Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the formal ranking system used by the PDQ Editorial Boards to assess evidence supporting the use of specific interventions or approaches. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Patients with early unfavorable HL showed relapse rates over 30% at 5 years with radiation therapy alone, prompting evaluation of chemotherapy plus involved-field radiation therapy (IF-XRT) versus chemotherapy alone. The late mortality from solid tumors, especially in the lung, breast, gastrointestinal tract, and connective tissue, and from cardiovascular disease makes radiation therapy a less attractive option unless therapeutic benefits exceed the long-term complications.[2,3,4,5,6]
A randomized, prospective trial from the National Cancer Institute of Canada involving 276 patients with early unfavorable HL compared ABVD for four to six cycles to ABVD for two cycles plus extended-field radiation therapy (EF-XRT); with a median follow-up of 11.3 years, the freedom-from-progression favored combined modality therapy (86% vs. 94%; P = .006), but the overall survival was better for ABVD alone (92% vs. 81%; P = .04).[Level of evidence: 1iiA] The trend toward a worse survival for the combined modality arm was attributed to excess secondary malignancies and cardiovascular deaths. In this trial, the extended-field radiation used higher doses and significantly larger exposure to body sites than are employed in current practice.
A randomized study from the Southwest Oncology Group of clinically staged patients (no laparotomy) compared subtotal lymphoid radiation to 3 months of AV followed by subtotal lymphoid radiation therapy; the combined modality arm showed superior failure-free survival (94% vs. 81%; P < .001) but not OS at 3.3 years' median follow-up.[Level of evidence: 1iiDiii]
In a randomized study from the Milan Cancer Institute of patients with clinical early-stage Hodgkin lymphoma, 4 months of ABVD followed by either IF-XRT or EF-XRT showed similar OS and freedom-from-progression with 10 years' median follow-up, but the study had inadequate statistical power to determine noninferiority of IF-XRT versus EF-XRT.[Level of evidence: 1iiDii] Similarly, in a randomized study from the German Hodgkin Lymphoma Study Group (GHSG) of more than 1,000 patients with early unfavorable HL, 4 months of COPP plus ABVD followed by IF-XRT versus EF-XRT showed equivalent OS and freedom-from-treatment failure (FFTF) with 5 years' median follow-up.[Level of evidence: 1iiA] Another randomized study of 996 patients with early unfavorable HL also showed no difference in OS and event-free survival at 10 years comparing four to six cycles of MOPP-ABV plus IF-XRT versus the same chemotherapy plus subtotal nodal radiation therapy.[Level of evidence: 1iiA]