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In the last decade the delivery of high quality MR guided adaptive brachytherapy has led to improved local control. However, this impact is not uniform across histological types. The differences in cervical cancer biology (HPV dependent or independent or PDL-1 positive vs not, presence of hypoxia or not ) in reference to radiation response needs to be further investigated for feasibility of dose deescalation. or escalation in future trials. The first leads from international BIOEMBRACE study are available and further investigation of intratumoral and systemic immune mileiu is needed for it's potential impact on brachytherapy outcomes. This talk will focus on early observations from Phase III Akt pathway inhibitor randomised trial (Nelfinavir), and HPV/PDL-1 biology within BIOEMBRACE study. The speaker will also focus on scheduling or timing of combination of anti PDL-1, AKT and VEGF inhibitors during chemoradiation and brachytherapy in ongoing trials and soon to be initiated EMBRACE studies in locally advanced high-risk and oligorecurrent setting.