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

• Published in: Journal of clinical oncology Vol. 21; no. 19; pp. 3601 - 3608
• Main Authors: ENGERT, Andreas, SCHILLER, Petra, WILLICH, Normann, MÜLLER, Rolf-Peter, SCHMIDT, Bernhard F, RENNER, Helmut, MÜLLER-HERMELINK, Hans Konrad, PFISTNER, Beate, WOLF, Jürgen, HASENCLEVER, Dirk, LÖFFLER, Markus, DIEHL, Volker, JOSTING, Andreas, HERRMANN, Richard, KOCH, Peter, SIEBER, Markus, BOISSEVAIN, Friederike, DE WIT, Maike, MEZGER, Jörg, DÜHMKE, Eckhart
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01-10-2003; Lippincott Williams & Wilkins
• Subjects: Adolescent; Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bleomycin - administration & dosage; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Cyclophosphamide - administration & dosage; Dacarbazine - administration & dosage; Disease Progression; Doxorubicin - administration & dosage; Female; Hodgkin Disease - drug therapy; Hodgkin Disease - pathology; Hodgkin Disease - radiotherapy; Humans; Male; Medical sciences; Middle Aged; Neoplasm Staging; Pharmacology. Drug treatments; Prednisone - administration & dosage; Procarbazine - administration & dosage; Prognosis; Radiotherapy - adverse effects; Recurrence; Survival Analysis; Treatment Outcome; Vinblastine - administration & dosage; Vincristine - administration & dosage; Antineoplastic agent; Procarbazine; Prognosis; Early stage; Doxorubicin; Glucocorticoid; Dacarbazine; Alkaloid; Isomerases; Bleomycin; Lymphoproliferative syndrome; Complication; Irradiation field; Antimitotic; Human; Corticosteroid; DNA topoisomerase (ATP-hydrolysing); Drug combination; Vinblastine; Enzyme; Enzyme inhibitor; Hodgkin disease; Malignant hemopathy; Prednisone; Radiotherapy; Lymphoma; Vincristine; Alkylating agent; Antibiotic; Chemotherapy; Cyclophosphamide; Oxazaphosphinane derivatives; Nitrogen mustard; Anthracyclins; Combined treatment; Therapeutic protocol; Comparative study
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2003.03.023

To investigate whether radiotherapy can be reduced without loss of efficacy from extended field (EF) to involved field (IF) after four cycles of chemotherapy.
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).
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 (OSran) for all eligible patients was 91% and freedom from treatment failure (FFTFran) 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.
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.