Response-Based Chemotherapy and Involved Field Radiation for Intermediate Stage Hodgkin Disease. A GISL/NHLSG Trial.

Background.

Most of the patients with advanced stage Hodgkin lymphoma can be cured with a standard course of six cycle of ABVD chemotherapy plus involved field (IF)radiotherapy. Patients with less advanced stage or with a more responsive disease could possibly achieve a cure with a shorter course of chemotherapy. In 1992, in the pre-PET era, the GISL addressed the issue of the proper number of chemotherapy cycles planning a response-oriented, ABVD-based study for intermediate-stage Hodgkin’s lymphoma patients.

Patients and Methods.

From January 1992 to December 2002, 218 patients younger than 70 were enrolled. Eligible patients had histologically confirmed and clinically staged Hodgkin’s disease. Patients with unfavourable disease included those with Ann Arbor I-III plus at least one among the following: B-symptoms, bulky tumor or extranodal localization. The required clinical staging evaluation included: history and physical examination; CBC count with differential, erythrocyte sedimentation rate, and routine renal and hepatic chemistries; chest radiograph, cervical, thoracic and abdominal computed tomography (CT) scan with contrast. Treatment Plan. Treatment included a first step of three ABVD cycles followed by an “early” restaging. Those patients in CR or CRu after 3 cycles were planned to receive one additional ABVD cycle while patients in PR were planned to receive 3 additional ABVD cycles. IF radiotherapy was recommended at the end of ABVD courses on sites involved at diagnosis.

Results:

The median age was 30 years (15–68) with an M/F ratio of 0.7. Nodular sclerosis accounted for 75% of the diagnoses. Seventy-eight percent of cases were in stage II, 7% stage I and 15% stage III; B-symptoms, bulky tumor and ESR>30 were recorded, respectively in 15%, 20%, 25%, and 80% of cases. Of the 206 evaluable cases, 34% of patients were in CR at early restaging, 11 in CRu and 47% in PR; four patients did not respond, and four were early drop-outs. Overall 57% of patients received 4 ABVD cycles, 47% six cycles, and 85% received the planned IF-RT. The CR-CRu rate was 72% at the end of chemotherapy and increased to 93% after the radiotherapy. First events included: 18 relapses, 14 less-than-CRs or progressive diseases and two deaths in CR. Of the 34 patients with recurrent or progressive disease, 12 subsequently died, the others were in second or third remission. With a median follow-up of 60 months (24–162), five-year OS and EFS (median-standard error) are 96.7%-2.7% and 83.8%-3.6%, respectively. Early responders who received four ABVD cycles had an excellent outcome with similar EFS (90% vs 84%) and better OS (100% vs 91% p=0.003) compared to the late responders.

Conclusions.

A response oriented chemotherapy program is feasible and safe in intermediate stage Hodgkin’s lymphoma patients. Overall, with a flexible number of ABVD the OS and EFS of the present series nicely match those expected for this setting of patients. Early clinical restaging identifies cases who have an excellent outcome even with a shortened ABVD course.