Long-term outcome of treatment for Ann Arbor Stage I Hodgkin's disease: prognostic factors for survival and freedom from progression

Abstract

Purpose: The earliest stages of Hodgkin's disease are associated with excellent short-term survival with radiation therapy. This has led to controversies regarding pretreatment evaluation, the extent of irradiation, the role of chemotherapy, and the relative importance of prognostic factors. Long-term results were sought to address these controversies.

Methods and materials: A retrospective study was conducted of patients with Stage I Hodgkin's disease treated at the M. D. Anderson Cancer Center from 1967 through 1987. The median age at presentation of 145 patients was 31 years, and the male-to-female ratio was 1.8. Pretreatment evaluation included lymphangiography and bone marrow aspiration and biopsy in all patients. Laparotomy was performed in 101 of the 145 patients (70%). There were 133 patients with supradiaphragmatic presentations; 12 patients had infradiaphragmatic adenopathy. Only five patients had B symptoms (3.5%). Histologic subtypes of the disease included lymphocyte predominance 17.9%, nodular sclerosis 40.7%, mixed cellularity 40.7%, and one unclassified Hodgkin's disease with primary splenic involvement. All patients were treated with radiotherapy, and 16 (11%) also received combination chemotherapy as part of their initial treatment. Radiotherapy techniques included involved/regional field in 49%, extended field in 42.7% (mantle or inverted Y), and subtotal nodal irradiation in 8.3%. Follow-up extended from a minimum of 30-339 months, with a median period of observation of 16.5 years.

Results: The median survival was 13.7 years. The 10- and 20-year survival rates were 83% and 66%, respectively. The only factor important for decreased survival was age >40 years at diagnosis (p < 0.0001). Out of 43 deaths, 11 were the result of Hodgkin's disease and the remaining 32 resulted from intercurrent disease, including treatment-related causes. Median freedom from progression was 10.5 years, and the 10- and 20-year freedom from progression were 76% and 69%, respectively. Out of 39 relapses, 5 (13%) occurred beyond 10 years. Women had higher freedom from progression (p = 0.0534) than men. Age, histology, bulk of disease, site of involvement including the mediastinal presentations, and the addition of chemotherapy did not influence the freedom of progression. Although very few patients (12 of 145) received subtotal nodal irradiation, the freedom from progression at 10 years was 91.7% for this group versus 64.7% for the group of patients who were treated with more limited techniques.

Conclusion: Treatment with radiation therapy for patients with Stage I Hodgkin's disease leads to an excellent outcome, but patients require long-term surveillance as late relapses are not rare. Age is the only factor that affects survival, and gender marginally affects freedom from progression. Subtotal nodal irradiation may improve freedom from progression; further investigation of this treatment is justified.