- © 2010 by American Society of Clinical Oncology
Reply to M. Ozsahin et al
Ozsahin et al1 have reacted to our study, which might be expected; however, it should be clear that this was a hypothesis-generating study involving a group of patients with quite favorable presentations (45 years of age or younger and no bulky mediastinal disease).
There are two questions in the debate concerning the appropriate therapy for young patients with favorable presentations of Hodgkin's lymphoma. First, if the event-free survival is minimally different and supports combined-modality treatment without an overall survival advantage, then is it justified to place more than 85% of patients at risk of unnecessary long-term cardiac or neoplastic toxicity? The second question relates to the appropriate salvage treatment for the small number of recurrences in the chemotherapy-only group—an issue that is unresolved.
The authors should use caution in quoting the meta-analysis publication by Herbst et al.2 The survival advantage of combined-modality treatment was derived from a statistical exercise involving only five trials, most of which are from the previous century, one of which was published in an obscure journal using outdated chemotherapy of uncertain dosage. The Argentine Group for the Treatment of Acute Leukemia trial did not have a survival advantage, in general, or in the favorable group, in particular.3 The Memorial Sloan-Kettering Cancer Center trial that was reported on by Straus et al4 also showed no survival advantage, despite a small event-free advantage. In fact, all trials, randomized or comparative, conducted in Europe or North America in the last decade show no overall survival advantage for combined-modality treatment, notwithstanding a small progression-free difference—a testimonial to the efficacy of salvage therapy in such patients. The article by Doria et al5 referenced by Ozsahin et al1 is not comparable because all patients had advanced disease that was treated initially with radiation and chemotherapy involving mechlorethamine, vincristine, procarbazine, prednisone, and then salvage treatment was administered with more chemotherapy and radiation.
Ideally, positron emission tomography scans may help identify those who require radiation or more intensive therapy, but there may be biologic assays that can identify patients who are more chemotherapy resistant, such as the macrophage marker, CD68.6
It is clear from the more recent trials using chemotherapy alone that the majority of young patients with early-stage disease and favorable presentations can be cured without radiation therapy. Patients should be told the facts as they are known before initiation of treatment.
AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.
Employment or Leadership Position: None Consultant or Advisory Role: George P. Canellos, Celgene (C) Stock Ownership: None Honoraria: George P. Canellos, Celgene Research Funding: None Expert Testimony: None Other Remuneration: None
