Research in context
Evidence before this study
An increased risk of premature gonadal failure has been shown in survivors of paediatric cancer treated with chemotherapy and radiotherapy. 6% of female survivors of childhood cancer lose ovarian function within 5 years of treatment (acute ovarian failure), and an additional 9% have premature, non-surgical menopause before the age of 40 years. The timeframe between primary cancer diagnosis and treatment resulting in acute ovarian failure is short to identify high-risk patients that will benefit from interventions aimed at fertility preservation. We searched PubMed with no date or language restrictions for all studies to evaluate the current knowledge of acute ovarian failure and the associated risk factors in survivors of childhood cancer using the search terms “pediatric cancer OR childhood cancer” AND “acute ovarian failure OR primary ovarian insufficiency” AND “risk”. Five publications were considered for further review as they described acute ovarian failure as an independent condition without grouping patients in a broader premature menopause category. Although high-dose pelvic radiotherapy, haematopoietic stem-cell transplantation, and alkylating chemotherapy have been identified as risk factors associated with acute ovarian failure, clinicians do not have a tool that accurately estimates the risk of acute ovarian failure for individual paediatric patients with cancer at the time of cancer diagnosis. We did not find any study that aimed to develop risk estimates of acute ovarian failure for individual paediatric patients with cancer at the time of cancer diagnosis.
Added value of this study
To our knowledge, we have developed and validated the first models for predicting the risk of acute ovarian failure in female survivors of childhood cancer. Although physicians are aware of the gonadotoxic treatment exposures with a high likelihood of causing acute ovarian failure, there are no available prediction tools to estimate the risk of acute ovarian failure for a given patient on the basis of a planned oncological treatment regimen. A precise risk estimate available to clinicians will guide informed discussions with patients and their families for time-sensitive interventions to preserve fertility function before initiation of cancer treatment and inform the need for future ovarian hormone replacement treatment after completion of cancer therapy. We provide an easily accessible and user-friendly online calculator for acute ovarian failure risk for clinicians to directly calculate each patient's risk for acute ovarian failure on the basis of their planned cancer treatment. The developed models performed well both internally and externally, highlighting the validity of the risk estimates and ensuring that clinical recommendations are provided with confidence.
Implications of all the available evidence
Since most patients with childhood cancer will become long-term survivors, the focus of cancer survivorship research has shifted toward maximising survivor quality of life. Our models and the associated web application can help inform discussions with female patients and their families at the time of cancer diagnosis regarding the need for fertility preservation before cancer treatment and the possible need for ovarian hormone replacement after completion of cancer therapy.