The EORTC strategy in the treatment of Hodgkin's lymphoma

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Eghbali et al. 6 yr, in the VF group there was a 23% rate of relapses and 71% EFS. In the F group, the EFS rate was 80% for STNI and 90% for EBVP + IF (P ¼ 0.0228) without any difference in overall survival (P ¼ 0.7) and in the U group, MOPP/ ABV + IF radiotherapy yielded a lesser proportion of failures than EBVP + IF (99% vs. 77%). Overall survivals were respectively 97%, 95%, and 83% for VF, F, and U groups (Table 2 and 3) without any significant difference in different arms (3, 4). These data were not available when the next trial H8 was started in 1998. The objectives of this trial were also a twin reduction of chemotherapy and radiotherapy burden in order to reduce the late treatment toxicity and maintain the EFS already experienced previously. Based on these objectives H8 had also STNI as standard in the favourable group (H8F with 543 patients) and which was compared to combined modality treatment using three MOPP/ABV + IF (the same duration as for H7F). In the unfavourable group (H8U with 995 patients) the standard was six courses of MOPP/ ABV + IF, compared to four MOPP/ABV + IF Table 1. Prognostic factors in limited HD according to the EORTC Lymphoma Group Criterion Very favourable (VF) Favourable (F) Unfavourable (U) Age
The EORTC strategy in the treatment of Hodgkin’s lymphoma based on our previous experience and we openly wondered whether we could skip radiotherapy in a subset of F patients in CR after chemotherapy or at least lower the dose to 20 Gy in the same conditions while 36 Gy remained the standard dose. Patients who achieved partial remission were all irradiated by IF at standard dose. In the H9U group however the newly analysed BEACOPP seemed promising for a higher rate of CR and then a better survival for aggressive cases (8–10). This regimen was compared to the standard with ABVD, both arms having 30 Gy involved field radiotherapy afterwards. We have currently no mature data about this trial but some conclusions are already available. In the H9F group the no radiotherapy arm met the stopping rules (an increased failure rate as compared to the radiotherapy arms) 2 yr after its beginning (11) meaning clearly that with the chosen (slight non-leukaemogenic) chemotherapy, IF radiotherapy could not be skipped. But it appeared also that radiotherapy doses could be lowered to 20 Gy providing that the complete remission is confirmed (by usual means, CT and standard radiography). So far the EFS is the same for 36 or 20 Gy (11). We need of course a longer follow-up duration to confirm that this low dosage after CR is enough to ensure the cure. And if this is confirmed it would be a significant advance in Hodgkin’s treatment and joins the German group’s conclusions (12, 13). In the H9U group, comparing three arms either with 4 ABVD, 6 ABVD or with 4 BEACOPP all followed by 30 Gy IF we have not yet all data to draw a definitive conclusion. Although BEA- COPP regimen showed very good results in advanced and intermediate stages its potential leukaemogenicity due to etoposide and cyclophosphamide imposes a rather long follow-up. But so far, in H9 the EFS rates are the same in three arms (14). How to go on and what is the next step? What is then the crucial question in Hodgkin’s treatment? Could we lower again the treatment intensity without jeopardising the good results we have had for more than 20 yr? These questions seem difficult to answer for practical, ethical and strategic reasons. The HD is a rare disease and a sensitive one. Its evolution lasts for a long time even when the treatment fails. Late complications appear more than 15 yr after treatment has finished and patient is cured, and often the physician who had taken care of the patient is not the same one who meets the late complication. Other parameters are new techniques and new drugs, which change and improve rapidly; they have to be taken into account. All these questions were debated among lymphoma Group members and some conclusions are emerging for the next steps and future treatment strategy for limited stages of HD. – First, the concept of prognostic factors has to be reviewed. The previous prognostic system was framed after a retrospective analysis of old trials from 1965 to 1987 (1–7) and one could reasonably believe that this system could no longer work or would not fit the current technological possibilities of imaging and radiotherapy or recent advances in chemotherapy. Since this system was framed we have had spread facilities for Galium scintigraphy and especially and now FDG–PET-scan and MRI that are not clearly evaluated on a large scale or at least in controlled trials. But there are accumulating data that these techniques could better define the (real) remission and distinguish an active mass from a residual fibrous one (15–17). Now a quick and early complete remission is considered to be one of the most powerful prognostic factors (in fact a surrogate Ôpredictive factorÕ), not only in Hodgkin’s lymphoma but also generally in haematology–oncology (18–20). Whether we have to use other new prognostic factors, e.g. eosinophilic infiltration, angiogenesis or cell epitopes (21, 22) that is another matter of debate, which cannot be put aside in the future. – Second, recent advances in radiotherapy for target definition and computerised dosimetry allow to precise accurately the limits of the radiotherapy fields and avoid other critical tissues, especially those that should be protected, e.g. heart, lung, spinal cord and even main arteries. – Third, even with adapted treatments some cases whatever the group, respond slowly or partially and are clinically in partial remission at the end of chemotherapy. So far the treatment of the early stages has been a global approach with combined modality treatment. But if we want to skip radiotherapy we have to be sure that the remission is really complete. Otherwise this incomplete remission has to be translated to a complete remission Ôby any meansÕ. Such an approach has proved to be effective in advanced stages where partial remitters have an excellent outcome close to that of complete remitters (23, 24). Considering these three assumptions the next trial H10 takes into account the prognostic value of early response according to PET scan, the accurate definition of radiotherapy fields (involved node radiotherapy), and adversely the need of a more 137
Page 1: Eur J Haematol 2005: 75 (Suppl. 66)
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The EORTC strategy in the treatment of Hodgkin's lymphoma

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