The Role of Clinical Prognostic Factors in the PET Era

EHA 2014: Meeting Highlights in Hodgkin Lymphoma published on July 16, 2014
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Peter Johnson, MA, MD, FRCP
Professor of Medical Oncology
University of Southampton
Southampton, United Kingdom
The Role of Clinical Prognostic Factors in the PET Era

I am Peter Johnson. I am the chair of medical oncology in Southampton in the UK. I am going to talk to you today about the education session that we have just had, particularly dealing with the role of PET scanning in the management of Hodgkin lymphoma and the relationship to the traditional clinical prognostic factors which we have all got used to using such as the Hasenclever index for advanced Hodgkin’s disease and the classification of early Hodgkin lymphoma into favorable and unfavorable types. What we are seeing is a gradual migration away from the traditional prognostic factors used at the baseline. What we have seen over the last 20 years of treatment is that as our results have improved, so the prognostic factors become much less dominant, and even the worst prognosis groups have improved dramatically during this time. Where we are using PET these days is firstly at staging, at the initial evaluation of the disease, what we are finding is that probably we can use PET scanning instead of doing a bone marrow biopsy in the great majority of patients. There is some good retrospective data analyzing the staging process with PET scanning which show that in most cases you do not need to do a bone marrow provided the PET scan is clear. It is very unlikely that you will upstage the patients with the bone marrow, and it is extremely unlikely that you will make any difference to the therapeutic approach.

We have also got emerging data on the value of interim PET scanning in both early and advanced Hodgkin lymphoma. In early Hodgkin lymphoma, we are starting to get an indication that an early PET response may give us the opportunity to omit consolidation radiotherapy. The standard approach to treating early Hodgkin lymphoma is an abbreviated course of usually ABVD chemotherapy followed by involved-field radiation. The two trials which have recently concluded, the rapid trial from the U.K. and the EORTC Intergroup Study has both shown that if you omit radiotherapy, there is a small increase in the number of progressions at the end of treatment for early Hodgkin lymphoma, but that overall survival does not appear to be adversely affected. So in discussing the results of these trials with patients, what we can say is that if you have a negative PET scan after 2 or 3 cycles of ABVD, there is a choice. You can either go on and have consolidation radiotherapy if you are not concerned about the long-term side effects, for example, if it is in a field where you are very unlikely to do damage to the coronary arteries or to irradiate the breast in significant amounts, or if you do not mind a slightly increased risk of progression, and that is probably of the order of 5%, then you can omit the radiotherapy, and the great majority of patients will remain in remission following this approach if they have a negative PET scan after 2 or 3 cycles of ABVD.

When we come to the management of advanced Hodgkin lymphoma, the results of interim PET scanning are really pending from the trials such as RAPID and the German Hodgkin Study Group study and the U.S. Intergroup Study, all of which have been examining the role of interim PET in advanced Hodgkin lymphoma. What we do know from the results already available is that escalating therapy from ABVD to BEACOPP produces a good number of responses. Around 75% of patients will respond to BEACOPP if they are PET positive after 2 cycles of ABVD. So we await the longer-term analysis of this to see the true value of interim PET scanning, and not all centers in the world are using interim PET, and Laurie Sehn from the British Columbia Cancer Center presented data today about the algorithm which they used there, which does not take account of interim PET but does use PET at the completion of therapy. PET scanning is increasingly being used at the completion of treatment for advanced Hodgkin lymphoma in order to determine whether or not consolidation radiotherapy is required. The biggest study in this area is the German Hodgkin Study Group HD15 study which showed that in patients with residual masses of 2.5 cm or more, the PET scan was highly predictive of the outcome. Those who had PET-negative residual masses were treated without radiotherapy, and this group did just as well as those who had no residual mass after 6 or 8 cycles of BEACOPP. Those who had PET-positive residual masses underwent involved-field therapy and the results in that group were not quite as good as those that were PET negative, were nonetheless very promising with a good level of progression-free survival. The Canadian Group and the British Columbia Cancer Agency have used this very similar algorithm, but they used ABVD as the chemotherapy before doing a PET scan at the completion of treatment. And what they have shown is that PET-negative cases with residual masses again do as well as those who have no residual mass, but the PET-positive cases in that series seem to do rather less well with consolidation radiotherapy than in the German Group, and the concern here is whether there is some interaction between the chemotherapy which goes up to the point under the PET scan at the end of treatment, so those that have had BEACOPP seemed to do very well with consolidation radiotherapy, those that have had ABVD seemed to do less well with consolidation radiotherapy, and I think what this does is make the case for interim PET scanning in order to determine the response much sooner because I think a positive PET scan at the end of ABVD may mean that you have been giving ineffective treatment for quite some time and that consolidation with radiotherapy may not be as effective in this context.

One of the areas in which PET is overused in some places is the follow-up of patients with Hodgkin lymphoma, and there is really no data to suggest that PET scans carried out in the follow-up of patients who have already achieved remission is at all valuable in detecting relapse. We already know that the great majority of recurrences in Hodgkin lymphoma will be detected by the patient themselves, and that most of the surveillance investigations, chest x-rays, ESRs, PET scans contribute very little to management and certainly have very little influence on the survival figures, so the international guidelines at the moment would be very much against the use of PET surveillance in remission.

Last modified: July 16, 2014

Managing HL would like to recognize and thank Merck & Co., Inc., Seattle Genetics, and Takeda Oncology for their educational support of

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