Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial
Introduction Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a...
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BMJ Publishing Group
2023-06-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/13/6/e065010.full |
| _version_ | 1797802929216815104 |
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| author | Miangela M Lacle Sjoerd G Elias Leon M G Moons Helena M Verkooijen Manon N G J A Braat Myriam Chalabi Corrie A M Marijnen Femke P Peters Brechtje A Grotenhuis Miriam Koopman Petur Snaebjornsson Esther Consten Wilhelmina M U van Grevenstein Maaike E Verweij Max D Tanaka Chavelli M Kensen Uulke A van der Heide Tomas Janssen Tineke Vijlbrief Monique Maas Inge L Huibregtse Remond Fijneman Apollo Pronk Anke B Smits Joost T Heikens Hidde Eijkelenkamp Maartje M C Schoenmakers Gert J Meijer Martijn Intven |
| author_facet | Miangela M Lacle Sjoerd G Elias Leon M G Moons Helena M Verkooijen Manon N G J A Braat Myriam Chalabi Corrie A M Marijnen Femke P Peters Brechtje A Grotenhuis Miriam Koopman Petur Snaebjornsson Esther Consten Wilhelmina M U van Grevenstein Maaike E Verweij Max D Tanaka Chavelli M Kensen Uulke A van der Heide Tomas Janssen Tineke Vijlbrief Monique Maas Inge L Huibregtse Remond Fijneman Apollo Pronk Anke B Smits Joost T Heikens Hidde Eijkelenkamp Maartje M C Schoenmakers Gert J Meijer Martijn Intven |
| author_sort | Miangela M Lacle |
| collection | DOAJ |
| description | Introduction Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4–8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT.Methods and analysis The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction.Ethics and dissemination The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals.Trial registration number WHO International Clinical Trials Registry (NL8997; https://trialsearch.who.int). |
| first_indexed | 2024-03-13T05:13:08Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-03-13T05:13:08Z |
| publishDate | 2023-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-8286f62013fd42359e5ab23a6da2c02a2023-06-16T02:00:06ZengBMJ Publishing GroupBMJ Open2044-60552023-06-0113610.1136/bmjopen-2022-065010Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trialMiangela M Lacle0Sjoerd G Elias1Leon M G Moons2Helena M Verkooijen3Manon N G J A Braat4Myriam Chalabi5Corrie A M Marijnen6Femke P Peters7Brechtje A Grotenhuis8Miriam Koopman9Petur Snaebjornsson10Esther Consten11Wilhelmina M U van Grevenstein12Maaike E Verweij13Max D Tanaka14Chavelli M Kensen15Uulke A van der Heide16Tomas Janssen17Tineke Vijlbrief18Monique Maas19Inge L Huibregtse20Remond Fijneman21Apollo Pronk22Anke B Smits23Joost T Heikens24Hidde Eijkelenkamp25Maartje M C Schoenmakers26Gert J Meijer27Martijn Intven2810 Department of Pathology, University Medical Center Utrecht, Utrecht, The NetherlandsJulius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands1 Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The NetherlandsprofessorDivision of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The NetherlandsMedical Oncology, Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis, Amsterdam, The Netherlands12 Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands12 Department of Radiotherapy, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Surgery, Erasmus Medical Centre, Rotterdam, The NetherlandsDepartment of Medical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands2Department of Pathology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Surgery, Meander Medical Centre, Amersfoort, The NetherlandsDepartment of Surgical Oncology, General Surgery, UMC Utrecht, Utrecht, The NetherlandsDepartment of Radiation-Oncology, University Medical Centre Utrecht, Utrecht, The NetherlandsDepartment of Radiation-Oncology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Radiation-Oncology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Radiation-Oncology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Radiation-Oncology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Radiation-Oncology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Radiology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Gastroenterology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Surgery, Diakonessenhuis Utrecht Zeist Doorn, Utrecht, The NetherlandsDepartment of Surgery, Sint Antonius Hospital, Nieuwegein, The NetherlandsDepartment of Surgery, Hospital Rivierenland, Tiel, The NetherlandsDepartment of Radiation-Oncology, University Medical Centre Utrecht, Utrecht, The NetherlandsDepartment of Radiation-Oncology, University Medical Centre Utrecht, Utrecht, The NetherlandsDepartment of Radiation-Oncology, University Medical Centre Utrecht, Utrecht, The NetherlandsDepartment of Radiation-Oncology, University Medical Centre Utrecht, Utrecht, The NetherlandsIntroduction Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4–8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT.Methods and analysis The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction.Ethics and dissemination The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals.Trial registration number WHO International Clinical Trials Registry (NL8997; https://trialsearch.who.int).https://bmjopen.bmj.com/content/13/6/e065010.full |
| spellingShingle | Miangela M Lacle Sjoerd G Elias Leon M G Moons Helena M Verkooijen Manon N G J A Braat Myriam Chalabi Corrie A M Marijnen Femke P Peters Brechtje A Grotenhuis Miriam Koopman Petur Snaebjornsson Esther Consten Wilhelmina M U van Grevenstein Maaike E Verweij Max D Tanaka Chavelli M Kensen Uulke A van der Heide Tomas Janssen Tineke Vijlbrief Monique Maas Inge L Huibregtse Remond Fijneman Apollo Pronk Anke B Smits Joost T Heikens Hidde Eijkelenkamp Maartje M C Schoenmakers Gert J Meijer Martijn Intven Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial BMJ Open |
| title | Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial |
| title_full | Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial |
| title_fullStr | Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial |
| title_full_unstemmed | Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial |
| title_short | Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial |
| title_sort | towards response adaptive radiotherapy for organ preservation for intermediate risk rectal cancer preradar protocol of a phase i dose escalation trial |
| url | https://bmjopen.bmj.com/content/13/6/e065010.full |
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