The role of radiotherapy for early stage Hodgkin's disease: Limitations and perspectives

For limited stage Hodgkin's disease (HD), the role of radiotherapy has been changing during the last decades, the main point being the (almost) complete disappearance of irradiation used alone. Actually, exclusive radiotherapy yielded satisfactory results in terms of long-term survival, but in 1998, it was becoming impossible not to take into account the late overmortality observed in all large cohorts of HD patients. This overmortality has been shown to be related (1) to cardiac toxicity of irradiation and (2) to secondary radiation-induced solid tumors. So the search for new strategies, as efficient, but less toxic, could not be avoided any more. For surgically staged patients (pathological stages I and II), irradiation alone (i.e., mantle field radiotherapy) can still be proposed to patients without unfavourable prognostic factors after a negative surgical infra-diaphragmatic exploration. For clinically staged patients with limited disease and favourable prognostic indicators, the association of chemotherapy and radiotherapy appears more and more as a standard. In parallel, efforts are bring made to alleviate the therapeutic burden. For radiotherapy, previous experience showed that, after a chemotherapy-induced complete remission, irradiation of the initially involved areas only was enough treatment. Ongoing trials are now exploring the possibility of a dose desescalation from the conventional 36 Gy to 20 Gy (as for children HD), and maybe to ... 0 Gy (no radiotherapy at all). Desescalation in the number of chemotherapy cycles is also bring investigated. For clinically staged patients with unfavourable prognostic indicators, a higher percentage of cases still appears to be refractory to treatment. So, while chemo-radiotherapy clearly became the standard strategy, efforts are essentially being devoted to identify new - and hopefully more efficient - chemotherapy schemes. In parallel, irradiation dose desescalation is being investigated. Most of these pending questions are addressed in a number of ongoing trials, as well in the US as in Europe, with the aim of offering to patients treatments at least as efficient as the presently used schedules, and less toxic in the long term.