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 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).

Clinical workflow for treating patients with a metallic hip prosthesis using magnetic resonance imaging-guided radiotherapy.

BACKGROUND & PURPOSE: Metallic prostheses distort the magnetic field during magnetic resonance imaging (MRI), leading to geometric distortions and signal loss. The purpose of this work was to develop a method to determine eligibility for MRI-guided radiotherapy (MRIgRT) on a per patient basis by estimating the magnitude of geometric distortions inside the clinical target volume (CTV). MATERIALS & METHODS: Three patients with prostate cancer and hip prosthesis, treated using MRIgRT, were included. Eligibility for MRIgRT was based on computed tomography and associated CTV delineations, together with a field-distortion (B0) map and anatomical images acquired during MR simulation. To verify the method, B0 maps made during MR simulation and each MRIgRT treatment fraction were compared. RESULTS: Estimates made during MR simulation of the magnitude of distortions inside the CTV were 0.43 mm, 0.19 mm and 2.79 mm compared to the average over all treatment fractions of 1.40 mm, 0.32 mm and 1.81 mm, per patient respectively. CONCLUSIONS: B0 map acquisitions prior to treatment can be used to estimate the magnitude of distortions during MRIgRT to guide the decision on eligibility for MRIgRT of prostate cancer patients with metallic hip implants.

Reproducibility of the MRI-defined spinal cord position in stereotactic radiotherapy for spinal oligometastases.

PURPOSE: To establish the reproducibility of the MRI-defined spinal cord position within the spinal canal. MATERIALS AND METHODS: We acquired T1- and T2-weighted MRI scans of 15 volunteers on spine levels C7, T8 or L2. The scan protocol was repeated several times for different postures and time intervals. We determined the spinal cord shift (LR, AP, CC) using a rigid, grey value, vertebral body registration, followed by a spinal cord registration. We tested the sensitivity of our method, introducing artificial spinal cord shifts by varying the size and direction of the water-fat-shift (WFS) of the MR sequences. RESULTS: The spinal cord position on MRI is reproducible within approximately 0.2mm SD (LR, AP) and 0.7mm SD (CC) when reproducing the posture on the same day, as well as several weeks later. However, when comparing different postures, shifts of ∼1.5mm were found. Varying the WFS difference between scans (0.6-3.0mm) induced equivalent virtual spinal cord shifts (0.5-2.5mm). CONCLUSIONS: Displacement of the spinal cord inside the spinal canal may occur as a result of posture change. Considering the total geometric accuracy of spine SBRT, MRI-defined spinal cord position is sufficiently reproducible and requires no addition to the typical setup-and-intrafraction motion PRV margin if posture is identical throughout the RT process.