Toxicity reporting
Local trial centers conducted mandatory documentation of toxicities for each treatment element based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, modified by the German Society of Pediatric Oncology and Hematology on a patient-specific therapy flowsheet. In addition, treatment-related toxicities were documented in medical records. Severe adverse events (SAE) were reported instantaneously. Treatment-related toxicities were assigned to a specific treatment element, if they occurred during the application of chemotherapy or before the next treatment element had started.
As an additional surrogate marker for toxicity related to AEP treatment we calculated the duration from the start of AEP until the beginning of the subsequent therapy element.