Radiation-Induced Brachial Plexopathy (RIBP) after Stereotactic Body Radiotherapy (SBRT): Pooled Analyses of Risks

Abstract

RIBP, with symptomatic upper extremity motor or sensory deficits, is a risk after SBRT. We herein model dosimetric factors associated with risks of RIBP of the inferior aspect of the brachial plexus following SBRT for apical lung tumors. Literature searches (PubMed & Embase databases) were performed to identify reports published from 2000-2021, using search criteria of ["brachial plex*" and stereotactic]. From a PRISMA systematic review, studies were identified that included individual patient data on: (1) RIBP endpoints after SBRT for apical lung tumors; and (2) brachial plexus Dmax, or maximum point doses (i.e., D0.035cc or D0.03cc). These data were amenable to normal tissue complication probability (NTCP) modelling. Doses were converted using the linear-quadratic model with an alpha-beta ratio of 3 Gy. For the probit models, the parameter values were determined using the maximum likelihood method and the 95% confidence intervals (CI) were determined using the profile likelihood method. The ability of the NTCP models to distinguish patients with and without RIBP was evaluated using the area under the curve (AUC). Two probit NTCP models were derived: one from 3 studies (185 patients with 192 targets and 11 events) and another from 4 studies (221 patients with 229 targets and 18 events). NTCP models (summarized in table) suggest ≈10% risks associated with brachial plexus maximum dose (Dmax) of ∼32-34 Gy in 3 fractions and ∼40-43 Gy in 5 fractions, with a clear dose response. These dose-responses with SBRT (with steep dose gradients beyond the target volume and thus only partial-irradiation of the brachial plexus) are far less steep than those reported following conventionally-fractionated or moderately-hypofractionated radiotherapy used for breast, lung and head and neck cancers (that tend to use radiotherapy fields that circumferentially irradiate the brachial plexus). A dose-response for risk of RIBP after SBRT is observed relative to brachial plexus Dmax. The less-steep dose-response compared to that seen from conventionally-fractionated or moderately-hypofractionated radiotherapy (with large irradiated plexus volumes) suggest a possible volume dependence of RIBP risks. Future work should focus on understanding possible volume effects.