Abstract 363P
Background
The clinical significance of TERT promoter mutations, telomere length and their interactions with MGMT status in patients with IDHwt GBM PTS is unclear. We performed a large study to investigate their impact on clinical outcomes.
Methods
TERT promoter mutations (C228T, C250T), relative telomere length (RTL) and MGMT status were assessed in 278 newly diagnosed (ND) and in 65 recurrent (REC) IDHwt GBM PTS which were treated from Dec 2016 to Jan 2020. We retrospectively explored association between gene characteristics and radiological response, progression free survival (PFS), overall survival (OS). Telomere length was measured by monochrome multiplex PCR and RTL values were calculated as a telomere/single-copy gene ratio.
Results
Characteristics of ND GBM PTS were median age 63, ECOG PS 0-1 in 71%, radical surgery in 38%, 78% received radiotherapy plus TMZ, MGMTmet in 53%, TERT promoter was mutated in 80% (75% C228T, 25% C250T), median RTL was 1.57 (range 0.4-11.37). ORR was reported in 15% of PTS, mOS was 15ms (95%CI 13-18), mPFS was 8ms (95%CI 7-9). At multivariable analysis TERT mutations and RTL were not associated with clinical outcomes and about OS, reported a HR of 1.05 (95% CI 0.64-1.64) and 0.99 (95% CI 0.89-1.10), respectively; MGMTmet tumors showed significant improved PFS and OS with a HR of 0.54 (95% CI 0.40-0.71) and 0.47 (95% CI 0.34-0.64), respectively. All interactions among MGMT, TERT mutation and RTL were not significant. Characteristics of REC GBM PTS were median age 55, ECOG PS 0-1 in 60%, MGMTmet in 37%, TERT mutations in 75% (75% C228T, 25% C250T), RTL was 1.67 (0.68-8.87). At multivariable analysis only MGMTmet tumors resulted significantly associated to prolonged OS (HR 0.16 95% CI 0.07-0.40). No gene interaction was significant.
Conclusions
We analyzed the impact of TERT mutations, RTL and MGMT status in both nd and rec IDHwt GBM PTS. TERT status and RTL were not associated with clinical outcomes at both diagnosis and relapse. MGMT status was the only prognostic factor in both cases. No significant interaction was demonstrated between TERT mutations, RTL and MGMT status.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.