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

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.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer; Markerless Image Guidance; Intrafraction Kolovoltage X-ray Imaging
• Intervention / Treatment: Radiation: Markerless Tumour Tracking

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

• Study Contact: Name: Carol Kwong, RN; Phone Number: 31339 +61294631339; Email: carolyn.kwong@health.nsw.gov.au
• Study Contact Backup: Name: Heidi Tsang, RN; Phone Number: 31340 +61294631340; Email: heidi.tsang@health.nsw.gov.au

Study Locations

• Australia
  • New South Wales
    • Saint Leonards, New South Wales, Australia, 2065
      • Recruiting
      • Royal North Shore Hospital
      • Contact: Heidi Tsang, RN; Phone Number: 31340 +61294631340; Email: heidi.tsang@health.nsw.gov.au
      • Contact: Carol Kwong, RN; Phone Number: 31339 +61 29463 1339; Email: carolyn.kwong@health.nsw.gov.au
      • Principal Investigator: Dasantha Jayamanne, MBBS/FRANZCR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Adults >=18 years with NSCLC

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Markerless; Markerless Tumour Tracking will be used to observe the radiation beam is accurately targeting the tumour.	Radiation: Markerless Tumour Tracking; Intrafraction Kolovoltage X-ray Imaging using Fiducials

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Markerless Tumour Tracking	to demonstrate the feasibility of Markerless Tumour Tracking for motion-adaptive lung cancer radiotherapy as assessed by agreement between markerless and marker-based tracking within 3 mm for at least 80% of the beam-on time as assessed in off-line analyses.	6 months after recruitment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Markerless Tumour Tracking outcome	To identify cohort of patients on which markerless Tumour tracking performs well or poorly	6 months after treatment of last fraction
Accuracy	To quantify the accuracy of marker-based tracking by comparison with MV-kV triangulation or visual inspection	6 months after treatment of last fraction
Magnitude	To investigate the magnitude of surrogacy of lung tumour motion, ie the difference between tumour motion and implanted marker motion	6 months after treatment of last fraction
Correlation	To investigate the correlation between external and internal motion using infrared/optical imaging	6 months after treatment of last fraction
Suitability	To investigate the suitability and frequency of correcting for tumour baseline shifts based on a variety of tolerance criteria and with different methods	6 months after treatment of last fraction
Frequency	To investigate the frequency of correcting for tumour baseline shifts based on a variety of tolerance criteria and with different methods	6 months after treatment of last fraction
Feasibility of outcomes prediction	To investigate the feasibility of predicting treatment outcomes based on patient and imaging information	6 months after treatment of last fraction
Outcomes	Participants will be followed for 2 years to determine patient outcomes, including radiation therapy toxicity, local control (whether the tumour has spread) and survival	6 months after treatment of last fraction
Historical	2 year outcomes will be compared to historical outcomes reported from our lung Departmental SBRT database	6 months after treatment of last fraction
Ineligibility	To record the number of patients ineligible after marker insertion due to positioning of markers, or due to complications with the implantation procedure	6 months after treatment of last fraction
Radiomic Features	To investigate the feasibility of extracting radiomic features from CT, CBCT, and kV images to predict tumour volumes, tracking accuracy, treatment response, and patient outcomes.	6 months after treatment of last fraction
X-ray dose	To report additional x-ray dose caused by imaging during treatment	6 months after treatment of last fraction

Collaborators and Investigators

• Sponsor: Royal North Shore Hospital
• Collaborators: University of Sydney
• Investigators: Principal Investigator: Dasantha Jayamanne, MD, Royal North Shore Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2020
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 12, 2020
• First Submitted That Met QC Criteria: March 12, 2020
• First Posted (Actual): March 17, 2020

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Lung Cancer; Radiotherapy; Fiducials; Markerless Tumour Tracking
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: VALKIM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No