A1 Refereed original research article in a scientific journal
Comparative Clinical and Imaging‐Based Evaluation of Therapeutic Modalities in CNS Embryonal Tumours With PLAGL Amplification
Authors: Keck, Michaela-Kristina; Tietze, Anna; Bison, Brigitte; Avula, Shivaram; Engelhardt, Julien; Faure-Conter, Cecile; Fenouil, Tanguy; Figarella-Branger, Dominique; Goebell, Einar; Gojo, Johannes; Haberler, Christine; Hakumaki, Juhana; Hayden, James T.; Korhonen, Laura S.; Koscielniak, Ewa; Kramm, Christof M.; Kranendonk, Mariette E. G.; Lequin, Maarten; Ludlow, Louise E.; Meyronet, David; Nyman, Per; Ora, Ingrid; Perwein, Thomas; Pesola, Jouni; Rauramaa, Tuomas; Reddingius, Roel; Samuel, David; Schouten-van Meeteren, Antoinette Y. N.; Sexton-Oates, Alexandra; Vasiljevic, Alexandre; von Kalle, Thekla; Wefers, Annika K.; Wesseling, Pieter; Zamecnik, Josef; Zapotocky, Michal; von Hoff, Katja; Jones, David T. W.
Publisher: Wiley
Publishing place: HOBOKEN
Publication year: 2025
Journal: Neuropathology and Applied Neurobiology
Journal name in source: Neuropathology and Applied Neurobiology
Journal acronym: NEUROPATH APPL NEURO
Article number: e70015
Volume: 51
Issue: 2
Number of pages: 11
ISSN: 0305-1846
eISSN: 1365-2990
DOI: https://doi.org/10.1111/nan.70015
Web address : https://doi.org/10.1111/nan.70015
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/491847085
Aims: Embryonal tumours with PLAGL1 or PLAGL2 amplification (ET, PLAGL) show substantial heterogeneity regarding their clinical characteristics and have been treated inconsistently, resulting in diverse outcomes. In this study, we aimed to evaluate the clinical behaviour of ET, PLAGL and elucidate their response pattern across the different applied treatment regimens.
Methods: We conducted an in-depth retrospective analysis of clinical and serial imaging data of 18 patients with ET, PLAGL (nine each of PLAGL1 and PLAGL2 amplified).
Results: Patients with PLAGL1-amplified tumours (ET, PLAGL1) had fewer relapses (3/9), while PLAGL2-amplified tumours (ET, PLAGL2) were prone to early relapse or progression (8/9) and to distant, leptomeningeal and intraventricular relapses. Progression-free survival differed significantly between the subtypes (log-rank test, p = 0.0055). Postoperative treatment included chemotherapy (n = 17, various protocols), alone (n = 8) or combined with radiotherapy (n = 9). Responses to chemotherapy were observed in both subtypes, and incomplete resection was not associated with inferior survival. All three survivors with ET, PLAGL2 were treated with induction and high-dose chemotherapy with (n = 1-low-dose CSI and boost) or without (n = 2) radiotherapy, whereas five patients with less intensive chemotherapy relapsed. All six survivors with ET, PLAGL1 were treated with conventional chemotherapy regimens, with (n = 4-local radiotherapy n = 3; CSI and boost n = 1) or without (n = 2) radiotherapy. Two patients with ET, PLAGL1 relapsed after 8 years.
Conclusions: Adjuvant therapy should be considered for all ET, PLAGL patients: Patients with ET, PLAGL2 might benefit from intensified chemotherapy regimens. In contrast, patients with ET, PLAGL1 showed superior outcomes without high-dose chemotherapy or craniospinal irradiation.
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Funding information in the publication:
We thank all contributors of clinical data for the cases presented in Table 1, namely, Martin McCabe (University of Manchester, UK), Federico Roncaroli (University of Manchester, UK), David Solomon (University of California San Francisco, USA), Nasir Ud Din (The Aga Khan University, Pakistan), Suzanne J. Baker (St. Jude Children's Research Hospital, USA), Florian Selt (Hopp Children's Cancer Center Heidelberg [KiTZ], Germany), Jonas Ecker (Hopp Children's Cancer Center Heidelberg [KiTZ], Germany), Till Milde (Hopp Children's Cancer Center Heidelberg [KiTZ], Germany), Andreas von Deimling (University Hospital Heidelberg, Germany) and Andrey Korshunov (University Hospital Heidelberg, Germany). Open Access funding enabled and organized by Projekt DEAL.
