Salvage Radiotherapy in Patients With Relapsed and Refractory Hodgkin's Lymphoma: A Retrospective Analysis From the German Hodgkin Lymphoma Study Group

Authors: Andreas Josting, Lucia Nogová, Jeremy Franklin, Jan-Peter Glossmann, Hans Theodor Eich, Markus Sieber, Thomas Schober, Heinz-Dietrich Boettcher, Ulrich Schulz, Rolf-Peter Müller, Volker Diehl, Andreas Engert
Source: Journal of Clinical Oncology, Vol 23, No 7 (March 1), 2005: pp. 1522-1529

Background

This is a retrospective report by the German Hodgkin Lymphoma Study Group. It describes their success with salvage radiotherapy in patients with relapsed and refractory Hodgkin's lymphoma following initial treatment. It represents the largest series published on this topic.

Method

• From a database of 4,754 patients enrolled in the GHSG between 1988 and 1999, 624 patients were identified with progressive or relapsed disease. Progressive disease was defined as the occurrence of new lesions, or increase of at least one existing lesion by more than 25% during or within 3 months after therapy; early relapse was determined as complete response (CR) lasting 3 to 12 months after first-line therapy; and late relapse was defined as CR lasting more than 12 months after completion of induction treatment. There were 202 patients with progressive disease, 170 with early relapse, and 252 with late relapse. From this group, a subset of 100 patients was identified with progression or relapse who were then treated with salvage radiotherapy. This group of 100 patients formed the basis of this analysis.
• Of the subset of 100 patients, 47% had primary progressive disease, 23% had early relapse, and 30% had late relapse.
• At progression or relapse, patients were staged by Ann Arbor criteria: 87% were found to be early stage I/II, 11% were stage III, and 2% were stage IV.
• Regarding progression: 44 patients had progression at the same anatomic sites as first diagnosis, and 3 patients developed out-of-field progression following primary radiation. Thirty-two patients relapsed outside the initial anatomic sites, and 21 patients had an in-field relapse.
• As far as systemic symptoms, 14% of patients had B symptoms, and only 12% had a Karnofsky performance score of less than 90% at time of progression/relapse.
• Salvage radiotherapy as second-line treatment included mantle-field radiation in 42% of patients, inverted-Y field in 8% of patients, total or subtotal nodal irradiation in 12% of patients, and involved-field radiotherapy in 37% of patients. The median dose delivered was 40 Gy (range 15-50 Gy).

Results

• Overall, 77% of patients had a CR with salvage radiotherapy. When considering only early stage I/II patients, there was an 88% response rate, versus a response rate of 12% in stage III/IV patients. There were 19 patients who failed to respond, and 16 of these comprised early stage relapsed patients.
• The overall 5-year survival rate was 51%, and freedom-from-second failure was 28%.
• Prognostic variables predicting overall survival and freedom-from-second failure included duration of first remission, presence of B-symptoms at progression or relapse, and KPS.
• The data on toxicity of salvage radiotherapy was limited, as data were not gathered as judiciously on patients who had progressed or relapsed. Nonetheless, 6 patients developed pulmonary toxicity, 2 developed myocardial infarctions, and 1 developed a cerebrovascular accident. Although follow-up was limited, there was no acute myelogenous leukemia or myelodysplastic syndrome reported.

Discussion

This study provides useful data regarding the salvage with radiation of progressive or relapsed Hodgkin's Disease, with an overall 77% response rate (88% among those with early stage at progression or relapse), a 5-year overall survival of 51%, and a 5-year freedom-from-second failure of 28%. Radiation should be strongly considered as a salvage option in patients with progressive or relapsing Hodgkin's lymphoma based on these data. Longer-term outcomes will shed light on continued efficacy of salvage radiation, with possibly newer systemic therapies emerging in the future to either replace or enhance the radiation treatments.