Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
In general, the use of combined chemotherapy and low-dose involved-field radiation therapy (LD-IFRT) broadens the spectrum of potential toxicities, while reducing the severity of individual drug-related or radiation-related toxicities. Current approaches use chemotherapy with or without LD-IFRT. The volume of radiation and the intensity/duration of chemotherapy are determined by prognostic factors at presentation, including presence of constitutional symptoms, disease stage, and bulk.
ABVD: doxorubicin plus bleomycin plus vinblastine plus dacarbazine (1 cycle = 1 month of therapy).
AV: doxorubicin plus vinblastine.
BEACOPP: bleomycin plus etoposide plus doxorubicin plus cyclophosphamide plus vincristine plus procarbazine plus prednisone.
COPP/ABVD: cyclophosphamide plus vincristine plus procarbazine plus prednisone/doxorubicin plus bleomycin plus vinblastine plus dacarbazine.
MOPP-ABV: mechlorethamine plus vincristine plus procarbazine plus prednisone plus doxorubicin plus bleomycin plus vincristine.
Patients are designated as having early unfavorable Hodgkin lymphoma (HL) if they have clinical stage I or stage II disease and one or more of the following risk factors:
B symptoms (fever ?38�C, soaking night sweats, weight loss ?10% within 6 months).
Bulky disease (?10 cm or >33% of the chest diameter on chest x-ray).
Three or more sites of nodal involvement.
Sedimentation rate of 50 or more.
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 4.2 years, the freedom-from-progression favored combined modality therapy (95% vs. 88%; P = .004), with no difference in overall survival (OS).[Level of evidence: 1iiDiii]
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 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]