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SO019LBA/#875  Molecular features predicts outcomes in multicentric international study of chemoradiation and MRI based image guided brachytherapy for cervical cancer (EMBRACE): final analysis from bioembrace-I
  1. Supriya Chopra1,
  2. Nanda Horeweg2,
  3. Kedar Deodhar3,
  4. Santosh Menon3,
  5. Tynisha Rafael4,
  6. Venkatesh Pai1,
  7. Katja Jordanova4,
  8. Lucia Rijstenberg5,
  9. Sadhana Kannan6,
  10. Barbara Šegedin7,
  11. Fleur Huang8,
  12. Kjersti Bruheim9,
  13. Margarita Pérez-Mosso Pérez-Mosso10,
  14. Bhavana Rai11,
  15. Li Tee Tan12,
  16. Maximilian Schmid13,
  17. Kari Tanderup14,
  18. Richard Pötter13,
  19. Tjalling Bosse15 and
  20. Remi Nout16
  1. 1Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Homi Bhabha National Institute, Radiation Oncology, Navi Mumbai, India
  2. 2Leiden University Medical Center, Radiation Oncology, Leiden, Netherlands
  3. 3Tata Memorial Hospital, Tata Memorial Cente, Homi Bhabha National Institute, Pathology, Mumbai, India
  4. 4Leiden University Medical Centre, Pathology, Leiden, Netherlands
  5. 5Erasmus University Medical Centre, Pathology, Rotterdam, Netherlands
  6. 6Advanced Centre for Treatment Education and Research in Cancer, Tata Memorial Centre, Homi Bhabha National Institute, Biostatistics, Navi Mumbai, India
  7. 7Institute of Oncology Ljubljana, University of Ljubljana, Radiotherapy, Faculty of Medicine, Ljubljana, Slovenia
  8. 8Cross Cancer Institute, Radiation Oncology, Edmonton, Canada
  9. 9The Radium Hospital, Oslo University Hospital, Oncology, Oslo, Norway
  10. 10Hospital of Navarra, Radiation Oncology, Pamplona, Spain
  11. 11Postgraduate Institute of Medical Education and Research, Radiotherapy and Oncology, Chandigarh, India
  12. 12Addenbrooke’s Hospital, Radiation Oncology, Cambridge, UK
  13. 13Medical University Vienna, Radiation Oncology, Vienna, Austria
  14. 14Aarhus University Hospital, Oncology, Aarhus N, Denmark
  15. 15Leids Universitair Medisch Centrum (LUMC), Department of Pathology, Leiden, Netherlands
  16. 16Erasmus MC Cancer Institute, University Medical Center, Radiotherapy, Rotterdam, Netherlands


Introduction BIOEMBRACE-I was designed to investigate biomarkers of response and disease control in patients treated with chemo-radiation and MRI guided brachytherapy (BT) for cervix cancer.

Methods Between 2018–2021, eight EMBRACE-I sites contributed tumor tissue for immunohistochemistry (p16, PD-L1 and L1CAM). Biomarkers and clinicopathological factors (FIGO stage, nodal status, histology, necrosis on MR) were used to determine predictors of poor response (high-risk clinical target volume (HRCTV>40cc) at BT and 5-year local, pelvic control and disease-free survival (DFS). Interaction between p16, PDL-1, radiotherapy dose (HRCTV D90) and local control was investigated. Univariate and multivariable analysis (MVA) was performed.

Results Two hundred sixty-four patients were included. The median D90 was 89 (86–95) Gy. P16, PD-L1>1% and L1CAM>10% expression was noted in 81.4%, 17% and 17.4% respectively. P16 -ve status (OR 2.4 (1–5.7), p=0.04), necrosis on MRI (OR=2.1(1.1–4.3), p<0.02) independently predicted for HRCTV-BT >40cc in addition to FIGO stage and tumor width. PD-L1>1% was associated with reduced local (82% vs. 94%, p=0.02) and pelvic control (79% vs 89%, p=0.02). HRCTV D90 <85Gy was associated with inferior 5-year local control in p16+ patients especially if PDL-1 was co-expressed (figure 1). On MVA, PD-L1>1% was the only independent predictive factor for 5-year local event (HR 3.3, p=0.04) and L1CAM for pelvic event (HR 5.5 (1.3–23.3), p =0.02) (table 1).

Conclusion/Implications P16 -ve status and necrosis on MRI independently predict for poor response to EBRT (HRCTV-BT >40cc) and PD-L1 and L1CAM independently predict local and pelvic control suggesting impact of molecular features on radiotherapy response.Further validation is planned in EMBRACE-II.

Abstract SO019LBA/#875 Figure 1

Abstract SO019LBA/#875 Table 1

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