Combined Modality Treatment for Poor Prognosis Stages I and II Hodgkin's Disease

Recommendations for the treatment of "poor prognosis" stages I and II Hodgkin's disease (HD) depend on the extent of staging. For centers that favor exploratory laparotomy and splenectomy, the standard treatment after negative surgical staging remains subtotal lymphoid irradiation. However, most centers recommend excluding selected patients from surgical staging. In particular, most specialists agree that patients with bulky mediastinal disease (large mediastinal adenopathy) should receive combined chemotherapy and radiotherapy without surgical staging. Centers that have eliminated staging laparotomy rely on clinical staging and have identified a number of poor prognostic factors that influence treatment recommendations. In 1995, the following factors were considered to be associated with an unfavorable prognosis in clinical stages (CS) I and II HD: advanced age, systemic symptoms, high erythrocyte sedimentation rate, large number of individual sites, and presence of bulky disease. For example, these factors have been used in the H7 and H8 European Organization for the Research and Treatment of Cancer trials and have been adopted by almost 100 participant groups. For CS I and II patients with unfavorable presentations, the literature suggests that the optimal treatment is a combination of chemotherapy and radiotherapy. Nevertheless, the optimal delivery of chemotherapy and radiotherapy is still debated and a number of the questions listed below are awaiting answers: 1. The chemotherapy schedule: Mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alone can no longer be recommended (for toxicity reasons) for the routine treatment of poor prognosis CS I and II HD. Many centers, on theoretical arguments, favor seven or eight drug combinations (MOPP/ABV hybrid), although the advantage of these combinations in toxicity and efficacy over doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone has not been demonstrated. 2. The number of chemotherapy courses: Most groups use six cycle regimens, but reduction to three to four cycles is currently being investigated both in pilot and randomized studies. 3. Timing of chemotherapy: Chemotherapy is given first in most instances. Whether or not a "sandwiched" scheme is better than all the chemotherapy given upfront remains to be answered. 4. Volumes to be irradiated: Data suggest that the irradiated volumes can be safely limited to initially involved lymph node regions after effective chemotherapy. The question is presently being addressed in a few ongoing randomized trials. 5. Radiation dose to be delivered: The decrease of the radiation dose to 35 to 36 Gy after effective chemotherapy has gained a wide acceptance. Further dose reduction is being investigated. In conclusion, except for selected CS I and II patients still referred for surgical staging, combined modality therapy appears to be the treatment of choice for poor prognosis CS I and II HD.