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Palliation is a controversial indication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients with peritoneal carcinomatosis (PC) are living longer, and the roles of palliative CRS and HIPEC are increasingly challenged. The purpose of this study is to evaluate indications, morbidity, and symptom improvement from CRS/HIPEC in advanced PC.A retrospective review of patients undergoing CRS and/or HIPEC with a palliative intent at a single institution from February 2008 to February 2018 was performed. Main end points included symptom improvement, symptom-free interval, and overall survival.Two hundred and seventy seven patients were referred for CRS/HIPEC during the study period and 17 underwent 20 palliative procedures. Appendiceal (n = 6) and colorectal cancers (n = 6) were the most common malignancies. Ascites (n = 8) and bowel obstruction (n = 8) were the most common indications for intervention. The postoperative complication rate was 50% and major complication rate was 20%. Partial symptom improvement or resolution of symptoms was achieved in 18 (90%) cases. A durable symptom control at 90 d was achieved in 13 (65%) cases. The median time to symptom recurrence was 5.1 mo (interquartile range: 2-11.4), and the median overall survival was 11.6 mo (interquartile range: 3.8-28.5).Palliative CRS and/or HIPEC achieve symptom improvement in patients with advanced PC. Risk assessment and expected time to recovery from surgery remain paramount for patient selection.

BackgroundUnrecognised changes in a hospitalised patient’s clinical course may lead to a preventable adverse event. Early warning systems (EWS) use patient data, such as vital signs, nursing assessments and laboratory values, to aid in the detection of early clinical deterioration. In 2018, an EWS programme was deployed at an academic hospital that consisted of a commercially available EWS algorithm and a centralised virtual nurse team to monitor alerts. Our objective was to understand the nursing perspective on the use of an EWS programme with centralised monitoring.MethodsWe conducted and audio-recorded semistructured focus groups during nurse staff meetings on six inpatient units, stratified by alert frequency (high: >100 alerts/month; medium: 50–100 alerts/month; low: ResultsWe conducted 28 focus groups with 227 bedside nurses across all shifts. We identified six principal themes: (1) Alert timeliness, nurses reported being aware of the patient’s deterioration before the EWS alert, (2) Lack of accuracy, nurses perceived most alerts as false positives, (3) Workflow interruptions caused by EWS alerts, (4) Questions of actionability of alerts, nurses were often uncertain about next steps, (5) Concerns around an underappreciation of core nursing skills via reliance on the EWS programme and (6) The opportunity cost of deploying the EWS programme.ConclusionThis qualitative study of nurses demonstrates the importance of earning user trust, ensuring timeliness and outlining actionable next steps when implementing an EWS. Careful attention to user workflow is required to maximise EWS impact on improving hospital quality and patient safety.

The molecular signature response classifier (MSRC) is a blood-based precision medicine test that predicts nonresponders to tumor necrosis factor-�� inhibitors (TNFi) in rheumatoid arthritis (RA) so that patients with a molecular signature of non-response to TNFi can be directed to a treatment with an alternative mechanism of action. This study evaluated decision choice and treatment outcomes resulting from MSRC-informed treatment selection within a real-world cohort. Therapy selection by providers was informed by MSRC results for 73.5% (277/377) of patients. When MSRC results were not incorporated into decision-making, 62.0% (62/100) of providers reported deviating from test recommendations due to insurance-related restrictions. The 24-week ACR50 responses in patients prescribed a therapy in alignment with MSRC results were 39.6%. Patients with a molecular signature of non-response had significantly improved responses to non-TNFi therapies compared with TNFi therapies (ACR50 34.8% vs 10.3%, p-value = 0.05). This indicates that predicted non-responders to TNFi therapies are not nonresponders to other classes of RA targeted therapy. Significant changes were also observed for CDAI, ACR20, ACR70, and for responses at 12 weeks. Adoption of the MSRC into patient care could fundamentally shift treatment paradigms in RA, resulting in substantial improvements in real-world treatment outcomes.

Introduction Timely matching of patients to beneficial targeted therapy is an unmet need in rheumatoid arthritis (RA). A molecular signature response classifier (MSRC) that predicts which patients with RA are unlikely to respond to tumor necrosis factor-α inhibitor (TNFi) therapy would have wide clinical utility. Methods The protein–protein interaction map specific to the rheumatoid arthritis pathophysiology and gene expression data in blood patient samples was used to discover a molecular signature of non-response to TNFi therapy. Inadequate response predictions were validated in blood samples from the CERTAIN cohort and a multicenter blinded prospective observational clinical study (NETWORK-004) among 391 targeted therapy-naïve and 113 TNFi-exposed patient samples. The primary endpoint evaluated the ability of the MSRC to identify patients who inadequately responded to TNFi therapy at 6 months according to ACR50. Additional endpoints evaluated the prediction of inadequate response at 3 and 6 months by ACR70, DAS28-CRP, and CDAI. Results The 23-feature molecular signature considers pathways upstream and downstream of TNFα involvement in RA pathophysiology. Predictive performance was consistent between the CERTAIN cohort and NETWORK-004 study. The NETWORK-004 study met primary and secondary endpoints. A molecular signature of non-response was detected in 45% of targeted therapy-naïve patients. The MSRC had an area under the curve (AUC) of 0.64 and patients were unlikely to adequately respond to TNFi therapy according to ACR50 at 6 months with an odds ratio of 4.1 (95% confidence interval 2.0–8.3, p value 0.0001). Odds ratios (3.4–8.8) were significant (p value, Plain Language Summary A blood-based molecular signature response classifier (MSRC) integrating next-generation RNA sequencing data with clinical features predicts the likelihood that a patient with rheumatoid arthritis will have an inadequate response to TNFi therapy. Treatment selection guided by test results, with likely inadequate responders appropriately redirected to a different therapy, could improve response rates to TNFi therapies, generate healthcare cost savings, and increase rheumatologists’ confidence in prescribing decisions and altered treatment choices. The MSRC described in this study predicts the likelihood of inadequate response to TNFi therapies among targeted therapy-naïve and TNFi-exposed patients in a multicenter, 24-week blinded prospective clinical study: NETWORK-004. Patients with a molecular signature of non-response are less likely to have an adequate response to TNFi therapies than those patients lacking the signature according to ACR50, ACR70, CDAI, and DAS28-CRP with significant odds ratios of 3.4–8.8 for targeted therapy-naïve patients and 3.3–26.6 for TNFi-exposed patients. This MSRC provides a solution to the long-standing need for precision medicine tools to predict drug response in rheumatoid arthritis—a heterogeneous and progressive disease with an abundance of therapeutic options. These data validate the performance of the MSRC in a blinded prospective clinical study of targeted therapy-naïve and TNFi therapy-exposed patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00330-y.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death in the United States despite a decline in mortality. Adenocarcinoma of the lung usually evolves from the mucosal glands and represents about 40% of all lung cancers. A significant proportion of lung adenocarcinoma patients present alterations in oncogenic driver genes. Next-Generation Sequencing (NGS) allows the sequencing of several genomic regions in a single test. There are multiple NGS approaches including Targeted Panel Sequencing (TPS), Whole Exome Sequencing (WES), and Whole Genome Sequencing (WGS). Methods: The detection of actionable genomic mutations in 60 lung adenocarcinoma surgical specimens was evaluated through two NGS approaches TPS and WGS. TPS was performed using the Seoul National University Hospital (SNUH) TPS consisting of 75 total genes, with a total coverage of 1.92Mb (exon 0.69Mb, intron 1.23Mb). WGS was performed using Illumina’s NovaSeq 6000 platform and data were processed with BWA and variant callers including Mutect2 and Delly. Functional mutations were determined by Ensembl VEP, while putative driver mutations were identified via the Genome Insight pipeline (San Diego). Results: A total of 120 driver mutations were detected by TPS. WGS identified 114 out of the 120 driver mutations (95% match). An additional 9 driver mutations were detected by WGS, along with thousands of additional non-driver mutations. (Table 1) Conclusion: An NGS-based approach allows for the identification of actionable molecular changes which leads to more informed clinical decision making. These results validate that Genome Insight’s WGS workflow and pipeline are comparable to TPS in detecting key driver mutations. Furthermore, this study demonstrated that WGS provides a more comprehensive genetic characterization of lung cancer, which may impact the therapeutic options and patients’ prognosis. Table 1. Driver mutations # of mutations detected by TPS # of mutations detected by WGS Detected by TPS EGFR 20 19 KRAS 9 9 TP53 30 30 Fusion oncogenes 17 17 PIK3 genes 1 1 BRAF 2 2 Secondary drivers detected by TPS 41 36 Sub-total 120 114 Missed by TPS Other drivers not detected by TPS 0 9 Total 120 123 Citation Format: Ji-Hyung Park, Young Tae Kim, Erin Connolly-Strong, Young Seok Ju. Whole genome sequencing provides a more comprehensive genetic characterization of lung cancer compared to a targeted panel sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 261.

Surgical palliative care, palliative care interventions, and palliative surgery all reference a blend of these 2 sub-specialty fields. Despite prior published definitions, use of these phrases both clinically and in the literature is varied and can lead to confusion and misunderstanding. Herein, we proposed the adoption of standardized nomenclature to guide the consistent use of these phrases.

In the 20 years since the American College of Surgeons outlined the first research agenda for surgical palliative care, there has been immense growth in the evidence. In this article, we briefly review the state of the science and priority research areas in surgical palliative care.

A blood-based molecular signature response classifier (MSRC) predicts non-response to tumor necrosis factor-ɑ inhibitors (TNFi) in rheumatoid arthritis (RA).This is an interim analysis of data collected in the Study to Accelerate Information of Molecular Signatures (AIMS) in RA from patients who received the MSRC test between September 2020 and November 2021. Absolute changes in clinical disease activity index (CDAI) scores from baseline were evaluated at 12 weeks (n = 470) and 24 weeks (n = 274).Predicted TNFi non-responders who received a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) with an alternative mechanism of action (altMOA) experienced up to 1.8-fold greater improvements in CDAI scores than those treated with a TNFi (12 weeks: 12.2 vs 8.0; p-value = 0.083; 24 weeks: 14.2 vs 7.8 p-value = 0.009). In patients with a molecular signature of non-response to TNFi in high disease activity at baseline, this corresponded to 43.2% relative improvement in achieving a lower CDAI disease activity level when likely TNFi non-responders were treated with a non-TNFi therapy (38.9% vs 55.7%). Commensurate improvements in efficiency of spend are expected when TNFi are avoided in favor of altMOA.RA treatment selection informed by MSRC test results improves clinical outcomes in real-world care and offers improvements in efficiency of healthcare spending.

Soft tissue sarcomas are a heterogenous group of neoplasms without well-validated biomarkers. Cancer-related inflammation is a known driver of tumor growth and progression. Recent studies have implicated a high circulating neutrophil-lymphocyte ratio as a surrogate marker for the inflammatory tumor microenvironment and a poor prognosticator in multiple solid tumors, including colorectal and pancreatic cancers. The impact of circulating neutrophil-lymphocyte ratio in soft tissue sarcomas has yet to be elucidated.We performed a retrospective analysis of patients undergoing curative resection for primary or recurrent extremity soft tissue sarcomas at academic centers within the US Sarcoma Collaborative. Neutrophil-lymphocyte ratio was calculated retrospectively in treatment-naïve patients using blood counts at or near diagnosis.A high neutrophil-lymphocyte ratio (≥4.5) was associated with worse survival on univariable analysis in patients with extremity soft tissue sarcomas (hazard ratio 2.07; 95% confidence interval, 1.54-2.8; P.001). On multivariable analysis, increasing age (hazard ratio 1.03; 95% confidence interval, 1.02-1.04; P.001), American Joint Committee on Cancer T3 (hazard ratio 1.89; 95% confidence interval, 1.16-3.09; P = .011), American Joint Committee on Cancer T4 (hazard ratio 2.36; 95% confidence interval, 1.42-3.92; P = .001), high tumor grade (hazard ratio 4.56; 95% confidence interval, 2.2-9.45; P.001), and radiotherapy (hazard ratio 0.58; 95% confidence interval, 0.41-0.82; P = .002) were independently predictive of overall survival, but a high neutrophil-lymphocyte ratio was not predictive of survival (hazard ratio 1.26; 95% confidence interval, 0.87-1.82; P = .22).Tumor inflammation as measured by high pretreatment neutrophil-lymphocyte ratio was not independently associated with overall survival in patients undergoing resection for extremity soft tissue sarcomas.

To understand the influence of the systemic lupus erythematosus (SLE)-related flares on patient’s health-related quality of life (HRQoL). An online survey included individuals with self-reported physician’s diagnosis of SLE or lupus nephritis (LN). Lupus impact tracker (LIT) assessed lupus symptoms and HRQoL, SLE-Family questionnaire measured family role functioning, and Healthy Days Core Module (HDCM) measured overall mental and physical health. Chi-square and analysis of variance evaluated differences by flare frequency. Multivariable linear regression and generalized linear models evaluated the independent relationships of flare frequency to HRQoL. 1066 respondents with SLE or LN completed the survey. Mean (SD) duration of illness was 12.4 (10.1) years. 93.4% (n = 996) were women, 82.3% (n = 830) were White, and 49.7% (n = 530) were employed or students. More frequent flares were associated with significantly worse scores on all HRQoL measures: LIT (adjusted means: 0 flares, 31.8; 1–3 flares, 47.0; 4–6 flares, 56.1; ≥ 7 flares, 63.6; P

Objective To describe the characteristics, treatment patterns, health care resource utilization (HCRU), and cost of care for members of a large United States (US) health insurance plan with lupus nephritis (LN). Methods A retrospective observational study was conducted using a health insurance plan database to identify adult members with a diagnosis of LN. Medical and pharmacy claims were used to describe demographics, comorbidities, HCRU, and cost patterns over a 12-month follow-up period for each patient, between January 1, 2014, and December 31, 2016. All study variables were examined descriptively. Results A total of 1039 patients were available for analysis (median age, 47 years; 83% female). The median Charlson Comorbidity Index (CCI) was 3.3. Less than half (41%) of patients received immunosuppressive therapies commonly used to treat LN. Evidence indicated that 58% of the study population were prescribed corticosteroid therapy, in most cases (73%) for more than 60 days. Adverse events known to be associated with corticosteroid therapy were recorded in 58% of patients. Guideline-recommended preventive therapy with hydroxychloroquine was prescribed for 54% of members with LN. Nearly half (47%) of members with LN did not see a nephrologist and more than one-third (36%) did not see a rheumatologist over 1 year of follow-up. Rates of all-cause hospitalization and emergency department (ED) use were 25% and 35%, respectively. The mean all-cause per-member-per-month (PMPM) medical cost for the study population was $2801, with LN-specific costs accounting for $1147 PMPM. Conclusion Patients with LN who are insured through a large US health plan appeared to underutilize outpatient specialist services and guideline-recommended hydroxychloroquine therapy. Corticosteroid use and adverse events known to be associated with corticosteroids were common in this cohort.

Screening guidelines in patients with inherited endocrine syndromes and others at high risk for developing endocrine cancers have significant implications as early tumor detection is associated with improved outcomes. Given the unique challenges in diagnosis and treatment, patients at high risk for developing endocrine cancers require multidisciplinary care. The complexity of decision making and rarity of these syndromes support referral to high-volume centers with the experience and knowledge to treat these at-risk patients.

Introduction The objective of this study was to assess efficacy and safety of repository corticotropin injection (RCI) in subjects with active rheumatoid arthritis (RA) despite treatment with a corticosteroid and one or two disease-modifying antirheumatic drugs (DMARDs). Methods All subjects received open-label RCI (80 U) twice weekly for 12 weeks (part 1); only those with low disease activity [LDA; i.e., Disease Activity Score 28 joint count and erythrocyte sedimentation rate (DAS28-ESR) 60% of patients achieved LDA, which was maintained with 12 additional weeks of treatment. Most patients who achieved LDA maintained it for 3 months after RCI discontinuation. Trial Registration Clinicaltrials.gov identifier NCT02919761. Electronic Supplementary Material The online version of this article (10.1007/s40744-020-00199-3) contains supplementary material, which is available to authorized users.

BACKGROUND: Patients with moderate to severe rheumatoid arthritis (RA) can be treated with a range of targeted therapies following inadequate response to conventional synthetic disease-modifying antirheumatic drugs such as methotrexate. Whereas clinical practice guidelines provide no formal recommendations for initial targeted therapies, the tumor necrosis factor alpha inhibitor (TNFi) class is the prevalent first-line selection based on clinician experience, its safety profile, and/or formulary requirements, while also being the costliest. Most patients do not achieve adequate clinical response with a first-line TNFi, however. A molecular signature response classifier (MSRC) test that assesses RA-related biomarkers can identify patients who are unlikely to achieve adequate response to TNFi-class therapies. OBJECTIVE: To model cost-effectiveness of MSRC-guided, first-line targeted therapy selection compared with current standard care. METHODS: This budget impact analysis used data sourced from August to September 2020. The prevalence of each first-line targeted therapy was obtained using market intelligence from Datamonitor/Informa PLC Rheumatology Dashboard Forecast 2020, and the average first-year cost of treatment for each class was calculated using wholesale acquisition costs from IBM Micromedex RED BOOK Online. Average effectiveness for each class was based on manufacturer-reported ACR50 response rates (American College of Rheumatology adequate response criteria of 50% improvement at 6 months after therapy initiation). The impact of MSRC testing on first therapy selection was predicted based on a third party-generated decision-impact study that analyzed potential alterations in rheumatologist prescribing patterns after receiving MSRC test reports. Sensitivity analysis evaluated potential impacts of variation in first-year medication cost, adherence to MSRC report, and test price on the first-year cost of treatment. Cost for response (first-year therapy cost therapy divided by probability of achieving ACR50) was compared between standard care and MSRC-guided care. RESULTS: The estimated cost for first-year, standard-care treatment was $65,117, with 80% of patients initiating treatment with a TNFi. Cost for achieving ACR50 response was $177,046. After applying MSRC-guided patient stratification and therapy selection, the first-year cost was $56,543, net of test price, with 49.0% of patients initiating with a TNFi. First-year MSRC-guided care cost, including test price, was estimated at $117,103, a 33.9% improvement over standard care. Sensitivity analysis showed a net cost improvement for guided care vs standard care across all scenarios. Patients predicted to be inadequate TNFi responders, when modeled with lower-priced alternatives, were predicted to show increased ACR50 response rates. Those with MSRC test results indicating a first-line TNFi were predicted to show an ACR50 response rate superior to that for any other class. In this model, if implemented clinically, MSRC-guided care might save the US health care system more than $850 million annually and improve ACR50 by up to 31.3%. CONCLUSIONS: Precision medicine using MSRC-guided patient stratification and therapy selection may both decrease cost and improve efficacy of targeted RA therapies. DISCLOSURES: This work was funded in full by Scipher Medicine Corporation, which participated in data analysis and interpretation and drafting, reviewing, and approving the publication. All authors contributed to data analysis and interpretation and publication preparation, maintaining control over the final content. Arnell, Withers, and Connolly-Strong are employees of and have stock ownership in Scipher Medicine Corporation. Bergman has received consulting fees from AbbVie, Gilead, GlaxoSmithKline, Novartis, Pfizer, Regeneron, Sanofi, and Scipher Medicine and owns stock or stock options in Johnson & Johnson. Kenney, Logan, and Lim-Harashima are consultants for Scipher Medicine Corporation. Basu has nothing to disclose.

The Addressing Lupus Pillars for Health Advancement (ALPHA) Project is a global consensus effort to identify, prioritise and address top barriers in lupus impacting diagnosis, care, treatment and research. To conduct this process, the ALPHA Project convened a multistakeholder Global Advisory Committee (GAC) of lupus experts and collected input from global audiences, including patients. In phase I, the ALPHA Project used expert interviews and a global survey of lupus experts to identify and categorise barriers into three overarching pillars: drug development, clinical care and access to care. In phase II, reported here, the GAC developed recommended actionable solutions to address these previously identified barriers through an in-person stakeholder meeting, followed by a two-round scoring process. Recommendations were assessed for feasibility, impact and timeline for implementation (FIT), where potential FIT component values were between 1 and 3 and total scores were between 3 and 9. Higher scores represented higher achievability based on the composite of the three criteria. Simplifying and standardising outcomes measures, including steroid sparing as an outcome (drug development) and defining the lupus spectrum (clinical care) ranked as the highest two priority solutions during the GAC meeting and received high FIT scores (7.67 and 7.44, respectively). Leveraging social media (access to care) received the highest FIT score across all pillars (7.86). Cross-cutting themes of many solutions include leveraging digital technology and applying specific considerations for special populations, including paediatrics. Implementing the recommendations to address key barriers to drug development, clinical care and access to care is essential to improving the quality of life of adults and children with lupus. Multistakeholder collaboration and guidance across existing efforts globally is warranted.

Lupus flares significantly contribute to health resource utilization and hospitalizations. Identification of flare activity may be hindered since validated assessment scales are rarely used in clinical practice and flare severity may fall below clinician-assessed thresholds. Therefore, patient-reported outcomes of lupus flare frequency are important assessment tools for lupus management.To better understand the relationship between lupus flares as reported by persons with lupus and specific direct and indirect costs, including hospital admission, unplanned urgent care (UC)/emergency department (ED) visits, work productivity loss, and nonwork activity impairment.In this cross-sectional analysis, persons with lupus were drawn from 2 enriched sampling sources. Data were collected via an online survey and included individuals with self-reported physician's diagnosis of systemic lupus erythematosus, skin or discoid lupus, or lupus nephritis. Respondents were asked the total number of hospitalizations and ED/UC visits for any reason and for lupus-related hospitalizations and ED/UC visits. Work productivity loss and nonwork activity impairment were measured via the Work Productivity and Activity Impairment - General Health scale. The sample was stratified into those with 0 flares, 1-3 flares, 4-6 flares, and 7 or more flares, with 0 flares used as the reference. Chi-square tests for trend and analyses of variance were used to evaluate differences among flare frequency groups. Multivariable regression modeling was conducted to evaluate the independent relationship of flare frequency to health care use and productivity loss.We studied 1,288 survey respondents with known flare frequency in the past 12 months. Flare frequency increased with duration of illness. The mean number of lupus-related hospital admissions was significantly associated with increasing flare frequency for the total sample (F = 3.9;Increased lupus-related flare frequency is associated with worsened patient outcomes as measured by increased hospitalizations, visits to the ED/UC, work productivity loss, and activity impairment. This association may be an important indicator of disease severity and resource burden and therefore suggests an unmet need among patients experiencing lupus-related flares.This study was sponsored by Mallinckrodt Pharmaceuticals via grants to Vedanta Research and The Lupus Foundation of America. Katz received consulting fees from Vedanta Research, which received grant support from Mallinckrodt Pharmaceuticals to support data collection and analysis. Nelson and Connolly-Strong are employees of Mallinckrodt Pharmaceuticals and are stockholders in the company. Reed is an employee of Vedanta Research. Daly and Topf are employees of the Lupus Foundation of America, which received grant funding to support data collection. This study was a podium presentation at The American College of Rheumatology (ACR) Annual Meeting 2018; October 19-24, 2018; Chicago, IL.

Background Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an increasingly utilized strategy for patients with peritoneal surface malignancies (PSM). Methods The US HIPEC Collaborative was retrospectively reviewed to compare the indications and perioperative outcomes of patients who underwent CRS ± HIPEC between 2000 and 2012 (P1) versus 2013–2017 (P2). Results Among 2,364 patients, 39% were from P1 and 61% from P2. The most common primary site was appendiceal (64%) while the median PCI was 13 and most patients had CCR 0 (60%) or 1 (25%). Over time, median estimated blood loss, need for transfusion, and length of hospital stay decreased. While the incidence of any (55% vs. 57%; p = 0.426) and Clavien III/IV complications did not change over time, there was a decrease in 90-day mortality (5% vs. 3%; p = 0.045). Conclusion CRS-HIPEC is increasingly performed for PSM at high-volume centers. Despite improvements in some perioperative outcomes and a reduction in postoperative mortality, morbidity rates remain high.

Background: Repository corticotropin injection (RCI) is a complex mixture containing purified porcine pituitary adrenocorticotropic hormone (ACTH)-analogue with potential anti–inflammatory and immunomodulatory effects through the melanocortin receptors (MC1R, MC3R-MC5R) and endogenous steroid production. RCI is approved by the US FDA for the treatment of acute exacerbations (ie, disease flares) or as maintenance therapy in patients with systemic lupus erythematosus (SLE). In a pilot study, RCI was well tolerated with improvements in disease activity for lupus patients treated with RCI compared to those who received placebo (Furie et al, 2016). Objectives: To discuss the design, demographics, and baseline characteristics of a clinical trial evaluating the role of RCI in the treatment of patients with inadequately controlled SLE disease activity. Methods: This is a multicenter, double-blind, randomized, placebo-controlled, 24-week clinical trial aiming to determine the effect of RCI in reducing disease activity for patients with persistently active SLE despite moderate-dose corticosteroids (CSs). Patients are required to have SLE (≥4 of 11 ACR criteria from 1997) and active disease (moderate to severe rash and/or arthritis) despite stable dose CSs ≥ 4 weeks prior to screening (7.5 - 30 mg/day of prednisone or equivalent). Patients are treated with RCI 1 mL (80 U) subcutaneously (SC) or placebo 1 mL, every other day for 4 weeks followed by twice per week for 20 weeks. Randomization is stratified by study site location and prednisone or equivalent dose (≤ 20 and > 20 mg/day). Patients remain on stable doses of CSs through Week 16, with tapering encouraged between Weeks 16 and 24. Efficacy is evaluated using the SLE Responder Index-4 (SRI-4) and changes from baseline in SLE Disease Activity Index-2000 (SLEDAI-2K), British Isles Lupus Assessment Group-2004 (BILAG-2004) scores, and Physician’s Global Assessment (PGA). The primary efficacy endpoint is the proportion of SRI-4 responders at Week 16. Secondary and exploratory endpoints include changes in disease activity scores over time, prednisone dose, and biomarkers (ie, complements, autoantibodies, inflammatory, bone turnover). Results: As of 14 December 2018, 124 patients comprised the intent–to–treat (ITT) population. Target enrollment is 270 patients, of which 162 patients are expected to be randomized at approximately 60 sites globally. Demographic and baseline characteristics (Table) were collected, including circulating lymphocyte profiles (CD19+ B Cells, CD3+ total T cells, and CD4 Treg cells), which are consistent with the pilot study of RCI (Furie et al, 2016). Conclusion: This on-going study assesses the efficacy and safety of RCI for the treatment of refractory SLE in a racially and ethnically diverse population. The rapid onset of action of RCI allows for a 16–week primary endpoint. Patients enrolled in this trial have moderate or high disease activity (as shown by the mean SLEDAI-2K, BILAG, and PGA) and are likely to provide valuable data on the role of RCI in refractory lupus. Bone turnover markers will further define the safety profile of RCI in lupus. Reference: [1] Furie, et al. Lupus Sci Med. 2016 Oct 21;3:e000180. Acknowledgement: Editorial support provided by MedLogix Communications, LLC and funded by Mallinckrodt, ARD LLC. Disclosure of Interests: Anca Askanase: None declared, Enxu Zhao Shareholder of: Mallinckrodt ARD LLC, Employee of: Mallinckrodt ARD LLC, Julie Zhu Shareholder of: Mallinckrodt ARC, LLC, Employee of: Mallinckrodt ARC, LLC, Erin Connolly-Strong Shareholder of: Mallinckrodt ARC, LLC, Employee of: Mallinckrodt ARC, LLC, Richard Furie Grant/research support from: Biogen, UCB Pharma, but not in the last 12 months, Consultant for: Biogen, UCB Pharma, but not in the last 12 months

The role of somatic mutation profiling in the management of appendiceal mucinous tumors (AMTs) is evolving. Using a systematic review, we identified somatic alterations (SAs) that comprise histopathologic types of AMTs and those associated with aggressive clinical phenotypes. MEDLINE/PubMed was searched for studies on AMTs including molecular markers or genomic alterations, published between 1990 and 2018. Studies were grouped under low- and high-grade histological type for primary and metastatic tumors. Twenty-one studies involving 1099 tumors (primary/metastatic) were identified. Seven studies involving 101 primary low-grade AMTs identified KRAS (76.5%) as the predominant SA. Four studies noted GNAS in 45.2% of 42 low-grade appendiceal mucinous neoplasms, and KRAS was identified in 74.4% of 14 studies with 238 low-grade pseudomyxoma peritonei (PMP). GNAS was noted in 56% of 101 tumors and TP53 was noted in only 9.7% of 31 tumors. Primary high-grade tumors demonstrated lower SAs in KRAS (50.4% of 369 tumors) and GNAS (27.8% of 97 tumors), and higher SAs in TP53 (26.0% of 123 tumors). In high-grade PMP, SAs were noted in KRAS (55.0% of 200 tumors), GNAS (35.0% of 60 tumors), and TP53 (26.3% of 19 tumors). No clear association was noted between SAs and survival. KRAS and GNAS are frequently altered in low-grade AMTs, while TP53 is frequently altered in high-grade AMTs, with no apparent change in expression between primary and metastatic tumors. Although SAs may provide valuable insights into variability in tumor biology, larger studies utilizing clinically annotated genomic databases from multi-institutional consortiums are needed to improve their identification and clinical applicability.

Background Metastatic colorectal cancer (mCRC) with peritoneal carcinomatosis is an increasingly prevalent disease that carries significant mortality if left untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in this patient population is associated with improved outcomes but high morbidity. We sought to study the prognostic significance of the known genomic driver, RAS, in patients with mCRC undergoing CRS/HIPEC to allow for improved assessment of risk-benefit ratio in this patient population. Methods Patients undergoing CRS/HIPEC for mCRC between 2010 and 2017 at our institution were identified. Patient demographics, RAS mutation status, perioperative morbidity, overall survival (OS), and relapse-free survival (RFS) were evaluated. Results Forty-seven patients met inclusion criteria. RAS mutant versus RAS wild-type groups were well matched with no difference in the clinicopathologic factors between groups. RAS mutation was associated with decreased RFS but no difference in OS. Conclusions RAS mutation is an independent marker of early recurrence in patients undergoing CRS/HIPEC for mCRC and may identify patients who do not derive benefit from this high-risk procedure.

ObjectiveSLE is a chronic inflammatory autoimmune disease characterised by the excessive production of autoantibodies, immune complexes and proinflammatory cytokines. Repository corticotropin injection (RCI) is a naturally sourced complex mixture of adrenocorticotropic hormone analogues and other pituitary peptides. RCI is approved by the US Food and Drug Administration for use during an exacerbation or as maintenance therapy in select cases of SLE. This paper discusses the design and baseline characteristics of a multicentre, double-blind, randomised, placebo-controlled, 24-week clinical trial evaluating the effect of RCI in reducing disease activity for patients with persistently active SLE despite moderate-dose corticosteroid use.MethodsEfficacy will be evaluated using the SLE Responder Index-4 (SRI-4), SLE Disease Activity Index-2000 (SLEDAI-2K), British Isles Lupus Assessment Group-2004 (BILAG-2004) and Physician’s Global Assessment (PGA). The primary efficacy endpoint will be the proportion of SRI-4 responders at week 16. Secondary and exploratory endpoints will include changes in disease activity scores over time, prednisone dose and biomarkers of inflammation and bone turnover. The safety and tolerability profile of RCI will also be evaluated through adverse event profiles, physical examination, clinical laboratory tests and serum cortisol levels.ResultsTarget enrolment for this global study is 270 patients, and as of 15 November 2019, the modified intent-to-treat population included 169 patients. The study cohort had 91.7% women, had a mean age of 39.7 years, mean SLEDAI-2K total score of 9.9, mean BILAG-2004 total score of 18.1, mean PGA of 59.7 and mean prednisone or equivalent daily dose of 11.1 mg. A total of 79.3% and 64.5% of patients were receiving concomitant antimalarial or immunosuppressive therapy, respectively.ConclusionsData from this study will provide valuable insights into the therapeutic role of RCI in refractory SLE, as well as important information regarding its safety profile.

Outcome disparities related to racial/ethnic identity have been documented in the literature for both invasive breast cancer and ductal carcinoma in situ (DCIS). The complex interplay of socioeconomic and biologic factors accounting for these disparities is difficult to disentangle, as racial-ethnic minorities are overrepresented among the impoverished and underinsured/noninsured population of the USA, but African American background has also been associated with higher risk of inherently unfavorable patterns of breast cancer. Since DCIS is largely a screen-detected disease, disparities in socioeconomic resources and health-care access are closely linked to the observed outcome disparities as a downstream effect of mammography screening patterns as well as delays in diagnosis/treatment. Advancing our understanding of the entire spectrum of factors that contribute to disparities will enhance the development of multidimensional remedies, including health-care reform, clinical research, and patient education/advocacy.