I'll be talking about, got it, gosh it's not moving, so in 2012 we looked at the multivariable analysis in endometrial cancer patients who were intermediate high risk and high risk patient. And we found that the LBSI had a hazard ratio of 4.9 and that increased to 8.8 in presence of the positive nodes. And looking at the overall survival in multivariable analysis, only LBSI was significant and no other prognostic factor was significant with intermediate and high risk endometrial cancer patients. So, we looked at the survival and patterns of failure in 1,187 patients. Figure stage were from 1 to 3. 96 to 2014 were the all patient, all comers who came for the adjuvant treatment in our centers have been included. And the adjuvant treatment was either pelvic radiotherapy or vaginal valve brachytherapy. Very few people or patients actually receive systemic chemotherapy and most of those patients who received systemic chemotherapy were also entered in the PORTEC-3 trial. Histology were endometrioid, mucinous, or cleocyl and serous. And we looked at the survival and pattern of failure in relation to histology, grade, tumor volume, myometrial invasion, LBSI status, and the nodal status. Now, in order to clarify the role of LBSI and nodes, we decided that we will take in the first stage only FIGO stage 1 and 2 patient. And those who obviously had no other negative nodes. And the idea for this was that often the LBSI is actually scored in the uterus and in the myometrium at the tumor myometrial interface. And therefore, it is better to take only stage 1 and 2 where the tumor is limited to this area. And there were 483 patients. Of these, grade 1 and 2 were 314, grade 3 endometrioid were 90, cleocyl were 34, and serous were 45. Now, in absence of LBSI and nodes, all these patients did not have LBSI and nodes were negative. If you look at the inner half of myometrium and the outer half of myometrium, fortunately, they, anyway, the relapse rate was 8% and 10%. So, in other words, if LBSI is absent, then myometrial invasion did not appear to make any difference. And when we look at the tumor volume, the tumor volume or the tumor size varied from 5 millimeter to about 15 centimeter. And the median tumor volume size was 3.6 centimeter. So, if you take the below the median volume or the tumor size or the higher than the median tumor size, the patterns of failure were similar 8.5% and 9%. Now, these patients were treated with Vajanavar Brachytherapy, mostly, but some also received external beam radiotherapy, because you will notice that we started collecting these patients since 1996 onwards. So, the treatment policy about not giving external beam and so on, so forth, that changed. But nevertheless, when these patients were treated with Vajanavar Brachytherapy or with external beam radiotherapy, and if you look at the broken lines and the solid line, solid lines are the pelvic radiotherapy lines and broken lines are Vajanavar Brachytherapy line, you will notice that Vajanavar relapse, within pelvic relapse and beyond pelvic relapse, there was no statistical difference. So, when the nodes are negative and LBSI is absent, irrespective of histology, we find similar outcome. Now, the relationship between the LBSI and nodes, since these, my series only had the intermediate high risk and high risk patient, I did not have low risk patient. And therefore, the endometrioid data of grade one and two, I have taken from the Aztec study group, where the LBSI rate was about 20%. And the node positivity was about 9%. So, these are not my figure, these are low risk patient. But if you look at the endometrioid grade three, clear cell and serous, these are my figures, you find that the LBSI rate is actually more or less similar. And the node positivity is similar with grade three and clear cell and was slightly higher with the serous. So, ratio of 2 to 1, sorry, 3 to 1 was seen in endometrioid and clear cell, whereas in serous, it was 2 to 1. Now, if you look at the patterns of failure or relapse rates, this is a busy slide, I'm afraid, but the upper four rows, endometrioid grade one and two, grade three, clear cell and serous, these are LBSI negative and node negative. And you will see that even clear cell carcinoma, the relapse rate, 9%, 9%, and 11%. It was slightly higher in serous. And when you go to the LBSI positive and node negative, obviously the relapse rate is still not substantially high in endometrioid and grade one and two and grade three, although in clear cell, it then started to go up and it certainly was higher in the serous. But when it comes to the node positive patients, in grade one and two, relapse rate was still lower, which was almost the same as LBSI positive, but node negative. However, with grade three, clear cell and serous, the relapse rate was more than 50% in all three. And it was almost similar in grade three, clear cell and serous. If you look at the pelvic relapse alone, it was not really very common. And not only that, many of these patients could be salvaged. But if you look at the relapses, which were either in the pelvis or outside, but definitely there was a component which was outside pelvis, then you find that all those who fail, although fewer fail, but those who fail, most of them have actually failed outside pelvis. So what I'm trying to say here is that whatever local regional treatment we have considered, surgery and adjuvant radiotherapy, the pelvic control is excellent. And if the pelvic control failed, then 75% to almost 100% patient also failed outside pelvis. So when I tried to, when I sent this study for publication, then the reviewers actually suggested that there are so many categories. And since the LBSI negative, node negative, and LBSI positive, node positive, and node positive patient are discrete group, why not combine them and just give three groups? Since LBSI nodes are actually exerting effect, histology is exerting effect through LBSI nodes. So then I divided them like that, and these are the three groups. And you can see the hazard ratio of the LBSI positive, node positive, node negative rather is 1.65 and 2.83 for the node positive patient. So this was the overall survival and the relapse free survival, 2.43 and 4.78 was the hazard ratio. The overall relapse rate was about 20%. And now the patterns of failure. So this is in LBSI negative and node negative patient. And these are the sites of failure. You can see that this is the vagina and the pelvis. Here is the pariotic area. And this is the beyond pariotic area, including systemic. So you can see that most of the patients who are failing, they are failing at multiple sites. The interesting thing was that the number of patients who failed in LBSI negative, node negative were obviously quite small. Nevertheless, the proportion of patient failing at each site was almost similar to intermediate and high risk patients. But isolated failure in the pelvis was only seen in 2% when in a low risk patient. And in LBSI positive, again, the isolated pelvic failure was only seen in 2%. But you can now see that the pariotic failure has gone up and so has the beyond pariotic failure. And with node positive, again, the isolated pelvic failure is 1%. However, the pariotic and abdominal failure is 28% and 28% also 26% in the beyond pelvic failure. So this is my short talk. I hope that I finished in 15 minutes or 20 minutes. Thank you.

endometrial cancer

lymphovascular space invasion

nodal status

patient survival

patterns of failure