Elderly glioblastoma patients: Survival analysis according adjuvant therapy and tumor molecular analysis.
Authors: Vaz Maria Angeles , Ceballos Lenza Isaac , Berron Sonia Del Barco , Martin Soberón Maria Cruz , Gallego Rubio Oscar , Gironés Sarrió Regina , Quintanar Verduguez Maria Teresa , Sarabia Rosario , Benavides Manuel , Ivars Rubio Alejandra , Fernandez Isaura , Gutierrez Toribio María , Tuñón Alvarez Maria Teresa , Cunquero Tomas Alberto Jacobo , Moya Horno Irene , Sepulveda Sánchez José Manuel , Peralta Muñoz Sergio , De Las Peñas Bataller Ramon 
Published: June 2021

e14046

Background: Glioblastoma (GBM) grade IV represents the most frequent and aggressive primary brain tumor. Despite complete surgical resection, GBM infiltrative potential leads to local recurrence rates of around 100%. Standard treatment with adjuvant chemotherapy (CT) and radiotherapy (RT) according Stupp regimen aims to reduce relapse and improve survival, but toxicities associated with these therapies represent a problem in elderly unfit population. O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status has been recognized as a predictive factor of response to alkylating agents as temozolomide. We aimed to compare overall survival (OS) results in elderly GBM patients according with MGMT promoter status and systemic treatment after surgery. Methods: We performed a database from the information available from RETSINE (Registro Nacional Español de Tumores de Sistema Nervioso Central). We selected ≥ 65 years GBM diagnosed patients. Relevant information was tumor MGMT promoter methylation status and adjuvant CT and/or RT after resection. Kaplan- Meier analysis was performed. Selected outcome was OS and 95% confidence intervals (CI) and p value < 0.05 were used as measures of statistical significance. Results: We identified 400 eligible GBM patients diagnosed ≥ 65 years (male = 232- 58%; female = 168-42% ). According tumor MGMT status: 125 (31.3%) methylated tumors, 115 (28.7%) non methylated and 160 unknown MGMT status. Included population median age was 72 years (65-88 years). Median global population OS was 7.93 months (IC95% 6.84-9.02). Survival analysis showed better OS for methylated tumors group, median OS 7.33 (IC 95%4.1-10.56) vs. unmethylated OS 7.06 (IC95% 4.9-9.1) (p = 0.021). Survival analysis in methylated patients showed improved OS in patients treated with RT + CT vs. no adjuvant therapy. Median OS for methylated patients treated with CT + RT was 11.46m (IC95%7.6-15.9) vs 9.6 months with only RT(IC95%3.67-7.26) and 2.1m with no treatment (IC95%2.03-3.76) p = 0,00. Unmethylated patients median OS was 9.36m (IC95%3.67-7.26) for RT-CT, 5.4 m (IC95%2.37-8.42) for RT only and 2.76 (IC95% 1.37-4.15) for no treatment p = 0.00. Conclusions: Elderly GBM patients have similar treatment options than young patients and comprise surgical resection, RT and alkylating CT with temozolomide. Comorbidities and performance status have relevant implications in elderly population treatment decisions. The MGMT promoter status has been described as a prognostic and predictive marker of response to temozolomide. In our series both methylated and unmethylated patients can benefit with systemic treatment.