The impact of dose intensity in the adolescent and young adult cancer population

Survival rates for Adolescent and Young adults (AYA) with cancer lag behind those of some children and many older adults with the same cancers. The reason for this is multifactorial but this study focuses on variation in treatment received. For many cancers common in AYAs there is the evidence that maintaining dose intensity (DI) improves outcomes. This can be problematic as the more intense regimes carry greater toxicity. In AYA there is both poor recruitment and access to available clinical trials. The use of routinely collected healthcare data in this cohort is therefore appealing to investigate the efficacy of treatments.

In this study data was utilised from sources spanning regional, national and international population datasets and registries. The utility of each dataset was reviewed and described. Kaplan-Meir survival estimation was used to describe survival over time and cox proportional hazards regression methods used to determine the adjusted effect of DI on mortality risk.

Linked national data was used to investigate the impact of chemotherapy DI on survival in patients with germ cell and bone tumours. In germ cell comparisons were made to treatment received within international clinical trials. Variations in DI received in trials compared to routine care were seen alongside variations across tumour types. The impact on survival of toxicity induced modifications of treatment (TIMT) in patients receiving chemotherapy for bone tumours was investigated using linked regional data. Differences were seen in TIMT across age categories and sex. TIMT were positively associated with survival. Patient and public involvement and engagement was conducted to identify existing barriers to trust in the use of existing healthcare data for research purposes. Recommendations for changes to practice and research priorities were ascertained through use of thematic analysis.

The findings of this study have identified a patient group for which dose de-escalation of treatment may be possible and provide evidence for further research into sex and age differences in chemotherapy efficacy.