A Drug-Specific, Half-Life-Adjusted Framework for Classifying CNS-Active Systemic Therapy Exposure During and After Radiotherapy

The article presents a new methodological framework for classifying patient exposure to central nervous system (CNS)-active drugs during and after radiotherapy. Current clinical studies often use empirical drug lists and fixed time windows to define CNS activity and exposure concurrency, leading to substantial heterogeneity. The proposed framework uses a transparent scoring model based on three clinical components: intracranial objective response rate, consensus CNS endorsement, and intrathecal route of administration. Exposure is classified using a pharmacokinetic proxy model that accounts for the recorded treatment end date plus five drug half-lives. The framework distinguishes between continued exposure and true adjuvant treatment initiation after radiotherapy. This is a methodological framework requiring further validation audits before use as a definitive exposure classifier.