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Early Unfavorable Hodgkin Lymphoma

    Drug combinations described in this section:

    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:

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    • B symptoms (fever ≥38°C, soaking night sweats, weight loss ≥10% within 6 months).
    • Extranodal disease.
    • 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 mm/h.

    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.[1] 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).[7][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.[8][Level of evidence: 1iiDiii]

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