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Clinical trial
PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer
  1. Anne Sophie V M van den Heerik1,
  2. Nanda Horeweg1,
  3. Remi A Nout2,
  4. Ludy C H W Lutgens3,
  5. Elzbieta M van der Steen-Banasik4,
  6. G Henrieke Westerveld5,
  7. Hetty A van den Berg6,
  8. Annerie Slot7,
  9. Friederike L A Koppe8,
  10. Stefan Kommoss9,
  11. Jan Willem M Mens2,
  12. Marlies E Nowee10,
  13. Stefan Bijmolt11,
  14. David Cibula12,
  15. Tanja C Stam13,
  16. Ina M Jurgenliemk-Schulz14,
  17. An Snyers15,
  18. Moritz Hamann16,
  19. Aleida G Zwanenburg17,
  20. Veronique L M A Coen18,
  21. Katrien Vandecasteele19,
  22. Charles Gillham20,
  23. Cyrus Chargari21,
  24. Karen W Verhoeven-Adema22,
  25. Hein Putter23,
  26. Wilbert B van den Hout24,
  27. Bastiaan G Wortman1,
  28. Hans W Nijman25,
  29. Tjalling Bosse26 and
  30. Carien L Creutzberg1
  1. 1Radiation Oncology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
  2. 2Radiation Oncology, Erasmus Medical Center - Cancer Institute, Rotterdam, Zuid-Holland, The Netherlands
  3. 3Radiation Oncology, Maastricht University Medical Centre+, Maastricht, Limburg, The Netherlands
  4. 4Radation Oncology, Radiotherapy Group, Arnhem, Gelderland, The Netherlands
  5. 5Radiation Oncology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Noord-Holland, The Netherlands
  6. 6Radiation Oncology, Catharina Hospital, Eindhoven, Noord-Brabant, The Netherlands
  7. 7Radiation Oncology, Radiotherapy Institute Friesland, Leeuwarden, Friesland, The Netherlands
  8. 8Radiation Oncology, Institute Verbeeten, Tilburg, Noord-Brabant, The Netherlands
  9. 9Women's Health, Universitätsklinikum Tübingen, Tübingen, Baden-Württemberg, Germany
  10. 10Radiation Oncology, Netherlands Cancer Institute, Amsterdam, Noord-Holland, The Netherlands
  11. 11Radiation Oncology, University Medical Centre Groningen, University of Groningen, Groningen, Groningen, The Netherlands
  12. 12Gynecologic Oncology Centre, Department of Obstetrics and Gynaecology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
  13. 13Radiation Oncology, Haaglanden Medical Center, Den Haag, Zuid-Holland, The Netherlands
  14. 14Radiation Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands
  15. 15Radiation Oncology, Radboudumc, Nijmegen, Gelderland, The Netherlands
  16. 16Women's Health, Rotkreuzklinikum Munchen, Munchen, Bayern, Germany
  17. 17Radiation Oncology, Isala Klinieken, Zwolle, Overijssel, The Netherlands
  18. 18Radiation Oncology, Zuidwest Radiotherapeutic Institute, Vlissingen, Zeeland, The Netherlands
  19. 19Radiation Oncology, University Hospital Ghent, Gent, Oost-Vlaanderen, Belgium
  20. 20Radiation Oncology, St. Luke's Hospital Dublin, Dublin, Ireland
  21. 21Radiation Oncology, Institut Gustave-Roussy, Villejuif, Île-de-France, France
  22. 22Comprehensive Cancer Centre Utrecht, Utrecht, The Netherlands
  23. 23Medical Statistics, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
  24. 24Biomedical Data Sciences, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
  25. 25Obstetrics & Gynecology, University Medical Centre Groningen, University of Groningen, Groningen, Groningen, The Netherlands
  26. 26Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
  1. Correspondence to Anne Sophie V M van den Heerik, Radiotherapy, Leiden Universitair Medisch Centrum, 2333 ZA Leiden, Zuid-Holland, Netherlands; a.v.m.van_den_heerik{at}lumc.nl

Abstract

Background Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients’ risk of recurrence based on molecular tumor characteristics.

Primary objectives To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy

Study hypothesis Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs.

Trial design A multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm).

Major inclusion/exclusion criteria Women aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1).

Endpoints The primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs.

Sample size 500 eligible and evaluable patients.

Estimated dates for completing accrual and presenting results Estimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023.

Trial registration The trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).

  • radiation oncology
  • endometrium
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/ijgc-2020-001929

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    Footnotes

    • Twitter @NandaHoreweg

    • Contributors ASVMvdH drafted the original manuscript, all authors contributed in reviewing, editing, and approving the final manuscript.

    • Funding This study was funded by KWF Kankerbestrijding (UL2011-5336 and 12376).

    • Competing interests ASVMvdH and NH report a research grant from the Dutch Cancer Society, during the conduct of the PORTEC-4a study. HWN reports non-financial support from Merck, grants from the Dutch Cancer Society, grants from AIMM, outside the submitted work. RAN reports grants from the Dutch Cancer Society, grants from the Dutch Research Council, grants from Elekta, grants from Varian, grants from Accuray, outside the submitted work. CC reports non-financial support from Roche, non-financial support from TherAguix, personal fees from Elekta, personal fees from MSD, personal fees from GSK, outside the submitted work. CLC reports grants from the Dutch Cancer Society, non-financial support from Elekta-Nucletron, during the conduct of the PORTEC-4a study. SK reports personal fees from GSK, personal fees from Roche, personal fees from MSD, personal fees from AstraZeneca, outside the submitted work.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; internally peer reviewed.

    • Data availability statement There are no data in this work.