Philipp Karschnia1,2, Jacob S Young3, Antonio Dono4, Levin Häni5, Tommaso Sciortino6, Francesco Bruno7, Stephanie T Juenger8, Nico Teske1, Ramin A Morshed3, Alexander F Haddad3, Yalan Zhang3, Sophia Stoecklein9, Michael Weller10, Michael A Vogelbaum11, Juergen Beck5, Nitin Tandon4, Shawn Hervey-Jumper3, Annette M Molinaro3, Roberta Rudà7,12, Lorenzo Bello6, Oliver Schnell5, Yoshua Esquenazi4, Maximilian I Ruge13, Stefan J Grau8,14, Mitchel S Berger3, Susan M Chang3, Martin van den Bent15, Joerg-Christian Tonn1,2. 1. Department of Neurosurgery, Ludwig-Maximilians-University, Munich, Germany. 2. German Cancer Consortium (DKTK), Partner Site Munich, Germany. 3. Department of Neurosurgery & Division of Neuro-Oncology, University of San Francisco, San Francisco, CA, USA. 4. Department of Neurosurgery, McGovern Medical School at UT Health Houston, Houston, Texas, United States of America. 5. Department of Neurosurgery, University of Freiburg, Freiburg, Germany. 6. Division for Neuro-Oncology, Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. 7. Division of Neuro-Oncology, Department of Neuroscience, University of Turin, Italy. 8. Department of Neurosurgery, University of Cologne, Cologne, Germany. 9. Department of Radiology, University Hospital, LMU Munich, Munich, Germany. 10. Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland. 11. Department of NeuroOncology, Moffitt Cancer Center, Tampa, Florida, United States of America. 12. Division of Neurology, Castelfranco Veneto and Treviso Hospital, Italy. 13. Department Stereotactic and Functional Neurosurgery, Centre for Neurosurgery, University Hospital Cologne, Cologne, Germany. 14. Klinikum Fulda, Academic Hospital of Marburg University, Fulda, Germany. 15. Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Abstract
BACKGROUND: Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (I) explore the prognostic utility of the classification system and (II) define how much removed non-CE tumor translates into a survival benefit. METHODS: The international RANO resect group retrospectively searched previously compiled databases from seven neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and post-operative MRI were collected. RESULTS: We collected 1008 patients with newly diagnosed IDHwt glioblastoma. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC 26981/22981 (TMZ/RT→TMZ) following surgery. Among these homogenously treated patients, lower absolute residual tumor volumes (in cm 3) were favorably associated with outcome: patients with 'maximal CE resection' (class 2) had superior outcome compared to patients with 'submaximal CE resection' (class 3) or 'biopsy' (class 4). Extensive resection of non-CE tumor (≤5 cm 3 residual non-CE tumor) was associated with better survival among patients with complete CE resection, thus defining class 1 ('supramaximal CE resection'). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers. CONCLUSIONS: The proposed "RANO categories for extent of resection in glioblastoma" are highly prognostic and may serve for stratification within clinical trials. Removal of non-CE tumor beyond the CE tumor borders may translate into additional survival benefit, providing a rationale to explicitly denominate such 'supramaximal CE resection'.
BACKGROUND: Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (I) explore the prognostic utility of the classification system and (II) define how much removed non-CE tumor translates into a survival benefit. METHODS: The international RANO resect group retrospectively searched previously compiled databases from seven neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and post-operative MRI were collected. RESULTS: We collected 1008 patients with newly diagnosed IDHwt glioblastoma. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC 26981/22981 (TMZ/RT→TMZ) following surgery. Among these homogenously treated patients, lower absolute residual tumor volumes (in cm 3) were favorably associated with outcome: patients with 'maximal CE resection' (class 2) had superior outcome compared to patients with 'submaximal CE resection' (class 3) or 'biopsy' (class 4). Extensive resection of non-CE tumor (≤5 cm 3 residual non-CE tumor) was associated with better survival among patients with complete CE resection, thus defining class 1 ('supramaximal CE resection'). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers. CONCLUSIONS: The proposed "RANO categories for extent of resection in glioblastoma" are highly prognostic and may serve for stratification within clinical trials. Removal of non-CE tumor beyond the CE tumor borders may translate into additional survival benefit, providing a rationale to explicitly denominate such 'supramaximal CE resection'.