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Publications

Journal Article Ahead of print 4 citations

PubMed: 42391581 DOI: 10.1200/JCO-25-02735

Temozolomide Versus Radiotherapy as First-Line Therapy for Low-Grade Glioma: Mature Results of a Randomized Phase III Trial (EORTC 22033-26033/NCIC-CTG/TROG/MRC-CTU).

J Clin Oncol

Authors: Brigitta G Baumert, Monika E Hegi, Martin J van den Bent, Andreas von Deimling, Thierry Gorlia, Khê Hoang-Xuan, Alba A Brandes, Paul Sargos, Martin J B Taphoorn, Elodie Vauleon, Claire Philips, Johan M Kros, Pierre Bady, Wolfgang Wick, Roelien Enting, Michele Reni, Brian Thiessen, Frédéric Dhermain, Jacoline E Bromberg, Julian Jacob, Jaap C Reijneveld, Olivier Chinot, Johanna M M Gijtenbeek, John P Rossiter, Carmen Balana, Ana Luisa Silva Azevedo, Paul M Clement, Anna Berghoff, Tzahala Tzuk-Shina, Michael Weller, Robert A Nordal, Jeremy Rees, Denis A Lacombe, Warren P Mason, Roger Stupp

Affiliations

  • Department of Radiotherapy, Haaglanden Medisch Centrum, The Hague, the Netherlands.
  • Department of Radiation-Oncology (MAASTRO), Maastricht University Medical Center (MUMC) and GROW (School for Oncology), Maastricht, the Netherlands.
  • Neuroscience Research Center and Service of Neurosurgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Departments of Oncology and Clinical Neurosciences, L. Lundin and Family Brain Tumor Research Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Erasmus MC University MC Cancer Center, Rotterdam, the Netherlands.
  • Department of Neuropathology, Institute of Pathology, University of Heidelberg, INF 224, and CCU Neuropathology German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
  • Department of Neuro-Oncology, Institute of Neurology, Pitié-Salpêtrière Hospital, APHP, Sorbonne Universités, IHU, Paris, France.
  • Department of Medical Oncology, AUSL-IRCCS Scienze Neurologiche, Bologna, Italy.
  • Department of Radiotherapy, Institut Bergonié, Bordeaux, France.
  • Department of Neurology, Medical Center Haaglanden, The Hague, the Netherlands.
  • Department of Medical Oncology and Radiotherapy, Centre Eugène Marquis, Rennes, France.
  • Department of Radiation Oncology and Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
  • Department of Pathology, Erasmus Medical Center, Rotterdam, the Netherlands.
  • Translational Data Science & Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Neurology Clinic, University of Heidelberg Medical Center and NCT Neurooncology Within DKTK of the German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • IRCCS San Raffaele Scientific Institute, Milano, Italy.
  • BC Cancer Agency, Vancouver, BC, Canada.
  • Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
  • Department of Radiation-Oncology, Pitié-Salpêtrière Hospital, AP-HP, Sorbonne University, Paris, France.
  • Department of Neurology & Brain Tumor Center Amsterdam, Amsterdam University Medical Center, Amsterdam, the Netherlands.
  • Hôpital La Timone, Marseille, France.
  • Department of Neurology, Radboud University Medical Centre, Nijmegen, the Netherlands.
  • Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
  • Institut Investigació Germans Trias i Pujol (IGTP), Badalona, Spain.
  • Applied Research Group in Oncology (B-ARGO Group), Badalona, Spain.
  • Instituto Oncológico de Barcelona (IOB), Badalona, Spain.
  • Instituto Portugues de Oncologia de Lisboa (IPO), Lissabon, Portugal.
  • Department of Oncology, KU Leuven, Leuven, Belgium.
  • Medical University of Vienna: Clinical Division of Oncology Vienna, Vienna, Austria.
  • Rambam, Haifa, Israel.
  • Department of Neurology & Brain Tumor Center, University Hospital Zurich & University of Zurich, Zurich, Switzerland.
  • Department of Oncology, Arthur Child Comprehensive Cancer Centre, University of Calgary, Calgary, Canada.
  • National Hospital for Neurology and Neurosurgery, London, United Kingdom.
  • Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
  • Departments of Clinical Neurosciences and Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland.
  • Departments of Neurological Surgery, Neurology, and Medicine (Hem/Onc), Northwestern University Feinberg School of Medicine, Chicago, IL.
  • Lou and Jean Malnati Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.

Abstract

PURPOSE

Prognosis in low-grade gliomas (LGGs) remains highly variable, and treatment-related late toxicity is a concern. This trial was comparing single-modality therapies in patients who often survive for years or decades and investigating differential responses according to molecular markers.

METHODS

Four hundred seventy-eight patients with clinical high-risk LGG (WHO grade 2) were randomly assigned to standard radiotherapy (RT; 28 × 1.8 Gy) or dose-dense temozolomide (TMZ; 75 mg/m 2 once daily × 21/28 days, up to 12 cycles).

RESULTS

There was no significant difference in progression-free survival or overall survival (OS) between study arms. Analyzable tumor tissue in 73% (351/478) of patients allowed for post hoc reclassification according to the 2021 WHO pathologic criteria. In astrocytoma, IDHmt/1p/19q noncodeleted (n = 178), median OS was similar, 6.6-6.7 years irrespective of arm (0.67-1.44, P = .93). In oligodendroglioma, IDHmt/1p/19q codeleted (n = 109), median OS was 12.9 years (9.4-not reached) with RT and 14.9 years (10.1-number of events not reached) with TMZ (hazard ratio [HR], 0.88 [0.52-1.49], P = .63). In 64 tumors without isocitrate dehydrogenase (IDH) mutations, survival favored the TMZ arm: OS 2.5 (1.8-3.3) versus 4.7 (2.2-7.2) years (HR, 0.47 [0.27-0.82], P = .0068). Patients age 40 years and older fared better than patients younger than 40 years, challenging the current notion of age alone as a negative prognostic factor.

CONCLUSION

The assigned initial treatment modality did not affect progression-free survival or OS, regardless of the molecular subtype. Combined-modality therapy was not tested in this trial but has since become a standard of care for IDH-mutant astrocytoma. With emerging novel therapeutic options, rational treatment strategies tailored at the individual clinical and pathologic recurrence risk profiles will be needed. The validity of an age cutoff as prognostic factor is challenged when tumors are molecularly classified.

MeSH

Radiotherapy, Glioma, Progression-Free Survival, Temozolomide, Astrocytoma, Neoplasms, Therapeutics