MArkerless image Guidance using Intrafraction Kilovoltage x-ray imaging (MAGIK): study protocol for a phase I interventional study for lung cancer radiotherapy

Abstract

Introduction: In radiotherapy, tumour tracking leads the radiation beam to accurately target the tumour while it moves in a complex and unpredictable way due to respiration. Several tumour tracking techniques require the implantation of fiducial markers around the tumour, a procedure that involves unnecessary risks and costs. Markerless tumour tracking (MTT) negates the need for implanted markers, potentially enabling accurate and optimal radiotherapy in a non-invasive way.

Methods and analysis: We will perform a phase I interventional trial called MArkerless image Guidance using Intrafraction Kilovoltage x-ray imaging (MAGIK) to investigate the technical feasibility of the MTT technology developed at the University of Sydney (sponsor). 30 participants will undergo the current standard of care lung stereotactic ablative radiation therapy, with the exception that kilovoltage X-ray images will be acquired continuously during treatment delivery to enable MTT. If MTT indicates that the mean lung tumour position has shifted >3 mm, a warning message will be displayed to indicate the need for a treatment intervention. The radiation therapist will then pause the treatment, shift the treatment couch to account for the shift in tumour position and resume the treatment. Participants will be implanted with fiducial markers, which act as the ground truth for evaluating the accuracy of MTT. MTT is considered feasible if the tracking accuracy is <3 mm in each dimension for >80% of the treatment time.

Ethics and dissemination: The MAGIK trial has received ethical approval from The Alfred Human Research Ethics Committee and has been registered with ClinicalTrials.gov with the Identifier: NCT04086082. Estimated time of first recruitment is early 2022. The study recruitment and data analysis phases will be performed concurrently. Treatment for all 30 participants is expected to be completed within 2 years and participant follow-up within a total duration of 7 years. Findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number: NCT04086082; Pre-result.

Keywords: medical physics; radiation oncology; radiotherapy.

Figure 1

MTT will monitor the tumour position in real-time, ensuring optimal targeting, thereby improving local control and reducing radiation toxicity. MTT, markerless tumour tracking.

Figure 2

The workflow of the developed MTT. A personalised anatomic model of the patient is built using the four-dimensional-CT after treatment planning. during treatment, Kv X-ray images are streamed and processed in real time. The diaphragm position is first identified as a guide to localising the tumour. Then, the anatomic model is used to identify the tumour position. Using a statistical model, the three-dimensional (3D) position of the tumour is then estimated from the two-dimensional (2D) segmented position. This process is repeated for every new Kv image at a frequency of seven frames per second.

Figure 3

Participant recruitment flow chart for the MAGIK trial. MAGIK, MArkerless image Guidance using Intrafraction Kilovoltage X-ray imaging; NSCLC, non-small cell lung cancer; SABR, stereotactic ablative radiation therapy.

Figure 4

Flowchart of the lung stereotactic ablative radiation therapy (SABR) treatment procedure with markerless tumour tracking (MTT). The steps of MTT (blue blocks) are integrated into the original lung SABR workflow (grey blocks) throughout the stages treatment planning (planning), patient setup (setup), treatment delivery and post-treatment (post).