26. Malignancy and Treatment of Malignancies in Children

Bruce Hullett¹

(1)

Department of Anaesthesia and Pain Management, Perth Children’s Hospital, Nedlands, WA, Australia

Bruce Hullett

Email: Bruce.Hullett@health.wa.gov.au

Keywords

Anterior mediastinal mass anesthesiaAnesthesia for pediatric oncology proceduresMucositis in children

Children with cancer have multiple anesthetics during their treatment. Their clinical state may be related directly to the cancer or to the complications of therapy and they may be very unwell at times. The children and their families are under considerable stress and require an empathic approach from all of their health care providers

Cancer is uncommon in children compared to adults—15% of all cancer occurs in children, half of which occurs in children 4 years and younger. Cancers however are the second commonest cause of death in children after trauma (road accidents and drowning). One third of all cancers are leukemia, and 1 in 5 cancers are CNS tumors, although the different cancers occur at different rates in various age groups (Fig. 26.1). Childhood cancers have a survival rate higher than for adults, approaching 85% for hematological malignancies.

../images/467929_2_En_26_Chapter/467929_2_En_26_Fig1_HTML.jpg — Fig. 26.1

Incidence of the commonest tumor types in different age groups. Darker shading indicates higher incidence. Adapted from Steliarova-Foucher E. Lancet Oncology 2017;18: 719–31

Although the commonest cause of pain in children with cancer is chemotherapy treatment, these children report that medical procedures or surgery cause the worst pain during their treatment. General anesthesia during medical procedures such as lumbar punctures and bone marrow biopsies avoids this pain—anesthetists can make a huge contribution to the care of these children by reducing the most severe pain during cancer treatment. Anesthetists may also provide IV access, anesthesia for imaging procedures, surgical tumor resection, radiotherapy and pain management.

The issues arising in the oncology patient vary over the course of their treatment. Direct effects of the tumor give way to systemic effects of treatment—particularly hematopoietic effects of chemotherapy that can result in potentially life-threatening complications. Pain is often present at the time of diagnosis, but its character may change as therapy is begun and pain from procedures and mucositis become predominant. Many children participate in oncology trials that follow set treatment protocols. These protocols may be compromised by issues such as anesthesia not being available at the correct time in the treatment cycle, or simply by using dexamethasone as an antiemetic.

26.1 Chemotherapeutic Agents

Chemotherapy is based on the age of the child and the type and stage of the tumor. It may be used alone or in conjunction with surgery or radiotherapy. Chemotherapy has significant side effects, and multiple agents are usually used to improve outcome and reduce toxicity. Chemotherapeutic agents may be considered either as conventional agents directed at rapidly dividing cancer cells by various mechanisms, or as more modern molecularly targeted agents directed at tumor cell receptors or specific processes such as angiogenesis or immunomodulation. Conventional agents are commonly used at maximally tolerated doses, whilst molecular target agents have greater specificity with possibly fewer side effects. Many of these drugs, however, are in early development and their full potential is yet to be realized. Corticosteroids are also commonly used in treatment for their cytotoxic, immunosuppressive and antiemetic properties. Suppression of the hypothalamic-pituitary axis is common.

Chemotherapy is used to treat the commonest childhood leukemias—acute lymphatic leukemia (ALL) and acute myeloid leukemia (AML). The treatment for ALL is more protracted than for AML and has 3 phases—induction and intensification lasting about 1 month each, followed by a maintenance phase lasting 1 or 2 years. Treatment includes intrathecal methotrexate or cytarabine, which has decreased the need for central nervous system radiotherapy and its longer-term effects on neurodevelopment and body growth. The treatment of AML requires more aggressive chemotherapy with an increased risk of complications, but treatment is shorter and without a maintenance phase. Hematological malignancies with poor prognostic features or that have relapsed may be considered for a stem cell transplant if a suitable donor can be found.

26.1.1 Toxicity

Chemotherapeutic agents cause myelotoxicity with anemia, neutropenia and thrombocytopenia, as well as gastrointestinal toxicity with nausea, vomiting and mucositis. Toxicity may also affect every other organ system in the body. Myelotoxicity often causes anemia that may require transfusion before surgery, depending on the clinical status of the child. Transfused blood is usually leucodepleted to reduce fevers and infection, and irradiated to stop donor T-cell replication and reduce graft vs. host disease. Thrombocytopenia may delay procedures such as lumbar puncture or line insertion. Platelet levels of 30,000/μL or higher are usually acceptable in these children, although the lower acceptable limit varies as evidence-based guidelines are lacking. Children with severe leucopenia are vulnerable to infection and sepsis, and strict attention should be paid to aseptic techniques during anesthesia care. Many of these children have long term surgical IV lines (Hickman, Broviac, Portacath, Infusaport) that need to be accessed carefully to avoid infection—the anesthetist should wash their hands, clean the access point, wear gloves and use a no-touch technique to access the device. Early placement of indwelling venous devices reduces the need for multiple peripheral IV lines, reduces the child’s anxiety, and allows recovery from the surgical insertion before the effects of chemotherapy become problematic.

Fortunately for anesthetists, the oncology team are very experienced with the toxicity and problems from these chemotherapeutic agents and are careful to monitor for them and manage them. The anesthetist is usually alerted to their presence. Some chemotherapeutic agents have specific effects on organ systems—the most important are outlined in Table 26.1.

Table 26.1

Effects of chemotherapy on specific organ systems side effects

System	Drug	Comment
Cardiac	Doxorubicin Daunorubicin Cyclophosphamide Cisplatin, 5-fluorouracil	Rhythm abnormality, cardiomyopathy
Pulmonary	Bleomycin	Pneumonitis, non-cardiogenic edema (may be increased by supplemental oxygen) Fibrosis
	Mitomycin
	Methotrexate	Pneumonitis, bronchospasm, effusion
Nervous system	Cisplatin	Sub-clinical neuropathy