title: A prospective observational study of Gallium-68 ventilation and perfusion PET/CT during and after radiotherapy in patients with non-small cell lung cancer.
abstract: BACKGROUND
  Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancers, and is the leading cause of cancer deaths. Radiation therapy (RT), alone or in combination with chemotherapy, is the standard of care for curative intent treatment of patients with locally advanced or inoperable NSCLC. The ability to intensify treatment to achieve a better chance for cure is limited by the risk of injury to the surrounding lung.
  
  
  METHODS
  This is a prospective observational study of 60 patients with NSCLC receiving curative intent RT. Independent human ethics board approval was received from the Peter MacCallum Cancer Centre ethics committee. In this research, Galligas and Gallium-68 macroaggregated albumin (MAA) positron emission tomography (PET) imaging will be used to measure ventilation (V) and perfusion (Q) in the lungs. This is combined with computed tomography (CT) and both performed with a four dimensional (4D) technique that tracks respiratory motion. This state-of-the-art scan has superior resolution, accuracy and quantitative ability than previous techniques. The primary objective of this research is to observe changes in ventilation and perfusion secondary to RT as measured by 4D V/Q PET/CT. Additionally, we plan to model personalised RT plans based on an individual's lung capacity. Increasing radiation delivery through areas of poorly functioning lung may enable delivery of larger, more effective doses to tumours without increasing toxicity. By performing a second 4D V/Q PET/CT scan during treatment, we plan to simulate biologically adapted RT depending on the individual's accumulated radiation injury. Tertiary aims of the study are assess the prognostic significance of a novel combination of clinical, imaging and serum biomarkers in predicting for the risk of lung toxicity. These biomarkers include spirometry, (18)F-Fluorodeoxyglucose PET/CT, gamma-H2AX signals in hair and lymphocytes, as well as assessment of blood cytokines.
  
  
  CONCLUSIONS
  By correlating these biomarkers to toxicity outcomes, we aim to identify those patients early who will not tolerate RT intensification during treatment. This research is an essential step leading towards the design of future biologically adapted radiotherapy strategies to mitigate the risk of lung injury during dose escalation for patients with locally advanced lung cancer.
  
  
  BACKGROUND
  Universal Trial Number (UTN) U1111-1138-4421.
authors.affiliation: Division of Radiation Oncology and Cancer Imaging, St Andrews Place, East Melbourne 3002, Australia. shankar.siva@petermac.org.
authors.forename: Shankar
authors.initials: S
authors.lastname: Siva
authors.forename: Jason
authors.initials: J
authors.lastname: Callahan
authors.forename: Tomas
authors.initials: T
authors.lastname: Kron
authors.forename: Olga A
authors.initials: OA
authors.lastname: Martin
authors.forename: Michael P
authors.initials: MP
authors.lastname: MacManus
authors.forename: David L
authors.initials: DL
authors.lastname: Ball
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hofman
mesh_terms: D006801:Humans; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000532:radiotherapy; D004307:Dose-Response Relationship, Radiation; D005710:Gallium Radioisotopes; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D014057:Tomography, X-Ray Computed; D014692:Ventilation-Perfusion Ratio
chemical_list: D014408:Biomarkers, Tumor; D005710:Gallium Radioisotopes; D019275:Radiopharmaceuticals