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Session Item

Sunday
August 29
10:30 - 11:30
Room 1
Proffered papers 17: Gynaecological
Gabriella Macchia, Italy;
Remi Nout, The Netherlands
Proffered papers
Clinical
10:30 - 10:40
New Prognostic factors in locally advanced cervical cancer treated with MR-IGABT in EMBRACE Study.
Umesh Mahantshetty, India
OC-0295

Abstract

New Prognostic factors in locally advanced cervical cancer treated with MR-IGABT in EMBRACE Study.
Authors:

UMESH MAHANTSHETTY1, Maximilian Schmid2, Christian Kirisits3, Kari Tanderup4, Christine Haie-Meder5, Lars Fokdal6, Alina Sturdza7, Peter Hoskin8, Barbara Segredin9, Kjersti Bruheim10, Fleur Huang11, Bhavana Rai12, Rachel Cooper13, Elzbieta van der Steen-Banasik14, Erik van Limbergen15, Bradley Pieters16, Li Tee Tan17, Rohini Hawaldar18, Sadhana Kannan19, Remi Nout20, Astrid A.C. de Leeuw21, Nicole Nesvacil22, Ina Jürgenliemk-Schulz23, Jacob Lindegaard24, Richard Pötter 22

1Tata Memorial Hospital, (Homi Bhabha Caner Hospital & Research Centre, Visakhapatnam), , Radiation Oncology , Vishakhapatnam, India; 2Medical University of Vienna, Comprehensive Cancer Center, Department of Radiation Oncology-, Vienna, Austria; 3Medical University of Vienna, Comprehensive Cancer Center, Department of Radiation Oncology, Vienna, Austria; 4Aarhus University Hospital , Department of Oncology, Aarhus, Denmark; 5Institute Gustave-Roussy , Department of Radiotherapy, Villejuif, France; 6Aarhus University Hospital, Department of Oncology, Aarhus, Denmark; 7Medical University of Vienna, Comprehensive Cancer Center,, Department of Radiation Oncology, Vienna, Austria; 8Mount Vernon Hospital, Mount Vernon Cancer Centre , Department of Radiotherapy , Northwood, United Kingdom; 9Institute of Oncology Ljubljana, University of Ljubljana, Department of Radiotherapy,, Ljubljana, Slovenia; 10The Norwegian Radium Hospital- Oslo University Hospital Norway, Department of Oncology, Oslo, Norway; 11Cross Cancer Institute and University of Alberta, Department of Oncology, Edmonton, Canada; 12Postgraduate Institute of Medical Education and Research , Department of Radiotherapy and Oncology,, Chandigarh, India; 13St James's University Hospital, Leeds Cancer Centre, Department of Radiotherapy , Leeds, United Kingdom; 14Radiotherapie groep Arnhem, Department of Radiotherapy, Arnhem, The Netherlands; 15UZ Leuven, Department of Radiation Oncology, Leuven, Belgium; 16 Amsterdam University Medical Centers, University of Amsterdam, Department of Radiation Oncology,, Amsterdam, The Netherlands; 17Addenbrooke´s Hospital, Cambridge University Hospitals, Department of Oncology, Cambridge, United Kingdom; 18Tata Memorial Centre, Department of Clinical Research Secretariat, Mumbai, India; 19ACTREC, Tata Memorial Centre, Department of Biostatisitcs, Navi Mumbai , India; 20Leiden University Medical Center, Department of Radiation Oncology , Leiden, The Netherlands; 21University Medical Centre Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands; 22Medical University of Vienna, Comprehensive Cancer Center, Department of Radiation Oncology , Vienna, Austria; 23University Medical Centre Utrecht, , Department of Radiation Oncology , Utrecht, The Netherlands; 24Aarhus University Hospital , Department of Oncology, Aarhus, Denmark

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Purpose or Objective

The aim is to investigate prognostic factors affecting overall disease outcome and survival  in patients treated with chemoradiation and MR Image Guided Adaptive Brachytherapy (IGABT) in the prospective observational multi-centre IntErnational study on MRI-guided BRAchytherapy in locally advanced CErvical Cancer (EMBRACE)  study. 

Material and Methods

Between 2008-2015 a total of 1416 pts with LACC were prospectively enrolled in EMBRACE  from 24 centers. Patient, tumor (clinical/ MRI at diagnosis & BT)  and treatment related parameters (EBRT, Concomitant chemotherapy and BT details, dose volume parameters, total doses and overall treatment time) were analyzed. Disease Control (DC) was defined as absence of any recurrence or progression, Disease Free Survival (DFS) as absence of any disease event or death from any cause and Overall Survival (OS) as death from any cause, respectively. Kaplan-Meier method were used to estimate survival and Cox proportional regression models were used for multivariate analyses (MVA). Hazard Ratio’s (HR) & 95% Confidence Interval (CI) with a p-value < 0.05 were considered statistically significant. The model was carefully selected to define independent factors related with various patient, tumor and treatment parameters including age, FIGO stage, hemoglobin, clinical & MR tumor parameters, nodal involvement etc. 

Results

1341 patients were eligible for analysis. With a median follow up of 51 months, in total  331/ 1318 patients had events and/or deaths for DC, 427/1341 for DFS and 363 / 13 41 for OS. FIGO2009 stage distribution was IB 241 (18%), IIA 67 (5%), IIB 683 (52%), IIIA 13 (1%), IIIB 183 (14%), IVA 34 (3%), IVB(para-aortic nodes) 97 (7%); 52% were node-positive, 82% had squamous Cell Carcinoma.  Median (Inter Quartile Range [IQR]) high risk CTV volume was 28 (20, 40) cm3. Median (IQR)  D90% was 90 (85, 94) Gy EQD2.The overall DC, DFS and OS at 5 years was 74%, 68% and 74% respectively. Table 1 shows the hazard ratio (95% CI) and p-value of MVA for DC, DFS and OS.  Presence of tumor necrosis at diagnosis, distal parametrial involvement and larger CTVHR volume at BT showed a significant impact on DC, DFS and OS apart from classical prognostic factors as age, histological type, nodal involvement and OTT. The concordance indices (C-index with 95% CI) were 0.6735 (0.6417 – 0.7053), 0.6872 (0.6586 – 0.7158) and  0.6981 (0.6669 – 0.7292) for DC, DFS and OS respectively. 



Conclusion

We report new prognostic factors for disease control and survival in patients treated with IGABT for locally advanced cervical cancers.:  tumor necrosis at diagnosis, distal parametrial involvement and larger CTVHR volumes at brachytherapy. These factors seem to be even more important than the FIGO Stage after chemoradiation and IGABT.