Acute gastrointestinal toxicity after robotic stereotactic ablative radiotherapy for treatment of metastatic gynecological malignancies.

AIMS: The aim of this study was to assess acute and subacacute gastrointestinal toxicity after fractionated stereotactic ablative radiotherapy (SABR) in women having recurrent gynecological cancers in the upper abdomen. MATERIALS & METHODS: In total, 34 women underwent upper abdominal SABR (24 Gy/three divided 8 Gy consecutive daily doses) using a robotic Cyberknife® (Accuray, CA, USA) platform. Volumes of the duodenum receiving 10% increments of the prescription dose were associated to post-therapy gastrointestinal toxicities using binary logistic regression analyses. RESULTS: Median clinical follow-up was 10 months. In total, 14 (41%) of the 34 women manifested grade 2 or higher post-therapy gastrointestinal adverse events. The duodenal volume, receiving 80% of a 24-Gy dose, was significantly associated with gastrointestinal toxicity (p = 0.03). However, in a multivariate analysis, only patient age at SABR adjusted the odds of experiencing gastrointestinal toxicity (p = 0.02). CONCLUSION: The duodenal volume receiving 80% of 24 Gy dose may be associated with gastrointestinal toxicity from upper abdominal SABR.

Variation in Androgen Deprivation Therapy Use Among Men With Intermediate-Risk Prostate Cancer: Results From a Statewide Radiation Oncology Quality Consortium.

PURPOSE: For men with intermediate-risk prostate cancer treated with definitive therapy, the addition of androgen deprivation therapy (ADT) reduces the risk of distant metastasis and cancer-related mortality. However, the absolute benefit of ADT varies by baseline cancer risk. Estimates of prognosis have improved over time, and little is known about ADT decision making in the modern era. We sought to characterize variability and identify factors associated with intended ADT use within the Michigan Radiation Oncology Quality Consoritum (MROQC). MATERIALS AND METHODS: Patients with localized prostate cancer undergoing definitive radiation therapy were enrolled from June 9, 2020, to June 26, 2023 (n = 815). Prospective data were collected using standardized patient, physician, and physicist forms. Intended ADT use was prospectively defined and was the primary outcome. Associations with patient, tumor, and practice-related factors were tested with multivariable analyses. Random intercept modeling was used to estimate facility-level variability. RESULTS: Five hundred seventy patients across 26 facilities were enrolled with intermediate-risk disease. ADT was intended for 46% of men (n = 262/570), which differed by National Comprehensive Cancer Network favorable intermediate-risk (23.5%, n = 38/172) versus unfavorable intermediate-risk disease (56.3%, n = 224/398; P < .001). After adjusting for the statewide case mix, the predicted probability of intended ADT use varied significantly across facilities, ranging from 15.4% (95% CI, 5.4%-37.0%) to 71.7% (95% CI, 57.0%-82.9%), with P < .01. Multivariable analyses showed that grade group 3 (OR, 4.60 [3.20-6.67]), ≥50% positive cores (OR, 2.15 [1.43-3.25]), and prostate-specific antigen 10 to 20 (OR, 1.87 [1.24-2.84]) were associated with ADT use. Area under the curve was improved when incorporating MRI adverse features (0.76) or radiation treatment variables (0.76), but there remained significant facility-level heterogeneity in all models evaluated (P < .05). CONCLUSIONS: Within a state-wide consortium, there is substantial facility-level heterogeneity in intended ADT use for men with intermediate-risk prostate cancer. Future efforts are necessary to identify patients who will benefit most from ADT and to develop strategies to standardize appropriate use.

Development and Validation of a Small Animal Immobilizer and Positioning System for the Study of Delivery of Intracranial and Extracranial Radiotherapy Using the Gamma Knife System.

The purpose of this research is to establish a process of irradiating mice using the Gamma Knife as a versatile system for small animal irradiation and to validate accurate intracranial and extracranial dose delivery using this system. A stereotactic immobilization device was developed for small animals for the Gamma Knife head frame allowing for isocentric dose delivery. Intercranial positional reproducibility of a reference point from a primary reference animal was verified on an additional mouse. Extracranial positional reproducibility of the mouse aorta was verified using 3 mice. Accurate dose delivery was validated using film and thermoluminescent dosimeter measurements with a solid water phantom. Gamma Knife plans were developed to irradiate intracranial and extracranial targets. Mice were irradiated validating successful targeted radiation dose delivery. Intramouse positional variability of the right mandible reference point across 10 micro-computed tomography scans was 0.65 ± 0.48 mm. Intermouse positional reproducibility across 2 mice at the same reference point was 0.76 ± 0.46 mm. The accuracy of dose delivery was 0.67 ± 0.29 mm and 1.01 ± 0.43 mm in the coronal and sagittal planes, respectively. The planned dose delivered to a mouse phantom was 2 Gy at the 50% isodose with a measured thermoluminescent dosimeter dose of 2.9 ± 0.3 Gy. The phosphorylated form of member X of histone family H2A (γH2AX) staining of irradiated mouse brain and mouse aorta demonstrated adjacent tissue sparing. In conclusion, our system for preclinical studies of small animal irradiation using the Gamma Knife is able to accurately deliver intracranial and extracranial targeted focal radiation allowing for preclinical experiments studying focal radiation.

SAT1 and glioblastoma multiforme: Disarming the resistance.

Glioblastoma multiforme is the most common and most detrimental form of brain tumor, with a current survival time of as little as 14 months. We have recently identified a novel mechanism of therapeutic resistance based on overexpression of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase, which promotes DNA repair via chromatin modification.

Phase I Trial of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Ablative Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer.

BACKGROUND: We conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR) in women with persistent or recurrent gynecologic cancers. METHODS: Patients were assigned to dose-finding cohorts of day 1 carboplatin (AUC 2 or 4) and gemcitabine (600 or 800 mg/m(2)) followed by day 2 to day 4 Cyberknife SABR (8 Gy × three consecutive daily doses). Toxicities were graded prospectively by common terminology criteria for adverse events, version 4.0. SABR target and best overall treatment responses were recorded according to response evaluation criteria in solid tumors, version 1.1. FINDINGS: The maximum tolerated dose of chemotherapy preceding SABR was carboplatin AUC 4 and gemcitabine 600 mg/m(2). One patient experienced manageable, dose-limiting grade 4 neutropenia, grade 4 hypokalemia, and grade 3 nausea attributed to study treatment. One patient had a late grade 3 rectovaginal fistula 16 months after trial therapy. Among 28 SABR targets, 22 (79%) showed a partial response and 6 (21%) remained stable. INTERPRETATION: Systemic chemotherapy may be given safely prior to abdominopelvic robotic SABR with further investigation warranted.