PURPOSE: Patients with IDH-mutant 1p/19q-codeleted grade 3 oligodendroglioma (O3 ^IDHmt/Codel ) benefit from adding alkylating agent chemotherapy to radiotherapy (RT). However, the optimal chemotherapy regimen between procarbazine, 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine (PCV) and temozolomide (TMZ) remains unclear given the lack of randomized trial data comparing both regimens. METHODS: The objective was to assess the overall survival (OS) and progression-free survival (PFS) associated with first-line PCV/RT versus TMZ/RT in patients newly diagnosed with O3 ^IDHmt/Codel . We included patients with histologically proven O3 ^IDHmt/Codel (according to WHO criteria) from the French national prospective cohort Prise en charge des OLigodendrogliomes Anaplasiques (POLA). All tumors underwent central pathologic review. OS and PFS from surgery were estimated using the Kaplan-Meier method and Cox regression model. RESULTS: 305 newly diagnosed patients with O3 ^IDHmt/Codel treated with RT and chemotherapy between 2008 and 2022 were included, of which 67.9% of patients (n = 207) were treated with PCV/RT and 32.1% with TMZ/RT (n = 98). The median follow-up was 78.4 months (IQR, 44.3-102.7). The median OS was not reached (95% CI, Not reached [NR] to NR) in the PCV/RT group and was 140 months (95% CI, 110 to NR) in the TMZ/RT group (log-rank P = .0033). On univariable analysis, there was a significant difference in favor of PCV/RT in both 5-year (PCV/RT: 89%, 95% CI, 85 to 94; TMZ/RT: 75%, 95% CI, 66 to 84) and 10-year OS (PCV/RT: 72%, 95% CI, 61 to 85; TMZ/RT: 60%, 95% CI, 49 to 73), which was confirmed using the multivariable Cox model adjusted for age, type of surgery, gender, Eastern Cooperative Oncology Group performance status, and CDKN2A homozygous deletion (hazard ratio, 0.53 for PCV/RT, 95% CI, 0.30 to 0.92, P = .025). CONCLUSION: In patients with newly diagnosed O3 ^IDHmt/Codel from the POLA cohort, first-line PCV/RT was associated with better OS outcomes compared with TMZ/RT. Our data suggest that the improved safety profile associated with TMZ comes at the cost of inferior efficacy in this population. Further investigation using prospective randomized studies is warranted.

Purpose: Radiochemotherapy remains the mainstay of glioblastoma (GBM) first-line treatment after extended surgery, but the prognosis is still poor. PARP inhibitors like olaparib may improve GBM outcomes. We implemented a phase I to IIa trial to assess the safety and efficacy of olaparib combined with standard radiochemotherapy as a first-line treatment in patients with unresected GBM. We herein present results of phase I. Patients and Methods: Based on the Stupp regimen, two sequential dose escalations of olaparib were performed to distinguish the radiotherapy period and the maintenance period for assessing the MTD of olaparib separately for each treatment period. Dose escalations were performed by a Time-to-Event Continual Reassessment Method. Results: A total of 30 patients were enrolled: 20 (66.7%) men, median age 59 years (range, 25–70), and 12 patients (42.9%) with Eastern Cooperative Oncology Group performance status of 0. Among them, 16 and 11 patients were assessable for determining MTD in each period. Hematologic dose-limiting toxicities were experienced by four and one patients in each sequential dose escalation, respectively. The MTD was olaparib 100 mg twice daily for 3 days a week in concomitant during both the radiochemotherapy and maintenance periods of the standard treatment. The median progression-free and overall survival were 6.2 and 19.8 months, respectively. The 2-year survival rate was 36.7% (22.9–58.7). Conclusions: Intermittent dosing of olaparib at radiosensitizing concentrations in concomitant with the Stupp protocol has an acceptable safety profile with promising outcomes in patients with unresectable GBM. Further efficacy determination is ongoing in the phase IIa step.

Gliomas, the most common type of primary malignant brain tumors in adults, pose significant challenges in diagnosis and management due to their heterogeneity and potential aggressiveness. This review evaluates the utility of O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET) positron emission tomography (PET), a promising imaging modality, to enhance the clinical management of gliomas. We reviewed 82 studies involving 4657 patients, focusing on the application of [¹⁸F]FET in several key areas: diagnosis, grading, identification of IDH status and presence of oligodendroglial component, guided resection or biopsy, detection of residual tumor, guided radiotherapy, detection of malignant transformation in low-grade glioma, differentiation of recurrence versus treatment-related changes and prognostic factors, and treatment response evaluation. Our findings confirm that [¹⁸F]FET helps delineate tumor tissue, improves diagnostic accuracy, and aids in therapeutic decision-making by providing crucial insights into tumor metabolism. This review underscores the need for standardized parameters and further multicentric studies to solidify the role of [¹⁸F]FET PET in routine clinical practice. By offering a comprehensive overview of current research and practical implications, this paper highlights the added value of [¹⁸F]FET PET in improving management of glioma patients from diagnosis to follow-up.

A. Progression-free (left) and overall (right) survival among the 30 patients enrolled in the two sequential olaparib dose-escalations of the trial.

Representativeness of Study Participants

Magnetic Resonance Imaging (gadolinium, FLAIR and perfusion sequences from left to right) at baseline (top) and 60 months (bottom) after start of treatment in first line treatment of a partially resected glioblastoma patient.