Substantial improvements in prognosis following a pediatric cancer diagnosis over the last half century have led to increasing focus on improving the long-term health of pediatric cancer survivors. The occurrence of subsequent cancers is one of the leading causes of non-relapse morbidity and mortality in this patient population. In recent years, both radiotherapy and systemic therapy have emerged as clearly associated with increased risk for a wide range of subsequent cancer types. Additionally, expansion of large-scale genomics studies has led to the identification certain survivors with a genetic predisposition for subsequent cancers, and, more recently, the potential for lifestyle or other modifiable risk factors to impact risk has also been explored. Accordingly, long-term follow-up guidelines have been developed to attempt to inform clinical care to optimize the health of patients over their lifetime. However, major changes in treatment approaches with the advent of new radiotherapeutic techniques and novel therapies as well as a relative lack of uptake of screening guidelines have led to the need to engage a group of cutting-edge experts to advance the design and conduct of clinical and population studies that will impact clinical practice to reduce subsequent cancer risk and improve outcomes among children with cancer. The proposed Forbeck Forum will cover four primary sessions on 1) radiotherapy, 2) systemic therapy, 3) genetics, lifestyle, and co-morbid conditions as modifiers of treatment-related risks, and 4) clinical translation, with major questions outlined below.

Radiotherapy

• What are the most important advances in our understanding of radiotherapy-related subsequent neoplasms after childhood cancer?

• What are the key questions in the field that remain that, if answered, would have a significant and lasting impact on the field?

• What are the present and future practice changes that may change risk?  What research is needed to study these changes to determine risk reduction, or unanticipated effects?

• How should we consider dose volume and fractionation in relation to risk?

• What are the biggest statistical challenges in studying radiotherapy-related subsequent neoplasms after childhood cancer?

Systemic therapy

• What are the most important advances in our understanding of chemotherapy -related subsequent neoplasms after childhood cancer

• What are the key questions in the field that remain that, if answered, would have a significant and lasting impact on the field?  

• What are the present and future practice changes that may change risk?  What research is needed to study these changes to determine risk reduction, or unanticipated effects?

• What is the risk for subsequent neoplasms due to novel therapies for children with cancer (immunotherapy, cellular therapy, targeted therapies)?  

• How should we consider combination therapy and treatment for relapsed/refractory disease in relation to risk?

• What are the biggest statistical challenges in studying chemotherapy-related subsequent neoplasms after childhood cancer?

Genetics, lifestyle, and co-morbid conditions as modifiers of treatment-related risks  

• Which lifestyle modifiers of treatment-related risks are of greatest importance?

• How should we integrate genetic risk for subsequent neoplasms into research and clinical practice?

• How should we model the non-treatment risk factors in the presence of such strong treatment-related risks?

Clinical translation  

• What are the optimal screening strategies? What are the best strategies for early detection or prevention?

• What evidence base is needed to translate research findings into clinical practice?  

• What intervention strategies are efficacious to improved screening and early detection of subsequent neoplasms?  What are the interventions that will advance the field?

• What are the barriers to Implementation? i.e., why is uptake of screening/surveillance so low? Address issues related to cost/reimbursement and effective health communication

• How to we translate evidence into effective health policy?