Estimating the tolerance of brachial plexus to hypofractionated stereotactic body radiotherapy: a modelling-based approach from clinical experience.

BACKGROUND: Brachial plexopathy is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose-response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor. METHODS: Two published SBRT datasets were pooled and modeled from patients at Indiana University and the Richard L. Roudebush Veterans Administration Medical Center from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies were treated with SBRT for apically located lung tumors localized superior to the aortic arch. Toxicities were graded according to Common Terminology Criteria for Adverse Events, and a probit dose response model was created with maximum likelihood parameter fitting. RESULTS: This analysis includes a total of 89 brachial plexus maximum point dose (Dmax) values from both institutions. Among the 14 patients who developed brachial plexopathy, the most common complications were grade 2, comprising 7 patients. The median follow-up was 30 months (range 6.1-72.2) in the Karolinska dataset, and the Indiana dataset had a median of 13 months (range 1-71). Both studies had a median range of 3 fractions, but in the Indiana dataset, 9 patients were treated in 4 fractions, and the paper did not differentiate between the two, so our analysis is considered to be in 3-4 fractions, one of the main limitations. The probit model showed that the risk of brachial plexopathy with Dmax of 26 Gy in 3-4 fractions is 10%, and 50% with Dmax of 70 Gy in 3-4 fractions. CONCLUSIONS: This analysis is only a preliminary result because more details are needed as well as additional comprehensive datasets from a much broader cross-section of clinical practices. When more institutions join the QUANTEC and HyTEC methodology of reporting sufficient details to enable data pooling, our field will finally reach an improved understanding of human dose tolerance.

Dose-response model for severe late laryngeal toxicity after stereotactic body radiation therapy for previously-irradiated head and neck cancer.

We sought to evaluate the association between larynx dose and risk of severe late laryngeal toxicity in patients undergoing re-irradiation SBRT for recurrent HNC. Fifty-five patients with an intact larynx underwent re-irradiation SBRT to a median dose of 44 Gy in 5 fractions. Five (41.7%) patients treated for a laryngeal/hypopharyngeal recurrence experienced late grade ≥3 laryngeal toxicity, compared to 0.0-7.1% for other sites. Logistic dose-response models were created to predict risk of severe late laryngeal toxicity, including dysphagia and airway compromise. According to the model, the risk of severe laryngeal toxicity with a larynx D5cc of 5 Gy is 5.8% (95% CI 2.9-9.9%) and rises to 11.4% with a D5cc of 20 Gy and 25.3% with a D5cc of 40 Gy. In patients with a laryngeal/hypopharyngeal recurrence, SBRT planning should carefully assess the dose to laryngeal structures given these dose findings, and SBRT should be approached with significant caution in such patients.

Dose-response modeling the risk of carotid bleeding events after stereotactic body radiation therapy for previously irradiated head and neck cancer.

Given the lack of clear dose constraints for the carotid artery, we created dose-response models to better quantify the risk of carotid bleeding events following re-irradiation stereotactic body radiation therapy (SBRT) for head and neck cancer (HNC). We performed a retrospective analysis on 75 patients treated with SBRT for recurrent, previously irradiated HNC. Logistic dose-response models were created to predict the risk of a carotid bleeding event, defined as any mucosal bleeding event or bleeding resulting from rupture of the carotid artery or its major branches in the setting of controlled disease. According to the models, the risk of a carotid bleeding event with a cumulative D0.1cc of 20 Gy from SBRT is 0.8% (95% CI 0.1%-3.9%), and rises to 5.0% with a D0.1cc of 50 Gy. No patient experienced a carotid bleeding event with D0.1cc < 39.4 Gy, and none experienced carotid blowout syndrome with a cumulative D0.1cc < 47.6 Gy.