Survivors of childhood cancer, particularly those treated for childhood Hodgkin lymphoma or Wilms tumor with abdominal radiation, procarbazine (Matulane), and platinum chemotherapy, are at an increased risk of developing gastrointestinal subsequent malignant neoplasms, according to a retrospective cohort study among 14,358 survivors. “These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population,” the study authors stated in the Annals of Internal Medicine.
The Childhood Cancer Survivor Study includes patients at 26 centers in the United States and Canada diagnosed with leukemia, central nervous system cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, neuroblastoma, soft-tissue sarcoma, Wilms tumor, or bone cancer. The patients were diagnosed when they were younger than 21 and survived 5 or more years after the initial diagnosis. The increased risk for gastrointestinal cancer occurred as soon as 5.5 years after the diagnosis of childhood cancer. The study is ongoing, and the authors stated that they expect the incidence of gastrointestinal subsequent malignant neoplasms to continue to increase as the cohort ages.
In a cohort of 14,337 childhood cancer survivors, 802 subsequent malignant neoplasms were identified in 732 individuals. Of that group, 45 (5.6%) gastrointestinal cancers were identified (in 45 patients) at a median follow-up of 22.8 years after primary diagnosis. The median age at diagnosis of gastrointestinal subsequent malignant neoplasms was 33.5 years. The risk for developing a gastrointestinal cancer was 4.6-fold higher in childhood cancer survivors than in the general population, the researchers reported.
Subsequent Tumor Sites
According to the investigators, the most frequent site of a subsequent neoplasm was the colon, followed by the rectum or anus. Of the 45 identified gastrointestinal subsequent malignant neoplasms, 25 (56%) were adenocarcinomas. Of those 45 patients, 23 (51%) had died, 15 (65%) of the subsequent malignant neoplasms.
While the researchers anticipated that “survivors treated with abdominal radiation would be at greatest risk for gastrointestinal cancer,” they reported that 13 of the 45 subsequent malignant neoplasms occurred outside of the radiation field or in survivors who did not receive radiotherapy as part of their primary treatment. In addition, procarbazine and platinum drugs were independently associated with a greater risk for subsequent cancers in the radiation field, suggesting that these agents may “potentiate the carcinogenic effects of radiation,” the authors noted.
“Because cure of the primary childhood cancer is a priority, we do not advocate for modification of the current treatment protocols used for childhood cancer to decrease the long-term risk for gastrointestinal [subsequent malignant neoplasms]. However, pediatric oncologists strive to reduce or eliminate late toxicity without affecting the probability of cure; therefore, the necessity of such therapies as radiation is under constant scrutiny. Our observations should enable researchers and clinicians to better identify survivors at highest risk for gastrointestinal [subsequent malignant neoplasms], potentially facilitating the implementation of better surveillance in clinical practice,” the authors concluded.
The Children’s Oncology Group currently recommends that “survivors exposed to more than 30 Gy of abdominal radiation have colonoscopy at a minimum of every 5 years, beginning 10 years after radiation or at age 35 years, whichever is later,” the authors added. “If the findings of this study are confirmed, physicians should also consider chemotherapy exposures when determining the indications for early colorectal cancer surveillance in childhood cancer survivors.”
Henderson TO, et al: Ann Intern Med 156:757-766, 2012.