Medical Systems Inc Research Articles

The Impact of Heat-Not-Burn, E-Cigarettes, and Cigarettes on Small Airway Function.

E-cigarettes and heated tobacco products (HTPs) are gaining worldwide significance. The tobacco industry is promoting these products as healthier alternatives to conventional cigarettes. In this four-arm crossover study, we examined the acute effects of cigarette smoking, vaping IQOS, or vaping e-cigarettes (with or without nicotine) on hemodynamics, arterial stiffness, and small airways. Twenty subjects (10 male, 10 female), all occasional smokers, completed each study arm. There was at least a 48h washout period before each test day. Arterial stiffness and peripheral and central hemodynamics were assessed using Mobil-O-Graph™ (I.E.M., Germany), whereas tremoFlo® c-100 (Thoracic Medical Systems Inc) was used to evaluate the effects on the small airways and resistance. Cigarettes, IQOS, e-cigarettes containing nicotine, and nicotine-free e-cigarettes had similar effects on peripheral and central hemodynamics as well as on arterial stiffness. We observed a significant increase in all parameters. However, only nicotine-containing products lead to increased bronchial obstruction, higher reactance, and a higher tidal volume. Therefore, we concluded that cigarettes, IQOS, and e-cigarettes have similar effects on hemodynamics. No differences were observed between the nicotine-containing and nicotine-free e-cigarettes. All nicotine-containing products also influence small airways. These findings suggest that e-cigarettes and HTPs are not healthier alternatives than conventional cigarettes.

Development of an FRα Companion Diagnostic Immunohistochemical Assay for Mirvetuximab Soravtansine.

Folate receptor-α (FRα, encoded by the FOLR1 gene) is overexpressed in several solid tumor types, including epithelial ovarian cancer (EOC), making it an attractive biomarker and target for FRα-based therapy in ovarian cancer. To describe the development, analytic verification, and clinical performance of the VENTANA FOLR1 Assay (Ventana Medical Systems Inc) in EOC. We used industry standard studies to establish the analytic verification of the VENTANA FOLR1 Assay. Furthermore, the VENTANA FOLR1 Assay was used in the ImmunoGen Inc-sponsored SORAYA study to select patients for treatment with mirvetuximab soravtansine (MIRV) in platinum-resistant EOC. The VENTANA FOLR1 Assay is highly reproducible, demonstrated by a greater than 98% overall percent agreement (OPA) for repeatability and intermediate precision studies, greater than 93% OPA for interreader and greater than 96% for intrareader studies, and greater than 90% OPA across all observations in the interlaboratory reproducibility study. The performance of the VENTANA FOLR1 Assay in the SORAYA study was evaluated by the overall staining acceptability rate, which was calculated using the number of patient specimens that were tested with the VENTANA FOLR1 Assay that had an evaluable result. In the SORAYA trial, data in patients who received MIRV demonstrated clinically meaningful efficacy, and the overall staining acceptability rate of the assay was 98.4%, demonstrating that the VENTANA FOLR1 Assay is safe and effective for selecting patients who may benefit from MIRV. Together, these data showed that the assay is highly reliable, consistently producing evaluable results in the clinical setting. The VENTANA FOLR1 Assay is a robust and reproducible assay for detecting FRα expression and identifying a patient population that derived clinically meaningful benefit from MIRV in the SORAYA study.

Validation of Dual-Color Dual In Situ Hybridization for HER2/neu Gene in Breast Cancer.

Human epidermal growth factor (HER2/neu) gene amplification, a poor prognostic factor in invasive breast cancer, has shown substantial utility as a predictive marker, with significantly improved survival following anti-HER2 therapies like trastuzumab. Dual-color dual in situ hybridization (D-DISH), a recently introduced fully automated assay for HER2/neu evaluation on light microscopy, has several advantages over fluorescence in situ hybridization (FISH). To standardize and validate the D-DISH assay using FISH as the gold standard and assess interobserver reproducibility in interpreting the D-DISH assay. D-DISH was performed using the latest HER2 Dual ISH DNA Probe Cocktail assay (Ventana Medical Systems Inc, Tucson, Arizona) in 148 cases of invasive breast cancer. The same block was used for performing immunohistochemistry by Ventana PATHWAY anti-HER2/neu (4B5) antibody and FISH assay by ZytoLight SPEC ERBB2/CEN17 Dual Color Probe. D-DISH was separately interpreted by 4 pathologists blinded to FISH results. Concordance of 98.65% and a Cohen κ value of 0.97 were observed between FISH and D-DISH. Intraclass correlation coefficient (0.93-0.97) and κ values (0.98-1.0) for interobserver reproducibility showed almost perfect agreement by D-DISH. Interobserver reproducibility was also evaluated for genomic heterogeneity, HER2 group categorization, and polysomy (κ values 0.42-0.74, 0.89-0.93, and 0.98-1.0, respectively). We successfully validated the latest version of D-DISH assay as a substitute for FISH in predicting HER2 gene status with significant interobserver reproducibility, concluding that this D-DISH assay may be introduced in routine diagnostic services as a reflex test to ascertain HER2 gene status.

Is Thalamic DBS Synergistic With VNS in Drug Resistant Genetic Generalized Epilepsy? (P5-1.001)

<h3>Objective:</h3> To report prolonged seizure freedom and improved quality of life after combining anterior nucleus of the thalamus deep brain stimulation (ANT-DBS) with vagus nerve stimulation (VNS) in a patient with drug resistant genetic generalized epilepsy (GGE). <h3>Background:</h3> Neuromodulation remains at forefront of management in patients with drug-resistant epilepsies though efficacy has been palliative and FDA approved in focal epilepsies. While polytherapy with anti-seizure medications (ASMs) is common, dual neuromodulation has received limited attention. <h3>Design/Methods:</h3> A 32-year-old female patient with drug resistant GGE who failed 10 antiseizure medications underwent video-EEG monitoring. EEG revealed 3–3.5 Hz generalized polyspike-and-wave discharges and generalized paroxysmal fast activity in brief run lasting less than 3 seconds increased during sleep. Seizures were not recorded. VNS model 106 Aspire SR was implanted at age 23 achieving parameters of 1.5 mA, 25 Hz, 250 μs, 14 sec on, 1.1 min off. Despite improvement with seizure reduction, ongoing monthly convulsions resulted in recurrent injuries. The patient subsequently underwent bilateral ANT-DBS placement with inferior most contacts on both sides well-positioned at the junction of the mammillothalamic tracts for monopolar stimulation at 5 V, 145 Hz, and 90 μs. <h3>Results:</h3> Neuro- “modulation” was observed in our patient with VNS following implantation of ANT-DBS by gradual reduction diminishing seizure frequency, intensity, and duration to ultimately become seizure-free for 21 months. Stable doses of Onfi 20 mg po bid and Keppra 1500 mg po bid were continued. After combining ANT-DBS with her incomplete VNS response she married, became employed, and was able to retain driving privileges and lead an independent lifestyle. <h3>Conclusions:</h3> Identifying a subset of patients with GGE responsive to polyneuromodulation promises personalized therapy for those with life-altering effects from generalized seizures. We speculate that the thalamic network connectivity may be modulated by dual ANT-DBS and VNS, leading to targeted neurobiological therapy in some patients with GGE. <b>Disclosure:</b> Dr. Khan has nothing to disclose. Erik Middlebrooks has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Varian Medical Systems Inc. Erik Middlebrooks has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific Corp. The institution of Erik Middlebrooks has received research support from Varian Medical Systems Inc. Dr. Freund has nothing to disclose. Sanjeet S. Grewal, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Dr. Tatum has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bioserenity. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Defense Law Firm on behalf of a patient with epilepsy with funds donated to the Epilepsy Foundation of America. The institution of Dr. Tatum has received research support from Esai. The institution of Dr. Tatum has received research support from Mayo Clinic. The institution of Dr. Tatum has received research support from Liva Nova. The institution of Dr. Tatum has received research support from Engage Pharmaceuticals. The institution of Dr. Tatum has received research support from Xenon. Dr. Tatum has received publishing royalties from a publication relating to health care. Dr. Tatum has received publishing royalties from a publication relating to health care.

Protective Effect of APOE-ɛ2 on Cortical Thickness and Volume in a Cerebrovascular Registry (S36.010)

<h3>Objective:</h3> To compare cortical thickness across APOE genotypes, and to assess the potential protective effect of APOE2 on brain cortical thinning and grey matter volume. <h3>Background:</h3> Studies have shown a negative association of APOE-ɛ4 allele with regional cortical thickness and volume. The role of the APOE-ɛ3 allele has been considered neutral in several studies. The protective role of APOE-ɛ2 against cortical thinning has not been well established. <h3>Design/Methods:</h3> From a biomarker cerebrovascular registry, 187 individuals with APOE testing and MRI brain from 2010 to 2020 were included. APOE genotype tested were ɛ2ɛ2, ɛ2ɛ3, ɛ2ɛ4, ɛ3ɛ3, ɛ3ɛ4, ɛ4ɛ4, stratified to APOE-ɛ2 carrier or APOE-ɛ2 non-carrier. Cortical thickness, cortical volume and gray matter volume were estimated on T1-weighted images using FreeSurfer. Measures of brain atrophy were compared across APOE genotypes, and between ɛ2 vs non-ɛ2 allele carriers. Mini-Mental Status Examination (MMSE) were compared between groups. <h3>Results:</h3> In our cohort (n=187), mean age was 60±16 years and 55.4% were female. Of the APOE genotypes, 18.5% were APOE-ɛ2 carriers (ɛ2ɛ2 3, ɛ2ɛ3 33), 81.5% were APOE-ɛ2 non-carriers (ɛ3ɛ3 114, ɛ3ɛ4 43, ɛ4ɛ4 2). Compared to ɛ2 non-carriers, ɛ2 carriers were less likely to have hypertension, diabetes, coronary artery disease, and had higher LDL (p&lt;0.05). Across APOE genotypes, cortex was thickest in ɛ2ɛ2 (2.35 mm) and thinnest in ɛ4ɛ4 (1.92 mm) (p = 0.0137). APOE-ɛ2 carriers had significantly thicker cortex (2.13 mm vs 1.96 mm, p=0.001), larger cortical volume (313.26 cm3 vs 266.09 cm3, p=&lt;0.001) and grey matter volumes (459.93 cm3 vs 411.01 cm3, p=0.001), compared to ɛ2 non-carriers. There was no difference in MMSE between ɛ2carriers vs non-carriers (24.4 vs 25.6, p=0.316). <h3>Conclusions:</h3> Our study suggested a protective effect of APOE-ɛ2 allele against cortical thinning and grey matter volume loss. Future study may examine the effect of APOE-ɛ2 on brain resilience after brain injury such as stroke. <b>Disclosure:</b> Mr. Youssef has nothing to disclose. Mr. Mateti has nothing to disclose. Erik Middlebrooks has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Varian Medical Systems Inc. Erik Middlebrooks has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific Corp. The institution of Erik Middlebrooks has received research support from Varian Medical Systems Inc. The institution of Dr. Taner has received research support from NIH. The institution of Dr. Meschia has received research support from NINDS. The institution of Dr. Meschia has received research support from NINDS. Dr. Lin has nothing to disclose.

THE CONTRALATERAL LIMB IS NOT AN ADEQUATE REHABILITATION GOAL FOR ASSESSING MUSCLE FUNCTION IN AN ANTERIOR CRUCIATE LIGAMENT-INJURED PAEDIATRIC POPULATION

To investigate changes in quadriceps and hamstrings muscle groups during sustained isokinetic knee flexion and extension.125 paediatric participants (45 males and 80 females, mean age 14.2 years) were divided into two groups: participants with a confirmed ACL tear (ACLi, n = 64), and puberty- and activity-level matched control participants with no prior history of knee injuries (CON, n = 61). Participants completed a series of 44 repetitions of isokinetic knee flexion and extension at 90 deg/ sec using a Biodex dynamometer (Biodex Medical Systems Inc, Shirley, New York). Surface EMG sensors (Delsys Incorporated, Natick, MA) simultaneously recorded the quadriceps and hamstring activations. Muscle function was assessed as the change in quadriceps activation and extension torque were calculated using the percent difference between the mean of the first five trials, and the mean of the last five trials.ACLi participants had significantly higher percent change in quadriceps activation for both healthy and injured legs, in comparison to CON dominant leg. As such, the healthy leg of the ACLi participants is activating significantly more than their health matched controls, while also demonstrating reduced muscular endurance (less torque in later repetitions). Therefore, we conclude that the non-injured limb of the ACLi participant is not performing as a healthy limb. Since return to activity clearance following ACLi implies return to sport against age- and activity matched opponents, clearing young athletes based on the non-injured contralateral limb may put them at greater risk of reinjury.

Phase II Clinical Trial of Image-Guided Cognitive-Sparing SRS in Patients With Brain Metastases

SRS for brain metastases is associated with a high rate (52%-64%) of cognitive deterioration. We performed a phase II clinical trial of critical white matter and hippocampal sparing brain SRS in patients with limited brain metastases, to improve cognitive preservation. We present feasibility of this approach and interim results.Adult patients with limited volume (< 10cc) brain metastases were enrolled on this single institution clinical trial from 2018-2021. Inclusion criteria include: age ≥ 18, expected life expectancy > 6 months, pathologic confirmation of malignancy. Prior WBRT was exclusionary. High resolution volumetric MRI with diffusion tensor imaging was performed pre-SRS and at 1-, 3- and 6-months post SRS. Regions of interest (ROIs) were segmented using robust, automated atlas-based tractography and hippocampal (HC) parcellation methods. 20 white matter (WM) tracts critical for cognitive functioning and fine motor skills, and the HC were designated as ROIs to spare during SRS planning. Knowledge-based SRS planning was employed, and all attempts were made to achieve ROI dose constraints without sacrificing target coverage or other OAR doses. Single fraction max dose constraints were 12 Gy for WM/8.4 Gy for HC (iso-effective doses used for 3 and 5 fraction SRS). A well-validated battery of neurocognitive (NCA) tests, including verbal memory and language, was performed pre and 3 months post SRS. Raw scores were converted to t-scores adjusting for age, sex, and years of education. Decline was considered > 1 standard deviation drop.Median age of cohort (n = 31) was 66 years and 58% were female. Most common primary was NSCLC (39%) or melanoma (23%), and 90% of patients had 1-3 brain metastases. Prescription doses ranged from 21-30 Gy in 1-5 fractions; 10 patients were treated with both single and multi-fraction SRS to different targets. Max dose constraints for ROIs were met on 69% of SRS plans. Across plans, constraints were met for 98% of 595 WM tracts and 97% of 64 HC treated. At 6 months post SRS there were no local failures. To date (median follow up: 6 months), 5 patients have died from systemic disease progression and 1 patient from distant brain disease progression. For patients in whom pre and 3-month NCA scores were available (n = 13), 97% of WM ROIs and 100% of HC ROIs met study constraints. At 3 months, 74% of patients had no decline on HVLT total/delayed recall memory tests. Similarly, 93% and 89% showed no decline on BNT and DKEFS letter fluency language tests, respectively. There was no significant change in NCA test scores in the cohort from pre to 3 months post SRS (paired t-test, P-values > 0.05).Critical WM and HC sparing brain SRS using automated segmentation/planning tools is achievable and feasible, though can depend on proximity to targets. Sparing these critical structures may improve cognitive preservation in domains such as verbal memory and language.S. Unnikrishnan: None. R. Karunamuni: None. G. Kim: None. M. Connor: None. M.A. Salans: None. P. Sanghvi: Speaker's Bureau; Varian, VisionRT.A. Bruggeman: Research Grant; American Society of Clinical Oncology. D.R. Simpson: None. J. Yu: None. A. Reyes: None. A. Stasenko: None. K.L. Moore: Research Grant; Varian Medical Systems Inc. Honoraria; Varian Medical Systems Inc. Travel Expenses; Varian Medical Systems Inc. V. Moiseenko: None. C. McDonald: Research Grant; GE.J.A. Hattangadi-Gluth: Research Grant; NIH/NCI. Honoraria; Varian Medical Systems. Consultant; Varian Medical Systems. Site PI for cooperative group trials at UCSD for CNS; Site-PI; NCCN.

Abstract TP479: Early Effect of Human Immunodeficiency Virus on Cerebral Blood Flow and Autoregulation

Introduction: Human immunodeficiency virus (HIV)-infected individuals are at high risk for ischemic stroke. We measured cerebral blood flow (CBF), oxygen extraction fraction (OEF), and autoregulation in HIV infected subjects and controls. Methods: In treatment-naive HIV infected subjects and age-, gender-, and race-matched controls, OEF was measured by using MRI T2*-weighted echo-planar imaging sequences and CBF was measured by MRI pulsed arterial spin labeling (PASL) approach. Static cerebral autoregulation was determined by measuring changes in CBF and OEF, in response to ≈10% reductions in MAP induced by using IV Nicardipine infusion. All images were acquired using a Siemens 3T MR scanner (Treo, Siemens Medical Systems Inc). Cerebral autoregulation was measured globally and regionally in gray matter (GM), white matter (WM) and subcortical GM. Autoregulatory Index (AI) was computed using the equation AI = %CBF change/% MAP change supplemented by CBF associated OEF changes. Nominal p-values are uncorrected for multiple comparisons. Results: Forty-one treatment naive HIV-infected subjects and 47 age-, gender-, race-matched controls participated. HIV-infected subjects had higher CBF in cortical GM compared to the controls (76.8± 12 mL/100 g/min versus 71.6 ± 11 mL/100 g/min; p= 0.04), but not in white matter (30.9± 8 mL/100 g/min versus 30.0 ± 8 mL/100 g/min; p = 0.60) or subcortical GM (62.8± 13 mL/100 g/min versus 61.3 ± 13 mL/100 g/min; p = 0.57). Whole brain (WB), GM, WM, and subcortical GM, OEF were similar between the groups (p &gt; .05). The median AI were similar between cases and controls in WB (0.40 vs 0.18, p=0.86), GM (0.10 vs. 0.16, p=0.87), WM (0.80 vs. 0.87, p=0.31), and subcortical GM (1.65 vs. 1.77, p=0.26). A 12-month follow-up (N=30) in HIV-subjects on antiretroviral therapy did not produce a significant change in CBF or OEF in the WB, GM, WM, or subcortical GM (Paired sample t test p&gt;0.05). Similarly, no changes were noted on the AI (Wilcoxon Match Rank test p&gt;0.05). Conclusions: AI was similar between HIV cases and control and remained so after 12-months of antiretroviral therapy. We found no evidence of a defect in autoregulation to explain the high-risk of ischemic stroke documented in other studies.

225P - Predictors of adherence among post-menopausal women receiving adjuvant endocrine therapy for breast cancer in Ontario, Canada

BackgroundAdjuvant endocrine therapy (AET) is an important treatment for post-menopausal hormone receptor positive breast cancer. We used health administrative data to explore factors associated with AET adherence and survival. MethodsWe used health administrative databases to investigate adherence of post-menopausal women (aged ≥ 66 years) who started endocrine therapy from 2005-2010. Adherence was measured by medical possession ratio (MPR) and characterized as low (<40% MPR), intermediate (40-79% MPR) or high (≥80% MPR) over a five-year period. We investigated factors influencing AET adherence using a multinomial logistic regression model and the association with all-cause death (5-years after starting AET) using a multivariable cox-proportional hazards model. ResultsWe identified 5,692 eligible patients with a median age of 73 years (IQR: 69-78), 67% received lumpectomy, 33% mastectomy, 26% adjuvant radiation, 13% adjuvant chemotherapy and 70% of patient originally started on an aromatase inhibitor versus tamoxifen. AET adherence was low in 13% (n=749), intermediate in 13% (n=733) and high in 74% (n=4,210) of patients. Lower levels of adherence were observed among older patients [low vs. high adherence: odds ratio (OR)=1.03, 95% CI: 1.02-1.05 (per year); intermediate vs. high adherence: OR=1.02, 95% CI: 1.01-1.04 (per year)]. High adherence was associated with use of adjuvant chemotherapy (low versus high adherence OR=0.42 95% CI: 0.30-0.59) and short-term follow-up with a medical oncologist within 4 months of starting AET (low vs. high adherence OR=0.83, 95% CI: 0.69-0.99). Unadjusted analysis showed an increased risk of death among patients with lower AET adherence [low vs. high adherence: hazard ratio (HR)=1.31, 95% CI: 1.12-1.53 and intermediate vs. high adherence: HR=1.40, 95% CI: 1.21-1.62]. However, a significant association could no longer be detected after multivariable adjustment. ConclusionsNon-adherence to endocrine therapy appears to be more common among older breast cancer patients. Short-term follow-up visit by a patient’s medical oncologist after starting AET may help to improve adherence. Developing strategies to optimize endocrine therapy adherence are warranted. Legal entity responsible for the studyThe authors. FundingAcademic Medical Association of South Western Ontario (AMOSO). DisclosureT. Vandenberg: Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche. K. Pritchard: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Eisai; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: Myriad Genetics. A. Louie: Advisory / Consultancy: AstraZeneca; Honoraria (self): Varian Medical Systems Inc. J. Raphael: Honoraria (self): Hoffmann La Roche. All other authors have declared no conflicts of interest.

Programmed death-ligand 1 expression on direct Pap-stained cytology smears from non-small cell lung cancer: Comparison with cell blocks and surgical resection specimens.

Programmed death-ligand 1 (PD-L1) expression, as assessed by immunohistochemistry (IHC), is used to select patients with non-small cell lung cancer (NSCLC) for anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy. The current study evaluated the feasibility and efficacy of PD-L1 immunostaining and quantitation on direct Papanicolaou-stained cytological smears compared with formalin-fixed paraffin-embedded samples (cytological cell blocks and surgical resection specimens) in NSCLC cases using 2 commercially available assays: the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies/Dako, Carpinteria, CA, USA) and the Ventana SP263 Assay (Ventana Medical Systems Inc, Tucson, Arizona). PD-L1 immunostaining using either both or one of the assays was tested in 117 sets of paired samples obtained from 62 NSCLC cases. The tumor proportion score was reported in every case following the recommendations of the International Association for the Study of Lung Cancer (IASLC). In 57 sets of samples, both PD-L1 assays were used. Due to the availability of samples, only 1 assay was performed in 3 sets of samples and in 2 cases, only cytology smears were used and tested for both assays. A total of 113 sets of paired samples finally were evaluated; 4 cases could not be studied due to intense nonspecific background staining. A significant concordance between the 2 assays on cytological smears was found. Concordance between paired cytological smears and formalin-fixed paraffin-embedded samples was observed in 97.3% of the cases. The quantification of PD-L1 expression on direct Papanicolaou-stained cytology smears is feasible and reliable for both PD-L1 assays.

Verification of the Elekta Monaco TPS Monte Carlo in modelling radiation transmission through metals in a water equivalent phantom.

Many studies have performed dosimetric studies using various metal implants however these are difficult to translate to other implants of a different geometry or material (Rijken and Colyer, J Appl Clin Med Phys 18:5:301-306, 2017; Ade and du Plessis, J Appl Clin Med Phys 18:5:162-173, 2017; Prabhakar et al. Rep Pract Oncol Radiother 18:209-213, 2013; Ng et al. Rep Pract Oncol Radiother 20:273-277, 2015; Reft et al. Med Phys 30:1162-1182, 2003; Sasaki et al., Nihon Hoshasen Gijutsu Gakkai Zasshi 72(9):735-745, 2016). In this study, the ability of the Monaco Monte Carlo algorithm (Elekta AB, Stockholm, Sweden) to model radiation transport through different types of metals was evaluated. Investigation of the capabilities and limitations of the algorithm is required for the potential use of Monaco for planning radiotherapy treatments when avoidance of metal implants is clinically undesirable. A MapCHECK 2 diode array (Sun Nuclear Corp, Melbourne, USA) and a PTW 30013 Farmer chamber was used to measure the dose at depth, downstream of 1cm × 5cm × 5cm metal blocks of three known compositions; stainless steel, aluminium and MCP96. The setup was imaged using a CT scanner and imported into the Monaco TPS where the beam arrangement was replicated. The density of the metals was overridden using the known electron density of each (IMPAC Medical Systems Inc, Monaco dose calculation technical reference. IMPAC Medical Systems, Sunnydale, CA, 2013). The differences between the dose measured using the ion chamber and calculated using Monaco downstream of the 1cm metal blocks were respectively: - 1.2%, - 2.2% and 9.5% when irradiated using a 6 MV beam, and - 0.9%, - 1.3% and 14%, when irradiated using a 15 MV beam. This was then repeated using 2cm and 3cm of each metal type giving similar results for aluminium and stainless steel and increased discrepancy for MCP96. Discrepancies between treatment planning software and measurements at depth have been shown to give uncertainties between 5 and 23% in previous studies (Rijken and Colyer, J Appl Clin Med Phys 18:5:301-306, 2017; Ade and du Plessis, J Appl Clin Med Phys 18:5:162-173, 2017; Prabhakar et al. Rep Pract Oncol Radiother 18:209-213, 2013; Ng et al. Rep Pract Oncol Radiother 20:273-277, 2015; Reft et al. Med Phys 30:1162-1182, 2003; Sasaki et al., Nihon Hoshasen Gijutsu Gakkai Zasshi 72(9):735-745, 2016). This study uses basic shapes providing results that remove the uncertainties in geometry and can therefore be applied to any shape. This will help determine whether errors in dose calculations are due to the TPS particle transport algorithms or due to other effects, such as inaccurate contouring or incorrect densities. Thus giving the planner an additional degree of freedom in their planning and decision making process.

3-Piece Inflatable Penile Prosthesis Placement Following Radical Cystoprostatectomy and Urinary Diversion: Technique and Outcomes

BackgroundAfter radical cystoprostatectomy (RC), postoperative erectile dysfunction (ED) is a common consequence with multiple contributing etiologies. The inflatable penile prosthesis (IPP) offers patients a definitive treatment option when ED is refractory to medical therapies. Because of the hostile postoperative anatomy of these patients, a careful surgical approach is necessary for successful outcomes and to avoid adjacent organ injury. To date, there is no series describing the outcomes of 3-piece IPP placement in patients with urinary diversions. AimTo present contemporary outcomes and a description of our technique in placing a 3-piece IPP for postoperative ED in patients with a history of RC with orthotopic neobladder, ileal conduit, or continent cutaneous diversion. MethodsWe retrospectively reviewed 80 patients who underwent primary placement of a 3-piece IPP (AMS 700; American Medical Systems Inc, Minnetonka, MN, USA) after RC and urinary diversion from 2003 through 2016. 79 patients underwent RC in their treatment of urologic malignancy (71 for bladder cancer, 8 for prostate cancer) and 1 underwent RC for refractory interstitial cystitis. An infrapubic approach was used in most patients, with reservoir placement in the lateral retroperitoneal space through a counterincision medial to the anterior superior iliac spine. Patient demographics, perioperative data, and postoperative outcomes including prosthetic infection and mechanical failure were examined and statistical analysis was performed. OutcomesRates of device infection, revision surgery, and reservoir complications. ResultsAfter mean follow-up of 53.9 months (6.5–150.7 months), 4 patients developed infection of the prosthesis that required explantation. 3 of those patients underwent successful IPP reimplantation. 5 patients required revision surgery (pump replacement, n = 3; pump relocation, n = 1; cylinder replacement for cylinder aneurysm, n = 1) for mechanical failure. No statistically significant associations were found between infection and comorbidities, urinary diversion, exposure to chemotherapy, radiation, or presence of an artificial urinary sphincter. Clinical ImplicationsThe 3-piece IPP is an effective treatment option for medication-refractory ED that can be placed safely in patients with all forms of urinary diversion. Strengths and LimitationsThis study represents the 1st series that describes a successful technique and long-term outcomes of patients with urinary diversion. It is limited by its single-surgeon, single-center experience and lacks validated patient satisfaction data in follow-up. ConclusionsThe 3-piece IPP, with reservoir placement in the lateral retroperitoneum, can be implanted successfully in patients with all forms of urinary diversion without a significant increase in infectious complications, reservoir erosion, or mechanical failure.Loh-Doyle J, Patil MB, Sawkar H, et al. 3-Piece Inflatable Penile Prosthesis Placement Following Radical Cystoprostatectomy and Urinary Diversion: Technique and Outcomes. J Sex Med 2018;15:907–913.

Trunk flexor and extensor muscle performance in chronic stroke patients: a case–control study

BackgroundAlthough chronic stroke patients commonly show impairment of trunk muscle performance, this disability has only been analyzed in terms of peak torque. Therefore, other measures are needed for a more adequate description. ObjectiveThis study aimed to compare concentric muscle performance of trunk flexor/extensor muscles between chronic stroke patients and matched-healthy subjects. Methods18 chronic stroke patients and 18 healthy subjects were matched according to their age, sex, body mass index and level of physical activity. After familiarization, trunk flexor/extensor concentric muscle strength was measured using an isokinetic dynamometer (Biodex Medical Systems Inc, Shirley, NY, USA) with 3 repetitions at a velocity of 60°/s and 5 repetitions at a velocity of 120°/s. Trunk muscular performance was characterized by peak torque, torque at 90°, total work, and total work normalized by trunk mass. Student's t-test was used for independent samples (α=0.05) for group comparisons. ResultsAll trunk muscle performance variables values investigated were significantly lower in chronic stroke patients when compared to matched-healthy subjects (p≤0.001). The obtained ratios of chronic stroke patients scores to that of the matched-healthy subjects at velocities of 60°/s and 120°/s were, respectively: flexor peak torque (60% & 53%)/extensor (54% & 53%); flexor torque at 90° (56.20% & 36.58%)/extensor (57.92% & 30.65%); flexor total muscular work (51.27% & 38.03%)/extensor (47.97% & 39.52%); and flexor total muscular work normalized by trunk mass (55.57% & 40%)/extensor (51.40% & 42%). ConclusionsChronic stroke patients showed decreased trunk muscle performance when compared to matched-healthy subjects in all variables investigated.

Programmed death-ligand 1 testing in patients with non-small cell lung cancer: Ready for prime time?

Programmed death-ligand 1 testing in patients with non-small cell lung cancer: Ready for prime time?

Relationship between Muscular Strength and Functional Balance in People Post-Stroke

Impaired balance and weak muscle strength are common deficits associated with stroke. These deficits increase the risk of fall among people post-stroke. The relationship between muscular strength and balance was previously reported to be weak. However, the conclusion was made based on clinical balance assessments instead of biomechanical data. Limited research examined the relationship between balance and strength in people post-stroke. PURPOSE: To investigate the relationship between muscular strength and functional balance in people post-stroke. METHODS: A total of 20 people post-stroke completed balance and strength assessments over two separate visits. A computerized dynamic posturography system (NeuroCom International, Clackamas, OR, 2010) was used to perform four balance tests including limits of stability test (LOS), sit to stand test (STS), walk across test (WA), and step up and over test (SUO). In addition, participants completed isometric muscle strength tests of the trunk, hip, knee, and ankle. Peak torque was measured with a computerized dynamometer (Biodex Medical Systems Inc, Shirley, NY, 2012). Pearson’s correlation test was used for statistical analysis. RESULTS: There was a strong correlation between max excursion (LOS test) and muscle strengths of knee flexor/extensor on the affected side (r values ranged between 0.721 and 0.793, p<0.04). A strong correlation was also found between step width (WA test) and muscular strengths of trunk extensor, knee flexor, ankle plantar-flexor, hip flexor and extensor on the unaffected side (r values ranged between 0.797 and 0.902, p<0.01). STS and SUO did not show any significant correlation with muscle strength. CONCLUSIONS: Our findings suggest that strengthening of the knee flexor/extensor may help people post-stroke to shift the weight to maximum range without losing balance. Also, our results indicate that the strength of the core and lower extremities muscles is strongly associated with gait stability.

RETINAL VASCULAR DEVELOPMENT WITH 0.312 MG INTRAVITREAL BEVACIZUMAB TO TREAT SEVERE POSTERIOR RETINOPATHY OF PREMATURITY: A Longitudinal Fluorescein Angiographic Study.

To report the outcome of intravitreal 0.312 mg bevacizumab (IVB) monotherapy in acute retinopathy of prematurity (ROP) and to describe the vascular development over time. Seventeen prematurely born infants were treated with IVB (0.312 mg in 0.025 mL per eye) because of acute ROP in posterior Zone II or Zone I, including aggressive posterior ROP. Infants were examined by fluorescein angiography (FA) using RetCam II or III (Clarity Medical Systems Inc) before IVB (n = 21 eyes), within 6 weeks (n = 23 eyes), 8 to 13 weeks (n = 22 eyes), and up to 45 months (n = 10 eyes). Acute ROP regressed in 19 out of 27 analyzed eyes (70%), including 100% and 80% of posterior Zone II and Zone I eyes, respectively, but only 25% of aggressive posterior ROP eyes. Early recurrences (11%, all aggressive posterior ROP) and late reactivations (18%) were observed within 1 week and at 9 to 12 weeks, respectively. All eyes showed leakage at the junction of the vascularized zone and capillary malformation on FA before treatment. Vessel branching abnormalities and circumferential vessel formation were typical FA features after treatment. Vascular outgrowth after one IVB became complete in 87.5% of eyes for which FA was available up to at least 9 weeks after IVB. A single dose of 0.312 mg bevacizumab was efficient to induce regression of ROP in posterior Zone II and most of Zone I cases, but not in aggressive posterior ROP. FA describes vascular abnormalities, the importance of which warrants further investigation.

Correction parameters of respiratory support in endoscopic resection of the stomach in patients with the morbid obesity

In recent years, steadily increasing the number of operations for morbid obesity. One of the most frequently performed worldwide operations at this pathology is the sleeve gastrectomy are approximately 28% of all bariatric surgeries per year It must be stressed that obesity is accompanied by hard changes andfunctional disorders of all body systems, including the respiratory and cardiovascular The aim: to study the effect of respiratory support options combined with high thoracic epidural analgesia, as a component of anesthetic management on central hemodynamics during anesthesia providing endoscopic gastroplasty in patients with morbid obesity. a randomized study of 37 patients with morbid obesity who underwent endoscopic sleeve gastroplasty under anesthesia combined with high thoracic epidural analgesia. Depending on the choice of tactics respiratory support patients were divided into two groups; In group 1 (n-17), the traditional mode of ventilation in group 2 (n-20) modified the ventilation mode. Intraoperative central hemodynamic parameters, external respiration were monitored; acid-base balance is achieved partly by recycling carbon dioxide in a closed breathing circuit using NICO 7300 system (Novametrix Medical Systems Inc. USA), based on the Fick principle. the use of ventilation mode with inversion of the respiratory cycle, high-level application of PEEP titration in stages so you can optimize the parameters of external respiration, gas exchange without adverse effects on the central hemodynamics. The continued elevated levels PaCO₂, PvCO₂, when applying carboxiperitoneum, did not cause gross changes in acid-base balance.

TH‐CD‐206‐08: An Anthropopathic Deformable Phantom for Geometric and Dose Accumulation Accuracy Validation of Deformable Image Registration

Purpose:To design and construct a three‐dimensional (3D) anthropopathic abdominal phantom for evaluating deformable image registration (DIR) accuracy on images and dose deformation in adaptive radiation therapy (ART).Method:Organ moulds, including liver, kidney, spleen, stomach, vertebra and two metastasis tumors, are 3D printed using the contours from an ovarian cancer patient. The organ moulds are molded with deformable gels that made of different mixtures of polyvinyl chloride (PVC) and the softener dioctyl terephthalate. Gels with different densities are obtained by a polynomial fitting curve which describes the relation between the CT number and PVC‐softener blending ratio. The rigid vertebras are constructed by moulding with white cement. The final abdominal phantom is assembled by arranging all the fabricated organs inside a hollow dummy according to their anatomies and sealed with deformable gel with averaged CT number of muscle and fat. Geometric and dosimetric landmarks are embedded inside the phantom for spatial accuracy and dose accumulation accuracy studies. Three DIR algorithms available in the open source DIR toolkit‐DIRART, including the Demons, the Horn‐Schunck and Lucas‐Kanade method and the Level‐Set Motion method, are tested using the constructed phantom.Results:Viscoelastic behavior is observed in the constructed deformable gel, which serves as an ideal material for the deformable phantom. The constructed abdominal phantom consists of highly realistic anatomy and the fabricated organs inside have close CT number to its reference patient. DIR accuracy studies conducted on the constructed phantom using three DIR approaches indicate that geometric accuracy of a DIR algorithm has achieved does not guarantee accuracy in dose accumulation.Conclusions:We have designed and constructed an anthropopathic abdominal deformable phantom with satisfactory elastic property, realistic organ density and anatomy. This physical phantom is recyclable and can be used for routine validations of DIR geometric accuracy and dose accumulation accuracy in ART.This work is supported in part by grant from VARIAN MEDICAL SYSTEMS INC, the National Natural Science Foundation of China (no 81428019 and no 81301940), the Guangdong Natural Science Foundation (2015A030313302) and the 2015 Pearl River S&amp;T Nova Program of Guangzhou (201506010096).

TH-CD-207A-03: A Surface Deformation Driven Respiratory Model for Organ Motion Tracking in Lung Cancer Radiotherapy

Purpose: To propose and validate a novel real-time surface-mesh-based internal organ-external surface motion and deformation tracking method for lung cancer radiotherapy. Methods: Deformation vector fields (DVFs) which characterizes the internal and external motion are obtained by registering the internal organ and tumor contours and external surface meshes to a reference phase in the 4D CT images using a recent developed local topology preserved non-rigid point matching algorithm (TOP). A composite matrix is constructed by combing the estimated internal and external DVFs. Principle component analysis (PCA) is then applied on the composite matrix to extract principal motion characteristics and finally yield the respiratory motion model parameters which correlates the internal and external motion and deformation. The accuracy of the respiratory motion model is evaluated using a 4D NURBS-based cardiac-torso (NCAT) synthetic phantom and three lung cancer cases. The center of mass (COM) difference is used to measure the tumor motion tracking accuracy, and the Dice's coefficient (DC), percent error (PE) and Housdourf's distance (HD) are used to measure the agreement between the predicted and ground truth tumor shape. Results: The mean COM is 0.84±0.49mm and 0.50±0.47mm for the phantom and patient data respectively. The mean DC, PE and HD are 0.93±0.01, 0.13±0.03 and 1.24±0.34 voxels for the phantom, and 0.91±0.04, 0.17±0.07 and 3.93±2.12 voxels for the three lung cancer patients, respectively. Conclusions: We have proposed and validate a real-time surface-mesh-based organ motion and deformation tracking method with an internal-external motion modeling. The preliminary results conducted on a synthetic 4D NCAT phantom and 4D CT images from three lung cancer cases show that the proposed method is reliable and accurate in tracking both the tumor motion trajectory and deformation, which can serve as a potential tool for real-time organ motion and deformation monitoring in lung cancer radiotherapy. This work is supported in part by grant from VARIAN MEDICAL SYSTEMS INC, the National Natural Science Foundation of China (no 81428019 and no 81301940), the Guangdong Natural Science Foundation (2015A030313302)and the 2015 Pearl River S&T Nova Program of Guangzhou (201506010096).

SU‐F‐J‐217: Accurate Dose Volume Parameters Calculation for Revealing Rectum Dose‐Toxicity Effect Using Deformable Registration in Cervical Cancer Brachytherapy: A Pilot Study

Purpose:To study the feasibility of employing deformable registration methods for accurate rectum dose volume parameters calculation and their potentials in revealing rectum dose‐toxicity between complication and non‐complication cervical cancer patients with brachytherapy treatment.Method and Materials:Data from 60 patients treated with BT including planning images, treatment plans, and follow‐up clinical exam were retrospectively collected. Among them, 12 patients complained about hematochezia were further examined with colonoscopy and scored as Grade 1–3 complication (CP). Meanwhile, another 12 non‐complication (NCP) patients were selected as a reference group. To seek for potential gains in rectum toxicity prediction when fractional anatomical deformations are account for, the rectum dose volume parameters D0.1/1/2cc of the selected patients were retrospectively computed by three different approaches: the simple “worstcase scenario” (WS) addition method, an intensity‐based deformable image registration (DIR) algorithm‐Demons, and a more accurate, recent developed local topology preserved non‐rigid point matching algorithm (TOP). Statistical significance of the differences between rectum doses of the CP group and the NCP group were tested by a two‐tailed t‐test and results were considered to be statistically significant if p &lt; 0.05.Results:For the D0.1cc, no statistical differences are found between the CP and NCP group in all three methods. For the D1cc, dose difference is not detected by the WS method, however, statistical differences between the two groups are observed by both Demons and TOP, and more evident in TOP. For the D2cc, the CP and NCP cases are statistically significance of the difference for all three methods but more pronounced with TOP.Conclusion:In this study, we calculated the rectum D0.1/1/2cc by simple WS addition and two DIR methods and seek for gains in rectum toxicity prediction. The results favor the claim that accurate dose deformation and summation tend to be more sensitive in unveiling the dose‐toxicity relationship.This work is supported in part by grant from VARIAN MEDICAL SYSTEMS INC, the National Natural Science Foundation of China (no 81428019 and no 81301940), the Guangdong Natural Science Foundation (2015A030313302)and the 2015 Pearl River S&amp;T Nova Program of Guangzhou (201506010096).