Don't Throw Out the Baby With the Bathwater: On Optimizing Cure and Reducing Toxicity in Hodgkin's Lymphoma

The metaphorical phrase — don’t throw out the baby with the bathwater—is actually of German origin and first appeared in writing in a satirical book published in 1512 describing fools who by trying to rid themselves of a bad thing succeed in destroying whatever good there was as well. This metaphor is worthy of consideration in the light of a salvo of recent editorials that called for elimination of radiotherapy from treatment programs of Hodgkin’s lymphoma (HL) regardless of stage. These recent editorials assert that chemotherapy alone provides equivalent outcome to that attained by using a combined modality program and also imply that by avoiding radiotherapy, one could keep the high cure rate of HL and avoid the late risks of developing second tumors and coronary heart disease. It is important to recognize that the increased risk for solid second cancers and particularly for breast cancer appears late (median, 15 years) and thus it has been detected mostly in patients cured of HL by treatments administered 20 to 40 years ago. This is the era when radical radiation alone or radiotherapy followed by consolidation or salvage chemotherapy (mostly mechlorethamine, vincristine, procarbazine, and prednisone [MOPP]) were the primary treatments for this disease. The alarm of excessive long-term risks draws from series of patients treated with the obsolete radical treatments of the past without accounting for the fact that the current practice of combined modality is dramatically different from antiquated treatment approaches. Current standards combine short chemotherapy with only mini radiotherapy. Emerging data from recent randomized trials and retrospective analyses such as the report in this issue of the Journal of Clinical Oncology by Koontz et al from Duke University (Durham, NC) support the notion that the long-term survival of currently treated patients is unlikely to be affected by long-term treatment-related complications. At the same time, several recent randomized studies that attempted to eliminate radiotherapy in early-stage HL, either had excessive relapse rate in the no-radiation arm and had to close early, or showed inferior disease control when chemotherapy alone was used; as will be detailed in this editorial. Unfortunately, although the National Cancer Comprehensive Network guidelines advocate combined-modality as the preferred treatment for early-stage disease, some practices in the United States have already adopted the chemotherapy alone approach. Clearly, clinicians and patients are hearing conflicting recommendations on the appropriate management of HL today. Are we compromising disease control by eliminating radiation and merely substituting one set of risks with another? Are there other ways to reduce the risks of radiotherapy and of chemotherapy while still maintaining excellent outcome? Is more of one modality better than less of two? In a disease for which we have treatment programs that have achieved a remarkable cure rate of 80 to more than 90% (stage-dependent), this is not a trivial issue. Recently reported randomized trials, case-control studies, and retrospective long-term data analysis, including the Duke University study reported in this issue are helpful in examining the real risk of modern treatments in comparison to the outdated radical radiation alone approach. The controversial issue of optimal and balanced choices for HL is worthy of further examination, this time from a different perspective.