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Comparative Study
. 2025 Apr;51(2):e70015.
doi: 10.1111/nan.70015.

Comparative Clinical and Imaging-Based Evaluation of Therapeutic Modalities in CNS Embryonal Tumours With PLAGL Amplification

Michaela-Kristina Keck  1   2   3 , Anna Tietze  4 , Brigitte Bison  5 , Shivaram Avula  6 , Julien Engelhardt  7   8 , Cécile Faure-Conter  9 , Tanguy Fenouil  10 , Dominique Figarella-Branger  11 , Einar Goebell  12 , Johannes Gojo  13 , Christine Haberler  14 , Juhana Hakumäki  15   16 , James T Hayden  17 , Laura S Korhonen  18 , Ewa Koscielniak  19 , Christof M Kramm  20 , Mariëtte E G Kranendonk  21 , Maarten Lequin  22 , Louise E Ludlow  23   24   25 , David Meyronet  10 , Per Nyman  26   27 , Ingrid Øra  28 , Thomas Perwein  29   30 , Jouni Pesola  31 , Tuomas Rauramaa  32 , Roel Reddingius  33 , David Samuel  34 , Antoinette Y N Schouten-van Meeteren  33 , Alexandra Sexton-Oates  35 , Alexandre Vasiljevic  10 , Thekla von Kalle  36 , Annika K Wefers  37   38 , Pieter Wesseling  21   39 , Josef Zamecnik  40 , Michal Zapotocky  41   42 , Katja von Hoff  43   44 , David T W Jones  1   2   3
Affiliations
Comparative Study

Comparative Clinical and Imaging-Based Evaluation of Therapeutic Modalities in CNS Embryonal Tumours With PLAGL Amplification

Michaela-Kristina Keck et al. Neuropathol Appl Neurobiol. 2025 Apr.

Abstract

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.

Keywords: PLAGL1; PLAGL2; ET, PLAGL; embryonal CNS tumour; treatment.

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Conflict of interest statement

The corresponding authors report no potential conflict of interest. Per Nyman reports minority private shareholding (SyntheticMR AB). Laura S. Korhonen is a NOPHO (Nordic Society of Paediatric Haematology) board member. Pieter Wesseling received a travel grant from Chimerix for contributing to a session during the Annual SNO 2023 meeting in Vancouver and is chair of the cIMPACT‐NOW Steering Committee. Ingrid Øra is supported by the Swedish Childhood Cancer Fund (Stockholm, Sweden). Christof M. Kramm is supported by the Deutsche Kinderkrebsstiftung (Bonn, Germany) and has received grants/contracts from Blueprint Rover and Novartis. He is also on the advisory board on glioblastoma medication (Boehringer Ingelheim), chairman of the HIT‐HGG study group, (Goettingen, Germany), executive committee member of the SIOPE DIPG Registry, Utrecht, the Netherlands, and executive committee member of the Neurooncological Working Group (Berlin, Germany). Juhana Hakumäki is president of the Finnish Radiological Society. Michal Zapotocky has received an honorarium from AstraZeneca. Where authors are identified as personnel of the IARC/WHO, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policies or views of the IARC/WHO.

Figures

FIGURE 1
FIGURE 1
Detailed summary of clinical information and outcome of all 18 patients separated according to amplification status, PLAGL1 (n = 9) and PLAGL2 (n = 9). OS is shown on the x axis. IDs and clinical data are listed for each patient on the left. Bars are coloured according to treatment (CT and RT). The extent of resection, amount of residual tumour after resection and response to treatment were determined through a review of MRI scans and displayed through the different symbols. The death of a patient is symbolised by an obelisk behind the respective bar. ASCR, autologous stem cell rescue; Bx, biopsy; Carbo, carboplatin; CSI, craniospinal irradiation; CT, chemotherapy; Dx, diagnosis; emb, embryonal; ETANTR, embryonal tumour with abundant neuropil and true rosettes; GTR, gross total resection; HDCT, high‐dose chemotherapy; HGG, high‐grade glioma; HGNET, high‐grade neuroepithelial tumour; MB, medulloblastoma; NEC, not elsewhere classified; NOS, not otherwise specified; PNET, primitive neuroectodermal tumour; pt., patient; RT, radiotherapy; Rx, resection; VP, VePesid.
FIGURE 2
FIGURE 2
Separate sunburst plots are shown for ET, PLAGL1 and ET, PLAGL2. (A) Localisation of the tumours is shown in conjunction with resection status and survival for male and female patients. (B) Age is shown in conjunction with RT and survival for male and female patients.
FIGURE 3
FIGURE 3
Kaplan–Meier plots showing 10‐year OS and PFS stratified by (A) subtype, (B) sex and (C) application of radiotherapy during primary treatment. The log‐rank test was used to show differences between the curves, p values of the log‐rank test are shown in each graph.
See this image and copyright information in PMC

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