The ATLAS/NOA-29 study protocol: a phase III randomized controlled trial of anterior temporal lobectomy versus gross-total resection in newly-diagnosed temporal lobe glioblastoma
Authors: Schneider Matthias , Potthoff Anna-Laura , Ahmadipour Yahya , Borger Valeri , Clusmann Hans , Combs Stephanie E. , Czabanka Marcus , Dührsen Lasse , Etminan Nima , Freiman Thomas M. , Gerlach Ruediger , Gessler Florian , Giordano Frank A. , Gkika Eleni , Goldbrunner Roland , Güresir Erdem , Hamou Hussam , Hau Peter , Ille Sebastian , Jägersberg Max , Keric Naureen , Khaleghi-Ghadiri Maryam , König Ralph , Konczalla Jürgen , Krenzlin Harald , Krieg Sandro , McLean Aaron Lawson , Layer Julian P. , Lehmberg Jens , Malinova Vesna , Meyer Bernhard , Meyer Hanno S. , Miller Dorothea , Müller Oliver , Musahl Christian , Pregler Barbara E. F. , Rashidi Ali , Ringel Florian , Roder Constantin , Rössler Karl , Rohde Veit , Sandalcioglu I. Erol , Schäfer Niklas , Schaub Christina , Schmidt Nils Ole , Schubert Gerrit A. , Seidel Clemens , Seliger Corinna , Senft Christian , Shawarba Julia , Steinbach Joachim , Stöcklein Veit , Stummer Walter , Sure Ulrich , Tabatabai Ghazaleh , Tatagiba Marcos , Thon Niklas , Timmer Marco , Wach Johannes , Wagner Arthur , Wirtz Christian Rainer , Zeiler Katharina , Zeyen Thomas , Schuss Patrick , Surges Rainer , Fuhrmann Christine , Paech Daniel , Schmid Matthias , Borck Yvonne , Pietsch Torsten , Struck Rafael , Radbruch Alexander , Helmstaedter Christoph , Németh Robert , Herrlinger Ulrich , Vatter Hartmut 
Published: February 2025

Abstract

Background
The discovery of cellular tumor networks in glioblastoma, with routes of malignant communication extending far beyond the detectable tumor margins, has highlighted the potential of supramarginal resection strategies. Retrospective data suggest that these approaches may improve long-term disease control. However, their application is limited by the proximity of critical brain regions and vasculature, posing challenges for validation in randomized trials. Anterior temporal lobectomy (ATL) is a standardized surgical procedure commonly performed in patients with pharmacoresistant temporal lobe epilepsy. Translating the ATL approach from epilepsy surgery to the neuro-oncological field may provide a model for investigating supramarginal resection in glioblastomas located in the anterior temporal lobe.

Methods
The ATLAS/NOA-29 trial is a prospective, multicenter, multinational, phase III randomized controlled trial designed to compare ATL with standard gross-total resection (GTR) in patients with newly-diagnosed anterior temporal lobe glioblastoma. The primary endpoint is overall survival (OS), with superiority defined by significant improvements in OS and non-inferiority in the co-primary endpoint, quality of life (QoL; “global health” domain of the European organization for research and treatment of cancer (EORTC) QLQ-C30 questionnaire). Secondary endpoints include progression-free survival (PFS), seizure outcomes, neurocognitive performance, and the longitudinal assessment of six selected domains from the EORTC QLQ-C30 and BN20 questionnaires. Randomization will be performed intraoperatively upon receipt of the fresh frozen section result. A total of 178 patients will be randomized in a 1:1 ratio over a 3-year recruitment period and followed-up for a minimum of 3 years. The trial will be supervised by a Data Safety Monitoring Board, with an interim safety analysis planned after the recruitment of the 57th patient to assess potential differences in modified Rankin Scale (mRS) scores between the treatment arms 6 months after resection. Assuming a median improvement in OS from 17 to 27.5 months, the trial is powered at > 80% to detect OS differences with a two-sided log-rank test at a 5% significance level.

Discussion
The ATLAS/NOA-29 trial aims to determine whether ATL provides superior outcomes at equal patients’ Qol compared to GTR in anterior temporal lobe glioblastoma, potentially establishing ATL as the surgical approach of choice for isolated temporal glioblastoma and redefining the standard of care for this patient population.

Trial registration
German Clinical Trials Register (DRKS00035314), registered on October 18, 2024.