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PURPOSE Among patients receiving chemotherapy, symptom monitoring with electronic patient-reported outcomes (ePROs) is associated with improved clinical outcomes, satisfaction, and compliance with therapy. Standard approaches for ePRO implementation are not established, warranting evaluation in community cancer practices. We present implementation findings of ePRO symptom monitoring across a large multisite community oncology practice network. METHODS Patients initiating a new systemic therapy at one of the 210 practice sites at Texas Oncology were invited to use the Navigating Cancer ePRO platform, with stepped-wedge implementation from July to December 2020. Participating patients received a weekly prompt by text message or e-mail to self-report common symptoms and well-being. Severe self-reported symptoms triggered a real-time notification to nursing triage to address the symptom. Enrollment and compliance were systematically tracked weekly with evaluation of barriers and facilitators to adoption and sustainability. RESULTS Four thousand three hundred seventy-five patients planning systemic treatment were enrolled and participated. Seventy-three percent (1,841 of 2,522) of enrolled patients completed at least one ePRO assessment. Among these individuals, 64% (16,299 of 25,061) of available weekly ePRO assessments were completed. Over a 10-week period, compliance declined from 72% to 52%. Barriers currently being addressed include lack of a second reminder text or e-mail prompt, inconsistent discussion of reported ePROs by clinicians at visits, and COVID-related changes in workflow. Facilitators included ease of use and patient and staff engagement on the importance of PROs for symptom management. CONCLUSION ePROs can be effectively implemented in community oncology practice. Utilization of ePROs is high but diminishes over time without attention to barriers. Ongoing work to address barriers and optimize compliance are underway.

Purpose: Doxorubicin is standard therapy for advanced soft-tissue sarcoma (STS) with minimal improvement in efficacy and increased toxicity with addition of other cytotoxic agents. Pembrolizumab monotherapy has demonstrated modest activity and tolerability in previous advanced STS studies. This study combined pembrolizumab with doxorubicin to assess safety and efficacy in frontline and relapsed settings of advanced STS. Patients and Methods: This single-center, single-arm, phase II trial enrolled patients with unresectable or metastatic STS with no prior anthracycline therapy. Patients received pembrolizumab 200 mg i.v. and doxorubicin (60 mg/m2 cycle 1 with subsequent escalation to 75 mg/m2 as tolerated). The primary endpoint was safety. Secondary endpoints included overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) based on RECIST v1.1 guidelines. Results: Thirty patients were enrolled (53.3% female; median age 61.5 years; 87% previously untreated) with 4 (13.3%) patients continuing treatment. The study met its primary safety endpoint by prespecified Bayesian stopping rules. The majority of grade 3+ treatment-emergent adverse events were hematologic (36.7% 3+ neutropenia). ORR was 36.7% [95% confidence interval (CI), 19.9–56.1%], with documented disease control in 80.0% (95% CI, 61.4–92.3%) of patients. Ten (33.3%) patients achieved partial response, 1 (3.3%) patient achieved complete response, and 13 (43.3%) patients had stable disease. Median PFS and OS were 5.7 months (6-month PFS rate: 44%) and 17 months (12-month OS rate: 62%), respectively. Programmed cell death ligand-1 (PD-L1) expression was associated with improved ORR, but not OS or PFS. Conclusions: Combination pembrolizumab and doxorubicin has manageable toxicity and preliminary promising activity in treatment of patients with anthracycline-naive advanced STS.

This protocol describes a complete data acquisition, analysis and computational forecasting pipeline for employing quantitative MRI data to predict the response of locally advanced breast cancer to neoadjuvant therapy in a community-based care setting. The methodology has previously been successfully applied to a heterogeneous patient population. The protocol details how to acquire the necessary images followed by registration, segmentation, quantitative perfusion and diffusion analysis, model calibration, and prediction. The data collection portion of the protocol requires ~25 min of scanning, postprocessing requires 2–3 h, and the model calibration and prediction components require ~10 h per patient depending on tumor size. The response of individual breast cancer patients to neoadjuvant therapy is forecast by application of a biophysical, reaction–diffusion mathematical model to these data. Successful application of the protocol results in coregistered MRI data from at least two scan visits that quantifies an individual tumor’s size, cellularity and vascular properties. This enables a spatially resolved prediction of how a particular patient’s tumor will respond to therapy. Expertise in image acquisition and analysis, as well as the numerical solution of partial differential equations, is required to carry out this protocol.

PURPOSE To provide standards and practice recommendations specific to telehealth in oncology. METHODS A systematic review of the literature on telehealth in oncology was performed, including the use of technologies and telecommunications systems, and other electronic methods of care delivery and sharing of information with patients. The evidence base was combined with the opinion of the ASCO Telehealth Expert Panel to develop telehealth standards and guidance. Public comments were solicited and considered in preparation of the final manuscript. RESULTS The Expert Panel determined that general guidance on implementing telehealth across general and specialty settings has been published previously and these resources are endorsed. A systematic search for studies on topics specific to oncology resulted in the inclusion of two clinical practice guidelines, 12 systematic reviews, and six primary studies. STANDARDS AND GUIDANCE Standards and guidance are provided for which patients in oncology can be seen via telehealth, establishment of the doctor-physician relationship, role of allied health professionals, role of advanced practice providers, multidisciplinary cancer conferences, and teletrials in oncology. Additional information is available at www.asco.org/standards .

Spinal metastases are an increasing societal health burden secondary to improvements in systemic therapy. Estimates indicate that 100,000 or more people have symptomatic spine metastases requiring management. While open surgery and external beam radiotherapy have been the pillars of treatment, there is growing interest in more minimally invasive technologies (eg separation surgery) and non-operative interventions (eg percutaneous cementoplasty, stereotactic radiosurgery). The great expansion of these alternatives to open surgery and the prevalence of adjuvant therapeutic options means that treatment decision making is now complex and reliant upon multidisciplinary collaboration. To help facilitate construction of care plans that meet patient goals and expectations, clinical decision aids and prognostic scores have been developed. These have been shown to have superior predictive value relative to more classic prediction models and may become an increasingly important aspect of the clinical practice of spinal oncology. Here we overview current therapeutic advances in the management of spine metastases and highlight emerging areas for research. Given the rapid advancements in surgical technologies and adjuvants, the field is likely to undergo further transformative changes in the coming decade.

Purpose In MONARCH 1 (NCT02102490), single-agent abemaciclib demonstrated promising efficacy activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2− metastatic breast cancer (MBC). To help interpret these results and put in clinical context, we compared overall survival (OS) and duration of therapy (DoT) between MONARCH 1 and a real-world single-agent chemotherapy cohort. Methods The real-world chemotherapy cohort was created from a Flatiron Health electronic health records-derived database based on key eligibility criteria from MONARCH 1. The chemotherapies included in the cohort were single-agent capecitabine, gemcitabine, eribulin, or vinorelbine. Results were adjusted for baseline demographics and clinical differences using Mahalanobis distance matching (primary analysis) and entropy balancing (sensitivity analysis). OS and DoT were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results A real-world single-agent chemotherapy cohort (n = 281) with eligibility criteria similar to the MONARCH 1 population (n = 132) was identified. The MONARCH 1 (n = 108) cohort was matched to the real-world chemotherapy cohort (n = 108). Median OS was 22.3 months in the abemaciclib arm versus 13.6 months in the matched real-world chemotherapy cohort with an estimated hazard ratio (HR) of 0.54. The median DoT was 4.1 months in MONARCH 1 compared to 2.9 months in the real-world chemotherapy cohort with HR of 0.76. Conclusions This study demonstrates an approach to create a real-world chemotherapy cohort suitable to serve as a comparator for trial data. These exploratory results suggest a survival advantage and place the benefit of abemaciclib monotherapy in clinical context.

Purpose Roux-en-Y gastric bypass (RYGB) surgery is currently the most efficient treatment to achieve long-term weight loss in individuals with severe obesity. This is largely attributed to marked reductions in food intake mediated in part by changes in gut-brain communication. Here, we investigated for the first time whether weight loss after RYGB is associated with alterations in central noradrenaline (NA) neurotransmission. Materials and Methods We longitudinally studied 10 individuals with severe obesity (8 females; age 43.9 ± 13.1 years; body mass index (BMI) 46.5 ± 4.8 kg/m2) using (S,S)-[11C]O-methylreboxetine and positron emission tomography to estimate NA transporter (NAT) availability before and 6 months after surgery. NAT distribution volume ratios (DVR) were calculated by volume-of-interest analysis and the two-parameter multilinear reference tissue model (reference region: occipital cortex). Results The participants responded to RYGB surgery with a reduction in BMI of 12.0 ± 3.5 kg/m2 (p p = 0.019) and a general tendency towards reduced DVR throughout the brain. Furthermore, we found a strong positive correlation between pre-surgery DVR in hypothalamus and the change in BMI (r = 0.78; p = 0.01). Conclusion Reductions in BMI after RYGB surgery are associated with NAT availability in brain regions responsible for decision-making and homeostasis. However, these results need further validation in larger cohorts, to assess whether brain NAT availability could prognosticate the outcome of RYGB on BMI. Graphical abstract

School closures during the COVID-19 pandemic presented a threat to student learning and motivation. Suspension of achievement testing created a barrier to understanding the extent of this threat. L...

Im vorliegenden CME-Beitrag sollen die Grundlagen des Theranostik-Prinzips beginnend bei den Eigenschaften der Radionuklide sowie deren Verfügbarkeit erläutert werden. Anhand von medizinischen und chemischen Beispielen aus den prominentesten Anwendungsgebieten der Theranostik (Prostatakarzinom/PSMA, neuroendokrine Tumoren und Fibroblasten-Aktivierungsprotein Inhibitoren) werden die unterschiedlichen Arten von theranostischen Radionuklid- und Radioliganden-Paaren beschrieben. Abgerundet wird der Artikel durch Ausführungen zu den regulatorischen Randbedingungen wie Verfügbarkeit und Verkehrsfähigkeit von Radionuklidvorstufen und radioaktiven Arzneimitteln sowie zu deren Eigenherstellung.

To assess the current opinions and state of knowledge in primary sports injury prevention among members of the On 21 August 2019, a web-based questionnaire was sent to the members of the tri-national society A total of 272 participants completed the survey, representing a total survey participation of 17.7 % of all members. The study population consisted of orthopaedic surgeons (55 % with surgical and 21 % with non-operative orientation), medical students (10 %), physical therapists (8 %) and sports scientists (4 %). Ninety-four percent of all participants stated that they considered the importance of sports injury prevention to be "very high" (68 %) or "high" (26 %). However, almost 70 % of all participants stated that they spend less than one hour per week on injury prevention work. The term "prevention" was clearly defined and practicable for only 40 %, understandable but difficult to implement for 51 %, and unclear and difficult to implement for 9 % of the participants. Seventy-two percent of respondents were aware of existing prevention programs such as "Stop-X" or "FIFA 11 +", whereas 28 % of participants were uninformed regarding these programs. A strong divergence was identified between participants' perception of the importance of sports injury prevention and the existing implementation of preventive measures. Future funding of prevention programs, expansion of research strategies for injury prevention and better financial reimbursement are of utmost importance. Erhebung und Beurteilung des aktuellen Meinungs- und Wissensstandes bzgl. der Prävention von Sportverletzungen unter den Mitgliedern der Gesellschaft für Orthopädisch-Traumatologische Sportmedizin (GOTS). Am 21. August 2019 wurde ein Online-Fragebogen an die Mitglieder der Gesellschaft (Österreich, Deutschland und Schweiz) verschickt. Die Umfrage war bis zum 21. November 2019 online und umfasste 22 Fragen, die in 5 Abschnitte unterteilt waren: 1. allgemeine Bedeutung der Prävention (n = 4), 2. Spezifikationen der Studienpopulation (n = 3), 3. Umsetzung von Prävention (n = 8), 4. Verbesserungsmöglichkeiten in der Prävention (n = 4) und 5. zukünftige Forschungsbereiche (n = 3). Insgesamt nahmen 272 Teilnehmer an der Umfrage teil, was einem Anteil von 17,7 % aller Mitglieder entspricht. Die Studienpopulation bestand aus orthopädischen Chirurgen (55 % operativer und 21 % konservativer Schwerpunkt), Medizinstudenten (10 %), Physiotherapeuten (8 %) und Sportwissenschaftlern (4 %). 94 % aller Teilnehmer gaben an, dass sie die Bedeutung der Prävention von Sportverletzungen als „sehr hoch“ (68 %) oder „hoch“ (26 %) einschätzen. Allerdings gaben fast 70 % aller Teilnehmer an, dass sie weniger als eine Stunde pro Woche für die Arbeit zur Verletzungsprävention aufwenden. Der Begriff „Prävention“ war nur für 40 % klar definiert und praktikabel, für 51 % verständlich, aber schwierig umzusetzen, und für 9 % der Teilnehmer unklar und schwierig umzusetzen. 72 % der Befragten gaben an, bestehende Präventionsprogramme wie „Stop-X“ oder „FIFA 11 +“ zu kennen, während 28 % der Teilnehmer über diese Programme nicht informiert waren. Es wurde eine starke Divergenz zwischen der Wahrnehmung der Bedeutung der Prävention von Sportverletzungen durch die Mitglieder und der bestehenden Umsetzung von Präventionsmaßnahmen festgestellt. Die künftige Finanzierung von Präventionsprogrammen, die Ausweitung von Forschungsstrategien zur Verletzungsprävention und eine bessere finanzielle Rückerstattung sind von größter Bedeutung.

Military working dog handlers and their canine partners continue to be invaluable team members on missions of national importance, but little information exists in the medical literature regarding specific musculoskeletal injuries to military working dog handlers. We report a case of a dog handler with overuse shoulder traction injuries due to leash lunges from their dog in an effort to provide diagnostic insight and treatment options and look at prevention of common musculoskeletal manifestations of overuse in working dog handlers.

Background: This study evaluates the ability to predict the response of locally advanced breast cancers to neoadjuvant therapy (NAT) using patient-specific magnetic resonance imaging (MRI) data and a biophysical mathematical model. The 3D mathematical model consists of three parts: tumor cell proliferation, tumor spread (diffusion), and treatment. In particular, the tumor cells proliferate according to logistic growth, and the diffusion term is coupled to the mechanical properties of the surrounding fibroglandular and adipose tissues to inform individual tumor growth patterns (specific to each patient’s anatomy). The model’s treatment term accounts for tumor cell reduction according to approximate local drug delivery for each patient. Methods: Patients (N = 21) with intermediate to high grade invasive breast cancers with varying receptor status, who were eligible for NAT as a component of their clinical care, were recruited. Each patient was treated with standard-of-care consisting of one or two NAT regimens in sequence followed by surgical resection of any residual tumor. MRI data are acquired at four time points: 1) prior to initiation of NAT, 2) after 1 cycle of NAT, 3) after 2-4 cycles of NAT, and 4) 1 cycle after scan 3. The MRI data is processed and evaluated using our semi-automated pipeline. Specifically, diffusion-weighted MRI data is utilized to characterize the cellularity throughout the tumor tissue, and dynamic contrast-enhanced (DCE-) MRI data is used to segment the breast tissue and analyze the local drug delivery using pharmacokinetic analysis and population-derived plasma curves of drug concentrations. The model’s predictive ability is assessed using three different strategies. First, the model is calibrated using each patient’s first two scans to enable predictions of the total tumor cellularity, volume, and longest axis that are directly compared to the values measured from their third scan. Second, the model’s predictions for tumor response are compared to the corresponding response evaluation criteria in solid tumors (RECIST) results. Third, the model is re-calibrated using scans 3 and 4 and simulated to the time of surgery to compare the model’s predictions to each patient’s response status determined by surgical pathology. Results: Calibrating the model with MRI data for one cycle of therapy yields predictions strongly correlated with tumor response measured from each patient’s third scan, concordance correlation coefficients of 0.91, 0.90, and 0.86 for total cellularity, volume, and longest axis, respectively (p < 0.01, N = 18). The model’s predictions are significantly (p < 0.01) correlated with tumor response as designated by RECIST for the cohort. Specifically, the model predicts greater percent reduction in the longest axis for the RECIST designated responder group (i.e., complete response and partial response) compared to non-responders. At the time of surgery, the model predicts changes in total tumor cellularity from baseline that are significantly (p < 0.01) correlated with pathological response status—an area under the receiver operator characteristic curve of 0.92 and a sensitivity and specificity of 1.0 and 0.74, respectively. Discussion: These preliminary results suggest that this clinical-mathematical approach can be predictive of tumor response very early in the course of NAT on a patient-specific basis. Moreover, the study was performed in the community-care setting across a heterogenous group of patients, indicating the approach may be practical for wide-spread application. NCI U01 CA174706, NCI U01 CA154602, CPRIT RR160005, ACS-RSG-18-006-01-CCE, R01CA240589, NCI-U24CA226110, CPRIT RR160093 Citation Format: Angela M Jarrett, David A. Hormuth, II, Anum K Syed, Chengyue Wu, John Virostko, Anna G Sorace, Julie C DiCarlo, Jeanne Kowalski, Debra Patt, Boone Goodgame, Sarah Avery, Thomas E Yankeelov. Predicting breast cancer response to neoadjuvant therapies using a mathematical model individualized with patient-specific magnetic resonance imaging data: Preliminary Results [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-18.

The ability to accurately predict response and then rigorously optimize a therapeutic regimen on a patient-specific basis, would transform oncology. Toward this end, we have developed an experimental-mathematical framework that integrates quantitative magnetic resonance imaging (MRI) data into a biophysical model to predict patient-specific treatment response of locally advanced breast cancer to neoadjuvant therapy. Diffusion-weighted and dynamic contrast-enhanced MRI data is collected prior to therapy, after 1 cycle of therapy, and at the completion of the first therapeutic regimen. The model is initialized and calibrated with the first 2 patient-specific MRI data sets to predict response at the third, which is then compared to patient outcomes (N = 18). The model's predictions for total cellularity, total volume, and the longest axis at the completion of the regimen are significant within expected measurement precision (P< 0.05) and strongly correlated with measured response (P < 0.01). Further, we use the model to investigate, in silico, a range of (practical) alternative treatment plans to achieve the greatest possible tumor control for each individual in a subgroup of patients (N = 13). The model identifies alternative dosing strategies predicted to achieve greater tumor control compared to the standard of care for 12 of 13 patients (P < 0.01). In summary, a predictive, mechanism-based mathematical model has demonstrated the ability to identify alternative treatment regimens that are forecasted to outperform the therapeutic regimens the patients clinically. This has important implications for clinical trial design with the opportunity to alter oncology care in the future.

Introduction The numeric score for the United States Medical Licensing Examination Step 1 is one of the only universal, objective, scaled criteria for comparing the many students who apply to orthopaedic surgery residency. However, on February 12, 2020, it was announced that Step 1 would be transitioning to pass/fail scoring. The purpose of this study was to (1) determine the most important factors used for interview and resident selection after this change and (2) to assess how these factors have changed compared with a previous report on resident selection. Methods A survey was distributed to the program directors (PDs) of all 179 orthopaedic surgery programs accredited by the Accreditation Council for Graduate Medical Education. Questions focused on current resident selection practices and the impact of the Step 1 score transition on expected future practices. Results A total of 78 PDs (44%) responded to the survey. Over half of PDs (59%) responded that United States Medical Licensing Examination Step 2 clinical knowledge (CK) score is the factor that will increase most in importance after Step 1 transitions to pass/fail, and 90% will encourage applicants to include their Step 2 CK score on their applications. The factors rated most important in resident selection from zero to 10 were subinternship performance (9.05), various aspects of interview performance (7.49 to 9.01), rank in medical school (7.95), letters of recommendation (7.90), and Step 2 CK score (7.27). Compared with a 2002 report, performance on manual skills testing, subinternship performance, published research, letters of recommendations, and telephone call on applicants' behalf showed notable increases in importance. Discussion As Step 2 CK is expected to become more important in the residency application process, current applicant stress on Step 1 scores may simply move to Step 2 CK scores. Performance on subinternships will remain a critical aspect of residency application, as it was viewed as the most important resident selection factor and has grown in importance compared with a previous report.

Regional variation in prevalence of genetic mutations in growth hormone deficiency (GHD) is known. Study phenotype and prevalence of mutations in GH1, GHRHR, POU1F1, PROP1 genes in GHD cohort. One hundred and two patients {Isolated GHD (IGHD): 79; combined pituitary hormone deficiency (CPHD): 23} with orthotopic posterior pituitary were included. Auxologic, hormonal and radiological details were studied. All four genes were analysed in IGHD patients. POU1F1 and PROP1 were studied in CPHD patients. Of 102, 19.6% were familial cases. Height SDS, mean (SD) was − 5.14 (1.63). Peak GH, median (range) was 0.47 ng/ml (0–6.59), 72.5% patients had anterior pituitary hypoplasia (APH). Twenty mutations (novel: 11) were found in 43.1% patients (n = 44, IGHD-36, CPHD-8). GHRHR mutations (n = 32, p.Glu72* = 24) were more common than GH1 mutations (n = 4) in IGHD cohort. POU1F1 mutations (n = 6) were more common than PROP1 mutations (n = 2) in CPHD cohort. With few exceptions, this prevalence pattern is contrary to most studies in world-literature. No patients with peak GH > 4 ng/ml had mutations, signifying it as negative predictor. While many parameters were significant on univariate analysis, only positive family history and lower median peak GH levels were significant predictors of mutations on multivariate analysis in IGHD patients. At variance with world literature, we found reverse predominance of GHRHR over GH1 mutations, POU1F1 over PROP1 mutations and predominance of GHRHR p.Glu72* mutations thus re-affirming the regional diversity in GHD genetics. We report positive and negative predictors of mutations in GHD.

Pridopidine is an investigational drug in late stage development for the treatment of Huntington disease and originally postulated to act as dopamine stabilizer by modulating dopamine-dependent motor behavior. However, preclinical studies show pridopidine has highest affinity to sigma-1 receptors. Importantly, mediated by sigma-1 receptors, pridopidine has neuroprotective properties and enhances neuronal plasticity. The aim of our study was to determine the in-vivo the target engagement (receptor occupancy) of pridopidine at clinically relevant doses in healthy volunteers and Huntington disease patients. We used sigma-1 receptor-specific (S)-(-)-[18F]Fluspidine and dopamine D2/D3 receptor-specific [18F]Fallypride PET imaging to quantify the sigma-1 and dopamine D2/D3 receptor occupancy of pridopidine. Eleven male healthy volunteers (pridopidine 0.5 to 90 mg in six dose groups) and three male Huntington disease patients (pridopidine 90 mg) were studied twice before and 2h following single oral doses of pridopidine using S-(-)-[18F]Fluspidine PET (300 MBq, 0-90min p.i.). Distribution volume VT was quantified using kinetic modeling (One-tissue compartment model; metabolite correction). Four male healthy volunteers were studied twice using [18F]Fallpride PET (200 MBq, 0-210min p.i.) before and 2h after a single oral dose of pridopidine (90 mg). Binding potential BPND was assessed by the simplified reference model. Volume-of-interest analyses were performed. For each subject/tracer, the receptor occupancy was calculated by the Lassen plot analysis. In healthy volunteers, there was high sigma-1 receptor occupancy (87 to 91%) across all brain regions at doses ranging from 22.5 to 90 mg. The sigma-1 receptor occupancy was 43% at 1 mg pridopidine. In Huntington disease patients, very similar to healthy volunteers, at 90 mg pridopidine, there was high sigma-1 receptor occupancy (87±7%, n.s.). In contrast, in healthy volunteers, there was only negligible dopamine D2/D3 receptor occupancy (3±2%) at 90 mg pridopidine. We established a sigmoid-shaped dose/sigma-1 receptor occupancy relation (Hill equation) with Hill coefficient larger than 1 in healthy volunteers, suggesting a positive cooperative binding nature of the sigma-1 receptor. Using PET, we report for the first time in the living human brain that after a single dose of 90 mg, pridopidine acts as a selective sigma-1 receptor ligand showing near to complete sigma-1 receptor occupancy (~90%) but only minimal (~3%) dopamine D2/D3 receptor occupancy. Our findings provide significant clarification about pridopidine’s mechanism of action and support further use of the 45 mg bidaily dose to achieve full and selective targeting of the sigma-1 receptor in future clinical trials in Huntington disease and amyotrophic lateral sclerosis.

Objective: To summarize significant research contributions on cancer informatics published in 2019. Methods: An extensive search using PubMed/Medline and manual review was conducted to identify the scientific contributions published in 2019 that address topics in cancer informatics. The selection process comprised three steps: (i) 15 candidate best papers were first selected by the two section editors, (ii) external reviewers from internationally renowned research teams reviewed each candidate best paper, and (iii) the final selection of two best papers was conducted by the editorial committee of the Yearbook. Results: The two selected best papers demonstrate the clinical utility of deep learning in two important cancer domains: radiology and pathology. Conclusion: Cancer informatics is a broad and vigorous subfield of biomedical informatics. Applications of new and emerging computational technologies are especially notable in 2019.

Cortical superficial siderosis (cSS) is a common feature in patients with cerebral amyloid angiopathy (CAA). The correlation between β-amyloid and/or tau pathology and the occurrence of cSS is unclear. We report on an 80-year-old male patient who was diagnosed with probable CAA according to modified Boston criteria and underwent longitudinal magnetic resonance imaging, amyloid positron emission tomography (PET), and additional tau PET imaging. Amyloid deposition presented predominantly in the contralateral hemisphere not affected by cSS. In contrast, tau deposition was predominantly overlapping with brain regions affected by cSS. Amyloid deposition was not different in the vicinity of cSS whereas tau depositions were elevated in the vicinity of CSS-affected regions compared to non-cSS-affected brain regions. This case of probable CAA suggests that cSS may be associated with a locally elevated tau pathology but not with increased fibrillary amyloid deposition.

Horticulture is one of the fastest growing subsectors of agriculture in Tanzania. Gender relations in vegetable-producing and vegetable-trading households need to be understood to make value chain development equitable. This study, carried out in northern and central Tanzania, is based on data from surveys, focus group discussions and semi-structured interviews. The perceptions of men and women traders and producers are investigated with regard to labour participation in traditional vegetable value chains and gains (income and expenditure) from it. Farmers were found to report more balanced intra-household labour arrangements paired with less-balanced income and expenditure shares, while traders indicated less-balanced labour contributions that went hand in hand with more-balanced shares of benefits. Farmers related limited household development not only to imbalances in benefits but also to a lack of trust and cooperation between spouses. The importance of gender-transformative approaches in agricultural value chains is emphasized herein.

Introduction: Tumor forecasting methods for predicting treatment response of individual breast cancer patients to neoadjuvant therapy (NAT) have shown promise in clinical application. Our framework for predicting tumor response integrates quantitative magnetic resonance imaging (MRI) data acquired early in the course of NAT into a mechanism-based, biophysical model that predicts the eventual treatment response of breast tumors. Being able to predict which patient will respond effectively to NAT would have a fundamental and lasting impact on healthcare. However, the ultimate goal is to optimize therapy given the unique characteristics of each patient. Here we show that the detailed combination of advanced image analysis and rigorous mathematical modeling can accurately predict response for the individual patient. Further, we use the model to demonstrate the potential selection of personalized therapeutic regimens. This is accomplished by initializing the mathematical model with patient-specific characteristics and then varying, in silico, a range of treatment plans to achieve the greatest tumor control. Methods: Quantitative MRI was acquired from breast cancer patients (N = 11) at three time points during the course of NAT: 1) prior to NAT, 2) after 1 cycle of their initial chemotherapy, and 3) after the completion of the initial chemotherapy regimen. With these data, we implemented our recently established mechanically coupled, reaction-diffusion model at the tissue scale for predicting breast tumor response to therapy. The 3D model is initialized with patient-specific, diffusion-weighted MRI data characterizing tumor cellularity. Additionally, the model includes a tumor cell reduction term for local drug delivery as estimated from pharmacokinetic analysis of dynamic contrast-enhanced MRI data and population-derived plasma curves of therapeutic concentrations. The model’s predictive ability was assessed using three different measures. Using the first two scans, the model is calibrated and simulated forward to the third scan time to compare the predicted total tumor cellularity, volume, and longest axis to the actual values measured from the patient’s third scan. We then simulate alternate regimens using the same total dose each patient received during their standard regimen, while varying dosages and frequency between their second and third scans. Results: After calibrating the model using the first two imaging time points, the model’s predictions are significantly correlated to the measured tumor burden at scan three with Pearson Correlation Coefficients of 0.93, 0.89, 0.96 (p < 0.01) for total cellularity, total volume, and longest axis, respectively. The model predicts that for the alternative dosing regimens assessed, individual patients could have achieved an additional 0-43% reduction in total cellularity compared to the therapeutic regimens patients actually received. This indicates that standard regimens may not be the most effective for every patient. Discussion and future directions: These results demonstrate that the mathematical model can be predictive of tumor response using data at the earliest times of therapy regimens. The in silico results illustrate how for individual patients (depending on their unique tumor characteristics and vasculature—captured by the calibrated parameters of the model), therapy regimens can be tailored and even optimized (via established optimal control theory methods) to each patient using a mathematical model and simulation studies. The present investigation represents a significant first step towards personalizing patient regimens through quantitative imaging and mathematical modeling. NCI U01 CA174706, NCI U01 CA154602, CPRIT RR160005, ACS-RSG-18-006-01-CCE Citation Format: Angela M Jarrett, David A Hormuth II, Chengyue Wu, John Virostko, Anna G Sorace, Julie C DiCarlo, Debra Patt, Boone Goodgame, Sarah Avery, Thomas E Yankeelov. Optimizing neoadjuvant regimens for individual breast cancer patients generated by a mathematical model utilizing quantitative magnetic resonance imaging data: Preliminary results [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-17.

Background: In the FAIRLANE trial (NCT02301988) in early TNBC, adding the oral AKT inhibitor IPAT to neoadjuvant PAC led to numerical increases in rates of pathologic complete response (pCR; primary endpoint) and complete response by MRI in unselected patients, with a numerically greater treatment effect in patients with PIK3CA/AKT1/PTEN-altered tumors [Oliveira et al., Ann Oncol 2019]. The IMpassion130 trial established the efficacy of first-line atezolizumab + nab-PAC in patients with PD-L1-positive advanced TNBC [Schmid et al., NEJM 2018]. Preliminary phase 1b results showed promising activity with a triplet combination of IPAT, atezolizumab, and taxane as first-line therapy for advanced TNBC across PIK3CA/AKT1/PTEN and PD-L1 biomarker subgroups [Schmid et al., AACR 2019]. Using samples from the FAIRLANE trial, PD-L1 expression was characterized to evaluate relationships between IPAT treatment effect and expression of PD-L1 and biomarkers relevant to IPAT. Methods: Pretreatment tumor samples were evaluated for genomic alterations using the FoundationOne® assay (Foundation Medicine). Pretreatment PD-L1 status was determined using the SP142 immunohistochemistry assay (VENTANA Medical Systems), with PD-L1 positivity defined as PD-L1 expression on ≥1% of tumor-infiltrating immune cells. Tumor-infiltrating lymphocytes (TILs) were quantified using the Salgado method [Salgado et al., Ann Oncol 2015]. Gene expression was measured by RNA sequencing. Results: Samples were evaluable for genomic alterations in 144 patients, TILs in 135 patients, gene expression in 111 patients, and PD-L1 expression in 99 patients. The prevalence of PD-L1 positivity was 39%, consistent with the reported prevalence in IMpassion130. Compared with PD-L1-negative tumor samples, PD-L1-positive tumor samples showed significantly higher levels of TILs (mean 37% vs 24%; p=0.004) and significantly higher expression of the genes encoding for PD-L1 (CD274: geometric mean 10.5 vs 3.9 counts per million; p Citation Format: Matthew J Wongchenko, Mafalda Oliveira, Cristina Saura, Paolo Nuciforo, Isabel Calvo, Jay Andersen, José L Passos Coelho, Miguel Gil Gil, Begoña Bermejo, Debra A Patt, Eva Ciruelos, Zhen Shi, Na Xu, Patricia Villagrasa, Aruna Mani, Steven J Isakoff. Expression of PD-L1 is independent of PIK3CA/AKT1/PTEN alterations in triple-negative breast cancer (TNBC) and is not associated with response to ipatasertib (IPAT) plus paclitaxel (PAC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-23.

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to describe trends in the field. Results: This commentary of highlights has resulted in 19 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Conclusion: Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Contains fulltext : 232903.pdf (Publisher’s version ) (Open Access) This guideline on current good radiopharmacy practice (cGRPP) for small-scale preparation of radiopharmaceuticals represents the view of the Radiopharmacy Committee of the European Association of Nuclear Medicine (EANM). The guideline is laid out in the format of the EU Good Manufacturing Practice (GMP) guidelines as defined in EudraLex volume 4. It is intended for non-commercial sites such as hospital radiopharmacies, nuclear medicine departments, research PET centres and in general any healthcare establishments. In the first section, general aspects which are applicable to all levels of operations are discussed. The second section discusses the preparation of small-scale radiopharmaceuticals (SSRP) using licensed generators and kits. Finally, the third section goes into the more complex preparation of SSRP from non-licensed starting materials, often requiring a purification step and sterile filtration. The intention is that the guideline will assist radiopharmacies in the preparation of diagnostic and therapeutic SSRP's safe for human administration.

Background The purpose of this study was to determine whether advanced quantitative magnetic resonance imaging (MRI) can be deployed outside of large, research-oriented academic hospitals and into community care settings to predict eventual pathological complete response (pCR) to neoadjuvant therapy (NAT) in patients with locally advanced breast cancer. Methods Patients with stage II/III breast cancer (N = 28) were enrolled in a multicenter study performed in community radiology settings. Dynamic contrast-enhanced (DCE) and diffusion-weighted (DW)-MRI data were acquired at four time points during the course of NAT. Estimates of the vascular perfusion and permeability, as assessed by the volume transfer rate (Ktrans) using the Patlak model, were generated from the DCE-MRI data while estimates of cell density, as assessed by the apparent diffusion coefficient (ADC), were calculated from DW-MRI data. Tumor volume was calculated using semi-automatic segmentation and combined with Ktrans and ADC to yield bulk tumor blood flow and cellularity, respectively. The percent change in quantitative parameters at each MRI scan was calculated and compared to pathological response at the time of surgery. The predictive accuracy of each MRI parameter at different time points was quantified using receiver operating characteristic curves. Results Tumor size and quantitative MRI parameters were similar at baseline between groups that achieved pCR (n = 8) and those that did not (n = 20). Patients achieving a pCR had a larger decline in volume and cellularity than those who did not achieve pCR after one cycle of NAT (p Ktrans, ADC, cellularity, and bulk tumor flow from baseline (pre-treatment) were all significantly greater (p Conclusions Quantitative analysis of DCE-MRI and DW-MRI can be implemented in the community care setting to accurately predict the response of breast cancer to NAT. Dissemination of quantitative MRI into the community setting allows for the incorporation of these parameters into the standard of care and increases the number of clinical community sites able to participate in novel drug trials that require quantitative MRI.

Alcoholic fatty liver disease (AFLD) is characterized by lipid accumulation and inflammation and can progress to cirrhosis and cancer in the liver. AFLD diagnosis currently relies on histological analysis of liver biopsies. Early detection permits interventions that would prevent progression to cirrhosis or later stages of the disease. Herein, we have conducted the first comprehensive time-course study of lipids using novel state-of-the art lipidomics methods in plasma and liver in the early stages of a mouse model of AFLD, i.e., Lieber-DeCarli diet model. In ethanol-treated mice, changes in liver tissue included up-regulation of triglycerides (TGs) and oxidized TGs and down-regulation of phosphatidylcholine, lysophosphatidylcholine, and 20-22-carbon-containing lipid-mediator precursors. An increase in oxidized TGs preceded histological signs of early AFLD, i.e., steatosis, with these changes observed in both the liver and plasma. The major lipid classes dysregulated by ethanol play important roles in hepatic inflammation, steatosis, and oxidative damage. Conclusion: Alcohol consumption alters the liver lipidome before overt histological markers of early AFLD. This introduces the exciting possibility that specific lipids may serve as earlier biomarkers of AFLD than those currently being used.

Background: Different indications and treatment options for combined injuries to the anterior cruciate ligament (ACL) and medial collateral ligament complex (MCL) are not clearly defined. Purpose: To perform a modified Delphi process with the Committee for Ligament Injuries of the German Knee Society (DKG) in order to structure and optimize the process of treating a combined injury to the ACL and MCL. Study Design: Consensus statement. Methods: Scientific questions and answers were created based on a comprehensive literature review using the central registers for controlled studies of Medline, Scopus, and Cochrane including the terms medial collateral ligament, anterior cruciate ligament, MCL, ACL, and outcome used in various combinations. The obtained statements passed 3 cycles of a modified Delphi process during which each was readjusted and rated according to the available evidence (grades A-E) by the members of the DKG Ligament Injuries Committee and its registered guests. Results: The majority of answers, including several questions with >1 graded answer, were evaluated as grade E (n = 16) or C (n = 10), indicating that a low level of scientific evidence was available for most of the answers. Only 5 answers were graded better than C: 3 answers with a grade of A and 2 answers with a grade of B. Only 1 answer was evaluated as grade D. An agreement of >80% (range, 83%-100%) among committee members was achieved for all statements. Conclusion: The results of this modified Delphi process offer a guideline for standardized patient care in cases of combined injuries to the ACL and MCL.

Introduction: Osteoporosis is a critical public health issue with substantial morbidity and healthcare costs. Resident education on osteoporosis is not standardized. Little is known about the barriers to osteoporosis treatment and the usefulness of educational programming from the perspective of orthopaedic residency program directors (PDs). Methods: This study aims to evaluate the current state and perception of bone health education from the perspective of orthopaedic residency PDs. Therefore, a self-designed 29-question online survey was sent to 129 PDs in the United States to assess bone health education. The information, collected from August to October 2020, included program characteristics, participation in the American Orthopaedic Association’s Own the Bone (AOA/OTB) program or any fracture liaison service (FLS) program, availability of faculty, potential barriers, and educational resources. Data collection was performed anonymously with a 47% response rate. Results: The results were compared between programs that used the AOA/OTB program (30%) or any FLS program (28%) (58% OTB or any FLS) vs. programs that did not have any program (42%). Subsequent subanalysis was performed comparing AOA/OTB vs. any FLS vs. no program. Programs that did not have any FLS were least likely to have a formal education syllabus (p = 0.01). When comparing clinical education of residents on bone health, 64% of programs without any system did not provide any formal clinical exposure such as a bone health clinic vs. assessment in patients with fracture compared with 24% of OTB programs and 44% of programs with any FLS (p = 0.02). When asked about desired resources, 47% would find a bone health rotation useful. Among all PDs, 60% support the concept of a 5-year AOA Council of Orthopaedic Residency Directors (CORD)/OTB osteoporosis curriculum. Discussion: The key findings were that institutions including OTB or any FLS in their programs had better availability of specialty consultants, faculty, and a FLS coordinator.

The Representative Concentration Pathway 2.6 (RCP2.6), which is broadly compatible with the Paris Agreement's temperature goal by 1.5-2°C, contains substantial reductions in agricultural non-CO2 emissions besides the deployment of Carbon Dioxide Removal (CDR). Failing to mitigate agricultural methane and nitrous oxide emissions could contribute to an overshoot of the RCP2.6 warming by about 0.4°C. We explore using additional CDR to offset alternative agricultural non-CO2 emission pathways in which emissions either remain constant or rise. We assess the effects on the climate of calculating CDR rates to offset agricultural emission under two different approaches: relying on the 100-year global warming potential conversion metric (GWP100) and maintaining effective radiative forcing levels at exactly those of RCP2.6. Using a reduced-complexity climate model, we find that the conversion metric leads to a systematic underestimation of needed CDR, reaching only around 50% of the temperature mitigation needed to remain on the RCP2.6 track. This is mostly because the metric underestimates, in the near term, forcing from short-lived climate pollutants such as methane. We test whether alternative conversion metrics, the GWP20 and GWP∗, are more suitable for offsetting purposes, and found that they both lead to an overestimation of the CDR requirements. Under alternative agricultural emissions pathways, holding to RCP2.6 total radiative forcing requires up to twice the amount of CDR that is already included in the RCP2.6. We examine the costs of this additional CDR, and the effects of internalizing these in several agricultural commodities. Assuming an average CDR cost by $150/tCO2, we find increases in prices of up to 41% for beef, 14% for rice, and 40% for milk in the United States relative to current retail prices. These figures are significantly higher (for beef and rice) under a global scenario, potentially threatening food security and welfare. Although the policy delivers a mechanism to finance the early deployment of CDR, using CDR to offset remaining high emissions may well hit other non-financial constraints and can thus only support, and not substitute, emission reductions., PLoS ONE, 16 (3), ISSN:1932-6203

This study characterizes the error that results when performing quantitative analysis of abbreviated dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data of the breast with the Standard Kety–Tofts (SKT) model and its Patlak variant. More specifically, we used simulations and patient data to determine the accuracy with which abbreviated time course data could reproduce the pharmacokinetic parameters, Ktrans (volume transfer constant) and ve (extravascular/extracellular volume fraction), when compared to the full time course data. SKT analysis of simulated abbreviated time courses (ATCs) based on the imaging parameters from two available datasets (collected with a 3T MRI scanner) at a temporal resolution of 15 s (N = 15) and 7.23 s (N = 15) found a concordance correlation coefficient (CCC) greater than 0.80 for ATCs of length 3.0 and 2.5 min, respectively, for the Ktrans parameter. Analysis of the experimental data found that at least 90% of patients met this CCC cut-off of 0.80 for the ATCs of the aforementioned lengths. Patlak analysis of experimental data found that 80% of patients from the 15 s resolution dataset and 90% of patients from the 7.27 s resolution dataset met the 0.80 CCC cut-off for ATC lengths of 1.25 and 1.09 min, respectively. This study provides evidence for both the feasibility and potential utility of performing a quantitative analysis of abbreviated breast DCE-MRI in conjunction with acquisition of current standard-of-care high resolution scans without significant loss of information in the community setting.

During the coronavirus disease 2019 (COVID-19) pandemic, many of us have faced new challenges as we manage some of the country's most vulnerable citizens, our patients with cancer The telemedicine policy changes and the resultant implementation empowers cancer providers to better serve our patients [Extracted from the article] Copyright of JCO Clinical Cancer Informatics is the property of American Society of Clinical Oncology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )

The norepinephrine transporter (NET) has been suggested to play a critical role in attention-deficit/hyperactivity disorder (ADHD). In this prospective controlled study we tested the a-priori-hypothesis that central NET availability is altered in adult ADHD patients compared to healthy controls. Study participants underwent single positron emission tomography-magnetic resonance imaging (PET-MRI). MRI sequences included high resolution T1-MPRAGE data for regions of interest (ROI) delineation and voxel-based morphometry (VBM) and T2-weighted fluid-attenuated inversion-recovery for detection and exclusion of pathological abnormalities. NET availability was assessed by NET-selective (S,S)-O-[11C]methylreboxetine; regional distribution volume ratios (DVR) were calculated based on individual PET-MRI data co-registration and a multi-linear reference tissue model with two constraints (MRTM2; reference region: occipital cortex). VBM analysis revealed no difference in local distribution of gray matter between the 20 ADHD patients (9 females, age 31.8 ± 7.9 years, 488 ± 8 MBq injected activity) and the 20 age-matched and sex-matched control participants (9 females, age 32.3 ± 7.9 years, 472 ± 72 MBq). In mixed-model repeated-measures analysis with NET availability as dependent and ROI as repeated measure we found a significant main effect group in fronto-parietal-thalamic-cerebellar regions (regions on the right: F1,25 = 12.30, p = .002; regions on the left: F1,41 = 6.80, p = .013) indicating a reduced NET availability in ADHD patients. None of the other investigated brain regions yielded significant differences in NET availability between groups after applying a Benjamini-Hochberg correction at a significance level of 0.05. Overall our findings demonstrate the pathophysiological involvement of NET availability in adult ADHD.

Hintergrund Eine gangige Meinung ist, dass eine akute Rekonstruktion des vorderen Kreuzbandes (VKB) mit einem erhohten Arthrofibroserisiko einhergeht. Dies beruht jedoch haufig auf Arbeiten aus den 1990er-Jahren mit Nachbehandlungskonzepten, welche mit der aktuellen Therapie nicht mehr vereinbar sind.

Introduction: The aging population reintroduces the need to establish early identification of falls risk as a means of primary and secondary prevention of falls. While there are several existing to...

Purpose The effects of chemotherapy dose intensity on survival in patients with advanced non-small-cell lung cancer (NSCLC) are poorly understood. We retrospectively analyzed dose delays/reduction, relative dose intensity (RDI), and the association between chemotherapy intensity and survival in advanced NSCLC. Methods This retrospective cohort study included adults with advanced lung cancer who received first-line myelosuppressive platinum-based chemotherapy (January 2007–December 2010) in ~ 230 US Oncology Network community practices. Dose delays ≥ 7 days, dose reductions ≥ 15%, and RDI relative to standard regimens were described. Overall survival (OS) was measured using Kaplan-Meier and Cox proportional hazard (PH) models. Results Among 3866 patients with advanced NSCLC, 32.4% experienced dose delays ≥ 7 days, 50.1% experienced dose reductions ≥ 15%, and 40.4% had RDI

We describe two cases of hypertension and hypokalemia due to mineralocorticoid excess caused by posaconazole treatment of coccidioidomycosis and rhinocerebral mucormycosis infections, respectively. Clinical laboratory evaluations, including a comprehensive analysis of blood and urine steroid profiles, revealed low renin and aldosterone and indicated as the underlying mechanism primarily a block of 11β-hydroxylase activity in patient 1, whereas patient 2 displayed weaker 11β-hydroxylase but more pronounced 11β-hydroxysteroid dehydrogenase 2 inhibition. The results show that both previously suggested mechanisms must be considered and emphasize significant interindividual differences in the contribution of each enzyme to the observed mineralocorticoid excess phenotype. The mineralocorticoid symptoms of patient 1 resolved after replacement of posaconazole therapy by isavoconazole, and posaconazole dosage de-escalation ameliorated the effects in patient 2. By providing a thorough analysis of the patients’ blood and urine steroid metabolites, this report adds further evidence for two individually pronounced mechanisms of posaconazole-induced hypertension and hypokalemia. The elucidation of the factors responsible for the individual phenotype warrants further research.

Big data and predictive analytics have immense potential to improve risk stratification, particularly in data-rich fields like oncology. This article reviews the literature published on use cases and challenges in applying predictive analytics to improve risk stratification in oncology. We characterized evidence-based use cases of predictive analytics in oncology into three distinct fields: (1) population health management, (2) radiomics, and (3) pathology. We then highlight promising future use cases of predictive analytics in clinical decision support and genomic risk stratification. We conclude by describing challenges in the future applications of big data in oncology, namely (1) difficulties in acquisition of comprehensive data and endpoints, (2) the lack of prospective validation of predictive tools, and (3) the risk of automating bias in observational datasets. If such challenges can be overcome, computational techniques for clinical risk stratification will in short order improve clinical risk stratification for patients with cancer.

Ambitious goals for climate change mitigation and energy security policies are driving deployment of renewable energy sources globally. However, the deployment of renewable energies at scale requires not only public but also private capital, such as foreign direct investment (FDI). Many countries with favourable conditions for renewables, such as the countries of the Middle East and North African (MENA) region, are not attracting sufficient FDI. Risk perceptions of FDI stakeholders are one of the reasons. This paper discusses the de-risking approach as a possible tool to address subjective risk perceptions and assesses with a Computable General Equilibrium (CGE) model macroeconomic feedback-effects of employing a de-risking strategy for FDI into a particular kind of renewable electricity (RES-E) technology, concentrated solar power, in the MENA region. Our results show that the application of a de-risking approach reduces the costs for deployment of CSP, and therefore, also volumes of subsidies that would be needed to make CSP cost competitive with fossil fuel based electricity generation. This, in turn, leads to positive GDP and welfare effects in the MENA region. Our results allow us developing of recommendations for energy policy the implementation of the de-risking approach as a potential consensual option with high political feasibility to reduce climate change mitigation costs.

Background In MONARCH 1 (NCT02102490), abemaciclib demonstrated promising single-agent activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2- metastatic breast cancer (MBC).1 Confirmed objective response rate (ORR) was 19.7% (95% CI: 13.3, 27.5) and at 18 months minimum follow-up median overall survival (OS) was 22.3 months. Due to the single-arm trial design of MONARCH 1, there is a need to view these results in clinical context relative to available treatment options. This study compared the OS results of abemaciclib in MONARCH 1 vs that in a real-world single-agent chemotherapy cohort with similar patient and disease characteristics. Methods MONARCH 1 study design and key eligibility criteria were previously described.1 The real-world cohort was based on Flatiron Health electronic health records-derived, nationally representative (USA-based) database comprising patient-level structured and unstructured data, curated via technology-enabled abstraction, for patients with MBC between January 1, 2011 through February 28, 2018. A real-world single-agent chemotherapy cohort was created based on the key eligibility criteria of MONARCH 1 and included patients diagnosed with HR+, HER2- MBC who received single-agent chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) following 1-2 prior chemotherapy regimens in the metastatic setting, had an ECOG PS of 0-1, and no prior CDK4 & 6 therapy. The index date was the start of the eligible single-agent chemotherapy, and patients were followed from the index date until date of death, loss to follow-up, or end of the database, whichever occurred earlier. OS results were adjusted using 2 methods (Mahalanobis distance matching and entropy balancing with bootstrapping) to account for baseline demographic and clinical differences between the real-world and trial cohorts. Results A real-world cohort (n=281) with eligibility criteria similar to the MONARCH 1 population (n=132) was identified. A subsequent matching based on Mahalanobis distance was performed to match MONARCH 1 population (n=108) with the real-world cohort (n=108). The matched cohorts demonstrated similar patient and disease characteristics. Median OS was 22.3 months in the abemaciclib arm vs 13.6 months in the matched cohort with an estimated hazard ratio (HR) of 0.54 (95% CI: 0.37, 0.77). Results of a sensitivity analysis performed using entropy balancing were consistent with an adjusted median OS of 12.7 months in the real-world cohort (n=281)with HR of 0.57 (95% CI from bootstrapping: 0.44, 0.78). Conclusion Methodological advances to adjust for potential biases, and improvements in data quality, have evolved enabling the ability to leverage a real-world cohort as an external comparator arm. This study demonstrates the ability to create a real-world chemotherapy cohort suitable to serve as a comparator for MONARCH 1. These exploratory results suggest a survival advantage and adequately place the clinical benefit of abemaciclib monotherapy in clinical context. References Dickler et al, CCR 2017 Citation Format: Rugo H, Dieras V, Cortes J, Patt D, Wildiers H, O'Shaughnessy J, Zamora E, Yardley DY, Carter GC, Sheffield KM, Li L, Andre VA, Derbyshire RE, Li XI, Frenzel M, Huang Y-J, Dickler MN, Tolaney SM. Real-world survival of heavily pretreated patients with refractory HR+, HER2- metastatic breast cancer receiving single-agent chemotherapy - A comparison with MONARCH 1 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-19.

Background: The oral AKT inhibitor IPAT is being evaluated in cancers with a high prevalence of PI3K/AKT pathway activation. In the PBO-controlled randomized phase II FAIRLANE trial (NCT02301988), adding IPAT to PAC as neoadjuvant therapy for TNBC led to a numerical increase in pathologic complete response (pCR) in unselected patients (17.1% vs 13.3%), with a greater treatment effect in patients with PIK3CA/AKT1/PTEN-altered tumors (17.9% vs 11.8%). The addition of IPAT also led to an increase in complete response (CR) by MRI (27.6% vs 13.3%) that was enhanced in patients with PIK3CA/AKT1/PTEN-altered tumors (39.3% vs 8.8%) [Oliveira, AACR 2018]. We report an exploratory analysis performed to provide better understanding of potential biomarkers for response. Methods: Pretreatment tumor samples were evaluated for genomic alterations using the FoundationOne® (Foundation Medicine) assay (n=144) and gene expression by RNA-Seq (n=92). Samples were classified into TNBC subtypes based on the method developed by Lehmann and Pietenpol [Lehmann, J Clin Invest 2011]. Tumor-infiltrating lymphocytes (TILs) were quantified using the Salgado method [Salgado, Ann Oncol 2015] (n=135). Results: Of 62 patients (43%) with PIK3CA/AKT1/PTEN-altered tumors, 21 had an activating mutation in PIK3CA or AKT1 and 47 had an alteration in PTEN (6 [3 in each arm] had both PIK3CA mutation and PTEN alteration). Although only 3 patients with PIK3CA/AKT1-mutant tumors achieved a pCR, there was an increased rate of MRI CR with the addition of IPAT to PAC [Table]. In patients with PTEN alterations, both pCR rate and MRI CR rate were increased with IPAT. In patients treated with PBO + PAC, all 4 pCR patients evaluable by RNA-Seq were of the immunomodulatory (IM) subtype. However, in the IPAT + PAC arm, pCRs were also seen in patients with basal-like 1 (BL-1), mesenchymal (M), and mesenchymal stem-like (MSL) subtypes. Consistent with this observation, in the PBO + PAC arm, samples from patients achieving a pCR had significantly higher levels of stromal TILs than those from patients who did not have a pCR, while no difference was observed in the IPAT + PAC arm. Response, n (%)PIK3CA/AKT mutation (n=21)PTEN alteration (n=47) IPAT + PAC (n=11)PBO + PAC (n=10)IPAT + PAC (n=21)PBO + PAC (n=26)pCR1 (9%)2 (20%)4 (19%)3 (12%)CR by MRI5 (45%)1 (10%)8 (38%)2 (8%) Conclusions: This retrospective exploratory biomarker analysis of the phase II FAIRLANE trial of neoadjuvant IPAT for TNBC provides insight into the potential heterogeneity of response and resistance to taxane therapy. The results also hint that response to PAC alone is dependent on baseline immune infiltration and that this dependency might be relieved with the addition of AKT inhibition. Citation Format: Wongchenko MJ, Oliveira M, Saura C, Nuciforo P, Calvo I, Andersen J, Passos Coelho JI, Gil Gil M, Bermejo B, Patt DA, Ciruelos E, Singel SM, Maslyar DJ, Xu N, de la Peña L, Baselga J, Gendreau S, Isakoff SJ. Exploratory biomarker analyses of FAIRLANE, a double-blind placebo (PBO)-controlled randomized phase II trial of neoadjuvant ipatasertib (IPAT) + paclitaxel (PAC) for early triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-19.

Purpose and objectives Effective community-based programs to manage arthritis exist, but many adults with arthritis are unaware that these programs are available in their communities. An electronic health record (EHR) referral intervention was designed to strengthen health care and community-based partnerships and increase participation in these arthritis programs. The intervention was developed in response to a national effort that aimed to enhance the health, wellness, and quality of life for people with arthritis by increasing the awareness and availability of, and participation in arthritis-appropriate evidence-based interventions. Intervention approach The National Recreation and Park Association recruited 4 park and recreation agencies and their health care partners to implement an EHR-based retrospective and point-of-care referral intervention. Eligible for referral were adults aged 45 or older with an arthritis condition who were seen by a physician within the past 18 months, and were living within the park and recreation service area. After health care organizations identified eligible adults, they either mailed communication packages describing the availability and benefits of the intervention and conducted phone calls to encourage arthritis-appropriate intervention participation or counseled and referred patients during an office visit. Evaluation methods The pilot was assessed by using semi-structured interviews with key intervention staff members and the Consolidated Framework for Implementation Research. Results Our approach resulted in referrals for 3,660 people, 1,063 (29%) of whom participated in an intervention. Analysis of key informant interviews also highlighted the specific contextual factors, facilitators, and barriers that influenced the adaptation and overall implementation of the referral intervention. Implications for public health Our pilot demonstrates that successful coordination between health care organizations and community-based organizations can promote awareness of and participation in community-based programs. An understanding of the contextual factors and lessons learned can be used to inform processes that can lead to more effective and sustainable health care and community-based partnerships.

Background At present, orthopedic surgery applicants do not universally include Step 2 Clinical Knowledge (Step 2 CK) scores on their applications and current inclusion rates are not yet reported. As Step 1 transitions to pass/fail scoring, we suspect more applicants will include Step 2 CK scores. We sought to identify what percentage of applications currently include Step 2 CK, if applicants who include Step 2 CK (Step 1+CK) score lower on Step 1 than those not including Step 2 CK (Step 1-CK), and what correlations exist between Step 1 and Step 2 CK scores among those who include the scores on their applications. Methodology Applicants to one residency program over two application cycles (2019-2020) were analyzed. The percentage including Step 1 and Step 2 scores was recorded. Step 1 scores were compared between Step 1+CK and Step 1-CK applicants. Differences between Step 2 CK and Step 1 scores were stratified by Step 1 score. Results A total of 1,688 applicants applied to our institution from 2019 to 2020. Of those reporting United States Medical Licensing Examination scores, 1,316/1,660 (79%) reported a Step 2 CK score. Step 1-CK applicants scored higher on Step 1 (250.7 ± 10.9) versus Step 1+CK applicants (244.3 ± 13.1) (p < 0.0001). More applicants who scored lower on Step 1 improved upon their percentile rank between Step 1 and Step 2 CK than those who scored higher on Step 1 (χ2 (8,1316) = 79.1, p < 0.0001). Conclusions From 2019 to 2020, 79% of applicants included Step 2 CK. Lower Step 1 scores were more likely to include Step 2 CK and improve upon their percentile score. It is unclear how Step 1 scoring change will affect current practice.