How's she around? OK. So can you see my slides? You can see, yes. You can see them. OK. So last time we were talking, my last lecture, my last presentation was four months ago. I spoke about adjuvant treatment for endometrial cancer. And I presented our protocol for the, or our current protocol, for the adjuvant treatment for endometrial cancer. We stopped after I presented the recommendation or the protocol for all the stages. And now I want to tell you a little bit about the future, I think. It's not currently done, at least not in Israel. But I think it will be incorporated in the very near future. And I wanted to tell you about it. So all the recommendation that has been, I mean, the protocol and the recommendation that we use today is based on a clinical and pathological characteristic. But now, seven years ago, a study was published, the Cancer Genome Atlas Project, that identified four molecular subclasses based on somatic mutation burden and copy number alteration. The first group was the ultramutated endometrial cancer with mutation in pol gene, P-O-L-E. The second group was the hypermutated endometrial cancer with microsatellite instability. The third one was copy number high endometrial cancer, which is characterized by a frequent P53 mutation. And the last group is the copy number low group. And as you can see, the four subgroups has a completely different prognostic characteristics with the first group with the permutation has an excellent prognosis. And the fourth group, what we call a cell-like group with the frequent P53 mutation absent, I'm sorry, P53 absent, has almost a half chance of surviving after three years with approximately 50% relapse-free survival in five years. Since then, two other research groups have classified the molecular subgroups by their surrogate markers and show basically the same correlation to prognosis. The first was the PORTE group, and the second was what is called the PROMIS group, the Vancouver one. And they've showed that prognostic strength and risk stratification was at least equivalent to the clinical pathological features that we know from today. Based on this study, last year was published a trial based on the PORTEX-3 trial. It was a translational research, and they took all the patients from the PORTEX-3 trials, which were all high-risk patients. And they showed that there were clear differences in prognosis between the subgroups, even though they were all high-risk patients. The study also showed, and I'll show you now, that unrelated to prognosis, the PORTE group, the group that had the P53 absent, benefited the most from chemotherapy. And these are the results. First of all, the four groups, as you can see now, the pole mutation is the smallest group with approximately one quarter of the patient allocated to this group. But the other group contains between one third to one quarter to one third of the patient on the other group. And you can see here as well that the pole mutation, the pole gene group has an excellent prognosis. And the P53 absent group has the poorest prognosis. And if you look only at the P53 group, what we call P53 absent group, you can see that they benefited most from chemotherapy. Here is the relapse-free survival, and here is the overall survival. And you can see when you add chemotherapy to the radiation therapy, at least from the relapse-free survival aspect, you benefit at least twice in respect of reducing the risk of recurrence. On the other side, you have the pole mutant group that has an excellent prognosis in relapse-free survival and overall survival, again, regardless of the treatment they receive. The clinical implication of this study, I think, will be very important. We have a clear prognostic value of each of the groups. And it is regardless of the histology, regardless of the stage. We can better identify patients who might benefit from the combined treatment and potentially de-escalate treatment for pole mutant tumors. And we have the potential for targeted therapy. And this is the first prospective trial done using the molecular profile when they basically define the group based both on clinical pathological and molecular profiling. They classify the groups into favorable, intermediate, and unfavorable, and target the adjuvant treatment based on this. And we wait for the result of this study that will decide what will be our recommendation in the future regarding adjuvant treatment for endometrial cancer. Thank you. Thanks, Shira. May I just say that the Vancouver group is also starting a collaborative multi-center prospective trial looking at de-escalation of treatment based on molecular profile, which we're hoping to be a part of here. So yeah, fingers crossed for lots of interesting results in the future. Yeah, no, we've been behind in the field in endometrial cancer. So this is a good starting point.

adjuvant treatment

endometrial cancer

molecular profiling

molecular subclasses

prognosis