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Purpose: Dose-volume data for injury to carotid artery and other major vessels in stereotactic body radiation therapy (SBRT)/SABR head and neck reirradiation were reviewed, modeled, and summarized., Methods and Materials: A PubMed search of the English-language literature (stereotactic and carotid and radiation) in April 2018 found 238 major vessel maximum point doses in 6 articles that were pooled for logistic modeling. Two subsequent studies with dose-volume major vessel data were modeled separately for comparison. Attempts were made to separate carotid blowout syndrome from other bleeding events (BE) in the analysis, but we acknowledge that all except 1 data set has some element of BE interspersed., Results: Prior radiation therapy (RT) dose was not uniformly reported per patient in the studies included, but a course on the order of conventionally fractionated 70 Gy was considered for the purposes of the analysis (with an approximately ≥6-month estimated interval between prior and subsequent treatment in most cases). Factors likely associated with reduced risk of BE include nonconsecutive daily treatment, lower extent of circumferential tumor involvement around the vessel, and no surgical manipulation before or after SBRT., Conclusions: Initial data pooling for reirradiation involving the carotid artery resulted in 3 preliminary models compared in this Hypofractionated Treatment Effects in the Clinic (HyTEC) report. More recent experiences with alternating fractionation schedules and additional risk-reduction strategies are also presented. Complications data for the most critical structures such as spinal cord and carotid artery are so limited that they cannot be viewed as strong conclusions of probability of risk, but rather, as a general guideline for consideration. There is a great need for better reporting standards as noted in the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic introductory paper., (Copyright © 2020. Published by Elsevier Inc.)

A literature review of more than 200 stereotactic body radiation therapy spine articles from the past 20 years found only a single article that provided dose-volume data and outcomes for each spinal cord of a clinical dataset: the Gibbs 2007 article (Gibbs et al, 2007(1)), which essentially contains the first 100 stereotactic body radiation therapy (SBRT) spine treatments from Stanford University Medical Center. The dataset is modeled and compared in detail to the rest of the literature review, which found 59 dose tolerance limits for the spinal cord in 1-5 fractions. We partitioned these limits into a unified format of high-risk and low-risk dose tolerance limits. To estimate the corresponding risk level of each limit we used the Gibbs 2007 clinical spinal cord dose-volume data for 102 spinal metastases in 74 patients treated by spinal radiosurgery. In all, 50 of the patients were previously irradiated to a median dose of 40Gy in 2-3Gy fractions and 3 patients developed treatment-related myelopathy. These dose-volume data were digitized into the dose-volume histogram (DVH) Evaluator software tool where parameters of the probit dose-response model were fitted using the maximum likelihood approach (Jackson et al, 1995(3)). Based on this limited dataset, for de novo cases the unified low-risk dose tolerance limits yielded an estimated risk of spinal cord injury of ≤1% in 1-5 fractions, and the high-risk limits yielded an estimated risk of ≤3%. The QUANTEC Dmax limits of 13Gy in a single fraction and 20Gy in 3 fractions had less than 1% risk estimated from this dataset, so we consider these among the low-risk limits. In the previously irradiated cohort, the estimated risk levels for 10 and 14Gy maximum cord dose limits in 5 fractions are 0.4% and 0.6%, respectively. Longer follow-up and more patients are required to improve the risk estimates and provide more complete validation., Competing Interests: Conflict of Interests Notification: None of the authors has received any funding for this research. Dr. Grimm developed and holds intellectual property rights to the DVH Evaluator software tool which is an FDA-cleared product in commercial use, which has been used for this analysis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Inconsistencies permeate the literature regarding small bowel dose tolerance limits for stereotactic body radiation therapy (SBRT) treatments. In this review, we organized these diverse published limits with MD Anderson at Cooper data into a unified framework, constructing the dose-volume histogram (DVH) Risk Map, demonstrating low-risk and high-risk SBRT dose tolerance limits for small bowel. Statistical models of clinical data from 2 institutions were used to assess the safety spectrum of doses used in the exposure of the gastrointestinal tract in SBRT; 30% of the analyzed cases had vascular endothelial growth factor inhibitors (VEGFI) or other biological agents within 2 years before or after SBRT. For every dose tolerance limit in the DVH Risk Map, the probit dose-response model was used to estimate the risk level from our clinical data. Using the current literature, 21Gy to 5cc of small bowel in 3 fractions has low toxicity and is reasonably safe, with 6.5% estimated risk of grade 3 or higher complications, per Common Terminology Criteria for Adverse Events version 4.0. In the same fractionation for the same volume, if lower risk is required, 16.2Gy has an estimated risk of only 2.5%. Other volumes and fractionations are also reviewed; for all analyzed high-risk small bowel limits, the risk is 8.2% or less, and the low-risk limits have 4% or lower estimated risk. The results support current clinical practice, with some possibility for dose escalation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Understanding dose constraints for critical structures in stereotactic body radiation therapy (SBRT) is essential to generate a plan for optimal efficacy and safety. Published dose constraints are derived by a variety of methods, including crude statistics, actuarial analysis, modeling, and simple biologically effective dose (BED) conversion. Many dose constraints reported in the literature are not consistent with each other, secondary to differences in clinical and dosimetric parameters. Application of a dose constraint without discriminating the variation of all the factors involved may result in suboptimal treatment. This issue of Seminars in Radiation Oncology validates dose tolerance limits for 10 critical anatomic structures based on dose response modeling of clinical outcomes data to include detailed dose-volume metrics. This article presents a logistic dose-response model for aorta and major vessels based on 238 cases from the literature in addition to 387 cases from MD Anderson Cancer Center at Cooper University Hospital, for a total of 625 cases. The Radiation Therapy Oncology Group (RTOG) 0813 dose-tolerance limit of Dmax = 52.5Gy in 5 fractions was found to have a 1.2% risk of grade 3-5 toxicity, and the Timmerman 2008 limit of Dmax = 45Gy in 3 fractions had 2.3% risk. From the model, the 1% and 2% risk levels for D4cc, D1cc, and D0.5cc are also provided in 1-5 fractions, in the form of a dose-volume histogram (DVH) Risk Map., (Copyright © 2016 Elsevier Inc. All rights reserved.)

PurposeDosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation.Methods and materialsEligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION).ResultsThirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P = .66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in