Background
No systemic treatment has been established for meningioma progressing after local therapies.
Methods
This randomized, multicenter, open-label, phase 2 study included adult patients with recurrent WHO grade 2 or 3 meningioma. Patients were 2:1 randomly assigned to intravenous trabectedin (1.5 mg/m 2 every three weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Secondary endpoints comprised overall survival (OS), objective radiological response, safety, quality of life (QoL) assessment using the QLQ-C30 and QLQ-BN20 questionnaires, and we performed tissue-based exploratory molecular analyses.
Results
Ninety patients were randomized (n=29 in LOC, n=61 in trabectedin arm). With 71 events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR]=1.42; 80% CI, 1.00-2.03; p=0.294) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) and 21.1% (95% CI, 11.3%-32.9%), respectively. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR=0.98; 95% CI, 0.54-1.76; p=0.94). Grade ≥3 adverse events occurred in 44.4% patients in the LOC and 59% of patients in the trabectedin arm. Enrolled patients had impeded global QoL and overall functionality and high fatigue before initiation of systemic therapy. DNA methylation class, performance status, presence of a relevant co-morbidity, steroid use, and right hemisphere involvement at baseline were independently associated with OS.
Conclusions
Trabectedin did not improve PFS and OS and was associated with higher toxicity than LOC treatment in patients with non-benign meningioma. Tumour DNA methylation class is an independent prognostic factor for OS.
Background
Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described.
Methods
We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (with or without chemotherapy), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (reference cohort, n=200). Pseudoprogression misdiagnosis was estimated in this cohort and in an independent cohort (control cohort, n=543) based on progression free survival before and after first progression.
Results
In the reference cohort, 38 patients (19%) presented a pseudoprogression after a median time of 10.5 months after radiotherapy. Pseudoprogression characteristics were similar across IDHmt HGG subtypes. In most patients, it consisted in the appearance of one or several infracentimetric, asymptomatic, contrast-enhanced lesions occurring within 2 years after radiotherapy. The only factor associated with pseudoprogression occurrence was adjuvant PCV chemotherapy. Among patients considered as having a first true progression, 7 out of 41 (17%) in the reference cohort and 35 out of 203 (17%) in the control cohort were retrospectively suspected to have a misdiagnosed pseudoprogression. Patients with a misdiagnosed pseudoprogression were characterized by a time to event and an outcome similar to that of patients with a pseudoprogression but presented with larger and more symptomatic lesions.
Conclusion
In patients with an IDHmt HGG, pseudoprogression occurs later than in IDH-wildtype glioblastomas and seems not only frequent but also frequently misdiagnosed. Within the first 2 years after radiotherapy, the possibility of a pseudoprogression should be carefully considered.
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