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Highlights • DCA in most cases is superior to VMAT for multi metastases single isocenter SRS. • Normal brain V12Gy was significantly reduced with DCA, predicting for lower S-NEC. • Maximum doses to critical organs-at-risk were significantly lower with DCA. • Conformity was comparable between VMAT and DCA., Background and purpose Whole brain radiation therapy use has decreased in favor of stereotactic radiosurgery (SRS) for the treatment of multiple brain metastases due to reduced neurotoxicity. Here we compare two single isocenter radiosurgery planning techniques, volumetric modulated arc therapy (VMAT) and dynamic conformal arcs (DCA) in terms of their dosimetric and delivery performance. Materials and methods Sixteen patients with 2– 18 brain metastases (total 103; median 4) previously treated with single fraction SRS were replanned for multiple lesion single isocenter treatments using VMAT and DCA using different treatment planning systems for each and three different plan geometries for DCA. Plans were evaluated using the Paddick conformity index, normal tissue V12Gy, the probability for symptomatic brain necrosis (S-NEC), maximum organ-at-risk (OAR) point doses, and total number of monitor units (MU). Results Conformity was not significantly different between VMAT and DCA plans. VMAT plans showed a trend towards higher MU with a median difference between 18% and 24% (p ≤ 0.09). Median V12Gy differences were 7.0 cm3–8.6 cm3 favoring DCA plans (p

Megavoltage computed tomography (MVCT) image quality metrics were evaluated on an Accuray Radixact unit to recommend scan settings for the implementation of a consistent adaptive radiotherapy program. Megavoltage computed tomography image quality was evaluated and compared to a kilovoltage CT (kVCT) simulator using a commercial cone beam computed tomography image quality phantom. Megavoltage computed tomographies were acquired on the Accuray Radixact using fine, normal, and coarse pitches, with all available reconstruction slice thicknesses, each of which were reconstructed using standard and iterative reconstruction (IR). Image quality metrics (IQM) were evaluated using DoseLab: automatically and manually calculated spatial resolution, subject contrast, and contrast‐to‐noise ratio (CNR). Scanning time was 15.6 s/cm for fine, 8.1 s/cm for normal, and 5.6 s/cm for coarse pitch. Automatically evaluated spatial resolutions ranged from 0.39, 0.41, to 0.42 lp/mm for standard reconstruction and from 0.24, 0.21, to 0.18 lp/mm for soft‐tissue IR, respectively, with general IR yielding values in between these. Spatial resolution for kVCT was measured to be at least 0.42 lp/mm. Contrast was consistent across MVCT settings with 8.1 ± 0.2%, while kVCT contrast was 10.27 ± 0.05%. CNR was calculated to be 3.3 ± 0.4 for standard reconstruction, 7.4 ± 0.4 for general IR, and 12.0 ± 1.9 for soft‐tissue IR. It was found that increasing reconstruction slice thickness for a given pitch does not improve IQMs. Based on the consistency of contrast metrics across pitch values and the only slightly reduced spatial resolution using normal compared to fine pitch, we recommend the use of normal pitch with 2 mm slice thickness to maximize image quality for ART while limiting scanning time. Only for sites for which improved CNR is required and reduced spatial resolution is acceptable, soft‐tissue IR is recommended.

Purpose/objective(s) To assess outcomes after definitive chemo-irradiation in HIV patients with anal cancer, and evaluate hemato-immunologic (HI) toxicity by dynamics of CD4+ cell counts and lymphocytes and their association with the dose received by active bone marrow (ABM). Materials/methods Patients treated for anal cancer with HIV infection at a single institution between 2007-2020 were identified. Characteristics were tabulated along with CD4+ cell counts and lymphocytes ranging from before treatment to length of follow-up. Dose to ABM was derived by overlaying the bone contours and 3D dose matrix on a pre-treatment PET/CT scan using deformable registration. Parts of the bone with greater than the mean PET standardized uptake value (SUV) in the bone were designated as ABM. Differences in HI parameters over time points were compared using Wilcoxon rank sum tests; risk of recurrence, overall survival (OS) and progression-free survival (PFS) were modeled using Kaplan-Meier methods. Results A total of 44 patients with anal cancer and HIV were identified, of which 7 had detectable HIV viral load pre-treatment. Radiation was most commonly 50.4-54 Gy via IMRT; 3 patients underwent RT alone. Chemotherapy was 5-fluorouracil+mitomycin (n = 27), Capecitabine+mitomycin (n = 11), or other (n = 3). With median follow-up 59 months (range: 5-164) there were 7 loco-regional recurrences, 2 distant metastases and 9 deaths. The 2- and 5-year OS for patients with stage I/II disease was 100% and 93.3% vs. 88.1% and 66.6% for stage III, the 2- and 5-year PFS were both 93.8% for stage I/II disease vs. 76.5% and 56.7% for stage III. Outcomes with 5FU vs. capecitabine were comparable with 2-year OS of 92.3% and 90.9% (P = 0.89) and PFS of 77.4% and 90.9% (P = 0.26). CD4 counts dropped from a pre-treatment median of 320 cells/ul to 101 at nadir (after ∼3 months), to 163 at 1 year and 214 at 2 years post IMRT. Lymphocyte counts changed from 1,600 per ul to 400 at nadir, to 1,200 and 1,400 at 1 and 2 years. Patients with distant or locoregional recurrence showed trends (P Conclusion Outcomes after definitive chemo-IMRT were promising with excellent OS and PFS in this vulnerable patient group, with no difference when substituting 5-fluorouracil for capecitabine. There was some acute HI toxicity with worse recovery in patients who experienced disease recurrence and strategies to better spare ABM including dose de-escalation are ongoing.

Purpose: To assess clinically relevant image quality metrics (IQMs) of helical fan beam kilovoltage (kV) fan beam computed tomography (CT). Methods and Materials: kVCT IQMs were evaluated on an Accuray Radixact unit equipped with helical fan beam kVCT to assess the capabilities of this newly available modality. kVCT IQMs were evaluated and compared to a kVCT simulator and linear accelerator-based cone beam CTs (CBCT) using a commercial CBCT image quality phantom. kVCTs were acquired on the Accuray Radixact for all combinations of kVp and mAs in fine mode using a 440-mm field of view (FOV). Evaluated IQMs were spatial resolution, overall uniformity, subject contrast, contrast-to-noise ratio (CNR), and effective slice thickness. Imaging dose was assessed for planar kV imaging. Results: On this kVCT system spatial resolution and contrast were consistent across all settings with 0.28 ± 0.03 lp/mm and 9.8% ± 0.7% (both 95% confidence interval). CNR strongly depended on selected mode (views per rotation) and body size (mA per view) and ranged between 7.9 and 34.9. Overall uniformity was greater than 97% for all settings. Large FOV was not found to substantially affect the IQMs whereas small FOV affected IQMs due to its effect on pitch. Technique-matched CT simulator scans were comparable for uniformity and contrast, while spatial resolution was higher (0.43 ± 0.06 lp/mm), and CNR was between 4% (140 kVp) and 51% (100 kVp) lower. For kV-CBCT, spatial resolutions ranging from 0.37 to 0.44 lp/mm were achieved with comparable contrast, CNR, and uniformity to kVCT. All kVCT scans exhibit imaging artifacts due to helical acquisition. Clinical acquisitions of megavoltage (MV) CT, kV-CBCT, and kVCT on the same patient showed improved and comparable image quality of kVCT compared to MVCT and kV-CBCT, respectively. Conclusions: Helical fan beam kVCT allows for daily image guidance for localization and setup verification with comparable performance to existing kV-CBCT systems. Scan parameters must be selected carefully to maximize image quality for the desired tasks. Due to the large effective slice thicknesses for all parameter combinations, kVCT scans should not be used for simulation or planning of stereotactic procedures. Finally, improved image quality over MVCT has the potential to greatly improve manual and automated adaptive monitoring and planning.

Objectives: We conducted the first systematic literature review and analysis of psychiatric manifestations in Niemann-Pick disease type C (NPC) to describe: (1) time of occurrence of psychiatric ma...

Background Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales. Methods This retrospective, observational chart review included patients with NP-C from five expert NP-C centers. Patient disability scores were recorded using three published NP-C disability scales, and a unified disability scale was developed to allow comparison of data from each scale. Disease progression was represented by scores on the unified NP-C disability scale. Patients were stratified as infantile (

Objective There is a need for fast, minimally invasive sutureless replacement of mitral valves. Methods Unchanged FDA-approved biological valve prostheses were sutured to Nitinol attachment rings (Endosmart, Stutensee, Germany) that were covered with textile (devices). The lower flange of the device was stretched in ice water and maintained in a stretched position with stretching sutures. In 9 acute pig experiments through a limited left thoracotomy, a single suture was placed around the mitral annulus, the device was positioned, the annular suture tied, the stretching sutures retracted, and the device activated by warm saline. Position of the device, heart and valve function, coronary arteries, left ventricular outflow tract, and surrounding structures were observed with transoesophageal echocardiography, left ventricular and coronary angiograms, and pathologic examination at autopsy. Results The devices could be easily navigated to the mitral valve annulus and actuated within seconds. Three devices were placed with warm blood in the operative field and were tilted or dislocated at autopsy. In the other 6 devices, transesophageal echocardiography and left ventricular and coronary angiography demonstrated normal prosthetic valve and heart function, without valvular or para-device leakage, and with normal aortic valve and coronary arteries. At autopsy in these 6 cases, the devices were strongly fixed at the anatomic mitral valve annulus, without abnormalities of the device, heart valve prosthesis, left ventricular outflow tract, or aortic valve ostium. Conclusions Nitinol attachments rings combined with unchanged biological valve prostheses can make fast and strong sutureless replacement of the mitral valve feasible in acute pig experiments. Applicators that constrain and release the device mechanically need to be developed.