Clinical validation of integrated diagnosis in low-grade glioma (LGG)

The importance of adding molecular data to histology for better stratifying tumor patients has been recently proposed by WHO; an integrated diagnosis has been recommended for routine pathological practice, in which molecular data obtained from the most representative area of the tumor are associated to histological appearance. We have evaluated the impact of the integrated diagnosis classification on LGGs progression in a series of tumors operated in our center. Inclusion criteria were a) histological diagnosis of grade II diffuse gliomas; b) full radiological, surgical and clinical data on admission and at follow up (mean 6.3 years (5–9 years), to evaluate extent of resection (EOR), seizure control, eventual treatment and PFS; c) presence of IDH1 mutation. 242 patients fulfilled the criteria and were reevaluated according to integrated diagnosis. Tumors initially classified as 101 oligodendrogliomas, 76 astrocytomas, and 65 oligoastrocytomas, were reclassified accordingly as 167 grade II oligodendrogliomas and 75 astrocytomas. Tumors were then further stratified according to EOR and seizure control in low (79,3%) and high (20,7%) risk. The impact of tumor reclassification was evaluated in term of PFS, looking at the rate of recurrence, divided as early (within 3 years from surgery) and late (after 5 years), and rate of malignant transformation. When tumors were classified according to traditional histological subgroups (oligodendrogliomas, astrocytomas, mixed gliomas) PFS of oligodedrogliomas was better than that of astrocytomas (5.3 vs 4.2 yrs) but without reaching statistical difference. When classified according to integrated diagnosis, some flaws appeared as showed by the occurrence of early recurrence (5,9%) and malignant transformation (5,1%) even in tumors with the best clinical (GTR) and molecular prognostic factors (IDH1 mut, codelation). True astrocytoma (IDH1 mut, ATRX loss, no codel) did worst then true oligodendroglioma (26,8% early recurrence and 10,7% malignant transformation, in low risk).These data indicate that integrated diagnosis a) better stratified patients than traditional histology, b) still does not fully describe the biological behavior of the tumor. Additional biological markers may be also important for additionally stratify LGGs.