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An overview of common approaches used to assess a dose response for radiation therapy-associated endpoints is presented, using lung toxicity data sets analyzed as a part of the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic effort as an example. Each component presented (eg, data-driven analysis, dose-response analysis, and calculating uncertainties on model prediction) is addressed using established approaches. Specifically, the maximum likelihood method was used to calculate best parameter values of the commonly used logistic model, the profile-likelihood to calculate confidence intervals on model parameters, and the likelihood ratio to determine whether the observed data fit is statistically significant. The bootstrap method was used to calculate confidence intervals for model predictions. Correlated behavior of model parameters and implication for interpreting dose response are discussed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Tumor treating fields (TTFields) is a novel antimitotic treatment that was first proven effective for glioblastoma multiforme, now with trials for several extracranial indications underway. Several studies focused on concurrent TTFields therapy with radiation in the same time period, but were not given simultaneously. This study evaluates the targeting accuracy of simultaneous radiation therapy while TTFields arrays are in place and powered on, ensuring that radiation does not interfere with TTFields and TTFields does not interfere with radiation. This is one of several options to enable TTFields to begin several weeks sooner, and opens potential for synergistic effects of combined therapy. Methods: TTFields arrays were attached to a warm saline water bath and salt was added until the TTFields generator reached the maximal 2000 mA peak-to-peak current. A ball cube phantom containing 2 orthogonal films surrounded by fiducials was placed in the water phantom, CT scanned, and a radiation treatment plan with 58 isocentric beams was created using a 3 cm circular collimator. Fiducial tracking was used to deliver radiation, the films were scanned, and end-to-end targeting error was measured with vendor-supplied software. In addition, radiation effects on electric fields generated by the TTFields system were assessed by examining logfiles generated from the field generator. Results: With TTFields arrays in place and powered on, the robotic radiosurgery system achieved a final targeting result of 0.47 mm, which was well within the submillimeter specification. No discernible effects on TTFields current output beyond 0.3% were observed in the logfiles when the radiation beam pulsed on and off. Conclusion: A robotic radiosurgery system was used to verify that radiation targeting was not adversely affected when the TTFields arrays were in place and the TTFields delivery device was powered on. In addition, this study verified that radiation delivered simultaneously with TTFields did not interfere with the generation of the electric fields.

Object: The efficacy and safety of treatment with whole-brain radiotherapy (WBRT) or with stereotactic radiosurgery (SRS) for multiple brain metastases (> 10) are topics of ongoing debate. This study presents detailed dosimetric and biological information to investigate the possible clinical outcomes of these 2 modalities., Methods: Five patients with multiple brain metastases (n = 11-23) underwent SRS. Whole-brain radiotherapy plans were retrospectively designed with the same MR image set and the same structure set for each patient, using the standard opposing lateral beams and fractionation (3 Gy × 10). Physical radiation doses and biologically effective doses (BEDs) in WBRT and SRS were calculated for each lesion target and for the normal brain tissues for comparison of the 2 modalities in the context of clinical efficacy and published toxicities., Results: The BEDs targeted to the tumor were higher in SRS than in WBRT by factors ranging from 2.4- to 3.0- fold for the mean dose and from 3.2- to 5.3-fold for the maximum dose. In the 5 patients, mean BEDs in SRS (calculated as percentages of BEDs in WBRT) were 1.3%-34.3% for normal brain tissue, 0.7%-31.6% for the brainstem, 0.5%-5.7% for the chiasm, 0.2%-5.7% for optic nerves, and 0.6%-18.1% for the hippocampus., Conclusions: The dose-volume metrics presented in this study were essential to understanding the safety and efficacy of WBRT and SRS for multiple brain metastases. Whole-brain radiotherapy results in a higher incidence of radiation-related toxicities than SRS. Even in patients with > 10 brain metastases, the normal CNS tissues receive significantly lower doses in SRS. The mean normal brain dose in SRS correlated with the total volume of the lesions rather than with the number of lesions treated.

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. [ABSTRACT FROM AUTHOR]

Purpose: We sought to investigate the tumor control probability (TCP) of spinal metastases treated with stereotactic body radiation therapy (SBRT) in 1 to 5 fractions.Methods and Materials: PubMed-indexed articles from 1995 to 2018 were eligible for data extraction if they contained SBRT dosimetric details correlated with actuarial 2-year local tumor control rates. Logistic dose-response models of collected data were compared in terms of physical dose and 3-fraction equivalent dose.Results: Data were extracted from 24 articles with 2619 spinal metastases. Physical dose TCP modeling of 2-year local tumor control from the single-fraction data were compared with data from 2 to 5 fractions, resulting in an estimated α/β = 6 Gy, and this was used to pool data. Acknowledging the uncertainty intrinsic to the data extraction and modeling process, the 90% TCP corresponded to 20 Gy in 1 fraction, 28 Gy in 2 fractions, 33 Gy in 3 fractions, and (with extrapolation) 40 Gy in 5 fractions. The estimated TCP for common fractionation schemes was 82% at 18 Gy, 90% for 20 Gy, and 96% for 24 Gy in a single fraction, 82% for 24 Gy in 2 fractions, and 78% for 27 Gy in 3 fractions.Conclusions: Spinal SBRT with the most common fractionation schemes yields 2-year estimates of local control of 82% to 96%. Given the heterogeneity in the tumor control estimates extracted from the literature, with variability in reporting of dosimetry data and the definition of and statistical methods of reporting tumor control, care should be taken interpreting the resultant model-based estimates. Depending on the clinical intent, the improved TCP with higher dose regimens should be weighed against the potential risks for greater toxicity. We encourage future reports to provide full dosimetric data correlated with tumor local control to allow future efforts of modeling pooled data. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the radiobiological parameters of three popular NTCP models, which describe the dose–response relations of carotid blowout syndrome (CBOS) after stereotactic body radiotherapy (SBRT). To evaluate the goodness‐of‐fit and the correlation of those models with CBOS. Methods: The study included 61 patients with inoperable locally recurrent head and neck cancer treated with SBRT using CyberKnife (Accuray, Sunnyvale, CA) at the Department of Radiation Oncology, Hacettepe University, Ankara, Turkey between June 2007 and March 2011. The dose‐volume histograms of the internal carotid were exported from the plans of all the patients. The follow‐up results regarding the end point of carotid blowout syndrome were collected retrospectively. Initially, univariable analyses (Wilcoxon rank‐sum or Chi‐square tests) and a multivariate logistic regression analysis were performed between the outcome data and a list of clinical and treatment factors to identify significant correlations. Additionally, the Lyman–Kutcher–Burman (LKB), Relative Seriality (RS), and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC), and Odds Ratio methods. Results: The clinical/treatment factors that were found to have a significant or close to significant correlations with acute CBOS were Age at the time of CK (P‐value = 0.03), Maximum carotid dose (P‐value = 0.06), and CK prescription dose (P‐value = 0.08). Using Dmax, physical DVH, and EQD2 Gy‐DVH as the dosimetric metrics in the NTCP models, the derived LKB model parameters were: (a) D50 = 45.8 Gy, m = 0.24, n = n/a; (b) D50 = 44.8 Gy, m = 0.28, n = 0.01; and (c) D50 = 115.8 Gy, m = 0.45, n = 0.01, respectively. The AUC values for the dosimetric metrics were 0.70, 0.68, and 0.61, respectively. The differences in AIC between the different models were less than 2 and ranged within ±0.9. Conclusion: The maximum dose to the internal carotid less than 34 Gy appears to significantly reduce the risk for CBOS. Age at the time of CK, Maximum carotid dose, and CK prescription dose were also found to correlate with CBOS. The values of the parameters of three NTCP models were determined for this endpoint. A threshold of gEUD <34.5 Gy appears to be significantly associated with lower risks of CBOS. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiation therapy (SBRT) and stereotactic ablative body radiation therapy is being increasingly used for pancreatic cancer (PCa), particularly in patients with locally advanced and borderline resectable disease. A wide variety of dose fractionation schemes have been reported in the literature. This HyTEC review uses tumor control probability models to evaluate the comparative effectiveness of the various SBRT treatment regimens used in the treatment of patients with localized PCa.Methods and Materials: A PubMed search was performed to review the published literature on the use of hypofractionated SBRT (usually in 1-5 fractions) for PCa in various clinical scenarios (eg, preoperative [neoadjuvant], borderline resectable, and locally advanced PCa). The linear quadratic model with α/β= 10 Gy was used to address differences in fractionation. Logistic tumor control probability models were generated using maximum likelihood parameter fitting.Results: After converting to 3-fraction equivalent doses, the pooled reported data and associated models suggests that 1-year local control (LC) without surgery is ≈79% to 86% after the equivalent of 30 to 36 Gy in 3 fractions, showing a dose response in the range of 25 to 36 Gy, and decreasing to less than 70% 1-year LC at doses below 24 Gy in 3 fractions. The 33 Gy in 5 fraction regimen (Alliance A021501) corresponds to 28.2 Gy in 3 fractions, for which the HyTEC pooled model had 77% 1-year LC without surgery. Above an equivalent dose of 28 Gy in 3 fractions, with margin-negative resection the 1-year LC exceeded 90%.Conclusions: Pooled analyses of reported tumor control probabilities for commonly used SBRT dose-fractionation schedules for PCa suggests a dose response. These findings should be viewed with caution given the challenges and limitations of this review. Additional data are needed to better understand the dose or fractionation-response of SBRT for PCa. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiation therapy (SBRT) has emerged as a viable reirradiation strategy for locally recurrent previously-irradiated head and neck cancer. Doses in the literature have varied, which challenges clinical application of SBRT as well as clinical trial design.Material& Methods: A working group was formed through the American Association of Physicists in Medicine to study tumor control probabilities for SBRT in head and neck cancer. We herein present a systematic review of the available literature addressing the dose/volume data for tumor control probability with SBRT in patients with locally recurrent previously-irradiated head and neck cancer. Dose-response models are generated that present tumor control probability as a function of dose.Results: Data from more than 300 cases in 8 publications suggest that there is a dose-response relationship, with superior local control and possibly improved overall survival for doses of 35 to 45 Gy (in 5 fractions) compared with <30 Gy.Conclusion: Stereotactic body radiation therapy doses equivalent to 5-fraction doses of 40 to 50 Gy are suggested for retreatment. [ABSTRACT FROM AUTHOR]

We sought to systematically review and summarize dosimetric factors associated with radiation-induced brachial plexopathy (RIBP) after stereotactic body radiation therapy (SBRT) or hypofractionated image guided radiation therapy (HIGRT). From published studies identified from searches of PubMed and Embase databases, data quantifying risks of RIBP after 1- to 10-fraction SBRT/HIGRT were extracted and summarized. Published studies have reported <10% risks of RIBP with maximum doses (D max) to the inferior aspect of the brachial plexus of 32 Gy in 5 fractions and 25 Gy in 3 fractions. For 10-fraction HIGRT, risks of RIBP appear to be low with D max < 40 to 50 Gy. For a given dose value, greater risks are anticipated with point volume-based metrics (ie, D 0.03-0.035cc : minimum dose to hottest 0.03-0.035 cc) versus D max. With SBRT/HIGRT, there were insufficient published data to predict risks of RIBP relative to brachial plexus dose-volume exposure. Minimizing maximum doses and possibly volume exposure of the brachial plexus can reduce risks of RIBP after SBRT/HIGRT. Further study is needed to better understand the effect of volume exposure on the brachial plexus and whether there are location-specific susceptibilities along or within the brachial plexus structure. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiation therapy (SBRT) in the management of adrenal metastases is emerging as a well-tolerated, effective method of treatment for patients with limited metastatic disease. SBRT planning and treatment utilization are widely variable, and publications report heterogeneous radiation dose fractionation schemes and treatment outcomes. The objective of this analysis was to review the current literature on SBRT for adrenal metastases and to develop treatment guidelines and a model for tumor control probability of SBRT for adrenal metastases based on these publications.Methods and Materials: A literature search of all studies on SBRT for adrenal metastases published from 2008 to 2017 was performed, and outcomes in these studies were reviewed. Local control (LC) rates were fit to a statistically significant Poisson model using maximum likelihood estimation techniques.Results: One-year LC greater than 95% was achieved at an approximated biological equivalent dose with α/β = 10 Gy of 116.4 Gy.Conclusions: While respecting normal tissue tolerances, tumor doses greater than or equal to a biological equivalent dose with α/β = 10 Gy of 116.4 Gy are recommended to achieve high LC. Further studies following unified reporting standards are needed for more robust prediction. [ABSTRACT FROM AUTHOR]

Purpose: Ultrahypofractionationed radiation therapy for prostate cancer is increasingly studied and adopted. The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiotherapy therefore aimed to review studies examining toxicity and quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer and model its effect.Methods and Materials: We performed a systematic PubMed search of prostate SBRT studies published between 2001 and 2018. Those that analyzed factors associated with late urinary, bowel, or sexual toxicity and/or quality of life were included and reviewed. Normal tissue complication probability modelling was performed on studies that contained detailed dose/volume and outcome data.Results: We found 13 studies that examined urinary effects, 6 that examined bowel effects, and 4 that examined sexual effects. Most studies included patients with low-intermediate risk prostate cancer treated to 35-40 Gy. Most patients were treated with 5 fractions, with several centers using 4 fractions. Endpoints were heterogeneous and included both physician-scored toxicity and patient-reported quality of life. Most toxicities were mild-moderate (eg, grade 1-2) with a very low overall incidence of severe toxicity (eg, grade 3 or higher, usually <3%). Side effects were associated with both dosimetric and non-dosimetric factors.Conclusions: Prostate SBRT appears to be overall well tolerated, with determinants of toxicity that include dosimetric factors and patient factors. Suggested dose constraints include bladder V(Rx Dose)Gy <5-10 cc, urethra Dmax <38-42 Gy, and rectum Dmax <35-38 Gy, though current data do not offer firm guidance on tolerance doses. Several areas for future research are suggested. [ABSTRACT FROM AUTHOR]

Purpose: Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation. The evolving treatment approach of ultrahypofractionation with stereotactic body radiation therapy (SBRT) allows possible further biological dose escalation (biologically equivalent dose [BED]) and shortened treatment time.Methods and Materials: The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiation Therapy/SBRT included a subgroup to study the prostate tumor control probability (TCP) with SBRT. We performed a systematic review of the available literature and created a dose-response TCP model for the endpoint of freedom from biochemical relapse. Results were stratified by prostate cancer risk group.Results: Twenty-five published cohorts were identified for inclusion, with a total of 4821 patients (2235 with low-risk, 1894 with intermediate-risk, and 446 with high-risk disease, when reported) treated with a variety of dose/fractionation schemes, permitting dose-response modeling. Five studies had a median follow-up of more than 5 years. Dosing regimens ranged from 32 to 50 Gy in 4 to 5 fractions, with total BED (α/β = 1.5 Gy) between 183.1 and 383.3 Gy. At 5 years, we found that in patients with low-intermediate risk disease, an equivalent doses of 2 Gy per fraction (EQD2) of 71 Gy (31.7 Gy in 5 fractions) achieved a TCP of 90% and an EQD2 of 90 Gy (36.1 Gy in 5 fractions) achieved a TCP of 95%. In patients with high-risk disease, an EQD2 of 97 Gy (37.6 Gy in 5 fractions) can achieve a TCP of 90% and an EQD2 of 102 Gy (38.7 Gy in 5 fractions) can achieve a TCP of 95%.Conclusions: We found significant variation in the published literature on target delineation, margins used, dose/fractionation, and treatment schedule. Despite this variation, TCP was excellent. Most prescription doses range from 35 to 40 Gy, delivered in 4 to 5 fractions. The literature did not provide detailed dose-volume data, and our dosimetric analysis was constrained to prescription doses. There are many areas in need of continued research as SBRT continues to evolve as a treatment modality for prostate cancer, including the durability of local control with longer follow-up across risk groups, the efficacy and safety of SBRT as a boost to intensity modulated radiation therapy (IMRT), and the impact of incorporating novel imaging techniques into treatment planning. [ABSTRACT FROM AUTHOR]

Spinal cord tolerance data for stereotactic body radiation therapy (SBRT) were extracted from published reports, reviewed, and modelled. For de novo SBRT delivered in 1 to 5 fractions, the following spinal cord point maximum doses (Dmax) are estimated to be associated with a 1% to 5% risk of radiation myelopathy (RM): 12.4 to 14.0 Gy in 1 fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions. For reirradiation SBRT delivered in 1 to 5 fractions, reported factors associated with a lower risk of RM include cumulative thecal sac equivalent dose in 2 Gy fractions with an alpha/beta of 2 (EQD22) Dmax ≤70 Gy; SBRT thecal sac EQD22 Dmax ≤25 Gy, thecal sac SBRT EQD22 Dmax to cumulative EQD22 Dmax ratio ≤0.5, and a minimum time interval to reirradiation of ≥5 months. Larger studies containing complete institutional cohorts with dosimetric data of patients treated with spine SBRT, with and without RM, are required to refine RM risk estimates. [ABSTRACT FROM AUTHOR]

Purpose: To review the radiobiological mechanisms of stereotactic body radiation therapy stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS).Methods and Materials: We reviewed previous reports and recent observations on the effects of high-dose irradiation on tumor cell survival, tumor vasculature, and antitumor immunity. We then assessed the potential implications of these biological changes associated with SBRT and SRS.Results: Irradiation with doses higher than approximately 10 Gy/fraction causes significant vascular injury in tumors, leading to secondary tumor cell death. Irradiation of tumors with high doses has also been reported to increase the antitumor immunity, and various approaches are being investigated to further elevate antitumor immunity. The mechanism of normal tissue damage by high-dose irradiation needs to be further investigated.Conclusions: In addition to directly killing tumor cells, high-dose irradiation used in SBRT and SRS induces indirect tumor cell death via vascular damage and antitumor immunity. Further studies are warranted to better understand the biological mechanisms underlying the high efficacy of clinical SBRT and SRS and to further improve the efficacy of SBRT and SRS. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiation therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer and is often used for recurrent lung cancer and pulmonary metastases. Radiation-induced lung toxicity (RILT), including radiation pneumonitis and pulmonary fibrosis, is a major concern for which it is important to understand dosimetric and clinical predictors.Methods and Materials: This study was undertaken through the American Association of Physicists in Medicine's Working Group on Biological Effects of Stereotactic Body Radiotherapy. Data from studies of lung SBRT published through the summer of 2016 that provided detailed information about RILT were analyzed.Results: Ninety-seven studies were ultimately considered. Definitions of the risk organ and complication endpoints as well as dose-volume information presented varied among studies. The risk of RILT, including radiation pneumonitis and pulmonary fibrosis, was reported to be associated with the size and location of the tumor. Patients with interstitial lung disease appear to be especially susceptible to severe RILT. A variety of dosimetric parameters were reported to be associated with RILT. There was no apparent threshold "tolerance dose-volume" level. However, most studies noted safe treatment with a rate of symptomatic RILT of <10% to 15% after lung SBRT with a mean lung dose (MLD) of the combined lungs ≤8 Gy in 3 to 5 fractions and the percent of total lung volume receiving more than 20 Gy (V20) <10% to 15%.Conclusions: To allow more rigorous analysis of this complication, future studies should standardize reporting by including standardized endpoint and volume definitions and providing dose-volume information for all patients, with and without RILT. [ABSTRACT FROM AUTHOR]

Purpose: To quantitatively evaluate published experiences with hepatic stereotactic body radiation therapy (SBRT), to determine local control rates after treatment of primary and metastatic liver tumors and to examine whether outcomes are affected by SBRT dosing regimen.Methods and Materials: We identified published articles that reported local control rates after SBRT for primary or metastatic liver tumors. Biologically effective doses (BEDs) were calculated for each dosing regimen using the linear-quadratic equation. We excluded series in which a wide range of BEDs was used. Individual lesion data for local control were extracted from actuarial survival curves, and data were aggregated to form a single dataset. Actuarial local control curves were generated using the Kaplan-Meier method after grouping lesions by disease type and BED (<100 Gy10 vs >100 Gy10). Comparisons were made using log-rank testing.Results: Thirteen articles met all inclusion criteria and formed the dataset for this analysis. The 1-, 2-, and 3-year actuarial local control rates after SBRT for primary liver tumors (n = 431) were 93%, 89%, and 86%, respectively. Lower 1- (90%), 2- (79%), and 3-year (76%) actuarial local control rates were observed for liver metastases (n = 290, log-rank P = .011). Among patients treated with SBRT for primary liver tumors, there was no evidence that local control is influenced by BED within the range of schedules used. For liver metastases, on the other hand, outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy10 (3-year local control 93%) than for those treated with BEDs of ≤100 Gy10 (3-year local control 65%, P < .001).Conclusions: Stereotactic body radiation therapy for primary liver tumors provides high rates of durable local control, with no clear evidence for a dose-response relationship among commonly utilized schedules. Excellent local control rates are also seen after SBRT for liver metastases when BEDs of >100 Gy10 are utilized. [ABSTRACT FROM AUTHOR]

Purpose: In patients with spinal instability, cord compression, or neurologic deficits, the standard of care is surgery followed by radiation therapy (RT). Recurrence rates after conventional RT remain high. The purpose of this study is to prospectively examine the efficacy of postoperative stereotactic body RT (SBRT) in patients who have undergone surgical intervention for spine metastases. We hypothesize that postoperative SBRT to the spine would be associated with higher local control than historical rates after conventional RT.Methods and Materials: Thirty-five adult patients with a Karnofsky Performance Status score ≥40 and spine metastases from solid tumors with no prior overlapping RT and target volumes ≤3 consecutive vertebral levels were enrolled. Thirty-three patients were treated. Two patients underwent treatment to 2 target volumes for a total of 35 target volumes. All patients received SBRT 30 Gy in 5 fractions. Patients were followed with neurological examinations and computed tomography and/or magnetic resonance imaging every 3 months. Neurologic function was assessed at the same time points using the American Spinal Injury Association (ASIA) impairment score. Pain was rated according to the 10-point visual analogue scale and MD Anderson Cancer Center brief pain index. Toxicity was recorded according to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4. The primary objective was the rate of radiographic local recurrence at 12 months after completion of SBRT.Results: Patient characteristics were as follows: 34.3% had radioresistant primaries; 71.4% were ASIA E and the remainder ASIA D; and the median baseline Karnofsky Performance Status score was 70 (range, 50-100). Radiographic and symptomatic local control at 1 year were 90% (95% confidence interval, 76%-98%). The median time to recurrence in these 3 patients was 3.5 months (range, 3.4-5.8 months), all had radiosensitive tumors, and all recurrences were epidural. No patients experienced wound dehiscence, hardware failure, or spinal cord myelopathy. The median time to return to systemic therapy was 0.5 months (range, 0-9.4 months).Conclusions: This prospective study of postoperative spine SBRT demonstrates excellent local control with low toxicity. These data suggest superior rates of local control compared with conventional RT; however, a formal comparative study is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Treatment effect or radiation necrosis after stereotactic radiosurgery (SRS) for brain metastases is a common phenomenon often indistinguishable from true progression. Radiomics is an emerging field that promises to improve on conventional imaging. In this study, we sought to apply a radiomics-based prediction model to the problem of diagnosing treatment effect after SRS.Methods and Materials: We included patients in the Johns Hopkins Health System who were treated with SRS for brain metastases who subsequently underwent resection for symptomatic growth. We also included cases of likely treatment effect in which lesions grew but subsequently regressed spontaneously. Lesions were segmented semiautomatically on preoperative T1 postcontrast and T2 fluid-attenuated inversion recovery magnetic resonance imaging, and radiomic features were extracted with software developed in-house. Top-performing features on univariate logistic regression were entered into a hybrid feature selection/classification model, IsoSVM, with parameter optimization and further feature selection performed using leave-one-out cross-validation. Final model performance was assessed by 10-fold cross-validation with 100 repeats. All cases were independently reviewed by a board-certified neuroradiologist for comparison.Results: We identified 82 treated lesions across 66 patients, with 77 lesions having pathologic confirmation. There were 51 radiomic features extracted per segmented lesion on each magnetic resonance imaging sequence. An optimized IsoSVM classifier based on top-ranked radiomic features had sensitivity and specificity of 65.38% and 86.67%, respectively, with an area under the curve of 0.81 on leave-one-out cross-validation. Only 73% of cases were classifiable by the neuroradiologist, with a sensitivity of 97% and specificity of 19%.Conclusions: Radiomics holds promise for differentiating between treatment effect and true progression in brain metastases treated with SRS. A predictive model built on radiomic features from an institutional cohort performed well on cross-validation testing. These results warrant further validation in independent datasets. Such work could prove invaluable for guiding management of individual patients and assessing outcomes of novel interventions. [ABSTRACT FROM AUTHOR]

Purpose: To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiation therapy (SBRT) of the thorax.Methods and Materials: Published studies on lung toxicity in patients with early-stage non-small cell lung cancer (NSCLC) or metastatic lung tumors treated with SBRT were pooled and analyzed. The primary endpoint was RILT, including pneumonitis and fibrosis. Data of RILT and risk factors were extracted from each study, and rates of grade 2 to 5 (G2+) and grade 3 to 5 (G3+) RILT were computed. Patient, tumor, and dosimetric factors were analyzed for their correlation with RILT.Results: Eighty-eight studies (7752 patients) that reported RILT incidence were eligible. The pooled rates of G2+ and G3+ RILT from all 88 studies were 9.1% (95% confidence interval [CI]: 7.15-11.4) and 1.8% (95% CI: 1.3-2.5), respectively. The median of median tumor sizes was 2.3 (range, 1.4-4.1) cm. Among the factors analyzed, older patient age (P=.044) and larger tumor size (the greatest diameter) were significantly correlated with higher rates of G2+ (P=.049) and G3+ RILT (P=.001). Patients with stage IA versus stage IB NSCLC had significantly lower risks of G2+ RILT (8.3% vs 17.1%, odds ratio = 0.43, 95% CI: 0.29-0.64, P<.0001). Among studies that provided detailed dosimetric data, the pooled analysis demonstrated a significantly higher mean lung dose (MLD) (P=.027) and V20 (P=.019) in patients with G2+ RILT than in those with grade 0 to 1 RILT.Conclusions: The overall rate of RILT is relatively low after thoracic SBRT. Older age and larger tumor size are significant adverse risk factors for RILT. Lung dosimetry, specifically lung V20 and MLD, also significantly affect RILT risk. [ABSTRACT FROM AUTHOR]

Purpose: To perform an independent validation of an anatomy-based inverse planning simulated annealing (IPSA) algorithm in obtaining superior target coverage and reducing the dose to the organs at risk. Method and Materials: In a recent prostate high-dose-rate brachytherapy protocol study by the Radiation Therapy Oncology Group (0321), our institution treated 20 patients between June 1, 2005 and November 30, 2006. These patients had received a high-dose-rate boost dose of 19 Gy to the prostate, in addition to an external beam radiotherapy dose of 45 Gy with intensity-modulated radiotherapy. Three-dimensional dosimetry was obtained for the following optimization schemes in the Plato Brachytherapy Planning System, version 14.3.2, using the same dose constraints for all the patients treated during this period: anatomy-based IPSA optimization, geometric optimization, and dose point optimization. Dose–volume histograms were generated for the planning target volume and organs at risk for each optimization method, from which the volume receiving at least 75% of the dose (V75%) for the rectum and bladder, volume receiving at least 125% of the dose (V125%) for the urethra, and total volume receiving the reference dose (V100%) and volume receiving 150% of the dose (V150%) for the planning target volume were determined. The dose homogeneity index and conformal index for the planning target volume for each optimization technique were compared. Results: Despite suboptimal needle position in some implants, the IPSA algorithm was able to comply with the tight Radiation Therapy Oncology Group dose constraints for 90% of the patients in this study. In contrast, the compliance was only 30% for dose point optimization and only 5% for geometric optimization. Conclusions: Anatomy-based IPSA optimization proved to be the superior technique and also the fastest for reducing the dose to the organs at risk without compromising the target coverage. [Copyright &y& Elsevier]