Abstract
BACKGROUND
Initial chemotherapy with temozolomide (TMZ) may provide benefit in high-risk low-grade gliomas. To date, no standard treatment is validated at first progression. The aim of this retrospective study was to investigate the optimal salvage therapy after the first progression and the factors that influence the PFS and overall survival (OS).
MATERIAL AND METHODS
we evaluated 71 patients with an histological diagnosis of grade II glioma according to WHO 2016 classification, who were included in a phase II AINO (Italian Association for Neuro-Oncology) trial, and progressed following initial chemotherapy with TMZ. Molecular data were available in all patients: 32 (45.1%) patients were oligodendrogliomas IDH 1/2 mutated and 1p19q codeleted, 11 (15.5%) were diffuse astrocytomas IDH mutant, and 28 (39.4%) were diffuse astrocytomas IDH wild-type. Thirty-five (49.3%) patients were MGMT methylated. Median follow up was 144 months (range 23–180).
RESULTS
thirty-one patients (43.7%) underwent second surgery, 24 patients (33.8%) second-line chemotherapy (rechallenge with TMZ or nitrosoureas), and 16 patients (22.5%) radiotherapy with a median PFS of 58 months (IC 95% 49–116). The association between prognostic factors and type of salvage therapy revealed a prevalence of younger age (≤ 45 years), non-enhancing tumor and location in eloquent area among patients treated with second surgery or chemotherapy, while aolder age (> 45 years) and contrast-enhancing tumors prevailed among patients receiving radiotherapy. Overall, median PFS was 60 months after second surgery (IC95% 43–116) and chemotherapy (IC95% 51–69), and 38 months after radiotherapy (IC95% 15–64) (p 0.09). No significant benefit in length of PFS was achieved in oligodendrogliomas undergoing second surgery (60 months) as compared with oligodendrogliomas treated with radiation or chemotherapy (58 months, p 0.11). PFS of diffuse astrocytomas IDH wild-type following second surgery (53 months) did not differ from that of patients treated with adjuvant treatments (65 months, p 0.28). Overall, median OS from the first salvage therapy was 117 months (IC95% 93 - 123+): 120 months (IC95% 108–140+) after second surgery, 94 months (IC95% 75–117+) after chemotherapy, and 62 months (IC95% 27–112) after radiotherapy (p 0.04). Median OS (123 months, IC95% 106–154) was prolonged in oligodendrogliomas receiving second surgery as compared to those receiving radiotherapy or chemotherapy (93 months, IC 95% 61–112, p 0.07), while median OS in diffuse astrocytomas IDH wild-type did not differ between those who received second surgery or radiotherapy or chemotherapy.
CONCLUSION: W
hen feasible, reoperation as first salvage treatment following initial TMZ in grade II gliomas seems to offer a probability of a longer OS as compared with second-line chemotherapy or radiotherapy, and this could hold true especially for oligodendrogliomas.
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