Toxicity-induced modification of treatment: what is in a name?

Severe treatment-induced toxicities can have clinical consequences such as hospitalisation or treatment modifications, which in turn may deteriorate the prognosis of patients with cancer. Identification of determinants of treatment-induced toxicities is essential to develop strategies that promote therapy compliance and enhance the quality of life. Whereas toxicities are systematically recorded and graded per protocol in most clinical trials, observational studies often depend on retrospective data collection from medical records collected as standard care. Existing population-based or patient cohorts are a valuable source of information, even when relying on retrospective data collection, but comparisons across studies are hampered by a lack of a uniform definition for toxicity outcomes. We propose a new standardised approach to summarise toxicities in observational studies that rely on medical records for outcome assessment. We recommend the term 'toxicity-induced modification of treatment' (TIMT) to cover all toxicities that are responsible for changes in a planned treatment schedule. We define a TIMT as (i) a dose reduction, (ii) temporary interruption, (iii) discontinuation of therapy or (iv) an unanticipated switch to another regimen, as a result of treatment-induced toxicities and not because of progressive disease. This definition will provide clinically relevant information, especially when data on specific adverse events and Common Terminology Criteria for Adverse Events (CTCAE) grades are not uniformly available. Implementation of this definition empowers comparisons across studies, facilitates communication between clinicians and researchers and will allow new research questions in this active field of research.