The treatment of Hodgkin's disease is one of the most significant successes in modern clinical medicine, and the disease is now considered one of the most curable cancers. However, the management of Hodgkin's disease is still a challenge. In early Hodgkin's disease (stages I and II), the challenge is to minimise the long-term side- effects.

In the early 1920s Rene Gilbert, a Swiss radiotherapist recognised the importance of treating contiguous lymph-node-bearing areas that were not clinically affected, and in 1950s, Peters first reported that early-stage Hodgkin's disease can be cured with radiation alone.

It was only in the late 1960s that Kaplan and Rosenberg popularised the use of radiation therapy for early-stage Hodgkin's disease. This popularity eventually led, after 1970, to the first-ever decline in the age-adjusted mortality rate for Hodgkin's disease. Since then, many patients with early-stage Hodgkin's disease have been treated with subtotal nodal irradiation (STNI) (also known as extended- field radiation therapy, which includes the treatment of mantle and para-aortic regions and the spleen).

Radiation treatment remains the single most important mode of therapy, with 95% of the patients achieving complete response, and with high cure rates of 90% or more for patients receiving STNI alone for early-stage Hodgkin's disease.

The use of combination chemotherapy for Hodgkin's disease began with the MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) regimen in the 1960s. Subsequently, ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) showed promise of being as effective as but much less toxic than MOPP. The role of chemotherapy attained prominence with increasing recognition of the long-term morbidity and mortality brought about by STNI, the two major serious effects being second malignancies and cardiac toxicity.

Of note, the cumulative risk of developing solid tumours such as osteosarcoma and cancers of the breast, thyroid, lung, stomach, and colon is approximately 0.3 to 0.5 % per year and increases with time. The incidence of breast cancer is increased especially in women younger than 30 years at the time of mantle irradiation. The risks of late morbidity and potential mortality makes STNI a less attractive option, especially for a disease that tends to occur in younger patients and that has a high cure rate.

Attempts have therefore been made to modify the treatment for early-stage Hodgkin's disease so as to reduce the adverse effects of the treatment, either by reducing the radiation treatment volume or the total radiation dose, while maintaining the high cure rates.

Combining chemotherapy with radiation has been promising in various trials. An Italian trial has shown that there is no statistical difference in survival of patients receiving STNI or a combination of four cycles of ABVD and involved-field radiation. It is now a common practice in North America and Europe to combine two to four cycles of chemotherapy (typically ABVD) with involved-field radiation in early stage Hodgkin's disease with good prognostic factors. The long-term cure and morbidity rates in these trials are pending.

However, chemotherapy is not without its own toxicity. At 10 years, the risk of developing acute myelocytic leukaemia is 3% after MOPP, but much lower after ABVD. Fertility is also an issue, especially with MOPP-containing regimens. Combined modality also may further increase the inherent risk of second malignancies and also potentiate the cardiac and pulmonary toxic effects associated with mantle irradiation. The goal of reducing therapy-induced morbidity and mortality in Hodgkin's disease, yet maintaining a high cure rate, still remains.

Dr Susan Loong		Dr Yap Swee Peng
Consultant		Assoc. Consultant
Therapeutic Radiology		Therapeutic Radiology