Late effects of high-dose methotrexate in childhood cancer survivors: a Swiss single centre observational study

Abstract

ImportanceChildhood cancer survivors (CCS) are at risk for late effects of different organ systems. The currently available screening recommendations for those treated with high-dose methotrexate (HD-MTX) are not uniform and the available literature is limited.ObjectiveWe aim to assess the prevalence and severity of late effects in CCS treated with HD-MTX at a single centre in Switzerland. We focus on organ systems defined at risk by the long-term follow-up care guidelines of the children’s oncology group (COG), because this guideline has a holistic approach, is evidence based, and up to date.MethodsWe used the modified Common Terminology Criteria for Adverse Events (CTCAE) to assess late effects in 15 different organ systems. Eligible were CCS diagnosed with cancer younger than 18 years and treated with HD-MTX, defined as at least 1 g per body surface area (≥ 1 g/m2).ResultsWe analysed 32 CCS with a median follow-up of 12.1 years. The endocrine system was most frequently affected by adverse events (69%), followed by the musculoskeletal (57%) and neuropsychological (38%) systems. The hepatobiliary (9%) and immunological (6%) systems were the least affected ones. Within the endocrine system, overweight/obesity was the most frequent and severe diagnosis.ConclusionLate effects in CCS treated with HD-MTX are frequent. Our findings could add to the COG guidelines, where only screening for the musculoskeletal, neuropsychological, and hepatobiliary systems are recommended. More patient data need to be collected and analysed using the suggested standardised approach, to increase the quality of evidence for future screening recommendations.