High Intensity Functional Image Guided Vmat Lung Evasion (HI-FIVE)

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.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer Stage III
• Intervention / Treatment: Radiation: Functionally adapted, dose escalated VMAT radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalated functionally adapted radiation therapy; This is a single arm study	Radiation: Functionally adapted, dose escalated VMAT radiotherapy; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peter MacCallum Cancer Centre, Australia
• Investigators: Principal Investigator: Nicholas W Bucknell, MBBS (hons), Peter Mac Callum Cancer Centre

Publications and helpful links

General Publications

• Bucknell N, Hardcastle N, Jackson P, Hofman M, Callahan J, Eu P, Iravani A, Lawrence R, Martin O, Bressel M, Woon B, Blyth B, MacManus M, Byrne K, Steinfort D, Kron T, Hanna G, Ball D, Siva S. Single-arm prospective interventional study assessing feasibility of using gallium-68 ventilation and perfusion PET/CT to avoid functional lung in patients with stage III non-small cell lung cancer. BMJ Open. 2020 Dec 10;10(12):e042465. doi: 10.1136/bmjopen-2020-042465.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): January 27, 2021
• Study Completion (Actual): January 27, 2021

Study Registration Dates

• First Submitted: May 30, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): May 19, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: HREC/18/PMCC/23; U1111-1208-1546 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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