What Is the Clinical Course of Pediatric Cancers?

Introduction and Scope of the Problem

Children rarely develop the cancers that predominate in high-income countries in adulthood, including breast cancer, lung cancer, prostate cancer, and colon cancer. Instead, children develop leukemias, lymphomas, brain tumors, and extracranial solid tumors arising from muscle, neural tissue, bone, or internal organs. Approximately 16,000 children are diagnosed with cancer annually in the United States (U.S.), accounting for ~1% of all cancer diagnoses. Though the clinical course varies substantially depending on the type of cancer diagnosed and the underlying health of the child, most children diagnosed with cancer in high-income countries in the current era are expected to survive their cancer and its initial treatment. Children who develop cancer, receive treatment, and live beyond the period of treatment are frequently called “survivors.” Data from the Surveillance, Epidemiology, and End Results (SEER) database show that in the period between 2011 and 2017, 85.1% of children aged 0 to 19 years who were diagnosed with cancer were expected to be alive 5 years after their diagnosis. In the period between 1975 and 1979, only 63% of such children were expected to be alive 5 years after their diagnosis, and between 1960 and 1963, only 28% of such children lived 5 years beyond diagnosis.

The change in prognostic outlook has been most dramatic for acute lymphoblastic leukemia, the single most common form of childhood cancer and the form of cancer that launched the paradigm of combination chemotherapy as a potentially curative treatment for cancer. In 1968, Audrey Evans, MD, published an article titled “If a Child Must Die …” and in 1978, Myra Bluebond-Langner, PhD, published the book The Private Worlds of Dying Children . These works operated from the then-incontrovertible perspective that childhood leukemia was a disease that was relatively rapidly fatal for most children who developed it. Yet it was in the 1970s that more efficacious chemotherapeutic treatments led to the emergence of the idea of the childhood cancer “survivor.” By 1981, Koocher and O’Malley had published The Damocles Syndrome , detailing the psychosocial sequelae of childhood cancer and its treatment; the title comes from the writings of Cicero, in which the character Damocles, a courtier eager to experience what it means to be King, sits down to a lavish dinner, only to find that he is seated beneath a sword that is held aloft by a single horsehair. Throughout the late 1970s and 1980s, the word “cure” was being applied with increasing frequency and confidence, though, as Mauer astutely warned, “defining cure for a child with cancer is not so simple.” Today, a diagnosis of childhood cancer marks the beginning of an explicitly uncertain life. Most children will survive their initial cancer and its treatment, and most adult survivors of childhood cancer will contend with chronic health conditions, including risks of a second cancer and heart disease. Yet at the same time, cancer remains a leading cause of childhood death. Cancers that convey a high risk of death due to progressive disease include midline gliomas such as diffuse intrinsic pontine glioma, glioblastoma multiforme, forms of acute myeloid leukemia, and some metastatic solid malignancies such as neuroblastoma characterized by MYCN amplification, alveolar rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma. For any child diagnosed with cancer, cancer and cancer treatment are likely to produce physical suffering, emotional distress, and disruptions to life both immediately and in the future.

Relevant Stages in the Trajectories of Pediatric Cancer