BRAF Poster: Dr Maddelena (2025)

Manju George 0:00
Hello everyone. Welcome to Doc talks. I’m Dr Manju George, the Scientific Director at PALTOWN Development Foundation, the nonprofit that supports COLONTOWN. Today, we are doing a slightly different format. We have Dr Maddelina here with us, and she is going to go over her ASCO GI 25 poster, Dr Maddelina, welcome.

Dr. Giulia Maddelena 0:24
Thank you so much for this introduction. I’m back in Italy now. I’m Giulia Maddalena. I spent the last two years at MD Anderson with Dr Kopetz, great mentor, and I’m now back to Italy, in clinic in Istituto oncologica Veneto in Padua, and I’m briefly presenting today cooperation between the two institution with this project about V600E BRAF mutated metastatic colorectal cancer, subgroup of patients. So my poster presentation at ASCO GI was entitled “Challenges in patient selection for surgical option in the V600E BRAF mutated metastatic colorectal cancer”. As we know, metastatic colorectal cancer, there are different mutational subgroups of disease, and in particular, V600E BRAF mutated patients are about 10% of the entire metastatic coloreactal cancer patients, and this is associated with poor prognosis, but also it’s been studied, and it’s been noted that this is a very heterogeneous subgroup of patients. So not every history is the same, and we know that a great improvement in the treatment of colorectal cancer is from surgery of metastatic disease. So the integration of surgery, along with systemic treatment, really improved the outcome for our patients. So while many patients with these mutations have a very aggressive disease and unfortunately, never have the chance to undergo surgery, it is not clear how to navigate the clinical heterogeneity, and if we, as physicians, if we are able to select better patients that may benefit the most from the surgery on metastatic disease.

Dr. Giulia Maddelena 2:57
So we collected 71 cases of V600E BRAF mutated colorectal cancer patients between the two institutions. And we tried to evaluate outcomes according to clinicopathological features such as sex, such as histology, differentiation of the tumor, site of metastasis, such as liver or peritoneum, and sideness of the primary tumor. In the entire cohort, the medium relapse free survival was about 7.9 months after the surgery, and we were not able to highlight clinico pathological variables that may help in patient selection. The only element that was clearly associated with poorer outcome was R-1 resection in the pathological report. It means when in the pathological report, some cells are detected really close to the margin of resection. This is helpful, because it adds information in the prognosis evaluation and clinical management. However, it is not something that we can know before surgery. So to the point of the project, how can we better select those patients who may benefit the most, we don’t have an answer yet. This was a retrospective collection. Therefore it is supposed to be hypothesis generating. And basically the take home message is that the heterogeneity of the subgroup of patients deserve a better evaluation of every single case and when surgical rejection, is an option, at least the discussion is worth it to surgery. I really hope this may help some patients to understand their treatment management, and I’m happy to take any questions.

Manju George 5:28
Okay, thank you very much. Dr Maddelina That this was very helpful. So one of the things that I was interested to know is that, what kind of treatments did these patients get, did they get targeted therapy?

Dr. Giulia Maddelena 5:48
Because this is a limited subgroup of patients, this comes from also few years ago when targeted treatment was not available. Therefore, this is a very important point, and thank you for the question, and it is something that we really need to look at, but the information is not available right now.

Manju George 6:15
Okay, thank you very much. So it was very informative that you said that even though your goal was to find out something that would help, learn about the heterogeneity, yeah, it is after the results that the main or the only thing that was different was clean margins versus, R-1 resection status, right? So perhaps, from a patient perspective, looking at it like somebody with a higher chance of getting to an R0 resection may have a better chance of having longer recurrence free survival. Would that be okay to interpret it like that?

Dr. Giulia Maddelena 7:00
Yes, I believe it’s a good interpretation to the point is that, not always what we see in a CT scan is what a surgeon then detect in the OR. So, of course, the entire evaluation has to be to the point to get a radicality, but we really know that after the surgery.

Manju George 7:32
Okay, yeah, thank you. That’s a great point, because you mentioned you’re looking at patients with liver disease and peritoneal mets, and sometimes peritoneal mets, only after the surgeon opens the patient up can they have a better understanding of the extent of disease. So in the end, what you’re really saying is that if you are able to get to patients early in the disease with limited metastatic disease, which are surgically resectable to get clean margins, those patients might have better outcomes, right? So because among patients, the general opinion is that somebody with a BRAF mutation, they are usually not, when you go to a surgeon, they are usually the people who are told that you can’t have surgery because these have poor outcomes. And there is also the conversation that because the disease so aggressive, the physical issues with or the time off treatment while the patient is having surgery, in recovery, that also has to be factored in. So we usually hear that, these are patients who are told no surgery for you. So this information that you have from this perspective, so the study is important in showing that there is a subset of patients who may benefit from having surgery, and learning more about that subset would help greatly, right?

Dr. Giulia Maddelena 9:01
Yes, I agree with you. Unfortunately, for this subgroup of patients, surgery is not always an option, even to the discussion of the surgery, right? But for those patients with a more indolent disease, and this is something that we can see along the treatment plan and how things are going, how the patient is feeling, what’s the response to the treatment, even if it’s not, we still need to, provide data and evaluate this integration with the treatment, especially with targeted treatment. But for those patients with a more indolent disease, a discussion, and a limited amount a limited disease burden, a discussion could be worth it.

Manju George 9:55
Okay, thank you very much. This is very helpful.