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. 2025 Feb 20;25(1):306.
doi: 10.1186/s12885-025-13682-3.

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

Matthias Schneider  1   2 , Anna-Laura Potthoff  3   4 , Yahya Ahmadipour  5 , Valeri Borger  3 , Hans Clusmann  6 , Stephanie E Combs  7 , Marcus Czabanka  8 , Lasse Dührsen  9 , Nima Etminan  10 , Thomas M Freiman  11 , Ruediger Gerlach  12 , Florian Gessler  11 , Frank A Giordano  13 , Eleni Gkika  14 , Roland Goldbrunner  15 , Erdem Güresir  16 , Hussam Hamou  6 , Peter Hau  17 , Sebastian Ille  18 , Max Jägersberg  19 , Naureen Keric  20 , Maryam Khaleghi-Ghadiri  21 , Ralph König  22 , Jürgen Konczalla  8 , Harald Krenzlin  20 , Sandro Krieg  18 , Aaron Lawson McLean  23 , Julian P Layer  14   24 , Jens Lehmberg  25 , Vesna Malinova  26 , Bernhard Meyer  27 , Hanno S Meyer  9 , Dorothea Miller  28 , Oliver Müller  29 , Christian Musahl  30 , Barbara E F Pregler  3   4 , Ali Rashidi  31 , Florian Ringel  32 , Constantin Roder  33 , Karl Rössler  34 , Veit Rohde  26 , I Erol Sandalcioglu  31 , Niklas Schäfer  35 , Christina Schaub  36 , Nils Ole Schmidt  37 , Gerrit A Schubert  6   30 , Clemens Seidel  38 , Corinna Seliger  36 , Christian Senft  23 , Julia Shawarba  34 , Joachim Steinbach  39 , Veit Stöcklein  32 , Walter Stummer  21 , Ulrich Sure  5 , Ghazaleh Tabatabai  40 , Marcos Tatagiba  33 , Niklas Thon  28 , Marco Timmer  15 , Johannes Wach  16 , Arthur Wagner  27 , Christian Rainer Wirtz  22 , Katharina Zeiler  25 , Thomas Zeyen  4   35 , Patrick Schuss  41 , Rainer Surges  42 , Christine Fuhrmann  43 , Daniel Paech  44   45 , Matthias Schmid  46 , Yvonne Borck  43 , Torsten Pietsch  47 , Rafael Struck  43 , Alexander Radbruch  46 , Christoph Helmstaedter  42 , Robert Németh  46 , Ulrich Herrlinger #  4   35 , Hartmut Vatter #  3   4
Affiliations

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

Matthias Schneider et al. BMC Cancer. .

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.

Keywords: Anterior temporal lobectomy; Epilepsy surgery; Gross-total resection; Supramarginal resection; Temporal lobe glioblastoma.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The ATLAS/NOA-29 trial protocol has been approved by the local ethics committee of the University Hospital Bonn (reference number: 290/23). The trial complies with the guidelines and regulations outlined in the Berufsordnung für Ärzte, the Declaration of Helsinki, the Datenschutz-Grundverordnung (DSGVO), and the Gesundheitsdatenschutzgesetz (GDSG) of the state of North Rhine-Westphalia, as confirmed by the ethics committee of the University Hospital Bonn. Written informed consent will be obtained from all participants prior to their inclusion in the trial. Consent for publication: All authors agreed to the publication of the manuscript. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The ATL as a surgical approach for anterior temporal lobe glioblastoma. The adaptation of ATL from epilepsy surgery to glioblastoma surgery enables the resection of both the tumor bulk (depicted in dark red for this example) and extensive surrounding infiltrative tissue as an in-toto specimen. Scheme modified from Wiebe et al. [18]. ATL, anterior temporal lobectomy
Fig. 2
Fig. 2
Graphical synopsis of the ATLAS/NOA-29 trial. ATL, anterior temporal lobectomy; EORTC, European Organization for Research and Treatment of Cancer; GTR, gross-total resection; ILAE, International League Against Epilepsy; QoL, quality of life; mo, months; mOS, median overall survival; mRS, modified Rankin Scale; PFS, progression-free survival; QLQ-C30/BN20, quality of life questionnaire modules; yrs, years
Fig. 3
Fig. 3
ATLAS/NOA-29 trial logo
Fig. 4
Fig. 4
Overview of study visits. FU, follow-up
Fig. 5
Fig. 5
Graphical overview of the ILAE classification system for assessing postoperative seizure outcome. Scheme adapted from Wieser et al. [68]. ILAE, International League Against Epilepsy; yr, year
See this image and copyright information in PMC

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