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

SIMPLE SUMMARY: High-dose radiotherapy is frequently used to treat lung cancer, however, it can cause serious central airway toxicity. Although radiation toxicity of the lung parenchyma has been studied extensively, relatively little has been published on bronchoscopic findings in the central airways and no standard classification/reporting system exists. With the growing use of high-dose (chemo)radiotherapy and high-dose hypo-fractionated radiotherapy in close proximity to central airways, as well as potential interactions with new systemic therapies, the risks and incidence of central airway toxicity may increase. In this retrospective study, we analyzed patient characteristics and clinical outcomes of 70 patients with central airway toxicity after high-dose radiotherapy. Furthermore, we analyzed the post-radiotherapy bronchoscopic images to identify main patterns of airway toxicity. We identified luminal stenosis and vascular changes as the two main patterns and have proposed a classification system. Preliminary analysis suggests that the pattern and severity of radiation toxicity may be of prognostic value. ABSTRACT: The study’s purpose was to identify the bronchoscopic patterns of central airway toxicity following high-dose radiotherapy or chemoradiotherapy, and to look at the consequences of these findings. Our institutional bronchoscopy database was accessed to identify main patterns of airway toxicity observed in a seven-year period. A total of 70 patients were identified with central airway toxicity, and the findings of bronchoscopy were used to derive a classification system. Patient characteristics, time from radiotherapy to toxicity, follow-up and survival were retrospectively analyzed. Results: The main bronchoscopic patterns of airway toxicity were vascular changes (telangiectasia, loss of vascularity, necrosis) and stenosis of the lumen (moderate, severe). Indications for bronchoscopy were airway symptoms (n = 28), assessment post-CRT/surgery (n = 12), (suspected) recurrence (n = 21) or assessment of radiological findings (n = 9). Stenosis was revealed by bronchoscopy at a median time of 10.0 months (IQR: 4–23.5) after radiotherapy and subsequent follow-up after identification was 23 months (IQR: 1.5–55). The corresponding findings for vascular changes were 29 months (IQR: 10.5–48.5), and follow-up after identification was nine months (IQR: 2.5–19.5). There was a statistically significant difference in survival rates between patients with necrosis and telangiectasia (p = 0.002) and loss of vascularity (p = 0.001). Eight out of 10 deceased patients with telangiectasia died of other causes and 4/8 patients with necrosis died of other causes. We identified two main patterns of central airway toxicity visualized with bronchoscopy after high-dose radiotherapy or chemoradiotherapy, and propose a bronchoscopic classification system based on these findings. Preliminary analysis suggests that the pattern and severity of radiation damage might be of prognostic value. Prospective data are required to confirm our findings.