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.

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.