HOW TO PREDICT PROGRESSION FREE SURVIVAL IN PATIENTS WITH GRADE 2 IDH MUTATED DIFFUSE GLIOMAS AFTER SURGERY A long term follow up analysis

Marta Aprile¹Vincenzo Di Nunno^1*Lidia Gatto¹Alicia Tosoni¹Vania Ramponi^2,3Alfredo Conti^3,4Monica Maffei⁵Stella Battaglia⁵Chiara Maria Argento¹Enrico Zuliani⁶Stefania Bartolini¹Marzia Margotti¹Francesca Gentilini^2,4Giovanni Tallini^7,8Sofia Asioli⁴Enrico Franceshi¹

• ¹Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
• ²IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy
• ³Unit of Neurosurgery, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
• ⁴Department of Biomedical and NeuroMotor Sciences (DIBINEM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
• ⁵Programma Neuroradiologia Con Tecniche Ad Elevata Complessità, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Bologna, Italy
• ⁶Department of Experimental, Diagnostic & Specialty Medicine, University of Bologna, 40138 Bologna, Bologna, Italy
• ⁷Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
• ⁸Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

Purpose: Available prognostic scores for adult-type diffuse glioma Isocitrate dehydrogenase (IDH)- mutant have been validated before the evaluation of biomolecular features. The selection of patients who did not receive postoperative radiotherapy and chemotherapy would provide an ideal setting to describe the natural history of these tumors. Methods: We investigated clinical outcomes of patients (pts) with adult-type diffuse glioma Isocitrate dehydrogenase IDH mutated approached with active surveillance after primary surgery. Results: We evaluated 61 pts consisting of 35 pts with IDH mutant astrocytomas and 26 pts with IDH mutant 1p19q oligodendrogliomas. The median follow-up was 13.1 years (95% CI, 11.4-17.7). 56 Progression free survival events were available at time of analyses. The median age was 32.2 years, higher in IDH mutant 1p19q oligodendrogliomas (39.5 years) compared to IDH mutant astrocytomas (31.4 years; p 0.003). Residual tumor (HR 2.63, 95%CI - 1.23 – 5.58, p = 0.007), post-surgical diameters product (HR 1.11, 95% CI 1 – 1.22, p=0.03) and midline crossing (HR 6.79 ; 95%CI 1.5-30.4; p = 0.005) were the only factors directly influencing progression free survival at univariate analyses. No variables confirmed their predictive role on multivariate models. At the time of data analysis, we registered 22 overall survival (OS) events. In a multivariate Cox regression model, histo-molecular diagnosis (oligodendroglioma vs astrocytoma HR 0.28; 95%CI 0.10-0.8; p=0.02) and initial tumor area assessed as continuous variables (HR 1.82; 95%CI 1.01-3.3; p=0.05) independently affected survival of patients (p=0.01). Conclusions: In our series, presence and dimension of residual tumors and midline crossing were the only independent variables predicting progression free survival after primary surgery in grade 2 diffuse glioma.