Treatment response as surrogate to predict risk for disease progression in pediatric medulloblastoma with persistent MRI lesions after first-line treatment

Denise Obrecht-Sturm; Lena Schömig; Martin Mynarek; Brigitte Bison; Rudolf Schwarz; Torsten Pietsch; Stefan M Pfister; Martin Sill; Dominik Sturm; Felix Sahm; Rolf-Dieter Kortmann; Nicolas U Gerber; André O von Bueren; Gudrun Fleischhack; Ulrich Schüller; Gunther Nussbaumer; Martin Benesch; Stefan Rutkowski

doi:10.1093/neuonc/noae071

Treatment response as surrogate to predict risk for disease progression in pediatric medulloblastoma with persistent MRI lesions after first-line treatment

Neuro Oncol. 2024 Apr 5:noae071. doi: 10.1093/neuonc/noae071. Online ahead of print.

Authors

Denise Obrecht-Sturm¹, Lena Schömig¹, Martin Mynarek^{1

2}, Brigitte Bison³, Rudolf Schwarz⁴, Torsten Pietsch⁵, Stefan M Pfister^{6

7

8}, Martin Sill^{6

7

8}, Dominik Sturm^{6

8

9}, Felix Sahm^{6

10

11}, Rolf-Dieter Kortmann¹², Nicolas U Gerber¹³, André O von Bueren¹⁴, Gudrun Fleischhack¹⁵, Ulrich Schüller^{1

16

17}, Gunther Nussbaumer¹⁸, Martin Benesch¹⁸, Stefan Rutkowski¹

Affiliations

¹ Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
² Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³ Department of Neuroradiology, University Hospital Augsburg, Augsburg, Germany.
⁴ Department for Radiotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁵ Institute of Neuropathology, Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy (DGNN), University of Bonn, DZNE German Center for Neurodegenerative Diseases, Bonn, Germany.
⁶ Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
⁷ Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
⁸ Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
⁹ Pediatric Glioma Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁰ Department of Neuropathology, University Heidelberg Heidelberg, Germany.
¹¹ CCU Neuropathology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg University Hospital, Heidelberg, Germany.
¹² Department of Radiation Oncology, University Hospital Leipzig, Leipzig, Germany.
¹³ Department of Pediatric Oncology, University Children's Hospital Zürich, Zürich, Switzerland.
¹⁴ Department of Pediatrics, Obstetrics and Gynecology, Division of Pediatric Hematology and Oncology, University Hospital of Geneva, Geneva, Switzerland.
¹⁵ Pediatrics III, Pediatric Oncology and Hematology, University Hospital Essen, Essen, Germany.
¹⁶ Department of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁷ Research Institute Kinderkrebs-Zentrum Hamburg, Hamburg, Germany.
¹⁸ Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.

PMID: 38578306
DOI: 10.1093/neuonc/noae071

Abstract

Background: This study aims at clarifying the impact of persistent residual lesions following first-line treatment for pediatric medulloblastoma.

Methods: Data on 84 pediatric patients with medulloblastoma and persistent residual lesions on centrally reviewed MRI at the end of first-line therapy were analyzed.

Results: Twenty patients (23.8%) had residual lesions in the tumor bed (R+/M0), 51 (60.7%) had distant lesions (R0/M+) and 13 (15.5%) had both (R+/M+). Overall response to first-line therapy was minor or partial (≥25% reduction, MR/PR) for 64 (76.2%) and stable disease (SD) for 20 patients (23.8%). Five-year post-primary-treatment progression-free (pptPFS) and overall survival (pptOS) were superior after MR/PR (pptPFS: 62.5±7.0%[MR/PR] vs. 35.9±12.8%[SD], p=0.03; pptOS: 79.7±5.9[MR/PR] vs. 55.5±13.9[SD], p=0.04). Further, R+/M+ was associated with a higher risk for progression (5-year pptPFS: 22.9±17.9%[R+,M+] vs. 72.4±12.0%[R+,M0]; p=0.03). Watch-and-wait was pursued in 58 patients, while n=26 received additional treatments (chemotherapy only, n=19; surgery only, n=2; combined, n=3; valproic acid, n=2), and their outcomes were not superior to watch-and-wait (5-year pptPFS: 58.5±7.7% vs. 51.6±10.7% p=0.71; 5-year pptOS: 76.3±6.9% vs. 69.8±9.7%, p=0.74). For the whole cohort, five-year pptPFS by molecular subgroup (58 cases) were WNT: 100%, SHH: 50.0±35.4%, Group-4, 52.5±10.5, Group-3 54.2±13.8%; (p=0.08).

Conclusion: Overall response and extent of lesions can function as surrogate parameters to predict outcomes in pediatric MB patients with persistent lesions after first-line therapy. Especially in case of solitary persistent medulloblastoma MRI lesion, additional therapy was not beneficial. Therefore, treatment response, extent/kind of residual lesions and further diagnostic information needs consideration for indication of additional treatments for persisting lesions.

Keywords: MRI; children; medulloblastoma; persistent residual disease.