Key issues in early-stage HL

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James O. Armitage, MD
Professor, Internal Medicine
Division of Hematology & Oncology
University of Nebraska Medical Center
Omaha, Nebraska
Hodgkin lymphoma compared to most other cancers has given us the luxury now with effective therapies to begin worrying about not hurting people in addition to trying to cure them, and to that end for the last decade or so, much of the research has been aimed at trying to reduce the intensity of therapy or the amount of therapy or the specific types of therapies to reduce late toxicity. Those approaches have included trying to do away with radiotherapy, which was of course the first way we cured Hodgkin lymphoma, and to try to reduce the amount that is either the total duration or the intensity of chemotherapy, and all those ideas are being tested. At this meeting, there were updates on some important studies presented. Two of them were looking that whether or not it is possible to do away with or at least significantly reduce radiotherapy and/or chemotherapy in the treatment of these patients. There is a study from the UK that tried giving just three ABVDs versus those plus radiotherapy. The patients with very early stage Hodgkin lymphoma had good prognostic factors. Don’t forget that even though people don’t do the same way, everybody tries to take low-stage, early stage patients, which means basically stage 1 and 2, and to divide them into really good ones or favorable subtypes or subgroups and unfavorable or a bit more aggressive that might mean more disease, higher sed rate, lots of different ways. Different groups have done that, and they all have not done it the same way actually, to divide unfavorable with favorable. At any rate as defined by the study in the UK, favorable patients were studied to see whether or not just giving three ABVDs will be adequate therapy, and to make a long story short, at the present time with only a few years’ follow up, there is a higher relapse rate if you don’t get radiotherapy, maybe 7% or 8% higher relapse rate within a few years. There is no difference at all in survival, and so, you could interpret that two ways. You could say, wow, you should begin radiotherapy because a whole bunch more people relapse, several times more relapse in the first few years if you do not get the radiotherapy, or you could say is, what it means is around 90% of the people did not need radiotherapy, and they avoided the toxicity of it, and we rescued those few people that relapsed with second-line therapies. A similar study from the EORTC reached the conclusion that it is unsafe not to give radiotherapy with about the same data, and they said the relapse rate is higher without radiotherapy, and so, it is not right to let those people relapse, and also by the way, it showed no difference in survival. So two studies really got kind of the same answer and drew different conclusions about how to interpret the data. In the long run, it is either going to be if there is higher relapses in the people who do not get radiotherapy and get minimal chemotherapy, only do higher eventual death rate and then a lower survival, or it may be the people who get more therapy with the radiotherapy added and/or more chemotherapy will have more late toxicity and eventually that will lead to a lower survival, or salvage therapy will save them and whether or not there is an excess toxicity, in the end, it will be about a wash. We will see. Time will tell. So today, a reasonable person I think if they explained to their patients what the risks were could offer either approach. People are trying to base those decisions based often on early PET scans. It is interesting that Andreas Engert here, who now runs the German Hodgkin Lymphoma Study Group, Andreas in his presentation said that he does not believe it is appropriate to base therapy outside a trial on PET scans. He thinks early PET scanning is not yet proven as a good way to do that. That is interesting because in the US, NCCN Guidelines recommend using that. So for a disease in which we cure most people and the survival rate with different approaches at the moment do not appear to be significantly different, there is still quite a bit of controversy about what the right way to do things might be.
Last modified: November 18, 2013