High Intensity Functional Image Guided Vmat Lung Evasion

Study Overview
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Brief Summary
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This study is being performed to assess the feasibility of adapting radiotherapy plans based on functional lung information and increasing the dose to the primary tumour. This is a single arm interventional pilot study involving 20 patients. Aims Primary: to assess the feasibility of using ventilation and perfusion positron emission computed tomography (V/Q PET/CT) scans to adapt radiotherapy plans using Volumetric Modulated Arc Therapy (VMAT) to avoid regions of functional lung and deliver a higher dose to the primary tumour Secondary: to assess the incidence of acute and late radiotherapy toxicities, to quantify regional ventilation loss and regional perfusion loss on post treatment V/Q PET/CT, to assess associations of V/Q PET/CT with other functional lung imaging techniques, to assess overall survival, progression free survival and quality of life outcomes. Participants: 20 patients stage IIIa-c non-small cell lung cancer for curative intent radiotherapy. Methods: All patients will receive functional lung adapted 60 Gray (Gy) in 30 fractions to the primary and nodal planning target volume with a simultaneous integrated boost to the primary tumour to a total dose 69Gy in 30 fractions. Expected outcomes: That functionally adapted lung radiotherapy using V/Q PET/CT imaging and VMAT planning is technically feasible.

Official Title
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High Intensity Functional Image Guided Vmat Lung Evasion

Conditions
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Non Small Cell Lung Cancer Stage III

Intervention / Treatment
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* Radiation: Functionally adapted, dose escalated VMAT radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years; Written informed consent has been provided. Histologically or cytologically confirmed Non-Small Cell Lung Cancer Eastern Cooperative Oncology Group (ECOG) performance status 0-2 within 2 weeks prior to registration Locally advanced disease (stage IIIA, IIIB, IIIC as per American Joint Committee on Cancer AJCC, 8th ed.) as confirmed on staging 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) PET/CT No evidence of metastatic intracranial disease on CT brain with contrast or MRI Willing to participate in the full follow up schedule Planned for treatment with curative intent Exclusion Criteria: Participant is not able to tolerate supine position on PET/CT bed for the duration of the PET/CT acquisitions, is not cooperative, or needs continuous nursing (e.g. patient from Intensive Care Unit) or is unable to attend full course of follow up visits Pregnancy or Breast-feeding If history of a prior extra thoracic invasive malignancy (except non-melanomatous skin cancer) must be free from recurrence for a minimum of 3 years at the time of registration Prior radiotherapy to the lungs or mediastinum (a history of prior breast radiotherapy is not an exclusion) Prior known history of interstitial lung disease * A history of renal impairment or reaction to iodine contrast is not an exclusion criteria, if a patient has medical comorbidities that exclude the use of iodine contrasts, these exploratory investigations can be omitted.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalated functionally adapted radiation therapy<br>This is a single arm study | Radiation: Functionally adapted, dose escalated VMAT radiotherapy<br>* Volumetric Modulated Arc Therapy planning and treatment delivery to treat primary and nodal planning target volume with 60 Gy in 30 fractions and a simultaneous integrated boost to the primary tumour to a total dose 69Gy in 30 fractions while avoiding organs at risk including functional lung, heart and oesophagus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment will be considered feasible if all of the following criteria is met: Reduction in mean functional lung dose of ≥2%, functional lung volume receiving 20Gy of ≥4%, Mean heart dose is ≤30 Gy and relative heart volume receiving 50 Gy is <25% | To assess the technical feasibility of the delivery of personalised functional lung radiotherapy. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients with radiation pneumonitis will be assessed and graded using CTCAE v4.03 | To determine the incidence of grade ≥ 2 clinical or radiological pneumonitis after high dose functionally adapted radiotherapy | 1 year | 
| Quantitative voxel-wise comparison of ventilation PET/CT measures will be contoured using semi-automatic threshold based on the operator's discretion and compared with the pre-treatment ventilation PET/CT. | To quantify regional ventilation loss on post treatment ventilation PET/CT following functionally adapted lung radiotherapy. Measures will use the end-inspiratory and end-expiratory volume for each lung and lobe. Assessed on V PET/CT imaging from baseline to 3 months post treatment and from baseline to 12 months. | 3 months and 12 months following completion of radiotherapy | 
| Quantitative voxel-wise comparison of perfusion PET/CT measures will be contoured using semi-automatic threshold based on the operator's discretion and compared with the pre-treatment perfusion PET/CT. | To quantify regional perfusion loss on post treatment ventilation PET/CT following functionally adapted lung radiotherapy. Measures will use the end-inspiratory and end-expiratory volume for each lung and lobe. Assessed on Q PET/CT imaging from baseline to 3 months post treatment and from baseline to 12 months | 3 months and 12 months following completion of radiotherapy | 
| Quantitative voxel-wise comparison of CT Ventilation with Ventilation PET/CT | To assess the associations between ventilation PET/CT with inhale/exhale CT ventilation. This will be compared on imaging at baseline, 3 months post treatment and 12 month post treatment. | 3 months and 12 months following completion of radiotherapy | 
| Quantitative voxel-wise comparison of dual energy CT (DECT) iodine mapping with Perfusion PET/CT | To assess the associations between perfusion PET/CT with dual energy CT iodine mapping ventilation (DECT iodine mapping is regarded as a surrogate for pulmonary perfusion). This will be compared on imaging at baseline, 3 months post treatment and 12 month post treatment. | 3 months and 12 months following completion of radiotherapy | 
| The number of patients with Grade ≥ 2 cardiac toxicity will be assessed and graded using CTCAE v4.03. | This will be assessed by pre, 3 and 12 month post treatment transthoracic echocardiograms and ECG investigations. | 3 months and 12 months following completion of radiotherapy |