Improving Outcomes for Children With Rare Cancers

childhood cancers: childhood cancersThe Orphan Drug Act of 1983 and U.S. Rare Diseases Act 2002 define a rare disease as one that affects fewer than 200,000 people. By this definition all pediatric cancers, which comprise 1 percent of cancer diagnoses in the U.S., would be classified as rare. Within childhood cancers, however, there are certain diagnoses that a typical pediatric oncologist might only see once or twice during their career. As a result, children with rare tumors face specific challenges in their care, including delays in diagnosis, a shortage of available clinical trials, and a lack of standardized treatment regimens. There is no single accepted criteria for childhood rare tumors. The Children's Oncology Group (COG) rare tumor committee defines them as those “classified as other malignant epithelial neoplasms and melanomas in the International Classification of Childhood Cancer subgroup XI of the SEER database.” This definition includes diagnoses such as adrenocortical carcinoma, thyroid carcinoma, nasopharyngeal carcinoma, malignant melanoma, and skin carcinoma, but excludes other rare malignancies such as pleuropulmonary blastoma (PPB) and pancreatoblastoma. The Italian rare tumor project, Tumori Rari in Etá Pediatrica, on the other hand, defines rare pediatric cancer as any cancer with an annual incidence of less than two per million and not considered in any clinical trials. Although individually these tumors are considered rare, as a group they account for 14 percent of all malignancies in the 0-14 year age group and 24 percent of all malignancies in the 0-19 year age group. Pediatric rare tumors typically fall into one of two categories: those that occur commonly in adults but rarely occur in children, or those that are exclusive to pediatrics. For pediatric tumors that fall into the first category, such as melanoma or colorectal cancer, many of the treatment regimens are adapted from those used in adults. This is less than ideal, however, as molecular genetic studies sometimes find significant differences in these rare tumors in children, and also because children have an increased risk of late effects compared with adults. For tumors that occur exclusively in children, such as pancreatoblastoma, oncologists often do not have a standardized treatment regimen to follow, and instead need to create individualized protocols for each patient. Over the years, clinical trials have led to significant advances for many childhood cancer patients with more common diagnoses. Acute lymphoblastic leukemia, for example, now boasts a 5-year, event-free survival rate of 80 percent. Unfortunately, due to the low incidence of pediatric rare tumors, clinical trials are often unavailable for these patients. For this reason, it is crucial to centralize the care of such patients in programs with experience. Rare Tumor Registry Created Texas Children's Cancer Center (TXCC) cares for nearly 75 patients with rare cancers every year. Texas Children's Rare Tumors Program was established in 2015 with the mission to improve the outcomes of children with rare tumors in North America. To accomplish this, clinicians have embarked on a two-pronged approach: helping individual patients through free consultations, and improving outcomes for pediatric rare cancers as a whole through creation of a rare tumor registry. As a service to patients and providers, the facility offers free consultations for physicians in the U.S. and Canada to help guide management for patients with rare tumors. The program has established standardized management guidelines for multiple rare tumors utilizing the best available evidence. Advanced molecular diagnostic tests to confirm diagnoses for patients with rare tumors are offered. For instance, TXCC is the only pediatric center to offer CLIA-certified BCOR mutation testing for clear cell sarcoma of the kidney and undifferentiated round cell sarcoma. Additionally, the program has founded the North American Pediatric Rare Tumor Registry. While efforts to establish pediatric rare tumor registries in countries with centralized health care systems have been successful in Europe, similar efforts through COG have not produced the desired results in the U.S. This is due both to a lack of enthusiasm from clinicians for enrolling patients on non-therapeutic trials and to the shortage of resources at individual institutions. Meanwhile, registries dedicated to individual tumors, such as the PPB registry (www.ppbregistry.org) and the NUT midline carcinoma registry (nmcregistry.org), have been successful in advancing both patient care and science. For example, research on tissue from the PPB registry led to the discovery of DICER1 syndrome, an inherited tumor susceptibility syndrome that has implications beyond PPB. The existence of such tumor specific registries are largely due to the effort of passionate clinicians, researchers, and patient groups. The facility has expanded on this model by establishing a registry for all rare pediatric tumors. The goal is to take away the workload from individual physicians and institutions and enroll patients directly. Patients may find out about the registry through their physicians, the TXCC website, or outreach efforts to patient groups. Individuals are consented over the phone, and medical records are obtained from the treating institutions. In addition, program clinicians request a blood sample from the patient and a buccal swab sample from each of their parents. DNA is subsequently extracted from these paired samples and stored for future research. Patient data and samples are available to all researchers interested in specific rare tumors. The program's hope is to help advance knowledge of pediatric rare tumors through collaboration with patients, physicians, and researchers. More information Texas Children's Cancer Center's free consultation services and the North American Rare Tumor Registry can be obtained by emailing [email protected]. SAMARA L. POTTER, MD, MBA, is a Clinical Fellow, Texas Children's Cancer Center, Houston. RAJKUMAR VENKATRAMANI, MD, MS, is the Director of the Rare Tumors Program at Texas Children's Cancer Center, Houston, which is a top 10 pediatric cancer hospital according to U.S. News & World Report.Samara L. Potter, MD, MBA: Samara L. Potter, MD, MBARajkumar Venkatramani, MD, MS: Rajkumar Venkatramani, MD, MS

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