tbuckley/cabot-search huggingface dataset:
Clinical outcomes in advanced cervical cancer (CC) and endometrial cancer (EC) patients (pts) treated in phase I trials of novel molecularly targeted agents (MTAs).
Authors: Angela George, Vasiliki Michalarea, Saeed Rafii, Caroline O Michie, Mabel Wong, Rebecca Bowen, Liz Y. Han, Tom van Hagen, Grigorios Rallis, Udai Banerji, Rebecca Sophie Kristeleit, Johann Sebastian De Bono, Susana N. Banerjee, L Rhoda Molife, Martin Eric Gore, Stanley B. Kaye, Timothy Anthony Yap
Journal: Journal of Clinical Oncology (2015)

5596 Background: The prognosis for advanced CC and EC pts is poor, with relapse to approved chemotherapies inevitable. In view of the high rate of putative driver mutations, novel MTAs in phase I trials may benefit such pts. Methods: Retrospective study of pt records of CC (01/03-12/14) and EC (11/98-12/14) pts allocated to Phase I trials including efficacy expansion phases of MTAs in the Drug Development Unit at the Royal Marsden. Results: 93 CC pts were allocated to 51 trials (186 events); allocation was based on mutational profiles whenever possible. 57 (61%) pts began ≥ 1 trials (134 events). 36 (39%) pts did not start; 22 (24%) due to rapid progressive disease (PD), 7 (7.5%) due to other therapy options and 7 (7.5%) due to other reasons. 14 (10%) RECIST responses were seen; chemotherapy/MTA combinations (1 complete response and 7 partial responses [PR]), anti-angiogenics (AA) (2 PR), PI3K/AKT inhibitors (i) (2 PR) and immunotherapy (2 PR) in molecularly selected CC pts. 20 (15%) pts had RECIST stable disease > 4 months (SD > 4m), for a clinical benefit rate (CBR) of 25%. Mean survival was improved in CC pts with CR/PR (662 days) versus (vs) pts who did not start trial (257 days) (p < 0.001). Treatments were well tolerated: of 169 toxicities - G1/2: 127 (69%); G3/4: 42 (31%). 78 EC pts were allocated to 39 trials (93 events); 35 (45%) pts began ≥ 1 trials (48 events). Of 43 (55%) pts who did not start, 34 (44%) had rapid PD, 5 (6%) had other therapies and 4 (5%) for other reasons. There were 5 (10%) PRs observed in molecularly selected EC pts with mTORC1/2i, IGF-1Ri, AA, RAF/MEKi, and immunotherapy (all n = 1); a further 4 pts (8%) had SD > 4m, for a CBR of 18%. Mean survival was improved in EC pts with PR/SD > 4m (402 days) vs pts with PD (174 days) and pts who did not start trial (178 days) (p < 0.0001). Treatments were well tolerated: of 83 toxicities - G1/2: 67 (81%); G3/4: 16 (19%). Conclusions: Signs of pt benefit to novel MTAs in phase I trials were observed in molecularly selected pts with advanced EC and CC. A large proportion of pts allocated to such trials did not start treatment due to rapid PD. These data suggest that earlier phase I trial referral and knowledge of mutational profiles may improve pt outcomes.
Authors’ reply to Wise’s letter on including palliative care doctors in treatment discussions
Authors: Scott A Murray, M Kendall, G Mitchell, S Moine, J Amblàs-Novellas, K Boyd
Journal: BMJ (2017)

In response to our recent analysis,1 Wise calls for palliative care doctors to be included in treatment decisions when palliative oncology or radiotherapy is being considered.2 He states that both patients and oncologists are frequently overoptimistic about treatment outcomes, and suggests that if a palliative medicine specialist were present, “best supportive care ” alone might then be a more …
Protein kinase C Zeta mediates EGF-induced growth of head and neck tumor cells by regulating MAP kinase
Authors: Ezra Ew Cohen, Mark W. Lingen, Michael W. Straza, Carolyn Pierce, Bangmin Zhu, Leslie E. Martin, Marsha R. Rosner
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

70 

Protein kinase C zeta (PKCζ) has been implicated as a mediator of epidermal growth factor receptor (EGFR) and MAP kinase (ERK) signaling in epithelial cells. Since EGFR is ubiquitously expressed in squamous cell carcinomas of the head and neck (SCCHN) and plays a key role in tumor progression, we determined whether PKCζ is required for tumor cell proliferation. Examination of total and phosphorylated PKCζ expression in normal oral mucosa, dysplasia, and carcinoma as well as SCCHN tumor cell lines revealed a significant increase in activated PKCζ expression from normal to malignant tissue. PKCζ activity is required for EGF-induced ERK activation in both normal adult epidermal keratinocytes and 5 of 7 SCCHN cell lines. SCCHN cells express constitutively activated EGFR family receptors, and inhibition of either EGFR or MAP kinase activity suppressed DNA synthesis. Consistent with this observation, transfection of SCCHN cells with a kinase-dead PKCζ construct inhibited autocrine or EGF-induced DNA synthesis. Finally, PKCζ inhibition enhanced the anti-proliferative effects of both a MEK (U0126) and a broad spectrum PKC inhibitor (chelerythrine chloride). The results indicate that 1) PKCζ is associated with SCCHN progression; 2) PKCζ mediates EGF stimulated MAP kinase activation in keratinocytes and SCCHN cell lines; 3) PKCζ mediates EGFR and MAP kinase-dependent autocrine proliferation in SCCHN cell lines; and 4) PKCζ inactivation potentiates the action of other inhibitors that target similar or complementary signaling pathways.
Prognostic impact of clinicopathologic features in metastatic rectal versus colon cancer.
Authors: Anna Lomax, Hui-Li Wong, Kathryn Maree Field, Michael Harold, Jeremy David Shapiro, Joseph James McKendrick, Allan Solomon Zimet, Desmond Yip, Louise M. Nott, Ross Jennens, Gary Edward Richardson, Jeanne Tie, Suzanne Kosmider, Phillip Parente, Lionel Lim, Prasad Cooray, Ben Tran, Jayesh Desai, Rachel Wong, Peter Gibbs
Journal: Journal of Clinical Oncology (2014)

e14518 Background: Variation in outcomes for rectal (RC) and colon (CC) cancer have been reported, particularly in the advanced disease setting. Established differences in patterns of metastatic spread and recently described molecular analyses suggest differences in clinicopathological features that may impact on prognosis. Here we aim to compare presenting features and outcomes in metastatic RC vs. CC. Methods: Analysis of patients (pts) with newly diagnosed metastatic colorectal cancer enrolled onto an Australian prospective multicenter registry. Data collection commenced in July 2009, with 14 sites now contributing. Disease characteristics, treatment and overall survival (OS) were compared for pts with RC vs. CC using the chi square and Cox proportional hazards methods. Results: Of 1,048 pts, 305 (29%) had RC and 730 (70%) CC. Pts with RC were younger (median age 65 v.s 70 years, p<0.0001) and more likely male (64 vs. 55%, p=0.01). Significant differences in metastatic spread were observed; RC pts had more lung (40 vs 26%, p<0.0001), bone (4.3 vs. 1.9%, p=0.031) and brain (1.6 vs. 0.1%, p=0.004) metastases, whereas pts with CC had more liver (67 vs. 58%, p=0.006) and peritoneal (22 vs. 6%, p<0.0001) disease. Pts with RC were more likely to have metachronous (42 vs. 33%, p=0.005) and resectable (26 vs. 19%, p=0.015) metastatic disease, whereas more pts with CC had palliative primary tumor resections (55 vs. 26%, p<0.0001). There was no significant difference in chemotherapy use. KRAS mutation status was available for 391 (37%) pts, with a trend towards fewer KRAS mutations in pts with RC (34 vs 43%, p=0.1328). Adjusted OS was significantly longer for RC pts (median 30.9 vs. 22.8 months, HR 0.65 (0.52-0.82, p=0.0002). Conclusions: Significant differences were observed between the presenting features of RC and CC, possibly contributed to by underlying differences in tumor biology. Further exploring these may allow an improved understanding of differences in survival outcome and potentially define differences in the optimal approach to managing metastatic colon vs rectal cancer. Accrual to this patient cohort is continuing, with additional centers being added, and further available molecular data, including MSI and BRAF mutation, is being retrieved.
Time to Treatment and Mortality during Mandated Emergency Care for Sepsis
Authors: Christopher W. Seymour, Foster Gesten, Hallie C. Prescott, Marcus E. Friedrich, Theodore J. Iwashyna, Gary S. Phillips, Stanley Lemeshow, Tiffany Osborn, Kathleen M. Terry, Mitchell M. Levy
Journal: New England Journal of Medicine (2017)

In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients.
Validation of a cancer-specific Oncological-Multidimensional Prognostic Index (Onco-MPI) for mortality prediction in older cancer patients.
Authors: Antonella Brunello, Andrea Fontana, Valeria Zafferri, Ramona Chiarini, Pasquale Fiduccia, Umberto Basso, Massimiliano Copetti, Sara Lonardi, Cristina Falci, Silvio Monfardini, Alberto Pilotto, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2013)

6593 Background: Recently, a Multidimensional Prognostic Index (MPI) based on a Comprehensive Geriatric Assessment (CGA) was developed and validated in independent cohorts of older patients (pts) demonstrating good accuracy in predicting 1-year mortality. Aim of the study was to validate a cancer-specific modified MPI (Onco-MPI) for mortality prediction in older cancer pts. Methods: 658 consecutive new cancer pts aged ≥70 years (mean age 77,1 years, 433 females, 65.8%) referred to the Geriatric Oncology Program from Sep 2004 to June 2011 were included. MPI was calculated according to a previously validated algorithm (derived from multivariate Cox regressions) as a weighted linear combination of the CGA domains: age, sex, basal and instrumental activities of daily living (ADL, IADL), Performance Status, Mini Mental State Examination, Body Mass Index, comorbidity by Cumulative Illness Rating Scale, number of drugs and presence of caregiver. To develop the Onco-MPI, cancer sites (breast 46.5%, colorectal 21.3%, lung 6.4%, prostate 5.5%, urinary tract 5.0%, other 15.3%) and cancer stages (I 37%, II 22%, III 19%, IV 22%) were also included in the model. Pts were followed for a median of 2,5 years and mortality was recorded. Three grades of severity of the onco-MPI (low 0.0-0.46, medium 0.47-0.63, high-risk 0.64-1.0 score) were calculated on the basis of estimated recursive partition and amalgamation method (RECPAM) cut-offs. Discriminatory power and calibration were further assessed. Results: Overall 1-year mortality incidence rate (events/person-years) was 17.4%. A significant difference in mortality rates was observed for Onco-MPI low-risk compared to medium- and high- risk pts (2.1% vs 17.7% vs 80.8%, p&lt;0.0001). The discriminatory power of 1-year mortality prediction of the Onco-MPI was very good (survival C index 0.86, 95%CI 0.83-0.89). The Onco-MPI was well calibrated showing &lt; 10% differences between predicted and observed mortality. Conclusions: The Onco-MPI is an accurate and well-calibrated predictive tool for 1-year mortality in older cancer pts and can be useful for clinical decision making in geriatric oncology.
Exenatide Improves HDL Particle Counts and Size Distribution in Patients With Long-standing Type 1 Diabetes
Authors: Evgenia A. Gourgari, Mihriye Mete, Maureen L. Sampson, David M. Harlan, Alan T. Remaley, Kristina I. Rother
Journal: Diabetes Care (2017)

Glucagon-like peptide 1 agonists such as exenatide have been reported to improve fasting and postprandial lipid profiles and cardiovascular outcomes in patients with type 2 diabetes but to have minimal effects on fasting profiles in patients with type 1 diabetes based on standard lipid measurements.

In this study, we used nuclear magnetic resonance (NMR) to determine the effects of exenatide on lipoprotein particle characteristics, which might be indicative of a change in cardiovascular risk in patients with type 1 diabetes.

This is an ancillary study of a previously published clinical trial (ClinicalTrials.gov identifier NCT00064714) (1). Briefly, 14 patients were randomized to receive exenatide (10 µg four times daily) either in the first or the second 6-month study period in addition to insulin (1). The patients were also randomized to treatment with or without the immunomodulatory drug daclizumab for 12 months (1). Patients underwent repeated mixed-meal tests after an overnight fast. Tests were conducted at the beginning and end of each 6-month period. To estimate the mean differences between treatment groups, linear mixed models were used to control for sequence and period effects and to allow for correlation within the same group using Stata's pkcross command for the analysis of crossover experiments. Results are …
Tetanus in the United States (1965–1966)
Authors: F. Marc LaForce, Lowell S. Young, John V. Bennett
Journal: New England Journal of Medicine (1969)

The case-fatality ratio of 507 cases of tetanus occurring in the United States in 1965 and 1966 was 68 per cent, but it was greater than 75 per cent at the extremes of age. The incidence was highest in the lower Mississippi Valley and the Southeast. Fifty-four patients were neonates, and the median age of the remainder was 48 years. Incidence and mortality rates were more than five times higher for nonwhites than for whites. Case-fatality ratios for patients with convulsions were significantly greater than those for patients without convulsions. The incubation period was considered to be a useful prognostic sign only in patients under 50 years of age. In 97 per cent of cases, a history of immunization was not obtained. Injuries incurred at home led the list of predisposing conditions.
Cardiovascular Mortality Differences—Place Matters
Authors: George A. Mensah, David C. Goff, Gary H. Gibbons
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Uncommon Syndromes and Treatment Manifestations of Malignancy
Authors: Nancy J. Freeman, Debra Holik
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES ERRATUM. September 21, 2016 ARTICLE CITATION DOI: 10.1200/JCO.2003.21.1.170 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12506188 Uncommon Syndromes and Treatment Manifestations of Malignancy Case 3. Richter's Syndrome Heralded by Refractory Hypercalcemia Nancy J. FreemanxNancy J. FreemanSearch for articles by this author , Debra HolikxDebra HolikSearch for articles by this author Show More Hematology/Oncology Section, Brown University School of Medicine, Providence VA Medical Center, Providence, RI https://doi.org/10.1200/JCO.2003.21.1.170 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology Errata ERRATUM
Nearly one in 20 European adolescents is obese, survey finds
Authors: Susan Mayor
Journal: BMJ (2017)

Nearly one in 20 European adolescents is obese, suggests a report on trends and inequalities in obesity among teenagers around Europe, based on latest observations from the Health Behaviour in School Aged Children survey.1

This is a cross national study run by the World Health Organization that monitors the health behaviours, health outcomes, and social environments of teenagers aged 11, 13, and 15 every four years. It has collected …
Biases in the reporting of hepatocellular carcinoma tumor sizes on the liver transplant waiting list
Authors: Mariya L. Samoylova, Mark J. Nigrini, Jennifer L. Dodge, John P. Roberts
Journal: Hepatology (2017)

We investigated the possibility that patients with hepatocellular carcinoma (HCC) listed for liver transplant with tumors just outside stage T2 size criteria may be inaccurately reported as just meeting the tumor size criteria for transplant. The United Network for Organ Sharing/Standard Transplant Analysis and Research database identified 12,958 patients listed for liver transplants with HCC exception points from 2006 to 2013, 9,168 of whom were listed with one tumor. A logistic power peak function was fitted to the single‐tumor size histogram, with the fitted values representing unbiased expected values. The difference between the observed and expected tumor counts for 2.0 cm and 5.0 cm was 238 (22%) and 66 (57%), respectively. This suggests that up to 304 (3.0%) patients with tumors outside of transplant criteria had their measurements recorded at the margins of eligibility. A risk‐adjusted Poisson model evaluated the ratio of observed to expected HCC recurrence by tumor size. There were 435 HCC recurrences among 6,049 transplants. Only 2.0‐cm tumors had observed to expected recurrence differing from 1 (ratio 0.73, 95% confidence interval 0.57‐0.94), indicating a 27% lower than expected rate of recurrence. Conclusion : Higher than expected observed tumor counts at the lower transplant criteria margin were corroborated by lower than expected HCC recurrence, suggesting that tumor sizes at the margins of HCC transplant criteria may be subject to inaccurate reporting. (H epatology 2017;66:1144‐1150)
Controversies in the Treatment of Ductal Carcinoma in Situ
Authors: Andrea V. Barrio, Kimberly J. Van Zee
Journal: Annual Review of Medicine (2017)

Ductal carcinoma in situ (DCIS) accounts for 20% of all newly diagnosed breast cancers. Mastectomy was once the gold standard for the treatment of DCIS; however, breast-conserving surgery (BCS) has been adopted as the treatment of choice for patients with small, screen-detected lesions. Both adjuvant radiation and hormonal therapy following BCS have been demonstrated in randomized trials to reduce the risk of both invasive and DCIS recurrence, but neither affects survival. With the variety of surgical and adjuvant treatment options available, there has been great interest in tailoring the treatment to the individual, with the goal of optimizing the balance of risks and benefits according to the values and priorities of the woman herself. Prospective studies of women with "low-risk" DCIS treated with BCS alone have successfully identified women at lower than average risk but have not achieved the goal of identifying a subset of women with DCIS at minimal risk of recurrence after surgical excision alone. No studies have evaluated the safety of medical management alone.
PWE-217 Pancreatic enzyme replacement therapy in chronic pancreatitis and pancreatic cancer – are we getting it right?: Abstract PWE-217 Table 1
Authors: S Subramaniam, N Nobar, K Besherdas
Journal: Gut (2015)

<h3>Introduction</h3> Pancreatic enzyme insufficiency (PEI) is a well recognised cause of malnutrition in chronic pancreatitis and pancreatic cancer. Pancreatic enzyme replacement therapy (PERT) in the form of enteric coated pancreatin microspheres is recommended in both these groups of patients with symptoms of PEI to prevent weight loss and malnutrition and improve quality of life. Given that the probability of PEI is high in PC (80–90%), PERT is recommended without the use of formal diagnostic tests. The optimal starting dose of PERT is 40–50000 lipase units per main meal. The aim of this study was to evaluate the use of PERT including appropriate dosing in chronic pancreatitis (CP) and pancreatic cancer (PC) and to ascertain if there was a difference in prescribing practice between these groups. <h3>Method</h3> A single centre retrospective analysis of patients diagnosed with CP and PC since 2010 in a large North London district general hospital was performed using local upper gastrointestinal cancer multidisciplinary team records and clinical coding. We identified 149 patients with PC and 110 with CP though 32 patients from the PC group and 4 from CP were excluded from the study due to poor documentation in the records leading to insufficient information surrounding enzyme supplementation and dosages. Information was collected from electronic patient records on the patients’ symptoms, evidence of PERT and the dose prescribed. <h3>Results</h3> Symptoms of pancreatic enzyme insufficiency (abdominal pain, weight loss or steatorrhoea) were recorded in 72/117 (61.5%) of PC patients compared with 75/106 (70.8%) of CP patients. PERT was prescribed in 14/72 (19.5%) patients with PC versus 53/75 (70.7%) with CP. The Table 1shows the enzyme formulation and dosages used in both groups. <h3>Conclusion</h3> In our study we demonstrate that the majority of patients with PEI in CP are prescribed PERT, a stark contrast with a mere 20% in PC. However in both groups, most patients were not prescribed optimal doses of PERT though again, this figure was better in the CP group (14/53 or 26.4%) compared to the PC group (2/14 or 14.3%). This study highlights the missed opportunity to reduce symptoms and improve quality of life in CP and PC patients with a simple intervention. Increased awareness of the availability and appropriate dosing of PERT in conditions resulting in PEI is required. <h3>Disclosure of interest</h3> None Declared.