tbuckley/cabot-search huggingface dataset:
Cancer stage at diagnosis, treatment, and survival among US- and foreign-born Asians and Pacific Islanders with gastric cancer
Authors: S. DaCosta Byfield, C. C. Earle, D. Li, J. Z. Ayanian, E. P. McCarthy
Journal: Journal of Clinical Oncology (2007)

15018 Background: Asians and Pacific Islanders (APIs) have increased risk of developing gastric cancer, but whether cancer treatments and outcomes vary by birthplace is unknown. We examined the association between birthplace and cancer stage at diagnosis, treatment, and survival comparing API and non-Hispanic white (NHW) patients. Methods: We studied 6840 NHW and 4485 API patients diagnosed with gastric cancer from the Surveillance, Epidemiology and End Results Program between 1992 and 2003. We used bivariable analyses to compare stage, receipt of adequate lymph node assessment and surgery across groups: US-born APIs, foreign-born (FB) APIs and NHWs. We used multivariable polychotomous logistic and proportional hazards regression models to determine differences between US-born and FB APIs compared to NHWs in cancer stage and survival, respectively. Models included age, marital status, tumor grade, location, and stage (survival only). Results: Of API patients, 29% were US-born, 49% FB and 22% of unknown birthplace. APIs were more likely than NHWs to present with earlier-stage diagnoses and receive surgery and adequate lymph node assessment (p&lt;0. 001). After adjustment, US-born [aOR=0.86 (0.75–0.93)] and FB APIs [aOR=0.76 (0.68–0.84)] were less likely to present at later stages than NHWs. Among APIs, FB patients had fewer lymph node assessed than US-born (p&lt;0.001), but were as likely to present with earlier stage disease and receive surgery. After adjustment, US-born [aHR= 0.90 (0.85–0.98)] and FB APIs [(aHR= 0.85 (0.78–0.92)] had higher survival rates than NHWs. Results were similar after adjusting for treatment. *p &lt;0.001 for comparison with NHW + p&gt;0.05 for comparison among API Conclusions: Compared to US-born APIs, FB API patients with gastric cancer present at later stages and are less likely to receive adequate surgical lymph node assessment. However, both US-born and FB API patients present at earlier stages and experience better survival than non-Hispanic white patients. [Table: see text] No significant financial relationships to disclose.
Interim analysis of phase I trial of 17-DMAG
Authors: E. P. Cartwright, S. Kummar, C. A. Muir, P. Ivy, B. A. Conley, C. D. Scripture, W. D. Figg, A. J. Murgo, J. H. Doroshow, M. E. Gutierrez
Journal: Journal of Clinical Oncology (2006)

13148 Background: 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (17-DMAG) binds specifically to heat-shock protein 90, leading to degradation of oncogene client proteins, inhibiting tumor growth. Based on in vitro/in vivo data, 17-DMAG has potent antitumor activity. Methods: 17-DMAG was administered by 1–2 hour infusion twice weekly for 4 weeks/cycle. Eligibility criteria included: solid tumor or lymphoma, ECOG ≤ 2 and adequate organ function. Exclusion criteria: brain metastases, pregnancy, prolonged QTc, or uncontrolled illness. Accelerated titration escalation design, one patient/cohort enters until a single patient experiences dose-limiting toxicity (DLT) or two patients exhibit grade ≥ 2 (G2) toxicity (except nausea / vomiting) during the first cycle. The maximum tolerable dose (MTD) is the dose level at which no more than 1/6 patients experience DLT and the dose below that at which at least 2/6 patients have DLT. Primary objectives: to determine the toxicity profile, and MTD of twice weekly 17-DMAG. Secondary endpoints: pharmacokinetics (PK) and pharmacodynamics of 17-DMAG. PK were determined by LC-MS on blood samples collected before and serially up to 48 hours after 17-DMAG infusion. Results: 6 patients (one patient per dose level) with the following diagnoses were accrued and treated: renal cell, pancreatic, medullary thyroid, NSCLC, and two colorectal cancers. The DLT and MTD have not yet been achieved. 17-DMAG toxicities have been acceptable, nausea/vomiting being the most common toxicity observed. Three patients developed G1 nausea, one patient had G3 nausea. Two patients had G2 vomiting. Other G1 toxicities included: diarrhea, weight loss, fatigue, elevated transaminases, hair loss, and leukocytopenia. PK results showed significant intra-patient variability as the dose was increased from 1–12 mg/m 2 over 6 dose levels; the mean AUC increased from 370–970 ng*hr/mL, and the mean C max increased from 36–79 ng/mL. There was a 5-fold range in clearance (range: 6.5–33.1 L/h), but there was no association between dose and clearance. Following a single dose, the terminal phase half-life ranged from 16.4 - 24.3 hours. Conclusions: Since the DLT and MTD have not been reached, accrual will continue. No significant financial relationships to disclose.
Enhancement of antitumor immunity following depletion of CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells
Authors: J. Vieweg, Z. Su, J. Dannull
Journal: Journal of Clinical Oncology (2004)

2506 Background: The recent discovery of human CD4+CD25+ regulatory T cells (Treg) has made it feasible to develop strategies that modulate the immunosuppressive effects of Treg in a vaccination setting. In this study we hypothesized that in vivo elimination of Treg using the fusion protein denileukin diftitox, ONTAK can enhance the efficacy of tumor RNA-transfected DC vaccines to stimulate a tumor-specific T cell response. Methods: In order to test this hypothesis, we initiated a phase I clinical trial in which patients received a single dose of denileukin diftitox, followed by vaccination with total tumor RNA transfected DC. The RNA loaded DC were administered intradermally using three cycles of 1x107 cells applied in weekly intervals. The levels of regulatory T cell subsets and tumor specific T cell responses were monitored at baseline, during and after vaccination. Results: We show that CD4+/CD25high Treg can be effectively eliminated in a dose-dependent manner, without bystander toxicity to CD25negative cells. We further demonstrate that denileukin diftitox treatment resulted in the selective elimination of Treg without negatively impacting on the CD4+/CD25intermed memory/effector T cell pool as evidenced by ELISPOT and proliferation assays. Finally, we show, as hypothesized, that Treg depletion followed by vaccination reproducibly led to improved stimulation of tumor-specific T-cells when compared to vaccination alone. Denileukin diftitox-mediated Treg depletion resulted not only in increased frequencies of tumor-specific T cells, but also in an increased proliferative and cytotoxic response against renal tumor targets suggesting the functional intactness of the vaccine-induced T cells. Conclusions: In summary, we present the first ‘clinical proof of principle’ that Denileukin diftitox-mediated elimination of Treg is capable of enhancing the magnitude of renal tumor specific T-cell responses in a vaccination setting. No significant financial relationships to disclose.
A feasibility study of combination therapy with trastuzumab (T), cyclophosphamide (CY), and an allogeneic GM-CSF-secreting breast tumor vaccine for the treatment of HER2+ metastatic breast cancer.
Authors: L. A. Emens, R. Gupta, S. Petrik, M. Laiko, J. M. Leatherman, J. Levi, J. M. Asquith, M. M. Daphtary, E. Garrett-Mayer, B. J. Kobrin, N. E. Davidson, T. Dauses, S. Atay-Rosenthal, X. Ye, A. C. Wolff, V. Stearns, E. M. Jaffee
Journal: Journal of Clinical Oncology (2011)

2535 Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burdens and immune tolerance. Cyclophosphamide (CY) augments the activity of a GM-CSF-secreting breast tumor vaccine in ER+ metastatic breast cancer (MBC) patients. HER-2-specific monoclonal antibodies given with GM-CSF-secreting HER-2-targeted vaccination enhance CD8+ effector T cell function and tumor-free survival in immune tolerant neu transgenic mice. Here, we test the hypothesis that CY-modulated vaccination with weekly Trastuzumab (T) can induce clinically-relevant HER-2-specific immunity in HER-2+ MBC patients. Methods: We conducted a single arm, open label, two-stage feasibility study of CY, an allogeneic HER-2+ GM-CSF-secreting breast tumor vaccine, and standard T in patients with measurable/evaluable HER-2+ MBC. Vaccinations were given every 4-6 weeks for 3 cycles, with a 4th vaccination given 6-8 months from trial entry. Primary objectives included safety, bioactivity, and clinical benefit (CB=complete response+partial response+stable disease). A secondary outcome was delayed type hypersensitivity (DTH) to the MHC Class II HER-2 epitopes p369 and p776. This study has a power of 0.86 to detect a CB rate of 0.45 from a null hypothesis rate of 0.20 at an alpha level of 0.08. Results: Twenty patients were vaccinated. 75% received at least 3 vaccinations, and 40% completed all 4 vaccinations. Toxicities were limited to low grade fever, myalgias, injection site reactions, and urticaria. No dose limiting toxicities were observed. The CB rates at 6 months and 1 year were 10/20 (50%, 95% CI:27-72%) and 7/20 (35%, 95%CI:15-59%) respectively. HER-2-specific DTH developed in 7/20 subjects (35%); four (57%, 95% CI:18-90%) of these had a CB. Conclusions: CY-modulated immunotherapy with an allogeneic, HER-2+ GM-CSF-secreting breast tumor vaccine and weekly T is safe, bioactive, and induces new HER-2-specific DTH in HER-2+ MBC patients. The 50% CB rate at 6 months supports further investigation of CY-modulated vaccination with standard T. The GM-CSF-secreting vaccine platform is licensed from Johns Hopkins University to BioSante. The Johns Hopkins University has the potential to receive royalties in the future.
CEA response as a prognostic marker in non-small-cell lung carcinoma (NSCLC) patients treated with gefitinib or erlotinib
Authors: J. Ceballos, J. Lopez-Picazo, C. Reyna, M. Moreno Jimenez, J. L. Pérez-Gracia, M. Ponz Sarvise, C. Olier, I. Gil Bazo, A. Gurpide, J. Garcia-Foncillas
Journal: Journal of Clinical Oncology (2008)

19071 Background: Gefitinib and Erlotinib are oral selective epidermal growth factor receptor tyrosine kinase inhibitors active in advanced NSCLC. CEA has been evaluated as a tumor marker for NSCLC and a correlation between marker response and survival in patients treated with chemotherapy has been observed. Nevertheless, its potential role in the assessment of biological therapies efficacy has been poorly analyzed. Methods: This is a retrospective data analysis from advanced NSCLC patients treated at our institution in two prospective studies: Iressa Expanded Access Program and the Tarceva Open Access phase II study (Target study). Previous studies have defined CEA response and progression as a 20–50% decrease or increase respectively in CEA levels. For our study, we defined CEA response as a decline of ≥20% and CEA progression as an increase of ≥20%, compared with baseline levels. Results: Between April 2001 and October 2006, 231 patients (163 M/68 F) with metastatic NSCLC (67 squamous/81 adenocarcinoma/14 bronquioloalveolar carcinoma/69 other) received either Gefitinib (153 patients) or Erlotinib (78 patients). Baseline CEA was available in 93 patients and it was elevated in 49 patients (53%). Additional CEA levels were obtained during follow up in 58 patients. According to our previously defined criteria, 19 patients (33%) achieved CEA response, 16 patients (27%) stabilization and 23 (40%) patients progressed. Median progression-free survival was 38 weeks in patients that presented CEA response and 13 weeks in patients with stable or progressive levels of CEA (p=0.013). Conclusions: CEA response appears to correlate favourably with prognosis in patients with advanced NSCLC treated with Erlotinib or Gefitinib. Additional studies to confirm the role of CEA response as a surrogate marker in patients treated with targeted agents are warranted. No significant financial relationships to disclose.
Phase II trial of S-1 in combination with oxaliplatin (SOx) in previously untreated patients with recurrent or inoperable biliary tract cancer
Authors: S. Oh, G. Lee, H. Kim, T. Kim, H. Kim, J. Kang
Journal: Journal of Clinical Oncology (2008)

15611 Background: Biliary tract cancers (BTC) are one of the most aggressive tumors with a poor prognosis. Although the benefit of chemotherapy has been suggested, there is no defined standard regimen. We performed a phase II study of combination chemotherapy with S-1 and oxaliplatin in previously untreated BTC patients to evaluate efficacy and toxicity of the regimen prospectively. Patients and Methods: Histologically confirmed relapsed or metastatic BTC were treated with S-1 40 mg/m2 twice daily given as a orally on days 1–28, and oxaliplatin 85 mg/m2 given as a 90-min intravenous infusion on days 1, 15, and 29. Results: Fifteen patients were enrolled, 9 (60%) were male and 6 (40%) were female and the median age was 61 years (50–72 years). Nine patients (60%) had intrahepatic cholangiocarcinoma, 3 (20%) had extrahepatic cholangiocarcinoma, 2 (13.3%) had ampulla of vater cancer, and one had gall bladder cancer. The most frequent metastatic site was liver (53.3 %). No complete response was observed and partial response was observed in 1/15 (6.6%) patients. Stable disease was observed in 4 patients (26.7%), and 10 patients (66.7%) had progressive disease. The median TTP was 1.4 (95% CI, 0.9–1.9) months, and the median OS was 3.1 (95% CI, 0.0–7.0) months after the median follow-up duration of 13.8 months. A total of 18 cycles of chemotherapy was delivered. Grade 3 hematologic toxicities included neutropenia (1, 5.6%) and thrombocytopenia (1, 5.6%) per cycle. Grade 3 non-hematologic toxicities included mucositis (1, 6.7%) per patient. There was no treatment-related death. Because response rate in stage I did not reached to target to proceed stage II (≥ 2/15), this study had to been closed by protocol. Conclusion: The combination chemotherapy of S-1 and oxaliplatin did not demonstrate a promising antitumor activity. But it was observed mild toxicity profile. No significant financial relationships to disclose.
Pharmacokinetic (PK) and tolerance profiles of oral tegafur/uracil (UFT) given as three versus two daily intakes
Authors: M. C. Etienne-Grimaldi, E. François, N. Renée, J. M. Cardot, J. Y. Douillard, E. Gamelin, Y. Chateau, J. Clouet, S. Dupuis, G. Milano
Journal: Journal of Clinical Oncology (2006)

12013 Background: This phase II randomized bioequivalence cross-over study compared the tolerance and PK profiles of oral UFT (tegafur-uracil) given as 3 daily intakes (tid, usual schedule) to that obtained with 2 daily intakes (bid). Methods: Twenty-one metastatic colorectal cancer patients were enrolled (16 men, 5 women ; mean age 64, extremes 42–79 ; ECOG PS ≤ 1). Tegafur-uracil (300 mg/m 2 /d) and leucovorin (90 mg/d) were given for 2 consecutive four-week cycles separated by one rest week. Patients were randomized for receiving 1st cycle either tid (arm A, 12 patients) or bid (arm B, 9 patients). For each schedule, PK was evaluated at steady state, over 24 h. Plasma concentrations of tegafur, uracil and fluorouracil (FU) were analyzed by HPLC. Results: Analysis of tolerance (digestive toxicity mainly, OMS grade) showed a tendency (p = 0.08) for a greater toxicity with the bid schedule (29% grade 2, 14% grade 3) relative to tid (24% grade 2 only). Although daily doses were similar, FU and uracil AUC0–24h were respectively 1.8 and 2.0-fold higher for bid as compared to tid (95% CI were 1.5–2.1 and 1.6–2.6, respectively, p &lt; 0.0001). For tegafur, the 1.2-fold difference was of borderline significance (p = 0.057). The greater the FU AUC0–24h, the higher the toxicity intensity (p = 0.044). Analysis of systemic exposure with respect to daily time revealed that FU (p &lt; 0.01) and uracil (p &lt; 0.03) AUC corresponding to the morning intake were significantly higher than those corresponding to the afternoon or evening intakes, with AUC ratio as high as 1.6 for FU and 2.9 for uracil. Such a circadian influence was not observed for tegafur. Conclusions: To reach bioequivalence, bid tegafur-uracil administration will require lower doses than those given tid. The circadian variability observed for FU and uracil PK concords with that previously reported for dihydropyrimidine deshydrogenase activity. No significant financial relationships to disclose.
Scandinavian phase III trial of neoadjuvant chemotherapy in NSCLC stages IB-IIIA/T3
Authors: J. B. Sorensen, H. Riska, J. Ravn, O. Hansen, T. Palshof, C. Rytter, K. Mattson, L. Ladegaard, H. C. Pilegaard, U. Aaseboe
Journal: Journal of Clinical Oncology (2005)

7146 Background: Neoadjuvant chemotherapy before surgery for NSCLC has previously shown somewhat promising results, but all prior randomised studies included also patients (pts) with N2-disease or stage IIIB. The aim was thus to evaluate the impact of neoadjuvant chemotherapy for early stage disease (stages IB - IIIA/T3). Methods: Pts had histologically verified NSCLC stages IB, IIA, IIB, and IIIA/T3 based on CT-scan and negative mediastinoscopy, and were randomised to 3 courses of Paclitaxel 225 mg/m2 and Carboplatin AUC 6 day 1 q 3 weeks followed by surgery (regimen A) or immidiate surgery (regimen B). Chest radiotherapy 60 Gy were administered in case of incomplete resection. Survival was primary end-point. It was required to randomise totally 280 pts to detect an 15% increment in 5-year survival rate with a two-sided type I error of 5% and 80% power. The study was stopped prematurely due to slow patient recruitment. Results: 44 pts with a median age of 66 years were randomised to regimen A and 46 with median age 62 years to regimen B from November 1998 to October 2004. There were no differences with respect to performance status, gender, histology, LDH, or stage groups between the treatment regimens. In regimen A, 46% achieved a partial response to the neoadjuvant chemotherapy. Microscopically complete resection was achieved in 79% and 70% in regimen A and B, respectively. Median survival and 5-year survival rates were 34.4 months and 36% compared to 22.5 months and 24% in regimen A and B, respectively (not significant). Conclusions: No statistically significant differences were noted in this prematurely closed trial, but median survival was increased by one year and 5-year survival rate increased by 12% for pts receiving neoadjuvant chemotherapy, suggesting that a beneficial effect can not be ruled out. Follow-up and survival update continues. No significant financial relationships to disclose.
Valproate, a Histone Deacetylase Inhibitor, Enhances Purine Nucleoside Analogues Induced Apoptosis of B-Chronic Lymphocytic Leukemia Cells.
Authors: Amel B. Bouzar, Mathieu Boxus, Julien Defoiche, Hervé Balon Techn, Guy Berchem, Derek Macallan, Ruth Pettengel, Fenella Willis, Arsene Burny, Laurence Lagneaux, Dominique Bron, Bernard Chatelain, Christian Chatelain, Luc Willems
Journal: Blood (2007)
Phase II study of S-1 plus irinotecan (SIR) in patients with advanced colorectal cancer
Authors: A. Goto, Y. Yamada, Y. Shimada, K. Shirao, T. Hamaguchi, K. Muro, H. Yasui, K. Kato
Journal: Journal of Clinical Oncology (2006)

13508 Background: Infusional fluorouracil and leucovorin (5-FU/LV) plus irinotecan is one of the standard regimens for the treatment of metastatic colorectal cancer (MCRC). S-1, a combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and oxonic acid, is an oral DPD inhibitory fluoropyrimidine shown to be very effective as first-line treatment for MCRC. The response rate with S-1 was 35–40% in patients with chemo-naïve MCRC. This study evaluated the efficacy and toxicity of S-1 plus irinotecan (SIR). Methods: Eligible patients had untreated MCRC as confirmed histologically, PS 0–1, adequate organ function, and provided written informed consent. First-line SIR was given in 3-week treatment cycles: intravenous irinotecan 150 mg/m 2 (day 1) and oral S-1 40 mg/m 2 twice daily for 14 days followed by 7 days of rest. Results: Forty-one patients were enrolled; 40 fulfilled all eligibility criteria, and 1 had double cancers. There were 28 men; median age 60 years (range, 23–74); ECOG PS 0/1, 35/6. The overall response rate was 63% (95%CI, 48–78%). Five patients had a CR, 20 a PR, 11 SD, and 2 PD. Median TTP was 8.0 months (range, 1.4–13.8 months); MST was not reached. The most frequent grade 3/4 toxicities included: neutropenia (17%), diarrhea (15%), and anorexia (12%). One patient had Grade 4 constipation. The relative dose intensity of irinotecan was 84%, and that of S-1 was 79%. Dose reduction of irinotecan was required in 41 of 327 administered cycles, and that of S-1 was required in 15 of 327. Conclusions: SIR is a highly active and convenient first-line therapy for MCRC, with an acceptable toxicity profile. S-1 has the potential to replace infusional 5-FU/LV plus irinotecan for MCRC. No significant financial relationships to disclose.
Lesson of the Week: Something in the air: survival after dramatic, unsuspected case of accidental carbon monoxide poisoning
Authors: R. Pullinger
Journal: BMJ (1996)

In cases of intentional carbon monoxide poisoning the diagnosis is usually straightforward and is suggested by the circumstances in which the patient is found. In contrast, accidental carbon monoxide poisoning remains underdiagnosed because the source of carbon monoxide is often not obvious and may be remote and because the symptoms of poisoning—headache, lethargy, nausea, and vomiting—are non-specific.

In the United States a review of death certificates over 10 years identified 56 133 deaths in which carbon monoxide poisoning was implicated.1 Of these, 46% were suicide, 28% were associated with burns, and 21% were unintentional for other reasons. Fifty seven per cent of these last unintentional deaths were related to exhaust fumes from a motor vehicle, which in most cases was stationary. A three year study of carbon monoxide poisoning in France identified 735 cases, of which 196 had domestic causes.2 The domestic sources of carbon monoxide were water heaters (57%), boilers (21%), coal stoves (9%), braziers (4%), cookers (2%), and heating devices (1.5%). In addition, reports of carbon monoxide poisoning due to poorly maintained or poorly ventilated domestic appliances have come from Switzerland,3 Denmark,4 5 and Belgium.6 In one report of domestic carbon monoxide poisoning from the United States patients were poisoned far from the source of the gas: carbon monoxide had been drawn into a motel's air conditioning system from the heating vents of a nearby swimming pool.7

The indoor use of cooking devices designed for outdoor use is also an important cause of carbon monoxide poisoning. Foutch and Henrichs reported the death due to …
Developing a Therapeutic Anti - Dendritic Cell Antibody to Prevent Graft Versus Host Disease.
Authors: Derek Hart, Therese Seldon, Martina Jones, Yonghua Sheng, Anna Palkova, Hannah Cullup, Trent Munro, Laura Sinfield, Alison M Rice, John Wilson, Peter Gray, Ross Barnard, Stephen Mahler, David Munster
Journal: Blood (2009)
Abstract 17103: Comparison of Non-Cardiac Findings by a Cardiologist with Those by a Radiologist in 320 Slice CT Images
Authors: Sawako Horie, Nobusada Funabashi, Takashi Higashide, Hiroyuki Takaoka, Masae Uehara, Yoshio Kobayashi
Journal: Circulation (2012)

Purpose: We compared non-cardiac findings, in particular lung findings, by a cardiologist with those by a radiologist in 320 slice CT heart images. Methods: Non-cardiac findings using full field vi...
TCT- 290 Assessment Of Myocardial Viability After Acute Myocardial Infarction: A Head-To-Head Comparison Of The Perfusable Tissue Index By PET And Delayed Contrast-Enhanced CMR
Authors: Paul F. Teunissen, Stefan A. Timmer, Ibrahim Danad, Lourens F. Robbers, Pieter G. Raijmakers, Aernout M. Beek, Albert C. van Rossum, Adriaan A. Lammertsma, Niels van Royen, Paul Knaapen
Journal: Journal of the American College of Cardiology (2014)