OncologyTube: [00:00:00] Okay, we’re here at ASCO GI 2024 and we have Jeanne Tie, MD a medical doctor, the medical oncology lead for the lower GI tumor stream at Peter MacCallum Cancer Center and senior research fellow within the Division of Personalized Oncology at the Walter and Eliza Hall Institute in Australia. Dr. Tie, thank you so much for joining us today.
Jeanne Tie, MD: You’re welcome. Pleasure to
OncologyTube: be here. Today we’ll be discussing circulating tumor DNA analysis informing adjuvant chemotherapy and locally advanced rectal cancer. The randomized AGI TG dynamic rectal study, which is being highlighted here at ASCOGI 2024. So Dr. Tie, can you provide an overview of the AGI TG dynamic rectal
Jeanne Tie, MD: study?
Yeah, sure. So, as we all know, [00:01:00] um, circuit human DNA analysis has the ability to pick up microscopic residual disease after surgery, for example. And given the modest, um, survival benefit of chemotherapy following, um, surgery for low care advanced rectal cancer, this study is really, um, aimed, designed to test a hypothesis that using the blood test to guide adjuvant chemotherapy.
could reduce the number of patients, uh, being given adjuvant chemotherapy, uh, without compromising their recurrence outcome compared to not using the blood test. So we randomize, um, patients. with locally advanced rectal cancer flowing, um, near adjuvant chemo radiation and following their surgery, um, taking blood tests at four weeks aft and seven weeks after surgery.
Two thirds of patients are randomized to what we call a ctDNA informed group, where patients with the positive results receive four months of adjuvant chemotherapy. Well, ctDNA [00:02:00] negative patients, if they have, uh, pathological nodal, uh, negative disease, they will just observe without any adjuvant chemotherapy.
If they have, um, negative result and have a no positive status, then the clinician decide what they’d like to do. In the one third of patients, that’s just randomised in the control arm, which just a standard of care. Um, the decision, decision about chemotherapy is at the clinician’s discretion. So the primary endpoint of the study is the proportion of patient receiving chemotherapy and then the secondary endpoint is three year recurrence free survival.
Um, but unfortunately, um, although the study was designed initially with about 408 patients, um, due to COVID 19 as well as increasing adoption of total new age event therapy. Uh, the study sees recruitment prematurely. Um, so we will be presenting the results of the 230 eligible patients that’s included in the analysis.
OncologyTube: Alright. [00:03:00] Um, Can you discuss the implications of the AGI TG Dynamic Rectal Studies findings which suggest that a ctDNA guided approach to adjuvant therapy in locally advanced rectal cancer reduced the rate of chemotherapy compared to standard management?
Jeanne Tie, MD: Shows us in this study we, um, in the ctDNA guided arm we, um, detect ctDNA in about 28 percent of patients.
Um, and overall, um, we did, um, demonstrate that, um, using CT and a guy therapy reduced the use of chemotherapy from 77 percent down to 46%. Um, and the use of oxaliplatin regimen between the two groups are very similar. So I think in a sense for. Um, oncologists who are, you know, who are hesitant or, or not sure about whether they should be offering adjuvant chemotherapy given the modest benefit.
It does suggest that by using a blood test, we could cerTienly reduce the number of patients receiving adjuvant chemotherapy. [00:04:00] Um, another important finding we, we found was that we actually looked at recurrence free survival, the outcome between ctDNA positive. patient and a ctDNA negative patient and we saw a significantly worse outcome in the ctDNA positive patients despite all of them receiving atrivine chemotherapy compared so their recurrence free survival was 53 percent only compared to recurrence free survival 83 percent in the ctDNA negative patient where only 23 percent of them had chemotherapy.
OncologyTube: Okay, so you touched on this already, but could you elaborate on the challenges faced and conducting this study, including the impact of COVID 19 and the increasing adoption of total neoadjuvant therapy and recruitment and data collection?
Jeanne Tie, MD: So, during COVID 19, long course haemorrhagiation goes over five and a half to six weeks.
And during COVID 19, a lot of centres pivot to given short course radiation, which is [00:05:00] only five days of treatment. So, that really excluded a lot of our patients, um, in terms of eligibility for the clinical trial. That was one of the main reasons why recruitment went down significantly, in addition to the lack of resources.
created by COVID 19 around a trials unit, uh, in Australia. Um, and around the same time, there was increasing data that given chemotherapy, um, before surgery can, uh, reduce, um, the number of recurrences, um, in patients, uh, in low carrier virus rectal cancer. So patient with high risk, very high risk, low carrier virus rectal cancer, uh, more than are being offered chemotherapy before surgery.
OncologyTube: Alright, so what are the key takeaways from the study regarding the recurrence rates and the sites of recurrence in patients with ctDNA positive and ctDNA negative LARC post neoadjuvant treatment and surgery?
Jeanne Tie, MD: So, [00:06:00] as I alluded to before, I think the CTD negative patients, despite, um, only a few of them receiving adjuvant chemotherapy, they tend to do quite well, suggesting these patient potentially could avoid chemotherapy altogether.
Um, what is very interesting that came out of the study was the differential pattern of, uh, recurrence between, uh, CTD and a positive and negative patient, where we found, That majority of relapses in negative patient were in the lung only, and this was really rarely seen in the ctDNA positive patient liver metastasis seemed to be a dominant cyto metastasis in the positive patient.
This may speak to the biology of the ctDNA negative and positive patient, which hopefully over time will delve more into it. Understand the biology a bit more. My feeling is that possibly they’re more indolent. The ccDNA negative disease are more indolent. And we cerTienly see this in patients with lung metastases.
They tend to have a better [00:07:00] outcome. Their cancer tends to be slower growing. And the implication of that may be, my hypothesis is that they may be less sensitive to chemotherapy. And so chemotherapy may not cure these patients regardless, um, of their, um, of the relapse. So we may need to look into. other method of treatment for these patients.
OncologyTube: Okay. Well, this has been an interview with Jeanne Tie, MD medical doctor and medical oncology lead for the lower GI tumor stream at Peter McCallum Cancer Center and senior research fellow within the division of personalized oncology at the Walter and Eliza Hall Institute, uh, in Australia. Dr. Tie, thank you so much for chatting with us today.