Long-term outcome of treatment for Ann Arbor stage 1 Hodgkin's disease: patterns of failure, late toxicity and second malignancies

Abstract

Purpose: Radiation therapy results in excellent short-term survival in patients with early-stage Hodgkin's disease. However, the optimal therapeutic scheme that achieves the highest disease-free survival with the minimum long-term toxicity is yet to be determined. An analysis of the patterns of failure and late complications after radiation therapy was conducted to address this question.

Methods and materials: A retrospective study was conducted of 145 patients with Stage I Hodgkin's disease treated at M. D. Anderson Cancer Center from 1967 through 1987. Follow-up extended from a minimum of 30 to 339 months, with a median period of observation of 16.5 years. All the patients were treated with radiation therapy and, and 16 received combination MOPP-based chemotherapy as part of their initial treatment. The radiotherapy technique, was involved/regional in 71 (49%), extended in 62 (43%), and subtotal nodal irradiation in 12 patients. The median total dose was 40 Gy.

Results: The actuarial freedom from progression at 10 and 20 years was 76% and 69%, respectively. Forty of 145 patients relapsed (27.6%). The site of primary disease was cervical adenopathy in 30 (75%), axillary in 7 (17.5%), mediastinal in 2 patients and subdiaphragmatic in one patient. Twenty-two patients were treated with involved/regional technique (55%), 17 with extended (42.5%), and 1 with subtotal nodal irradiation technique. There were three in field and four marginal recurrences. Six relapses occurred in non-irradiated nodal regions at the same side of the diaphragm and 17 in non-irradiated transdiaphragmatic lymph nodes (57.5%). Nine patients (22.5%) relapsed with visceral disease. Nineteen patients (47.5%) relapsed within the first 2 years, 15 (37.5%) 3 to 10 years after diagnosis and the remaining 6 (15%) after 10 years. Eleven of 40 patients died of disease after the first or subsequent relapses (27.5%). Three of six patients with late relapses had progression in viscera but only two died with disease. Thirty-eight of 145 patients developed late toxicity from the treatment (26.2%). Twenty-three patients experienced ischemic heart disease (15.9%), only 13 of whom received mediastinal irradiation (9%). Fifteen patients developed secondary malignant solid tumors (10.3%). Nine of those (6.2%) occurred within the irradiation field (two were also treated with chemotherapy). Two additional patients, one of whom received chemotherapy as part of the initial treatment, died of acute myelogenous leukemia. Non-Hodgkin's lymphoma and lung cancer were the most common second malignancies.

Conclusions: Limited field radiotherapy results in a significant number of relapses in non-irradiated, especially transdiaphragmatic lymph nodes. Subtotal nodal irradiation can prevent some relapses and therefore improve freedom from progression. Careful design of the treatment fields may decrease the risk of morbidity and mortality from coronary artery disease and second malignancies in early-stage Hodgkin's disease. Careful long-term surveillance may permit early detection and management of late relapses and treatment complications.