The HI-FIVE Trial: A Prospective Trial Using 4-Dimensional 68Ga Ventilation-Perfusion Positron Emission Tomography-Computed Tomography for Functional Lung Avoidance in Locally Advanced Non-small Cell Lung Cancer

Purpose: Functional lung avoidance (FLA) radiation therapy aims to spare regions of functional lung to reduce toxicity. We report the results of the first prospective trial of FLA using 4-dimensional gallium 68 ventilation-perfusion positron emission tomography-computed tomography (Ga-68-4D-V/Q PET/CT).Methods and materials: Inclusion criteria required a diagnosis of stage III non-small cell lung cancer and the ability to undergo radical-intent chemoradiation therapy. Functional volumes were generated using planning Ga-68-4D-V/Q PET/CT. These volumes were used to generate a clinical FLA plan to 60 Gy in 30 fractions. The primary tumor was boosted to 69 Gy. A comparison anatomic plan was generated for each patient. Feasibility was met if FLA plans (compared with anatomic plans) allowed (1) a reduction in functional mean lung dose of >= 2% and a reduction in the functional lung volume receiving 20 Gy (fV20Gy) of >= 4%, and (2) a mean heart dose <= 30 Gy and relative heart volume receiving 50 Gy of <25%.Results: In total, 19 patients were recruited; 1 withdrew consent. Eighteen patients underwent chemoradiation with FLA. Of the 18 patients, 15 met criteria for feasibility. All patients completed the entire course of chemoradiation therapy. Using FLA resulted in an average reduction of the functional mean lung dose of 12.4% (SD, +/- 12.8%) and a mean relative reduction of the fV20Gy of 22.9% (SD, +/- 11.9%). At 12 months, Kaplan-Meier estimates for overall survival were 83% (95% CI, 56%-94%) and estimates for progression-free survival were 50% (95% CI, 26%-70%). Quality-of-life scores were stable across all time points.Conclusions: Using Ga-68-4D-V/Q PET/CT to image and avoid functional lung is feasible.Copyright (c) 2023 Elsevier Inc. All rights reserved.

Automated summary

The study explores the use of 4-dimensional gallium 68 ventilation-perfusion positron emission tomography-computed tomography (Ga-68-4D-V/Q PET/CT) to spare functional lung during radiation therapy. The results demonstrate that FLA significantly reduces the radiation dose to functional lung, leading to positive outcomes in terms of survival rates and quality of life.