Long-term survival in patients with IDH-wildtype glioblastoma: clinical and molecular characteristics.

BACKG ROUND: Glioblastoma is an aggressive tumor that has a dismal prognosis even with multimodal treatment. However, some patients survive longer than expected. The objective of this study was to revisit patients diagnosed with glioblastoma according to the 2021 WHO classification and analyze clinical and molecular characteristics associated with long-term survival (LTS). METHODS: We retrospectively analyzed 120 IDH-wildtype glioblastomas operated on at our institution between 2013 and 2018. We divided them into LTS patients, surviving more than 3 years, and non-LTS patients, and then compared their features. Additionally, we performed DNA methylation-based brain tumor classification in LTS patients. RESULTS: Sixteen patients were long-term survivors. Age < 70 years, MGMT promoter methylation, extent of resection ≥ 95%, and administration of radiochemotherapy were associated with LTS (P = 0.005, P < 0.001, P = 0.048, and P = 0.008, respectively). In addition, when these factors were combined, the probability of LTS was 74% (95% CI: 62--84). The methylome analysis confirmed the diagnosis of glioblastoma in the majority of the tested LTS patients. Regarding subtypes, 29% of cases were mesenchymal (MES), 43% were RTK1, and 29% were RTK2. Interestingly, RTK1 and RTK2 cases tended to have longer overall survival than MES cases (P = 0.057). Moreover, the only tested LTS patient with an unmethylated MGMT promoter had an "adult-type diffuse high-grade glioma, IDH-wildtype, subtype E" rather than a glioblastoma. This tumor was characterized by multinucleated giant cells and a somatic mutation in POLE. CONCLUSIONS: We suggest that glioblastoma patients with a combination of favorable prognostic factors can achieve LTS in 74% of cases. In addition, methylome analysis is important to ascertain the type of glioma in LTS patients, especially when the MGMT promoter is unmethylated.

Immediate post-operative MRI suggestive of the site and timing of glioblastoma recurrence after gross total resection: a retrospective longitudinal preliminary study.

OBJECTIVES: To retrospectively identify morphological and physiological post-operative magnetic resonance imaging (MRI) characteristics predictive of glioblastoma recurrences after gross total resection (gross-TR). METHODS: Resection margins of 24 glioblastoma were analysed immediately post-operatively (MRI ≤ 2 h) and early post-operatively (24 h ≤ MRI ≤ 48 h), and subdivided into areas with and without subtle contrast enhancement previously considered non-specific. On follow-up MRI, tumour regrowth areas were subdivided according to recurrence extent (focally/extended) and delay (≤6 and ≥12 months). Co-registration of pre-operative, immediately post-operative and early post-operative MRI with the first follow-up MRI demonstrating recurrence authorised their morphological (contrast enhancements) and physiological (rCBV) characterisation. RESULTS: Morphologically, on immediately post-operative MRI, micro-nodular and frayed enhancements correlate significantly with early recurrences (≤6 months). After gross-TR the absence of these enhancements is associated with a significant increase in progression-free survival (61 vs 15 weeks respectively) and overall survival (125 vs 51 weeks respectively). Physiologically, areas with a future focal recurrence have a trend toward higher rCBV than other areas. CONCLUSION: Immediately post-operative topography of micro-nodular and frayed enhancements is suggestive of recurrence location and delay. Absence of such enhancements is associated with a fourfold increase in progression-free survival and a 2.5-fold increase in overall survival. KEY POINTS: • Immediately post-operative MRI reveals contrast enhancement after glioblastoma gross total resection. • Immediately post-operative micro-nodular and frayed enhancement correlate with early recurrence. • Absence of micro-nodular/frayed enhancement is associated with 61 weeks' progression-free survival. • Absence of micro-nodular/frayed enhancement is associated with 125 weeks' overall survival.