ESTRO 2023

Session Item

Saturday

May 13

09:00 - 10:00

Stolz 1

Gynaecology

Chair: , The Netherlands;

Co-Chair: Safia Yahiaoui, Tunisia

Session Type: Mini-Oral

Track: Clinical

Journey:

Feasibility of the determination of the molecular-integrated risk profile in the PORTEC-4a trial

Anne-Sophie van den Heerik, The Netherlands

Presentation Number: MO-0050

Abstract

Abstract Title:

Feasibility of the determination of the molecular-integrated risk profile in the PORTEC-4a trial

Authors:

Anne-Sophie van den Heerik¹, Nanda Horeweg¹, Ludy Lutgens², Dorien Haverkort³, Stefan Kommoss⁴, Annette Staebler⁵, Friederike Koppe⁶, Marlies Nowee⁷, Henrike Westerveld⁸, Marianne de Jong⁹, David Cibula¹⁰, Pavel Dundr¹¹, Jeltsje Cnossen¹², Jan Willem Mens¹³, Cyrus Chargari¹⁴, Catherine Genestie¹⁵, Stefan Bijmolt¹⁶, Charles Gillham¹⁷, Ciaran O’Riain¹⁸, Tanja Stam¹⁹, Ina Jurgenliemk-Schulz²⁰, Moritz Hamann²¹, Vincent Smit²², Tjalling Bosse²², Carien Creutzberg¹

¹Leiden University Medical Center, Radiation Oncology, Leiden, The Netherlands; ²Maastricht Radiation Oncology Clinic, Radiation Oncology, Maastricht, The Netherlands; ³Radiotherapy Group, Radiation Oncology, Arnhem, The Netherlands; ⁴University of Tübingen, Women’s Health, Tübingen, Germany; ⁵University of Tübingen, Pathology, Tübingen, Germany; ⁶Institute Verbeeten, Radiation Oncology, Tilburg, The Netherlands; ⁷Netherlands Cancer Institute, Radiation Oncology, Amsterdam, The Netherlands; ⁸Amsterdam University Medical Centers, Radiation Oncology, Amsterdam, The Netherlands; ⁹Radiotherapy Institute Friesland, Radiation Oncology, Leeuwarden, The Netherlands; ¹⁰First Faculty of Medicine, Charles University and General University Hospital, Obstetrics and Gynaecology, Prague, Czech Republic; ¹¹First Faculty of Medicine, Charles University and General University Hospital, Institute of Pathology, Prague, Czech Republic; ¹²Catharina Hospital, Radiation Oncology, Eindhoven, The Netherlands; ¹³Erasmus MC – Cancer Institute, Radiation Oncology, Rotterdam, The Netherlands; ¹⁴Institut Gustave Roussy, Radiation Oncology, Villejuif, France; ¹⁵Institut Gustave Roussy, Pathology, Villejuif, France; ¹⁶University Medical Center Groningen, Radiation Oncology, Groningen, The Netherlands; ¹⁷St. Luke’s Hospital, Radiation Oncology, Dublin, Ireland; ¹⁸Trinity St James’s Cancer Institute, St. James’s Hospital, Histopathology, Dublin, Ireland; ¹⁹Haaglanden Medical Center, Radiation Oncology, The Hague, The Netherlands; ²⁰University Medical Center Utrecht, Radiation Oncology, Utrecht, The Netherlands; ²¹Rotkreuzklinikum München, Women’s Health, München, The Netherlands; ²²Leiden University Medical Center, Pathology, Leiden, The Netherlands

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Purpose or Objective

The PORTEC-4a trial is the first study worldwide that introduced molecular factors in decision making on adjuvant treatment for women with high-intermediate risk endometrial cancer (HIR-EC). For patients randomised to the intervention arm, adjuvant treatment was based upon a molecular-integrated risk profile. Here we report on the feasibility of determining the molecular-integrated risk profile and starting adjuvant therapy within a clinically acceptable time frame after surgery.

Material and Methods

Women with complete surgical resection of HIR-EC were eligible. Patients were randomized (2:1) between individualized treatment based upon the molecular-integrated risk profile and standard vaginal brachytherapy (VBT). In patients with a favourable profile, adjuvant treatment was omitted; in those with an intermediate profile, VBT was recommended, and the small group with an unfavourable profile received pelvic radiotherapy. After randomisation, histopathological slides and representative tumour block were obtained by pathology laboratories which had been validated for review and determination of the molecular-integrated risk profile. Histopathological, immunohistochemical and molecular analyses were performed, after which risk groups assignment was done and adjuvant therapy could be initiated, figure 1. Accrual completed in December 2021 and final results are expected in 2024.

Results

Between 2016 and 2021, 569 patients were enrolled of whom 361 evaluable patients were allocated to the intervention arm. Twelve pathology laboratories in 8 European countries were validated during the conducted of the trial. Of 284 patients the molecular-integrated risk profile was determined at the LUMC department of Pathology and 77 at laboratories elsewhere. Average time between randomisation and result of the risk profile was 2 weeks (range 0 – 6 weeks) for LUMC and 3 weeks (0 – 12 weeks) for other laboratories. For 48.5% of participants pathology review took longer than 2 weeks, of which 1.1% more than 6 weeks. Median time between surgery and start of adjuvant treatment was 7 weeks (0 – 13 weeks); this was 7 weeks (5 – 12 weeks) for patients receiving VBT and 8 weeks (5 – 13 weeks) for pelvic radiotherapy. Less than 10% of patients started adjuvant treatment more than 9 weeks after surgery. Only in 2 (0.5%) cases determination of the risk profile failed due to technical issues; these patients received VBT according to protocol.

Conclusion

Determination of the molecular-integrated risk profile for participants of the PORTEC-4a trial was proven to be feasible within a clinically acceptable time frame. It is shown that prompt sending of the tumour material, excellent collaboration between clinicians, pathologists within and between centers is essential to ensure timely results and treatment. Development of quicker and cheaper DNA-sequencing methods might greatly facilitate implementation of the molecular-integrated risk profile in routine clinical practice.