Garrett M. Brodeur

Perspectives and Understanding of Radiation Risks in CPS: A Practitioner Survey

Children with cancer predisposition syndromes have an increased risk of developing certain cancers. Surveillance imaging plays an increasingly important role in the management of these children. The approach to imaging must account for several factors, including age of the child, onset and frequency of imaging, whether sedation is needed, and the types of tumors associated with a particular syndrome. Consideration must also be given to the potential risks and benefits associated with a given imaging technique. Whole-body MRI offers many advantages, including a comprehensive examination without ionizing radiation. Other techniques, such as CT, involve low doses of ionizing radiation but may be appropriate depending on the clinical circumstance. This article offers an overview of available imaging techniques along with potential strategies to guide the discussion with patients and families when deciding on the most appropriate surveillance imaging approach.

Main concerns or challenges practitioners report when assessing the relative risk of ionizing radiation-based imaging for pediatric cancer predisposition syndromes

Level of concern about the relative risk of ionizing radiation-based imaging for pediatric cancer predisposition syndromes contributing to future cancer risk

It is critical to share knowledge and harmonize approaches to optimize progress in rare cancers. The International Neuroblastoma Risk Group (INRG) Task Force was formed by the 4 major neuroblastoma cooperative groups in 2004 to achieve this goal. Strategies developed for neuroblastoma are an exemplar for other rare malignancies. Data from an initial cohort of 8800 patients were transferred to the INRG Data Commons, and a data-sharing model was developed. Currently, information on more than 25 000 patients is available to the research community. The INRG staging and risk classification systems have led to harmonized approaches for therapeutic groupings. INRG consensus manuscripts have led to uniform criteria for classifying biological data, evaluating the extent of disease, and defining treatment response. More than 40 INRG research studies have been performed by investigators from around the world, including analyses of rare patients, which would not otherwise be possible. The success of this approach for neuroblastoma has been leveraged to create the Pediatric Cancer Data Commons and the Data for the Common Good. Efforts to enrich the INRG Commons with additional genomic and biomarker data, extracted electronic health records, and digital medical images are ongoing. The international networking model developed by the INRG Task Force has led to new research discoveries and progress in neuroblastoma. The approach has now been applied to 16 other cancers and conditions, including rhabdomyosarcoma, germ cell tumor, Lynch syndrome, and cancer predisposition. This framework of international collaboration and data sharing serves as a model for advancing rare adult malignancies.

Hereditary endocrine neoplasia syndromes comprise multiple entities associated with an increased risk for the development of endocrine and nonendocrine neoplasms and other systemic manifestations. These syndromes typically demonstrate autosomal dominant inheritance, and each syndrome is associated with a unique genetic predisposition to a distinct spectrum of tumor susceptibility. Moreover, genotype–phenotype associations within each syndrome may affect the spectrum, penetrance, and age of onset of associated tumors. As many endocrine tumors are benign and/or indolent, a careful approach to monitoring is necessary, wherein the nature, timing of initiation, and frequency of presymptomatic surveillance balance the goal of detecting tumors at a point in which intervention would limit tumor-associated morbidity against the physical, emotional, and financial burdens of surveillance. In this study, we summarize changes in knowledge and practice recommendations related to children with multiple endocrine neoplasia syndromes (types 1, 2A, 2B, 4, and 5), hyperparathyroidism–jaw tumor syndrome, and Carney complex since an initial summary in 2017. These updates reflect the evolving understanding of these complex genetic disorders and aim to improve patient care and outcomes.

Children with cancer predisposition syndromes have an increased risk of developing certain cancers. Surveillance imaging plays an increasingly important role in the management of these children. The approach to imaging must account for several factors, including age of the child, onset and frequency of imaging, whether sedation is needed, and the types of tumors associated with a particular syndrome. Consideration must also be given to the potential risks and benefits associated with a given imaging technique. Whole-body MRI offers many advantages, including a comprehensive examination without ionizing radiation. Other techniques, such as CT, involve low doses of ionizing radiation but may be appropriate depending on the clinical circumstance. This article offers an overview of available imaging techniques along with potential strategies to guide the discussion with patients and families when deciding on the most appropriate surveillance imaging approach.

Hereditary Pheochromocytoma/Paraganglioma Syndromes (HPPS) are a collection of conditions caused by variants in genes producing subunits of the succinate dehydrogenase (SDH) complex or related proteins. These conditions are characterized by substantial lifetime risks for developing pheochromocytomas, paragangliomas, and other tumors. Affected individuals who develop these tumors may experience severe, acute and chronic problems. Indeed, aggressive, malignant, and/or disseminated tumors may result in death. Tumor surveillance enables early intervention, which, in turn, should lead to improved clinical outcomes. However, the desire for intensive surveillance strategies must be balanced against medical and psychosocial risks. In 2017, consensus HPPS surveillance recommendations addressing germline predisposition to SDHA, SDHAF2, SDHB, SDHC, SDHD, MAX, TMEM127 (collectively, SDHx+) related tumors were published after the inaugural AACR Childhood Cancer Predisposition Workshop. Based on the limited available clinical data at that time, these recommendations advocated a uniform approach to tumor surveillance in HPPS. Since then, several other groups have proposed alternative consensus surveillance guidelines. Although these surveillance approaches share some common elements, including recommendations tailored to emerging differences in tumor phenotype based on underlying specific SDHx+ genes, these approaches also vary significantly amongst each other. As clinical data continue to accrue, it is critical that surveillance strategies continue to be refined to address emerging genotype-phenotype differences. In this review, we provide a brief up-to-date clinical overview of HPPS and describe recently proposed tumor surveillance regimens. We then detail our updated consensus pediatric-focused tumor surveillance recommendations from the 2023 AACR Childhood Cancer Predisposition Workshop.

An increasing number of studies suggest that a significant proportion of children with cancer harbor an underlying predisposition to malignancy, and it is likely that this proportion will only increase. Targeted surveillance for these individuals would likely improve outcomes. Historically, however, for most predisposition syndromes, there were no standardized surveillance protocols for early detection of cancer in predisposed individuals. Therefore, the Pediatric Cancer Working Group of the American Association for Cancer Research convened a workshop in 2016 to develop consensus surveillance recommendations (published in 2017) for children and adolescents with the most common cancer predisposition syndromes. These recommendations provided a consistent approach for pediatric oncologists and other care providers to use as a plan for cancer surveillance in pediatric patients with these syndromes. We held a second workshop in 2023 to update recommendations based upon new data, as well as to add syndromes that were newly described or not addressed in the prior workshop. The resulting articles represent updated surveillance recommendations for currently recognized predisposition syndromes, organized along similar themes. We also address novel approaches to surveillance that are under investigation, as well as prospects for prevention trials for these high-risk populations.