Frequency and Prognostic Relevance of Volumetric MRI Changes in Contrast- and Non-Contrast-Enhancing Tumor Compartments between Surgery and Radiotherapy of IDHwt Glioblastoma

SIMPLE SUMMARY: The prognostic impact of early tumor regrowth in glioblastoma patients diagnosed according to WHO 2021 classification between surgery and postoperative adjuvant therapy remains unclear. In a retrospective cohort of 64 patients, we performed volumetric analyses of routine MRI obtained early after tumor resection and directly before initiation of radio(chemo-)therapy (time interval: 15.5 ± 1.9 days). About one third developed new contrast-enhancement after complete or incomplete resection due to progression of tumor remnants or breakdown of the blood–brain barrier in previously non-enhancing tumor compartments, but also related to postoperative ischemia and unspecific signals. Findings suggestive for tumor regrowth were not associated with unfavorable outcomes. Immediate postoperative MRI should, therefore, be used for prognostic stratification of the extent of resection, while additional imaging before the start of radiotherapy may be helpful for tumor volume and radiation target delineation. ABSTRACT: In newly diagnosed IDH-wildtype glioblastoma, the frequency and prognostic relevance of tumor regrowth between resection and the initiation of adjuvant radiochemotherapy are unclear. In this retrospective single-center study we included 64 consecutive cases, for whom magnetic resonance imaging (MRI) was available for both the volumetric assessment of the extent of resection immediately after surgery as well as the volumetric target delineation before the initiation of adjuvant radiochemotherapy (time interval: 15.5 ± 1.9 days). Overall, a median new contrast-enhancement volume was seen in 21/64 individuals (33%, 1.5 ± 1.5 cm(3)), and new non-contrast lesion volume in 18/64 patients (28%, 5.0 ± 2.3 cm(3)). A multidisciplinary in-depth review revealed that new contrast-enhancement was either due to (I) the progression of contrast-enhancing tumor remnants in 6/21 patients or (II) distant contrast-enhancing foci or breakdown of the blood–brain barrier in previously non-contrast-enhancing tumor remnants in 5/21 patients, whereas it was unspecific or due to ischemia in 10/21 patients. For non-contrast-enhancing lesions, three of eighteen had progression of non-contrast-enhancing tumor remnants and fifteen of eighteen had unspecific changes or changes due to ischemia. There was no significant association between findings consistent with tumor regrowth and a less favorable outcome (overall survival: 14 vs. 19 months; p = 0.423). These findings support the rationale that analysis of the postsurgical remaining tumor-volume for prognostic stratification should be carried out on immediate postoperative MRI (<72 h), as unspecific changes are common. However, tumor regrowth including distant foci may occur in a subset of IDH-wildtype glioblastoma patients diagnosed per WHO 2021 classification. Thus, MRI imaging prior to radiotherapy should be obtained to adjust radiotherapy planning accordingly.