alone versus alone for

The quote from Paracelsus is an interesting parry. He was called “the precursor of chemical pharmacology and therapeutics and the most original medical thinker of the sixteenth century” (1), and the quote refers to drugs and chemicals. unfortunately, the quote does not apply to radiation. An expert panel sponsored by the National Academy of Sciences, in the BEIR VII report (2), states that no dose of radiation is safe. We took fluoroscopes out of shoe stores and stopped treating adolescent acne with radiation therapy for that very reason—safety. The remaining arguments in the letter fail to stand up to closer scrutiny. The review by Diehl et al. cited to support the claim that cure rates are not as good with chemotherapy alone as with combined modality therapy actually concluded that “whether four to six cycles of chemotherapy without radiation are sufficient has still to be determined,” a true statement when it was made in 2004. The meta-analysis by Herbst et al. that claimed the superiority of combined modality therapy over chemotherapy alone included only five trials among the highly selected studies analyzed: one in which the chemotherapy was documented to be given at compromised doses that did not produce a single white blood cell nadir less than 2000 cells/μL (3), one that has been presented only in abstract form without the usual peer review (4), one in which doses and schedule of therapy cannot be evaluated from the published article (5), and one that focused on patients with bulky disease (6). The final study from memorial Sloan-Kettering (7) does not support the conclusion that combined modality therapy is more effective. The authors’ own recently published work was cited as evidence that lower doses of radiation result in a lower (but notably not zero) increased risk of breast cancer, and we truly hope that this result is borne out with further follow-up. Their study provided a median follow-up of 18 years, the point at which second breast cancers are usually just beginning to appear. Women who were in their 20s or younger at the time of radiation treatment are at the greatest risk of radiation-induced breast cancer. In this study, only 20 women treated with only mediastinal (rather than mantle) radiation were at risk for 20 years. Thus, the women at greatest risk were still in their 40s. Risk of breast cancer becomes much greater after age 50. Thus, it is not yet clear that these women will ultimately be found to have a lower risk of breast cancer with further follow-up. Keep in mind that radiation dose may influence the latent period (higher doses and shorter latent period) but not necessarily the overall incidence of complications (8). As a practical matter, even if one grants the unproven assertion that combined modality therapy is more effective than chemotherapy alone in early-stage Hodgkin’s disease, it is clear from the above metaanalysis that the margin is 10% or less. Let us say, for the sake of argument, that combined modality therapy results in 10% of people having more durable remissions than chemotherapy alone. At least half the 10 people treated with chemotherapy alone who relapsed but would not have done so with combined modality therapy are still curable with salvage therapy. Therefore, it would appear that those who favor combined modality therapy are willing to expose 100 patients to the late effects of radiation therapy (a minimum of 10 of whom will die from a radiation-induced complication) to benefit five of them. This point of view is very difficult to justify statistically. In our own randomized study that compared radiation therapy alone with mOPP (nitrogen mustard, vincristine [oncovin] procarbazine, prednisone) chemotherapy alone (9), if one determined overall survival of only the patients who achieved and remained in complete remission from Hodgkin’s disease with initial treatment, one could compare the impact of each modality alone on long-term survival. The survival of patients who were cured of their Hodgkin’s disease by chemotherapy at 25 years was 93%. For patients cured of their Hodgkin’s disease by radiation therapy, 25-year survival was 73%. The difference between them is statistically significant (P = .046). Late effects from radiation therapy are more common and more commonly fatal than late effects from chemotherapy. I believe that we should be aiming to cure as many people of Hodgkin’s disease as we can without using radiation therapy and to reserve radiation therapy only for the small subset who cannot be cured with chemotherapy alone.