Speaker: Supriya Chopra, MD, Professor, Tata Memorial Cancer Centre
Supriya Chopra, MD: Hello everyone. I'm Doctor Supriya Chopra. I'm a radiation oncologist from Tata Memorial Centre, specializing in gynecological cancers, and together with me is Doctor Remi Nout from Erasmus University Medical Center. As joint co-principal investigators of BIOEMBRACE, we are here to discuss with you the results of the manuscript that just came online in the Red Journal. We would like to discuss with you what these findings mean for the community and for cervical cancer. BIOEMBRACE is the largest international collaborative effort that utilized tumor tissue of patients from eight different countries in Europe, Canada and India. These were the centers that participated in EMBRACE study of image-guided adaptive brachytherapy for cervical cancer. The aim in BIOEMBRACE was to study the prognostic on predictive impact of these biomarkers, especially when co-tested in the setting of state-of-the-art external beam radiotherapy, concurrent chemo and brachytherapy. So what we did for this study was that we set up a digital pathology QA and there were six lead pathologists coming from three different centers: Leiden University Medical Center, Erasmus University Medical Center and Tata Memorial Centre. Together, the pathologists jointly agreed on the quality assurance and how to score these slides. And then we had two nodal pathology labs, one in Leiden, and another in Tata that took over the entire pathology work. 264 patients were included in this study and the outcomes of this cohort was considered to be representative of the overall EMBRACE cohort. We observed around 87% positivity of P16, around 20% for PDL1 and 18% for L1CAM more than 10%. And when we looked into these biomarkers, what we realized was that when patients have P16 positive tumors, they respond well, expectedly. The tumors are small at the time of brachytherapy. But when there were doses less than 85 Gy given to these tumors to high- risk clinical target volume, there was excessive relapse. Now this is very different from head and neck cancer where you expect that dose deescalation would lead to equivalent local control, so this is one difference and an important one that we observed in cervical cancer. The second important thing that we observed was a PDL1-guided radiotherapy dose response relationship, which is possibly previously not described in radiotherapy and patients who had PDL1 tumors, overall, they had excessive local failures, more so if we deliver doses less than 85 Gy. What was very interesting to us was that these PD-L1 expression, it did not predict for systemic events and in multivariable analysis when we tested parameters important for predicting local or pelvic control PD-L1 expression and L1CAM expression respectively came the only factors that were involved for predicting either local failure or pelvic failure. and none of the other established standard parameters stood the test when tested in a multivariable model. And we believe these results can be very interesting for the entire community. And I would now like our joint co-principal investigator, Professor Remi Nout, to give his perspective on BIOEMBRACE. Thank you.
Remi Nout, MD, PhD: BIOEMBRACE has for the first time demonstrated that in a cohort of uniformly treated patients with state-of-the -art chemoradiation and image-guided adaptive brachytherapy biomarkers outperform clinical and imaging features for predicting local and pelvic control. These observations will now be validated in an independent dataset to understand if individualized dose prescription is needed based on PD-L1 expression as P-L1 positivity in BIOEMBRACE is lower than recently reported in immunotherapy studies like CALLA and Keynote A-18. At Tata Memorial Centre we are now undertaking a cross comparison of the Clone SP-142 and 22-C3 to understand the variability of reported expression between these two clones. However, in the pilot cohort, the observations for PL1 are very similar between these two clones. In summary, we are very positive with these first observations of impact of biomarker on local and pelvic control and dose response in cervical cancer, and this paves the way for further development of individualized risk adaptive studies and testing of these biomarkers for risk-adaptive approaches. Thank you very much for your attention.
