Surgical Management and Outcome of Newly Diagnosed Glioblastoma Without Contrast Enhancement (Low-Grade Appearance): A Report of the RANO Resect Group

Authors

Philipp Karschnia
Jorg Dietrich
Francesco Bruno
Antonio Dono
Stephanie T Juenger
Nico Teske
Jacob S Young
Tommaso Sciortino
Levin Häni
Martin van den Bent
Michael Weller
Michael A Vogelbaum
Ramin A Morshed
Alexander F Haddad
Annette M Molinaro
Nitin Tandon
Juergen Beck
Oliver Schnell
Lorenzo Bello
Shawn Hervey-Jumper
Niklas Thon
Stefan J Grau
Yoshua Esquenazi
Roberta Rudà
Susan M Chang
Mitchel S Berger
Daniel P Cahill
Joerg-Christian Tonn

Publication Date

1-5-2024

Journal

Neuro-Oncology

Abstract

BACKGROUND: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement.

METHODS: The RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between postoperative tumor volumes and outcome were analyzed. Propensity score-matched analyses were constructed to compare glioblastomas with and without contrast enhancement.

RESULTS: Among 1323 newly diagnosed IDH-wildtype glioblastomas, we identified 98 patients (7.4%) without contrast enhancement. In such patients, smaller postoperative tumor volumes were associated with more favorable outcome. There was an exponential increase in risk for death with larger residual non-CE tumor. Accordingly, extensive resection was associated with improved survival compared to lesion biopsy. These findings were retained on a multivariable analysis adjusting for demographic and clinical markers. Compared to CE glioblastoma, patients with non-CE glioblastoma had a more favorable clinical profile and superior outcome as confirmed in propensity score analyses by matching the patients with non-CE glioblastoma to patients with CE glioblastoma using a large set of clinical variables.

CONCLUSIONS: The absence of contrast enhancement characterizes a less aggressive clinical phenotype of IDH-wildtype glioblastomas. Maximal resection of non-CE tumors has prognostic implications and translates into favorable outcome.

Keywords

contrast enhancement, extent of resection, glioblastoma, surgery, WHO 2021