OSLDs produce results with an uncertainty comparable to other dosimeters near the surface of the applicator but the uncertainty increases to an unacceptably high level with distance from the applicator. RTQA2 radiochromic film is shown to be accurate both at the surface of the applicator and at distances of 1-2 cm.
Objectives: Patients undergoing single fraction intraoperative radiation therapy (IORT) for early stage breast cancer were analyzed to determine rates of local recurrence and to identify predictors of local recurrence. Materials and Methods: Patients who underwent intraoperative radiotherapy (IORT 20 Gray at 50kV using the INTRABEAMTM IORT system) have been analyzed over a 7 year period. The procedures were performed at a single institution by a single surgical and radiation oncology group. Post-operative whole breast radiotherapy (WBRT) was generally recommended in high risk patients with positive sentinel lymph nodes (SLN), lymphovascular invasion (LVI), extensive intraductal component (EIC), or positive margins requiring re-excision. Local recurrence was defined as any same breast recurrence during the follow-up period. Results: A total of 438 patients were included in the analysis. Median follow-up was 35 months. Median age was 68 years, mean tumor size on preoperative ultrasound was 1.2 cm. Patient characteristics are listed below: Patient/Tumor CharacteristicnGrade 1-232474.5%Grade 311125.5%Presence of LVI429.9%Presence of EIC4811.6%ER Negative429.7%PR Negative7918.4%DCIS only6514.4%Invasive Lobular only102.2%Positive SLN276.9%Re-excision performed6013.7% A total of 16 patients (3.7%) had a local or simultaneous local/regional recurrence. Median time to recurrence was 24.5 months. When analyzing associations between predictor variables and local recurrence using logistic regression, it was found that high tumor grade, EIC, LVI, DCIS or DCIS component, and need for re-excision were significant (p<0.05) predictors of local recurrence. Furthermore, there was a strong association with local recurrence and time to local recurrence when adjuvant endocrine therapy was recommended but the patient was either non-compliant or discontinued use due to side-effects (odds ratio 0.064, p<0.0005). Conclusions: INTRABEAMTM IORT can be used in select breast cancer patients with low local recurrence rates. Unfavorable tumor features and non-compliance with adjuvant endocrine therapy result in the highest risk of local recurrence. Better patient selection and pre-treatment education should minimize this risk. Citation Format: Christina Munford, William E Burak Jr, Krista Miller, Jennifer Davis, Nicole Neal, Caleb Price, Matthew Bertke, Michael Hasselle, Aaron Pederson. A seven year single institution experience with IntrabeamTM intraoperative radiation therapy:recurrence rates and predictors of recurrence [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-16.
Introduction Immune effector cell-associated neurotoxicity syndrome (ICANS) is a neurologic syndrome that occurs in approximately 65% of adults undergoing CAR-T therapy for treatment of B-cell malignancies refractory to conventional chemotherapy. The presentation of ICANS is variable and sometimes progressive, including symptoms of headache, aphasia, seizure, cerebral edema, and coma. The exact mechanism of ICANS is unknown, but may be driven by cytokine release, endothelial activation, and blood-brain barrier disruption (BBBD). Prior studies show increases in angiopoietin 2 (ANG2) and lower angiopoietin 1 (ANG1) suggesting endothelial destabilization and consequent BBBD. It is not yet clear if cellular injury to the central nervous system (CNS) also occurs. Blood-based damage-associated protein biomarkers have shown promise in forecasting presence, severity, and prognostic outcomes following acute neurologic injuries such as traumatic brain injury, including S100 calcium binding protein B (S100b) and Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1). S100b is predominantly of astroglial origin and is established as a biomarker of secondary brain injury, while UCH-L1 is selectively expressed in neurons and reflects neuronal injury. Objective To characterize the relationship between the development of ICANS and plasma markers of inflammation, BBBD, and CNS cellular injury following CAR-T cell therapy. Methods We performed an interim analysis of an ongoing, prospectively enrolled cohort of adults receiving CD-19 targeted CAR-T therapy for hematologic malignancies. Blood samples are obtained at baseline prior to induction chemotherapy, and at 24-48 hours post-CAR-T infusion. Symptomatic samples are obtained when/if a patient develops ICANS as determined by interval screening using Immune Effector Cell-Associated Encephalopathy (ICE) scores, which assesses for the presence and severity of ICANS. Blood samples are centrifuged, aliquoted for plasma, and stored at -80° C. Markers of interest for this analysis were measured in batch by Luminex immunofluorescence, and included ANG1, ANG2, IL-6, S100b, and UCH-L1. Concentrations are reported in median [IQR] pg/mL. Parametric continuous variables were analyzed by independent two sample t-tests; Wilcoxon rank sum tests were used for non-parametric variables. Categorical variables were compared by chi-square tests. All analyses were conducted in R (R Core Team 2019, R Foundation for Statistical Computing, Vienna, Austria). Results The first 17 consecutive subjects (35% women) were included in this analysis in whom 8 (47%) developed ICANS. The most common diagnosis was diffuse large B-cell lymphoma (77%). No differences were observed in sex, race, ethnicity, and diagnosis categories between subjects who did and did not develop ICANS. All patients had baseline samples, however, only 14/17 patients had 24-48-hour samples, and only 2/8 patients with ICANS had symptomatic samples drawn. At baseline, there were no differences in median ANG1 (1172 [390-1609] v. 1651 [313-1910] pg/mL, P=0.96), ANG2 (1180 [732-1544] v. 1089 [592-2510] pg/mL, P=0.88) or ANG2/ANG1 ratio (P=0.96) between patients who later developed ICANS and those who did not. Similarly, there were no differences in baseline levels of IL-6 (2.6 [3.2-5.4] v. 1.5 [2.8-6.4] pg/mL, P=0.60) or S100b (0 [0-0] v. 0 [0-111] pg/mL, P=0.09) between ICANS groups. In the 2 patients who developed ICANS where symptomatic blood draws were obtained, both had precipitous rises in S100b from baseline to symptomatic levels (Case 1: 0 pg/mL ->153pg/mL, Case 2: 0 ->79 pg/mL) (Figure 1). Both of these patients died; one during acute hospitalization after CAR-T infusion while the other died 9 months after CAR-T due to cancer recurrence. UCH-L1 was below the detection limit in the plasma of all patients at all timepoints. Conclusions Our preliminary analysis suggests that baseline levels of inflammatory and endothelial permeability markers might be similar between those who do and do not develop ICANS after CAR-T infusion, and thus may not be informative about subsequent course. We also observed increases in the astrocytic marker S100b in symptomatic ICANS patients compared to baseline levels that appear to track with ICANS severity. In contrast, the neuronal marker UCH-L1 was undetectable in all patients. However, these observations must be confirmed in a larger cohort with complete data. Disclosures Hinson: Biogen (CHARM trial): Consultancy; Neurology (Journal): Other: Editorial Work; NIH NINDS Grant (1K23NS110828-01A1): Other: Grant funding TBI research (unrelated to present abstract).
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