x -axes show time since first diagnosis. Nature | Vol 592 | 15 April 2021 | 467to a molecularly matched cohort and previous reports (3 out of 60 patients, 5.0%)11 may indicate an intratumoral immune reaction that results in disruption of the blood–brain barrier and contrast enhance - ment. The Response Assessment in Neuro-Oncology (RANO) criteria applied in this trial consider PsPD to be secondary to radiotherapy or combined radiochemotherapy with TMZ, particularly four weeks after completion of radiotherapy12, and most trials mandate follow-up imaging to demonstrate true progression in cases of suspected PsPD, according to RANO13,14. We excluded patients with suspected PsPD from the NOA16 trial, thereby enriching for patients with IDH1-vac-induced PsPD, but we acknowledge that late PsPD may occur as a result of radio - therapy15. Also, late PsPD six months after initiation of immunotherapy may occur, as acknowledged in the immunotherapy RANO (iRANO) criteria13, which were not defined at the time of initiation of this trial. Notably, the rate of PsPD in NOA16 did not differ when analysed accord - ing to iRANO criteria. However, there are limitations to definitive proof of PsPD, even with positron emission tomography (PET) imaging or histologic analysis of re-resection, as no firm criteria exist16. NOA16 is based on strong preclinical data4,6 and the decision to integrate IDH1-vac into the primary treatment of newly diagnosed patients provided a sufficient therapeutic window and allowed us to exploit potential positive immune interactions between SOC and vaccination. While this strategy has been chosen in other trials that have targeted shared17 or personalized neoepitopes18,19, NOA16 tar - geted a shared clonal neoepitope to minimize the risk of immune evasion by clonal selection or spontaneous neoantigen loss17. Clonality of neoepitopes is a key determinant of efficacy for immune check - point inhibitors across many cancer entities20. Gliomas are particu - larly prone to the development of subclonal mutational events that contribute to resistance to immune checkpoint inhibitors21. Targeting a shared clonal driver mutation in newly diagnosed patients over - comes these limitations6 and may provide a basis for future trials that target MHCII-restricted clonal shared and personalized neoepitopes in cancer immunotherapy. Online content Any methods, additional references, Nature Research reporting sum- maries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author con - tributions and competing interests; and statements of data and code availability are available at https://doi.org/10.1038/s41586-021-03363-z.