Combining Serial and Parallel Functionality in Functional Lung Avoidance Radiation Therapy

Purpose: Functional lung avoidance (FLA) radiation therapy (RT) aims to minimize post-RT pulmonary toxicity by preferentially avoiding dose to high-functioning lung (HFL) regions. A common limitation is that FLA approaches do not consider the conducting architecture for gas exchange. We previously proposed the functionally weighted airway sparing (FWAS) method to spare airways connected to HFL regions, showing that it is possible to substantially reduce risk of radiation-induced airway injury. Here, we compare the performance of FLA and FWAS and propose a novel method combining both approaches. Methods: We used breath-hold computed tomography (BHCT) and simulation 4-dimensional computed tomography (4DCT) from 12 lung stereotactic ablative radiation therapy patients. Four planning strategies were examined: (1) Conventional: no sparing other than clinical dose-volume constraints; (2) FLA: using a 4DCT-based ventilation map to delineate the HFL, plans were optimized to reduce mean dose and V_13.50 in HFL; (3) FWAS: we autosegemented 11 to 13 generations of individual airways from each patient's BHCT and assigned priorities based on the relative contribution of each airway to total ventilation. We used these priorities in the optimization along with airway dose constraints, estimated as a function of airway diameter and 5% probability of collapse; and (4) FLA + FWAS: we combined information from the 2 strategies. We prioritized clinical dose constraints for organs at risk and planning target volume in all plans. We performed the evaluation in terms of ventilation preservation accounting for radiation-induced damage to both lung parenchyma and airways. Results: We observed average ventilation preservation for FLA, FWAS, and FLA + FWAS as 3%, 8.5%, and 14.5% higher, respectively, than for Conventional plans for patients with ventilation preservation in Conventional plans <90%. Generalized estimated equations showed that all improvements were statistically significant (P ≤ .036). We observed no clinically relevant improvements in outcomes of the sparing techniques in patients with ventilation preservation in Conventional plans ≥90%. Conclusions: These initial results suggest that it is crucial to consider the parallel and the serial nature of the lung to improve post-radiation therapy lung function and, consequently, quality of life for patients.