bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring cancer care experiences: Introducing SEER-CAHPS.
Authors: Rincon Maria Andrea , Kent Erin , Lines Lisa M , Gaillot Sarah , Schussler Nicola C. , Halpern Michael T. , Mollica Michelle , Smith Ashley Wilder 
Published: September 2018

6595 Background: Care experience ratings are recognized as measures of healthcare quality. Here we introduce a new, public data resource, SEER-CAHPS, which links cancer registry data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) program with Medicare claims and the Medicare Consumer Assessment of Healthcare Providers and Systems (MCAHPS) survey. Methods: The SEER-CAHPS resource includes cancer registry data from 1973-2011 (diagnosis, incidence, mortality, and sociodemographic data), Medicare CAHPS survey data from 1998-2013 (sociodemographic, health status, and care experience ratings), and Medicare fee-for-service (FFS) claims data from 2002-2013. The survey includes global ratings of overall care, personal doctor, specialist, health plan, and prescription drug plans, and composite ratings of doctor communication, care coordination, getting needed care, and getting care quickly. Data also contain survey weights to account for the Medicare CAHPS sampling design. Cross-sectional and longitudinal analyses are possible. Results: Currently, SEER-CAHPS includes 205,339 individuals with a history of cancer documented in SEER (FFS: 26,802 with a survey before cancer diagnosis, and 55,231 with a survey after cancer diagnosis; Medicare Advantage [MA]: 57,227 with a survey before cancer diagnosis and 71,436 with a survey after cancer diagnosis). The data resource also includes 724,965 MCAHPS respondents without cancer in SEER regions (FFS: 282,592; MA: 447,358). The data provide insights on topics including experiences of cancer patients in their last year of life; experiences of cancer survivors; and the associations of guideline-concordant follow-up care with patient experiences among cancer survivors. We will demonstrate project sample-size estimation and present instructions for submitting data access applications. Conclusions: SEER-CAHPS, a new, publicly available resource, provides population-based, cancer-specific data on patient experiences, health outcomes and healthcare utilization.
Trends in aggressive care at the end-of-life for stage IV lung cancer patients.
Authors: Mrad Chebli , Abougergi Marwan S , Daly Robert Michael 
Published: September 2018

6614 Background: Prior studies have demonstrated that high-intensity end-of-life care improves neither survival nor quality of life for cancer patients. The National Quality Forum endorses dying from cancer in an acute care setting, ICU admission in the last 30 days of life, and chemotherapy in the last 14 days of life as markers of poor quality care. Methods: Discharge data from the National Inpatient Sample database was analyzed for 3,030,866 acute care hospitalizations of metastatic lung cancer patients between 1998 and 2014. Longitudinal analysis was conducted to determine trends in aggressive care at the end-of-life and multivariate logistic regression was performed to determine associations with age, race, region, hospital characteristics, and aggressive care. Results: In-hospital mortality for metastatic lung cancer patients decreased from 17% to 11%. Among terminal hospitalizations, utilization of radiation therapy and chemotherapy decreased from 4.6% to 3.0% and from 4.8% to 3.0%, respectively. However, the proportion admitted to the ICU increased from 13.3% to 27.9% and invasive procedures increased from 1.2% to 2.0%. Reflecting this aggressive end-of-life care, mean total charges for a terminal hospitalization rose from $29,386 to $72,469, adjusted for inflation. Among patients who died in the inpatient setting, the ICU stay translated into higher total costs (+$16,962, CI: $15,859 to $18,064) compared to patients who avoided the ICU. Promisingly, palliative care encounters for terminal hospitalizations increased during this period from 8.7% to 53.0% and was correlated with a decrease in inpatient chemotherapy (OR = 0.56, CI: 0.47 to 0.68), radiotherapy (OR = 0.77, CI: 0.65 to 0.92), and ICU admissions (OR = 0.48, CI: 0.45 to 0.53) but had only a modest impact on terminal hospitalization cost (-$2,992, CI: -$3,710 to -$2,275). Multivariable analysis showed variation by patient and hospital characteristics in aggressive care utilization. Conclusions: Among patients with metastatic lung cancer there has been a substantial increase in ICU use during terminal hospitalizations, resulting in high cost for the health care system. Inpatient palliative care has the potential to reduce aggressive end-of-life interventions.
Bias in valuation of health care benefits in metastatic prostate cancer: A contingent valuation of willingness to pay.
Authors: Sousa Nuno , Costa Telma , Monteiro-Soares Matilde , Rocha Gonçalves Francisco , Azevedo Luis Filipe 
Published: September 2018

6616 Background: Willingness to pay (WTP) studies assess societal valuation of healthcare interventions. Prostate cancer (PC) is the most common cancer diagnosis in men. We explore factors that may bias valuation of health care benefits through contingent valuation of WTP for therapeutic innovation in metastatic castration-resistant PC. Methods: Cross-sectional study of Portuguese Society (SOC) and Healthcare Providers (HCP). Monthly WTP assessed through biding and open-ended questions by standardized survey with 2 baseline scenarios: ScA 12-month median survival, ScB 30-month median survival. Respondents considered own financial resources and expenses and for each therapeutic scenario reported WTP, out-of-pocket, and expected National Healthcare System (NHCS) WTP. Impact of demographic, personal medical history and household income assessed by tweedie generalized linear model. Results: 1000 subjects on societal cohort and 100 physicians provided valid responses. Subjects reported higher WTP values when NHCS was to provide treatment compared to out-of-pocket cost. For NHCS perspective median WTP for ScA was 2,133€ for HCP vs 5,510€ for SOC and ScB 1 963€ for HCP vs 5,479€ for SOC. Overall, societal cohort’s NHCS mean WTP was 2.6 (ScA) and 2.8 (ScB) times higher (p < .001) than healthcare providers, but with no difference for out-of-pocket WTP. This difference remained significant when adjusted for all other factors. Additionally, subjects with prior personal or familial history of cancer and subjects with higher household income provided higher WTP estimates. In HCP cohort, urologists reported higher WTP compared to Medical Oncologists. Conclusions: This study provides critical insight into differing valuation of cancer treatments between physicians and society and potential biases in individual valuation of healthcare benefits. Improvement of societal’s perception and understanding of cost-benefit assessments is critical to designing an equitable healthcare system.
Determinants of spending for metastatic breast, lung, and colorectal cancer in SEER-Medicare.
Authors: Hassett Michael J. , Banegas Matthew P. , Uno Hajime , Weng Shicheng , Cronin Angel M. , O'Keeffe-Rosetti Maureen Cecelia , Carroll Nikki , Hornbrook Mark C , Ritzwoller Debra P. 
Published: September 2018

6621 Background: A substantial proportion of cancer spending is directed towards patients with metastatic disease. Past efforts to characterize spending for metastatic cancer have been limited, because they have not included patients with recurrent disease or analyzed spending across the entire episode of care. Spending for stage IV and recurrent metastatic cancer patients may differ. Methods: Using SEER-Medicare data from 2008-13, we identified breast (BC), colorectal (CRC), and lung (LC) cancer patients who were continuously enrolled in parts A, B and D, and had either stage IV or recurrent disease (i.e., return of cancer after resection of stage I-III disease). Mean total Medicare spending/patient per month and per year (2012$US) were estimated from 12 months prior to 12 months after diagnosis, and described for relevant patient sub-groups. Results: In a cohort of 27,847 patients, total spending for stage IV vs. recurrent cancer was 61-73% lower in the year before diagnosis ($11,339 vs. $28,796 for BC; $13,359 and $49,804 for CRC; $15,118 and $49,555 for LC), and 28-88% higher in the year after diagnosis ($68,787 and $42,091 for BC; $111,304 and $58,657 for CRC; $92,181 and $72,354 for LC). When considering the 2 year-period spanning the diagnosis, spending was similar (≤14%) between groups. The primary drivers of spending differences between patients with stage IV and recurrent disease were cancer type and time from diagnosis (Table). Younger age, higher comorbidity, and SEER region were also drivers of higher spending, especially after diagnosis. Conclusions: Spending patterns differ for patients with stage IV vs. recurrent cancer, suggesting different patterns of care that warrant further investigation. Spending differences after diagnosis were driven largely by part B spending, which was due in part to differential chemotherapy use. [Table: see text]
Allogeneic hematopoietic cell transplant (alloHCT) for hematologic malignancies in human immunodeficiency virus infected (HIV) patients (pts): Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0903)/AIDS Malignancy Consortium (AMC-080) trial.
Authors: Ambinder Richard F. , Wu Juan , Logan Brent , Durand Christine , Shields Ryan , Popat Uday R. , Little Richard F. , Mcmahon Deborah , Mellors John Watson , Ayala Ernesto , Kaplan Lawrence D. , Noy Ariela , Howard Alan , Forman Stephen J. , Mendizabal Adam M , Horowitz Mary M. , Navarro Willis H. , Alvarnas Joseph C. 
Published: September 2018

7006 Background: AlloHCT has been regarded as risky in HIV pts, with concern about fatal infection. We set out to assess feasibility and safety of alloHCT in this first prospective multicenter trial. Methods: The primary endpoint was 100-day non-relapse mortality (NRM). Pts had drug-susceptible HIV; age ≥ 15 yr; adequate organ function; acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL), high risk myelodysplastic syndrome (MDS), or Hodgkin (HL) or non-Hodgkin lymphoma (NHL) beyond first CR; an 8/8 HLA-matched related or at least a 7/8 unrelated donor. Pts received myeloablative (MA) or reduced intensity (RI) regimens. HIV outgrowth assays (VOA) were performed with resting CD4+T-cells in pts who had clinically undetectable HIV plasma RNA at 1 yr. Results: Between 5/2012 and 12/2015, 17 pts underwent alloHCT. Pts were: male (17); white (11), African American (3), Other/Unknown (3); median age 47 yrs (25-64). Associated malignancies were AML (9), ALL (2), MDS (2), HL (1), NHL (3). Median CD4 was 224 (55-833). Conditioning was MA (8) and RI (9). At 100 days there was no NRM, 13 pts were in CR, 4 pts had relapsed/progressive disease; and 8 pts achieved complete chimerism. The cumulative incidence of Grades (Gr) II-IV acute Graft vs Host Disease (GvHD) was 41 % (95%CI: 18 %, 64%). At 6 mo, OS was 82 % (95% confidence interval [CI]: 55%, 94%); 9 pts achieved complete chimerism. At 1 year, OS was 57 % (CI: 31%, 77 %); 8 deaths were from relapsed/progressive disease (5), acute GvHD (1), adult respiratory distress syndrome (1) and liver failure (1). Infections were reported in 11 pts (3 Gr 2, 8 Gr 3). Infectious HIV was detected by VOA in 2 of 3 pts who were mixed chimeras but 0 of 2 who were 100% donor. Median follow up of survivors is 24 mo (7 to 27 ). Conclusions: HIV pts with heme malignancies underwent MA or RI alloHCT without any100-day NRM and there were no infectious deaths at 1 year. AlloHCT should be considered the standard of care for HIV pts who meet usual eligibility criteria. Clinical trial information: NCT01410344.
Updated results from phase II study of guadecitabine for patients with higher risk myelodysplastic syndromes or chronic myelomonocytic leukemia.
Authors: Montalban-Bravo Guillermo , Bose Prithviraj , Alvarado Yesid , Daver Naval Guastad , Ravandi Farhad , Borthakur Gautam , Takahashi Koichi , Andreeff Michael , Cortes Jorge E. , Dinardo Courtney Denton , Jabbour Elias , Kadia Tapan M. , Kornblau Steven , Ohanian Maro , Huang Xuelin , Nogueras-Gonzalez Graciela M. , Bodden Kristy , Pierce Sherry , Kantarjian Hagop M. , Garcia-Manero Guillermo 
Published: September 2018

7020 Background: Improving the current response and survival outcomes of patients with higher risk MDS and CMML is fundamental. Guadecitabine is a next generation hypomethylating agent with increased length of exposure compared to decitabine and clinical activity in patients with MDS. Methods: Single arm phase 2 clinical trial of guadecitabine at a dose of 60mg/m2 sc daily for 5 days (days 1-5) every 28 days for patients with newly diagnosed MDS or CMML classified as Intermediate-2 or High risk by IPSS. Primary endpoint is complete response (CR). Responses were evaluated following the revised 2006 International Working Group criteria. Sequencing data was obtained at the time of pre-treatment evaluation by the use of a 28-gene next generation sequencing platform. Study included stopping rules for response and toxicity. Overall survival (OS) was censored at the time of transplant. Results: A total of 53 patients have been enrolled: 50 (94%) are evaluable for toxicity and 44 (83%) for response. Median age is 67 years (49-87). A total of 43 (86%) patients have MDS and 7 (14%) have CMML. A total of 21 (42%) have complex karyotype. Sequencing data was available in 48 (96%) patients with TP53 mutations being the most frequently detected in 36% patients. After a median of 6 treatment cycles (1-20), the ORR is 71% including 32% CR. Median best response occurred by 3 cycles (1-6). Seven (21%) out of 33 evaluable patients achieved a complete cytogenetic response. Ten (20%) subjects proceed to allogeneic stem cell transplantation. Median follow up was 6.3 months (0-23). Median OS is 14.1 months (CI 13.3-14.9 months) and median EFS is 8.4 months (CI 5.6-11.2 months). Forty-five (90%) patients experienced at least one AE during therapy. Most common grade 1-2 AEs included fatigue (66%), nausea (38%) and dyspnea (26%). Dose reductions due to cytopenias were required in 17 (34%) patients. Early 8-week mortality occurred in 3 (6%) patients. Conclusions: Guadecitabine is well-tolerated and active in patients with higher-risk MDS and CMML even in the presence of adverse biological features such as high frequency of complex karyotype, therapy related disease and TP53 mutations. Clinical trial information: NCT02131597.
Genomic landscape of adult mixed phenotype acute leukemia (MPAL).
Authors: Morita Kiyomi , Wang Feng , Patel Keyur , Bueso-Ramos Carlos E. , Abou Zahr Abdallah , Gumbs Curtis , Zhang Jianhua , Song Xingzhi , Mendoza Marisela , Wu Chang-jiun , Kornblau Steven , Dinardo Courtney Denton , Ravandi Farhad , Garcia-Manero Guillermo , Jabbour Elias , Andreeff Michael , Kantarjian Hagop M. , Konopleva Marina , Futreal Andrew , Takahashi Koichi 
Published: September 2018

7023 Background: MPAL is a rare subgroup of acute leukemia characterized by both myeloid and lymphoid phenotypes. Genetic basis of MPAL is not well understood. Methods: We studied 31 patients (pts) with MPAL (median age 53) that met 2008 WHO criteria. Bone marrow samples were studied by targeted capture sequencing of 295 genes (median 393x), RNA sequencing, and Infinium methylation EPIC array (Illumina). Mutational landscape was compared to 194 AML, 71 B-ALL, and 6 T-ALL cases. Promoter methylation pattern was compared to the data from 194 AML (TCGA), 505 B-ALL and 101 T-ALL cases (Nordlund et al. Genome Biology. 2013). Results: Eighteen (58%) pts had myeloid-T and 13 (42%) had myeloid-B phenotype. Four pts had t(9;22), 1 had 11q23 rarrangement, and 8 had complex karyotype. MPAL had similar number of mutations with AML but had higher number of mutations than B-ALL or T-ALL. Both AML-type and ALL-type mutations were detected in MPAL, supporting the mixed phenotypic features. However, NPM1, CEBPA and GATA2 mutations were specific to AML and were not found in MPAL. Myeloid-T and myeloid-B showed distinct patterns of mutations, in which DNMT3A, IDH2, NOTCH1, IL7R, and FBXW7 mutations were enriched in myeloid-T whereas RUNX1 mutations were enriched in myeloid-B. Myeloid-T and myeloid-B also showed distinct patterns of promoter methylation. Overall, myeloid-T had more hypermethylated CpG loci than myeloid-B. Genes that have essential role in T-cell receptor (TCR) pathway ( CD3D, CD7, CD247, LCK, PRKCQ, CCR9, and TCL1A) were differentially methylated and differentially expressed between myeloid-T and myeloid-B. RNA sequencing revealed several known translocations such as, NSD1-NUP98, and KMT2A-MLLT4, in addition to the novel fusion proteins such as FOXP1-DNAJC15, RUNX1-NAP1L1, and BCL2-TM9SF3. Unbiased hierarchical clustering of MPAL, AML, B-ALL and T-ALL by promoter methylation revealed that myeloid-T had consistent similarity with T-ALL, while myeloid-B showed random similarity with either B-ALL or AML. Conclusions: MPAL is genetically heterogeneous and myeloid-T and myeloid-B shows distinct patterns of mutations, methylation and gene expressions. Therapy for MPAL may need to be tailored based on the genetic profiles.
Baseline and early post-treatment clinical and laboratory factors associated with severe neurotoxicity following 19-28z CAR T cells in adult patients with relapsed B-ALL.
Authors: Park Jae Hong , Santomasso Bianca , Riviere Isabelle , Senechal Brigitte , Wang Xiuyan , Purdon Terence , Wang Yongzeng , Halton Elizabeth , Diamonte Claudia , Li Daniel , Sadelain Michel , Brentjens Renier J. 
Published: September 2018

7024 Background: CD19-specific chimeric antigen receptor (CAR) modified T cells produce high anti-tumor activity in relapsed or refractory (R/R) ALL, but can be associated with cytokine release syndrome (CRS) and neurotoxicity (NTX). Herein, we report baseline and post-treatment clinical and laboratory factors associated with severe NTX (≥Grade 3) in our phase I clinical trial of CD19-specific 19-28z CAR T cells for adult patients (pts) with R/R B-ALL (NCT01044069). Methods: 51 adult pts with R/R B-ALL were treated with 19-28z CAR T cells following conditioning chemotherapy at MSKCC. In order to identify clinical and serum biomarkers associated with severe NTX (sNTX), we examined demographic, treatment, and clinical blood parameters as well as in vivo CAR T expansion and serum cytokines, and performed univariate and multivariate analysis. Results: In this cohort of ALL pts, 20, 8, 2, 18 and 3 pts experienced Gr 0, 1, 2, 3, and 4 NTX, respectively. No pt developed grade 5 NTX. Disease burden (≥50% blasts) at the time of T cell infusion (p = 0.0045) and post-treatment ≥Gr3 CRS (p = 0.0010) were significantly associated with sNTX, but we found no association with age, weight, T cell dose, choice of conditioning chemotherapy (Flu/Cy s. Cy), and prior lines of treatment. Among the clinical and blood parameters, fever, low PLT, high ferritin and MCHC as well as elevated GM-CSF, IFNγ, IL-15, IL-5, IL-10, IL-2 at day 3 of T cell infusion at day 3 of T cell infusion were significantly associated with sNTX (all p < 0.01). While some of these cytokines were also elevated in severe CRS cases, IL-5 and IL-2 at day 3 were unique to sNTX. Furthermore, in vivo peak CAR T expansion at day 7 (p = 0.0001) significantly correlated with sNTX (p < 0.01). Lastly, multivariate analysis revealed baseline PLT < 60 or MCHC > 33.2% and morphologic disease ( > 5% blasts) has 95% sensitivity and 70% specificity of identifying sNTX pts. Conclusions: These data provide a characterization of early clinical and serum biomarkers of sNTX in adult pts receiving 19-28z CAR T cells and should help identify appropriate pts for early intervention strategy to mitigate NTX. Clinical trial information: NCT01044069.
Inotuzumab ozogamicin (IO) combined with mini-hyper-CVD as salvage therapy for patients (pts) with R/R acute lymphoblastic leukemia (ALL).
Authors: Assi Rita , Kantarjian Hagop M. , Ravandi Farhad , O'Brien Susan Mary , Kebriaei Partow , Thomas Deborah A. , Garcia-Manero Guillermo , Khouri Issa F. , Champlin Richard E. , Kadia Tapan M. , Cortes Jorge E. , Jain Nitin , Konopleva Marina , Khouri Rita , Estrov Zeev , Takahashi Koichi , Sasaki Koji , Jacob Jovitta , Garris Rebecca , Jabbour Elias 
Published: September 2018

7025 Background: Outcome of pts with R/R ALL is poor. IO, a CD22 monoclonal antibody bound to a toxin, calicheamicin, has single-agent activity in R/R ALL with response rate of 80% and median survival of 7.7 months. Adding IO to low-intensity chemotherapy might further improve clinical outcomes. Methods: Pts ≥18 years with R/R ALL were eligible. Chemotherapy was of lower intensity than standard hyper-CVAD and referred to as mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction (DR), no anthracycline, methotrexate at 75% DR, cytarabine at 0.5 g/m2 x 4 doses). Rituximab (if CD20+ blasts) and intrathecal chemotherapy were given for first 4 courses. IO was given on day 3 of each of the first 4 courses at a dose of 1.8 mg/m2 for cycle 1 then 1.3 mg/m2 for subsequent cycles. After the occurrence of veno-occlusive disease (VOD), IO was modified to 1.3 mg/m2 for cycle 1 followed by 1.0 mg/m2 for subsequent cycles. Results: Sixty pts with a median age of 35 years (range 18-87) were treated. Overall, 47 pts (80%) responded, 32 of them (54%) achieving complete response. The overall minimal residual disease negativity rate among responders was 82%. Grade 3-4 toxicities included prolonged thrombocytopenia (79%), infections during induction and consolidations (52%, and 73% respectively), and hyperbilirubinemia (13%). VOD of any grade occurred in 9 patients (15%). At a median follow-up of 19 months, the median relapse-free survival (RFS) and overall survival (OS) were 9 and 11 months, respectively. The 2-year RFS and OS rates were 33% and 38%. The 2-year OS rates for patients treated in salvage (S)1, S2, and S3 and beyond were 53%, 0%, and 34%, respectively (p = 0.005). When compared to IO monotherapy in a similar pts population, a significant improvement in OS was observed (11 and 6 months, respectively; p = 0.003). Conclusions: The combination of IO with low-intensity mini-hyper-CVD chemotherapy is effective in pts with R/R ALL. Results are encouraging and appear superior to those obtained with IO alone, particularly in pts treated in S1. The risk of VOD should be considered carefully for transplant candidates and pts with previous liver damage. Lower dose of weekly schedules of IO are being explored Clinical trial information: NCT01371630.