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Proffered Paper - CNS tumours

361O - Defining the prognostic role of MGMT methylation value by pyrosequencing assay in glioblastoma patients: A large Italian multicenter study


20 Sep 2020


Proffered Paper - CNS tumours


Tumour Site

Central Nervous System Malignancies


Mario Caccese


Annals of Oncology (2020) 31 (suppl_4): S396-S408. 10.1016/annonc/annonc269


M. Caccese1, M. Simonelli2, L. Bellu3, V. Villani4, S. Rizzato5, T. Ius6, F. Pasqualetti7, M. Russo8, F. Franchino9, R. Amoroso10, R. Bertorelle11, F. Cavallin12, A. Dipasquale2, M. Carosi13, S. Pizzolitto14, D. Cesselli15, M.P. Gardiman16, M. Padovan1, V. Zagonel1, G. Lombardi1

Author affiliations

  • 1 Department Of Oncology, Oncology 1, Veneto Institute of Oncology - IRCCS, 35128 - Padova/IT
  • 2 Department Of Biomedical Sciences, Humanitas Cancer Center, Milan/IT
  • 3 Radiotherapy Unit, Veneto Institute of Oncology IOV - IRCCS, Padova/IT
  • 4 Neuro-oncology Unit, Regina Elena National Cancer Institute, Rome/IT
  • 5 Department Of Oncology, Azienda Sanitaria Universitaria Friuli Centrale, Udine/IT
  • 6 Department Of Neurosurgery, University Hospital of Udine, Udine/IT
  • 7 Radiation Oncology, Pisa University Hospital, Pisa/IT
  • 8 Neurology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia/IT
  • 9 Department Of Neuro-oncology, University of Turin and City of Health and Science Hospital, Turin/IT
  • 10 Divisione Di Neurochirurgia, Azienda Sanitaria Alto Adige-Comprensorio Sanitario di Bolzano, Bolzano/IT
  • 11 Immunology And Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova/IT
  • 12 Independent Statistician, Independent Statistician, Solagna/IT
  • 13 Pathology Unit, Regina Elena National Cancer Institute, Rome/IT
  • 14 Department Of Surgical Pathology, Azienda Sanitaria Universitaria Friuli Centrale, Udine/IT
  • 15 Department Of Medicine, University Of Udine, Udine, Italy; Institute Of Pathology, Azienda Sanitaria Universitaria Friuli Centrale, Udine/IT
  • 16 Department Of Medicine And Surgical Pathology And Cytopahology Unit, University Hospital of Padua, Padova/IT


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Abstract 361O


MGMT methylation (MGMTmet) status represents an important prognostic factor for glioblastoma (GBM) patients (PTS). Quantitative pyrosequencing approach has proven to be feasible for MGMTmet testing but its value is still unclear. We performed a large, multicentre, retrospective study to identify the association between MGMTmet values and clinical outcome.


From 9 Italian centres, we collected consecutive GBM PTS with assessment of MGMTmet by pyrosequencing approach evaluating CpGislands from 75 to 84. Other inclusion criteria were: histological diagnosis of GBM, ECOG PS≤2, therapy with RT+TMZ. Kaplan-Meier method was used to estimate the survival curves, time-dependent ROC curve for defining the optimal cut-off value of mean percentage of MGMTmet in terms of 2y-OS, Cox regression for multivariable analysis, and restricted cubic spline to investigate the non-linear association between methylation values and OS.


681 PTS were enrolled; median age was 60 ys; ECOG PS was 0 in 292, 1 in 306, 2 in 83; 391 (58%) had a complete resection. 8% received a second surgery. IDH was mutated in 6%. 2y-OS was 31.6%, median OS 17.4 ms. Median MGMTmet was 3.5% (IQR 0-22%). ROC curve identified a cutoff of 15% of MGMTmet in terms of 2y-OS (sens 78% spec 57% AUC=0.67). 2y-OS was 19.7% and 53.7% for MGMTmet< and ≥15%, respectively (p<0.0001). At multivariable analysis, MGMTmet<15% was associated with impaired survival (HR 2.7 95% CI 2.1-3.4 p<0.00001), adjusting for age, PS, type of surgery and second surgery. A non-linear association between MGMTmet and survival was identified (p<0.0001), with lower values of MGMTmet associated with lower survival; indeed, estimated median OS was lowest (14 ms 2ys-OS 17.4%) with MGMTmet of 4%, 21ms (2yr-OS 40.9%) with MGMTmet of 20%, 27ms (2yr-OS 40.9%) when MGMTmet was 40%, then leveled around 30ms (2yr-OS 54.5-59.8%) when MGMTmet was>40%.


This study represents one of the largest trials analyzing MGMTmet by pyrosequencing approach. Lower values of MGMTmet were associated with impaired survival and the relationship was non-linear. Noteworthy, we identified a strong prognostic value of MGMTmet which could be used as stratification factor in prospective clinical trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Giuseppe Lombardi.


Has not received any funding.


All authors have declared no conflicts of interest.

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