Markerless Image Guidance Using Intrafraction Kolovoltage X-ray Imaging for Lung Cancer Radiotherapy

Validation of Markerless Image Guidance Using Intrafraction Kolovoltage X-ray Imaging Using Implanted Fiducials: Phase I Observational Study of Lung Cancer Radiotherapy

In radiotherapy, tumour tracking allows us to ensure the radiation beam is accurately targeting the tumour while it moves in a complex and unpredictable way. Most tumour tracking techniques require the implantation of fiducial markers around the tumour. Markerless Tumour Tracking negates the need for implanted markers, enabling accurate and optimal cancer radiotherapy in a non-invasive way.

We will perform a phase I observational trial investigating the feasibility of the Markerless Tumour Tracking technology. Markerless Tumour Tracking will be integrated with existing treatment machines to provide real-time monitoring of tumour motion during treatment delivery. Eligible patients are implanted with fiducial markers, which act as the ground truth for evaluating the accuracy of Markerless Tumour Tracking. The patients will undergo the current standard of care radiotherapy, with the exception that kilovoltage x-ray images will be acquired continuously during treatment delivery and used to calculate online Markerless Tumour Tracking. Markerless Tumour Tracking determines the mean tumour position calculated over the most recent 15 seconds and displays shifts exceeding 3 mm.

The trial will be a single-institution study recruiting only at RNSH Radiation Oncology Department.

As this trial investigates feasibility, our focus will be on estimating the proportion of treatment time in which the Markerless Tumour Tracking is within acceptable limits.

Inclusion Criteria:

1. Aged 18 or older.
2. Has provided written Informed Consent for participation in this trial and is willing to comply with the study.
3. Patients undergoing external beam radiotherapy.
4. Histologically proven Stage I NSCLC or oligometastatic lung metastases (3 or less).
5. Diagnostic CT prior to insertion of fiducial markers.
6. Patient must be able to have fiducial markers placed in the lung (if on anticoagulants, must be cleared by LMO or cardiologist).
7. ECOG performance status 0-2.
8. A maximum of three metastases to the lung from any non-haematological malignancy. Multiple metastases will be treated separately.
9. 1 cm ≤ Tumour diameter in any dimension ≤ = 5 cm.
10. The distance between the tumour centroid and the top end of the diaphragm is <=8 cm.

Exclusion Criteria:

1. Patient has low respiratory performance as evaluated by the physicians.
2. Previous high-dose thoracic radiotherapy.
3. Less than one fiducial marker implanted in the lung.
4. Fiducial markers are too far from the tumour centroid (>9 cm).
5. Cytotoxic chemotherapy within 3 weeks of commencement of treatment, or concurrently with treatment. Hormonal manipulation agents are allowable (e.g. aromatase inhibitors, selective oestrogen receptor modulators, and gonadotropin releasing hormone receptor modulators).
6. Targeted agents (such as sunitinib, bevacizumab and tarceva) within 7 days of commencement of treatment, concurrently with treatment or 7 days after radiotherapy.
7. Women who are pregnant or lactating.
8. Unwilling or unable to give informed consent.
9. Unwilling or unable to complete quality of life questionnaires.