tbuckley/cabot-search huggingface dataset:
Phase 3 study of carboplatin-paclitaxel/nab-paclitaxel (Chemo) with or without pembrolizumab (Pembro) for patients (Pts) with metastatic squamous (Sq) non-small cell lung cancer (NSCLC).
Authors: Luis G. Paz-Ares, Alexander Luft, Ali Tafreshi, Mahmut Gumus, Julien Mazieres, Barbara Hermes, Filiz Cay Senler, Andrea Fülöp, Jeronimo Rodriguez-Cid, Shunichi Sugawara, Ying Cheng, Silvia Novello, Balazs Halmos, Yue Shentu, Dariusz Kowalski
Journal: Journal of Clinical Oncology (2018)

105 Background: Pembro plus pemetrexed and carboplatin resulted in superior objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) for untreated pts with non-sq NSCLC. Pembro is active in sq NSCLC, so combining with chemo is a rational next step. Methods: KEYNOTE-407 (NCT02775435) is a randomized, placebo-controlled, global study of 560 untreated pts with metastatic sq NSCLC with ECOG 0-1. Pts were stratified by type of taxane, PD-L1 (TPS <1% vs ≥1%), and site (East Asia vs other). Investigators chose taxane. Pts were randomized 1:1 to receive carboplatin 6 mg/mL/min and paclitaxel 200 mg/m2 every 3 weeks or nab-paclitaxel 100 mg/m2 weekly plus pembro or saline placebo for 4 cycles followed by pembro/placebo for a total of 35 treatments. Imaging is sent for blinded independent central review (BICR) per RECIST 1.1. The primary endpoints are PFS by BICR and OS in the intent-to-treat population. Alpha is strictly controlled at 0.025 one-sided; PFS and OS each have 0.01. A key secondary endpoint is ORR by BICR in about the first 200 pts randomized with 0.005 alpha. A second interim analysis will be performed on PFS and OS when approximately 332 PFS events will have occurred. The hazard ratio (target 0.7) will be estimated using a stratified Cox regression model. The arms will be compared with a stratified log-rank test. Enrollment completed at the end of 2017. Results: In the first interim analysis, the initial 204 pts were randomized 101 to pembro + chemo and 103 to chemo with median follow-up of 7.7 m (range 0.4, 13.9). Pts were 78% male, 48% < 65 y, and 28% ECOG PS 0. PD-L1 status was 35% TPS<1%. 32% used nab-paclitaxel. Per BICR pembro + chemo had an ORR of 58.4% compared to 35.0%, p-value 0.0004. Duration of response ≥6m was 65.8% for pembro + chemo and 45.6% for chemo by Kaplan-Meier estimates. Incidence grade ≥3 AEs was 64.4% for pembro + chemo and 74.5% for chemo. No new safety concerns were observed. Conclusions: Adding pembro almost doubled the ORR of chemo for pts with untreated metastatic sq NSCLC. Pembro + chemo has a tolerable safety profile. Results from a second interim analysis may be available prior to the meeting. Clinical trial information: NCT02775435.
Epacadostat plus nivolumab in patients with advanced solid tumors: Preliminary phase I/II results of ECHO-204.
Authors: Raymond P. Perez, Matthew John Riese, Karl D. Lewis, Mansoor N. Saleh, Adil Daud, Jordan Berlin, James J. Lee, Sutapa Mukhopadhyay, Li Zhou, Gul Serbest, Omid Hamid
Journal: Journal of Clinical Oncology (2017)

3003 Background: ECHO-204 is an ongoing, open-label, phase 1/2 (P1/2) study of epacadostat (E; potent and selective oral inhibitor of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1) plus PD-1 inhibitor nivolumab (N) in patients (pts) with advanced cancers (NSCLC, MEL, OVC, CRC, SCCHN, B-cell NHL [including DLBCL], GBM). Preliminary P1/2 safety and tolerability outcomes for the overall study population and P2 response for select tumor types (SCCHN, MEL, OVC, CRC) are reported. Methods: In P1 dose escalation, pts received E (25, 50, 100, 300 mg BID) + N (3 mg/kg Q2W); in P2 cohort expansion, pts received E (100 or 300 mg BID) + N (240 mg Q2W). Safety/tolerability was assessed in pts receiving ≥1 E + N dose. Response was assessed in RECIST v1.1 evaluable pts; for recently enrolled pt subgroups, only preliminary DCR (CR+PR+SD) is presented. Results: As of 29OCT2016,241 pts (P1, n = 36; P2, n = 205) were enrolled. No DLT was observed in P1. Most common TRAEs (≥15%) in pts treated with E 100 mg (n = 70) and E 300 mg (n = 135) were rash (33% and 22%, respectively), fatigue (26% and 31%), and nausea (24% and 19%). Rash was the most common grade ≥3 TRAE in E 100 mg and E 300 mg subgroups (10% and 12%). TRAEs led to discontinuation in 7% (E 100 mg) and 13% (E 300 mg) of pts. There were no TR-deaths. For the 23 recently enrolled, efficacy-evaluable SCCHN pts treated with E 300 mg, preliminary DCR was 70% (n = 16). Of 30 MEL pts, 8 were treated with E 100 mg and 22 were more recently enrolled and treated with E 300 mg. ORR (CR+PR) and DCR in MEL pts treated with E 100 mg were 75% (n = 6; all PR) and 100% (n = 8; 2 SD), respectively. Preliminary DCR in MEL pts treated with E 300 mg was 64% (n = 14). Of 29 OVC pts, 18 were treated with E 100 mg and 11 with E 300 mg.ORR and DCR for OVC pts treated with E 100 mg were 11% (n = 2; 2 PR) and 28% (n = 5; 3 SD); for 11 OVC pts treated with E 300 mg, ORR and DCR were 18% (n = 2; 2 PR) and 36% (n = 4; 2 SD).For 25 CRC pts (all E 100 mg), ORR and DCR were 4% (n = 1; PR) and 24% (n = 6; 5 SD).Safety/efficacy evaluations are ongoing for all cohorts. Conclusions: E + N was generally well tolerated up to the maximum E 300-mg dose. P2 ORR/DCR outcomes are promising, particularly in SCCHN and MEL pts. Updated data will be presented at the meeting. Clinical trial information: NCT02327078.
Comparison of Burnet's clonal selection theory with tumor cell-clone development
Authors: Borros Arneth
Journal: Theranostics (2018)

Increasing evidence has shown that Darwin's theory of evolution provides vital insights into the emergence and etiology of different types of cancer.On a microscopic scale, cancer stem cells meet the conditions for the Darwinian process of natural selection.In particular, cancer stem cells undergo cell reproduction characterized by the emergence of heritable variability that promotes replication and cell survival.Methods: Evidence from previous studies was gathered to compare Burnet's clonal selection theory with the tumor evolution theory. Results:The findings show that the Darwinian theory offers a general framework for understanding fundamental aspects of cancer.As fundamental theoretical frameworks, Burnet's clonal selection theory and the tumor evolution theory can be used to explain cancer cell evolution and identify the beneficial adaptations that contribute to cell survival in tissue landscapes and tissue ecosystems. Conclusions:In conclusion, this study shows that both Burnet's clonal selection theory and the tumor evolution theory postulate that cancer cells in tissue ecosystems evolve through reiterative processes, such as clonal expansion, clonal selection, and genetic diversification.Therefore, both theories provide insights into the complexities and dynamics of cancer, including its development and progression.Finally, we take into account the occurrence of biologic variation in both tumor cells and lymphocytes.It is important to note that the presence of lymphocyte variations appears to be advantageous in the framework of tumor defense but also dangerous within the framework of autoimmune disease development.
Progress Toward Rubella and Congenital Rubella Syndrome Control — South-East Asia Region, 2000–2016
Authors: Sudhir Khanal, Sunil Bahl, Mohammad Sharifuzzaman, Deepak Dhongde, Sirima Pattamadilok, Susan Reef, Michelle Morales, Alya Dabbagh, Katrina Kretsinger, Minal Patel
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR)* adopted the goal of elimination of measles and control† of rubella and congenital rubella syndrome (CRS) by 2020 (1). Rubella is the leading vaccine-preventable cause of birth defects. Although rubella typically causes a mild fever and rash in children and adults, rubella virus infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, or a constellation of congenital malformations known as CRS, commonly including visual, auditory, and/or cardiac defects, and developmental delay (2). Rubella and CRS control capitalizes on the momentum created by pursuing measles elimination because the efforts are programmatically linked. Rubella-containing vaccine (RCV) is administered as a combined measles and rubella vaccine, and rubella cases are detected through case-based surveillance for measles or fever and rash illness (3). This report summarizes progress toward rubella and CRS control in SEAR during 2000-2016. Estimated coverage with a first RCV dose (RCV1) increased from 3% of the birth cohort in 2000 to 15% in 2016 because of RCV introduction in six countries. RCV1 coverage is expected to increase rapidly with the phased introduction of RCV in India and Indonesia beginning in 2017; these countries are home to 83% of the SEAR birth cohort. During 2000-2016, approximately 83 million persons were vaccinated through 13 supplemental immunization activities (SIAs) conducted in eight countries. During 2010-2016, reported rubella incidence decreased by 37%, from 8.6 to 5.4 cases per 1 million population, and four countries (Bangladesh, Maldives, Sri Lanka, and Thailand) reported a decrease in incidence of ≥95% since 2010. To achieve rubella and CRS control in SEAR, sustained investment to increase routine RCV coverage, periodic high-quality SIAs to close immunity gaps, and strengthened rubella and CRS surveillance are needed.
Smoking cessation among cancer survivors: United States, 2015.
Authors: Michael Shayne Gallaway, Rebecca Glover-Kudon, Behnoosh Momin, Mary Puckett, Buchanan Lunsford Natasha, Kathleen Ragan, Elizabeth Rohan, Stephen Babb
Journal: Journal of Clinical Oncology (2018)

111 Background: The prevalence of smoking among persons with a history of cancer (cancer survivors) is similar to the general population. However, there is a paucity of evidence on the prevalence of specific smoking cessation behaviors among adult cancer survivors. Methods: Data from the 2015 National Health Interview Survey (NHIS) were analyzed to examine the prevalence of smoking cessation behaviors (interest in quitting, recent quit attempt, advised to quit by a healthcare professional visited in the past year) and treatments (counseling, medication) among cancer survivors. Weighted self-reported prevalence estimates and 95% confidence intervals were calculated, and chi-square test statistics were used to assess between group differences. Results: The sample included 2,541 cancer survivors, of which 12% were current smokers, 37% were former smokers, and 51% were never smokers. Compared with former and never smokers, cancer survivors who were current smokers were younger (less than 65 years), less educated, and reported being uninsured or reported having Medicaid health insurance less often (p &lt; 0.01). Fewer female cancer survivors reported being a former smoker than a current or never smoker. Most current smokers reported wanting to quit smoking (57%), a past year quit attempt (49%), or that a health professional advised them to quit smoking in the past 12 months (66%). Current smokers reported the use of smoking cessation counseling (8%), medication (38%), or either (41%). Conclusions: Approximately half of current smokers reported a recent quit attempt and more than half wanted to quit smoking. Less than 1 of 2 current smokers reported using any cessation assistance. The Centers for Disease Control and Prevention’s National Comprehensive Cancer Control Program supports increasing knowledge and availability of evidence-based tobacco cessation services among cancer survivors. Health professionals could consistently highlight the increased risks associated with continued smoking among cancer survivors, provide them with cessation counseling and/or medication, refer them to other free cessation resources, and inform them of cessation treatments covered by their health insurance. Population-level interventions may also be impactful.
<i>Trichophyton erinacei</i> Transmitted to a Pregnant Woman From Her Pet Hedgehogs
Authors: Christian Kromer, Pietro Nenoff, Silke Uhrlaß, Antje Apel, Michael Peter Schön, Undine Lippert
Journal: JAMA Dermatology (2018)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Dermatology journal
Isosulfan blue: Rates of perioperative anaphylaxis—A single center retrospective analysis.
Authors: Vinay Goswamy, Bushra Tbakhi, S. Shahzad Mustafa, Lori Medeiros
Journal: Journal of Clinical Oncology (2018)

e12617 Background: Isosulfan blue (IB), or Lymphazurin dye, is a synthetic triphenylmethane containing rosaniline dye used as a visual imaging agent in lymph node mapping procedures, particularly in sentinel lymph node biopsy for patients with breast cancer, melanoma, and other solid tumors. Anaphylaxis is a feared complication of IB administration, with a reported incidence ranging between 0.2% to 1.6%. Reported incidence of allergic reactions range from 1.6% to 2.0%. The incidence is based on a small number of studies and case reports. This study examines the degree of Isosulfan blue’s safety for use as a substitute for methylene blue, as the latter is sometimes available in limited supply due to manufacturing shortage. Methods: In this single center retrospective analysis, we reviewed 1163 consecutive charts of patients that underwent sentinel lymph node biopsy using IB dye between 2014 and 2017. All documentation of suspected allergic reactions to IB were recorded and reviewed by an independent board-certified allergist. Cases that involved methylene blue or that lacked documentation of IB use were excluded. Results: The rate of confirmed hypersensitivity reactions to isosulfan blue was 0.17% (2/1163). Both reactions resulted in urticaria. Zero cases of anaphylaxis were observed. Patients were also stratified by a history of allergy to sulfa antibiotics and asthma. Zero patients with a sulfa allergy had any type of allergic reaction to IB. Of all patients with a history of asthma, 0.71% (1/141) had a likely allergic reaction, manifested as a rash. Conclusions: This study shows that the incidence of hypersensitivity reactions, particularly anaphylaxis, to isosulfan blue is lower than previously reported. This supports the use of IB as a practical alternative to methylene blue in situations of shortage. Moreover, the low risk of hypersensitivity reactions to IB alludes to the possibility of its safe use in the outpatient setting, although further multi-center, prospective studies would be needed to determine the feasibility of this approach.
Hemophagocytic lymphohistiocytosis with immunotherapy: brief review and case report
Authors: Masood Sadaat, Sekwon Jang
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Hemophagocytic Lymphohistiocytosis (HLH), a rare but potentially fatal syndrome of immune hyperactivation, may be an under-recognized immune-related adverse event (irAE). Unlike other irAEs, HLH triggered by immune checkpoint blockade is not well described; no particular diagnostic guidelines and treatment regimens exist. The HLH-2004 criteria remain as the common diagnostic guide. For the treatment of HLH, various combinations of chemotherapeutic, immunosuppressive and glucocorticoid agents are used. <h3>Case presentation</h3> We report a case of HLH in a 58-year-old metastatic melanoma patient who was undergoing immune checkpoint blockade with pembrolizumab, a programmed cell death-1 (PD-1) receptor inhibitor. The patient presented with fever, upper normal sized spleen, anemia, thrombocytopenia, hypertriglyceridemia, hyperferritinemia, reduced NK cell activity and elevated sCD163 levels, fulfilling the Histiocyte Society HLH-2004 diagnostic criteria. Our patient was successfully treated with oral prednisone (1&nbsp;mg/kilogram/day), suggesting that HLH from immune checkpoint inhibitors may respond to steroids alone. <h3>Conclusion</h3> Early diagnosis and treatment of HLH are critical to avoid progressive tissue damage, organ failure and possibly death. HLH should be suspected in clinical presentations with fever, cytopenias and hyperinflammatory markers. HLH in the setting of immune checkpoint blockade may be treated with steroids only but further evidence is required.
Abstract 16952: Genetic Deficiency of 12/15Lipoxygenase Activates EP4 Receptor on Proresolving Macrophages to Attenuate Renal Inflammation After Myocardial Infarction
Authors: Vasundhara Kain, Kevin A Ingle, Sumanth D Prabhu, Ganesh V Halade
Journal: Circulation (2016)

Introduction: 12/15lipoxygenase (12/15LOX) metabolites and cyclooxygenase-2(COX-2)-derived prostaglandin E2 (PGE2) are key mediators of the inflammatory response after myocardial infarction (MI); t...
FDA Blitz on Nicotine Product Sales to Minors
Authors: Rebecca Voelker
Journal: JAMA (2018)

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
Pathological complete response in basal subtype tumors to predict improved distant metastasis free survival in the NBRST trial.
Authors: Pat W. Whitworth, Paul Baron, Peter D. Beitsch, Sarah Untch, Erin Yoder, Tina Treece, M. William Audeh
Journal: Journal of Clinical Oncology (2018)

590 Background: In the multi-institutional NBRST study (NCT01479101), conducted from June 2011 to December 2014, 20% of ER+/HER2- patients were classified as Basal subtype by the 80-gene functional subtype signature (80-GS). 3-year event-driven follow-up (FU) is now available. Methods: The 70-gene risk of recurrence signature (70-GS) and 80-GS results were combined to classify patients (Pts) into four molecular subtypes: Basal, HER2, Luminal-B (high risk Luminal), and Luminal-A (low risk Luminal). The rate of pathological complete response (pCR) was previously assessed following neoadjuvant therapy. Here we evaluated FU for these Pts to determine if pCR was predictive of positive outcome using distant metastasis free interval (DMFI) as an endpoint. Results: Of 706 NBRST Pts currently reporting FU, 35% were Basal, 16% HER2, 34% Luminal-B, and 15% Luminal-A. Overall 26% of Pts had a pCR, with notable differences by subtype: 34% in Basal, 67% in HER2, 9% in Luminal-B, and 5% pCR in Luminal-A patients. FU from diagnosis ranged from 0.3-70.8 months (median 34 months). Sixty-nine percent of Pts received some adjuvant therapy: 51% endocrine therapy (AET), 10% chemotherapy (ACT), and 16% received adjuvant targeted therapy (53% with AET/ACT). There were 94 DMFI events at last FU: 81 in Pts who did not have a pCR, 13 in Pts who did have a pCR. 80-GS basal subtype Pts who achieved a pCR exhibited better 3-yr probability of DMFI, compared to those who did not. Conclusions: NBRST’s event-driven FU supports the I-SPY2 TRIAL’s findings that a pCR predicts better distant metastasis free outcomes. The results in this population further show that 80-GS basal subtype patients with pCR have substantially better outcome at 3 years, compared to those who do not have pCR. 70-GS low risk Luminal Pts showed minimal impact with neoadjuvant chemotherapy. Clinical trial information: NCT01479101. pCR no pCR Hazard Ratio Subtype events/total Pts %DMFI at 3yrs events/total Pts %DMFI at 3yrs Ratio (95%CI) P value Basal 7/83 94% (88-100%) 52/163 68% (60-76%) 0.13 (0.048-0.36) < 0.001 HER2 3/77 96% (91-100%) 4/38 91% (81-100%) 0.37 (0.08-1.68) 0.20 Luminal-B 3/21 95% (87-100%) 22/216 91% (86-95%) 1.17 (0.35 -3.94) 0.81 Luminal-A 0/5 100% 3/103 96% (92-100%) 0 (NA) 0.61