Comparison of survival and progression after focal- or whole brain radiotherapy in patients with primary CNS lymphoma - Results from a large multicenter analysis of the German Society of Radiation Oncology's Neuro-Radio-Oncology Working Group (DEGRO AG-NRO)

Sina Heider; Luisa Allwohn; Alexander Rühle; Felix Ehret; David Kaul; Michael Oertel; Niklas B Pepper; Elgin Hoffmann; Raphael Bodensohn; Arne Ruder; Ilinca Popp; Roland Merten; Hans T Eich; Denise Bernhardt; Folker Schneller; Elisabeth Schorb; Nanna Wielenberg; Stephanie E Combs; Anca L Grosu; Nils H Nicolay; Clemens Seidel

doi:10.1016/j.radonc.2025.110984

Comparison of survival and progression after focal- or whole brain radiotherapy in patients with primary CNS lymphoma - Results from a large multicenter analysis of the German Society of Radiation Oncology's Neuro-Radio-Oncology Working Group (DEGRO AG-NRO)

Radiother Oncol. 2025 Jun 7:209:110984. doi: 10.1016/j.radonc.2025.110984. Online ahead of print.

Authors

Sina Heider¹, Luisa Allwohn², Alexander Rühle³, Felix Ehret⁴, David Kaul⁵, Michael Oertel⁶, Niklas B Pepper⁶, Elgin Hoffmann⁷, Raphael Bodensohn⁷, Arne Ruder⁸, Ilinca Popp⁹, Roland Merten¹⁰, Hans T Eich⁶, Denise Bernhardt¹¹, Folker Schneller¹², Elisabeth Schorb¹³, Nanna Wielenberg⁹, Stephanie E Combs¹¹, Anca L Grosu⁹, Nils H Nicolay¹, Clemens Seidel¹⁴

Affiliations

¹ Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany; Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany.
² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiation Oncology, Charitéplatz 1, 10117 Berlin, Germany.
³ Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany; Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany; Department of Radiation Oncology, Medical Center - University of Freiburg, Robert-Koch-Straße 3, 79106 Freiburg, German Cancer Consortium (DKTK), partner site DKTK-Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany.
⁴ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiation Oncology, Charitéplatz 1, 10117 Berlin, Germany; German Cancer Consortium (DKTK), partner site Berlin, a partnership between DKFZ and Charité - Universitätsmedizin Berlin, Invalidenstr. 80, 10115 Berlin Germany.
⁵ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiation Oncology, Charitéplatz 1, 10117 Berlin, Germany; German Cancer Consortium (DKTK), partner site Berlin, a partnership between DKFZ and Charité - Universitätsmedizin Berlin, Invalidenstr. 80, 10115 Berlin Germany; Department of Radiation Oncology, Health and Medical University Potsdam, Charlottenstraße 72, 14467 Potsdam, Germany.
⁶ Department of Radiation Oncology, Münster University Hospital, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.
⁷ Department of Radiation Oncology, University Hospital Tübingen, Hoppe-Seyler-Straße 3, 72076 Tübingen, Germany.
⁸ Department of Radiation Oncology, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
⁹ Department of Radiation Oncology, Medical Center - University of Freiburg, Robert-Koch-Straße 3, 79106 Freiburg, German Cancer Consortium (DKTK), partner site DKTK-Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany.
¹⁰ Hannover Medical School, Department of Radiotherapy, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
¹¹ Department of Radiation Oncology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Straße 22, Munich, Germany.
¹² 3rd Medical Department, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Straße 22, Munich, Germany.
¹³ Department of Medicine I, Medical Center, Faculty of Medicine, University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany.
¹⁴ Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany; Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany. Electronic address: Clemens.Seidel@medizin.uni-leipzig.de.

PMID: 40490053
DOI: 10.1016/j.radonc.2025.110984

Abstract

Background and purpose: Primary central nervous system lymphoma (PCNSL) is a rare but aggressive disease. The application of radiotherapy (RT) as part of treatment usually involved whole-brain radiotherapy (WBRT). Focal radiotherapy (fRT) might be locally active, but comparative outcome data is lacking.

Materials and methods: Data from a multicenter registry of the German Society of Radiation Oncology's Neuro-Radio-Oncology Working Group (DEGRO AG-NRO) was analyzed. Patients treated for PCNSL between 2007 and 2023 who received RT at any stage of their disease were included. Kaplan-Meier and Cox proportional hazards regression analyses were conducted to compare survival between focal (fRT) and whole-brain radiotherapy (WBRT).

Results: Survival data of 151 patients from eight centers were available. The median age at diagnosis was 66.5 years, and the median Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) was 2. Eighteen percent of patients (n = 27) received primary RT, 33 % (n = 49) consolidation RT, and 49 % (n = 73) RT for recurrent disease. Median overall survival (OS) from diagnosis was 24.1 months (95 % CI: 14.7-33.4), and median survival after RT was 7.2 months (95 % CI: 4.5-10.0). In patients treated with fRT (n = 28) median OS was 67.6 months (95 % CI: 35.7-99.6) compared to 20.1 months after WBRT (n = 123, 95 % CI: 10.5-29.8) (HR = 0.5, p = 0.016). Median survival after RT was also longer with fRT (44.0 months, 95 % CI: 5.9-82.1) than with WBRT (5.8 months, 95 % CI: 3.2-8.4) (HR = 0.5, p = 0.017). In recurrent disease median PFS after use of fRT was 3.8 months, compared to 3.0 months after WBRT (p = 0.164). After fRT, in 16/28 (39 %) patients tumor progression was observed (2/16 in-field, 3/16 out-field, 3/16 mixed, 8/16 unknown). In multivariate Cox-regression analysis, histology other than diffuse large B-cell lymphoma (HR = 0.345, p < 0.01) and fRT (HR = 0.518, p < 0.05) remained independently associated with improved OS.

Conclusion: fRT may be a beneficial treatment option for patients with PCNSL and needs to be studied further in prospective clinical trials.

Keywords: Focal radiotherapy; PCNSL; Primary CNS lymphoma; Stereotactic radiotherapy; Whole brain irradiation.