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Discussion
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Dr Richard A Prinz (Evanston, IL): Very nice presentation on a problem that continues to vex us. You mentioned that there was a difference in the frequency of recurrence after 2010. Is that related to the size of the tumors that you are seeing? Perhaps screening with CT and so forth is giving us a different type of disease in re- cent years?
Second, I know that this was not the focus of the study, but do you have any thoughts on how this information is changing your approach to the tumor bed, where hopefully we can limit the local recurrence?
Dr Jason Glenn: Thank you for your questions.
I think that the difference we see after 2010, at least at our institution, may be that we are picking up more of these on imag- ing, potentially earlier, which may translate to more operations. But really the protective effect after 2010, I think, is more due to the standardization of care. Around that time is when we formed our multidisciplinary endocrinology group. Hopefully, we are see- ing some improvements in surgical techniques and adjuvant ther- apies over time as well.
As far as changing our approach, I can’t really say at this point. We have developed a management algorithm for patients based on our experience, but any data related to operative conduct and out- comes specifically is still forthcoming.
Dr Janice Pasieka (Calgary, AB, Canada): Jason, very nicely pre- sented. I may have missed it, but was function of the tumors part of your analysis, since about 60% seem to be functioning?
The other question is whether you have any data on the histo- logic type? Oncocytic adrenocortical carcinomas we think may be- have a little bit differently, and I am wondering what your analysis would show if you looked at those separately.
Dr Jason Glenn: As this is a heterogeneous group, we are seeing patients as referrals from a number of different institutions over a long period of time. The beginning of the study period was 1983 and it ended in 2017. So there’s obviously some variability in re- porting of hormonal status and standardization between institu- tions.
We did not characterize each hormone (cortisol versus aldos- terone versus sex hormones) separately. We did look at the group as a whole, and it was not found to be significant.
As far as the histologic type, the limitations were similar. Again, we are looking at a wide range of time and institutions.
Our pathologist did look at all of the slides and cell blocks that we were able to obtain from these other institutions, but we did not specifically look at each individual histologic type as a variable.
Dr Scott Wilhelm (Cleveland, OH): I was curious if you looked specifically at the amount of time to recurrence? Obviously, the most common type is tumor-bed recurrence. For the time-to-bed recurrence, did that impact what percentage of patients on whom you went back and did that re-resection? I think you said your average was 14 months to your third recurrence for tumor-bed re- resections, but did that vary with the amount of time for the first occurrence or not? I think that is important for us to know in se- lecting patients for going back for re-resections.
Dr Jason Glenn: We didn’t look at it specifically. Definitely, those who had an initial recurrence rate interval longer than 12 months were more likely to undergo reoperation.
I was surprised to find that once they went down that reopera- tive arm, the recurrence-free interval became less important in the decision to reoperate after that.
Dr Peter Mazzaglia (Providence, RI): Congratulations on this large series of patients.
Correct me if I am wrong, but I think you managed to talk about over 300 ACC patients without mentioning mitotane. I may be opening Pandora’s box-but you talked about local radiation and its effect, and I’m just curious why you chose not to look at mi- totane. Did it complicate the picture too much? Do you plan to look at it in the future?
Dr Jason Glenn: Excellent question. We looked at radiation therapy because it was much easier to standardize between insti- tutions whether or not they got radiation therapy. For patients who are on mitotane at one point or another, it is very difficult to tell whether or not they were at therapeutic levels, if levels were even drawn, how much they were on, or if they had any interruptions
in therapy. We looked at whether or not they were on it at any point, and it didn’t come out to be significant.
Dr Amanda Laird (New Brunswick, NJ): I think that your data certainly show the importance of keeping databases on your pa- tients because it is quite a large series of patients with adrenocor- tical cancer.
I think we all expect patients with ACC to recur, and the ques- tion for me at least has been not exactly where, but when, and is it surgically resectable? So how is it that knowing where and how it might recur impacts or influences your treatment?
Dr Jason Glenn: Again, we clearly saw that a recurrence inter- val less than 12 months was a negative predictor of survival, so in many instances we use recurrence-free interval as a decision point.
We found that certain sites showed up at shorter intervals ver- sus longer intervals. If it’s treated adequately, survival and progno- sis can still be quite good. But again, it’s very site and procedure specific.