The HI-FIVE trial, a prospective trial using 68Ga-4D-V/Q PET/CT for functional lung avoidance in locally advanced NSCLC

Introduction 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 Four-Dimensional Gallium 68 Ventilation-Perfusion PET/CT (68Ga-4D-V/Q PET/CT). Methods Inclusion criteria required a diagnosis of stage III Non-Small Cell Lung cancer (NSCLC) and ability to undergo radical intent chemoradiation therapy. Functional volumes were generated using planning 68Ga-4D-V/Q PET/CT. These volumes were used to generate a clinical FLA plan to 60Gy in 30 fractions. The primary tumor was boosted to 69Gy. A comparison anatomical plan was generated for each patient. Feasibility was met if FLA plans (compared to anatomical plans) allowed (A) reduction in mean functional lung dose (fMLD) of ≥2% and reduction in the functional lung volume receiving 20 Gy (fV20Gy) of ≥4%; and (B) Mean heart dose ≤30 Gy and relative heart volume receiving 50 Gy <25%. Results 19 patients were recruited, one withdrew consent. Eighteen patients underwent chemoradiation with FLA. Of the 18 patients, 15 met criteria for feasibility. All patients completed the entire course of chemoradiotherapy. Using FLA resulted in an average reduction of the functional mean lung dose of 12.4% (SD ± 12.8%) and mean relative reduction of the fV20 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 over all timepoints. Conclusion Using 68Ga-4D-V/Q PET/CT to image and avoid functional lung is feasible.