10-YEAR RESULTS OF A STRATEGY COMBINING 3 CYCLES OF ABVD AND HIGH-DOSE EXTENDED IRRADIATION FOR TREATING HODGKINS-DISEASE AT ADVANCED STAGES

Background: The treatment of Hodgkin's disease (HD) at advanced stages relies mainly upon multi-agent chemotherapies (CT), while the role of radiation therapy has not been definitely identified. The aim of this report is to analyze the 10-year results of a prospective study inclu ding 133 patients with HD clinical stages (CS) IIIA to IVB treated by three monthly courses of ABVD (adriamycin, bleomycin, vinblastin, and dacarbazine) followed by high-dose subtotal or total lymphoid irradiat ion [(S)TLI]. Patients and methods. From 1 October 1981 to 30 Septembe r 1988, 133 adult patients with HD CS IIIA (45), IIIB (33), IVA (seven ) and IVB (48) were entered in the non-randomized multicentric prospec tive trial POF81/34. The number of involved nodal areas (NINA), and th e number of visceral sites (NVIS) involved were registered in all pati ents; patients with bulky mediastinal tumor (BuMT) (mediastinal mass r atio greater than or equal to 0.45) were also identified. All patients received three monthly cycles of ABVD. Patients in complete remission (CR) or partial remission (PR) after completion of CT received a (S)T LI including the spleen (involved sites 40 Gy, non-involved 30 Gy); in itially involved lung(s) and liver received 18 and 20 Gy, respectively ; and patients not in CR or PR after CT or RT received salvage treatme nts. Univariate and multivariate analyses were performed to identify t he factors contributing significantly to the prognosis; initial charac teristics, as well as status after the three cycles of CT, were entere d in the model. Results. Of the 133 patients, 74 (55.6%) entered in CR after CT and 116 (87.2%) after completion of radiation therapy. Ten-y ear freedom from progression (FFP), freedom from tumor mortality (FFTM ) and survival rates were 70.4%, 78.9% and 70.6%, respectively. Accord ing to univariate analysis the NVIS (less than or equal to one vs. gre ater than or equal to two) was the only initial factor simultaneously influencing 10-year FFP (73.9% vs. 38.2%) FFTM (82.5 vs. 34.1%) and su rvival (73.5% vs. 17.3%) rates; on the other hand, the NINA(less than or equal to four vs. greater than or equal to five) influenced FFP (81 .4% vs. 60.7%) and FFTM rates (87.3% vs. 71.4%) while symptoms (A vs. B) influenced FFP (80.7% vs. 63.3%) and survival (82.8% vs. 61.2%) rat es, Finally, age (<40 vs. greater than or equal to 40) influenced surv ival rate only (79.2% vs. 50%). According to multivariate analysis, NV IS and NINA had an independent impact on FFP and FFTM, while survival was modified by the NVIS and age. The post-CT status (CR vs, no CR) ha d a major impact on FFP (85.3% vs, 64.9%) FFTM (92.1% vs. 63.3%) as we ll as on survival (78.6% vs. 54.7%) rates in both univariate and multi variate analyses. Complications of therapy were mainly due to RT: 11 p atients acquired second malignancies, six developed lung fibrosis or s evere pulmonary infections, three developed intestinal obstructions an d six developed angina pectoris or carotid stenosis. Conclusions. Tumo r burden (identified by the number of involved nodal areas and the num ber of visceral sites) and the response to initial CT were the two ind ependent factors influencing the outcome of this group of 133 patients with HD, CSIII and IV treated by three cycles of ABVD followed by hig h-dose [(S)TLI].