NIMG-74. RESPONSE ASSESSMENT AFTER DOSE-ESCALATED RADIOTHERAPY: IMAGING PROTOCOL OF A MULTICENTER PHASE III TRIAL ON INTRAOPERATIVE RADIOTHERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA (INTRAGO-II;ARO2016-1;AG-NRO-03)
Abstract BACKGROUND Reliable response assessment of irradiated glioblastomas remains challenging. In an attempt to better distinguish post-therapeutic alterations (such as reactive gliosis, pseudoprogression and radionecrosis) from tumor progression, especially after (local) RT dose escalation as performed in the multinational INTRAGO-II trial, we modified the classical RANO criteria and developed a protocol and workflow for uniform assessment of post-irradiation tumor response. METHODS INTRAGO-II is a multinational randomized phase III trial (9 nations, 19 centers) that evaluates the benefit of intraoperative radiotherapy (IORT) with 20-30 Gy to the tumor bed after resection of glioblastoma in addition to standard of care (NCT02685605). Within this trial, advanced imaging is mandatory in addition to standard sequences and measurements (such as the sum of the products of perpendicular diameters, SPD). Specifically, the acquisition of dynamic susceptibility contrast (DSC) sequences as well as the calculation of the normalized relative cerebral blood volume (rCBV) is required. All local assessments are subjected to a central neuroradiology read, which is conclusive. The key modifications to RANO are that (i) an ≥25% increase SPD of the target lesions should be associated with a rCBV≥1 of at least one lesion to be considered radiological progression, (ii) new enhancing lesions should become measurable before they can constitute to radiological progression, (iii) rCBV is normalized against normal appearing white matter from the contralateral brain by reference ROI (with a minimal sphere size of 5x5mm) and (iv) confirmatory scans are mandatory for defining progressive disease. CONCLUSION/SUMMARY We present an imaging protocol based on updated RANO that accounts for post-irradiation image alterations. Funding: Carl Zeiss Meditec AG, Germany and MedWave Medical Imaging BV; Registered with ClinicalTrials.gov, number NCT02685605.