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Favorable radiation field decrease in gastric marginal zone lymphoma

Experience of the German Study Group on Gastrointestinal Lymphoma (DSGL)

Erfolgreiche Strahlenfeldverkleinerung bei gastralem Marginalzonenlymphom

Erfahrungen der Deutschen Studiengruppe Gastrointestinale Lymphome (DSGL)

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Abstract

Purpose

Long-term impact of stage-adapted field reduction in a large cohort of gastric marginal zone lymphoma (gMZL) patients treated conservatively with curative radiation therapy (RT).

Patients and methods

Prospective analysis of paper records of 290 patients with stage IE–IIE gMZL, treated in 78 radiotherapeutic institutions in Germany from 1992–2013. Stage-adapted radiation fields decreased from extended field (EF) to involved field (IF) over the course of three consecutive prospective trials of the German Study Group on Gastrointestinal Lymphoma (DSGL). Treatment results were compared between the three cohorts.

Results

Overall collective with median age of 60 years, slight male predominance (m:f = 1.1:1) and ratio of disease stage I:stage II = 2.1:1. Median follow-up 6.4 years in total: 13.0 years in the first gastrointestinal study (GIT 1992), 8.2 years in the second (GIT 1996) and 4.7 years in the third study (DSGL 01/2003). Stage-adapted radiation field decrease together with further technological development led to reduced relative frequencies of acute/chronic adverse effects and until now was accompanied by lower disease recurrence. The third study design with smallest field size (IF in stage I, locoregional EF in stage II) achieved the best survival outcome at the 5‑year follow-up (overall survival 92.7%, event-free survival 89.5% and lymphoma-specific survival 100.0%). Disease relapse observed in 10 patients. Cumulative incidence of disease-specific death was 1.7% of the followed patients. Primary disease stage associated with lymphoma-specific survival.

Conclusion

Stage-adapted reduction towards IF in gMZL resulted in favorable adverse effects, local control and survival rates. These results support further decreases in modern RT of gMZL.

Zusammenfassung

Zielsetzung

Langzeiteffekt der stadienadaptierten Strahlenfeldverkleinerung bei kurativer Radiotherapie (RT) in einer großen Kohorte von Patienten mit gastralem Marginalzonenlymphom (gMZL).

Patienten und Methoden

Prospektive Analyse der Papierakten von 290 Patienten mit gMZL im Stadium IE–IIE, behandelt in 78 radiotherapeutischen Institutionen in Deutschland von 1992–2013. Stadienadaptierte Strahlenfeldreduktion vom „extended field“ (EF) zum „involved field“ (IF) im Verlauf der drei konsekutiven prospektiven Studien der Deutschen Studiengruppe Gastrointestinale Lymphome (DSGL). Behandlungsergebnisse wurden zwischen den drei Studienkohorten verglichen.

Ergebnisse

Gesamtkollektiv mit medianem Alter von 60 Jahren; Geschlechterverhältnis m:w = 1,1:1 und Stadienverhältnis I:II = 2,1:1. Medianes Follow-up insgesamt 6,4 Jahre: 13,0 Jahre in der ersten gastrointestinalen Studie (GIT 1992), 8,2 Jahre in der zweiten (GIT 1996) und 4,7 Jahre in der dritten Studie (DSGL 01/2003). Die stadienadaptierte Strahlenfeldverkleinerung zusammen mit der technischen Weiterentwicklung führte zu reduzierten relativen Häufigkeiten der akuten/chronischen Nebenwirkungen und ist bislang begleitet von einer niedrigeren Rezidivrate. Das Konzept der dritten Studie mit der kleinsten Feldausdehnung (IF im Stadium I, lokoregionales EF im Stadium II) erreichte die besten Überlebensraten nach einem Follow-up von 5 Jahren (Gesamtüberleben 92,7%, ereignisfreies Überleben 89,5% und lymphomspezifisches Überleben 100,0%). Lymphomrezidive wurden bei 10 Patienten beobachtet. Die kumulative Inzidenz der krankheitsspezifischen Todesrate bei den nachbeobachteten Patienten betrug 1,7%. Das primäre Krankheitsstadium war assoziiert mit dem lymphomspezifischen Überleben.

Schlussfolgerung

Die stadienadaptierte Feldverkleinerung zum IF bei gMZL resultiert in günstigen Nebenwirkungen, lokaler Kontrolle und Überlebensraten. Diese Ergebnisse bekräftigen die weitere Deeskalation der modernen RT von gMZL.

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Acknowledgements

We thank all patients, treating physicians, investigators and participants, who provided ongoing support for these trials. This work was supported by 78 radiotherapeutic institutions in Germany, listed in the appendix. The biostatistical assistance of Dr. Rene Schmidt, Institute of Biostatistics and Clinical Research University of Münster, is gratefully acknowledged.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital of Münster, Building A1, Albert Schweitzer Campus 1, 48149, Münster, Germany

    Gabriele Reinartz, Regina P. Pyra, Normann Willich & Hans T. Eich

  2. Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital of Münster, Münster, Germany

    Georg Lenz, Rüdiger Liersch & Wolfgang E. Berdel

  3. Department of Radiation Oncology, Hospital Augsburg, Augsburg, Germany

    Georg Stüben

  4. Department of Radiotherapy and Radiation Oncology, Franziskus Hospital Bielefeld, Bielefeld, Germany

    Oliver Micke

  5. Department of Radiotherapy and Radiation Oncology, Pius Hospital Oldenburg, Oldenburg, Germany

    Kay Willborn

  6. Department of Radiation Oncology, University Hospital of Göttingen, Göttingen, Germany

    Clemens F. Hess

  7. Department of Gastroenterology, Central Hospital, Augsburg, Germany

    Andreas Probst

  8. Department of Radiation Oncology, University of Erlangen, Erlangen, Germany

    Rainer Fietkau

  9. Department of Radiation Oncology, Saint Marien Hospital, Hamm, Germany

    Ralf Jany

  10. Department of Radiation Oncology, University of Schleswig-Holstein, Kiel, Germany

    Jürgen Schultze

  11. Department of Radiation Oncology, University of Saarland, Homburg, Germany

    Christian Rübe

  12. Department of Medical Oncology, University of Greifswald, Greifswald, Germany

    Carsten Hirt

  13. Department of Gastroenterology and Oncology, Hospital of Aschaffenburg, Aschaffenburg, Germany

    Wolfgang Fischbach

  14. Department of Medical Oncology, Municipal Hospital of Karlsruhe, Karlsruhe, Germany

    Martin Bentz

  15. Department of Gastroenterology, University Charité, Berlin, Germany

    Severin Daum

  16. Department of Medical Oncology, University of Schleswig-Holstein, Kiel, Germany

    Christiane Pott

  17. Institute for Hematopathology Hamburg, Hamburg, Germany

    Markus Tiemann

  18. Department of Pathology, University of Ulm, Ulm, Germany

    Peter Möller

  19. Department of Medical Oncology, University of Marburg, Marburg, Germany

    Andreas Neubauer

  20. Department of Medical Oncology, Klinikum Nürnberg, Paracelsus Medical University, Nürnberg, Germany

    Martin Wilhelm

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  1. Gabriele Reinartz
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  7. Kay Willborn
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  8. Clemens F. Hess
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  17. Severin Daum
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  19. Markus Tiemann
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  21. Andreas Neubauer
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  22. Martin Wilhelm
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  23. Normann Willich
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  24. Wolfgang E. Berdel
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Corresponding author

Correspondence to Gabriele Reinartz.

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Conflict of interest

G. Reinartz, R.P. Pyra, G. Lenz, R. Liersch, G. Stüben, O. Micke, K. Willborn, C.F. Hess, A. Probst, R. Jany, J. Schultze, C. Rübe, C. Hirt, W. Fischbach, M. Bentz, S. Daum, C. Pott, M. Tiemann, P. Möller, A. Neubauer, M. Wilhelm, N. Willich, W.E. Berdel and H.T. Eich declare that they have no competing interests. R. Fietkau reports grants, personal fees and non-financial support from Merck Serono, personal fees and non-financial support from Fresenius Kabi, personal fees and non-financial support from Novocure, grants, personal fees and non-financial support from MSD, grants, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Brainlab, personal fees and non-financial support from Sennewald GmbH, personal fees and non-financial support from Bristol-Myers Squibb, outside the submitted work.

Ethical standards

The trials were conducted in accordance with the Declaration of Helsinki on Ethical Principles for Medical Research after approval of the Ethical Board of the physicians’ chamber of Westfalia-Lippe and the Westfalian Wilhelms-University of Münster. The studies were reviewed by the local Ethical Committees (institutional review boards) of the involved trials sites.

Appendix

Appendix

In addition to the authors listed on the manuscript, the supporting institutions were as follows: Aalen Radiotherapy, Aschaffenburg Radiotherapy Practice, Augsburg Radiotherapy Joint Practice, Aurich Norden Medical Care Center, Bad Saarow Helios Hospital, Bocholt Radiotherapy Practice, Bochum Catholic Hospital, Bonn University Hospital, Braunschweig Municipal Hospital, Bremen-Mitte Hospital, Celle General Hospital, Dessau Municipal Hospital, Dortmund Knappschafts-Hospital, Düsseldorf University Hospital, Düsseldorf Marienhospital, Essen University Hospital, Essen Alfried Krupp Hospital, Essen Radiotherapy Practice, Flensburg St. Franziskus Hospital, Frankfurt Nordwest Hospital, Fulda Hospital, Gießen Wilhelm Conrad Röntgen Hospital, Görlitz Radiotherapy Practice, Hagen General Hospital, Halle/Saale University Hospital, Hamburg St. Georg Radiotherapy Practice, Hamburg Altona Radiotherapy Practice, Hanau Hospital, Hannover Medical University, Hannover Diakovere Friederikenstift Hospital, Heidenheim Hospital, Herford Hospital, Jena University Hospital, Karlsruhe Vincentius Hospital, Kassel Municipal Hospital, Kassel Radiotherapy Practice, Kempten Hospital, Koblenz Radiological Institute, Köln University Hospital, Krefeld Helios Hospital, Lippstadt Dreifaltigkeits-Hospital, Lübeck University Hospital, Ludwigshafen Klinikum Ludwigshafen, Magdeburg University Hospital, Mannheim University Hospital, Minden Hospital, Mönchengladbach Maria Hilf Hospital, Mühlheim a.d. Ruhr Protestant Hospital, München Klinikum rechts d. Isar University Hospital, Neubrandenburg Dietrich Bonhoeffer Hospital, Neuss Lukas-Hospital, Nordhorn Radiotherapy Practice, Osnabrück Paracelsus Hospital, Osnabrück Radiotherapy Practice, Ostfildern Medius Hospital, Paderborn Brüderkrankenhaus St. Josef Hospital, Pinneberg Radiotherapy Joint Practice, Recklinghausen Knappschafts-Hospital, Rendsburg District Hospital, Rostock University Hospital, Schwerin Helios Hospital, Siegen St. Marien Hospital, Stuttgart Marienhospital, Trier Mutterhaus der Borromäerinnen Hospital, Vechta Medical Care Center, Wuppertal Radiotherapy Practice.

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Reinartz, G., Pyra, R.P., Lenz, G. et al. Favorable radiation field decrease in gastric marginal zone lymphoma. Strahlenther Onkol 195, 544–557 (2019). https://doi.org/10.1007/s00066-019-01446-5

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