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Abstract Purpose To assess the impact of two multileaf collimator (MLC) systems (2.5 and 5 mm leaf widths) on three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and dynamic conformal arc techniques for stereotactic body radiation therapy (SBRT) of liver and lung lesions. Methods Twenty-nine SBRT plans of primary liver (n = 11) and lung (n = 18) tumors were the basis of this study. Five-millimeter leaf width 120-leaf Varian Millennium (M120) MLC-based plans served as reference, and were designed using static conformal beams (3DCRT), sliding-window intensity-modulated beams (IMRT), or dynamic conformal arcs (DCA). Reference plans were either re-optimized or recomputed, with identical planning parameters, for a 2.5-mm width 120-leaf BrainLAB/Varian high-definition (HD120) MLC system. Dose computation was based on the anisotropic analytical algorithm (AAA, Varian Medical Systems) with tissue heterogeneity taken into account. Each plan was normalized such that 100% of the prescription dose covered 95% of the planning target volume (PTV). Isodose distributions and dose-volume histograms (DVHs) were computed and plans were evaluated with respect to target coverage criteria, normal tissue sparing criteria, as well as treatment efficiency. Results Dosimetric differences achieved using M120 and the HD120 MLC planning were generally small. Dose conformality improved in 51.7%, 62.1% and 55.2% of the IMRT, 3DCRT and DCA cases, respectively, with use of the HD120 MLC system. Dose heterogeneity increased in 75.9%, 51.7%, and 55.2% of the IMRT, 3DCRT and DCA cases, respectively, with use of the HD120 MLC system. DVH curves demonstrated a decreased volume of normal tissue irradiated to the lower (90%, 50% and 25%) isodose levels with the HD120 MLC. Conclusion Data derived from the present comparative assessment suggest dosimetric merit of the high definition MLC system over the millennium MLC system. However, the clinical significance of these results warrants further investigation in order to determine whether the observed dosimetric advantages translate into outcome improvements.

Abstract Background Intensity-modulated radiation therapy (IMRT) affords unparalleled capacity to deliver conformal radiation doses to tumors in the central nervous system. However, to date, there are few reported outcomes from using IMRT, either alone or as a boost technique, for standard fractionation radiotherapy for glioblastoma multiforme (GBM). Methods Forty-two patients were treated with IMRT alone (72%) or as a boost (28%) after 3-dimensional conformal radiation therapy (3D-CRT). Thirty-three patients with primary disease and 9 patients with recurrent tumors were included. Thirty-four patients (81%) had surgery, with gross tumor resection in 13 patients (36%); 22 patients (53%) received chemo-radiotherapy. The median total radiation dose for all patients was 60 Gy with a range from 30.6 to 74 Gy. Standard fractions of 1.8 Gy/day to 2.0 Gy/day were utilized. Results Median survival was 8.7 months, with 37 patients (88%) deceased at last contact. Nonparametric analysis showed no survival difference in IMRT-boost vs. IMRT-only groups. Conclusion While technically feasible, preliminary results suggest delivering standard radiation doses by IMRT did not improve survival outcomes in this series compared to historical controls. In light of this lack of a survival benefit and the costs associated with use of IMRT, future prospective trials are needed to evaluate non-survival endpoints such as quality of life and functional preservation. Short of such evidence, the use of IMRT for treatment of GBM needs to be carefully rationalized.

Abstract Purpose To quantify volumetric and positional aliasing during non-gated fast- and slow-scan acquisition CT in the presence of 3D target motion. Methods Single-slice fast, single-slice slow, and multi-slice fast scan helical CTs were acquired of dynamic spherical targets (1 and 3.15 cm in diameter), embedded in an anthropomorphic phantom. 3D target motions typical of clinically observed tumor motion parameters were investigated. Motion excursions included ± 5, ± 10, and ± 15 mm displacements in the S-I direction synchronized with constant displacements of ± 5 and ± 2 mm in the A-P and lateral directions, respectively. For each target, scan technique, and motion excursion, eight different initial motion-to-scan phase relationships were investigated. Results An anticipated general trend of target volume overestimation was observed. The mean percentage overestimation of the true physical target volume typically increased with target motion amplitude and decreasing target diameter. Slow-scan percentage overestimations were larger, and better approximated the time-averaged motion envelope, as opposed to fast-scans. Motion induced centroid misrepresentation was greater in the S-I direction for fast-scan techniques, and transaxial direction for the slow-scan technique. Overestimation is fairly uniform for slice widths < 5 mm, beyond which there is gross overestimation. Conclusion Non-gated CT imaging of targets describing clinically relevant, 3D motion results in aliased overestimation of the target volume and misrepresentation of centroid location, with little or no correlation between the physical target geometry and the CT-generated target geometry. Slow-scan techniques are a practical method for characterizing time-averaged target position. Fast-scan techniques provide a more reliable, albeit still distorted, target margin.

High-grade serous ovarian cancer (HGSC) is a challenging disease, especially for patients with immunologically "cold" tumors devoid of tumor-infiltrating lymphocytes (TILs). We found that HGSC exhibits among the highest levels of MYCN expression and transcriptional signature across human cancers, which is strongly linked to diminished features of antitumor immunity. N-MYC repressed basal and induced IFN type I signaling in HGSC cell lines, leading to decreased chemokine expression and T cell chemoattraction. N-MYC inhibited the induction of IFN type I by suppressing tumor cell-intrinsic STING signaling via reduced STING oligomerization, and by blunting RIG-I-like receptor signaling through inhibition of MAVS aggregation and localization in the mitochondria. Single-cell RNA sequencing of human clinical HGSC samples revealed a strong negative association between cancer cell-intrinsic MYCN transcriptional program and type I IFN signaling. Thus, N-MYC inhibits tumor cell-intrinsic innate immune signaling in HGSC, making it a compelling target for immunotherapy of cold tumors.

Background: Recent reports showed lack of effectiveness of pulmonary artery catheterization in critically ill medical patients and relatively late-stage surgical patients with organ failure. Since invasive monitoring requires critical care environments, the early hemodynamic patterns may have been missed. Ideally, early noninvasive hemodynamic monitoring systems, if reliable, could be used as the "front end" of invasive monitoring to supply more complete descriptions of circulatory pathophysiology., Objectives: To evaluate the accuracy and reliability of noninvasive hemodynamic monitoring consisting of a new bioimpedance method for estimating cardiac output combined with arterial BP, pulse oximetry, and transcutaneous PO2 and PCO2; we compared this system of noninvasive monitoring with simultaneous invasive measurements to evaluate circulatory deficiencies in acutely ill patients shortly after hospital admission where invasive monitoring was not readily available. We also preliminarily explored early differences in temporal hemodynamic patterns of survivors and nonsurvivors., Design and Setting: Prospective comparison of simultaneous invasive and noninvasive measurements of circulatory function with retrospective analysis of data in university-run county hospitals, university hospitals and affiliated teaching hospitals, and a community private hospital., Patients: We studied 680 patients, including 139 severely injured or hemorrhaging patients in the emergency department (ED), 129 medical (nontrauma) patients on admission to the ED, 274 high-risk surgical patients intraoperatively, and 138 patients recently admitted to the ICU., Results: A new noninvasive impedance device provided cardiac output estimations under conditions in which invasive thermodilution measurements were not usually applied. There were 2,192 simultaneous bioimpedance and thermodilution cardiac index measurements; the correlation coefficient, r = 0.85, r2 = 0.73, p < 0.001. The precision and bias was -0.124+/-0.75 L/min/m2. Both invasive and noninvasive monitoring systems provide similar information and identified episodes of hypotension, low cardiac index, arterial hemoglobin desaturation, low transcutaneous O2, high transcutaneous CO2, and low oxygen consumption before and during initial resuscitation. The limitations of noninvasive systems were described., Conclusions: Noninvasive monitoring systems gave continuous displays of physiologic data that provided information allowing early recognition of low flow and poor tissue perfusion that were more pronounced in the nonsurvivors. Noninvasive systems may be acceptable alternatives where invasive monitoring is not available.

Fever is a common clinical problem in patients hospitalized with trauma. When an infection is suspected, it is important to identify the source of fever and begin definitive care before more severe morbidity occurs. An undirected approach with "pan cultures" has resulted in a high rate of negative cultures obtained and has increased patient care costs. By developing and using an evidence-based fever workup guideline, this institution was able to evaluate and identify infections and reduce costs.