Undetected pseudoprogressions in the CeTeG/NOA-09 trial: hints from postprogression survival and MRI analyses

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Thomas Zeyen - , Universität Bonn (Autor:in)
  • Daniel Paech - , Universität Bonn (Autor:in)
  • Johannes Weller - , Universität Bonn (Autor:in)
  • Niklas Schäfer - , Universität Bonn (Autor:in)
  • Theophilos Tzaridis - , Universität Bonn (Autor:in)
  • Cathrina Duffy - , Universität Bonn (Autor:in)
  • Louisa Nitsch - , Universität Bonn (Autor:in)
  • Matthias Schneider - , Universität Bonn (Autor:in)
  • Anna Laura Potthoff - , Universität Bonn (Autor:in)
  • Joachim Peter Steinbach - , Universitätsklinikum Frankfurt (Autor:in)
  • Peter Hau - , Universität Regensburg (Autor:in)
  • Uwe Schlegel - , Klinik Hirslanden (Autor:in)
  • Clemens Seidel - , Universität Leipzig (Autor:in)
  • Dietmar Krex - , Klinik und Poliklinik für Neurochirurgie (Autor:in)
  • Oliver Grauer - , Westfälische Wilhelms-Universität Münster (Autor:in)
  • Roland Goldbrunner - , Universität zu Köln (Autor:in)
  • Pia Susan Zeiner - , Universitätsklinikum Frankfurt (Autor:in)
  • Ghazaleh Tabatabai - , Eberhard Karls Universität Tübingen (Autor:in)
  • Norbert Galldiks - , Universität zu Köln (Autor:in)
  • Walter Stummer - , Westfälische Wilhelms-Universität Münster (Autor:in)
  • Elke Hattingen - , Universitätsklinikum Frankfurt (Autor:in)
  • Martin Glas - , Universität Duisburg-Essen (Autor:in)
  • Alexander Radbruch - , Universität Bonn (Autor:in)
  • Ulrich Herrlinger - , Universität Bonn (Autor:in)
  • Christina Schaub - , Universität Bonn (Autor:in)

Abstract

Purpose: In the randomized CeTeG/NOA-09 trial, lomustine/temozolomide (CCNU/TMZ) was superior to TMZ therapy regarding overall survival (OS) in MGMT promotor-methylated glioblastoma. Progression-free survival (PFS) and pseudoprogression rates (about 10%) were similar in both arms. Further evaluating this discrepancy, we analyzed patterns of postprogression survival (PPS) and MRI features at first progression according to modified RANO criteria (mRANO). Methods: We classified the patients of the CeTeG/NOA-09 trial according to long vs. short PPS employing a cut-off of 18 months and compared baseline characteristics and survival times. In patients with available MRIs and confirmed progression, the increase in T1-enhancing, FLAIR hyperintense lesion volume and the change in ADC mean value of contrast-enhancing tumor upon progression were determined. Results: Patients with long PPS in the CCNU/TMZ arm had a particularly short PFS (5.6 months). PFS in this subgroup was shorter than in the long PPS subgroup of the TMZ arm (11.1 months, p = 0.01). At mRANO-defined progression, patients of the CCNU/TMZ long PPS subgroup had a significantly higher increase of mean ADC values (p = 0.015) and a tendency to a stronger volumetric increase in T1-enhancement (p = 0.22) as compared to long PPS patients of the TMZ arm. Conclusion: The combination of survival and MRI analyses identified a subgroup of CCNU/TMZ-treated patients with features that sets them apart from other patients in the trial: short first PFS despite long PPS and significant increase in mean ADC values upon mRANO-defined progression. The observed pattern is compatible with the features commonly observed in pseudoprogression suggesting mRANO-undetected pseudoprogressions in the CCNU/TMZ arm of CeTeG/NOA-09.

Details

OriginalspracheEnglisch
Seiten (von - bis)607-616
Seitenumfang10
FachzeitschriftJournal of neuro-oncology
Jahrgang164
Ausgabenummer3
PublikationsstatusVeröffentlicht - Sept. 2023
Peer-Review-StatusJa

Externe IDs

PubMed 37728779

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Glioblastoma, MGMT promotor methylation, MRI, Progression, Pseudoprogression, Brain Neoplasms/diagnostic imaging, Antineoplastic Agents, Alkylating/therapeutic use, Humans, Lomustine/therapeutic use, Temozolomide/therapeutic use, Dacarbazine/therapeutic use, Glioblastoma/diagnostic imaging, Magnetic Resonance Imaging