Artikel
Clinical and molecular factors impacting progression and survival in IDH1 mutant glioma patients
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Veröffentlicht: | 9. Juni 2017 |
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Gliederung
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Background: Isocitrate dehydrogenase 1 (IDH1) mutant tumors represent a distinct subtype among diffuse gliomas, with improved prognosis compared to histological grade-matched IDH1 wild-type tumors. Here, we sought to identify factors associated with outcome exclusively within the glioma subgroup defined by IDH1 mutation.
Methods: We retrospectively analyzed 214 IDH1 mutant glioma patients (112 WHO grade II, 76 grade III, 26 grade IV) treated at our institution to determine clinical and molecular factors associated with time-to-treatment-failure (TTF) and overall survival (OS). TERT promotor mutation analysis was performed to identify molecular subgroups in our population.
Results: At median follow-up in survivors of 8.38 years, 58 deaths (27.1%) were recorded in the cohort. Median TTF was 5.0 years (95% CI 4.6-5.8) and median OS was 14.6 years (95% CI 12.1–17.4). Adjuvant radiation (median 6.2 versus 4.5 years, p=.019) and more-extensive resection (MER) (median 6.7 versus 4.5 years, p<.001) were associated with prolonged TTF. Both remained significant predictive factors in a multivariate model of TTF including age and histological grade (HR=.395 for radiation, p=.0011 and HR=.520 for MER, p=.0062). MER was also significantly associated with prolonged OS (median 19.01 versus 13.23 years, p=.0119). In the TERT wild-type subgroup, both TTF (median 7.8 versus 3.8 years; p <.0001) and OS (median 19.0 versus 11.5 years; p=.0133) were significantly prolonged in patients that received a MER. Additionally, adjuvant radiation (median 6.2 versus 3.8 years; p=.0019) and adjuvant chemotherapy (median 6.2 versus 3.8 years; p=.0025) significantly improved TTF, but not OS. Interestingly, in the TERT mutated subgroup we did not observe a significant benefit from MER (p=.534), adjuvant radiation (p=.08) or chemotherapy (p=.88) for TTF.
Conclusion: Within IDH1 mutant gliomas, adjuvant radiation therapy and more-extensive resection are independently associated with improved TTF and OS. TERT wild-type patients seem to benefit from MER and adjuvant radiation or chemotherapy.