Mantle irradiation alone for pathologic stage I and II Hodgkin's disease: Long-term follow-up and patterns of failure

Purpose: We performed a retrospective study to determine the long-term outcome, patterns of failure, and prognostic factors for patients with pathologic Stage I or II Hodgkin's disease (HD) who were treated with mantle irradiation alone. Methods and Materials: The medical records of 145 patients with pathologic Stage I or II supradiaphragmatic Hodgkin's disease treated with mantle irradiation alone between June 1967 and June 1991 were reviewed. Patterns of failure, overall survival (OS) rate, and progression-free survival (PFS) rate were determined. Univariate and multivariate analyses were performed to identify adverse prognostic factors for OS and PFS. The number of adverse prognostic factors per patient was counted, and a prognostic score was assigned to each patient. The log-rank test was used to compare the OS or PFS rates among patients with prognostic scores 0, 1, and 2. Results: The median patient age was 27 years (range 10-66), with almost even male to female distribution. Every patient had splenectomy and negative laparotomy (LAP). Fifty-one patients had Stage I disease (IA-49, IB-2) and 94 Stage II (IIA-89, IIB-5). The histologic subtypes were nodular sclerosing in 110, mixed cellularity in 28, lymphocyte predominance in 5, lymphocyte depleted in 1, and unclassified in 1. Twelve patients with Stage II disease had ≥ 3 sites of nodal involvement. Fifty-four patients had a prognostic score of 0, 70 of 1, and 21 of 2. The median follow-up time for the 109 surviving patients was 146 months (range 25-381). The 10- and 20-year actuarial OS rates for the whole group were 87.6% and 65.3%, respectively. The corresponding actuarial PFS rates were 75.3% and 74.2%, respectively. Thirty-six patients (9 Stage I, 27 Stage II) had relapses in a total of 41 sites. Failures by histology were 29 patients with nodular sclerosing, 6 with mixed cellularity, and 1 with lymphocyte predominance. Failures by sites were: trans-diaphragmatic, 22 (para-aortic nodes, 15; as the only site of progression in 12; visceral, 7; as the only site of progression in 5); within radiation field, 8; marginal miss, 8 (as the only site of failure in 2); and unknown, 3. The majority of the failures occurred within 5 years of diagnosis. Long-term side effects of radiation included cardiac complications in 30 patients, with 10- and 20-year actuarial cardiac complication rates of 12.6% and 35.1%, respectively; secondary solid tumors in 14, with 10- and 20-year actuarial rates of 2.3% and 25.7%, respectively; leukemia in 4; non- Hodgkin's lymphoma in 4, with the 10- and 20-year actuarial rates for leukemia and non-Hodgkin's lymphoma of 4.0% and 13.9%; and hypothyroidism in 38. Four adverse prognostic factors were identified for PFS: age ≥ 40 years, ≥ 3 sites of involvement, male sex, and constitutional symptoms. The prognostic score correlated with patients' outcome as indicated by PFS and OS rates. Patients with a prognostic score of 0 did significantly better than those with a score of 1 or 2. Conclusion: In this select group of patients with pathologic Stage I and II Hodgkin's disease treated with mantle irradiation alone, the OS and PFS rates at 10 and 20 years were comparable to those reported in the literature. The major pattern of disease progression was relapse below the diaphragm, therefore close surveillance of the abdomen is warranted. The prognostic score used in our series may predict the patient's outcome, and might be worth testing in a prospective trial. In our series, patients with a prognostic score of 0 had excellent long-term survival, indicating adequate treatment with mantle irradiation alone. Late complications of the treatment pose a significant threat for the patient's survival with long-term follow-up.