The prognosis of cancer in children has improved dramatically over the past 40 years. Unlike many adult cancers, pediatric malignancies are often responsive to initial aggressive chemotherapy, radiation, and surgery. Currently, the estimated survival rate for a child (age 0-19) with cancer is 80%. However, these therapies often produce acute and chronic pain problems, such as mucositis, graft versus host disease (GVHD), peripheral and central neuropathic pain, phantom limb pain, prolonged postdural puncture headache, radiation dermatitis, and visceral hyperalgesia. Although treatment-related pain generally exceeds tumor-associated pain in pediatric cancer patients, tumor-associated pain is prevalent and may involve bone, viscera, nerves, and other tissues. In the most common diagnostic category of pediatric cancer, leukemia, presenting in children 2 to 6 years of age, bone pain is secondary to rapid growth of precursor cells in the bone marrow. In adolescents, malignant bone tumors and lymphomas produce most tumor-related pain. The most common solid tumor diagnosed during childhood, central nervous system (CNS) tumor, may induce headache caused by increased intracranial pressure (ICP).

Following the often successful treatment protocols for children with cancer, there is increasing risk of delayed and chronic complications of treatment, such as secondary malignancies, skeletal disorders, cardiac and pulmonary insufficiency, neurocognitive disability, and pain. At present, the estimated number of childhood cancer survivors in the United States is greater than 300,000, and there is a 75% risk of a chronic health disorder 30 years postdiagnosis. Early recognition and treatment of medical and psychological issues in children treated for cancer are a public health care concern.

As the assessment of pain in children is guided by the child’s cognitive and behavioral development and individualized coping skills,¹ the treatment of cancer pain in children should involve a multidimensional approach that uses medications for pain and symptom management and also cognitive-behavioral interventions and other nonpharmacologic therapies. This approach provides optimal pain control and addresses patients’ complex emotional needs related to grief and sense of loss.

In contrast to adults, children with cancer experience pain more frequently related to aspects of cancer treatment. This is in part because of higher rates of remission in children after initial chemotherapy induction and improved long-term survival rates in childhood cancers.^1,2

Procedures such as bone marrow biopsies and aspirates, lumbar punctures, and central venous line insertions are common sources of distress and pain in children with cancer. Pain related to the treatment of cancer includes painful mucositis, amputation pain, and painful neuropathies from surgery and chemotherapeutic agents.

Every attempt should be made to minimize distress, fear, and pain in children undergoing brief needle procedures and more invasive procedures because traumatic experiences with initial procedures make subsequent procedures more distressing. Treatment of procedure-related pain is combination of cognitive-behavioral interventions, local anesthesia, conscious sedation, and general anesthesia.

Evidence supports the use of cognitive-behavioral strategies in the management of procedure-related pain in children with cancer. Guided imagery, progressive muscle relaxation, and hypnosis can direct patients’ focus away from pain and the procedure to reduce their experience of pain, fear, and discomfort. Young children or those with developmental deficiencies, however, may not have the cognitive abilities to use these strategies. Explaining the procedure in age-appropriate terms can gain the child’s trust and confidence.

Local anesthetics and conscious sedation combined with cognitive-behavioral strategies can make procedures less terrifying for children. Traditional agents utilized as topical anesthetics for pediatric needlestick procedures include eutectic mixture of local anesthetics (EMLA), various lidocaine formulations, and vapocoolants. Newer agents and novel drug-delivery systems include lidocaine/tetracaine heating patches and pressurized lidocaine delivery systems (J-Tip, Zingo). Application of topical anesthetics to overlying intravenous (IV) catheter-insertion sites or lumbar puncture sites can decrease pain from needle insertion into the skin. This allows less painful infiltration of local anesthetics deep to the dermis. For more invasive procedures or for children who experience significant distress during brief needle procedures, conscious sedation or general anesthesia should be used. Conscious sedation is a level of sedation in which a child is comfortable but is able to maintain airway reflexes and spontaneous ventilation. Conscious sedation is often performed by pediatric subspecialists and is widely used for bone marrow aspirates or biopsies, lumbar punctures, and central venous line removals (Table 66-1). Consultation with a pediatric anesthesiologist is indicated for more invasive procedures or for children with certain risks of conscious sedation, such as airway anomalies, obstructive sleep apnea, and significant gastroesophageal reflux disease.

Centers that provide care for children with cancer often have a two-tiered approach in which specific procedures are performed under conscious sedation by pediatric subspecialists, such as oncologists and radiologists. Sedation protocols guide the choice of sedative, dosing, monitoring, and indications when a pediatric anesthesiologist is required. For young infants, or for patients with specific cardiac, neurologic, or airway diseases that increase risk, sedation or general anesthesia by pediatric anesthesiologist is indicated.

Mucositis is painful mucosal inflammation and necrosis caused by chemotherapy or radiation therapy. Although mucositis is a self-limiting condition in most patients, it causes significant pain and distress in children. Mucositis associated with bone marrow transplantation can be especially prolonged and painful. Topical therapies such as diphenhydramine, viscous lidocaine, antacids, and sucralfate may be used to provide symptomatic relief; however, there is little evidence to support efficacy. Patient-controlled analgesia (PCA) is frequently used in addition to topical agents. Some children, however, continue to experience significant pain despite aggressive opioid dosing. PCA permits dose titration and treatment of acute exacerbations associated with mouth or perineal care. Several studies have shown lower pain scores, fewer side effects, and lower opioid use in treating mucositis with PCA compared with staff-controlled analgesia.³

Vincristine is an antineoplastic agent associated with peripheral neuropathies such as sensory deficits, gastrointestinal dysmotility, and paresthesias. Some children treated with vincristine experience burning neuropathic pain of the lower extremities. Additional studies are needed to determine the best treatment strategy; however, opioids, tricyclic antidepressants (TCAs), and anticonvulsants are often used. In most patients, symptoms improve gradually but may recur with repeated use of vincristine. Chemotherapeutic agents associated with potential neuropathic pain include cisplatin, etoposide, and paclitaxel.

Most children experience tumor-related pain at initial diagnosis. A survey by Miser and colleagues showed that 62% of children reported pain prior to receiving an initial diagnosis of cancer.⁴ Additional studies show that 25% of outpatient pediatric patients with cancer report experiencing daily pain.⁵ Tumors can produce different types of pain through stretch or involvement of bone, viscera, nerves, and other tissues. Leukemia can produce constant, aching bone pain caused by proliferation of malignant cells in marrow causing compression of the marrow space. Bone pain can also result from metastasis of solid tumors to localized areas of bone. The involvement of lymphoma, leukemia, and neuroblastoma in solid viscera such as spleen and liver can cause abdominal pain by distension and capsular stretch. Tumors can spread to plexuses, peripheral nerves, or the epidural space, causing lancinating and sometimes refractory neuropathic pain. Children with brain tumors and increased ICP often present with headaches and, in some cases, focal neurologic signs or seizures. Spinal cord tumors or the extension of tumors into the intrathecal space typically cause back or neck pain.⁶

The assessment of pain in children with cancer can be challenging. Children with inadequately treated cancer pain may withdraw from their environment and may erroneously appear comfortable to health care providers (HCPs). Pain assessment scales developed to assess acute pain frequently underrate pain when used to assess persistent cancer pain. Physiologic signs such as blood pressure and heart rate may habituate with persistent pain. Gauvain-Piquard and colleagues designed an observational pain scale specifically for young children with cancer that includes depression and anxiety-like descriptors often reported by patients.⁷

Cancer pain is often best treated using a multidisciplinary approach that combines the aggressive use of pharmacologic agents, psychosocial support, cognitive and behavioral therapy, and nerve blocks. The World Health Organization (WHO) has developed an analgesia ladder to guide physicians in treating cancer pain. A study of children with terminal malignancies showed that over 90% of patients had effective pain relief when managed according to standard escalations based on WHO guidelines.⁸ According to this treatment guide, non-opioid analgesics such as acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) are a “Step 1” therapy. Selective COX-2-inhibitors may be used for children with platelet dysfunction or for children who experience gastric side effects with NSAIDs. Weak opioids, such as low-dose oxycodone, often combined with acetaminophen are “Step 2” in managing mild pain. Recommended oral dosing of oxycodone is 0.5 to 1 mg/kg every 4 hours. Patients tend to experience more nausea and other side effects with higher doses of codeine compared with other opioids. In addition, some patients lack sufficient enzyme activity to O-demethylate codeine to morphine, causing a marked reduction in analgesic effect.⁹ Dosing of acetaminophen and opioid combination preparations is usually limited by the maximum recommended acetaminophen dose. Weak opioids have a “ceiling effect” whereby escalation of dose typically causes increased side effects without improving analgesic effect. Strong opioids such as morphine, hydromorphone, and fentanyl used for moderate to severe pain, or worsening pain are “Step 3.”

With progression of cancer pain, μ-opioid agonists are the cornerstone of treatment (Table 66-2). Oral dosing of opioids is preferable where possible. Regular scheduled dosing of opioids should be used for patients who have continued pain in order to avoid breakthrough pain. Morphine is the most widely used opioid for treating cancer pain in children. Younger infants have an increased risk of hypoventilation with opioids because of both pharmacokinetic factors, such as diminished hepatic conjugation, and pharmacodynamic factors, such as immature ventilatory reflex response to hypoxemia and hypercapnia. A typical starting dose for immediate-release morphine in opioid-naïve patients is 0.3 mg/kg orally every 4 hours. Sustained-release preparations of morphine and oxycodone are frequently used and are effective alternatives to frequent dosing of short-acting agents. A significant number of children are unable to swallow pills, which limits the use of sustained-release preparations in these patients.