Stereotactic body radiation therapy (SBRT) for the treatment of primary breast cancer in patients not undergoing surgery.

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 â€‹Gy in 5 fractions for patients treated with SBRT alone and 25-32 â€‹Gy in 4-5 fractions for those treated with SBRT â€‹+ â€‹WBRT. LC and overall survival (OS) were estimated using Kaplan-Meier 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 â€‹% (range: 2-100 â€‹%) decrease in the largest diameter and median 68.7 â€‹% (range: 27.9-100 â€‹%) SUV reduction. There were 3 cases of local progression at 8.7-10.6 months. Estimated LC was 100 â€‹% at 6 months and 71.6 â€‹% at 12, 24 and 36 months. Estimated median OS was 100 â€‹% at 6 months, 76.9 â€‹% at 12 months, and 61.5 â€‹% at 24 and 36 months. Acute toxicity (n â€‹= â€‹13; 92.9 â€‹%) included grade (G)1 (n â€‹= â€‹8), G2 (n â€‹= â€‹4), and G4 (necrosis; n â€‹= â€‹1). Late toxicity included G2 edema (n â€‹= â€‹1) and G4 necrosis (n â€‹= â€‹2, including 1 consequential late effect). Only patients treated with SBRT â€‹+ â€‹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 â€‹= â€‹2) occurred in the SBRT â€‹+ â€‹WBRT group, it was successfully salvaged.

Pretreatment Spatially Aware Magnetic Resonance Imaging Radiomics Can Predict Distant Brain Metastases (DBMs) After Stereotactic Radiosurgery/Radiation Therapy (SRS/SRT).

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, fluid-attenuated inversion recovery). Three-dimensional 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) 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 identified radiomic signature was able to stratify patients into distinct risk groups with statistically significant 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 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 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 identification of patients with predisposition to DBM development and prompt subsequent changes in disease management.

Unilateral conjunctival Classic Kaposi Sarcoma following a COVID 19 booster.

Purpose: We describe a case of Classic Kaposi's sarcoma in a functionally monocular patient following a COVID19 vaccine booster and provide compelling evidence that suggests the booster was a relevant co-factor in the initiation of the disease process. Observations: The patient presented with red, irritated conjunctival area described as "bubbling" in her right eye. While her past medical history includes hypercholesterolemia and hypertension, she had no history of a compromised immune system. Her ophthalmologic history is more complex including treatment for glaucoma. The patient has 20/20 uncorrected vision OD and LP OS. Due to her ocular co-morbidities, the patient initially received interferon alpha 2-B qid for 6 weeks. However, topical therapy failed to decrease the size of the conjunctival lesions. After referral to Radiation Oncology, the right eye/orbit was treated with electron beam therapy for 1 month which caused a marked decrease in the size and vascularity of the conjunctival lesions. A slow improvement continued during followup. Conclusion and importance: In that the vaccine booster preceded the cancer, it appears etiologic to the appearance of Kaposi's sarcoma. The patient's monocular vision and glaucoma complicated her treatment. This case expands on current concepts of cofactors needed for the development of Kaposi's sarcoma in that vaccine booster administration was relevant to tumor progression and both clinical and mechanistic evidence is presented to support this hypothesis.

Phase I and pharmacodynamic study of arsenic trioxide plus radiotherapy in patients with newly diagnosed glioblastoma.

Background: When arsenic trioxide (ATO) was combined with radiation for treatment of transplanted murine gliomas in the brain, tumor response improved with disrupted tumor blood flow and survival was significantly prolonged. Methods: Total of 31 patients with newly diagnosed glioblastoma were accrued to a multi-institutional, NCI-funded, phase I study to determine the maximum tolerated dose (MTD) of ATO administered with radiation. Secondary objectives were survival and pharmacodynamic changes in perfusion on magnetic resonance imaging (MRI). Patients (unknown MGMT and IDH status) received ATO either once or twice weekly during radiation without concurrent or adjuvant temozolomide. Results: Median age: 54.9 years, male: 68%, KPS ≥ 90: 77%, debulking surgery: 77%. Treatments were well-tolerated: 81% of patients received all the planned ATO doses. Dose-limiting toxicities included elevated liver function tests, hypokalemia, and edema. The MTD on the weekly schedule was 0.4 mg/kg and on the biweekly was 0.3 mg/kg. The median survival (mOS) for all patients was 17.7 months. Survival on the biweekly schedule (22.8 months) was longer than on the weekly schedule (12.1 months) (P = .039) as was progression-free survival (P = .004). Similarly, cerebral blood flow was significantly reduced in patients treated on the biweekly schedule (P = .007). Conclusions: ATO with standard radiation is well tolerated in patients with newly diagnosed glioblastoma. Even without temozolomide or adjuvant therapy, the overall survival of all patients (17.7 months) and especially patients who received biweekly ATO (22.8 months) is surprising and accompanied by pharmacodynamic changes on MRI. Further studies of this regimen are warranted.

Intrafractional motion and dosimetric analysis in prostate stereotactic body radiation therapy with auto beam hold technique.

Objective: To summarize our institutional prostate stereotactic body radiation therapy (SBRT) experience using auto beam hold (ABH) technique for intrafractional prostate motion and assess ABH tolerance of 10-millimeter (mm) diameter.Approach: Thirty-two patients (160 fractions) treated using ABH technique between 01/2018 and 03/2021 were analyzed. During treatment, kV images were acquired every 20-degree gantry rotation to visualize 3-4 gold fiducials within prostate to track target motion. If the fiducial center fell outside the tolerance circle (diameter = 10 mm), beam was automatically turned off for reimaging and repositioning. Number of beam holds and couch translational movement magnitudes were recorded. Dosimetric differences from intrafractional motion were calculated by shifting planned isocenter.Main Results: Couch movement magnitude (mean ± SD) in vertical, longitudinal and lateral directions were -0.7 ± 2.5, 1.4 ± 2.9 and -0.1 ± 0.9 mm, respectively. For most fractions (77.5%), no correction was necessary. Number of fractions requiring one, two, or three corrections were 15.6%, 5.6% and 1.3%, respectively. Of the 49 corrections, couch shifts greater than 3 mm were seen primarily in the vertical (31%) and longitudinal (39%) directions; corresponding couch shifts greater than 5 mm occurred in 2% and 6% of cases. Dosimetrically, 100% coverage decreased less than 2% for clinical target volume (CTV) (-1 ± 2%) and less than 10% for PTV (-10 ± 6%). Dose to bladder, bowel and urethra tended to increase (Bladder: ΔD10%:184 ± 466 cGy, ΔD40%:139 ± 241 cGy, Bowel: ΔD1 cm3:54 ± 129 cGy; ΔD5 cm3:44 ± 116 cGy, Urethra: ΔD0.03 cm3:1 ± 1%). Doses to the rectum tended to decrease (Rectum: ΔD1 cm3:-206 ± 564 cGy, ΔD10%:-97 ± 426 cGy; ΔD20%:-50 ± 251 cGy).Significance: With the transition from conventionally fractionated intensity modulated radiation therapy to SBRT for localized prostate cancer treatment, it is imperative to ensure that dose delivery is spatially accurate for appropriate coverage to target volumes and limiting dose to surrounding organs. Intrafractional motion monitoring can be achieved using triggered imaging to image fiducial markers and ABH to allow for reimaging and repositioning for excessive motion.