Safety and early organ preservation outcomes after dose escalation with MR-guided radiotherapy for rectal cancer (preRADAR): A phase I trial

H Eijkelenkamp; M E Verweij; G Grimbergen; M Tanaka; C M Kensen; T Janssen; T Vijlbrief; W M U van Grevenstein; L M G Moons; M Koopman; M M Lacle; M N G J A Braat; M Maas; E C J Consten; A Pronk; A B Smits; J T Heikens; S G Elias; H M Verkooijen; G J Meijer; A Couwenberg; M P W Intven

doi:10.1016/j.ctro.2026.101191

Safety and early organ preservation outcomes after dose escalation with MR-guided radiotherapy for rectal cancer (preRADAR): A phase I trial

H Eijkelenkamp^*
, M E Verweij
, G Grimbergen
, M Tanaka
, C M Kensen
, T Janssen
, T Vijlbrief
, W M U van Grevenstein
, L M G Moons
, M Koopman
, M M Lacle
, M N G J A Braat
, M Maas
, E C J Consten
, A Pronk
, A B Smits
, J T Heikens
, S G Elias
, H M Verkooijen
, G J Meijer

A Couwenberg, M P W Intven

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND AND PURPOSE: Organ preservation is a desirable goal for patients with rectal cancer. Magnetic resonance-guided radiotherapy (MRgRT) enables precise dose delivery and online adaptation. This phase I study (preRADAR) evaluated maximum tolerated dose (MTD) of short course radiotherapy (SCRT; 5x5 Gy) with a subsequent boost using MRgRT in intermediate-risk rectal cancer.

MATERIALS AND METHODS: the trial had a 6 + 3 dose-escalation design. Patients staged T3c-d(MRF-)N0M0 or T1-3(MRF-)N1M0 were treated on a 1.5 Tesla MR-linac with short-course radiotherapy (SCRT; 5 × 5 Gy) followed by 2-4 daily 5 Gy GTV boosts according to the dose level. Safety was assessed by incidence of acute and perioperative dose-limiting toxicities (DLTs) within prespecified time windows and stopping boundaries. Secondary endpoints included technical feasibility (boost PTV V95% > 90%) and organ preservation at six months.

RESULTS: Out of 31 patients screened, sixteen were treated across three dose levels. All fractions were delivered as planned and all adaptive boost fractions achieved the predefined feasibility criterion (PTV V95% >90%). No acute DLTs occurred. Three perioperative DLTs were observed, including two anastomotic leaks requiring reoperation. The MTD was not identified; dose level 2 (SCRT + 4 × 5 Gy boosts) was the highest dose level completed within the DLT stopping boundaries, achieving a 26-week organ preservation rate of 56% (5/9).

CONCLUSION: MRgRT-based enables dose escalation following SCRT in intermediate-risk rectal cancer. The highest evaluated dose level, 4 × 5 Gy GTV boosts after SCRT, was considered safe within the predefined DLT boundaries and feasible for further evaluation.

Original language	English
Article number	101191
Journal	Clinical and translational radiation oncology
Volume	60
Early online date	24 May 2026
DOIs	https://doi.org/10.1016/j.ctro.2026.101191
Publication status	E-pub ahead of print - 24 May 2026

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PIIS2405630826000868Final published version, 1.62 MBLicence: CC BY

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Eijkelenkamp, H., Verweij, M. E., Grimbergen, G., Tanaka, M., Kensen, C. M., Janssen, T., Vijlbrief, T., van Grevenstein, W. M. U., Moons, L. M. G., Koopman, M., Lacle, M. M., Braat, M. N. G. J. A., Maas, M., Consten, E. C. J., Pronk, A., Smits, A. B., Heikens, J. T., Elias, S. G., Verkooijen, H. M., ... Intven, M. P. W. (2026). Safety and early organ preservation outcomes after dose escalation with MR-guided radiotherapy for rectal cancer (preRADAR): A phase I trial. Clinical and translational radiation oncology, 60, Article 101191. Advance online publication. https://doi.org/10.1016/j.ctro.2026.101191

@article{b31d00e8b6f844a59172503ec2264008,

title = "Safety and early organ preservation outcomes after dose escalation with MR-guided radiotherapy for rectal cancer (preRADAR): A phase I trial",

abstract = "BACKGROUND AND PURPOSE: Organ preservation is a desirable goal for patients with rectal cancer. Magnetic resonance-guided radiotherapy (MRgRT) enables precise dose delivery and online adaptation. This phase I study (preRADAR) evaluated maximum tolerated dose (MTD) of short course radiotherapy (SCRT; 5x5 Gy) with a subsequent boost using MRgRT in intermediate-risk rectal cancer.MATERIALS AND METHODS: the trial had a 6 + 3 dose-escalation design. Patients staged T3c-d(MRF-)N0M0 or T1-3(MRF-)N1M0 were treated on a 1.5 Tesla MR-linac with short-course radiotherapy (SCRT; 5 × 5 Gy) followed by 2-4 daily 5 Gy GTV boosts according to the dose level. Safety was assessed by incidence of acute and perioperative dose-limiting toxicities (DLTs) within prespecified time windows and stopping boundaries. Secondary endpoints included technical feasibility (boost PTV V95\% > 90\%) and organ preservation at six months.RESULTS: Out of 31 patients screened, sixteen were treated across three dose levels. All fractions were delivered as planned and all adaptive boost fractions achieved the predefined feasibility criterion (PTV V95\% >90\%). No acute DLTs occurred. Three perioperative DLTs were observed, including two anastomotic leaks requiring reoperation. The MTD was not identified; dose level 2 (SCRT + 4 × 5 Gy boosts) was the highest dose level completed within the DLT stopping boundaries, achieving a 26-week organ preservation rate of 56\% (5/9).CONCLUSION: MRgRT-based enables dose escalation following SCRT in intermediate-risk rectal cancer. The highest evaluated dose level, 4 × 5 Gy GTV boosts after SCRT, was considered safe within the predefined DLT boundaries and feasible for further evaluation.",

author = "H Eijkelenkamp and Verweij, \{M E\} and G Grimbergen and M Tanaka and Kensen, \{C M\} and T Janssen and T Vijlbrief and \{van Grevenstein\}, \{W M U\} and Moons, \{L M G\} and M Koopman and Lacle, \{M M\} and Braat, \{M N G J A\} and M Maas and Consten, \{E C J\} and A Pronk and Smits, \{A B\} and Heikens, \{J T\} and Elias, \{S G\} and Verkooijen, \{H M\} and Meijer, \{G J\} and A Couwenberg and Intven, \{M P W\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/",

year = "2026",

month = may,

day = "24",

doi = "10.1016/j.ctro.2026.101191",

language = "English",

volume = "60",

journal = "Clinical and translational radiation oncology",

issn = "2405-6308",

publisher = "Elsevier Ireland Ltd",

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Eijkelenkamp, H, Verweij, ME, Grimbergen, G, Tanaka, M, Kensen, CM, Janssen, T, Vijlbrief, T, van Grevenstein, WMU, Moons, LMG , Koopman, M , Lacle, MM, Braat, MNGJA, Maas, M, Consten, ECJ, Pronk, A, Smits, AB, Heikens, JT, Elias, SG , Verkooijen, HM, Meijer, GJ, Couwenberg, A & Intven, MPW 2026, 'Safety and early organ preservation outcomes after dose escalation with MR-guided radiotherapy for rectal cancer (preRADAR): A phase I trial', Clinical and translational radiation oncology, vol. 60, 101191. https://doi.org/10.1016/j.ctro.2026.101191

TY - JOUR

T1 - Safety and early organ preservation outcomes after dose escalation with MR-guided radiotherapy for rectal cancer (preRADAR)

T2 - A phase I trial

AU - Eijkelenkamp, H

AU - Verweij, M E

AU - Grimbergen, G

AU - Tanaka, M

AU - Kensen, C M

AU - Janssen, T

AU - Vijlbrief, T

AU - van Grevenstein, W M U

AU - Moons, L M G

AU - Koopman, M

AU - Lacle, M M

AU - Braat, M N G J A

AU - Maas, M

AU - Consten, E C J

AU - Pronk, A

AU - Smits, A B

AU - Heikens, J T

AU - Elias, S G

AU - Verkooijen, H M

AU - Meijer, G J

AU - Couwenberg, A

AU - Intven, M P W

N1 - Publisher Copyright: © 2026 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

PY - 2026/5/24

Y1 - 2026/5/24

N2 - BACKGROUND AND PURPOSE: Organ preservation is a desirable goal for patients with rectal cancer. Magnetic resonance-guided radiotherapy (MRgRT) enables precise dose delivery and online adaptation. This phase I study (preRADAR) evaluated maximum tolerated dose (MTD) of short course radiotherapy (SCRT; 5x5 Gy) with a subsequent boost using MRgRT in intermediate-risk rectal cancer.MATERIALS AND METHODS: the trial had a 6 + 3 dose-escalation design. Patients staged T3c-d(MRF-)N0M0 or T1-3(MRF-)N1M0 were treated on a 1.5 Tesla MR-linac with short-course radiotherapy (SCRT; 5 × 5 Gy) followed by 2-4 daily 5 Gy GTV boosts according to the dose level. Safety was assessed by incidence of acute and perioperative dose-limiting toxicities (DLTs) within prespecified time windows and stopping boundaries. Secondary endpoints included technical feasibility (boost PTV V95% > 90%) and organ preservation at six months.RESULTS: Out of 31 patients screened, sixteen were treated across three dose levels. All fractions were delivered as planned and all adaptive boost fractions achieved the predefined feasibility criterion (PTV V95% >90%). No acute DLTs occurred. Three perioperative DLTs were observed, including two anastomotic leaks requiring reoperation. The MTD was not identified; dose level 2 (SCRT + 4 × 5 Gy boosts) was the highest dose level completed within the DLT stopping boundaries, achieving a 26-week organ preservation rate of 56% (5/9).CONCLUSION: MRgRT-based enables dose escalation following SCRT in intermediate-risk rectal cancer. The highest evaluated dose level, 4 × 5 Gy GTV boosts after SCRT, was considered safe within the predefined DLT boundaries and feasible for further evaluation.

AB - BACKGROUND AND PURPOSE: Organ preservation is a desirable goal for patients with rectal cancer. Magnetic resonance-guided radiotherapy (MRgRT) enables precise dose delivery and online adaptation. This phase I study (preRADAR) evaluated maximum tolerated dose (MTD) of short course radiotherapy (SCRT; 5x5 Gy) with a subsequent boost using MRgRT in intermediate-risk rectal cancer.MATERIALS AND METHODS: the trial had a 6 + 3 dose-escalation design. Patients staged T3c-d(MRF-)N0M0 or T1-3(MRF-)N1M0 were treated on a 1.5 Tesla MR-linac with short-course radiotherapy (SCRT; 5 × 5 Gy) followed by 2-4 daily 5 Gy GTV boosts according to the dose level. Safety was assessed by incidence of acute and perioperative dose-limiting toxicities (DLTs) within prespecified time windows and stopping boundaries. Secondary endpoints included technical feasibility (boost PTV V95% > 90%) and organ preservation at six months.RESULTS: Out of 31 patients screened, sixteen were treated across three dose levels. All fractions were delivered as planned and all adaptive boost fractions achieved the predefined feasibility criterion (PTV V95% >90%). No acute DLTs occurred. Three perioperative DLTs were observed, including two anastomotic leaks requiring reoperation. The MTD was not identified; dose level 2 (SCRT + 4 × 5 Gy boosts) was the highest dose level completed within the DLT stopping boundaries, achieving a 26-week organ preservation rate of 56% (5/9).CONCLUSION: MRgRT-based enables dose escalation following SCRT in intermediate-risk rectal cancer. The highest evaluated dose level, 4 × 5 Gy GTV boosts after SCRT, was considered safe within the predefined DLT boundaries and feasible for further evaluation.

U2 - 10.1016/j.ctro.2026.101191

DO - 10.1016/j.ctro.2026.101191

M3 - Article

C2 - 42290893

SN - 2405-6308

VL - 60

JO - Clinical and translational radiation oncology

JF - Clinical and translational radiation oncology

M1 - 101191

ER -

Safety and early organ preservation outcomes after dose escalation with MR-guided radiotherapy for rectal cancer (preRADAR): A phase I trial

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