Purpose Stereotactic radiosurgery/radiotherapy (SRS/SRT) has increasingly been used to treat brain metastases. However, the development of distant brain metastases (DBMs) in the untreated brain remains a serious complication. We sought to develop a spatially aware radiomic signature to model the time-to-DBM development in a cohort of patients leveraging pre-treatment magnetic resonance imaging (MRI) and radiotherapy treatment planning data including radiation dose distribution maps. Methods and Materials We retrospectively analyzed a cohort of 105 patients with brain metastases treated by SRS/SRT with pre-treatment multi-parametric MRI (T1, T1 post-contrast, T2, FLAIR). 3D radiomic features were extracted from each MRI sequence within 5 isodose regions of interest (ROIs) identified via radiation dose distribution maps and gross target volume (GTV) contours. Clinical features including patient performance status, number of lesions treated, tumor volume, and tumor stage were collected to serve as a baseline for comparison. Cox proportional hazards (CPH) modelling and Kaplan Meier analysis were used to model time-to-DBM development. Results CPH models trained using radiomic features achieved a mean concordance index (c-index) of 0.63 (std=0.08) compared to a c-index of 0.49 (std=0.09) for CPH models trained using clinical factors. A CPH model trained using both radiomic and clinical features achieved a c-index of 0.69 (std=0.08). The identified radiomic signature was able to stratify patients into distinct risk groups with statistically significant differences (p=0.00007) in time-to-DBM development as measured by log-rank test. Clinical features were unable to do the same. Radiomic features from the peritumoral 50-75% isodose ROI and GTV region were most predictive of DBM development. Conclusions Our results suggest that radiomic features extracted from pre-treatment MRI and multiple isodose ROIs can model time-to-DBM development in patients receiving SRS/SRT for brain metastases, outperforming clinical feature baselines. Notably, we believe we are the first to leverage SRS/SRT dose maps for ROI identification and subsequent radiomic analysis of peritumoral and untargeted brain regions using multi-parametric MRI. We observed that the peritumoral environment may be implicated in DBM development for SRS/SRT-treated brain metastases. Our preliminary results might enable the identification of patients with predisposition to DBM development and prompt subsequent changes in disease management.

Purpose: The purpose was to explore the role of stereotactic body radiation therapy (SBRT) in providing local control (LC) for primary breast cancer in patients unable to undergo surgery. Materials/methods: Between 2015 and 2019, 13 non-surgical candidates with 14 lesions were treated with SBRT for primary breast cancer. In 4 cases, SBRT was used after whole breast radiation therapy (WBRT; 40-50 Gy/ 20-25 fractions). SBRT dose was 30-40 Gy in 5 fractions for patients treated with SBRT alone and 25-32 Gy in 4-5 fractions for those treated with SBRT + WBRT. LC and overall survival (OS) were estimated using KaplanMeier curves. Response was also assessed using RECIST guidelines. Results: Median follow-up was 32 (range: 3.4-70.4) months. Imaging at median 2.2 (0.6-8.1) months post-SBRT showed median 43.2 % (range: 2-100 %) decrease in the largest diameter and median 68.7 % (range: 27.9-100 %) SUV reduction. There were 3 cases of local progression at 8.7-10.6 months. Estimated LC was 100 % at 6 months and 71.6 % at 12, 24 and 36 months. Estimated median OS was 100 % at 6 months, 76.9 % at 12 months, and 61.5 % at 24 and 36 months. Acute toxicity (n = 13; 92.9 %) included grade (G)1 (n = 8), G2 (n = 4), and G4 (necrosis; n = 1). Late toxicity included G2 edema (n = 1) and G4 necrosis (n = 2, including 1 consequential late effect). Only patients treated with SBRT + WBRT experienced acute/late G4 toxicity, managed with resection or steroids. Conclusions: SBRT to primary breast cancer resulted in good LC in non-surgical/metastatic patients. Although necrosis (n = 2) occurred in the SBRT + WBRT group, it was successfully salvaged.

Purpose: Stereotactic radiosurgery/radiation therapy (SRS/SRT) increasingly has been used to treat brain metastases. However, the development of distant brain metastases (DBMs) in the untreated brain remains a serious complication. We sought to develop a spatially aware radiomic signature to model the time-to-DBM development in a cohort of patients leveraging pretreatment magnetic resonance imaging (MRI) and radiation therapy treatment planning data including radiation dose distribution maps. Methods and Materials: We retrospectively analyzed a cohort of 105 patients with brain metastases treated by SRS/SRT with pretreatment multiparametric MRI (T1, T1 postcontrast, T2, fl uid -attenuated inversion recovery). Three-dimensional radiomic features were extracted from each MRI sequence within 5 isodose regions of interest (ROIs) identi fi ed via radiation dose distribution maps and gross target volume (GTV) contours. Clinical features including patient performance status, number of lesions treated, tumor volume, and tumor stage were collected to serve as a baseline for comparison. Cox proportional hazards (CPH) modeling and Kaplan - Meier analysis were used to model time-to-DBM development. Results: CPH models trained using radiomic features achieved a mean concordance index (c -index) of 0.63 (standard deviation [SD], 0.08) compared with a c -index of 0.49 (SD, 0.09) for CPH models trained using clinical factors. A CPH model trained using both radiomic and clinical features achieved a c -index of 0.69 (SD, 0.08). The identi fi ed radiomic signature was able to stratify patients into distinct risk groups with statistically signi fi cant differences ( P = .00007) in time-to-DBM development as measured by log -rank test. Clinical features were unable to do the same. Radiomic features from the peritumoral 50% to 75% isodose ROI and GTV region were most predictive of DBM development. Conclusions: Our results suggest that radiomic features extracted from pretreatment MRI and multiple isodose ROIs can model timeto-DBM development in patients receiving SRS/SRT for brain metastases, outperforming clinical feature baselines. Notably, we believe we are the fi rst to leverage SRS/SRT dose maps for ROI identi fi cation and subsequent radiomic analysis of peritumoral and untargeted brain regions using multiparametric MRI. We observed that the peritumoral environment may be implicated in DBM development for SRS/SRT-treated brain metastases. Our preliminary results might enable the identi fi cation of patients with predisposition to DBM development and prompt subsequent changes in disease management.

PURPOSE:Surgery is the backbone of breast cancer (BC) treatment. For patients who cannot undergo surgery, improving local control (LC) of the primary tumor is paramount. To that end, this study explored the role of stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS:Between 2015 and 2022, 21 nonsurgical candidates (10 metastatic, 11 stage IA-IIIC) received 23 SBRT courses to primary BC. Seven were analyzed retrospectively; 15 are currently enrolled in a prospective study. SBRT (40 Gy/5 fractions) was delivered every other day. Follow-up imaging was reviewed. Acute (≤3 months) and late toxicities were evaluated using Common Terminology Criteria for Adverse Events, version 5. LC and overall survival (OS) were estimated using Kaplan-Meier curves. RESULTS:Median age was 78.4 years (45.9-97.3). Median follow-up was 14.7 months (3.3-70.3). Median pre-SBRT index lesion size was 3.1 cm (0.5-14.5) and planning treatment volume was 32.4 cc (11.5-522.4). Initial posttreatment imaging performed at a median 4.0 months (0.6-11.9) post-SBRT demonstrated median decrease in index lesion size of 20.8% (0%-100%); SUV reduction of 65.2% (20.8%-100%). Second follow-up scans at a median 7.8 months post-SBRT showed 62% (0%-100%) and 88% (33.3%-100%) median reduction in tumor size and SUV, respectively, compared with pre-SBRT values. The estimated LC rate was 100% at 6 months and 93.3% at 12, 24, and 36 months. Local progression occurred in 1 case 9.5 months after SBRT, after an initial response. Regional progression occurred in 4 cases (17.4%) at a median 18.6 months (5.2-22.7) post-SBRT. Six patients (35.3%) developed distant progression at a median 2.7 months (0.9-16.2). The estimated OS was 85.7% at 6 months, 69.6% at 12 months, and 63.8% at 24 and 36 months. The rates of acute toxicity were G1: 47.8%, G2: 4.3%, G3: 8.7%, and G4: 0%. CONCLUSIONS:Definitive SBRT for primary BC resulted in good LC in nonsurgical patients and was well-tolerated. Considering the pattern of progression, additional approaches to improve regional/distant control should be investigated.

Background and purpose:Incidental thyroid gland irradiation frequently occurs in breast cancer patients who receive regional nodal irradiation (RNI) to the supraclavicular (SCV) region. Recent studies suggest hypothyroidism (HT) is a complication of radiation therapy (RT) that includes SCV fields. We retrospectively analyzed patients who received RNI to evaluate thyroid gland evolution following RT as well as its association with the development of HT. Materials and methods:61 breast cancer patients received SCV-directed RT between 2007 and 2019 and met inclusion criteria. Thyroid glands were retrospectively contoured on CT simulation and follow-up images. Individual dose-volume histograms were analyzed to determine thyroid volume within and outside specific isodose lines. Relative thyroid volume changes based on different radiation doses were estimated by fusing post-RT scans with CT simulation. Logistic regression was performed to assess thyroid volume changes as a factor in the development of HT. Results:Median pre-treatment thyroid volume was 11.8 cc (range: 6.3-74.1 cc) with a median of 42.2 % within the 20 Gy and 23.2 % within the 40 Gy isodose lines. A significant decrease in thyroid volume was noted by 1-year post-treatment (p < 0.0001) and thereafter. By 4 years post-treatment, average thyroid volume was decreased by 29.7 % (range: 2.3-64.4 %). Thyroid volume receiving 40 Gy or higher demonstrated a greater decrease compared to those receiving lower irradiation dosage. HT occurred in 17 patients (27.9 %). Patients who developed HT displayed a larger decrease in the thyroid volume receiving between 20 and 40 Gy at 12 months (p = 0.033). Conclusion:Our study demonstrates for the first time that a reduction in thyroid volume may be seen as early as 6 months after SCV-directed RT for breast cancer, which correlates with development of clinical and subclinical HT. Furthermore, a dose-dependent correlation exists between thyroid subvolume reduction and SCV-directed RT in breast cancer patients. As feasible, efforts should be made to reduce the dose to the thyroid in patients who undergo RNI for breast cancer.

Stereotactic radiosurgery (SRS) is frequently employed to treat brain metastases. However, <50% of patients treated with this method develop distant brain metastases (DBMs). As a result, these patients are followed using Magnetic Resonance Imaging (MRI) to identify DBM development. There is no current pre-treatment risk metric to identify which patients might be likely to develop DBMs. In this study, pre-treatment MRIs and radiotherapy planning data including structure sets and radiation dose maps were obtained for 81 SRS brain metastases treatment courses. Clinical variables including performance status, age, number of tumors, and primary tumor type were also collected. Pre-treatment MRIs were skull-stripped and normalized. 3D radiomic features from grey-intensity, Laws Energy, Gabor, Haralick, and CoLlAGe feature families were extracted from T1, T1 contrast-enhanced (T1w), T2, and FLAIR pre-treatment MRI sequences in brain regions receiving 0-25%, 25-50%, 50-75%, and 75-100% of prescribed radiation dose. A baseline classification model for DBM was created using clinical variables. Ablation studies were performed to determine which dose region and MRI sequence contained radiomic features most predictive for DBM development using machine learning (ML) classifiers. An ML classifier trained on 3D radiomic features from the 50-75% dose region of pre-treatment T1w MRI (AUC: 0.71, 95% CI: 0.68-0.74) outperformed the baseline model (AUC: 0.50, 95% CI: 0.47-0.53) for DBM prediction. In conclusion, we leverage radiotherapy dose regions to identify subcompartments for radiomic feature extraction from multi-parametric pre-treatment MRI data. We demonstrate that radiomic features from these dose regions can be used to predict DBM for SRS-treated brain metastases.

Primary hepatic rhabdomyosarcoma is rare, making decisions regarding locoregional management with resection and/or conventional radiation difficult. We present a novel treatment approach for a pediatric patient diagnosed with rhabdomyosarcoma diffusely involving the liver. This patient underwent treatment with yttrium-90 (Y-90) microspheres followed by external beam radiation therapy (EBRT ) to residual disease, interdigitated with systemic chemotherapy. Initial post-radiation imaging showed significant response to treatment, and she experienced minimal acute toxicities and no long-term toxicities. She developed recurrent PET-avid disease 23 months after Y-90 treatment, necessitating further local and continued systemic therapies. We report on the tumor control following Y-90 and EBRT treatment.

PURPOSE: Radiotherapy with high-dose-rate (HDR) brachytherapy is used to treat nonmelanoma skin cancers. We retrospectively analyzed a hypofractionated regimen to assess its safety and efficacy in elderly patients >= 70 years. METHODS AND MATERIALS: Forty-eight patients with 67 lesions treated since 2016 with catheter-based iridium-192 HDR brachytherapy using a custom mold or three-dimensional-printed applicator met inclusion criteria. Treatment was 36 Gy in six weekly fractions. Local and locoregional control were assessed with Kaplan-Meier curves. Acute and late toxicity were graded as per Common Terminology Criteria for Adverse Events, version 5. Cosmesis was defined as "excellent" (indistinguishable from untreated skin), "good" (minimal changes), or "poor" (extensive changes). Univariate analyses were performed. RESULTS: Median age was 85.7 years, and 21 were female. Durable local control occurred in 63 lesions (94.0%), giving estimated local control of 100% at 6 months, 95.1% at 1 year, and 88.8% at 2 years. No factors were predictive of local control on univariate analysis. All experienced acute toxicity that ultimately resolved: 28.4% Grade 2 and 4.5% Grade 3. Larger treatment volume receiving >= 36 Gy was associated with increased Grade >= 2 acute toxicity. Patients experienced late Grade 2 and late Grade 4 toxicity after 6.5% treatments each. Younger age was associated with increased Grade >= 2 late toxicity. "Good" or better cosmesis occurred in 93.2%, and "poor" cosmesis was associated with lower extremities and larger lesions. CONCLUSIONS: Hypofractionated HDR brachytherapy using 36 Gy in six weekly fractions is associated with satisfactory locoregional control and cosmesis with minimal risk of severe acute or late toxicities. (c) 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Background and purpose: Hypothyroidism (HT) is a well-known complication of radiation (RT) that includes supraclavicular (SCV) fields. We analyzed breast cancer patients who received SCV-directed RT to evaluate predictors of HT and developed the first normal tissue complication probability (NTCP) model for HT specific to breast cancer patients. Materials and methods: 192 breast cancer patients received SCV-directed RT between 2007 and 2019 and met inclusion criteria. Individual dose-volume histograms were analyzed to determine thyroid volume within and outside specific isodose lines as well as minimum, mean, and maximum doses. Multivariable logistic regression was performed to assess potential clinical and treatment factors for the development of hypothyroidism. An NTCP model was created, and model validation was performed. Results: Thirty-seven patients (19.3%) developed HT following SCV-directed RT at a median 25 months (range: 2-83 months). Multivariable analysis revealed longer length of follow-up (p = 0.015) and larger thyroid volume receiving less than 20 Gy (CV20Gy[cc]; p = 0.045) were significant prognostic factors (p = 0.039). IMRT was not associated with an increased risk of hypothyroidism (p = 0.28) despite lower CV20Gy[cc] (p = 0.0002). On NTCP modeling, CV20Gy[cc] >= 8.5 cc was associated with a risk of HT < 15%. For smaller thyroids, mean dose and thyroid volume were found to be predictive of HT risk. Model validation demonstrated comparable performances between our model and other published models (AUC 0.69-0.72). Conclusion: NTCP modeling within our patient cohort suggested that greater than 8.5 cc thyroid volume receiving less than 20 Gy may be a recommended dosimetric guideline to minimize HT risk in breast cancer patients receiving SCV-directed RT. (C) 2020 Published by Elsevier B.V. Radiotherapy and Oncology

AIMTo further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 ((90)Y) microspheres.METHODSFifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following (90)Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity.RESULTSSevere (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043).CONCLUSIONClinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for (90)Y microsphere therapy.

Purpose of reviewThis article evaluates the field of radiogenomics within recent developments in genomics and radiation biology.Recent findingsMany pediatric cancer survivors have undergone treatment with radiation, putting them at risk for long-term side-effects associated with this therapy, especially cardiac disease and secondary malignancies. Advancements in our understanding of radiation biology have led to the understanding that genetics plays a major role in determining a patient's susceptibility to developing long-term side-effects, leading to the field of 'radiogenomics'. Although initial candidate gene studies did not demonstrate replicable genetic variants that affected radiosensitivity, genome-wide association studies have recently begun to identify genes that may help explain some of the observed variation in radiosensitivity. As genomic sciences continues to progress and whole genome studies become more accessible, our understanding of the genes responsible for radiosensitivity will continue to progress.SummaryThe field of radiogenomics continues to evolve with the availability and improved cost of genomic technologies allowing the study of an increasing fraction of the human genome. Studies into genetic factors influencing individual radiosensitivity will increase our understanding of radiobiology and improve our ability to counsel patients on the adverse effects they will likely experience.

409 Background: To further define factors associated with increased incidences of hepatic, constitutional, and gastrointestinal toxicities following administration of yttrium-90 (90Y) microspheres in a sequential cohort of heterogeneous patients. Methods: Fifty-seven patients who underwent 76 treatments were assessed for toxicity incidence following 90Y administration. Post-treatment clinical and liver function test (LFT) toxicities were assessed using Common Terminology Criteria for Adverse Events version 4.03. Binary logistic regression was used to evaluate the univariate effect of factors on toxicity incidences. A multivariate binary logistic regression model was performed for each toxicity using all factors with a p < 0.10 on univariate analysis. Results: Hepatic toxicities, including LFT toxicities, were present following 46.1% of treatments, while gastrointestinal and constitutional toxicities were present following 57.3% and 55.3%, respectively. Multivariate analyses revealed that colorectal adenocarcinoma, age at time of treatment, intraprocedural stasis, decreased Karnofsky Performance Status, increased body mass index (BMI), and decreased lung shunt were statistically significant (p < 0.05) predictors for increased incidence of toxicities most prevalent among our cohort. Increased pre-treatment laboratory values including albumin, alkaline phosphatase, total bilirubin, and white blood cells were also statistically significant predictors. Conclusions: Colorectal adenocarcinoma, declining functional status, decreased lung shunt, and increased pre-treatment laboratory values should be given more clinical attention when attempting to limit toxicities and improve the quality of life in patients following 90Y treatment. Specific constitutional, gastrointestinal, and hepatic toxicities including weakness, loss of appetite, and laboratory abnormalities are also associated with patients’ age, increased BMI, and intraprocedural stasis.