Originally published as JCO Early Release 10.1200/JCO.2003.03.023 on August 11 2003

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Involved-Field Radiotherapy Is Equally Effective and Less Toxic Compared With Extended-Field Radiotherapy After Four Cycles of Chemotherapy in Patients With Early-Stage Unfavorable Hodgkin’s Lymphoma: Results of the HD8 Trial of the German Hodgkin’s Lymphoma Study Group

Andreas Engert, Petra Schiller, Andreas Josting, Richard Herrmann, Peter Koch, Markus Sieber, Friederike Boissevain, Maike de Wit, Jörg Mezger, Eckhart Dühmke, Normann Willich, Rolf-Peter Müller, Bernhard F. Schmidt, Helmut Renner, Hans Konrad Müller-Hermelink, Beate Pfistner, Jürgen Wolf, Dirk Hasenclever, Markus Löffler, Volker Diehl

From the First Department of Internal Medicine, University Hospital of Cologne and Department of Radiotherapy, University Clinic of Cologne, Cologne; Medical Department and Department of Radiotherapy, University Clinic Münster, Münster; University Clinic Nürnberg, Nürnberg; University Clinic Hamburg, Hamburg; St Vincentius Hospital Karlsruhe, Karlsruhe; Department of Radiation Oncology, Ludwig Maximilian Universität München, München; Center of Radiotherapy, Katharinenhospital, Stuttgart; Center of Radiotherapy, Klinikum Nord, Nürnberg; Institute of Pathology, University of Würzburg; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; and University Hospital, Basel, Switzerland, for the Swiss Group for Clinical Cancer Research.

Address reprint requests to Volker Diehl, MD, Department I of Internal Medicine, University Hospital Cologne, Cologne 50924, Germany; e-mail: v.diehl{at}uni-koeln.de.

Purpose: To investigate whether radiotherapy can be reduced without loss of efficacy from extended field (EF) to involved field (IF) after four cycles of chemotherapy.

Patients and Methods: Between 1993 and 1998, patients with newly diagnosed early-stage unfavorable HD were enrolled onto this multicenter study. Patients were randomly assigned to receive cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) + doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for two cycles followed by radiotherapy of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B).

Results: Of 1,204 patients randomly assigned to treatment, 1,064 patients were informative and eligible for the arm comparison (532 patients in arm A; 532 patients in arm B). The median observation time was 54 months. Five years after random assignment, the overall survival (OS_ran) for all eligible patients was 91% and freedom from treatment failure (FFTF_ran) was 83%. Survival rates at 5 years after start of radiotherapy revealed no differences for arms A and B, respectively, in terms of FFTF (85.8% and 84.2%) and OS at 5 years (90.8% and 92.4%). There also were no differences between arms A and B, respectively, in terms of complete remission (98.5% and 97.2%), progressive disease (0.8% and 1.9%), relapse (6.4% and 7.7%), death (8.1% and 6.4%), and secondary neoplasia (4.5% and 2.8%). In contrast, acute side effects including leukopenia, thrombocytopenia, nausea, gastrointestinal toxicity, and pharyngeal toxicity were more frequent in the EF arm.

Conclusion: Radiotherapy volume size reduction from EF to IF after COPP + ABVD chemotherapy for two cycles produces similar results and less toxicity in patients with early-stage unfavorable HD.

Supported in part by the Deutsche Krebshilfe and by the Swiss Group for Clinical Cancer Research.

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