Over 75,000 children (ages 0–19 years) were diagnosed with cancer between 2010 and 2014 in the United States. Of these, leukemias and lymphomas were the most common, accounting for over 40% of cases. Central nervous system (CNS) tumors accounted for another 17%. Over the same time period, nearly 10,000 children died from cancer¹ (Fig. 63–1). Childhood cancer survival rates are improving, leading to an increasing population of adolescent and young-adult survivors. As the children age, the long-term effects of cancer and its treatment intermingle with comorbidities seen in any aging population.² Many physical and psychological sequelae of cancer and its treatment are amenable to rehabilitation interventions.

The appropriate rehabilitation treatment strategy will vary depending on a child’s tumor, treatments, and prognosis. Rehabilitative management strategies may require dynamic problem solving as a child ages and grows, even into adulthood. One framework for goal setting in cancer rehabilitation is the Dietz classification.³ It defines goals across four types of interventions: preventative, restorative, supportive, and palliative. For example, a child who has received curative treatment may benefit primarily from preventative and restorative interventions, whereas one with terminal disease would be more appropriate for supportive and palliative management. Preventing immobility-related complications is of paramount importance. Children should also be screened for attainment of age-appropriate developmental milestones, and their cognitive, psychological, and social/emotional well-being should be optimized. Members of rehabilitation team (including physiatrists; physical, occupational, speech, and recreational therapists; child life specialists; psychologists, social workers, and case managers) need to work together and communicate with oncology teams to create the most appropriate and uniform rehabilitation plan. Young children should be considered for early intervention services and preschool special education programs. School-aged children may need individualized education plans (IEPs) or other accommodations, including home schooling. Children with CNS tumors or those exposed to neurotoxic chemotherapy may need formalized neuropsychological testing. The importance of family and community support cannot be overstated, and available resources should be offered to caregivers to help prevent burnout and fatigue. Survivorship care and management of the long-term psychosocial sequelae of surviving childhood cancer become increasingly important.

Leukemia

Leukemia is the most common pediatric cancer and accounts for approximately 30% of all childhood cancer diagnoses. Acute lymphoblastic leukemia (ALL) is the most common subtype. Approximately 3,500 persons younger than 20 years of age are diagnosed with ALL every year.⁴ Fortunately, the overall survival rates for children with newly diagnosed ALL is approximately 85%. Acute myeloid leukemia (AML) is less commonly diagnosed, and the 5-year overall survival rate is between 60% and 70% depending on subtype.⁴ The management of childhood ALL is based on the type and risk stratification of the disease. The main treatment for childhood ALL is chemotherapy. For those with higher risk or relapsed disease, higher-dose chemotherapy and hematopoietic stem cell transplant (HSCT) may be used. CNS radiation has largely been replaced by intrathecal chemotherapy. Treatment for ALL follows typical phases, including induction (intensive treatment, 1 month), consolidation (1–2 months), delayed intensification (2 months), and maintenance (2 years). Treatment occurs primarily in the outpatient setting and lasts for 2.5 to 3 years. The primary chemotherapeutic agents include vincristine, L-asparaginase, dexamethasone, and methotrexate. Intrathecal (IT) methotrexate is typically used. For children with higher-risk ALL, additional drugs may be added, including anthracyclines, etoposide, cyclophosphamide, and cytarabine.

Side effects of treatment are common. Chemotherapy-induced peripheral neuropathy (CIPN) occurs in up to 80% of patients.^5,6 Unlike adults exposed to vincristine therapy who develop a primarily sensory neuropathy, children tend to develop a mixed sensorimotor distal polyneuropathy. Neuropathic pain can also occur. Osteonecrosis may occur in up to 17% of ALL patients and is related to corticosteroid treatment. It is more common in patients 10 years of age and older and occurs most frequently in the knee, but other joints can also be affected.⁷ Cardiotoxicity can also occur in patients treated with anthracyclines. Acute cardiotoxicity occurs in less than 1% of children treated, but this side effect can occur years after treatment has ended. Approximately 65% of survivors of childhood cancer treated with anthracyclines have detectable structural or functional left ventricular abnormalities 6 years after cessation of treatment.⁸

Similar to ALL, the main treatment for AML is chemotherapy with hematopoietic stem cell transplantation (HSCT) if necessary for high-risk, refractory, or relapsed disease. Induction therapy lasts a few cycles and typically occurs in the inpatient setting. Once in remission, the patient will receive consolidation treatment. HSCT is used in patients with poor prognostic markers or relapsed disease. Intrathecal (IT) chemotherapy is also used. Induction chemotherapy typically includes cytarabine and anthracycline. Consolidation treatment is a more intense phase that may include cytarabine and other agents. IT treatment may be given for CNS prophylaxis. As with ALL, cardiotoxicity can be seen in survivors of AML. Precautions for children undergoing active treatment may include bleeding and immunosuppression. Bracing in patients with CIPN may be necessary to improve flexibility, ankle/foot alignment, and gait pattern.

Lymphoma

Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL) are the main types. HL and NHL account for approximately 3% and 5% of childhood cancers, respectively.⁴ Diagnosis of lymphoma and differentiation between the types is accomplished by lymph node biopsy. Other imaging (computerized tomography, positron-emission tomography) is used to determine the stage of disease. HL is typically treated with chemotherapy and radiation. The chemotherapy can include doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine (ABVD), and other agents such as etoposide, vincristine, and prednisone. Radiation of the initial tumor site typically follows chemotherapy. Refractory or recurrent disease may be treated with high-dose chemotherapy and stem cell transplant, monoclonal antibody therapy (brentuximab), or immunotherapy.

CIPN can be problematic because it is commonly experienced as a distal sensory and motor neuropathy and may persist.⁵ Fatigue is a common complaint that can also persist after treatment is complete. Pulmonary fibrosis can be a side effect of bleomycin as well as chest wall irradiation. Radiation to the chest or neck may also affect thyroid function. Fertility can also be affected. NHL is treated primarily with chemotherapy, usually using combination chemotherapy, commonly including vincristine, cyclophosphamide, cytarabine, doxorubicin, methotrexate, L-asparaginase, prednisone, and/or dexamethasone. Radiation is less commonly used. The chemotherapeutic drugs used to treat NHL can lead to CIPN, metabolic bone disease, cardiac and pulmonary dysfunction, and fertility issues.

Hematopoietic Stem Cell Transplantation (HSCT)

HSCT is used to treat some malignant and nonmalignant hematologic and immunologic disorders. Autologous HSCT involves infusion of the individual’s own hematopoietic progenitor cells following ablative chemotherapy. Allogeneic HSCT involves the infusion of a related or unrelated donor’s progenitor cells. Graft-versus-host disease (GVHD) is the most dreaded complication of allogeneic HSCT. It is a T-cell-mediated process in which the engrafted immune system attacks the host’s tissues.⁹

The primary method of treatment is immunomodulation with agents such as corticosteroids, interleukin-2 inhibitors (e.g., tacrolimus), and cyclosporine. Extracorporeal photopheresis can be used to break down T-cell complexes. Although there are both acute and chronic forms, this section focuses on chronic GVHD because it carries the most physiatric implications. Any tissue can be affected, although highly mitotic tissues such as the gastrointestinal tract and skin are most frequently involved.^10,11 One manifestation of the most commonly affected integumentary system is sclerodermatous or fascial GVHD, which can lead to skin tightening, ulceration, and loss of range of motion (ROM). Peripheral edema is often the initial manifestation and should be treated aggressively¹² (Fig. 63–2).

Physical and occupational therapy (PT and OT) referrals should be provided to manage ROM. Braces such as ankle/foot orthoses (AFOs) to prevent plantarflexion contracture and improve gait and wrist splints to prevent wrist flexion contracture should be used as needed.¹³ Serial casting may be used in severe cases to restore functional ROM. Therapeutic modalities such as paraffin baths, phonophoresis, and iontophoresis with dexamethasone have not been tested on GVHD patients but may be useful.^12,14 Skin in affected areas will be at higher risk for breakdown as well.

Parental involvement in stretching, splinting, and rehabilitation programs is paramount to ensure compliance and to ensure proper orthotic usage and protect skin integrity. Although GVHD does not exert direct influence on bones, long-term corticosteroid use can increase the risk of fracture in children.¹⁵ Vitamin D levels should be monitored, and supplementation should be prescribed as needed.

Osteonecrosis, especially at the femoral head, is a potentially debilitating complication of prolonged corticosteroid use, especially in adolescents.⁷ Sudden pain and decreased ROM should be evaluated with imaging, beginning with plain radiographs and progressing to magnetic resonance imaging (MRI) if results are inconclusive but suspicion is high.

The neuromuscular system is at risk for complication as well. Steroid-induced myopathy causing painless weakness in proximal muscles is a common complication of prolonged corticosteroid use. Because discontinuation of steroid is often not an option, rehabilitation strategies should focus on improving strength, adaptive techniques, and equipment. Children with GVHD are also at risk for polyneuropathy from prior chemotherapy treatment and compressive neuropathies from fascial restrictions. There are numerous other manifestations of GVHD that require an interdisciplinary approach for adequate management. Gastrointestinal GVHD can reduce nutrient absorption and lead to poor growth and failure to thrive. Ocular GVHD can reduce vision and may require referral for low-vision therapy programs. Skin and mouth ulcers can be intensely painful, requiring adequate pain management. Each child should receive a tailored rehabilitation program directed at his or her specific GVHD manifestations and impairments.

Brain Tumors

Approximately 2,900 children under age 20 are diagnosed with brain tumors each year in the United States.⁴ It is the most common solid tumor in children and the leading cause of cancer-related mortality in children. Brain tumors are routinely classified based on the histology and the site of origin, although molecular features are becoming increasingly more important, dictating treatment and prognosis. Astrocytoma is the most common pediatric brain tumor overall, whereas medulloblastoma is the most common malignant brain tumor. About 60% of pediatric brain tumors are infratentorial. Supratentorial tumors are more common in the first 2 years of life and late adolescence, whereas infratentorial tumors predominate in children aged 3 to 11 years.

Treatment modalities include surgical resection, radiation therapy, chemotherapy, and immunotherapy. Sometimes high-dose chemotherapy followed by autologous HSCT is necessary (as in high-risk medulloblastoma). Side effects of cancer and its treatment depend on tumor histology, size, and location. Neurologic deficits including dysarthria, dysphagia, impaired vision and hearing, ataxia, apraxia, hemiparesis, sensory loss, spasticity, bowel and bladder dysfunction, seizures, and cognitive deficits may occur. Posterior fossa syndrome (mutism, dysphagia, cranial nerve dysfunction, weakness, emotional lability, etc.) may occur following posterior fossa tumor resection. Radiation therapy to the craniospinal axis has long-term neuropsychological sequelae and may also lead to radiation necrosis and secondary strokes. Comprehensive rehabilitation interventions should be initiated early and continued throughout the child’s treatment and into survivorship. Tone, bracing, and equipment needs should be addressed. Activity precautions may include seizure, postcraniotomy, postshunt, and spinal precautions.

Bone Tumors

About 700 children are diagnosed with malignant bone tumors in the United States each year. Malignant bone tumors account for 6% of all childhood malignancies, 56% of which are osteosarcomas and 34% Ewing’s sarcomas.⁴ Bone tumor incidence peaks at the age of 15, corresponding to the time of the adolescent growth spurt. Patients with newly diagnosed malignant bone tumors typically undergo extensive workup and imaging.

Treatment regimens typically consist of chemotherapy (systemic control) and surgery (local control—tumor resection, limb-salvage procedure, or amputation) and/or radiation therapy. Ewing’s sarcoma is radiation sensitive, whereas osteosarcoma is considered radiation resistant. Patients commonly undergo thoracotomies and/or lung radiation if there is a concern for or evidence of lung metastases. Multiregimen chemotherapy used for systemic control of disease may have negative physical, psychosocial, and socioeconomic sequelae. Physical complications include weakness, pain, neuropathy, impaired balance, and cardiac dysfunction. Surgery used for local control may result in impaired wound healing or wound dehiscence, infection, pain, hardware failure, and so on. Depending on the type of limb-salvage surgery performed, patients might have weight-bearing and activity restrictions. Radiation therapy may result in impaired skin integrity and fatigue. Other side effects of treatment may include edema/lymphedema, cardiac dysfunction, neuropathy, weakness, impaired balance, limited activity tolerance, and depression and anxiety.

Goals of rehabilitation interventions are to restore function, minimize disability/handicap, maximize energy conservation, provide caregiver education and training, and decrease caregiver burden. Following limb-salvage surgery or amputation, patients require rehabilitation interventions to assist with early mobility, learning of the use of assistive devices, weight-bearing and ROM precautions, gait training, and strengthening.

Neuroblastoma

Neuroblastoma is the most common cancer in infants. It accounts for 6% of all childhood cancers in the United States. Approximately 700 children are diagnosed with neuroblastoma each year, with most children under the age of 5 at diagnosis. The 5-year survival rate is 80%, but only 40% to 50% for children with high-risk disease. The tumor arises from embryonal cells of the sympathetic nervous system, and primary tumors can occur anywhere along the sympathetic train, most commonly in the abdomen. Discovery may be incidentally made with imaging or elevated catecholamine metabolites on screening urine studies.¹⁶ Tumors in the cervical region may produce Horner’s syndrome.¹⁷ Paraspinal tumors can occur at any level with nerve root compression or, more severely, cord compression in up to 5% of cases.^18,19 Common sites of metastasis include cortical bone, bone marrow, and the liver, with an unexplained preference for the bone of the orbit. Two paraneoplastic syndromes are recognized as well. Tumors secreting vasoactive intestinal peptide may present with intractable watery diarrhea.²⁰ Opsoclonus-myoclonus syndrome occurs in 2% to 4% of patients and presents with characteristic rapid eye movements, irregular muscle movement, and ataxia.²¹ Ultrasound is the most commonly employed imaging modality. Computerized tomography (CT) scans can identify anatomic considerations for surgical resection and evaluate for spinal cord compression in emergent cases. Meta-iodobenzylguanidine (MIBG) scintigraphy can evaluate for bone and soft tissue metastases.¹⁸ F-fluorodeoxyglucose positron-emission scans can also be used to evaluate for metastatic disease.¹⁶