tbuckley/cabot-search huggingface dataset:
Radiation Therapy Deviations in Trial of Locally Advanced Pancreatic Cancer—Reply
Authors: Florence Huguet, David Goldstein, Pascal Hammel
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Impact of combinatorial dysfunctions of Tet2 and Ezh2 on the epigenome in the pathogenesis of myelodysplastic syndrome
Authors: N Hasegawa, M Oshima, G Sashida, H Matsui, S Koide, A Saraya, C Wang, T Muto, K Takane, A Kaneda, K Shimoda, C Nakaseko, K Yokote, A Iwama
Journal: Leukemia (2016)
The RET E616Q Variant is a Gain of Function Mutation Present in a Family with Features of Multiple Endocrine Neoplasia 2A
Authors: William Grey, Rosaline Hulse, Anna Yakovleva, Dilyana Genkova, Benjamin Whitelaw, Ellen Solomon, Salvador J. Diaz-Cano, Louise Izatt
Journal: Endocrine Pathology (2016)
Coronary Artery Calcification and Rheumatoid Arthritis: Lack of Relationship to Risk Alleles for Coronary Artery Disease in the General Population
Authors: Iván Ferraz‐Amaro, Robert Winchester, Peter K. Gregersen, Richard J. Reynolds, Mary Chester Wasko, Anette Oeser, Cecilia P. Chung, C. Michael Stein, Jon T. Giles, Joan M. Bathon
Journal: Arthritis & Rheumatology (2016)

Objective Coronary artery disease (CAD) in the general population is characterized by an increased frequency of particular susceptibility single‐nucleotide polymorphisms (SNPs). Because the frequency of CAD is increased among patients with rheumatoid arthritis (RA), we sought to determine whether the frequency of these SNPs is increased in RA patients with CAD, hypothesizing that RA could enhance CAD risk by acting through established genetic pathways predisposing to CAD. Methods Coronary artery calcification (CAC) as detected by computed tomography was used as a measure of CAD in 561 patients with RA. One hundred SNPs associated with CAD in the general population were genotyped or imputed, and their relationship to CAC was established through multiple regression analysis for individual SNPs and a genetic risk score representing their cumulative effect. Results Ninety‐one CAD‐related SNPs were genotyped successfully; of these, 81 exhibited no association with CAC (Agatston units) or different CAC categorizations, either individually or collectively, in the genetic risk score. Only rs579459 ( ABO ) and rs17676451 ( HAL ) had a consistent positive association between genotype and CAC, with a significant increase in the frequency of the effect allele in both homozygous and heterozygous genotype distributions. Five were variably negatively associated. Furthermore, a positive association between the Disease Activity Score in 28 joints and CAC was observed, and after adjustment for traditional cardiovascular risk factors, it was not modified by correcting for the CAD‐related SNP genetic risk score. Conclusion The increased risk of CAC in patients with RA does not appear to operate primarily through established genetically regulated atherogenic mechanisms that are preponderant in the general population.
Proceedings in the palliative treatment of advanced gastric cancer including multimodal therapy.
Authors: Ralf Steinert, Ingo Gastinger, Frank Meyer, Henry Ptok, Karsten Ridwelski, Christiane Bruns, Hans Lippert
Journal: Journal of Clinical Oncology (2014)

e15008 Background: Prospective multicenter observational studies investigated the value of surgery and impact of multimodal therapy in palliative treatment of advanced gastric cancer. Methods: In 2002, 1,031 patients from 80 surgical departments underwent surgical intervention only whereas in a following study from 2007-2009 using multimodal therapy 2,805 patients from 141 surgical departments were documented. There were no reduction of advanced tumor stages and no significant differences in the distribution of tumor sites and UICC stages comparing these time periods. Results: 521 patients (18%) underwent neoadjuvant therapy from 2007 to 2009, 401 subjects (13.9%) out of patients with curative intention versus 120 individuals (4.1%) out of patients with palliative treatment. 32.5 % (n=223) of patients were treated with chemotherapy (neoadjuvant setting and/or postoperatively with palliative intention). There was a decrease of palliation rate from almost 40% in 2002 to 24.5% with an increase of overall 4-year survival from 40.0% to 48.5%. In 2002, median survival of patients with no resection was 7 months independently of surgical intention whereas resection of primary tumor lesion resulted in a median survival of 10 months (p=0.005). In case of tumor resection with primary palliative intention, patients had a longer survival of 2.3 months (6.9 vs. 4.6 months) compared to patients with no resection. From 2007 to 2009, median survival after non-resecting interventions and no subsequent chemotherapy was 1 month, but with chemotherapy 7 months (p<0.001). Median survival time of patients with R2-resection status was approximately 9 months, in case of leaving primary tumor in situ 4 months (p<0.005). Using postoperative chemotherapy with palliative intention, patients with former R2-resection status showed better median survival time (11 vs. 7 months; p<0.001). Patients with no postoperative chemotherapy in palliative intention did not benefit from resecting procedures. Conclusions: Palliative tumor resection should become part of the multimodal therapy concept in advanced gastric cancer since patients benefit from chemotherapy after former resection more than with no resection of the primary tumor.
Schedule-dependent antitumor effects of gemcitabine and S-1, a novel oral derivative of 5-fluorouracil, in human pancreatic cancer xenografts
Authors: S. Nakahira, S. Nakamori, M. Tsujie, Y. Takahashi, S. Marubashi, A. Miyamoto, H. Nagano, K. Dono, M. Sakon, M. Monden
Journal: Journal of Clinical Oncology (2005)

4154 Background: The systemic administration of gemcitabine (GEM) has been accepted as a standard treatment for patients with advanced pancreatic cancer. The major mediator of cellular uptake of GEM is the equilibrative nucleoside transporter 1 (ENT1) which expression is up-regulated by TS inhibitor such as 5-fluorouracil (5-FU). S-1 is a novel oral derivative of 5-FU prodrug tegafur combined with two modulators, 5-chloro-2, 4-dihydropridine and potassium oxonate, and recent clinical trials have reported the promising effect of S-1 in pancreatic cancer. The purpose of this study is to evaluate the relationship between different schedules and their effects of GEM/S-1 in combination therapy for pancreatic cancer in nude mouse xenograft model. Methods: Expression of ENT1 was determined by quantitative RT-PCR. GEM cellular uptake was determined using [3H]GEM. Seven pancreatic cancer cell lines (AsPC1, BxPC3, MiaPaCa-2, PSN1, Panc1, PCI6, and KMP4) were treated in vitro with 5-FU either before or following exposure to GEM. Growth inhibitory effects in vitro were determined by MTT assay. We compared 6 different treatment schedules (no treatment, single agent of GEM or S-1, combination treatment with gemcitabine either before, simultaneously or following administration of S-1) using MiaPaCa-2 xenograft model in BALB/c mice. The antitumor effects were evaluated with the tumor volume. Results: Significant increases in ENT1 expression and GEM cellular uptake were observed after 5-FU treatment in vitro and S-1 treatment in vivo. The in vitro growth inhibitory effect was significantly greater in the sequential treatment of 5-FU followed by GEM in all cell lines except for Panc1. Furthermore, the significant tumor growth inhibition in vivo was observed in the mice treated with S-1 followed by GEM compared with either untreated mice or the mice treated with gemcitabine followed by S-1. Conclusions: Based on the modulation of 5-FU on the uptake of GEM, 5-FU should be used before GEM treatment. The combination therapy with preadministarted S-1 and GEM in the patients with pancreatic cancer is promising and is worthwhile to be confirmed in clinical trials. No significant financial relationships to disclose.
Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit
Authors: Massimo Girardis, Stefano Busani, Elisa Damiani, Abele Donati, Laura Rinaldi, Andrea Marudi, Andrea Morelli, Massimo Antonelli, Mervyn Singer
Journal: JAMA (2016)

Despite suggestions of potential harm from unnecessary oxygen therapy, critically ill patients spend substantial periods in a hyperoxemic state. A strategy of controlled arterial oxygenation is thus rational but has not been validated in clinical practice.To assess whether a conservative protocol for oxygen supplementation could improve outcomes in patients admitted to intensive care units (ICUs).Oxygen-ICU was a single-center, open-label, randomized clinical trial conducted from March 2010 to October 2012 that included all adults admitted with an expected length of stay of 72 hours or longer to the medical-surgical ICU of Modena University Hospital, Italy. The originally planned sample size was 660 patients, but the study was stopped early due to difficulties in enrollment after inclusion of 480 patients.Patients were randomly assigned to receive oxygen therapy to maintain Pao2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation (Spo2) between 94% and 98% (conservative group) or, according to standard ICU practice, to allow Pao2 values up to 150 mm Hg or Spo2 values between 97% and 100% (conventional control group).The primary outcome was ICU mortality. Secondary outcomes included occurrence of new organ failure and infection 48 hours or more after ICU admission.A total of 434 patients (median age, 64 years; 188 [43.3%] women) received conventional (n = 218) or conservative (n = 216) oxygen therapy and were included in the modified intent-to-treat analysis. Daily time-weighted Pao2 averages during the ICU stay were significantly higher (P < .001) in the conventional group (median Pao2, 102 mm Hg [interquartile range, 88-116]) vs the conservative group (median Pao2, 87 mm Hg [interquartile range, 79-97]). Twenty-five patients in the conservative oxygen therapy group (11.6%) and 44 in the conventional oxygen therapy group (20.2%) died during their ICU stay (absolute risk reduction [ARR], 0.086 [95% CI, 0.017-0.150]; relative risk [RR], 0.57 [95% CI, 0.37-0.90]; P = .01). Occurrences were lower in the conservative oxygen therapy group for new shock episode (ARR, 0.068 [95% CI, 0.020-0.120]; RR, 0.35 [95% CI, 0.16-0.75]; P = .006) or liver failure (ARR, 0.046 [95% CI, 0.008-0.088]; RR, 0.29 [95% CI, 0.10-0.82]; P = .02) and new bloodstream infection (ARR, 0.05 [95% CI, 0.00-0.09]; RR, 0.50 [95% CI, 0.25-0.998; P = .049).Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy vs conventional therapy resulted in lower ICU mortality. These preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of this approach.clinicaltrials.gov Identifier: NCT01319643.
Image-guided radiosurgery for single spinal metastasis
Authors: S. Ryu, J. Rock, F.-F. Yin, M. Ajlouni, M. Rosenblum, J. H. Kim
Journal: Journal of Clinical Oncology (2004)

8033 Background: The precision and accuracy of image-guided spinal radiosurgery has been previously demonstrated. We have extended on the spinal radiosurgery to treat a single spinal metastasis. This study was carried out to determine the clinical efficacy of spinal radiosurgery for treatment of spinal metastases with or without cord compression. Methods: A total of 49 patients with 61 lesions of spinal metastasis were treated with radiosurgery at Henry Ford Hospital from May 2001 to May 2003. All patients had pathologically-proven primary cancers and had either synchronous or metachronous metastases to the spine. The majority of the patients had back pain as the presenting symptom and 17 lesions were associated with neurologic signs. The involved spine was treated with single dose radiosurgery. The range of radiation dose was 10 –16 Gy in 2 Gy increments. The entire radiosurgery procedure was performed on an out-patient basis. Endpoints of analysis were pain control, neurologic improvement, and radiologic tumor control. Results: The median time to pain relief was 14 days and the earliest time of pain relief was within 24 hours. The median duration of pain relief was 13.3 months. Complete and partial pain relief was achieved in 37.7 % and 47.6% of the lesions treated, respectively. Relapse of pain at the treated site was noted in 6.9%. Neurologic improvement and radiologic tumor control were noted in patients with cord compression by epidural soft tissue mass. Progressive metastasis in the adjacent spines was seen only in 4.9%. There was no acute or subacute radiation toxicity detected clinically during the maximum follow up of 24 months. Conclusions: A large single dose spinal radiosurgery achieves a rapid and durable pain relief as well as radiological tumor control and neurologic improvement. Tumor progression to the immediately adjacent spine was rare. The results support the use of single dose spinal radiosurgery as an effective treatment option for single spinal metastasis with or without spinal cord compression. No significant financial relationships to disclose.
NCIC-CTG MA14 Trial: Tamoxifen (tam) vs. tam + octreotide (oct) for adjuvant treatment of stage I or II postmenopausal breast cancer
Authors: M. N. Pollak, J. W. Chapman, K. I. Pritchard, J. E. Krook, H. S. Dhaliwal, T. A. Vandenberg, B. D. Norris, T. J. Whelan, C. F. Wilson, L. E. Shepherd
Journal: Journal of Clinical Oncology (2008)

532 Background: Our preclinical data (Cancer Res. 54:6334,1994) suggested mechanisms involving insulin/IGF physiology by which a somatostatin analogue + tam combination might be superior to tam alone for adjuvant BC therapy. Methods: In 1996, we began a Phase 3 trial randomizing stage I or II postmenopausal BC patients to tam 20mg daily for 5 yr with or without oct (monthly 90mg depot injection) for 5 yr, later reduced to 2 yr due to concern regarding cholelithiasis. Stratification factors included adjuvant chemotherapy, axillary nodal status, and ER status. Primary endpoint was event-free survival (EFS), defined as time from randomization to recurrence, second malignancy, or death due to any cause, assessed with the adjusted log-rank test statistic and an adjusted step-wise forward Cox regression. Objectives included studies of relevant biomarkers in relation to treatment and outcomes. Results: 667 women were accrued (333 to tam, 334 to tam +oct), with a median follow-up of 7.9 years and 220 events: 112 on tam (50.9%) and 108 on tam+oct (49.1%). The log-rank p=0.62, and the hazard ratio for tam+oct to tam is 0.93 (95% CI 0.71 to 1.22). Of 135 recurrences, 72 were on tam and 63 on tam+oct. As predicted by our lab model (Endocrinology. 130:3395,1992), there was a decline in mean IGF-1 on tam (baseline to nadir 121 to 75.3 ng/ml [p<0.0001]). On tam+oct this decline was from 121.2 to 61.2 (p<0.0001). On tam, a rise in c-peptide, 3.1 to 3.9 ng/ml (p<0.0001) was seen, while there was no significant change in c-peptide on tam+oct (3.3 to 3.4 ng/ml, p=0.22). Mean BMI increased significantly on tam (27.6 to 28.1, p=0.02), but not on tam +oct (28.0 to 27.7, p=0.20). In multivariate assessment, there was longer EFS for women <60 (p=0.01), T stage < T2 (p=0.004), N0 (p=0.01), and lower c-peptide (p<0.0001); lower BMI was associated with longer EFS (p<0.0001) in models that excluded c- peptide. Conclusions: No difference in EFS was seen between treatment arms, although there were differences in biomarkers. High c- peptide level was a strong negative prognostic factor, accounting for the adverse influence of obesity. Research is needed regarding the possibility that metabolically defined subsets of BC patients might benefit from oct+tam or other therapies that target insulin-IGF. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
Listeria outbreak associated with sandwich consumption from a hospital retail shop, United Kingdom
Authors: S J Dawson, M R Evans, D Willby, J Bardwell, N Chamberlain, D A Lewis
Journal: Eurosurveillance (2006)

An outbreak of listeriosis occurred in the Swindon area of the UK in autumn 2003. Five cases were detected in pregnant women. Four of these women were thought to have eaten prepacked sandwiches from a retail outlet in one particular hospital. Sampling at the supplier detected Listeria monocytogenes, which was indistinguishable on molecular testing from the patients isolates. Recent changes in UK food legislation should help diminish the risk of further outbreaks/cases such as ours occurring.
Utility of 3-year torso CT and head imaging in asymptomatic patients with high-risk melanoma.
Authors: E. R. DeRose, A. Pleet, V. J. Seery, M. Lee, S. Renzi, R. J. Sullivan, M. B. Atkins
Journal: Journal of Clinical Oncology (2010)

8594 Background: Patients (pts) with stage IIB to IIIC melanoma have a lifetime risk of melanoma related mortality of 30- 60%. By 3 years (yrs) from initial diagnosis, the risk of relapse in pts who remain disease free is decreased by 50%-75%. We sought to determine the utility and cost effectiveness of radiologic restaging of this pt population at the 3-yr follow-up (f/up) time point. Methods: In 2004, the BIDMC Cutaneous Oncology Program (COP) began obtaining torso CT scan and head imaging at the 3-yr f/up visit in all pts with stage IIB-IIIC melanoma who remained recurrence free. Chart review was performed on the 50 pts within the COP database who had undergone such restaging through 7/09. True positive (TP), false positive (FP) and normal scans were identified. Analysis of the cost of imaging and the cost of additional intervention for f/up of positive studies was performed, and a cost/diagnosis (TP) was calculated. Results: 25 head CT scans, 25 head MRIs, and 50 torso CTs were performed. One FP head CT and 5 abnormal torso CT scans (3 FP, 2 TP) were identified. FP and TP rates were 4/50 (8%); 2/50, (4%), respectively. The total cost including 3 yr f/up scans, additional imaging (1 repeat head CT, 2 chest CTs, 1 abdominal MRI) and diagnostic procedures (1 CT-guided lung biopsy (bx), one pelvic LN bx) was $600,406. The cost/diagnosis was $300,203. Both pts with TP scans developed symptomatic recurrence within weeks and died at 1 and 6.5 months after stage IV diagnosis. In the remaining 48 pts, at a median f/up of 14.5 months after the 3-yr f/up scan, 1 pt developed symptomatic stage IV disease and 1 developed local recurrence. Conclusions: In patients with stage IIB-IIIC melanoma who are asymptomatic and continuously disease free, extensive 3-yr f/up imaging appears to be of limited value. Two-thirds of abnormalities are FPs, and the cost of identifying a TP is > $300K/pt. Based on these findings, routine torso CT and head imaging of such pts is not recommended. Furthermore, given the low risk of recurrence beyond 3 yrs, it is likely that subsequent routine imaging would have similarly low utility. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience, Antigenics, Bayer, Genentech, Novartis, Onyx, Pfizer, Schering-Plough
Co-Transplantation of Haploidentical Bone Marrow Derived Mesenchymal Stem Cells Overcomes Graft Dysfunction and Improves Hematological and Lymphocyte Recovery in Haploidentical Stem Cell Transplantation.
Authors: Lynne Margaret van Velzen-Ball, Marie Ester Bernado, Franco Locatelli, Helene Roelofs, Arjan Lankester, R. Maarten Egeler, Willem E. Fibbe
Journal: Blood (2006)
Binding Of Recombinant Activated Factor VII (rFVIIa) To Human Platelets Identifies Donor Variation and Platelet Subpopulations With Increased Binding Of rFVIIa In Platelet Concentrates From Healthy Donors
Authors: Jadranka Koehn, Ernst Boehm, Michael Dockal, Andrea Sedivy, Friedrich Scheiflinger
Journal: Blood (2013)
Effect of treatment on the regression and growth rates of thymic epithelial tumors (TETs).
Authors: Mauricio Emmanuel Burotto Pichun, Anish Thomas, Julia Wilkerson, Raffit Hassan, Antonio Tito Fojo, Giuseppe Giaccone, Arun Rajan
Journal: Journal of Clinical Oncology (2015)

e18564 Background: TETs are rare tumors with limited treatment options that exhibit a wide range of growth characteristics. Standard measures of evaluating tumor response to investigational agents have their limitations and novel metrics of efficacy are under investigation. Using a simple mathematical model one can simultaneously estimate the rates of tumor regression (d, decay) and growth of drug sensitive and insensitive tumor fractions while a therapy is administered. The rate of growth (g) has been shown to correlate with overall survival (OS). We sought to characterize the effect of different therapies on these two concomitant processes in TETs. Methods: Data from one phase I/II (PACB: cisplatin, doxorubicin, cyclophosphamide, belinostat; NCT01100944) and three phase II clinical trials [single agent B (NCT00589290) or cixutumumab (C; NCT00965250) or sunitinib (S; NCT01621568)] conducted at the NCI were included in this analysis. The size of target lesions measured at baseline and at pre-defined timepoints during treatment was utilized. The data was fit to the basic [f(t) = exp (-d • t) + exp (g • t) -1] or a derivative equation and d and g estimated. Results: Data from74 patients comprise this analysis. The median number of tumor measurements was 3.7, 5.5, 6 and 5 for the PACB, B, C and S trials respectively. The objective response rate (ORR) was higher with PACB, but differences in OS could not be reliably discerned due to inter-trial differences. The estimated d and g rates were: PACB [d = 0.0114/day, g = 0.0021/day], B [d = 0.0022/day, g = 0.0050/day], C [d = 0.001 g = 0.0009/day], S [d = 0.0027/day, g = 0.0018/day]. There were no significant differences in g between the four therapies (p = 0.83). However, the d estimated for PAC-B was significantly higher compared to the other three therapies individually and combined (p = 7.7e-4 – 2.1e-8). Conclusions: The rates of regression of PACB are higher and this manifests clinically as a higher ORR. However, in the cases analyzed, the growth rates while receiving the four therapies were similar. While PACB may be used as initial therapy to render some disease resectable, novel therapies that can slow growth and can be tolerated for prolonged periods are needed to significantly prolong OS in TETs.