Pulmonary hypertension (PH) complicates the treatment of interstitial lung disease (ILD) patients resulting in poor functional status and worse outcomes. Early recognition of PH in ILD is important for initiating therapy and considering lung transplantation. However, no standard exists regarding which patients to screen for PH‐ILD or the optimal method to do so. The aim of this study was to create a risk assessment tool that could reliably predict PH in ILD patients. We developed a PH‐ILD Detection tool that incorporated history, exam, 6‐min walk distance, diffusion capacity for carbon monoxide, chest imaging, and cardiac biomarkers to create an eight‐component score. This tool was analyzed retrospectively in 154 ILD patients where each patient was given a score ranging from 0 to 12. The sensitivity (SN) and specificity (SP) of the PH‐ILD Detection tool and an area‐under‐the‐curve (AUC) were calculated. In this cohort, 74 patients (48.1%) had PH‐ILD. A score of ≥6 on the PH‐ILD Detection tool was associated with a diagnosis of PH‐ILD (SN: 86.5%; SP: 86.3%; area‐under‐the‐curve: 0.920, p < 0.001). The PH‐ILD Detection tool provides high SN and SP for detecting PH in ILD patients. With confirmation in larger cohorts, this tool could improve the diagnosis of PH in ILD and may suggest further testing with right heart catheterization and earlier intervention with inhaled treprostinil and/or lung transplant evaluation.

BACKGROUND Brain metastases constitute a major clinical concern occurring in 28–43% of women treated for HER2+ metastatic breast cancer (MBC). The initial diagnosis of Central Nervous System (CNS) lesion is commonly based upon development of neurological symptoms. Data to address incidence of CNS lesions in asymptomatic patients are rare and not generally reported. EGF111438/CEREBEL study requires systematic screening for brain metastases by brain MRI and the ineligible patients due to detection of asymptomatic brain metastases are reported here. METHODS The patients screened for CEREBEL have consented to a multi-centre, open-label Phase III study in subjects with HER2+ metastatic breast cancer who received prior treatment with anthracyclines or taxanes and trastuzumab in the adjuvant or metastatic setting. Eligible subjects must not have any history of CNS metastases (including leptomeningeal involvement) or have evidence of benign or malignant brain tumours and/or clinical evidence of spinal cord metastases at baseline. In order to confirm this, subjects must have negative brain MRI at baseline as confirmed by independent review (IR). All MRI scans of the brain had to be acquired with gadolinium contrast agent (T1 only) and 3mm slice thickness without gaps. The primary endpoint of CEREBEL is the incidence of CNS lesions as first site of relapse. A total of 650 subjects (325 per group) are expected to be randomized between capecitabine + trastuzumab versus capecitabine + lapatinib. RESULTS The study is currently recruiting with 322 patients enrolled as of 15.06.2011. At this date, the total number of patients screened were 492 and 170 of these patients were screen failures. There are 15 patients in screening. The percentage of screen failures due to asymptomatic brain metastases assessed by investigators was 13.5% (23/170). The overall incidence of clinically asymptomatic brain metastases assessed by investigators for this study is 4.7% (23/492). CONCLUSIONS Around 5% of all screened patients (14% of screen failures) in this study who were clinically thought to be free of brain lesions actually had brain metastases verified by brain MRI. We therefore conclude that screening for occult brain metastases by MRI is important for trials with defined CNS endpoints. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-03.

Despite the strong recommendations of guidelines, intensive obesity management is not offered to all obese patients. This study aimed to examine differences in obesity management between primary care physicians (PCPs) and non-PCPs. A cross-sectional study was performed using the 2006-2007 National Ambulatory Medical Care Survey. Adults (age ≥20 years) with obesity (body mass index (BMI)≥30 kg/m(2) or obesity diagnosis using International Classification of Diseases, Ninth Revision, Clinical Modification code 278) were included in the study cohort. A multivariate logistic regression model was constructed to examine differences between PCPs and non-PCPs (primary independent variable) for obesity management (dependent variable) while controlling for predisposing, enabling, and need characteristics per Anderson's behavioral model. In all, 32.66% of 214 million visits by obese patients in 2006-2007 resulted in obesity management. PCPs were 2.38 times more likely to provide obesity management compared to non-PCPs (odds ratio [OR]=2.37; 95% confidence interval [CI]: 1.69, 3.36). Patients who had preventive visits (OR=2.23; 95% CI: 1.50, 3.32) and chronic visits (OR=1.93; 95% CI: 1.46, 2.55) were more likely to receive obesity management than patients who had acute visits. More time spent with physician, more comorbid conditions, and BMI ≥ 40 significantly increased the likelihood of receiving obesity management, while older age and smoking reduced the likelihood of receiving obesity management. Only one third of ambulatory care visits in 2006-2007 resulted in obesity management. A difference in obesity management was noted between PCPs and non-PCPs. Future research should aim to identify the reasons for these observed differences, ensure equitable access, and address the undertreatment of obesity.

Introduction: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by cytopenia, splenomegaly, and debilitating constitutional symptoms, such as fatigue, night sweats, weight loss, bone pain, and pruritus. Prior to the approval of the selective Janus kinase-2 (JAK2) inhibitor fedratinib for adults with Intermediate (Int)-2 or High-risk MF in 2019, ruxolitinib (RUX) was the only FDA-approved JAK inhibitor and considered standard of care; treatment (tx) options after RUX were limited. Furthermore, although about 60% of pts carry JAK2 mutations, not all patients respond to RUX. The aim of this study was to describe real-world tx patterns and determine unmet need in pts with MF treated with RUX. Methods: We report interim data collected from the UK and USA as part of a global retrospective medical chart review of adult pts with Int-1, Int-2, or High-risk MF who started RUX tx between Jan 2012 and Dec 2016 in the USA, UK, Germany, Spain, Canada, and France, Pts were required to have discontinued RUX prior to data abstraction (Apr-May 2020). Prior tx was allowed, except for allogeneic hematopoietic cell transplantation or JAK2 inhibitor trial participation. Study measures included pt and tx characteristics at RUX initiation, tx patterns, dose modifications (DMs), and clinical outcomes. The rate of DMs (decrease or increase) during the first 6 months of tx was assessed. Recommended dose (REC) as per US FDA label of RUX was determined via baseline platelet count; atypical dose (ATY) was defined as non-REC RUX. The Kaplan-Meier method was used to estimate median overall survival (OS) from start of RUX tx. Descriptive statistics are used in this report. Results: A total of 183 pts (USA: 105, UK: 78) were included in the analysis. Mean age at diagnosis was 63 years, 69% were male, and 82% were White. Most pts had primary MF (84%), Int-2-risk disease (51%), and JAK2 V617F driver mutation (67%). RUX was first-line MF tx in 100 pts (55%). Of 140 pts with baseline platelet counts, 46% started on REC RUX, and 54% started ATY RUX. Of pts who initiated ATY RUX, those with platelet count below 200 ×109/L were more likely to receive a higher dose; those with a platelet count above 200 ×109/L, were more likely to receive a lower dose. The median time from diagnosis to RUX initiation overall was 1.3 months (mos); this was shorter in pts initiated on REC RUX and longer in pts initiated on ATY RUX (Table). The median duration of tx (DoT) was higher for pts who initiated ATY RUX vs REC RUX (Table). Among pts who had a dose change (n = 61), change in platelet/neutrophil count (43%), and inadequate response (33%) were the main reasons for the first dose change; dose changes due to toxicity were more common with ATY RUX (33%) vs REC RUX (5%). Eighty-six pts (47%) had clinician-defined inadequate response or progressed on RUX. Pts starting ATY RUX (63% vs 39% for REC RUX) or having a DM within 6 mos of initiation (59% vs 49% for no DM) had a higher proportion of progressive disease (PD). Of those with inadequate response/PD, 69% discontinued RUX and 22% continued RUX due to lack of other effective tx. Twenty-eight percent of pts that started REC RUX discontinued RUX due to experiencing no additional clinical benefit after initial improvement; for pts who started ATY RUX, progression due to anemia (33%) was the main reason for discontinuation. In pts who did not discontinue RUX immediately after inadequate response/PD, median time to RUX discontinuation from inadequate response/PD was higher in pts who received ATY RUX vs REC RUX (6.1 vs 1.9 mos). Of 164 evaluable pts, 32 (20%) received post-RUX tx, most commonly hydroxyurea (28%) or lenalidomide (27%, USA only). Median OS since RUX initiation was 44.2 mos. OS was shorter in pts who started ATY vs REC RUX (40.9 vs 43.1 mos) and those who had a DM vs no DM within 6 mos (38.6 vs 43.0). The most common causes of death were PD (34%) and progression to AML (19%) - pts who received DMs within the first 6 mos were more likely to die from progression to AML (27%) vs those with no DMs (19%). Conclusions: In this population of adults with MF, we provide observational data that indicates DMs, including starting ATY RUX at higher or lower than REC doses, may be associated with poorer survival outcomes and higher rates of discontinuation due to PD. Relatively few pts received subsequent tx after discontinuing RUX, underscoring a significant unmet need for newer and more effective tx for MF. Disclosures Passamonti: Novartis: Speakers Bureau; Roche: Other: Support of parent study and funding of editorial support; BMS: Speakers Bureau. Heidel:Novartis: Consultancy, Honoraria, Research Funding. Parikh:RTI Health Solutions: Other: I am a full-time employee of RTI Health Solutions, which received research funding from BMS to perform this study. RTI Health Solutions is a unit of Research Triangle Institute, an independent, nonprofit, research organization that does work for govern. Tang:BMS: Current Employment, Current equity holder in publicly-traded company. Lahue:BMS: Consultancy; Alkemi LLC: Current Employment. Nadal:BMS: Current Employment. Davis:RTI Health Solutions: Other: I am a full-time employee of RTI Health Solutions, which received research funding from BMS to perform this study. RTI Health Solutions is a unit of Research Triangle Institute, an independent, nonprofit, research organization that does work for govern; BMS, Astra Zeneca, Vertex, Novartis, Esai, United Therapeutics, Pfizer: Research Funding. Ajmera:RTI Health Solutions: Current Employment. Kee:Bristol Myers Squibb: Current Employment. Abraham:BMS: Current Employment, Current equity holder in publicly-traded company.

Pulmonary hypertension (PH) results in increased morbidity and mortality in patients with interstitial lung disease (ILD). Early recognition of PH in this population is essential for planning diagnostic testing, initiating therapy, and evaluating for lung transplantation. The previously developed PH‐ILD Detection tool has significant potential in the evaluation and treatment of ILD patients; the aim of this study was to validate the tool in an independent, multicenter cohort of patients. We conducted a retrospective review of prospectively collected data from 161 ILD patients. Patients were stratified into low‐ (n = 78, 48.4%), intermediate‐ (n = 54, 33.5%), and high‐risk (n = 29, 18.0%) groups based on the score obtained with the tool. Intermediate‐ and high‐risk patients underwent follow‐up echocardiogram (TTE); 49.4% (n = 41) had an abnormal TTE suggestive of underlying PH. These patients underwent right heart catheterization; PH‐ILD was diagnosed in 73.2% (n = 30) of these cases. The PH‐ILD Detection tool has a sensitivity of 93.3%, specificity of 90.9%, and area‐under‐the‐curve of 0.921 for diagnosing PH in ILD patients, validating the findings from the original study and establishing the tool as a fundamental resource for early recognition of PH in ILD patients.