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Background and study aims Endoscopic mucosal resection (EMR) is a standard method for removing sessile colorectal polyps ≥ 10 mm. Recently, underwater EMR (UEMR) has been introduced as a potential alternative. However, the effectiveness and safety of UEMR compared with conventional EMR is un clear. Patients and methods In this 1:1 propensity score (PS) matched retrospective cohort study, we compared the en bloc resection rates, procedure time, intraprocedural and delayed bleeding rates, and incidence of muscle layer injury. We also performed subgroup analyses by sizes of polyps ( Results Among 350 polyps in 315 patients from August 2012 to November 2017, we identified 121 PS-matched pairs. Mean polyp size was 16.8 mm. With similar en bloc resection rates (EMR: 82.6 % vs. UEMR: 87.6 %, rate difference: 5.0, 95 % confidence interval [95 % CI]: – 4 to 13.9 %), UEMR demonstrated a shorter resection time (10.8 min vs. 8.6 min, difference: – 2.2 min, 95 % CI: – 4.1 to – 0.3 min) and a lower intraprocedural bleeding rate (15.7 % vs. 5.8 %, rate difference: – 9.9 %, 95 % CI: – 17.6 to – 2.2 %). Incidence of delayed bleeding and muscle layer injury were low in both groups. For polyps Conclusions UEMR achieved an en bloc resection rate comparable to conventional EMR with less intraprocedural bleeding and a shorter procedure time.

Little is known about real-world treatment patterns and outcomes in Waldenström macroglobulinemia (WM) following the recent introduction of newer treatments, especially among older adults. We describe patterns of first-line (1 L) WM treatment in early (2006–2012) and modern (2013–2019) eras and report outcomes (overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse event (AE)-related discontinuation) in younger (≤70 years) and older (&gt, 70 years) populations. We followed 166 younger and 152 older WM patients who received 1 L treatment between January 2006 and April 2019 in the Veterans Health Administration. Median follow-up was 43.5 months (range: 0.6–147.2 months). Compared to the early era, older patients in the modern era achieved improved ORRs (early: 63.8%, modern: 72.3%) and 41% lower risk of death/progression (hazard ratio (HR) for PFS: 0.59, 95% CI (confidence interval): 0.36–0.95), with little change in AE-related discontinuation between eras (HR: 0.82, 95% CI: 0.4–1.7). In younger patients, the AE-related discontinuation risk increased almost fourfold (HR: 3.9, 95% CI: 1.1–14), whereas treatment effects did not change between eras (HR for OS: 1.4, 95% CI: 0.66–2.8, HR for PFS: 1.1, 95% CI: 0.67–1.7). Marked improvements in survival among older adults accompanied a profound shift in 1 L treatment patterns for WM.

Aim: To describe practices and outcomes in veterans with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Using Veteran Affairs Cancer Registry System and electronic health record data, we identified relapsed/refractory diffuse large B-cell lymphoma patients completing second-line treatment (2L) in 2000–2016. Treatments were classified as aggressive/nonaggressive. Analyses included descriptive statistics and the Kaplan–Meier estimation of progression-free survival and overall survival. Results: Two hundred and seventy patients received 2L. During median 9.7-month follow-up starting from 2L, 470 regimens were observed, averaging 2.7 regimens/patient: 219 aggressive, 251 nonaggressive. One hundred and twenty-one patients proceeded to third-line, 50 to fourth-line and 18 to fifth-line treatment. Median progression-free survival in 2L was 5.2 months. Median overall survival was 9.5 months. Forty-four patients (16.3%) proceeded to bone marrow transplant. Conclusion: More effective, less toxic treatments are needed and should be initiated earlier in treatment trajectory.

Tamoxifen or aromatase inhibitor (AI) therapy may prevent breast cancer recurrence, however, adverse effects may lead to treatment discontinuation. Evidence regarding the occurrence of AI-associated musculoskeletal problems among Asians is scarce. We identified women with breast cancer-initiating tamoxifen or AIs from the Taiwan National Health Insurance Research Database (2007&ndash, 2012). Using multivariable cause-specific hazard models, we examined the association between endocrine therapy and the risk of any arthritis and carpal tunnel syndrome, adjusting for age, prior cancer treatment, and other health status factors. Among 32,055 eligible women with breast cancer (mean age = 52.6 &plusmn, 11.5 years), 87.4% initiated tamoxifen, 3.9% initiated anastrozole, 8.0% initiated letrozole, and 0.7% initiated exemestane. AI users had a higher 1-year cumulative incidence for any arthritis (13.0% vs. 8.2%, p &lt, 0.0001) and carpal tunnel syndrome (1.4% vs. 0.8%, p = 0.008). Compared to tamoxifen users, AI users had a higher risk of any arthritis [adjusted hazard ratio (aHR) = 1.21, 95%CI = 1.09&ndash, 1.34] and carpal tunnel syndrome (aHR = 1.68, 95%CI = 1.22&ndash, 2.32). No significant difference was observed in the risks of any arthritis and carpal tunnel syndrome across different AIs. Taxane use was not associated with any arthritis (aHR = 0.92, 95%CI = 0.81&ndash, 1.05) or carpal tunnel syndrome (aHR = 0.97, 95%CI = 0.67&ndash, 1.40) compared to other chemotherapies. Taiwanese women with breast cancer-initiating AIs had an increased risk of arthritis and carpal tunnel syndrome compared to those who initiated tamoxifen.

The most accurate prognostic approach for follicular lymphoma (FL), progression of disease at 24 months (POD24), requires two years’ observation after initiating first-line therapy (L1) to predict outcomes. We applied machine learning to structured electronic health record (EHR) data to predict individual survival at L1 initiation. We grouped 523 observations and 1933 variables from a nationwide cohort of FL patients diagnosed 2006–2014 in the Veterans Health Administration into traditionally used prognostic variables (“curated”), commonly measured labs (“labs”), and International Classification of Diseases diagnostic codes (“ICD”) sets. We compared performance of random survival forests (RSF) vs. traditional Cox model using four datasets: curated, curated + labs, curated + ICD, and curated + ICD + labs, also using Cox on curated + POD24. We evaluated variable importance and partial dependence plots with area under the receiver operating characteristic curve (AUC). RSF with curated + labs performed best, with mean AUC 0.73 (95% CI: 0.71–0.75). It approximated, but did not surpass, Cox with POD24 (mean AUC 0.74 [95% CI: 0.71–0.77]). RSF using EHR data achieved better performance than traditional prognostic variables, setting the foundation for the incorporation of our algorithm into the EHR. It also provides for possible future scenarios in which clinicians could be provided an EHR-based tool which approximates the predictive ability of the most accurate known indicator, using information available 24 months earlier.

Background Waldenström's Macroglobulinemia (WM) is a rare indolent lymphoma with an estimated 1,500 new cases diagnosed each year in the United States (US). Over the last decade, several treatments have been introduced into the WM therapeutics landscape including, bendamustine, bortezomib, and most recently oral Bruton's kinase inhibitor (ibrutinib). There is limited information in the adoption of these WM treatments in real-world clinical settings in the US. We describe the practice patterns and clinical outcomes of first-line (1L) treatment of WM in a nationwide cohort of Veterans. Methods Using Veteran Affairs electronic health records (EHR) data, we identified Veterans who were diagnosed and received 1L treatment for WM between January 2006 and December 2018 in the Veterans Health Administration (VHA). Human annotation of EHR clinical records confirmed the diagnosis and 1L treatment regimens. Patients with another cancer diagnosis or patients with documentation that 1L treatment was received outside the VHA were excluded. Eligible patients were followed until loss to follow-up, death, or the end of the study period (June 30, 2019). Patient demographics, disease characteristics, and treatment patterns were identified. Local polynomial regression model curves were generated to demonstrate treatment changes over time. Unadjusted progression-free survival (PFS) and the unadjusted overall survival (OS) are also provided. Results We identified 505 patients diagnosed with WM in VHA between January 2006 thru December 2018. Of these, 318 patients received 1L treatment, with a median time from diagnosis to 1L treatment of 1.2 months (95% confidence interval [CI]: 0.5-5 months). The median age of WM patients was 69.9 years (standard deviation [SD]: 9.4 years), with approximately 73% of WM patients ≥65 years old. Prior to 1L treatment, the median hemoglobin and platelets observed were similar across all treatment groups, regardless of first 1L treatment. However, the median immunoglobulin M (IgM) was substantially lower in patient's treated with ibrutinib (2,570 mg/dL [range: 422-9,001 mg/dL]) and single-agent rituximab (R), 2,855 mg/dL (range: 84-7,880 mg/dL) when compared to those treated with chlorambucil +/- rituximab (4,416 mg/dL [range: (9-8,130 mg/dL]) and bortezomib/dexamethasone +/- rituximab (BDR), 4,086 mg/dL (range: 16-9,944 mg/dL). MYD88 testing occurred in 40 (13%) of patients, with testing most frequently occurring in patients treated with bendamustine +/- rituximab (BR), ibrutinib, and BDR- likely reflecting increased adoption in later periods. Hepatitis C testing occurred in 61 (19%) of patients, with testing most frequently occurring in patients treated with dexamethasone, rituximab, and cyclophosphamide (DRC), BDR, and BR. Over the study observation period, 1L practice patterns shift significantly with increased adoption of BR, BDR and ibrutinib and de-adoption of chemotherapy (Figure 1). The median follow-up time for all patients was 44 months (range: 1-147 months), although a shorter median follow-up time was observed in patients treated with therapeutics in recent years, such as ibrutinib (18 months [range: 2-53 months]) and BR (23 months [range: 4-86 months]). The median unadjusted PFS for all WM patients was 44 months (95% CI: 37-58 months) and the median unadjusted overall survival (OS) was 94 months (95% CI: 82-117 months). Conclusions The introduction of numerous therapeutic options throughout the past decade has profoundly altered the treatment landscape for WM, suggesting a shift in 1L practices from chlorambucil to BDR, BR, and most recently ibrutinib which has been increasingly adopted, since its approval in 2015, especially in older patients, suggesting that it may provide an effective therapeutic option for patients who may not be able to tolerate more aggressive treatment regimens. Limitations of this study include the differences observed in follow-up time as well as the limited number of patients in some 1L treatment groups. Further research is required to establish the long-term benefits and potential treatment-related toxicities of WM treatments in real-world clinical settings. Disclosures Sauer: Roche: Research Funding; Genentech, Inc.: Research Funding; Pharmacyclics: Research Funding; AbbVie: Research Funding. Halwani:AbbVie: Research Funding; Takeda: Research Funding; Roche: Research Funding; Genentech, Inc.: Research Funding; Miragen: Research Funding; Immunedesign: Research Funding; Kyowa Hakko Kirin: Research Funding; Seattle Genetics: Research Funding; Amgen: Research Funding; Pharmacyclics: Research Funding; Bristol Myers Squibb: Research Funding.

Background Patients with end stage renal disease have a high all-cause and cardiovascular mortality. Secondary hyperparathyroidism and vitamin D deficiency are considered part of the mechanism for the excess mortality observed. We aimed to evaluate the relationship between vitamin D use and all-cause mortality. Methods In this retrospective cohort study, we included all incident patients who started hemodialysis in Taiwan between 2001 and 2009. Patients were followed from landmark time, i.e., the 360th day from hemodialysis initiation, through the end of 2010 or death. We evaluated the association between activated vitamin D use or not before landmark time and all-cause mortality using conditional landmark analysis with Cox regression. We used group-based trajectory model to categorize high-dose versus average-dose users to evaluate dose-response relationships. Results During the median follow-up of 1019 days from landmark time, vitamin D users had a lower crude mortality rate than non-users (8.98 versus 12.93 per 100 person-years). Compared with non-users, vitamin D users was associated with a lower risk of death in multivariate Cox model (HR 0.91 [95% CI, 0.87–0.95]) and after propensity score matching (HR 0.94 [95% CI, 0.90–0.98]). High-dose vitamin D users had a lower risk of death than conventional-dose users, HR 0.75 [95% CI, 0.63–0.89]. The association of vitamin D treatment with reduced mortality did not alter when we re-defined landmark time as the 180th day or repeated analyses in patients who underwent hemodialysis in the hospital setting. Conclusions Our findings supported the survival benefits of activated vitamin D among incident hemodialysis patients. Electronic supplementary material The online version of this article (10.1186/s12882-018-1111-2) contains supplementary material, which is available to authorized users.

Background: This study describes the availability and characteristics of databases in Asian-Pacific countries and assesses the feasibility of a distributed network approach in the region. Methods: A web-based survey was conducted among investigators using healthcare databases in the Asia-Pacific countries. Potential survey participants were identified through the Asian Pharmacoepidemiology Network. Results: Investigators from a total of 11 databases participated in the survey. Database sources included four nationwide claims databases from Japan, South Korea, and Taiwan; two nationwide electronic health records from Hong Kong and Singapore; a regional electronic health record from western China; two electronic health records from Thailand; and cancer and stroke registries from Taiwan. Conclusions: We identified 11 databases with capabilities for distributed network approaches. Many country-specific coding systems and terminologies have been already converted to international coding systems. The harmonization of health expenditure data is a major obstacle for future investigations attempting to evaluate issues related to medical costs.

Introduction Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, accounting for 25-30% of all leukemias in the United States. During the past decade, there has been a paradigm shift in CLL treatment, with increasing adoption of novel oral agents (NOAs) such as acalabrutinib (ACALA), duvelisib (DUV), ibrutinib (IBR), idelalisib (IDELA), and venetoclax (VEN) instead of traditional chemoimmunotherapy (CIT). Unlike CIT, most NOAs are given daily for an indefinite period of time and are self-administered at home, raising concerns about adherence and discontinuation. The discontinuation patterns of NOAs in a real-world population of CLL patients is currently unknown. Methods Using the Veterans Administration (VA) Cancer Registry System and electronic healthcare records, we identified patients treated for CLL with NOAs in the VA from November 1, 2013 to November 30, 2018. Patients were followed from the first NOA dispensation until death or the end of the study observation (May 31, 2019). NOAs were selected in accordance with the National Comprehensive Cancer Network (NCCN) guidelinesfor CLL and were extracted using pharmacy dispensation records. Discontinuation was defined as the absence of NOA dispensation within 60 days of estimated exhaustion of patient's NOA supply from the last recorded dispensation. A discontinuation event for each NOA treatment episode in each patient was classified as either 1) a drug holiday, if there was evidence of resumption of the same treatment without any other treatment interventions after the first discontinuation; or 2) permanent discontinuation, in which the treatment ceased without evidence of resumption for 60 days or there was evidence of new treatment initiation after the discontinuation of previous treatment. We report the proportion of discontinuation and exposure-adjusted discontinuation rates (e-AR), which were calculated using the length of NOA duration in person-time. Results We identified 1,196 CLL patients treated with NOAs from November 1, 2013 to November 30, 2018. The mean age at NOA initiation was 70.7 years; 96.7% of patients were male. The median time from diagnosis to NOA initiation was 56.5 months (0-189.5 months). Of the 1,196 patients treated with NOAs, 1,172 received IBR, 53 received IDELA, and 106 received VEN. There were few patients ( During a median follow-up of 18.9 months (0-65.3 months), 48.2% NOA treatment courses were followed by a discontinuation event. The proportions of patients who discontinued for IBR, IDELA, and VEN were 47.5%, 77.4%, and 41.5%. The e-AR of IBR, IDELA, and VEN are reported in Table 2. At the end of the study observation (May 2019), 52.6% of IBR, 22.6% of IDELA, and 58.3% of VEN treatment courses were still being administered. In first-line (L1) IBR, the median NOA treatment duration until the first discontinuation was 10.7 months (0.8-55.8 months), 12.6 months (0.5-62.0 months) in second-line (L2) IBR, and 12.2 months (0.78-57.8 months) in third-line or subsequent lines (L3+) IBR. In IDELA treatment courses, the median treatment duration until the first discontinuation was 17.8 months (1.9-41.6 months) in L2 and 4.3 months (1.7-26.2 months) in L3+. In VEN, the median treatment duration until the first discontinuation was 8.4 months (3.1-26.0 months) in L2 and 7.4 months (1.7-18.5 months) in L3+. Of 532 L1 IBR treatment courses with >1 dispensation, 96 (18%) were associated with a drug holiday and 97 (18%) with permanent discontinuation. These numbers were 64 (27%) and 50 (21%) for L2 IBR courses, and 90 (28%) and 76 (24%) for L3+ IBR courses. Similarly, 24 (67%) of L3 IDELA treatment courses with >1 dispensation were associated with permanent discontinuation. Among 63 L3+ VEN courses with >1 dispensation, 6 (10%) were associated with a drug holiday and 14 (22%) with permanent discontinuation. Conclusions To our knowledge, this study is the first to report on the NOA discontinuation in a nationwide VA cohort of CLL patients treated in a real-world setting. Our results suggest there is a substantial proportion of drug holidays and permanent discontinuation among commonly used NOAs. Further efforts will focus on understanding factors leading to discontinuation and the impact of discontinuation/drug holidays on clinical outcomes. Disclosures Biondo: Genentech, Inc.: Employment; F. Hoffmann-La Roche Ltd: Equity Ownership. Halloran:Roche: Equity Ownership; Genentech, Inc.: Employment. Shapouri:Roche: Equity Ownership; Genentech, Inc.: Employment. Wu:Genentech, Inc.: Employment. Sauer:University of Utah and SLC VA Medical Center: Employment. Halwani:Miragen: Research Funding; Kyowa Hakko Kirin: Research Funding; Pharmacyclics: Research Funding; Amgen: Research Funding; Seattle Genetics: Research Funding; Genentech, Inc.: Research Funding; AbbVie: Research Funding; Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; Immune Design: Research Funding.

Background Waldenström's macroglobulinemia (WM) is a rare indolent cancer. Because of its low incidence, the treatment practices for WM primarily rely on data from phase 2 trials, which often have no consensus as to how to best treat this uncommon disease. The heterogeneity of treatments available can be observed in clinical practice guidelines, which recommend traditional chemotherapies, second-generation proteasome inhibitors, multiagent immunotherapies, and the novel Bruton's tyrosine kinase inhibitor, ibrutinib (IBR). Yet, despite clinical evidence and treatment guidelines recommending multiagent chemoimmunotherapy in first-line (1L) patients with WM, a majority of patients still receive monotherapy, namely chlorambucil in Europe and monotherapy rituximab (R) in the United States. To date, there have been no reports on the real-world treatment practices in 1L of WM since the introduction of IBR. The primary objective of this study is to understand the 1L treatment practices for WM in a nationwide cohort of Veterans treated in the largest integrated healthcare system in the United States, the Veterans Health Administration (VA). Methods Using the VA Cancer Registry System and electronic healthcare records, we identified Veterans diagnosed with WM between January 1, 2006, to December 31, 2018. Treatment regimens were classified in accordance with the National Comprehensive Cancer Network (NCCN) guidelines for WM (versions 1.2006, 2.2013, and 2.2019). Eligible patients were followed until loss to follow-up, death or the end of the study observation period (June 30, 2019). The 1L of treatment was examined; with the start date for 1L being the index date. Patients with a cancer diagnosis other than WM and patients who did not receive 1L treatment were excluded from the study. Results We identified 340 patients who were diagnosed with WM and received a 1L treatment regimen between 2006-2019 in the VA. Median age at diagnosis was 68 years (range: 37-92); 334 (98%) of patients were male. Demographics are further described in Table 1. At diagnosis, the median serum IgM was 3083 mg/dl (range: 10-11500), the median hemoglobin was 11 g/dl (range: 5-17), and the platelet count was 204 k/dl (range: 5-732). A noticeable shift in the adoption of treatments can be observed when comparing treatment practices in patients treated between 2006-2009, 2010-2014, and those treated between 2015-2019. From 2006-2009 the majority of 1L patients received monotherapy with R (23, 37%) or chlorambucil (14, 22%). Between 2010-2014, the majority of patients received monotherapy R (43, 34%), with increasing adoption of bendamustine + R (8, 6%) and bortezomib (27, 21%). Between 2015-2019, IBR became the leading 1L treatment (38, 25%), followed by bendamustine + R (33, 22%), monotherapy R (33, 22%), and bortezomib + R (28, 19%). The estimated survival rate of WM patients treated with 1L was 79% at three-years, 68% at 5-years, and 55% at 7-years. Conclusions Our study is one of the first to examine the real-world treatment practices of WM patients treated with 1L after the approval of novel agent IBR. Our results highlight the heterogeneity of treatment options available for WM patients. We also describe the evolution of treatment choices in 1L over the last decade: from chlorambucil and rituximab monotherapy, to ibrutinib, bendamustine, and bortezomib. Retrospective and/or observational studies examining treatments and outcomes in WM patients should take these shifts in treatment practices into consideration. Given the persistent utilization of monotherapy R as a treatment in 1L, despite the superior efficacy of other treatment options such as ibrutinib, bendamustine and bortezomib regimens, our results indicate the need for continued efforts to educate clinicians about the appropriate treatment options available for this rare disease. Acknowledgments: The study was sponsored by Pharmacyclics Disclosures Sauer: University of Utah and SLC VA Medical Center: Employment. Halwani:Genentech, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Amgen: Research Funding; Kyowa Hakko Kirin: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding; Miragen: Research Funding.

Background: Nearly 40% of patients with diffuse large B-cell lymphoma (DLBCL) are either refractory to or relapse (R/R) after initial first-line (L1) treatment. These patients frequently receive subsequent lines of treatment, although to achieve long-term remission requires aggressive chemoimmunotherapy followed by autologous bone marrow transplant (BMT). Few real-world studies have examined the treatments used in R/R DLBCL patients over the entire disease trajectory. Methods: Using the VA Cancer Registry System and electronic healthcare records (EHR), we identified Veterans diagnosed with DLBCL between January 1, 2000 to December 31, 2016 who relapsed or progressed after L1 RCHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab) ± etoposide and then proceeded to receive at least one additional line of treatment. Human annotation of EHR notes confirmed DLBCL diagnosis, treatment regimen(s) received (including BMT), and treating physician response assessment after each line. Treatment regimens were classified as aggressive (with intent to proceed to BMT) or non-aggressive per National Comprehensive Cancer Network (NCCN) guidelines. Eligible patients were followed until loss to follow-up, death or the end of the study period (March 31, 2019). Patients with a cancer diagnosis other than DLBCL were excluded from the study. Results: We identified 270 R/R DLBCL patients who received a second-line (L2) treatment after having previously received L1 with RCHOP ± etoposide. The mean age of patients was 64.6 years; 97.4% of patients were male. Of the 270 patients, 166 (61.5%) patients received an aggressive L2 treatment regimen. RICE (ifosfamide, carboplatin, and etoposide ± rituximab) and BR (bendamustine ± rituximab) were the most commonly used aggressive and non-aggressive regimens, accounting for 39.3% and 8.9% of L2 treatment, respectively. Compared with patients who received non-aggressive L2 treatment, aggressive L2 treatment patients were younger (61.4 versus 69.7 years). Following aggressive L2 treatment, 87 patients (52.4%) achieved complete or partial response (CR/PR), while CR/PR was achieved in 43 (41.3%) patients who received non-aggressive L2. Of the 29 (10.7%) patients who received BMT, 28 received an aggressive L2 regimen. Approximately half of all patients who received L2 therapy (121/270) proceeded to third-line (L3) treatment, of which 47 (38.8%) received an aggressive L3 regimen. Nearly half of those patients who received an aggressive L2 treatment (36, 47.4%) proceeded to an aggressive L3 regimen, while only 11 (18.8%) non-aggressive L2 patients proceeded to aggressive L3 treatment. Following L3 treatment, 7 (5.8%) patients proceeded to a BMT. The median overall survival (OS) in patients receiving L2 was 9.7 months (CI: 8.2-11.7 months). The median OS for patients treated with aggressive L2 was 9.7 months (CI: 8.1-12.2 months) compared with 9.7 months (CI: 6.8-12.9 months) in patients treated with a non-aggressive L2. The median progression-free survival (PFS) for patients treated with aggressive L2 was 5.6 months (CI: 4.6-7.9 months) and 4.9 months (CI: 3.5-8.4 months) for patients treated with non-aggressive L2. Median OS in patients receiving L3 was 6.3 months (CI: 5.1-8.7 months). The median OS for patients treated with aggressive L3 was 6.8 months (CI: 5.1-12.5 months) compared with 6.6 months (CI: 4.8-9.7 months) in patients treated with a non-aggressive L3. The median PFS for patients treated with aggressive L3 was 4.5 months (CI: 2.6-6.9 months) and 2.9 months (CI: 1.8-5.7 months) for patients treated with non-aggressive L3. Conclusions: Patients who receive aggressive L2 treatment tend to be younger, more likely to receive another aggressive therapy (if L3 treatment is needed), and were much more likely to proceed to BMT than patients who received non-aggressive L2 therapy. Patients who received aggressive L2 treatments resulted in higher response rates compared to less aggressive treatment. We did not find a difference in OS between patients who received aggressive and non-aggressive treatment, the cause of which may be multifactorial. Future studies will examine factors that may impact OS in these patient groups. Acknowledgments: The study was sponsored by Genentech, Inc. Masaquel, Halloran, DeLong-Sieg, Schulz, and Li are employees of Genentech and may receive stock options from Roche. Disclosures Halwani: Pharmacyclics: Research Funding; Immune Design: Research Funding; Seattle Genetics: Research Funding; Amgen: Research Funding; Takeda: Research Funding; Kyowa Hakko Kirin: Research Funding; Miragen: Research Funding; Genentech, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Research Funding. Masaquel:Roche: Equity Ownership; Genentech: Employment. Halloran:Genentech, Inc.: Employment; Roche: Equity Ownership. Delong-Sieg:Genentech/Roche: Employment, Equity Ownership. Schulz:Roche: Equity Ownership; Genentech, Inc.: Employment. Li:Genentech: Employment; Roche: Equity Ownership. Sauer:University of Utah and SLC VA Medical Center: Employment.

Objective The aim of this study was to determine the validity of in-hospital mortality records in the National Health Insurance Research Database (NHIRD) by cross-comparing with death records from the electronic medical records (EMR) of a medical center in southern Taiwan. Methods Data on patients admitted to the medical center for acute myocardial infarction (AMI) or stroke during the years 2005 to 2010 were extracted from the two databases and cross-linkages with patients' characteristics (birth date, gender, admission date, and discharge date). While the death record was available in the catastrophic illness registry data files (CIRD), we also estimated the insurance status and death record in the CIRD subset using confirmed death cases. Additionally, agreement in comorbidities between records from the two databases was evaluated. Results A total of 6197 cases were successfully linked, with a linkage rate of 96.56% of cases in the NHIRD when linked to those from the EMR. Among the linked population, 538 of 682 patients retrieved as expired in the NHIRD were also so recorded in the EMR. This yielded a positive predictive value of 0.79 when the EMR was used as the gold standard. Patients having death records in both the CIRD subset and the EMR totaled 364, which yielded a percentage positive agreement rate of 76%. The consistency in comorbidity diagnoses between the two databases was more than 90% among matched cases. Conclusions The accuracy of death records in the NHIRD was high, and appears to be a valid resource for population research in cardiovascular diseases.

PURPOSE Accurate diagnosis and early recognition of dry eye symptoms are important in the management of dry eye disease (DED). This study aimed to evaluate concordance between patient and clinician assessment of DED severity and treatment response. METHODS This cross-sectional study was conducted in 2 ophthalmology clinics in Taiwan. Clinicians assessed severity based on the Dry Eye Workshop severity grading (levels 1-4; where 4 = most severe), whereas patients completed the Ocular Surface Disease Index questionnaire. To evaluate the treatment response, patients completed the Subject Global Assessment scale, and clinicians independently assessed patients using the Clinical Global Impression scale. RESULTS A total of 466 patients were included. Clinicians graded 88.3% of patients as level 1/2, 9.0% as level 3, and 2.7% as level 4 Dry Eye Workshop severity, whereas 44.9% of patients reported normal/mild symptoms, 17.1% with moderate severity, and 38.0% with severe DED. Patients were primarily treated with artificial tears. The clinician assessed 10.3% of patients as unchanged on disease severity after treatment and 88.0% as improved, whereas 49.2% of patients reported dry eye symptoms being almost the same after treatment and 34.6% reported improved symptoms. There was low agreement between clinician and patient assessments in terms of disease severity (rho = 0.17, P < 0.001) and treatment response (rho = 0.22, P < 0.001). CONCLUSIONS There were marked differences in the degree of DED severity and treatment response between patient and clinician assessment. Clinicians may underestimate DED severity and persistence of dry eye symptoms after treatment with artificial tears.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01942226.

Importance Trastuzumab is an essential medicine per the World Health Organization Model List, but its cardiac safety information in Asian women is limited. Objective To estimate the rate and the risk of heart failure (HF) and/or cardiomyopathy (CM) in Asian women undergoing trastuzumab treatment. Design This cohort study used the Taiwanese National Health Insurance Research Database (NHIRD), a nationwide claim database covering more than 99% of the entire Taiwanese population, to identify 23 006 women with incident breast cancer (BC) who received chemotherapy from 2006 to 2009. We grouped women per their initial treatment regimens and found 1066 new trastuzumab users. We matched trastuzumab users with nonusers by year of BC diagnosis and propensity score (PS) with the caliper widths at 0.25 standard deviation of PS (up to 4 nonusers per trastuzumab user). The study lasted from January 2006 to December 2013 with a median follow-up of 5.29 years and a landmark design to avoid immortal time bias. Exposure Trastuzumab. Main Outcomes and Measures To estimate HF and/or CM rates and time to HF and/or CM, we employed a cause-specific hazard model. Trastuzumab exposure was a time-dependent variable, while cumulative courses of chemotherapy agents with known cardiotoxic effects (including anthracyclines, taxanes, and cyclophosphamide) were defined as time-dependent covariates in the analysis model. We also performed 6 sensitivity analyses. Results In this cohort of 23 006 women (mean age, 50.99 years), the crude incidence of HF and/or CM was 4.03% in trastuzumab users and 2.88% in nonusers. The median time to HF and/or CM was 456 days in trastuzumab users and 966 days in nonusers. The 1-year cumulative hazard ratio was 1.86 (95% CI, 1.08-3.19). The sensitivity analyses yielded similar results. Conclusions and Relevance Compared with the published results, the trastuzumab-related HF and/or CM rate was 5-fold lower in Taiwanese women with breast cancer. Nonetheless, our cohort had a similar trastuzumab-related HF and/or CM risk. Our study provides critical cardiac safety information of trastuzumab for Asian women with BC under current treatment guidelines and label information.