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In this prospective, observational, method comparison clinical study, the Xpert Xpress MVP test (MVP) was evaluated using both clinician-collected (CVS) and self-collected vaginal swabs (SVS) collected in a clinical setting. The study was conducted at 12 sites, including point-of-care (POC) settings, from geographically diverse locations in the United States.

Background: Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) is the most prevalent breast cancer (BC) subtype(≈60% of all BC in Spain), 95% of which are diagnosed in early stage. Despite several treatment options, approximately 20%-25% of them will experience metastatic relapse. Early and accurate identification of patients at high risk of recurrence is critical to improve patient outcomes. It would be relevant to know how high risk patients are identified and managed in Spain. The primary objective was to describe the current approaches to patient management and standards of care for patients with early stage (I-IIIc) HR+/HER2- BC in a real world setting in Spain.Methods: Real-world data were drawn from the Adelphi Early BC I Disease Specific Program. Data included physicians´ (medical oncologists) subjective perceptions such as factors used to determine patient´s risks of recurrence, and objective variables relating to the next 8 consecutive patients with HR+ HER2- BC they consulted and completed patient record forms for, such as demographic, clinical and gene expression profiles. Data were collected between June and October 2019. The sample was analyzed to identify patients similar to those meeting the high risk of recurrence criteria used in the monarchE (mE) trial: ≥4 positive nodes, OR 1-3 positive nodes AND [grade 3 or tumor ≥5 cm or Ki-67 ≥20%]. Those not meeting the criteria were categorised as Low/moderate (L/M) risk. Results: 50 oncologists provided data on 400 consecutive patients, of which 81 (20%) were categorized as high risk. Patients´ mean age was 58 years old at diagnosis and initiated first adjuvant treatment (AT) within four months of diagnosis. 19% had family history of BC, their disease stage was predominantly II (50%), 57% had grade 2 tumors and 74% had a tumor size of 1-3cm. 50 patients (13%) met high risk clinical pathologic criteria (≥4 positive nodes, OR 1-3 positive nodes AND [grade 3 or tumor ≥5 cm]) and an additional 31 patients (8%) met high risk mE criteria based on having a Ki-67 expression of ≥20%.At diagnosis, high risk patients compared to L/M tended to be younger (mean 54,3 vs 58,5 years), with higher likelihood of BC family history (32% vs 16%), more advanced disease at diagnosis (99% vs 59% stage II or III), more likely to have grade 3 tumors (41% vs 14%) and tumors >3cm (32% vs 14%). The most common biomarker/genetic tests at diagnosis were ER, PgR and Ki67, used in over 95% of patients.Genomic assays of the tumors were performed in 35% of patients, of which the most common were Oncotype Dx (58%) and MammaPrint (22%). High risk patients were less likely to have genomic assays (15% vs 40% received any). Genomic assays were more often conducted prior to starting AT therapy (66%) than at initial diagnosis (38%).Neoadjuvant and first adjuvant treatments are described in table 1. Factors frequently considered by oncologists (>45% of respondents) to evaluate risk of recurrence were tumor stage, size and grade, nodal, HER2 and HR status, genomic assays and Ki-67 expression level. Conclusion: One in five patients were classified as high risk according to mE criteria, although oncologists considered additional factors to categorize patients as high risk level in their daily practice. Consequently, many patients of L/M risk according to mE criteria could still be considered as high risk by their physicians, as suggested by nearly half of patients receiving ChT treatment as adjuvant therapy. Proportion of patients that were prescribed each class in each setting (not mutually exclusive)ChemotherapyAnthracyclineTaxaneEndocrine therapyAromatase inhibitorTamoxifenTargeted therapyTotal sampleNeoadjuvant therapy n (%)n (%)n (%)n (%)n (%)n (%)n (%)n (%)Overall (n=400)75 (19)69 (92)60 (80)64 (85)28 (37)22 (29)6 (8)-High risk (n=81)17 (21)16 (94)15 (88)16 (94)8 (47)7 (41)1 (6)-L/M risk (n=319)58 (18)53 (91)45 (78)48 (83)20 (34)15 (26)5 (9)-Total sampleFirst adjuvant n (%)n (%)n (%)n (%)n (%)n (%)n (%)n (%)Overall (n=400)400 (100)217 (54)129 (32)132 (33)256 (64)177 (44)79 (20)1 (0)High risk (n=81)81 (100)66 (81)56 (69)50 (62)27 (33)18 (22)9 (11)1 (1)L/M risk (n=319)319 (100)151 (47)73 (23)82 (26)229 (72)159 (50)70 (22)- Citation Format: Miguel Martín, Jose Ángel García Sáenz, Isabel Blancas, Alberto Molero, Manuel Atienza, Jose Manuel Cervera, Jacqueline Brown, Alex Rider, Rhys Williams, Emilio Alba. Patient profiles, management and treatment patterns in HR+, HER2- early breast cancer in a real-world setting in Spain [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-10.

Background: Previous studies have highlighted concerns regarding treatment persistence (TP) of patients with early breast cancer (EBC) taking adjuvant endocrine therapy (ET) but these data have not been analyzed based on patient’s risk of recurrence. The aim of this study is to evaluate the TP of patients at high risk of recurrence based on clinicopathologic criteria used in the monarchE trial. Methods: This observational retrospective cohort study used nationwide Flatiron Health electronic health record (EHR)-derived de-identified database of US patients diagnosed with EBC from Jan 2011 to Sept 2020. Overall, 4028 patients were selected based on the following criteria: adult female or male with diagnosis of HR+, HER2– EBC (stage IA-IIIC) with no evidence of distant metastasis who received surgical resection and adjuvant endocrine therapy. Patients were divided into 2 groups; GroupA: patients with clinicopathologic features suggestive of high risk of recurrence: ≥4 positive(+) axillary lymph nodes (ALN), OR 1-3+ ALN and either Grade3 disease, or tumor size ≥ 5 cm, or Ki-67 ≥ 20%. GroupB: patients with stage IA-IIIC disease who did not meet those high risk criteria. TP (time from start to discontinuation of adjuvant ET) was compared between the 2 groups. Patients who had a gap of >90 days after their last date of ET, as documented in the EHR, were considered to have discontinued ET. Patients whose last ET was ≤90 days from Sept 2020 were censored. Cumulative incidence functions of nonpersistence were estimated, treating recurrences or deaths occurring during ET as competing risks. Results: While gender and race distributions were similar between groups, patients in GroupA (n=557) were younger and more likely to be premenopausal, have an ECOG PS score of 1 or 2+, and have received mastectomy, radiation and chemotherapy compared to GroupB (n=3471). Estimates of the cumulative incidence functions of nonpersistence were statistically different between the groups (p Conclusions: This study suggests that patients at high risk of recurrence have higher ET-TP than those at lower risk. The separation was most pronounced at 5 years. The steep increase in 5-year nonpersistence in lower risk group could be due to a perception of less need to continue ET for longer periods of time in lower risk disease. The greater persistence in patients at high risk is noteworthy, but interventions to improve patient’s TP are still warranted. Table 1: Cumulative incidence of nonpersistence after initiating ET Citation Format: Kristin M. Sheffield, Alexandra S. Vitko, Jacqueline Brown. Persistence with adjuvant endocrine therapy in patients with early breast cancer at high risk of recurrence: a US-based real-world study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-01.

Background Recognized prognostic factors associated with increased risk of recurrence in patients (pts) with HR+, HER2- early breast cancer (EBC) are higher histologic grade, larger primary tumor size, and greater lymph node involvement. Genomic assays like Oncotype DX obtain prognostic information to indicate benefit of adjuvant therapy. The objective was to examine use of genomic assays and describe demographic, clinical, and pathological characteristics of pts tested. Methods Real-world data was drawn from the Adelphi EBC I Disease Specific Programme, a cross-sectional observational study in France, Germany, Italy, Spain, United Kingdom (UK), United States (US) and Japan. 765 consulting physicians were surveyed, including questions on use of genomic assays to assess risk of recurrence. In each country, 20-64 of the physicians also completed patient record forms from Mar-Sep 2019 for up to 8 eligible pts with HR+, HER2- EBC. Results Physicians in US (n=176), UK (n=52) and Spain (n=100) reported highest use of genomic assays to categorize patients from low to intermediate risk (US 61%; Spain 57%; UK 65%) and from intermediate to high risk of recurrence (US 64%; Spain 67%; UK 65%). Lowest use was in Japan (n=134), 13% and 20%, respectively. Oncotype DX was consistently reported as the most frequently used genomic assay to assess the risk of recurrence (see table). Patient record forms were completed for 2447 pts (98% female, mean age 59.6 years, SD 13.0). Frequency of Oncotype DX testing varied by stage, with less testing in stage III pts (stage I 26% (194/755); stage II 20% (221/1130); stage III 11% (56/505) p5 cm 11% (11/105); p=0.0503). Similar patterns were seen across countries except Italy, but generally not significant. Oncotype Dx testing was less frequent in pts >50 years (age ≤50 25% (161/657); age >50 18% (318/1790); p=0.0003). Similar patterns were seen across countries, and significant in Germany (p=0.0029) and Italy (p Conclusion Use of genomic assays to assess pt risk of recurrence varied across countries. The most commonly used assay was Oncotype DX. Oncotype DX testing was less frequent amongst stage III, grade 3, large, node +ve tumors or age >50, although there were some important country variations. These data contribute to the understanding of drivers in adopting multi-gene assays within clinical practice. Genomic AssayTotal(n=729)*US (n=171)Japan (n=122)France (n=93)Germany (n=97)Italy (n=96)Spain (n=100)UK (n=50)Oncotype DX67%91%45%54%64%60%63%94%Adjuvant! Online30%23%25%29%29%34%43%42%Mammaprint29%37%30%17%24%21%52%0%Breast Cancer Index17%29%25%13%14%17%2%4%EndoPredict13%8%20%20%12%11%8%18%Prosigna11%8%11%22%4%6%21%8%*729/765 physicians who assessed all or some of their patients with EBC for risk of recurrence Citation Format: Jacqueline Brown, Rhys Williams, Alex Rider, Rosie Wild, Michael Method. Multi-country study of the use of genomic assays in HR+, HER2- early breast cancer and characteristics of patients tested [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 PS4-34.

Aim: To assess invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, HER2-negative early breast cancer with combined clinicopathological criteria from monarchE, a phase III study of abemaciclib. Methods: US electronic health records were used to compare outcomes between high-risk (≥4 lymph nodes, or 1–3 lymph nodes and grade 3, tumor ≥5 cm or Ki-67 ≥20%) versus nonhigh-risk groups using Kaplan–Meier methods and Cox regression models. Results: The high-risk group (n = 557) was at higher risk for IDFS and DRFS events than the nonhigh-risk group (n = 3471). IDFS events (hazard ratio: 3.07; 95% CI: 2.45–3.83) and DRFS events (hazard ratio: 3.15; 95% CI: 2.49–3.97) were significantly higher for the high-risk group. Conclusion: Risk of recurrence was three-times greater in the high-risk group, highlighting the need for better therapies.

Background: Breast cancer in the United States is diagnosed in over 90% of cases prior to evidence of distant metastasis (stages I–III) with approximately 70% of these cases classified as hormone receptor positive human epidermal growth factor receptor 2 negative (HR+HER2-).1 Despite primary surgery, radiation, and adjuvant endocrine/chemotherapy treatment options, approximately 20-30% of patients will experience relapse with distant metastases.2 Some clinical and pathological characteristics are known to be prognostic factors, but there are no standard definitions associated with level of risk. The objective of this study was to determine the extent of mortality associated with clinical and pathological characteristics of early breast cancer (EBC) using real-world data. Methods: Eligible patients from 2010–2016 Surveillance, Epidemiology, and End Results (SEER) data were aged ≥18 years and had a diagnosis of stage I, II, or III breast cancer with no distant metastases. Patients with HR-HER2- breast cancer were excluded. Mortality rates (95% confidence interval) by HER2 status and, for HR+HER2- tumors, by cancer stage, Bloom-Richardson (BR) grade, ipsilateral auxiliary lymph nodes status, and tumor size were estimated using Kaplan-Meier methods. Results: A total of 257,278 breast cancer patients were included: 214,578 HR+HER2-, 30,122 HR+HER2+, and 12,578 HR-HER2+. Mean age was 61.5 years, 99.1% were female, and 70.1% were white/non-Hispanic. The 5-year mortality rates were similar for HR+HER2- (12.3%) and HR+HER2+ (12.2%), whereas HR-HER2+ was numerically higher (16.8%). Within the HR+HER2- group, the 5-year mortality rates for subgroups are shown in Table 1. The highest mortality rate for both the node positive and micrometastases subgroups was approximately 30% for those who had 1–3 ipsilateral auxiliary lymph nodes, BR grade 3, and tumor size ≥5 cm. Conclusions: Patients with HR+HER2- EBC had similar mortality rates to patients with HR+HER2+ EBC. In patients with HR+HER2- EBC, higher mortality rates were numerically associated with ≥4 positive lymph nodes, BR grade 3, and greater tumor size. The effect on mortality was compounded with combinations of these histopathologic characteristics. References: 1. Howlander N, et al. J Natl Cancer Inst 2014;106:dju055; 2. Cardoso F, et al. Breast 2018;39:131-8. Table 1. Kaplan-Meier 5-year mortality estimates for patients with HR+HER2- early breast cancer by stage, grade, nodal status, and tumor size Node positiveN1mi: micrometastasesNode negativen=50,321n=10,096n=154,161 Mortality rate, % (95% CI)Mortality rate, % (95% CI)Mortality rate, % (95% CI)Overall18.15 (17.70–18.60)10.31 (9.51–11.11)10.54 (10.33–10.74)Stage INA7.29 (6.39–8.20)8.35 (8.13–8.56)Stage II12.56 (12.06–13.06)13.39 (11.91–14.87)16.69 (16.17–17.21)Stage III26.41 (25.61–27.22)19.10 (15.13–23.07)44.46 (40.69–48.23)1–3 Ips Ax nodes positive12.93 (12.43–13.43)9.96 (9.14–10.78)NA≥4 Ips Ax nodes positive24.75 (23.82–25.69)22.23 (15.64–28.82)NABR grade 325.62 (24.63–26.61)15.25 (13.09–17.41)14.24 (13.60–14.89)Tumor size Citation Format: Jacqueline Brown, Michael W Method, David R Nelson. Mortality rates associated with clinical and pathological characteristics of hormone receptor positive human epidermal growth factor receptor 2 negative early breast cancer: An analysis of the 2010-2016 surveillance, epidemiology, and end results data [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 P5-08-18.

This study examined the relevance of the quality and quantity of courses offered in colleges of education to account for differences among students. Two research questions and hypotheses were each answered and tested respectively. The study adopted a survey design with a population target that comprised students from colleges of education in the North Central zone of Nigeria. 510 respondents were randomly selected from both federal and state colleges of education proportionately. A “Course Contents Requisite Questionnaire (CCRQ)” was drafted and validated of which its reliability tested with a Cronbach’s coefficient alpha gave .714. The data generated were analysed through descriptive and inferential statistics. Results showed that students found it difficult to properly grasp in-depth knowledge due to too many courses offered; GSE courses offered by students should be reduced and not beyond 200 level; no add and drop options and less than 40% of enrolled candidates complete within three years. It was recommended that a 3-term GSE courses be reduced and terminate at 200 level; NCCE to legitimately organize a workshop to address the inadequacies discovered in structural organization of the current contents; add and drop of course option be available in colleges among others.

Background: Globally, malaria is one of the six major causes of deaths from communicable diseases. In South Africa, malaria is known to be endemic in three provinces. Two large trials, AQUAMAT and SEAQUAMAT, demonstrated the superiority of intravenous (IV) artesunate compared to quinine. A systematic review (including the above trials) demonstrated a mortality benefit for adult patients treated with artesunate, but included studies that were conducted in Asia with no adult data available for Africa. Given the lack of local data, we conducted this study to investigate the use of artesunate for the treatment of severe malaria at two academic adult intensive care units (ICUs) in Johannesburg. Methods: We undertook a retrospective patient record review. All patients admitted to the two ICUs and treated for severe malaria using artesunate were included. The study period extended from April 2010 to April 2014. The primary outcome was to determine the observed mortality and relate it to the predicted mortality based on the Acute Physiology and Chronic Health Evaluation (APACHE II) severity of illness score. The ratio of the observed mortality to the expected mortality based on the APACHE II severity of illness score provides a standardised mortality ratio (SMR). Clinical and laboratory parameters data were analysed. Results: There were 56 patients included in the study, of which 40 were male (71.4%). The mean APACHE II score was 19 (standard deviation 5.4). We observed a lower than predicted mortality rate of 21.4% (SMR 0.66). Human immunodeficiency virus (HIV) was the most prevalent comorbidity (32%). There was no travel history in 26.8% of patients. Heart rate, respiratory rate and Glasgow Coma Scale (GCS) all improved significantly from admission to the time of discharge ( p ≤ 0.01). Acidaemia, bilirubin, urea and bleeding risk (platelet count) also improved ( p ≤ 0.01). Mechanical ventilation was associated with an increased risk of death (OR 35; CI 7.0–182). Conclusion: In this retrospective two-centre study, IV artesunate was associated with a lower than predicted mortality in adult patients with severe malaria requiring ICU admission.

In the last decade, design, development, and advancement in embedded processing, sensing, and wireless communication have fueled the emergence of Internet of Things (IoT), where various smart devices communicate and cooperate with each other and existing communication systems to achieve the goal of sharing information and coordinating decisions. Meanwhile, IPv6-based Low Power and Lossy Network (LLN), which is a major building block of IoT, has attracted a fair amount of attention for all sorts of IoT applications and deployments. In order to provide IPv6 connectivity to an enormous number of resource-constrained smart devices in IoT environment, an efficient routing protocol for IPv6-based LLNs, also widely known as RPL, has been standardized. However, RPL lacks security protection and is vulnerable to various Denial-of-Service (DoS) attacks. In this paper, we first present an advanced vampire attack, which is a novel routing layer specific service disruption and resource exhaustion attack, against RPL in IPv6-based LLNs. Then we propose a Theil index-based countermeasure to effectively detect and mitigate advanced vampire attack. The basic idea of the proposed Theil index-based countermeasure is that each node measures the distribution of destination MAC addresses in the received data packets to detect advanced vampire attack. Through experimental study, the effectiveness of the Theil index-based countermeasure is validated, indicating a viable approach against advanced vampire attack in the IoT.

Background Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with one of the highest world incidences in the Eastern Cape region of South Africa. Several genome wide studies have been performed on ESCC cohorts from Asian countries, North America, Malawi and other parts of the world but none have been conducted on ESCC tumors from South Africa to date, where the molecular pathology and etiology of this disease remains unclear. We report here tumor associated copy number changes observed in 51 ESCC patients’ samples from the Eastern Cape province of South Africa. Methods We extracted tumor DNA from 51 archived ESCC specimens and interrogated tumor associated DNA copy number changes using Affymetrix® 500 K SNP array technology. The Genomic Identification of Significant Targets in Cancer (GISTIC 2.0) algorithm was applied to identify significant focal regions of gains and losses. Gains of the top recurrent cancer genes were validated by fluorescence in situ hybridization and their protein expression assessed by immunohistochemistry. Results Twenty-three significant focal gains were identified across samples. Gains involving the CCND1, MYC, EGFR and JAG1 loci recapitulated those described in studies on Asian and Malawian cohorts. The two most significant gains involved the chromosomal sub-bands 3q28, encompassing the TPRG1 gene and 11q13.3 including the CTTN, PPFIA1and SHANK2 genes. There was no significant homozygous loss and the most recurrent hemizygous deletion involved the B3GAT1 gene on chromosome 11q25. Focal gains on 11q13.3 in 37% of cases (19/51), consistently involved CTTN and SHANK2 genes. Twelve of these cases (23,5%), had a broader region of gain that also included the CCND1, FGF19, FGF4 and FGF3 genes. SHANK2 and CTTN are co-amplified in several cancers, these proteins interact functionally together and are involved in cell motility. Immunohistochemistry confirmed both Shank2 (79%) and cortactin (69%) protein overexpression in samples with gains of these genes. In contrast, cyclin D1 (65%) was moderately expressed in samples with CCND1 DNA gain. Conclusions This study reports copy number changes in a South African ESCC cohort and highlights similarities and differences with cohorts from Asia and Malawi. Our results strongly suggest a role for CTTN and SHANK2 in the pathogenesis of ESCC in South Africa.

OBJECTIVE To describe treatment patterns and resource utilisation in France, Germany, Spain and the United Kingdom (UK) in patients with unresectable locally advanced and/or metastatic gastro-oesophageal adenocarcinoma (GEA), who failed first-line fluoropyrimidine/platinum treatment. METHODS Treating physicians completed a web-based chart review (2013-2015). Eligible patients were ≥ 18 years old; had unresectable locally advanced and/or metastatic gastric adenocarcinoma including the gastro-oesophageal junction; received first-line fluoropyrimidine/platinum-based therapy; and had ≥ 3 months of follow-up after first-line discontinuation. Data were summarised descriptively for each country. RESULTS There were n = 201 patients in France, n = 202 in Germany, n = 208 in Spain and n = 200 in the UK whose charts were reviewed. Percentages of patients receiving second-line therapy were 55% (France), 48% (Germany), 54% (Spain) and 29% (UK). At the start of second-line therapy, most patients had an ECOG performance status of 1 (range 0-3). Second-line therapy was primarily monotherapy, but agents used varied within and across countries. Supportive care use and resource utilisation were frequent whether receiving additional therapy or not; >60% patients had clinic visits unrelated to chemotherapy administration, and > 30% has ≥ 1 hospital admission. CONCLUSIONS For the time of study, established GEA treatment guidelines were generally followed. However, therapies varied widely in the second-line setting.

Necitumumab (Neci) was the first biologic approved by the FDA for use in combination with gemcitabine and cisplatin (Neci + GCis) in first-line treatment of metastatic squamous non-small cell lung cancer (msqNSCLC). The potential financial impact on a health plan of adding Neci + GCis to drug formularies may be important to value-based decision makers in the United States, given ever-tightening budget constraints.To estimate the budget impact of introducing Neci + GCis for first-line treatment of msqNSCLC from U.S. commercial and Medicare payer perspectives.The budget impact model estimates the costs of msqNSCLC before and after adoption of Neci + GCis in hypothetical U.S. commercial and Medicare health plans over a 3-year time horizon. The eligible patient population was estimated from U.S. epidemiology statistics. Clinical data were obtained from randomized clinical trials, U.S. prescribing information, and clinical guidelines. Market share projections were based on market research data. Cost data were obtained from online sources and published literature. The incremental aggregate annual health plan, per-patient-per-year (PPPY), and per-member-per-month (PMPM) costs were estimated in 2015 U.S. dollars. One-way sensitivity analyses were conducted to assess the effect of model parameters on results.In a hypothetical 1,000,000-member commercial health plan with an estimated population of 30 msqNSCLC patients receiving first-line chemotherapy, the introduction of Neci + GCis at an initial market share of approximately 5% had an overall year 1 incremental budget impact of $88,394 ($3,177 PPPY, $0.007 PMPM), representing a 2.9% cost increase and reaching $304,079 ($10,397 PPPY, $0.025 PMPM) or a 7.4% cost increase at a market share of 14.7% in year 3. This increase in total costs was largely attributable to Neci drug costs and, in part, due to longer survival and treatment duration for patients treated with Neci+GCis. Overall, treatment costs increased by $81,812 (13.5%), and disease costs increased by $7,951 (0.4%), whereas adverse event costs decreased by $1,368 (0.5%) in year 1. From the Medicare perspective, the overall year 1 incremental budget impact was $438,056 ($0.037 PMPM, $3,112 PPPY), representing a 3.0% cost increase. The higher incremental budget in Medicare, compared with commercial plans, was due to higher msqNSCLC incidence in the older Medicare patients (154 vs. 30 patients, respectively). Results were most sensitive to Neci drug costs.Based on projected market shares, coverage for first-line therapy with Neci + GCis appeared to modestly affect overall U.S. health care budgets for msqNSCLC-related care. Given the small eligible patient population, the PMPM budgetary impact on a commercial health plan of reimbursing Neci + GCis in the first year was less than $0.01, rising with increased use of Neci + GCis to $0.025 in the third year. The real-world effect of Neci + GCis needs to be evaluated to validate this analysis; however, these findings may help policymakers in making coverage decisions for Neci + GCis.This study was funded by Eli Lilly and Company. Molife, Brown, Tawney, and Cuyun Carter are equity holders and employees of Eli Lilly and Company. Bly, Cinfio, and Klein are employees of Medical Decision Modeling, which received funding from Eli Lilly and Company to conduct this research and prepare this manuscript.

The risk of venous thromboembolism (VTE) is increased in individuals with cancer, particularly in those with multiple myeloma. The immunomodulatory agents (IMiDs) thalidomide, lenalidomide and pomalidomide are commonly used to treat multiple myeloma and other hematologic malignancies and are associated with increased risk of VTE. Current National Comprehensive Cancer Network (NCCN) guidelines (v.1.2016) on cancer-associated VTE utilize a risk assessment model based on a few small studies to guide VTE prophylaxis for multiple myeloma patients being treated with an IMiD (Palumbo, et al. Leukemia, 2008). Aspirin is recommended for lower risk patients while prophylactic-dose low molecular weight heparin or therapeutic warfarin are recommended for higher risk patients. The use of direct oral anticoagulants (DOACs) for cancer-associated VTE is currently under investigation (Raskob, et al. Lancet Haematol, 2016). Little is known about their role in VTE prophylaxis in patients on IMiDs. The purpose of this study was to explore the use of DOACs in patients receiving IMiDs. We performed a retrospective chart review of all patients at the University of Virginia Health System who received an IMiD and who were taking either a DOAC or warfarin between January 1, 2010 and December 31, 2015. DOACs included dabigatran, rivaroxaban, and apixaban. IMiDs included lenalidomide, thalidomide, and pomalidomide. The primary endpoint was to assess the safety of DOACs as compared to warfarin, and the secondary endpoint was to assess their efficacy. We collected baseline patient information, as well as diagnosis, IMiD, anticoagulant, antiplatelet agent and dose, duration of treatment, concurrent antineoplastic therapies, and thrombotic risk factors. We utilized the NCCN definitions of individual and myeloma-related thrombotic risk factors. Many patients had changes in their IMiD or anticoagulation. Thus, separate encounters were collected, where an encounter was the combination of an IMiD agent and dose, the anticoagulant, the antiplatelet agent (if any), and the thrombotic risk profile for that time period. Descriptive analyses were performed on all encounters in both groups. Rates of bleeding and thrombotic events were calculated. There were 21 discrete patients in the DOAC group and 16 in the warfarin group. Characteristics and outcomes are described in Table 1. There were four non-major bleeding events in the DOAC group; two of the four bleeding events occurred while on concomitant aspirin therapy. The patient with hematuria stopped anticoagulation and cystoscopy revealed bladder cancer. The other patients did not change or stop therapy. There were six bleeding events in the warfarin group: two were major and four were non-major. The two major events were gastrointestinal bleeding (GIB) and a subarachnoid hemorrhage (SAH). Neither event occurred while on concomitant antiplatelet therapy. The GIB required cessation of therapy, hospitalization, and transfusions. The INR at the time is unknown. The SAH was preceded by a fall while INR was in therapeutic range. Both major and two of the non-major bleeding events occurred in the same patient at different time points and accounted for most of the warfarin-related bleeding events. There was one thrombotic event in the DOAC group. The patient had a non-ST segment elevation myocardial infarction (NSTEMI) while on prophylactic-dose rivaroxaban. She was not on concomitant antiplatelet therapy. Arterial thrombotic events are not typically seen with IMiDs, and the NSTEMI was thought to be related to the recent initiation of carfilzomib. There were no thrombotic events in the warfarin group. This was a retrospective, single-institution study assessing the safety and efficacy of DOACs as compared to warfarin in patients on IMiDs. In our study, all bleeding events in the DOAC group were non-major, while patients on warfarin experienced both major and non-major bleeds. Only one thrombotic event was recorded in the DOAC group. DOACs may represent an attractive alternative to warfarin for VTE prophylaxis in these patients, given no need for routine monitoring and fewer dietary restrictions. Prospective studies in this population are warranted. Disclosures No relevant conflicts of interest to declare.

Introduction: Cost-effectiveness analyses often inform healthcare reimbursement decisions. The preferred measure of effectiveness is the quality adjusted life year (QALY) gained, where the quality of life adjustment is measured in terms of utility. Areas covered: We assessed the availability and variation of utility values for health states associated with advanced or metastatic non-small cell lung cancer (NSCLC) to identify values appropriate for cost-effectiveness models assessing alternative treatments. Our systematic search of six electronic databases (January 2000 to August 2015) found the current literature to be sparse in terms of utility values associated with NSCLC, identifying 27 studies. Utility values were most frequently reported over time and by treatment type, and less frequently by disease response, stage of disease, adverse events or disease comorbidities. Expert commentary: In response to rising healthcare costs, payers increasingly consider the cost-effectiveness of novel treatments in reimbursement decisions, especially in oncology. As the number of therapies available to treat NSCLC increases, cost-effectiveness analyses will play a key role in reimbursement decisions in this area. Quantifying the relationship between health and quality of life for NSCLC patients via utility values is an important component of assessing the cost effectiveness of novel treatments.

BackgroundThe process of induction of labour (IOL) commonly involves cervical ripening, using mechanical or pharmacological methods. However, the optimum protocol of IOL remains undetermined.AimsTo report the maternal, neonatal and process outcomes for women being induced with a balloon catheter or prostaglandin E2 gel (PGE2).Materials and methodsMatched retrospective cohort study of women requiring IOL at term with a modified Bishop's score (MBS)

Background: The objectives of this systematic review and meta-analysis were to compare the survival, toxicity, and quality of life of patients treated with necitumumab in combination with gemcitabine and cisplatin. These agents were investigated in published randomized controlled trials (RCTs) of patients with squamous non-small cell lung cancer (NSCLC) in the first-line setting. Methods: The systematic review was executed on January 27, 2015, and updated on August 21, 2016, using a pre-specified search strategy. Searches were conducted using PubMed, Medline, and EMBASE, with supplemental searches using the Evidence Based Medicine Reviews and ClinicalTrials.gov to identify RCTs published in English from 1995–2016 and reporting at least one of the primary outcomes [overall survival (OS), progression-free survival (PFS), toxicity, or quality of life] in patients who received first-line treatment for advanced or metastatic squamous NSCLC. Study quality and risk of bias were assessed using the Physiotherapy Evidence Database (PEDro) scale and Cochrane risk of bias tool, respectively. A Baysian network meta-analysis was performed on the primary outcomes. Hazard ratios (HRs) were evaluated for the primary analysis; secondary analyses were conducted using median OS data. Planned sensitivity analyses were conducted including reanalysis using a Frequentist approach and limiting analyses to subsets based on clinical and demographic covariates. Results: The systematic literature review resulted in identification of 4,016 unique publications; 40 publications (35 unique trials) were eligible for inclusion. Eight studies connected to a common network for the OS analysis using HR data. The majority of studies were not limited to squamous NSCLC, thus analyzable data were limited to a subset of data within the published trials. Carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin were associated with lower HRs for OS versus all other comparators. Nine studies connected to the network for the PFS analysis in which necitumumab in combination with gemcitabine and cisplatin was associated with the lowest HR. Data were not available to analyze toxicity or quality of life. Conclusions: Although the results suggest that carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin may have value in terms of OS versus other comparators, the results should be interpreted with caution due to the limited number of studies (with few focused exclusively on squamous NSCLC) and wide credible intervals.

e18581 Background: While most patients (pts) with HR+, HER2- early breast cancer (EBC) do not experience disease recurrence, those with high risk clinicopathologic features may have recurrence within the first few years on adjuvant endocrine therapy (AET). This study estimates risk of recurrence in pts with EBC based on clinicopathologic features and evaluates the medical need for more efficacious treatments using US oncology practice data. Methods: This retrospective study used the nationwide Flatiron Health electronic health record derived deidentified database. The cohort included pts with HR+, HER2- stage I-III breast cancer, diagnosed Jan 2011-Mar 2020, who received surgery and AET. Clinicopathologic features were used to identify a ‘high risk (HiR) group’ (≥ 4 positive axillary lymph nodes (LN), or 1-3 positive axillary LN and ≥ 1 of the following: Grade 3, tumor size ≥ 5 cm, or Ki-67 ≥ 20%) and ‘low risk (LoR) group’ (pts who do not meet above criteria, including a subset with node negative (N0) disease). Cox proportional hazards regression models compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) from AET initiation between groups according to a sequential gatekeeping strategy and stepwise analysis: first compare HiR group to N0 pts; if significant then compare HiR to LoR group. Results: 557 (13.8%) pts were in the HiR group and 3,471 (86.2%) in the LoR group (including 2,867 N0 pts). The study population (median age 64 yrs) was predominantly female (99.2%), white (69.4%) and postmenopausal (75.6%) with median follow-up of 39.6 months. Pts in the HiR group were younger and more likely premenopausal, have a BRCA mutation, invasive lobular carcinoma and less likely to have received an Oncotype DX test compared to LoR pts. Of the 557 HiR pts, 231 (41.5%) had ≥ 4 positive LN and 326 (58.5%) had 1-3 positive axillary LN with additional risk factor(s): tumor size ≥ 5 cm (11.7%), histologic grade 3 (32.0%), and/or Ki-67 ≥ 20% (31.6%). Most HiR pts received radiotherapy (82.4%) and chemotherapy (68.1%). Significant differences in IDFS and DRFS were observed between HiR group and N0 and LoR groups (logrank test p < .0001 for all). The 2-year IDFS rate was 88.1% in the HiR group, compared to 97.4% in N0 pts and 97.1% in the LoR group; 2-year DRFS rates were 89.0% compared to 97.9% and 97.7%, respectively. Pts in the HiR group had significantly higher hazard of invasive disease recurrence or death compared to N0 (HR = 3.42, 95% CI: 2.69-4.34, p < .0001) and LoR group (HR = 3.07, 95% CI: 2.46-3.84, p < .0001). Similar results observed for DRFS (HiR vs N0: HR = 3.46, 95% CI: 2.70-4.44, p < .0001; HiR vs LoR HR = 3.16, 95% CI: 2.50-3.98, p < .0001). Conclusions: Approximately 12% of pts with EBC and high risk clinicopathologic features experienced invasive disease recurrence or death within 2 years of initiating AET. Optimal use of standard therapies and novel treatment options are needed to prevent early recurrence and metastases in these pts.

Direct oral anticoagulants have been shown safe and effective in the treatment of pulmonary emboli and deep vein thrombi. Their role in the treatment of patients with hypercoagulability is uncertain. We designed a retrospective exploratory analysis of all patients with definite heparin induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS) that were treated with either apixaban or rivaroxaban from September 2011 through November 2015. Patients were reviewed for several clinico-pathologic features, including efficacy and safety. 23 patients were identified (12 patients with HIT and 11 patients with APS). Sixteen patients (70 %) were treated with apixaban and seven patients (30 %) were treated with rivaroxaban over a median follow up of 7 months (range 2-39). Zero patients developed recurrent thrombi. Two patients being treated for HIT developed major bleeding leading to discontinuation of all anticoagulation. Therefore, apixaban and rivaroxaban appear safe and effective for treatment of patients with HIT and APS in this small retrospective cohort and should be considered on an individual basis for patients who refuse, fail or are intolerant of warfarin. There were no sources of funding.

Cancer patients treated with epidermal growth factor receptor inhibitors (EGFRIs) frequently experience skin toxicities (rash) that can compromise their quality of life and lead to dose reduction or discontinuation of treatment. Reflecting the need for effective management of EGFRI-associated rash, a number of clinical practice guidelines and management recommendations have been developed. The objective of this systematic review is to identify and summarize all available published recommendations of rash management strategies and evaluate their basis of evidence, to describe consensus in the recommendations, and where there is a lack of consensus to describe the opportunities for future clinical research to improve clinical practice in the management of EGFRI rash. Fifty-nine articles published from 2005-2011 were selected for inclusion in the systematic review. Common drug recommendations were oral and topical antibiotics, topical corticosteroids, and antihistamines; low-grade rash was generally recommended to be managed with topical antibiotics or corticosteroids, grade 2 rash with oral antibiotics or antihistamines, and severe grades of rash with oral corticosteroids or delay/dose reduction of EGFRI. The focus of clinical practice guidelines and recommendations was on reactive management. A better understanding of pre-emptive versus reactive treatment with the implementation of appropriately designed randomized controlled studies could support a more effective management of EGFRI-associated rash and improve patient outcomes. Consideration of patients' self-reported outcomes and consistent grading of rash toxicity are also recommended. Funding/sponsor: Eli Lilly & Co, Bristol-Myers Squibb.

Background: In the SQUIRE study, adding the anti-epidermal growth factor receptor (EGFR) IgG1 antibody necitumumab to first-line gemcitabine and cisplatin (GC + N) in advanced squamous non-small-cell lung cancer (sqNSCLC) significantly improved overall survival (OS); the safety profile was acceptable. We explored data for the German subpopulation (N = 96) of SQUIRE patients with EGFR-expressing tumors. Patient and Methods: Patients with stage IV sqNSCLC were randomized 1:1 to up to 6 cycles of open-label GC + N or GC alone. GC + N patients with no progression continued on necitumumab monotherapy until disease progression or intolerable toxicity. The primary endpoint was OS; the secondary endpoints included progression-free survival (PFS), safety and health-related quality of life (EQ-5D, Lung Cancer Symptom Scale (LCSS)). Results: The 96 German SQUIRE patients with EGFR-expressing tumors (GC + N 42, GC 54) received a median of 4 GC cycles; the GC + N patients received 5 cycles of necitumumab. Adding necitumumab was associated with 41% risk reduction of death (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.37-0.94, p = 0.026) and 44% risk reduction of progression (HR 0.56, 95% CI 0.33-0.95, p = 0.029). Adverse events typically associated with EGFR antibody treatment (including rash, hypomagnesemia) were more common with GC + N. The time to deterioration of the EQ-5D and LCSS scores showed no notable differences between the treatment arms, except for appetite loss (delayed for GC + N). Conclusion: The survival benefit from adding necitumumab to first-line GC was more pronounced in the German SQUIRE subpopulation with EGFR-expressing tumors than in the overall (intention-to-treat) population; toxicity was manageable and consistent with the overall population.

INTRODUCTION Malaria remains a devastating global parasitic disease, with the majority of malaria deaths caused by the highly virulent Plasmodium falciparum . The extreme AT-bias of the P. falciparum genome has hampered genetic studies through targeted approaches such as homologous recombination or CRISPR-Cas9, and only a few hundred P. falciparum mutants have been experimentally generated in the past decades. In this study, we have used high-throughput piggyBac transposon insertional mutagenesis and quantitative insertion site sequencing (QIseq) to reach saturation-level mutagenesis of this parasite. RATIONALE Our study exploits the AT-richness of the P. falciparum genome, which provides numerous piggyBac transposon insertion targets within both gene coding and noncoding flanking sequences, to generate more than 38,000 P. falciparum mutants. At this level of mutagenesis, we could distinguish essential genes as nonmutable and dispensable genes as mutable. Subsequently, we identified 2680 genes essential for in vitro asexual blood-stage growth. RESULTS We calculated mutagenesis index scores (MISs) and mutagenesis fitness scores (MFSs) in order to functionally define the relative fitness cost of disruption for 5399 genes. A competitive growth phenotype screen confirmed that MIS and MFS were predictive of the fitness cost for in vitro asexual growth. Genes predicted to be essential included genes implicated in drug resistance—such as the “ K13 ” Kelch propeller, mdr , and dhfr-ts —as well as targets considered to be high value for drugs development, such as pkg and cdpk5 . The screen revealed essential genes that are specific to human Plasmodium parasites but absent from rodent-infective species, such as lipid metabolic genes that may be crucial to transmission commitment in human infections. MIS and MFS profiling provides a clear ranking of the relative essentiality of gene ontology (GO) functions in P. falciparum . GO pathways associated with translation, RNA metabolism, and cell cycle control are more essential, whereas genes associated with protein phosphorylation, virulence factors, and transcription are more likely to be dispensable. Last, we confirm that the proteasome-degradation pathway is a high-value druggable target on the basis of its high ratio of essential to dispensable genes, and by functionally confirming its link to the mode of action of artemisinin, the current front-line antimalarial. CONCLUSION Saturation-scale mutagenesis allows prioritization of intervention targets in the genome of the most important cause of malaria. The identification of more than 2680 essential genes, including ~1000 Plasmodium -conserved essential genes, will be valuable for antimalarial therapeutic research.

Introducción. El aborto se ha convertido en un problema de salud pública. Una las causas que podría estar influyendo para su aumento es la falta de información sobre el control prenatal, por lo anterior, este es un tema que no escapa de la realidad y de la práctica médica. Objetivo. Caracterizar clínica y epidemioló-gicamente el aborto. Materiales y Métodos. Estudio observacional, descriptivo, retrospectivo, realizado en el Hospital “Gervasio Vera Custodio” Upata- Estado Bolívar, Venezuela, durantel periodo comprendido de enero a diciembre de 2013. Se recolecto datos de 207 historias clínicas de mujeres con diagnóstico de aborto. En el análisis estadístico se aplicó la prueba chi2 de Pearson. Resultados. Se encontró que la edad prevalente de aborto fue de 21 a 30 años con 42%. La edad gestacional más frecuente de las pacientes fue de 1 a 8 semanas con 50%. De estas 93,5% no cumplieron control prenatal. El tipo de aborto más frecuente fue espontáneo con 98,5%. Se realizó legrado uterino a 97%, de las cuales, 8,5% presentaron complicaciones. Se encontraron diferencias estadísticamente significativas al relacionar la edad materna con la edad gestacional. Conclusiones. Existió alta prevalencia de aborto espontáneo en el grupo de 21 a 30 años de edad, presentados entre las semanas 1 a 8 de gestación. La técnica más segura fue el legrado uterino. Finalmente, se encontró bajo cumplimiento del control prenatal.

It is estimated that up to 20%–25% of patients with colonic diverticula will progress to diverticulitis.1,2 The diagnosis of acute diverticulitis is typically made using a combination of history, clinical exam, biochemical investigations and diagnostic imaging. Computed tomography (CT) has emerged as the imaging modality of choice given its high sensitivity and specificity for the diagnosis of diverticulitis, with some studies reporting up to 100% in either measure.3–8 Computed tomography findings of diverticula, inflammation of pericolic fat, bowel wall thickness greater than 4 mm and/or pericolic fluid/abscess are highly suggestive of acute diverticulitis.1,8,9 A CT scan also provides prognostic information and guides management by determining whether the diverticulitis is complicated by abscess, fistula formation, stricture/obstruction or free rupture. While most cases of uncomplicated diverticulitis respond well to conservative treatment, complicated diverticulitis requires surgical intervention. There is overlap in the findings of acute diverticulitis and colorectal cancer (CRC), and CT findings alone are insufficient to exclude malignancy approximately 10% of the time.1,10 As a result, the American Society of Colon and Rectal Surgeons recommend performing a colonoscopy to exclude a potential malignancy after an episode of acute diverticulitis has resolved.1,9,11 However, since the advent of multidetector CT scanners that are capable of capturing images more quickly and thus reduce motion artifacts, the image qualities and diagnostic accuracy of CT scans have improved substantially. With increased resolution of the newer 64-slice CT scans that are currently in widespread use, acute diverticulitis can be diagnosed more accurately,12,13 and it may be possible to adequately distinguish acute diverticulitis from malignancy based on radiological features alone. Routine follow-up colonoscopy may no longer be required in patients with acute diverticulitis. The primary aim of this study was to determine the prevalence of colon cancer in patients with diverticulitis diagnosed on high-resolution CT scan to determine the need for follow-up colonoscopy in this patient population.

Rash toxicity is a common, expected class effect of epidermal growth factor receptor (EGFR) inhibitors. Although rash management is practiced, it is not well characterized in the real-world setting. We describe the management of rash that developed while receiving EGFR-inhibitor therapy and how rash affects treatment duration, using Truven MarketScan® Research Database, a US medical claims database.Adult patients who received EGFR-inhibitor treatment between 2004 and 2015 after a diagnosis of colon, head and neck, lung, breast, or thyroid cancer were identified. Descriptive analyses were conducted to describe occurrence of rash during the EGFR-inhibitor treatment period, EGFR-inhibitor treatment persistence and management of rash, including treatment and cost.Of 44,533 eligible patients, 4649 (10.4%) had records of rash during the EGFR-inhibitor treatment period, and of patients experiencing rash, 2891 (62.2%) received prescription drugs for rash treatment. Treatment persistence with an EGFR inhibitor was longer among patients experiencing rash compared with no rash (median 178 vs. 80 days for EGFR-TKIs, 85 vs. 57 days for EGFR-monoclonal antibodies), especially among patients with rash who were treated for rash (208 days for EGFR-tyrosine kinase inhibitors, 104 days for EGFR- monoclonal antibodies). Annualized cost during EGFR-inhibitor treatment was lowest among patients not experiencing rash (US$185,619), followed by rash patients receiving drugs for rash management (US$215,561), and highest among rash patients not treated for rash (US$267,105).Our findings suggest that management of EGFR inhibitor-associated rash could be important for EGFR-inhibitor treatment persistence.