Functionally weighted airway sparing (FWAS): a functional avoidance method for preserving post-treatment ventilation in lung radiotherapy

Abstract

Recent changes to the guidelines for screening and early diagnosis of lung cancer have increased the interest in preserving post-radiotherapy lung function. Current investigational approaches are based on spatially mapping functional regions and generating regional avoidance plans that preferentially spare highly ventilated/perfused lung. A potentially critical, yet overlooked, aspect of functional avoidance is radiation injury to peripheral airways, which serve as gas conduits to and from functional lung regions. Dose redistribution based solely on regional function may cause irreparable damage to the ‘supply chain’. To address this deficiency, we propose the functionally weighted airway sparing (FWAS) method. FWAS (i) maps the bronchial pathways to each functional sub-lobar lung volume; (ii) assigns a weighting factor to each airway based on the relative contribution of the sub-volume to overall lung function; and (iii) creates a treatment plan that aims to preserve these functional pathways. To evaluate it, we used four cases from a retrospective cohort of SAbR patients treated for lung cancer. Each patient’s airways were auto-segmented from a diagnostic-quality breath-hold CT using a research virtual bronchoscopy software. A ventilation map was generated from the planning 4DCT to map regional lung function. For each terminal airway, as resolved by the segmentation software, the total ventilation within the sub-lobar volume supported by that airway was estimated and used as a function-based weighting factor. Upstream airways were weighted based on the cumulative volumetric ventilation supported by corresponding downstream airways. Using a previously developed model for airway radiosensitivity, dose constraints were determined for each airway corresponding to a <5% probability of airway collapse. Airway dose constraints, ventilation scores, and clinical dose constraints were input to a swarm optimization–based inverse planning engine to create a 3D conformal SAbR plan (CRT). The FWAS plans were compared to the patients’ prescribed CRT clinical plans and the inverse-optimized clinical plans. Depending on the size and location of the tumour, the FWAS plan showed superior preservation of ventilation due to airflow preservation through open pathways (i.e. cumulative ventilation score from the sub-lobar volumes of open pathways). Improvements ranged between 3% and 23%, when comparing to the prescribed clinical plans, and between 3% and 35%, when comparing to the inverse-optimized clinical plans. The three plans satisfied clinical requirements for PTV coverage and OAR dose constraints. These initial results suggest that by sparing pathways to high-functioning lung subregions it is possible to reduce post-SAbR loss of respiratory function.

CT-derived vessel segmentation for analysis of post-radiation therapy changes in vasculature and perfusion

“…We believe this to be indication of an "indirect effect" where regions receiving no or minimal dose experience large functional declines. This effect has been observed previously in several studies (Wallat et al, 2021) (Vicente et al, 2020) (Thomas et al, 2019) (Farr et al, 2018).…”

“…In recent years, multiple groups have begun developing these models and some have tested their efficacy in clinical trials ( McDonald et al, 1995 ) ( Mah and Dyk, 1988 ) ( Mehta, 2005 ) ( Graves et al, 2010 ) ( Patton et al, 2018 ) ( Koike et al, 2015 ) ( Hopkins et al, 2012 ) ( Zhang et al, 2010 ) ( Vinogradskiy et al, 2013 ) ( Wallat et al, 2020 ) ( Wallat et al, 2021 ) ( Bates et al, 2009 ) ( Hoover et al, 2014 ) ( Ireland et al, 2016 ) ( Vicente et al, 2020 ). To date, the only prospective clinical trials using these techniques have been ventilation-based ( Bayouth et al, 2019 ) and all non-contrast CT-derived methods have been exclusively ventilation based ( Patton et al, 2018 ) ( Vinogradskiy et al, 2013 ) ( Vicente et al, 2020 ) ( Castillo et al, 2021 ). This does not create a comprehensive model to accurately model the function regions that need avoidance.…”

Measuring Indirect Radiation-Induced Perfusion Change in Fed Vasculature Using Dynamic Contrast CT

“…For clinical integration, CT is an exceptional option due to its high spatial resolution and routine use in treatment planning. Some groups have begun developing predictive models derived from CT, but to date, all functional-avoidance studies using CT have primarily focused on assessing only ventilation, neglecting perfusion and therefore providing an incomplete assessment of lung damage [ 7 , 18 , 23 ].…”

“…However, this evidence was not commented on in those works. Additionally, this work was done using SPECT, which has the issue of producing low-resolution images prone to artifacts and attenuation, making the nuances of the indirect effect difficult to localize [ 23 , 25 , 26 , 27 ]. Wallat et al presented the first CT-derived evidence of there being an indirect effect, focusing on post-RT ventilation change due to damage to the airways [ 28 ].…”

Late Central Airway Toxicity after High-Dose Radiotherapy: Clinical Outcomes and a Proposed Bronchoscopic Classification

“…Radiation dose reduction and conventionally fractionated treatment schedules may help to reduce the risk of toxicity, however, they may also result in increased local failure and poorer cancer control. Virtual bronchoscopy-guided treatment planning which aims to minimize the dose to individual airway segments, and therefore potentially reduce the risk of airway toxicity, has been described [24,25]. However, the impact on toxicity needs to be defined.…”