Evaluating Which Dose-Function Metrics Are Most Critical for Functional Guided Radiation Therapy with CT Ventilation Imaging

Abstract

4DCT-ventilation imaging is increasingly being used to calculate lung ventilation and implement functional guided radiotherapy in clinical trials. There has been little exhaustive work evaluating which dose-function metrics should be used for treatment planning and plan evaluation for functional guided radiotherapy. Our study evaluated which dose-function metrics are most critical in assessing the risk of radiation pneumonitis (RP). Seventy lung cancer patients with 4DCT imaging and RP grading were used. Pre-treatment 4DCTs of each patient were used to calculate ventilation images. We evaluated 3 different types of dose function metrics that combined that patient’s 4DCT-ventilation image and treatment planning dose distribution: 1) structure-based approaches 2) image-based approaches using the dose-function histogram (DFH) and 3) non-linear weighting schemes. Structure-based approaches used a binary approximation in which the lung was binned to either functional or non-functional status. A full range of cutoff values to delineate between functional and non-functional and the volume of functional lung receiving ≥ 5Gy, 10Gy, 20Gy, and 30Gy was investigated. Imaging-based and non-linear approaches investigated the fraction of lung function receiving ≥ 5Gy, 10Gy, 20Gy, and 30Gy. Maximum likelihood methods were used to generate normal tissue complication probability (NTCP) models predicting grade 3+ RP for the dose-function schemes and all tested dose-function metrics. The area under the curve (AUC) for each model was used to quantify the ability to predict for toxicity. All techniques were compared to NTCP models based on traditional, total lung dose metrics. The most predictive models for grade 3+ RP were structure-based approaches that focused on the volume of functional lung receiving ≥20Gy (AUC=0.70) where functional lung was treated as regions with ventilation values ≥84th percentile. Imaging-based analysis with the DFH and non-linear weighted ventilation values yielded AUCs of 0.66 and 0.67, respectively, when evaluating the fraction of functionality receiving ≥20Gy. All dose-function metrics outperformed the traditional lung dose metrics (mean lung dose, AUC = 0.55). A full range of dose-function metrics and functional thresholds were examined. The AUC values for the most predictive functional models occupied a narrow range (0.66-0.70) and all demonstrated improvements over AUC from traditional lung dose metrics (0.55). Identifying the dose-function parameters most predictive of grade 3+ RP provides valuable data for treatment planning and plan evaluation parameters. With prospective clinical trials of functional guided radiotherapy using 4DCT-ventilation imaging underway, this work provides seminal data to help establish guidelines for the implementation of functional guided radiotherapy.