tbuckley/cabot-search huggingface dataset:
Association of Income Inequality With Pediatric Hospitalizations for Ambulatory Care–Sensitive Conditions
Authors: Jessica L. Bettenhausen, Jeffrey D. Colvin, Jay G. Berry, Henry T. Puls, Jessica L. Markham, Laura M. Plencner, Molly K. Krager, Matthew B. Johnson, Mary Ann Queen, Jacqueline M. Walker, Grant M. Latta, Robert R. Riss, Matt Hall
Journal: JAMA Pediatrics (2017)

<h3>Importance</h3> The level of income inequality (ie, the variation in median household income among households within a geographic area), in addition to family-level income, is associated with worsened health outcomes in children. <h3>Objective</h3> To determine the influence of income inequality on pediatric hospitalization rates for ambulatory care–sensitive conditions (ACSCs) and whether income inequality affects use of resources per hospitalization for ACSCs. <h3>Design, Setting, and Participants</h3> This retrospective, cross-sectional analysis used the 2014 State Inpatient Databases of the Healthcare Cost and Utilization Project of 14 states to evaluate all hospital discharges for patients aged 0 to 17 years (hereafter referred to as children) from January 1 through December 31, 2014. <h3>Exposures</h3> Using the 2014 American Community Survey (US Census), income inequality (Gini index; range, 0 [perfect equality] to 1.00 [perfect inequality]), median household income, and total population of children aged 0 to 17 years for each zip code in the 14 states were measured. The Gini index for zip codes was divided into quartiles for low, low-middle, high-middle, and high income inequality. <h3>Main Outcomes and Measures</h3> Rate, length of stay, and charges for pediatric hospitalizations for ACSCs. <h3>Results</h3> A total of 79 275 hospitalizations for ACSCs occurred among the 21 737 661 children living in the 8375 zip codes in the 14 included states. After adjustment for median household income and state of residence, ACSC hospitalization rates per 10 000 children increased significantly as income inequality increased from low (27.2; 95% CI, 26.5-27.9) to low-middle (27.9; 95% CI, 27.4-28.5), high-middle (29.2; 95% CI, 28.6-29.7), and high (31.8; 95% CI, 31.2-32.3) categories (<i>P</i> &lt; .001). A significant, clinically unimportant longer length of stay was found for high inequality (2.5 days; 95% CI, 2.4-2.5 days) compared with low inequality (2.4 days; 95% CI, 2.4-2.5 days;<i>P</i> &lt; .001) zip codes and between charges ($765 difference among groups;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Children living in areas of high income inequality have higher rates of hospitalizations for ACSCs. Consideration of income inequality, in addition to income level, may provide a better understanding of the complex relationship between socioeconomic status and pediatric health outcomes for ACSCs. Efforts aimed at reducing rates of hospitalizations for ACSCs should consider focusing on areas with high income inequality.
SU011248, a novel tyrosine kinase inhibitor, shows antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma: Results of a phase 2 trial
Authors: R. J. Motzer, B. I. Rini, M. D. Michaelson, B. G. Redman, G. R. Hudes, G. Wilding, R. A. Figlin, J. Zhu, S. T. Kim, C. Baum
Journal: Journal of Clinical Oncology (2004)

4500 Background: SU011248 is an oral multi-targeted tyrosine kinase inhibitor with anti-tumor and anti-angiogenic activity through inhibition of PDGFR, VEGFR, KIT and FLT3. Methods: 63 patients with metastatic renal cell carcinoma (RCC) were treated with repeat cycles of SU011248 orally at 50 mg daily for 4 weeks followed by a 2-week rest period. Eligibility included measurable disease, ECOG performance status of 0 or 1, failure of one prior cytokine-based therapy, and adequate cardiac function. Results: The median age of patients was 60 years and 58 patients (92%) had prior nephrectomy. Best response to SU011248 as assessed by RECIST: Of 15 (24%) patients who achieved a PR, 1 patient progressed at 5 months and 14 remain progression-free with median duration of response of 6+ months. Of 29 patients with best response of SD, 5 (8%) patients had reduction of unidimensional measurement of at least 30% and await confirmation of response status. Currently there are 32 patients on treatment with continued PR/SD with median follow-up of 6+ months. Safety data on 63 patients indicates an acceptable toxicity profile with mostly grade 1/2 events including fatigue/asthenia (78%), nausea (56%), diarrhea (51%), and stomatitis (44%). Grade 3/4 toxicities include lymphopenia (30%), elevated lipase (21%) and amylase (8%) without clinical signs of pancreatitis, and fatigue/asthenia (8%). Two patients were taken off the study for decreases in left ventricular ejection fraction > 20% without clinical symptoms. Conclusions: SU011248 administered in repeat cycles of 50 mg daily for 4 weeks followed by a 2-week rest period exhibits promising antitumor activity as second-line therapy for patients with metastatic RCC. Additional studies are planned to further assess the role of SU011248 in the treatment of metastatic RCC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, Inc. Pfizer, Inc. Pfizer, Inc. Pfizer, Inc. Pfizer, Inc.
Fludarabine, cytarabine, and mitoxantrone (FLAM) for the treatment of relapsed and refractory acute lymphoblastic leukemia in adults. A phase II study by the Polish Adult Leukemia Group (PALG)
Authors: S. Giebel, M. Krawczyk-Kulis, B. Jakubas, M. Adamczyk-Cioch, G. Palynyczko, J. Holowiecki
Journal: Journal of Clinical Oncology (2004)

6723 Background: Outcome of adult ALL patients who fail to achieve CR or who relapse soon after initial response is poor. The goal of this phase II study by the Polish Adult Leukemia Group (PALG) was to evaluate safety and efficacy of a new FLAM regimen in this group of patients. Methods: The treatment consisted of fludarabine 2x30 mg/m2 iv on d. 1, 2, 8, 9 + AraC 8x100 mg/m2 iv on d. 1, 2, 8, 9 + mitoxantrone 10 mg/m2 on d. 3, 10. Thirty-five pts were included with primary (n=10) or secondary (n=2) refractoriness, early (before 6 months) 1st relapse (n=11), 1st relapse after HSCT regardless CR duration (n=8), 2nd or subsequent relapse (n=3), and 2nd lymphoblast crisis in course of CML (n=1). Median age was 32 (19–60) y, gender: m/f –49%/51%. 43% of pts were bcr/abl –positive. Results: 51% of patients responded to FLAM, including CR –17/34 (primary resistance 6/10, resistant relapse 1/2, untreated relapse 10/21) and return to chronic phase after CML blast crisis –1/1. Among those who failed to respond, 6 pts died in aplasia (bacterial sepsis –4, cerebral bleeding –1, cardiotoxicity –1) and 11 pts had leukemia regrowth after the transient cytopenia. Five out of 6 patients who died of severe adverse events were over >45 years old. All patients but one experienced grade IV neutropenia and thrombocytopenia. Median time to ANC >0.5 G/L and PLT >50 G/L recovery was 26 (0–36) d. and 29 (13–43) d., respectively. Non-hematological grade III-IV toxicity was as follows: infections –62%, vomiting –18%, bleeding –6%, cardiotoxicity –6%, hepatotoxicity –3%, and constipation –3%. Patients required 5 (0–12) RBC and 5 (0–16) PLT transfusions. 69% of pts received G-CSF for 11 (3–25) d. Median duration of iv. antibiotics was 27 (8–41) d. Patients stayed in hospital for a median of 32 (12–46) d. Conclusions: Our results indicate that FLAM regimen has a potent anti-leukemic activity and let achieve CR in approximately half of poor-prognosis resistant and relapsed adult ALL. Because of prolonged cytopenia, this therapy should be considered with caution for patients aged >45 years. No significant financial relationships to disclose.
Images in Endocrine Pathology: Unique Composite Adrenal Adenomatoid Tumor, Ganglioneuroma, Myelolipoma, and Cortical Nodular Hyperplasia
Authors: Eleonora Duregon, Marco Volante, Stefano Guzzetti, Ida Rapa, Simona Vatrano, Mauro Papotti
Journal: Endocrine Pathology (2017)
The use of real-world data to examine comparative effectiveness research (CER) and treatment patterns in HER2-negative and triple-negative metastatic breast cancer (MBC): A systematic literature review.
Authors: Monika Parisi, Corey Pelletier, Dasha Cherepanov, Michael S Broder, Nadia Noormohamed
Journal: Journal of Clinical Oncology (2017)

210 Background: With the accumulation of RWD in healthcare, CER continues to expand. RWD are becoming increasingly relevant in oncology, particularly since the onset of care pathways and CMS’ Oncology Care Model pilot program; yet, CER in oncology presents several challenges as disease biology differs by cancer type and many RWD sources do not capture clinical response, progression or survival. This review examined common endpoints reported in RWD studies on CER and TxP in MBC, focusing on HER2-negative and Triple Negative (TN) MBC. Methods: PubMed (2006-January 2016) and 4 conferences (2011-January 2016)—ASCO and SABC meetings/symposiums—were searched using MeSH/keywords, e.g., metastatic breast cancer, treatment, and comparative effectiveness. RWD CER and TxP studies in U.S. patients with HER2-negative or TNMBC were included; clinical trials were excluded. Results: Of1,782 total records, 17 articles and 9 conference abstracts were included. Studies using RWD increased over time with 2 studies published in 2010, 1 in 2012, 6 in 2013, 6 in 2014, 10 in 2015, and 1 as of January 2016. Of these, 8 were CER and 18 examined TxP. Most studies were retrospective chart reviews (7 CER; 10 TxP studies), others were retrospective secondary database analyses (1 CER; 6 TxP) and physician surveys (2 TxP). RWD sources included commercial insurance claims, SEER-Medicare, and California Cancer Registry data. Nineteen studies reported results in patients with HER2-negative MBC and 7 reported in TNMBC patients. Primary endpoints included overall survival (OS), progression-free survival (PFS), and treatment duration (TD). CER studies most commonly reported TD and survival outcomes (e.g., OS, PFS), each reported in 75% of the studies. TxP studies also most commonly examined survival outcomes (61% of studies), in addition to various treatment patterns and duration outcomes. Conclusions: This literature review indicates that in parallel to the availability of RWD, published CER studies and analysis of treatment patterns have grown in the last 5 years. The most commonly reported outcomes include OS, TD and PFS.
Effect of <i>ABCG2</i> genotype and mRNA expression on the bioavailability of topotecan
Authors: H. Gelderblom, W. J. Loos, T. M. Sissung, H. Burger, K. Nooter, O. Soepenberg, J. W. R. Nortier, J. Verweij, W. D. Figg, A. Sparreboom
Journal: Journal of Clinical Oncology (2004)

2015 Background: The ATP-binding cassette transporter ABCG2 (breast cancer resistance protein; BCRP) functions as an efflux transporter for many drugs and is expressed at high levels in the human small intestine. It has been demonstrated that some individuals possess a nonsynonymous single-nucleotide polymorphism at nucleotide 421, substituting lysine for glutamine on position 141 at exon 5, and express low amounts of ABCG2. Methods: In this prospective exploratory study, duodenal biopsies were obtained before oral administration of topotecan on day 1 (dose, 2.3 mg/m2) and i.v. infusion on day 2 (dose, 1.5 mg/m2) in 18 adult Caucasian cancer patients (10 female/8 male; median age, 54 years). Pharmacokinetic data were obtained on days 1 and 2. Topotecan concentrations in plasma were determined by liquid chromatography with fluorescence detection, and analyzed by noncompartmental methods. Enterocyte (villin)-corrected mRNA expression levels of ABCG2 and ABCB1 (P-glycoprotein) were measured by real-time TaqMan analysis, and all patients were genotyped by cycle sequencing for ABCG2 421C>A. Results: Complete topotecan pharmacokinetic data were available for 13 patients. The mean (± SD) area under the curves after oral and i.v. administration were 109 ± 35.7 ng×h/mL and 218 ± 62.3 ng×h/mL, respectively. Substantial intra- and interindividual variation in mRNA expression of ABCG2 and ABCB1 was observed in the intestinal samples (N = 12). Two patients were heterozygous variant for ABCG2421C>A (14%; allele frequency, 7.14%), and 12 patients carried the wild-type sequence; 4 samples showed no amplification. The heterozygous CA allele was associated with a 1.3-fold increased oral bioavailability of topotecan [31.4% (wild-type, N = 10) versus 42.0% (heterozygous, N = 2); P = 0.037]. The lowest combined mRNA expression of ABCG2 and ABCB1 was observed in one of the patients that was heterozygous variant for ABCG2 421C>A. Conclusions: This pilot study indicates that ABCG2 genotype is correlated with altered topotecan pharmacokin-etics. The current observation warrants confirmation and further investigation in a larger patient population involving different ethnic groups. No significant financial relationships to disclose.
Unique DNA methylation signature in HPV-positive head and neck squamous cell carcinomas
Authors: Davide Degli Esposti, Athena Sklias, Sheila C. Lima, Stéphanie Beghelli-de la Forest Divonne, Vincent Cahais, Nora Fernandez-Jimenez, Marie-Pierre Cros, Szilvia Ecsedi, Cyrille Cuenin, Liacine Bouaoun, Graham Byrnes, Rosita Accardi, Anne Sudaka, Valérie Giordanengo, Hector Hernandez-Vargas, Luis Felipe Ribeiro Pinto, Ellen Van Obberghen-Schilling, Zdenko Herceg
Journal: Genome Medicine (2017)

Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of cancers for which human papilloma virus (HPV) infection is an emerging risk factor. Previous studies showed promoter hypermethylation in HPV(+) oropharyngeal cancers, but only few consistent target genes have been so far described, and the evidence of a functional impact on gene expression is still limited. We performed global and stratified pooled analyses of epigenome-wide data in HNSCCs based on the Illumina HumanMethylation450 bead-array data in order to identify tissue-specific components and common viral epigenetic targets in HPV-associated tumours. We identified novel differentially methylated CpGs and regions associated with viral infection that are independent of the anatomic site. In particular, most hypomethylated regions were characterized by a marked loss of CpG island boundaries, which showed significant correlations with expression of neighbouring genes. Moreover, a subset of only five CpGs in a few hypomethylated regions predicted HPV status with a high level of specificity in different cohorts. Finally, this signature was a better predictor of survival compared with HPV status determined by viral gene expression by RNA sequencing in The Cancer Genome Atlas cohort. We identified a novel epigenetic signature of HPV infection in HNSCCs which is independent of the anatomic site, is functionally correlated with gene expression and may be leveraged for improved stratification of prognosis in HNSCCs.
INTEGRATE: A randomized, phase II, double-blind, placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC): A study by the Australasian Gastrointestinal Trials Group (AGITG)—Final overall and subgroup results.
Authors: Nick Pavlakis, Katrin Marie Sjoquist, Eric Tsobanis, Andrew James Martin, Yoon-Koo Kang, Yung-Jue Bang, Christopher J. O'Callaghan, Niall C. Tebbutt, Sun Young Rha, Jeeyun Lee, Jae Yong Cho, Lara Rachel Lipton, Margot J. Burnell, Thierry Alcindor, Andrew Strickland, Jin Won Kim, Sonia Yip, John Simes, John Raymond Zalcberg, David Goldstein
Journal: Journal of Clinical Oncology (2015)

4003 Background: REG is an oral multi-kinase inhibitor warranting evaluation in AOGC following failure of 1st or 2nd line chemotherapy (CT) where few options exist. Methods: International (Australia & New Zealand (ANZ), Korea, Canada (NCIC CTG)) phase II RCT with 2:1 randomization to 160 mg REG or matched Placebo (PBO) on days (D) 1-21 each 28 D cycle until disease progression (PD) or prohibitive adverse events. Primary endpoint: progression free survival (PFS). Final analysis used data to December 31, 2014. Results: 152 patients (pts) enrolled (November 2012 to February 2014) yielding 147 pts evaluable for analysis (97 REG and 50 PBO). M:F (118:29); primary site: OGJ (56), stomach (85); lines of prior CT: 1 (62), 2 (85); ECOG PS 0 (62): 1 (85). Median (med.) treatment wks: 8 (REG) v 4 (PBO). Med. REG dose intensity: 150 mg (130 mg Korea and 160mg ANZ/Can). 27 PBO pts received REG following PD. REG Med. PFS 11.1 wks (95% CI: 7.7 – 13.3) v PBO 3.9 wks (3.7 - 4.0), HR 0.40, p < 0.0001. Med. REG OS 25 wks (95% CI: 18.9-29.6) v PBO 19.4 wks (95% CI: 14.9 – 22.7), HR 0.74, p = 0.11. Pre-specified analyses found REG effect greater in Korea than ANZ/Can (HR 0.12 v 0.61, p = 0.0009) but consistent across age, NLR, primary site, lines of CT, peritoneal metastases (mets) presence, number of met. sites, and VEGF-A (Table). Results comparable for ITT population (n = 152). REG was well tolerated, with expected spectrum of toxicities. Conclusions: REG was highly effective in prolonging PFS across a broad range of pts, with a non-significant positive OS trend. Regional differences were found in the magnitude of effect but REG was effective in all regions and subgroups. A phase III trial is merited. Clinical trial information: 12612000239864. Key sub-groups PFS HR (95% CI) P value Interaction p Value Korea (n = 54) ANZ/Canada (n = 93) 0.12 (0.06 – 0.27) 0.61 (0.39 – 0.97) < 0.0001 0.03 0.0009 Lines of prior therapy 1 (n = 62) 2 (n = 85) 0.49 (0.28 – 0.86) 0.32 (0.19 – 0.55) 0.01 < 0.001 0.50 Neutrophil-lymphocyte ratio (NLR) <3 (n = 71) ≥ 3 (n = 76) 0.41 (0.23 – 0.70) 0.37 (0.22 – 0.64) 0.0007 0.0001 0.72 Plasma VEGF-A (pg/ml) Low (≤ 0.14), (n = 82) High (> 0.14), (n = 62) 0.39 (0.24 – 0.65) 0.42 (0.23 – 0.78) 0.0001 0.003 0.72
Bendamustine in combination with thalidomide and prednisolone (BPT) in patients with refractory or relapsed multiple myeloma: Results of a phase I clinical trial
Authors: W. Poenisch, M. Rozanski, F. Hoffmann, T. Boldt, A. Schwarzer, U. Ruffert, R. Rohrberg, U. Kreibich, D. Niederwieser
Journal: Journal of Clinical Oncology (2006)

7620 Background: Thalidomide is an active single agent in advanced relapsed or refractory multiple myeloma (MM). Combination of low dose thalidomide with bendamustine and prednisolone might be a way to maintain efficacy of the drug without dose limiting toxicity (DLT). Methods: The treatment consists of a fixed dose of bendamustine (60mg/qm) day 1, 8, and 15 and prednisolone (100 mg) day 1, 8, 15, and 22. At the same time, thalidomide was given in patients cohorts with escalating doses, starting with 50 mg to a maximum of 200 mg daily. 8 patients (4 after conventional chemotherapy and 4 after APBSCT) were enrolled at each dose level. Cycles were repeated every 28 days for a minimum of 2 and a maximum of 10 cycles until a maximal response was achieved, a DLT or a disease progression were observed. 23 patients ( 8 in the first dose level with 50 mg thalidomide, 8 in the second dose level with 100 mg and 7 patients in the third dose level with 200 mg) are enrolled until now. The number of prior treatment regimens was 2 or more in all patients. 6 patients were refractory for the last treatment. Median age was 67 years (range: 40 - 78). Results: All patients completed 2 cycles of BPT-treatment and were hence evaluable. Response was assessed using EBMT criteria modified to include near complete remission (nCR) and very good partial remission (VGPR). 20 of 23 patients responded after at least 2 cycles of chemotherapy with 3 CR, 5 VGPR, 11 PR and 2 MR. 2 patients had stable disease. With a median follow up of ten months, EFS and OS at twelfe months were 36 % and 85 %, respectively. Most common site effects were constipation (10 patients WHO grade 1, 8 patients WHO grade 2), polyneuropathy (14 patients WHO grade 1, 2 patients WHO grade 2) and somnolence (4 patients WHO grade 1). None of the 23 patients developed dose-limiting hematoxicity as defined by an ANC &lt; 1,0 Gpt/l for &gt; 7 days or an ANC &lt; 0,5 Gpt/l for &gt; 3 days or platelet count &lt; 25 Gpt/l. Short neutropenia was reported in 8 patients (WHO grade 3 and 4) but no thrombocytopenia was observed. Conclusions: BPT with a dose between 50 and 200 mg thalidomide daily is well tolerated in patients with relapsed or refractory MM. No significant financial relationships to disclose.
Phase II trial of preoperative radiotherapy (RT) and panitumumab (PAN) in KRAS wild type (wt) rectal cancer (RC).
Authors: Feby Ingriani Mardjuadi, Jean-Luc Canon, Jean-Charles Coche, Anne Jouret-Mourin, Christine Sempoux, Jean-Charles Goeminne, Thierry Delaunoit, Javier Carrasco, Peter Vuylsteke, Yves Humblet, Nicolas Meert, Marc Van den Eynde, Anne Moxhon, Jean-Pascal H. Machiels
Journal: Journal of Clinical Oncology (2012)

e14060 Background: The addition of anti Epidermal Growth Factor Receptor (EGFR) monoclonal antibodies (mabs) to preoperative chemoradiation in RC has produced low pathological complete response (pCR) rate. The postulated reasons for the poor outcome are: lack of patient selection, suboptimal treatment sequencing, and potential negative interaction between anti EGFR mabs and chemotherapy (CT) when used concurrently as radiosensitizers. Given these issues, we conducted a phase II trial of PAN in combination with preoperative RT in Kras wt RC. Methods: We studied several treatment sequences in murine models of Kras wt human colorectal cancer. Next, we used our preclinical results to design the treatment schedule of the phase II trial. PAN (6mg/kg/q2w) was combined with RT (45 Gy) to treat T3-4, Kras wt RC. Surgery was done 6-8 weeks after the end of RT. The primary endpoint, the pCR rate on surgical specimen, was assessed centrally (Simon: H0=5%, H1=17%, α=0.05, β=0.2). Results: In our murine models, the addition of anti EGFR mabs to RT significantly improved response when anti EGFR mabs were started during RT and extended after the end of RT (p&lt;0.05). No benefit was found when anti EGFR mabs were given before the start of RT. In the phase II trial, we therefore started RT on day 1 and introduced PAN 7 days later (day 8). After RT ended (day 36), PAN treatment was continued to day 50. To fully explore PAN’s potential as radiosensitizer, CT was not given during RT but postoperatively. 19 patients were evaluable for pCR. 47% of tumours were cT3N+. Hypomagnesemia (16%) and hypophosphatemia (16%) were most common grade ≥3 toxicities. As no pCR was found, the study was closed prematurely for lack of efficacy according to the statistical rule. 7 patients (41%) had &gt;50% pathological tumour regression (grade 3 Dworak) and 12 (70%) showed &gt;2mm of tumour-free circumferential resection margin. Conclusions: Preclinical data confirm the need of optimal treatment sequencing to potentiate synergism between anti EGFR mabs and RT. However, the pCR rate in our phase II trial remains low despite adequate patient selection and optimized study design. Thus, we do not recommend the concurrent use of anti EGFR mabs and RT in the neoadjuvant treatment of RC.