Radiotherapy After Partial Response to Chemotherapy Boosts Survival in Hodgkin’s Lymphoma

SAN FRANCISCO—Radiotherapy following chemotherapy does not improve survival in patients with stage III/IV Hodgkin’s lymphoma (HL) who have a complete response to chemotherapy. It does, however, improve survival in partial responders, according to results from the phase III EORTC (European Organization for Research and Treatment of Cancer) trial 20884. The findings were presented at the 43rd Annual Meeting of the American Society for Therapeutic Radiology and Oncology (plenary 3).

"For patients with stage III or IV Hodgkin’s lymphoma who have been treated with MOPP/ABV and reached complete remission, involved-field radiotherapy does not improve outcome," said Berthe Aleman, MD, of the Department of Radiotherapy, Netherlands Cancer Institute, Amsterdam. "If, however, they reach partial remission, involved-field radiotherapy results in the same excellent recurrence-free survival, event-free survival, and overall survival as patients who have reached complete remission."

Between November 1989 and April 2000, the EORTC Lymphoma Group enrolled 736 patients with stage III/IV Hodgkin’s lymphoma into the study. All patients were initially treated with four courses of MOPP/ABV chemotherapy.

Complete response to initial chemotherapy was defined as the complete disappearance of all measurable lesions and disease-related symptoms; 60% of the patients achieved complete remission and 35% achieved partial remission after initial chemotherapy.

Patients in complete remission after initial chemotherapy received another two courses of MOPP/ABV, for a total of six courses, and were then randomized to the control arm (no further treatment) or the experimental arm (involved-field radiotherapy).

Patients in partial remission after initial chemotherapy also received two more courses of standard chemotherapy and were then evaluated for remission status. If they were then in complete remission, they received yet another two courses of MOPP/ABV, for a total of eight courses, and were then randomized to the control or experimental arm.

All patients who were still in partial remission after six courses of MOPP/ABV were treated with radiotherapy to all initially involved organs and lymph node areas. Patients who failed at any time during the investigation went off study.

Patients in the experimental group received 24 Gy to all initially involved nodal areas and 16 to 24 Gy to all initially involved extranodal areas, in fractions of 1.5 to 2.0 Gy, five fractions a week.

Patients in partial remission after six courses of chemotherapy received 30 Gy to nodal areas, in 1.5 to 2.0 Gy fractions, and 18 to 24 Gy to extranodal areas, with localized boost when indicated by the treating physician.

Study Results

After a median follow-up of 6 years, there was no difference in relapse-free, event-free, or overall survival for the two groups of complete responders, Dr. Aleman reported. However, she said, patients in partial remission who were treated with involved-field radiotherapy after six courses of MOPP/ABV had the same results as patients who achieved complete remission after chemotherapy.

The 5-year event-free survival rates were 82%, 79%, and 80% for complete responders who did not receive involved-field radiotherapy, complete responders who did receive involved-field radiotherapy, and partial responders, respectively. Overall 5-year survival rates were 89%, 85%, and 87%, respectively.

From 48% to 60% of patients experienced grade 3-4 hematologic toxicity and 7% to 13% had grade 3-4 GI toxicity during or following chemotherapy. The rates during and following radiotherapy were 13% to 19% for hematologic toxicity and 0% to 9% for GI toxicity.

The discussant, Richard Hoppe, MD, of Stanford University, noted that four major trial groups, including the EORTC, have recently investigated the role of involved-field radiotherapy in the treatment of stage III/IV Hodgkin’s lymphoma.

Based on the results of these four trials, Dr. Hoppe said, "I believe it’s safe to say that for the typical patient with stage III/IV Hodgkin’s disease who has completed a full course of six to eight cycles of chemotherapy and has achieved a complete response, there is no role for low-dose involved-field radiation."

That does not mean that there is no role at all for involved-field radiotherapy in the treatment of stage III/IV Hodgkin’s lymphoma, Dr. Hoppe cautioned.

In addition to results showing that radiotherapy is effective when treating patients who are in partial remission, involved-field radiotherapy may also be helpful for patients with bulky disease, Dr. Hoppe said, and as a means of reducing the dose and resulting toxicity associated with chemotherapy for other patients with advanced Hodgkin’s disease, a concept incorporated into the Stanford V protocol approach.