Controversies in Early-Stage Hodgkin’s Disease

Drs. Ng and Mauch do an excellent job of summarizing the current conventional wisdom regarding the management of patients with clinical early-stage Hodgkin’s disease, although their citation of some studies is selective. Today nearly all patients with Hodgkin’s disease receive combined-modality therapy—usually an abbreviated course of a chemotherapy regimen (often one that has not been shown to cure the disease when used alone) followed by 20 to 40 Gy of involved-field radiation therapy. This approach certainly hides a multitude of sins. If you don’t give chemotherapy well, you can still achieve good disease control with the radiation therapy. If you can’t design a radiation port that encompasses known sites of disease, you can still get by because the systemic chemotherapy will leave relatively little for the radiation therapy to do.

Nearly all of the field’s intellectual capital is now being spent on attempts to define how little chemotherapy you can give and how small the radiation ports and doses can be without paying the price of higher recurrence rates. The strategy of using both chemotherapy and radiation therapy in every patient is, in my opinion, poorly considered and disregards much of what has been learned about Hodgkin’s disease treatment over the past 30-plus years.

Clinical Staging

It is important to understand why anatomic staging was ever important in the management of patients with Hodgkin’s disease. The major importance of anatomic staging was to identify patients who could be safely treated with radiation therapy alone. Ng and Mauch note that it is possible to use limited-field radiation alone with good results in patients who are shown at laparotomy to have no intra-abdominal disease. We have silently and with no remorse let lymphangiography disappear from the tool kit, although it was documented to be the single most sensitive way to detect intra-abdominal Hodgkin’s disease short of laparotomy.

Laparotomy has also largely been abandoned. The clinical staging work-up that is usually performed today omits lymphangiography and relies on abdominal computed tomography (CT) or magnetic resonance imaging (MRI) scanning to detect intra-abdominal disease. These techniques will miss at least two-thirds of patients with intra-abdominal involvement of Hodgkin’s disease. By current clinical staging methods, about 80% of patients will be considered to have early-stage Hodgkin’s disease when only 40% actually do. The abdomen has, by unofficial consensus, been declared a safe haven for Hodgkin’s disease clinical staging.

The take-home message is that if you are going to ignore intra-abdominal Hodgkin’s disease by making only a cursory attempt to detect it, you must use systemic chemotherapy to treat the disease because nearly half of the patients believed to have early-stage disease do not. This lesson has been amply learned in the studies (cited by Ng and Mauch) in which radiation therapy alone was used in clinically staged patients.

However, some clinicians have been slow to learn the lesson. They reason that patients who relapse can, in large part, be salvaged by combination chemotherapy....so what’s the harm? In fact, these clinicians note, because some patients are cured by radiation therapy alone, they do not need to receive chemotherapy, and thus, maximum disease control can be achieved while limiting exposure to combined-modality therapy to only 40% or so of patients rather than 100%.