thrombocytopenia in 15%–20% of those undergoing treatment, with thrombocytopenia often being prolonged and possibly irreversible. Aside from the changes to the chemotherapy regimen, there are only a few treatment options available for chemotherapy-induced thrombocytopenia. However, physical exercise regimens have been well tolerated in individuals undergoing active chemotherapy cycles with no signs of hemorrhage with platelets less than 10,000 cells/mm ³ . Therefore, the general recommendations are to limit activities to walking and ADL with platelet counts <20,000 cells/uL; light exercise with close symptom monitoring with platelet counts >20,000 cells/uL; and moderate exercise with light resistive exercises with platelet counts >30,000 cells/uL. While careful consideration should be taken when evaluating thrombocytopenic patients in the rehabilitation setting, physical activities do not necessarily need to be held as long as the patient is able to tolerate the exertion.

Chemotherapy-Induced Peripheral Neuropathy

The peripheral nervous system is vulnerable to the neurotoxic effects of chemotherapy agents. Chemotherapy-induced peripheral neuropathy (CIPN) is frequently a dose-limiting adverse effect and can produce a long-standing negative impact on a patient’s mobility. The nerve fibers and dorsal root ganglia of the primary sensory neurons are equally at risk of being affected, and the development of neuropathy is due to total cumulative dose and dose intensity. Neuropathic changes are most often seen with platinum-based, taxane, and vinca alkaloid agents, and usually occurs in a stocking/glove distribution with sensory disturbances more common than motor disturbances. Patients will often present with decreased vibratory sensation in the toes, as well as a loss of Achilles deep tendon reflexes, with associated numbness, tingling, and paresthesia in the fingers and toes, although some patients may also experience a loss of pain and temperature sensation with taxanes.

CIPN occurs during chemotherapy cycles, with symptoms decreasing after completion of treatment. However, a number of patients can continue to have altered sensation even after the cessation of the chemotherapy regimen. In a secondary data analysis of 512 female cancer survivors, 47% still reported symptoms of CIPN an average of 6 years after completion of chemotherapy, with significantly more disability and 1.8 times the risk of falls, effectively showing that those with CIPN continue to have proprioceptive and balance deficits that put them at risk for further functional disability. Therefore, proper management includes baseline assessments of strength, sensation, balance, proprioception, and gait should be done prior to initiating chemotherapy, with continued screening for changes in the aforementioned clinical measures throughout the duration of the chemotherapy cycles ^, . Patients who have been on a chemotherapy agent known to cause CIPN should be properly monitored for fall risk throughout their rehabilitation course.

Cognitive Impairments

Changes in cognition secondary to chemotherapy, referred to colloquially as “chemo brain,” can occur in a number of patients. However, cognitive impairment in this population can be multifactorial, as many of these patients not only have a brain tumor located in areas of the brain associated with memory, calculation, and executive functioning but also are on a number of medications that can cause confusion, lethargy, attention, and concentration deficits. Moreover, cognitive impairment can have serious ramifications on quality of life, with reduction in learning and memory the most commonly affected. There is strong evidence that chemotherapy in cancer patients can cause a decline in short-term cognitive ability, but data regarding long-term effects still remains unclear. For those who continue to have cognitive impairments despite stopping chemotherapy, an increase in physical activity and exercise has been shown to improve cognitive function. Yoga, meditation, and Tai Chi have been indirectly linked to improving cognitive function by decreasing stress and fatigue. Pharmacologically, methylphenidate in low doses has been found to be effective in glioblastoma multiforme patients with improvement seen in memory, reasoning, and verbal fluency. Donepezil, ginkgo biloba, hyperbaric oxygen, bevacizumab, and indomethacin have been studied for use in brain tumor populations as well, although the findings have been limited.

Side Effects of Seizures and Anticonvulsants

Seizures are a common presenting symptom of brain tumors, occurring in 20%–80% of patients, especially those with low-grade tumors. While some may have a seizure that leads to the diagnosis of their brain tumor, others develop seizures later in the progression of the disease. Seizures can occur with both primary brain tumors and brain metastases. Tumors involving cortical structures of the brain are more likely to produce seizures, especially those in the temporal and primary sensorimotor cortices.

Traditional first-line agents for seizure management included typical anticonvulsants, such as phenytoin, carbamazepine, and valproic acid for several years. Although these medications have great efficacy for seizure control, they have the common adverse effect of cytochrome P450 enzyme induction, which leads to several drug-drug interactions, especially with chemotherapy agents and glucocorticoids. This can reduce the effective serum concentrations of chemotherapy medications; it can also reduce the efficacy of glucocorticoids in the maintenance of vasogenic edema. In turn, chemotherapy metabolism by the same hepatic enzymes can cause reduction in the serum concentrations of the anticonvulsant agents, thereby increasing a patient’s risk of having seizure activity, which can have devastating neurologic consequences. Typical anticonvulsants also have a higher risk of causing morbilliform drug rashes when taken in conjunction with RT, with a small percentage of patients developing life-threatening reactions such as Stevens-Johnson syndrome.

There have been some reports that levetiracetam can cause increased agitation or negative behavioral changes, but this was seen more often in those with baseline psychologic and behavioral derangements. It is an otherwise well-tolerated anticonvulsant. Newer anticonvulsants, such as levetiracetam and lacosamide, have shown to be equally efficacious to the traditionally used medications, with less adverse effects experienced by the patient while undergoing treatment.

Side Effects of Steroids

Glucocorticoids are an essential part of the treatment of central nervous system tumors. They are used in about 70%–100% of patients with primary central nervous system tumors and metastases and can provide transient relief of neurologic symptoms by decreasing the vasogenic edema that causes increased intracranial pressure or spinal cord compression; a marked improvement is often seen within 24 hours of administration. Glucocorticoids have also been used in neuro-oncology because it can provide short-term relief of chemotherapy-induced nausea and vomiting. Dexamethasone, a fluorinated steroid, is the most commonly used of these medications because of its long half-life and low mineralocorticoid effects; it is known to be beneficial in the management of mass effect secondary to tumor-associated edema and may even protect against the development of acute encephalopathic changes related to RT. However, they are not without their own adverse effects ( Table 2.1 ).

Table 2.1

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