UEG Journal Best Paper Award

00:00:06: Hello and welcome to this special edition of UEG Journal podcast featuring the paper that received the outstanding contribution best paper award for twenty-twenty-four, twenty-five UEG.

00:00:19: I'm Mohsen Subani, trainee editor at UEG Journal and a hepatologist based at Nottingham University Hospitals.

00:00:26: And I'm Maria Manoela Svim, a Porsche's gastroenterologist

00:00:30: working mainly

00:00:31: in IBD based

00:00:33: in Gaia Port.

00:00:34: And I am Malte Buchholz.

00:00:35: Thanks for having me.

00:00:37: It's a great honor.

00:00:38: I'm a molecular biologist and the group leader in the clinic for gastroenterology at the University of Marburg.

00:00:44: Thank you very much, Prof.

00:00:46: Buchholz, for joining us.

00:00:49: He's a senior author in this multi-center study, actually exploring the role of serum microRNAs and CA- one nine nine in diagnosis of recurrence after resection of pancreatic ductal adenocarcinoma.

00:01:03: are in short form called PDAC.

00:01:05: Thank you very much professor for joining us.

00:01:08: So as

00:01:21: you said, pancreatic cancer poses many problems and clinical practice and one of them is that essentially the only chance at curing patients is to send them to surgery at very early stages and to attempt an R zero rejection of an early stage tumor.

00:01:40: but even in that situation most of these patients if not all will have a relapse at some point.

00:01:48: That again makes it important to catch this relapse as early as possible because that opens up therapeutic windows again.

00:01:57: So there could be surgical re-exploration or chemotherapy.

00:02:03: And there's several studies out there that show that the earlier the relapse is caught, the better, much, much better chances patients have for a good prognosis after secondary treatment.

00:02:15: That's all very interesting, Prof.

00:02:17: Thank you for sharing.

00:02:18: Can you please elaborate more on the study design and also if you could explain why the Biopak Consortium was crucial for this study?

00:02:27: So essentially the design of the study was we collected serum samples from patients after they went through surgery at the times when they visited again for follow-up visits in the clinics in the different centers that participated.

00:02:44: And then we collected the serum samples and we stored them for later.

00:02:48: because essentially what we did was compare two groups of samples.

00:02:54: And one group is very obvious samples that were collected at those patient visits when relapse was clinically evident or became evident.

00:03:04: So this group of samples was called relapse group, of course.

00:03:09: And the other group of samples that we wanted to collect was for the group that we called no evidence of disease.

00:03:16: And for a sample to be included in this set, it had to be collected at a point in time where the patients for at least another twelve months remained relapse free, right?

00:03:28: So to be sure that in this sample there would be no trace of recurrence.

00:03:34: and sampling started at the earliest three months after surgery.

00:03:39: So you can imagine that this required a lot of patient enrollment, patient visits, long follow-up times, and to be able to collect.

00:03:51: a high enough number of samples of this type in reasonable frame of time.

00:03:56: Of course, we had to have many centers involved because the numbers of patients that needed to go through intervention had to be high enough to also yield enough of these samples.

00:04:07: And then again, in addition to that, we needed, of course, specialized expertise.

00:04:12: We had centralized, specialized pathology to make sure that all the patients actually had PDAC, right?

00:04:19: And we needed, of course, the computer scientists to make sense of the data later and so on.

00:04:25: So we had what we needed to be consulting for this.

00:04:29: Yeah, that sounds like a very complex but very carefully designed study.

00:04:34: And Professor, could you please share the main findings from this work with us?

00:04:38: Yeah, so what we found to put it very short is, first of all, the technique that we selected, which was real-time PCR.

00:04:48: on microfluidic cards is a very good technology for this.

00:04:53: So it yielded very technically very sensitive results and very reliable and reproducible results.

00:05:01: And in the end, what we could show was that those markers that we selected together with the well-known markers CA-Ninety-Nine produced very, very reliable results and was able to very Yeah, reliably detect tumor recurrence as we had hoped.

00:05:20: Wonderful.

00:05:20: One of the novel aspects of your work is a combination of a sieven gene MRI microRNA signature with CA-Nineteen-Nine.

00:05:29: What kind of diagnostic performance did this panel shift, Professor?

00:05:33: Overall,

00:05:34: these seven markers together with CA-Ninety-Nine achieved total accuracy of ninety percent, which meant, in detail, sensitivity of eighty-nine percent, and sensitivity of specificity was eighty-four percent.

00:05:50: Excellent.

00:05:51: This all sounds very exciting.

00:05:53: Now you analyze serial sample from individual patients.

00:05:56: Could you share how this time series analysis sports the idea of early detection of recurrence in PDAC?

00:06:03: Yeah, so for some of these patients, we had not just one or two samples, but actually a whole series of samples over longer periods of time.

00:06:13: And we analyzed for these patients, we analyzed all of these samples, of course.

00:06:17: So in total, these were five patients.

00:06:20: And what we saw was that for all five of these patients, our combined marker panel detected the recurrence or put it the other way around.

00:06:31: At the time that recurrence was clinically becoming evident, the marker panel also said there should be a recurrence or there's a high probability of recurrence in these patients.

00:06:42: And in addition to that, so we were never later than the clinical diagnosis.

00:06:47: And in one of these patients, actually, the marker panel indicated in retrospect, of course, that recurrence might be there.

00:06:56: at the visit that preceded the follow-up visit where clinically the recurrence was diagnosed.

00:07:05: So we were at least as early and in at least one case earlier with the indication of recurrence.

00:07:13: Wonderful.

00:07:13: And how do you think, I mean, from a clinical perspective, that these results might change the way we follow up our patients, for example, after surgery?

00:07:24: So what we... Hope, of course, is and what the whole goal of the study was from the onset.

00:07:30: This is a very, well, it's not simple.

00:07:33: Let's not say that it's a simple test, but it's noninvasive, right?

00:07:36: It's a simple blood sample that's drawn.

00:07:40: It's relatively cheap.

00:07:43: So the total cost even in this format where it was all experimental.

00:07:47: The cost of analysis per patient is around a hundred euros or something.

00:07:52: So this would open up the possibility of having patients tested in much shorter intervals than is the case now.

00:08:01: And then that again would ideally make it easier to detect recurrence earlier than it is being detected now.

00:08:09: And as I said, the earlier recurrence can be detected, the better for the patients.

00:08:14: It's a much better prognosis.

00:08:17: if recurrence is called early.

00:08:19: Thanks Prof.

00:08:19: So taking on from there, so there is also literature around circulating tumor DNA or axosomal markers.

00:08:26: So when we're talking about this, how your approach stand out?

00:08:31: And also if you could share some of your experience to our listeners that how do you think that this will translate into the clinical practice?

00:08:40: What made our approach different from pretty much all the other studies that we saw in the literature is like you said there's a lot of studies that looked at different kinds of circulating markers right circulating molecular markers.

00:08:55: but actually all of the studies that we saw were prognostic in their nature.

00:09:02: so blood samples were analyzed at some.

00:09:06: point in time after surgery, in some cases even before surgery.

00:09:11: And then these markers were used to try and predict if a patient was prone to develop recurrence early or late.

00:09:21: Our approach is different in that we take the samples at follow-up visits and look for actual recurrence right now at a certain time point in the follow-up.

00:09:34: So we don't predict the risk.

00:09:36: we look for actual recurrence.

00:09:38: Thank you.

00:09:38: So just a follow-up question to that professor.

00:09:40: Do you think this is more like a risk prediction model which can stratify the patient which would benefit from more hands-on surveillance after surgery versus who we can sit a little bit more looser?

00:09:54: Now, our interpretation for our approach and our data is that we have an answer to the question, is there relapse going on right now?

00:10:05: So, other studies have looked at risk and then the strategy probably is to have those patients that may have a greater risk come in in shorter intervals.

00:10:15: Our goal and our result is that we think our combined market set detects actual recurrence at the time when it develops.

00:10:27: Thank you.

00:10:28: Thank you.

00:10:28: And Professor, what do you think are the next steps, I mean, for implementing tools like this one in our everyday clinical practice?

00:10:37: Well, the very first step, of course, is we need to substantiate these findings in much larger numbers of patients, right?

00:10:45: For this to really reach clinical practice, of course, all these steps need to be validated and translated into clinical.

00:10:54: or validated with all the formalities that clinical tests need to fulfill.

00:11:00: And also probably brought onto a point of care technology platform, because so far this is still experimental technology for labs, but not really for point of care.

00:11:16: But what we were able to show is that the potential is there.

00:11:21: That's what we would conclude.

00:11:24: Thank you very much for your time and sharing this exciting article with us and I'm sure our listener would be very keen to hear this episode of PhotoCost.

00:11:35: Yes, congratulations once again for receiving the Outstanding Contribution Best Paper Award.

00:11:40: We all agree that this work clearly shows the potential of these novel agnostic in improving outcomes in patients with pancreatic cancer and how important this is in this special subgroup of patients.

00:11:54: Thank you again for having me.

00:11:55: It was a pleasure to meet you, even if only virtually for now.

00:12:00: Thank you very much.

00:12:01: And we're hoping to catch up during the UEG week.

00:12:04: That's all for today, special edition for UEG Journal Podcast.

00:12:08: We hope you have enjoyed this deep dive into one of the most impactful paper of this year.

00:12:15: And thanks for listening.

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