Chemotherapy and Supportive Care Agents as Essential Medicines for Children With Cancer.

In resource-rich countries, 5-year survival rates for children with cancer approach 85%. This impressive statistic is largely the result of integrating research with clinical care. At the core of this endeavor are multiagent combination chemotherapy and supportive care agents (CASCA). Most CASCAs belong to the class of sterile injectable drugs, which make up the backbone of many proven and life-saving pediatric oncology regimens. There are few if any alternative agents available to treat most life-threatening childhood cancers. In the United States, shortages of CASCAs are now commonplace. The consequences of drug shortages are far reaching. Beyond the economic costs, these shortages directly affect patients' lives, and this is especially true for children with cancer. Drug shortages in general and shortages of CASCAs specifically result in increased medication errors, delayed administration of life-saving therapy, inferior outcomes, and patient deaths. One way to mitigate drug shortages is to adopt an essential medicines list and ensure that these medications remain in adequate supply at all times. We argue for creation of a CASCA-specific essential medicines list for childhood cancer and provide ethical and policy-based reasoning for this approach. We recognize that such a call has implications beyond pediatric cancer, in that children with other serious disease should have an equal claim to access to guaranteed evidence-based medicines. We provide these arguments as an example of what should be claimed for medical indications that are deemed essential to preserve life and function.

An Ethical Framework for Allocating Scarce Life-Saving Chemotherapy and Supportive Care Drugs for Childhood Cancer.

Shortages of life-saving chemotherapy and supportive care agents for children with cancer are frequent. These shortages directly affect patients' lives, compromise both standard of care therapies and clinical research, and create substantial ethical challenges. Efforts to prevent drug shortages have yet to gain traction, and existing prioritization frameworks lack concrete guidance clinicians need when faced with difficult prioritization decisions among equally deserving children with cancer. The ethical framework proposed in this Commentary is based upon multidisciplinary expert opinion, further strengthened by an independent panel of peer consultants. The two-step allocation process includes strategies to mitigate existing shortages by minimizing waste and addresses actual prioritization across and within diseases according to a modified utilitarian model that maximizes total benefit while respecting limited constraints on differential treatment of individuals. The framework provides reasoning for explicit decision-making in the face of an actual drug shortage. Moreover, it minimizes bias that might occur when individual clinicians or institutions are forced to make bedside rationing and prioritization decisions and addresses the challenge that individual clinicians face when confronted with bedside decisions regarding allocation. Whenever possible, allocation decisions should be supported by evidence-based recommendations. "Curability," prognosis, and the incremental importance of a particular drug to a given patient's outcome are the critical factors to consider when deciding how to allocate scarce life-saving cancer drugs.

Subsequent neoplasms of the CNS among survivors of childhood cancer: a systematic review.

Childhood cancer survivors are at risk for development of subsequent neoplasms of the CNS. Better understanding of the rates, risk factors, and outcomes of subsequent neoplasms of the CNS among survivors of childhood cancer could lead to more informed screening guidelines. Two investigators independently did a systematic search of Medline and Embase (from January, 1966, through March, 2012) for studies examining subsequent neoplasms of the CNS among survivors of childhood cancer. Articles were selected to answer three questions: what is the risk of CNS tumours after radiation to the cranium for a paediatric cancer, compared with the risk in the general population; what are the outcomes in children with subsequent neoplasms of the CNS who received CNS-directed radiation for a paediatric cancer; and, are outcomes of subsequent neoplasms different from primary neoplasms of the same histology? Our search identified 72 reports, of which 18 were included in this Review. These studies reported that childhood cancer survivors have an 8·1-52·3-times higher incidence of subsequent CNS neoplasms compared with the general population. Nearly all cancer survivors who developed a CNS neoplasm had been exposed to cranial radiation, and some studies showed a correlation between radiation dose and risk of subsequent CNS tumours. 5-year survival ranged from 0-19·5% for subsequent high-grade gliomas and 57·3-100% for meningiomas, which are similar rates to those observed in patients with primary gliomas or meningiomas. The quality of evidence was limited by variation in study design, heterogeneity of details regarding treatment and outcomes, limited follow-up, and small sample sizes. We conclude that survivors of childhood cancer who received cranial radiation therapy have an increased risk for subsequent CNS neoplasms. The current literature is insufficient to comment about the potential harms and benefits of routine screening for subsequent CNS neoplasms.

Guidelines for identification of, advocacy for, and intervention in neurocognitive problems in survivors of childhood cancer: a report from the Children's Oncology Group.

With modern therapies and supportive care, survival of childhood cancer has increased considerably. Patients who have survived cancers involving the central nervous system or who have received therapy toxic to the developing brain are at risk of long-term neurocognitive sequelae. Negative outcomes are observed most frequently in survivors of acute lymphoblastic leukemia and brain tumors. The Children's Oncology Group Long-term Follow-up Guidelines Task Force on Neurocognitive/Behavioral Complications After Childhood Cancer has generated risk-based, exposure-related guidelines designed to direct the follow-up care of survivors of pediatric malignancies based on a comprehensive literature review and expert opinion. This article expands on these guidelines by reviewing the risk factors for the development of neurocognitive sequelae and describing the expected pattern of these disabilities. We herein present recommendations for the screening and management of neurocognitive late effects and outline important areas of school and legal advocacy for survivors with disabilities. Finally, we list resources that can guide patients, their parents, and their medical caregivers as they face the long-term neurocognitive consequences of cancer therapy.