The optimal dose of radiation in Hodgkin’s disease: an analysis of clinical and treatment factors affecting in-field disease control

Abstract

Purpose: The purpose of this study is to analyze the effect of radiation dose, as well as other clinical and therapeutic factors, on in-field disease control.Patients and Materials: The study population comprised 232 patients with Stage I and II Hodgkin’s disease (HD) treated with curative intent at the University of Florida with radiotherapy (RT) alone (169 patients) or chemotherapy and radiotherapy (CMT) (63 patients). Sites of involvement and radiation doses were prospectively recorded and correlated with sites of disease recurrence.Results: Freedom from relapse and absolute survival rates at 10 years were as follows: 76% and 77%, entire group; 76% and 80%, RT group; 79% and 70%, CMT group; 85% and 78%, Stage I; and 71% and 77%, Stage II. Treatment failure occurred in 50 patients (22%) including in-field failure in 22 patients (9%). In-field failure was rare in electively treated sites. Multivariate analysis of clinical factors (tumor size, number of sites involved, B-symptoms, gender, histology, age, and site of involvement) and treatment factors (use of chemotherapy, number of cycles of chemotherapy, radiation dose, radiation treatment volume, and radiation treatment time) showed only tumor size (p = 0.0001) to be significantly correlated with in-field disease control. In RT patients, the in-field failure rate according to tumor size was as follows: 0% for ≤ 3 cm; 4% for > 3 cm and ≤ 6 cm; 23% for > 6 cm and ≤ 9 cm; and 36% for > 9 cm. In CMT patients, the in-field failure rate was as follows: 0% for ≤ 3 cm; 0% for > 3 and ≤ 6 cm; 5% for > 6 cm and ≤ 9 cm; and 26% for > 9 cm. In-field recurrence was not a predominant pattern of failure in RT patients with small tumors (≤ 6 cm); thus, the difference in in-field control in tumors ≤ 6 cm between doses ≤ 35 Gy (6%) and doses ≥ 36 Gy (0%) was not statistically significant. In larger tumors (> 6 cm), in-field recurrence was a predominant pattern of failure; the in-field failure rate in RT patients with tumors > 6 cm of 30% for doses ≤ 35 Gy was not significantly different from 25% for doses > 35 Gy. In moderately bulky tumors (> 6 cm and ≤ 9 cm), the addition of chemotherapy did appear to increase in-field disease control; the in-field failure rate was 23% with RT and 5% with CMT (p = 0.07).Conclusion: Our data do not demonstrate statistically significant evidence of increasing tumor control in HD with doses > 30 Gy. The data do show that increasing tumor size is associated with increased rates of in-field failure, and the addition of chemotherapy may improve in-field disease control in tumors > 6 cm. In-field recurrence in large tumors remains a predominant pattern of failure, however, and the role of radiation doses higher than 30–35 Gy in this high-risk subset warrants further study.