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Introduction Dose escalated radiotherapy has previously been investigated as a strategy to increase complete response rates in rectal cancer. However large safety margins are required using cone-beam computed tomography guided radiotherapy leading to high doses to organs at risk or insufficient target volume coverage in order to keep dose constraints. We herein present the first clinical application of a new technique for dose escalation in rectal cancer using online magnetic resonance (MR)-guidance and rectal ultrasound gel filling. Methods A 73-year-old patient with distal cT3a cN0 cM0 rectal cancer was referred for definitive radiochemotherapy with the goal of organ preservation after multidisciplinary discussion. A dose of 45 Gy in 25 fractions with a stereotactic integrated boost to the primary tumor of 50 Gy with concomitant 5-fluorouracil was prescribed. Furthermore, a boost to the primary tumor with 3 Gy per fraction using the adapt-to-shape workflow on a 1.5 T MR-Linac was planned once weekly. For the boost fractions 100 cc of ultrasound gel was applied rectally in order to improve tumor visibility and distancing of uninvolved rectal mucosa. In order to determine the required planning target volume margin diagnostic scans of ten rectal cancer patients conducted with rectal ultrasound gel filling were studied. Results Based on the ten diagnostic scans an average isotropic margin of 4 mm was found to be sufficient to cover 95% of the target volume during an online adaptive workflow. Three boost fractions were applied, mean treatment duration was 22:34 min. Treatment was well tolerated by the patient with no more than PRO-CTCAE grade I° toxicity of any kind. The rectal ultrasound gel filling resulted in superior visibility of the tumor and reduced the dose to the involved mucosa especially in the high dose range compared with a boost plan calculated without any filling. A considerable tumor shrinkage was observed during treatment from 17.43 cc at baseline to 4 cc in week four. Conclusion This novel method appears to be a simple but effective strategy for dose escalated radiotherapy in rectal cancer. Based on the encouraging observation, a prospective trial is currently under preparation.

Purpose The extent of lymphadenectomy and clinical features influence the risk of occult nodes in node-negative prostate cancer. We derived a simple estimation model for the negative predictive value (npv) of histopathologically node-negative prostate cancer patients (pN0) to guide adjuvant treatment. Methods Approximations of sensitivities in detecting lymph node metastasis from current publications depending on the number of removed lymph nodes were used for a theoretical deduction of a simplified formulation of npv assuming a false node positivity of 0. Results A theoretical formula of npv = p(N0IpN0) = (100 − prevalence) / (100 − sensitivity × prevalence) was calculated (sensitivity and preoperative prevalence in %). Depending on the number of removed lymph nodes (nLN), the sensitivity of pN0-staged prostate cancer was derived for three sensitivity levels accordingly: sensitivity = f(nLN) = 9 × nLN /100 for 0 ≤ nLN ≤ 8 and f(nLN) = (nLN + 70) /100 for 9 ≤ nLN ≤ 29 and f(nLN) = 1 for nLN ≥ 30. Conclusion We developed a theoretical formula for estimation of the npv in pN0-staged prostate cancer patients. It is a sine qua non to use the formula in a clinically experienced context before deciding to electively irradiate pelvic lymph nodes or to intensify adjuvant systemic treatment.

Zusammenfassung Hintergrund Der potenzielle Nutzen des verbesserten Weichteilkontrastes von MR-Sequenzen gegenüber der Computertomographie (CT) für die Radiotherapie des Prostatakarzinoms ist bekannt und führt zu konsistenteren und kleineren Zielvolumina sowie verbesserter Risikoorganschonung. Hybridgeräte aus Magnetresonanztomographie (MRT) und Linearbeschleuniger (MR-Linac) stellen eine neue vielversprechende Erweiterung der radioonkologischen Therapieoptionen dar. Material und Methoden Dieser Artikel gibt eine Übersicht über bisherige Erfahrungen, Indikationen, Vorteile und Herausforderungen für die Radiotherapie des primären Prostatakarzinoms mit dem 1,5-T-MR-Linac. Ergebnisse Alle strahlentherapeutischen Therapieindikationen für das primäre Prostatakarzinom können mit dem 1,5-T-MR-Linac abgedeckt werden. Die potenziellen Vorteile umfassen die tägliche MR-basierte Lagekontrolle in Bestrahlungsposition und die Möglichkeit der täglichen Echtzeitanpassung des Bestrahlungsplans an die aktuelle Anatomie der Beckenorgane (adaptive Strahlentherapie). Zusätzlich werden am 1,5-T-MR-Linac funktionelle MRT-Sequenzen für individuelles Response-Assessment für die Therapieanpassung untersucht. Dadurch soll das therapeutische Fenster weiter optimiert werden. Herausforderungen stellen u. a. die technische Komplexität und die Dauer der Behandlungssitzung dar. Schlussfolgerung Der 1,5-T-MR-Linac erweitert das radioonkologische Spektrum in der Therapie des Prostatakarzinoms und bietet Vorteile durch tagesaktuelle MRT-basierte Zielvolumendefinition und Planadaptation. Weitere klinische Untersuchungen sind notwendig, um die Patienten zu identifizieren, die von der Behandlung am MR-Linac gegenüber anderen strahlentherapeutischen Methoden besonders profitieren.

Background Cure- and toxicity rates after intensity-modulated radiotherapy (IMRT) of prostate cancer are dose-and volume dependent. We prospectively studied the potential for organ at risk (OAR) sparing and compensation of tumor movement with the coverage probability (CovP) concept. Patients and methods Twenty-eight prostate cancer patients (median age 70) with localized disease (cT1c–2c, N0, M0) and intermediate risk features (prostate-specific antigen [PSA] < 20, Gleason score ≤ 7b) were treated in a prospective study with the CovP concept. Planning-CTs were performed on three subsequent days to capture form changes and movement of prostate and OARs. The clinical target volume (CTV) prostate and the OARs (bladder and rectum) were contoured in each CT. The union of CTV1–3 was encompassed by an isotropic margin of 7 mm to define the internal target volume (ITV). Dose prescription/escalation depended on coverage of all CTVs within the ITV. IMRT was given in 39 fractions to 78 Gy using the Monte-Carlo algorithm. Short-term androgen deprivation was recommended and given in 78.6% of patients. Results Long-term toxicity was evaluated in 26/28 patients after a median follow-up of 7.1 years. At last follow-up, late bladder toxicity (Radiation Therapy Oncology Group, RTOG) G1 was observed in 14.3% of patients and late rectal toxicities (RTOG) of G1 (7.1%) and of G2 (3.6%) were observed. No higher graded toxicity occurred. After 7.1 years, biochemical control (biochemically no evidence of disease, bNED) was 95.5%, prostate cancer-specific survival and the distant metastasis-free survival after 7.1 years were 100% each. Conclusions CovP-based IMRT was feasible in a clinical study. Dose escalation with the CovP concept was associated by a low rate of toxicity and a high efficacy regarding local and distant control.

This chapter considers social constructivism as an educational theory for the development of multimedia content to assist primary-care providers, particularly those in HIV clinics and other clinicians, and support staff involved in the care of patients with substance use disorders in better understanding the intake processes at the Methadone clinics. Main aspects of social constructivism with its focus on the collaborative and generative learning and the importance of a cultural and social context are elaborated within the framework of the multimedia design. A series of four videos were developed that feature interviews with patients who describe their experience on Methadone. In addition, medical providers and medical staff describe the intake procedures for Methadone. Also discussed is the instructional design process and the Bergman and Moore instructional design model that informed the design.

The measurement of the jet cross sections by the H1 collaboration had been compared to various predictions including the next-to-next-to-leading order (NNLO) QCD calculations which are corrected in this erratum for an implementation error in one of the components of the NNLO calculations. The jet data and the other predictions remain unchanged. Eight figures, one table and conclusions are adapted accordingly, exhibiting even better agreement between the corrected NNLO predictions and the jet data.

Background: We evaluated efficacy and toxicity of 68Ga-PSMA-Positron Emission Tomography/Computed Tomography (PET/CT)-directed stereotactic body radiotherapy and image-guided radiotherapy (...

This retrospective analysis aimed to address the efficacy of total nodal irradiation (TNI)-based reconditioning regimens in pediatric patients with graft failure/rejection after allogeneic hematopoietic cell transplantation.Thirty-three pediatric patients with malignant (n = 25) and nonmalignant diseases (n = 8) were treated with a TNI-based reconditioning regimen. All patients received a 7-Gy single dose combined with anti-T lymphocyte antibody OKT3 (n = 16), anti-thymocyte globulin (n = 24), fludarabine (n = 31), and/or thiotepa (n = 28), followed by an infusion of peripheral blood stem cells (n = 31) or bone marrow transplant (n = 2). Twenty-eight of 33 patients had haploidentical family donors.After a median of 11 days, engraftment was seen in 32 of 33 children. Two children died 34 days after retransplantation because of either disease relapse or treatment-related multiple organ failure. Severe acute toxicity was reported in only 1 child (systemic inflammatory response syndrome-like reaction; recovery after cortisone treatment). The average follow-up was 60.2 months (range, 1.1-162.5 months). Event-free and overall survival rates at 2/5 years follow-up were 62.0%/58.6% and 65.1%/61.7%, respectively. Despite sustained engraftment, 12 patients died from disease relapse (n = 3), Moschkowitz syndrome (n = 1), or multiple organ failure (n = 8). Follow-up data were available for 18 of 21 survivors, with a median follow-up of 92.8 months (range, 3.6-162.5 months). Hypothyroidism was present in 78.6% of patients, and sex/growth hormonal insufficiencies were reported for 37.5%. Mean forced expiratory volume in 1 second after TNI was 84%; mean vital capacity was 79%. Severe growth failure (3rd percentile) occurred in 28.6% (height) and 35.7% (weight) of patients. No secondary malignancies were reported.In the high-risk group of patients with graft failure/rejection after allogeneic hematopoietic cell transplantation, the TNI-based reconditioning regimen seems to allow sustained engraftment combined with a favorable toxicity profile, leading to long-term event-free and overall survival. Late toxicity after a median follow-up of over 7.5 years includes growth failure, manageable hormonal deficiencies, and a low risk of decrease of lung function.

Biochemical recurrence (BCR) after prostate cancer surgery is common, even after additional salvage radiotherapy. BCR might be explained by target miss. Improved diagnostic accuracy provided by PET could potentially circumvent this therapeutic gap. Therefore, we evaluated consecutive 68Ga-prostate-specific membrane antigen (PSMA) PET/CT, 11C-choline PET/CT, and standard CT imaging in the same patient with regard to TNM-stage migration and accordingly adapted curative radiotherapy options including ablative treatment of oligometastases (n ≤ 5). The cost efficacy of PET- versus CT-based treatment was also calculated. Methods: The prospective register database (064/2013BO1) was retrospectively searched for patients fulfilling the following 3 inclusion criteria: BCR after radical prostatectomy (pT2–pT4 pN0–pN1 cM0, postoperative radiotherapy allowed); 11C-choline PET/CT, 68Ga-PSMA PET/CT, and diagnostic CT performed within 24 h; and available clinical data. Ten treatment routines were defined according to current practice. Furthermore, intention-to-treat and treatment-related costs depending on the shift of TNM stage after imaging were analyzed. Eighty-three patients were eligible (median prostate-specific antigen level, 1.9 ng/mL). Results: Both PET examinations led to concordant results in 72% of patients, whereas the concordance of TNM staging between 68Ga-PSMA PET and diagnostic CT was only 36%. Incorrect staging would lead to “wrong” treatment and therefore to additional costs. A 68Ga-PSMA PET study would be cost-effective if additional costs do not exceed €3,844 ($4,312) (vs. CT). The number needed to image was 2 (for CT) and 4 (for 11C-choline PET) to avoid 1 incorrect treatment. In addition, 68Ga-PSMA PET staging enabled new curative options in half the patients with previous radiotherapy who otherwise receive palliative androgen deprivation therapy. Conclusion:68Ga-PSMA PET/CT is cost-effective in all patients with regard to avoidance of incorrect treatment. It enabled new curative options for patients with previous radiotherapy who are usually treated palliatively. Therefore, 68Ga-PSMA PET/CT staging should become standard for BCR after surgery with or without radiotherapy.

Proceedings of the National Academy of Sciences of the United States of America 116(7), 2551 - 2560 (2019). doi:10.1073/pnas.1812963116, Since the late 1980s, mutations in the RAS genes have been recognized as major oncogenes with a high occurrence rate in human cancers. Such mutations reduce the ability of the small GTPase RAS to hydrolyze GTP, keeping this molecular switch in a constitutively active GTP-bound form that drives, unchecked, oncogenic downstream signaling. One strategy to reduce the levels of active RAS is to target guanine nucleotide exchange factors, which allow RAS to cycle from the inactive GDP-bound state to the active GTP-bound form. Here, we describe the identification of potent and cell-active small-molecule inhibitors which efficiently disrupt the interaction between KRAS and its exchange factor SOS1, a mode of action confirmed by a series of biophysical techniques. The binding sites, mode of action, and selectivity were elucidated using crystal structures of KRAS$^{G12C}$–SOS1, SOS1, and SOS2. By preventing formation of the KRAS–SOS1 complex, these inhibitors block reloading of KRAS with GTP, leading to antiproliferative activity. The final compound 23 (BAY-293) selectively inhibits the KRAS–SOS1 interaction with an IC$_{50}$ of 21 nM and is a valuable chemical probe for future investigations., Published by National Acad. of Sciences, Washington, DC

Purpose This retrospective analysis aims to address the toxicity and efficacy of a modified total nodal irradiation (TNI)-based conditioning regimen before haploidentical hematopoietic cell transplantation (HCT) in pediatric patients. Materials and methods Patient data including long-term follow-up were evaluated of 7 pediatric patients with malignant (n = 2) and non-malignant diseases (n = 5) who were treated by a primary TNI-based conditioning regimen. TNI was performed using anterior/posterior opposing fields. All patients received 7 Gy single-dose TNI combined with systemic agents followed by an infusion of peripheral blood stem cells (n = 7). All children had haploidentical family donors. Results Engraftment was reached in 6/7 children after a median time of 9.5 days; 1 child had primary graft failure but was successfully reconditioned shortly thereafter. After an average follow-up time of 103.5 months (range 8.8–138.5 months), event-free (EFS) and overall survival (OS) rates were 71.4% and 85.7%, respectively. One child with a non-malignant disease died 8.8 months after transplantation due to a relapse and a multiple organ failure. Follow-up data was available for 5/6 long-term survivors with a median follow-up (FU) of 106.2 months (range 54.5–138.5 months). Hypothyroidism and deficiency of sexual hormones was present in 3/5 patients each. Mean forced expiratory volume in 1 s (FEV1) after TNI was 71%; mean vital capacity (VC) was 78%. Growth failure ( Conclusion In this group of patients, a primary single-dose 7 Gy TNI-based conditioning regimen before HCT in pediatric patients allowed sustained engraftment combined with a tolerable toxicity profile leading to long-term OS/EFS. Late toxicity after a median FU of over 9 years includes growth failure, manageable hormonal deficiencies, and acceptable decrease in lung function.

Charged particle multiplicity distributions in positron-proton deep inelastic scattering at a centre-of-mass energy $$\sqrt{s}=319$$ s = 319 GeV are measured. The data are collected with the H1 detector at HERA corresponding to an integrated luminosity of 136 pb$$^{-1}$$ - 1 . Charged particle multiplicities are measured as a function of photon virtuality $$Q^2$$ Q 2 , inelasticity y and pseudorapidity $$\eta $$ η in the laboratory and the hadronic centre-of-mass frames. Predictions from different Monte Carlo models are compared to the data. The first and second moments of the multiplicity distributions are determined and the KNO scaling behaviour is investigated. The multiplicity distributions as a function of $$Q^2$$ Q 2 and the Bjorken variable $$x_{\mathrm{bj}}$$ x bj are converted to the hadron entropy $$S_{\mathrm{hadron}}$$ S hadron , and predictions from a quantum entanglement model are tested.

Background: The HIV cascade of care (CoC) model has been used to evaluate HIV-related health outcomes. Similar approaches have been applied to HCV mono-infected individuals; published CoC have relied on sources other than public health surveillance data. This study addresses this through a surveillance-only approach using two public health surveillance databases. Methods: We linked Connecticut’s (CT) HIV (the enhanced HIV/AIDS reporting System [eHARS]) and HCV (the CT Electronic Disease Surveillance System [CTEDSS]) surveillance databases, creating a co-infected list. We used HCV laboratory results to define the care status of each patient for appropriate CoC designation. Three CoC algorithms were assessed to measure their effects on calculated sustained virologic response (SVR) rates. Multivariate analysis was completed to measure those most likely to achieve SVR for each algorithm. Findings: HCV CoC SVR rates ranged from 37.1%-69.2%, depending on the algorithm used. Those significantly more likely to achieve SVR were baby-boomers and those with HIV viral suppression. Trends across CoC algorithms showed Black and Hispanic persons, females, and those with heterosexual HIV transmission were less likely to achieve SVR. Interpretation: We successfully developed a surveillance-based approach to creating a statewide HCV CoC for HIV/HCV co-infected individuals. Those not achieving SVR were identified, allowing future engagement strategies to focus on them. Furthermore, the methods presented can be adopted and implemented at state, local, or national level agencies. Funding: This work is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under award U90HA31462. Declaration of Interest: None to declare. Ethical Approval: The Department of Public Health Human Investigations Committee approved this research project

The European physical journal / C 81(8), 738 (2021). doi:10.1140/epjc/s10052-021-09394-0, Published by Springer, Heidelberg

Exclusive photoproduction of $${{\rho ^0}} (770)$$ ρ 0 ( 770 ) mesons is studied using the H1 detector at the ep collider HERA. A sample of about 900,000 events is used to measure single- and double-differential cross sections for the reaction $$\gamma p \rightarrow \pi ^{+}\pi ^{-}Y$$ γ p → π + π - Y . Reactions where the proton stays intact ($${{{m_Y}} {=}m_p}$$ m Y = m p ) are statistically separated from those where the proton dissociates to a low-mass hadronic system ($$m_p{ m p < m Y < 10 GeV ). The double-differential cross sections are measured as a function of the invariant mass $$m_{\pi \pi }$$ m π π of the decay pions and the squared 4-momentum transfer t at the proton vertex. The measurements are presented in various bins of the photon–proton collision energy $${{W_{\gamma p}}} $$ W γ p . The phase space restrictions are $$0.5\le m_{\pi \pi } \le 2.2~{{\text {GeV}}} $$ 0.5 ≤ m π π ≤ 2.2 GeV , $$\vert t\vert \le 1.5~{{\text {GeV}^2}} $$ | t | ≤ 1.5 GeV 2 , and $$20 \le W_{\gamma p} \le 80~{{\text {GeV}}} $$ 20 ≤ W γ p ≤ 80 GeV . Cross section measurements are presented for both elastic and proton-dissociative scattering. The observed cross section dependencies are described by analytic functions. Parametrising the $${m_{\pi \pi }}$$ m π π dependence with resonant and non-resonant contributions added at the amplitude level leads to a measurement of the $${{\rho ^0}} (770)$$ ρ 0 ( 770 ) meson mass and width at $$m_\rho = 770.8{}^{+2.6}_{-2.7}~({\text {tot.}})~{{\text {MeV}}} $$ m ρ = 770.8 - 2.7 + 2.6 ( tot. ) MeV and $$\Gamma _\rho = 151.3 {}^{+2.7}_{-3.6}~({\text {tot.}})~{{\text {MeV}}} $$ Γ ρ = 151.3 - 3.6 + 2.7 ( tot. ) MeV , respectively. The model is used to extract the $${{\rho ^0}} (770)$$ ρ 0 ( 770 ) contribution to the $$\pi ^{+}\pi ^{-}$$ π + π - cross sections and measure it as a function of t and $${W_{\gamma p}}$$ W γ p . In a Regge asymptotic limit in which one Regge trajectory $$\alpha (t)$$ α ( t ) dominates, the intercept $$\alpha (t{=}0) = 1.0654\ {}^{+0.0098}_{-0.0067}~({\text {tot.}})$$ α ( t = 0 ) = 1.0654 - 0.0067 + 0.0098 ( tot. ) and the slope $$\alpha ^\prime (t{=}0) = 0.233 {}^{+0.067 }_{-0.074 }~({\text {tot.}}) ~{{\text {GeV}^{-2}}} $$ α ′ ( t = 0 ) = 0.233 - 0.074 + 0.067 ( tot. ) GeV - 2 of the t dependence are extracted for the case $$m_Y{=}m_p$$ m Y = m p .

Introduction: To increase precision of radiation treatment (RT) delivery in prostate cancer, MRI-based RT as well as the use of fiducials like gold markers (GMs) have shown promising results. Their combined use is currently under investigation in clinical trials. Here, we aimed to evaluate a workflow of image registration based on GMs between CT and MRI as well as weekly MRI-MRI adaption based on T2 TSE sequence. Material and methods: A gel-phantom with two inserted GMs was scanned with CT and three different MR-scanners of 1.5 and 3 T (T2 TSE and T1 VIBE-Dixon, isotropic, voxel size 2 × 2 × 2 mm). After image fusion, deviations for fiducial and gel match were measured and artifacts were evaluated. Additionally, CT-MRI-match deviations and MRI-MRI-match deviations of 10 Patients from the M-basePro study using GMs were assessed. Results: GMs were visible in all imaging modalities. The outer gel contours were matched with Conclusions: Match inaccuracies for GMs between reference CT and voxel-isotropic T2-TSE sequences are small. Spatial deviations of CT- and MR-contoured fiducials were less than 2 mm, i.e., below SLT of the applied modalities. In patients, the average CT-MRI-match precision for GMs was 1.9 mm supporting their use in MR-guided high precision RT. Trial registration:ClinicalTrials.gov identifier: NCT02724670.

Background Published treatment cascades for HIV/HCV co-infection show WHO goals for HCV micro-elimination are not being met. Barriers include entry to care, access to DAA, treatment adherence, and out of care (OOC) patients. A Data to Care approach used to define persons with HIV (PWH) who are OOC, together with DPH-employed DIS to promote re-engagement has been successful for re-engaging OOC PWH. We modified this approach to re-engage OOC HIV/HCV coinfected persons. Methods Surveillance databases used: CTEDSS (CT Electronic Disease Surveillance System used for HCV) and eHARS (electronic HIV/AIDS Reporting System). Two OOC cohorts studied: HIV OOC for 12 months (no HIV lab 10/2018-10/2019) and 18 months (no HIV lab 12/2017-6/2019). Lists generated for the 2 cohorts matched to CTEDSS to determine the coinfected OOC. DIS supervisor performed pre-work/case conferencing on lists to assess DIS intervention eligibility. DIS success was defined as those who reengaged (made/kept appointment) out of those successfully contacted. Analysis: tests of homogeneity performed between those OOC and not OOC; evaluation of cases at each level of the intervention; measures of dispersion/central tendency performed illustrating reengagement workload. Project Flow Chart Results 12-month OOC: Non-baby boomers (p-value 0.05) and those with detectable HIV VLs (0.04) were more likely to be OOC; 53.7% were DIS-eligible; DIS initiation to client contact, 7 days average (range 4-11); 75 calls and 31 field visits for those successfully contacted; reengagement success rate, 39%. 18-month OOC: Non-baby boomers (0.017), Hispanic and Black race/ethnicity (0.043), and those with detectable HIV viral loads (0.002) were more likely to be OOC; 44% were DIS-eligible; DIS initiation to client contact, 12 days average (range 8-18); 74 calls and 36 field visits for those successfully contacted; reengagement success rate, 43%. Results for the Two Cohorts Out of Care and Workload Results Conclusion A data-to-care approach successfully identified, characterized, connected OOC HIV/HCV coinfected patients. DIS provided patient education, facilitating reengagement to care. DIS Success rates are encouraging but small; efforts were labor intensive. Additional strategies focused on preventing non-baby boomers, persons of color, and those with detectable HIV VLs from becoming OOC should be studied. Disclosures All Authors: No reported disclosures

Background Treatment cascade models focused on persons with HCV mono-infection have been created based on estimates from multiple data sources. Approximately 25% of persons with HIV are coinfected with HCV; no comparable treatment cascade has been reliably generated due to inadequate HCV surveillance data. Using expanded surveillance capacity and validated HIV matching algorithms, we created an HCV treatment cascade for HIV/HCV coinfected persons in Connecticut. Methods Surveillance databases used: CTEDSS (CT Electronic Disease Surveillance System used for HCV) and eHARS (electronic HIV/AIDS Reporting System). eHARS data timeline includes all surveillance entries with labs from 1/1/2015-10/1/2019. Two CTEDSS timelines analyzed: One, all surveillance entries (1/1/1994-1/1/2020); Two, all surveillance entries with labs from 1/1/2016-1/1/2020. Matching CTEDSS and eHARS, coinfected lists were generated and patient HCV labs (AB & PCR) were assessed to determine HCV care status on the treatment cascade. Inclusions and Exclusions for All HCV surveillance entries (1/1/1994 to 1/1/2020) Inclusions and Exclusions for All HCV Surveillance Entries with Labs from 1/1/2016 to 1/1/2020 Results All surveillance entries (1/1/1994 to 1/1/2020): The coinfected list had 3,689 entries; 1,938 had positive HCV screenings (AB+ and/or PCR+) and were eligible for further analysis based on lab dispositions: 567 HCV AB+ only; 721 HCV AB+ and PCR+; 149 PCR+ only; 453 AB+ then PCR+ then PCR-; 48 PCR+ then PCR-. Of 1,371 with evidence for chronic HCV, 501 had presumed sustained virologic response (SVR) (36.5%). All surveillance entries with HCV labs from 1/1/2016 to 1/1/2020: The coinfected list had 912 entries; 665 met inclusion criteria for positive HCV screenings with lab dispositions: 17 HCV AB+ only; 197 HCV AB+ and PCR+; 6 PCR+ only; 407 AB+ then PCR+ then PCR-; 38 PCR+ then PCR-. Of the 648 chronically infected, 445 had presumed SVR (68.6%). Treatment cascade for all surveillance entries (1/1/1994 to 1/1/2020) Treatment cascade for all surveillance entries with labs from 1/1/2016 to 1/1/2020 Conclusion It is feasible to create statewide treatment cascades for HIV/HCV coinfected individuals. SVR rates improved from 36.5% to 68.6% with the use a of more recent HCV surveillance timeline. Contributing factors include: 2016 HCV case definition change (increased HCV PCR testing); electronic lab interface with CTEDSS being able to record negative PCRs in 2018; enhanced DAA availability and implementation. Future studies should adopt this approach which more accurately represents the HCV care status of the current co-infected population. Disclosures All Authors: No reported disclosures

The objective of this study is to conduct a qualitative and a quantitative image quality and lesion evaluation in patients undergoing MR-guided radiation therapy (MRgRT) for prostate cancer on a hybrid magnetic resonance imaging and linear accelerator system (MR-Linac or MRL) at 1.5 Tesla. This prospective study was approved by the institutional review board. A total of 13 consecutive patients with biopsy-confirmed prostate cancer and an indication for MRgRT were included. Prior to radiation therapy, each patient underwent an MR-examination on an MRL and on a standard MRI scanner at 3 Tesla (MRI3T). Three readers (two radiologists and a radiation oncologist) conducted an independent qualitative and quantitative analysis of T2-weighted (T2w) and diffusion-weighted images (DWI). Qualitative outcome measures were as follows: zonal anatomy, capsule demarcation, resolution, visibility of the seminal vesicles, geometric distortion, artifacts, overall image quality, lesion conspicuity, and diagnostic confidence. All ratings were performed on an ordinal 4-point Likert scale. Lesion conspicuity and diagnostic confidence were firstly analyzed only on MRL. Afterwards, these outcome parameters were analyzed in consensus with the MRI3T. Quantitative outcome measures were as follows: anteroposterior and right left diameter of the prostate, lesion size, PI-RADS score (Prostate Imaging—Reporting and Data System) and apparent diffusion coefficient (ADC) of the lesions. Intergroup comparisons were computed using the Wilcoxon-sign rank test and t tests. A post-hoc regression analysis was computed for lesion evaluation. Finally, inter-/intra-reader agreement was analyzed using the Fleiss kappa and intraclass correlation coefficient. For T2w images, the MRL showed good results across all quality criteria (median 3 and 4). Furthermore, there were no significant differences between MRL and MRI3T regarding capsule demarcation or geometric distortion. For the DWI, the MRL performed significantly less than MRI3T across most image quality criteria with a median ranging between 2 and 3. However, there were no significant differences between MRL and MRI3T regarding geometric distortion. In terms of lesion conspicuity and diagnostic confidence, inter-reader agreement was fair for MRL alone (Kappa = 0.42) and good for MRL in consensus with MRI3T (Kappa = 0.708). Thus, lesion conspicuity and diagnostic confidence could be significantly improved when reading MRL images in consensus with MRI3T (Odds ratio: 9- to 11-fold for the T2w images and 5- to 8–fold for the DWI) (p &lt, 0.001). For measures of lesion size, anterior-posterior and right-left prostate diameter, inter-reader and intersequence agreement were excellent (ICC &gt, 0.90) and there were no significant differences between MRL and MRI3T among all three readers. In terms of Prostate Imaging Reporting and Data System (PIRADS) scoring, no significant differences were observed between MRL and MRI3T. Finally, there was a significant positive linear relationship between lesion ADC measurements (r = 0.76, p &lt, 0.01) between the ADC values measured on both systems. In conclusion, image quality for T2w was comparable and diagnostic even without administration of spasmolytic- or contrast agents, while DWI images did not reach diagnostic level and need to be optimized for further exploitation in the setting of MRgRT. Diagnostic confidence and lesion conspicuity were significantly improved by reading MRL in consensus with MRI3T which would be advisable for a safe planning and treatment workflow. Finally, ADC measurements of lesions on both systems were comparable indicating that, lesion ADC as measured on the MRL could be used as a biomarker for evaluation of treatment response, similar to examinations using MRI3T.

Background Hepatitis C (HCV) care cascades for persons with HIV/HCV co-infection are hampered by incomplete HCV surveillance data, lack of standardized matching algorithms, and incomplete ability to determine HCV treatment status from surveillance alone. However, client-level data from individual clinics can be combined into multi-site cascades to assess progress toward micro-elimination goals. To achieve these goals, characterization of treatment gaps is crucial. Looking at trends in 11 HIV clinics, we examine correlates of not entering/initiating HCV therapy. Methods We established a partnership with CT Dept. of Public Health and 11 HIV clinics through a HRSA SPNS grant (047). Lists of HIV/HCV co-infected individuals obtaining care from these clinics from 1/2009-9/2018 were created using data from HIV (eHARS) and HCV (CTEDSS) surveillance, individual clinic rosters and a validated matching algorithm. Clinic personnel reviewed these lists to determine who were treatment eligible (TE) and their current HCV treatment status (e.g. treatment initiated, SVR documented, untreated but in clinical care). Clinic lists were updated regularly to reflect changes in overall patient status (e.g. deceased, relocated, transferred care). We performed bivariate analysis to identify correlates of treatment initiation including odds ratios with 95% confidence intervals. Results Of 7265 patients receiving HIV-related services, 2117 matched to HCV surveillance, representing 1496 unique patients. As of 6/1/2020, 821 patients were TE, 727 (89% of TE) were in active care, 630 (77%) initiated treatment, 620 (76%) completed treatment, 584 (71%) achieved SVR. Of the TE group, 77 (9%) had not yet initiated treatment. Compared to initiators of HCV therapy, patients not yet initiating treatment are more likely to be women (OR 1.7 95% CI 1.1-2.8), and black (OR 1.9 95% CI 1.1-3.1), with unsupressed HIV viral loads (OR 2.5, 95% CI 1.5-4.0). Conclusion This work capitalizes on the feasibility of creating a care cascade for HIV/HCV by Data to Care methods. Patients in partner clinics who had not yet initiated treatment were more likely to be women, black, and have poorly controlled HIV. Further efforts are needed to determine the barriers to treatment initiation among these groups. Disclosures All Authors: No reported disclosures

The parameters of the electroweak theory are determined in a combined electroweak and QCD analysis using all deep-inelastic $e^+p$ and $e^-p$ neutral current and charged current scattering cross sections published by the H1 Collaboration, including data with longitudinally polarised lepton beams. Various fits to Standard Model parameters in the on-shell scheme are performed. The mass of the W boson is determined as $m_W=80.520\pm 0.115~\mathrm {GeV} $ . The axial-vector and vector couplings of the light quarks to the Z boson are also determined. Both results improve the precision of previous H1 determinations based on HERA-I data by about a factor of two. Possible scale dependence of the weak coupling parameters in both neutral and charged current interactions beyond the Standard Model is also studied. All results are found to be consistent with the Standard Model expectations.

The inclusive production cross sections of the charmed mesons D^0, D^+, D_s^+ and D^{*+} have been measured in interactions of 920 GeV protons on C, Ti, and W targets with the HERA-B detector at the HERA storage ring. Differential cross sections as a function of transverse momentum and Feynman's x variable are given for the central rapidity region and for transverse momenta up to $\pT=3.5$ GeV/$c$. The atomic mass number dependence and the leading to non-leading particle production asymmetries are presented as well., Comment: Submitted to EPJ C

The inclusive production cross sections of the strange vector mesons K*0, K*0bar, and phi have been measured in interactions of 920 GeV protons with C, Ti, and W targets with the HERA-B detector at the HERA storage ring. Differential cross sections as a function of rapidity and transverse momentum have been measured in the central rapidity region and for transverse momenta up to pT=3.5 GeV/c. The atomic number dependence is parametrised as sigma(pA) = sigma(pN)*A**alpha, where sigma(pN) is the proton-nucleon cross section. Within the phase space accessible, alpha(K*0) = 0.86+/-0.03, alpha(K*0bar) = 0.87+/-0.03, and alpha(phi) = 0.96+/-0.02. The total proton-nucleon cross sections, determined by extrapolating the differential measurements to full phase space, are sigma(pN->K*0) = 5.06+/-0.54 mb, sigma(pN->K*0bar) = 4.02+/-0.45 mb, and sigma(pN->phi) = 1.17+/-0.11 mb. The Cronin effect is observed for the first time for vector mesons containing strange quarks; compared to the measurements of Cronin et al. for K+- mesons, the measured values of alpha for phi mesons coincide with those of K- mesons for all transverse momenta, while the enhancement for K*0 / K*0bar mesons is smaller., Comment: 19 pages, 17 figures, submitted to Eur Phys J C

The results of a measurement of the proton structure function F_2(x,Q^2)and the virtual photon-proton cross section are reported for momentum transfers squared Q^2 between 0.35 GeV^2 and 3.5 GeV^2 and for Bjorken-x values down to 6 10^{-6} using data collected by the HERA experiment H1 in 1995. The data represent an increase in kinematic reach to lower x and Q^2 values of about a factor of 5 compared to previous H1 measurements. Including measurements from fixed target experiments the rise of F_2 with decreasing x is found to be less steep for the lowest Q^2 values measured. Phenomenological models at low Q^2 are compared with the data., Comment: 27 pages, 10 Figures