Enrico Franceschi1, Alicia Tosoni2, Stefania Bartolini2, Santino Minichillo2, Antonella Mura2, Sofia Asioli3, Daniela Bartolini4, Marina Gardiman5, Marco Gessi6, Claudio Ghimenton7, Felice Giangaspero8, Giovanni Lanza9, Gianluca Marucci10, Mariangela Novello11, Enrico M Silini12, Elena Zunarelli13, Alexandro Paccapelo2, Alba A Brandes2. 1. Department of Medical Oncology, AUSL / IRCCS Institute of Neurological Sciences, Bologna, Italy. Electronic address: enricofra@yahoo.it. 2. Department of Medical Oncology, AUSL / IRCCS Institute of Neurological Sciences, Bologna, Italy. 3. Section of Anatomic Pathology 'M. Malpighi', Bellaria Hospital, Bologna, Italy; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy. 4. Department of Pathology, Bufalini Hospital, Cesena, Italy. 5. Department of Pathology, University Hospital, Padova, Italy. 6. Division of Histopathology, Fondazione Policlinico Universitario "A.Gemelli,", Università Cattolica S.Cuore, Roma, Italy. 7. Department of Pathology, Azienda Ospedaliera Universitaria Integrata Verona, Ospedale Civile Maggiore, Borgo Trento, Verona, Italy. 8. Department of Radiological, Oncological and Anatomo-pathological Sciences, Sapienza University of Rome, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy. 9. Department of Pathology, S Anna University Hospital & University of Ferrara, Ferrara, Italy. 10. Neuropathology Unit, Fondazione IRCCS, Istituto Neurologico C. Besta, Milan, Italy. 11. Department of Anatomic Pathology, Catholic University, Rome, Italy. 12. Department of Pathology, University Hospital, Parma, Italy. 13. Department of Pathology, University Hospital, Modena, Italy.
Abstract
BACKGROUND: Diffuse grade II and grade III gliomas are actually classified in accordance with the presence of isocitrate dehydrogenase mutation (IDH-mut) and the deletion of both 1p and 19q chromosome arms (1p/19q codel). The role of tumour grading as independent prognostic factor in these group of tumours remains matter of debate. The aim of this study was to determine if grade is an independent prognostic factor and not somehow associated to IDH mutation and 1p/19q status of the tumour. METHODS: We analysed 399 consecutive patients with newly diagnosed, histologically proven World Health Organisation (WHO) 2016 grade II or grade III IDH-mut gliomas, assessed by polymerase chain reaction, immunohistochemistry or next-generation sequencing (NGS). RESULTS: The analysis included 399 patients with grade II (n = 250, 62.7%) or grade III (n = 149, 37.3%) diffuse gliomas. Median follow-up time was 105.3 months. Median survival was 148.1 months. In multivariate analysis, grade II (hazard ratio [HR] = 0.342, 95% confidence interval [CI]: 0.221-0.531; P < 0.001) and 1p/19q codeletion (HR = 0.440, 95% CI: 0.290-0.668; P < 0.001) were independently associated with a lower risk for death. The difference in survival remained significant (p = 0.006 in astrocytomas, p = 0.014 in oligodendrogliomas) when adjusted for histological subtype. Residual disease after surgery (or biopsy) negatively affected survival (HR: 2.151, 95% CI: 1.375-3.367, P = 0.001). Post-surgical treatment with radiotherapy + adjuvant chemotherapy improved survival compared with follow-up and other treatments (HR: 0.316, 95% CI: 0.156-0.641, P = 0.001). CONCLUSIONS: In our study, histopathological grade still affects survival in IDH-mutant WHO grade II and III diffuse gliomas. This effect appears to be independent from molecular features, extension of surgical resection and post-surgical treatments. Therefore, physicians should continue to take into account tumour grade, along their molecular characteristics, for a better clinical and therapeutic management of the patients.
BACKGROUND: Diffuse grade II and grade III gliomas are actually classified in accordance with the presence of isocitrate dehydrogenase mutation (IDH-mut) and the deletion of both 1p and 19q chromosome arms (1p/19q codel). The role of tumour grading as independent prognostic factor in these group of tumours remains matter of debate. The aim of this study was to determine if grade is an independent prognostic factor and not somehow associated to IDH mutation and 1p/19q status of the tumour. METHODS: We analysed 399 consecutive patients with newly diagnosed, histologically proven World Health Organisation (WHO) 2016 grade II or grade III IDH-mut gliomas, assessed by polymerase chain reaction, immunohistochemistry or next-generation sequencing (NGS). RESULTS: The analysis included 399 patients with grade II (n = 250, 62.7%) or grade III (n = 149, 37.3%) diffuse gliomas. Median follow-up time was 105.3 months. Median survival was 148.1 months. In multivariate analysis, grade II (hazard ratio [HR] = 0.342, 95% confidence interval [CI]: 0.221-0.531; P < 0.001) and 1p/19q codeletion (HR = 0.440, 95% CI: 0.290-0.668; P < 0.001) were independently associated with a lower risk for death. The difference in survival remained significant (p = 0.006 in astrocytomas, p = 0.014 in oligodendrogliomas) when adjusted for histological subtype. Residual disease after surgery (or biopsy) negatively affected survival (HR: 2.151, 95% CI: 1.375-3.367, P = 0.001). Post-surgical treatment with radiotherapy + adjuvant chemotherapy improved survival compared with follow-up and other treatments (HR: 0.316, 95% CI: 0.156-0.641, P = 0.001). CONCLUSIONS: In our study, histopathological grade still affects survival in IDH-mutant WHO grade II and III diffuse gliomas. This effect appears to be independent from molecular features, extension of surgical resection and post-surgical treatments. Therefore, physicians should continue to take into account tumour grade, along their molecular characteristics, for a better clinical and therapeutic management of the patients.
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