This document summarizes information about three cancer vaccines - MAGE-A3, Stimuvax (L-BLP25, Tecemotide), and Lucanix (Belagenpumatucel-L). It discusses past and ongoing clinical trials of these vaccines in non-small cell lung cancer (NSCLC), including trial designs, results, and potential efficacy in patient subgroups. Key information presented includes Phase 3 trial results for Stimuvax showing a possible survival benefit in patients receiving concurrent chemotherapy and radiation, and evidence that Belagenpumatucel-L may benefit certain NSCLC patient subgroups based on retrospective analyses.
Dr. David Mooney - Simposio Internacional 'Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
Sipuleucel_T Immunotherapy for Metastatic Prostate Cancer after Failing Hormo...mjavan2001
This PowerPoint presentation demonstrates findings on a clinical trial of sipuleucel-T in HRPC patients to evaluate overall survival in this group. The FDA approval of Provenge was based on the results of IMPACT study.
Current and Novel Immuno-Oncology Drug Evaluation Methods via Humanized Mouse...InsideScientific
Dr. Bin Xie discusses the current immuno-oncology drug development landscape, different humanized mouse models available for drug testing, and the investigation of potential mechanisms via imaging mass cytometry.
Since the first immune checkpoint blocker ipilimumab was approved by the US FDA in 2011, more drug companies have sought to develop their own immune therapy drugs. Humanized peripheral blood mononuclear cell (PBMC) reconstitution in immune deficient mice is becoming a valuable model for evaluating therapeutic antibodies, especially bispecific antibodies (BsAbs), which can mediate immune cells as well as target a tumor antigen.
However, this model has several drawbacks, including a limited dosing window due to graft-versus-host-disease and insufficient natural immune cell infiltration. This has hindered wide application of the model in the development of multiple immune checkpoint inhibitors or immune agonists.
To overcome these issues, LIDE has developed a unique human PBMC/cancer cell co-transfer model which can generate three-dimensional huPBMC-infiltrated tumor tissue for immunotherapy. This model has successfully been used to evaluate the biological function of several signaling proteins and biomarkers in multiple cancers, such as melanoma, breast cancer, and lung cancer.
In this webinar, Dr. Bin Xie discusses the current immuno-oncology drug development landscape, different humanized models available for drug testing, evaluates real-world case studies, and describes the investigation of potential mechanisms by imaging mass cytometry.
Key Topics Include:
- Introduction to immuno-oncology drug development and the importance of using humanized mouse models to address scientific questions
- Evaluation of current IO platforms and new methods from LIDE, including analysis of several case studies
- Understanding the spatiotemporal interaction between tissue-infiltrating immune cells and cancer cells via imaging mass cytometry
Dr. David Mooney - Simposio Internacional 'Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
Sipuleucel_T Immunotherapy for Metastatic Prostate Cancer after Failing Hormo...mjavan2001
This PowerPoint presentation demonstrates findings on a clinical trial of sipuleucel-T in HRPC patients to evaluate overall survival in this group. The FDA approval of Provenge was based on the results of IMPACT study.
Current and Novel Immuno-Oncology Drug Evaluation Methods via Humanized Mouse...InsideScientific
Dr. Bin Xie discusses the current immuno-oncology drug development landscape, different humanized mouse models available for drug testing, and the investigation of potential mechanisms via imaging mass cytometry.
Since the first immune checkpoint blocker ipilimumab was approved by the US FDA in 2011, more drug companies have sought to develop their own immune therapy drugs. Humanized peripheral blood mononuclear cell (PBMC) reconstitution in immune deficient mice is becoming a valuable model for evaluating therapeutic antibodies, especially bispecific antibodies (BsAbs), which can mediate immune cells as well as target a tumor antigen.
However, this model has several drawbacks, including a limited dosing window due to graft-versus-host-disease and insufficient natural immune cell infiltration. This has hindered wide application of the model in the development of multiple immune checkpoint inhibitors or immune agonists.
To overcome these issues, LIDE has developed a unique human PBMC/cancer cell co-transfer model which can generate three-dimensional huPBMC-infiltrated tumor tissue for immunotherapy. This model has successfully been used to evaluate the biological function of several signaling proteins and biomarkers in multiple cancers, such as melanoma, breast cancer, and lung cancer.
In this webinar, Dr. Bin Xie discusses the current immuno-oncology drug development landscape, different humanized models available for drug testing, evaluates real-world case studies, and describes the investigation of potential mechanisms by imaging mass cytometry.
Key Topics Include:
- Introduction to immuno-oncology drug development and the importance of using humanized mouse models to address scientific questions
- Evaluation of current IO platforms and new methods from LIDE, including analysis of several case studies
- Understanding the spatiotemporal interaction between tissue-infiltrating immune cells and cancer cells via imaging mass cytometry
Mackenzie Cottrell, PharmD
Assistant Professor
Co-Director of the UNC CFAR Clinical Pharmacology and Analytical Chemistry Core
Division of Pharmacotherapy and Experimental Therapeutics
University of North Carolina at Chapel Hill
The OncoScan(TM) platform for analysis of copy number and somatic mutations i...Lawrence Greenfield
The OncoScan microarray offers high-quality copy number, genotype, and somatic mutation data with whole-genome coverage and high resolution in cancer genes for use with challenging FFPE samples.
Sequencing 60,000 Samples: An Innovative Large Cohort Study for Breast Cancer...QIAGEN
This slidedeck focuses on the design of a large cohort study for assessing breast cancer risk and how an innovative digital sequencing approach is able to solve the previously unmet challenges of this type of NGS study design. Our speaker, Dr. Fergus J. Couch of the Mayo Clinic, presents on the design of this NCI-funded project, which comprises the sequencing of 60,000 samples to assess the risk of breast cancer through association with targeted genes. The design and size of the study requires an accurate, robust and high-throughput sequencing method. The investigators are using a digital DNA sequencing approach from QIAGEN that incorporates molecular barcodes to tag and remove PCR duplicates and increase NGS assay sensitivity. The approach also uses proprietary chemistry that enables uniform sequencing to efficiently utilize sequencing power and deliver optimized results.
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
Join Fight CRC in a webinar about biomarkers. In this session, Dr. Chris Lieu will focus the discussion on the NTRK biomarker, in addition to ctDNA, and Next-Generation Sequencing.
Dr. Patrick Hwu presents the latest information on immunotherapies for melanoma at the MRF's Patient Symposium at MD Anderson Cancer Center on January 31, 2015.
Learn about novel cell-based assays that enable improved immunotherapy drug development. See case studies utilizing checkpoint receptors such as PD-1, VISTA, and NIK.
Mackenzie Cottrell, PharmD
Assistant Professor
Co-Director of the UNC CFAR Clinical Pharmacology and Analytical Chemistry Core
Division of Pharmacotherapy and Experimental Therapeutics
University of North Carolina at Chapel Hill
The OncoScan(TM) platform for analysis of copy number and somatic mutations i...Lawrence Greenfield
The OncoScan microarray offers high-quality copy number, genotype, and somatic mutation data with whole-genome coverage and high resolution in cancer genes for use with challenging FFPE samples.
Sequencing 60,000 Samples: An Innovative Large Cohort Study for Breast Cancer...QIAGEN
This slidedeck focuses on the design of a large cohort study for assessing breast cancer risk and how an innovative digital sequencing approach is able to solve the previously unmet challenges of this type of NGS study design. Our speaker, Dr. Fergus J. Couch of the Mayo Clinic, presents on the design of this NCI-funded project, which comprises the sequencing of 60,000 samples to assess the risk of breast cancer through association with targeted genes. The design and size of the study requires an accurate, robust and high-throughput sequencing method. The investigators are using a digital DNA sequencing approach from QIAGEN that incorporates molecular barcodes to tag and remove PCR duplicates and increase NGS assay sensitivity. The approach also uses proprietary chemistry that enables uniform sequencing to efficiently utilize sequencing power and deliver optimized results.
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
Join Fight CRC in a webinar about biomarkers. In this session, Dr. Chris Lieu will focus the discussion on the NTRK biomarker, in addition to ctDNA, and Next-Generation Sequencing.
Dr. Patrick Hwu presents the latest information on immunotherapies for melanoma at the MRF's Patient Symposium at MD Anderson Cancer Center on January 31, 2015.
Learn about novel cell-based assays that enable improved immunotherapy drug development. See case studies utilizing checkpoint receptors such as PD-1, VISTA, and NIK.
Key Clinical Implications of how a Cancer EvolvesH. Jack West
Cancer adapts and evolves over time and under the selective pressure of systemic treatment, becoming increasingly resistant over time. This brief slidedoc fo summarizes key points in how cancer adaptation leads to resistance and changes our treatment recommendations.
Dinámica económica, desarrollo productivo exportador de lambayequeAREX Lambayeque
Ponencia realizada en elmarco del DÍA DEL EXPORTADOR, el pasao 9 de noviembre del 2016; a cargo del Mg. Eduardo Elera Hurtado, especialista de Comercio Exterior de la GERCETUR.
Presentación realizada por la Dra. Dolores Isla del
Servicio de Oncología Médica del Hospital Clínico Universitario Lozano Blesa de Zaragoza, en el marco de la I Jornada de actualización e innovación en Oncología que tuvo lugar en el CIBA en enero de 2015.
Talimogene laherparepvec (T-VEC, OncoVEX GM-CSF) phase 3 data in melanoma pre...Virotherapist
Phase 3 data from the OPTiM study in melanoma with talimogene laherparepvec presented as part of a talk on oncolytic immunotherapy at The Eighth International Conference on Oncolytic Virus Therapeutics, Oxford, UK,9-13 April 2014.
Dr. Manuel Hidalgo - Simposio Internacional ' Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
Moving Beyond the Hype: 3 Key Steps for Personalized Cancer MedicineH. Jack West
The concept of personalized or precision medicine is hot enough that President Obama is launching initiatives for it, but how close is it to moving beyond hype?
Here are 3 key steps we need to attain to know that personalized medicine, particularly in the world of cancer care, isn't just delivering false hope for most patients.
Best of ASCO Metastatic Non-Small Cell Lung CancerH. Jack West
Dr. Jack West's presentation on highlights in advanced non-small cell lung cancer from ASCO 2014, focusing on new agents ramucirumab and necitumumab for broad NSCLC populations, crizotinib and ceritinib for ALK-positive NSCLC, EGFR inhibitor-options of afatinib and bevacizumab added to erlotinib for first line treatment of EGFR mutation-positive NSCLC, and AZD9291 or CO1686 for EGFR mutation-positive patients with acquired resistance.
10 Key ASCO 2014 Presentations in Lung CancerH. Jack West
Dr. Jack West offers a list of 10 of the most important, timely abstract presentations in lung cancer, both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), at the annual ASCO 2014 conference.
Transitioning Survival from Months to Years in Advanced Non-Small Cell Lung C...H. Jack West
Dr. Jack West reviews the evolution of new treatment options for advanced NSCLC that have steadily improved survival. This progress has been incremental but now means that an ever-growing proportion of patients with advanced NSCLC have a realistic promise of potentially living several years after their diagnosis and the start of treatment. Note that this presentation does not address advances in immunotherapy, which were covered in a separate talk at the same conference at which Dr. West delivered this presentation.
What is the value of maintenance therapy in advanced NSCLC, and who should ge...H. Jack West
Dr. Jack West reviews the rationale for maintenance therapy in advanced NSCLC, what the evidence shows about its value, the limitations, and thoughts on which patients should or should not pursue it.
50 Shades of Cancer Progression: The Continuum of Progression & How We Decide...H. Jack West
Dr. Jack West reviews the importance of assessing the degree of progression when interpreting whether to change treatment of a cancer. It is important to ask not only whether a cancer has progressed, but HOW it has done so, and how much?
Treating Invisible Disease: How the Probability of Disease We Can't See Chang...H. Jack West
A brief slidedoc that reviews why we focus on both the cancer we can see and the potential cancer we can't when we shape our treatment recommendations in lung cancer and many other cancers.
Changes Afoot: Changing Relationships between Engaged Patients and Docs in Ca...H. Jack West
Discussion of how online patient communities and social media are changing relationships between engaged patients and oncologists, improving quality of cancer care.
Acquired Resistance to Targeted Therapy in EGFR and ALK-Positive Lung Cancer:...H. Jack West
This is a presentation I did for a meeting on new general management of acquired resistance in 2014, including the concept of local therapy for limited progression, and new treatment approaches and new agents for this setting. It features discussion of several of the most important trials.
West egfr mutation acquired resistanceH. Jack West
Review by Dr. H. Jack West of current understanding of mechanisms behind and emerging treatment options for patients with advanced NSCLC with acquired resistance to EGFR tyrosine kinase inhibitors after a good initial response.
Dr. Jack West Oncology 2.0, to WA AG's OfficeH. Jack West
Dr. H. Jack West, medical oncologist and Founder/CEO of Global Resource for Advancing Cancer Education (GRACE, www.CancerGRACE.org), spoke to WA state Attorney General's office about the changing landscape of cancer care and how the internet and specifically online patient communities and education will become disruptive in changing the patient/physician dynamic.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
5. Phase III Study - MAGRIT
MAGE-A3 as Adjuvant Non-Small Cell LunG CanceR ImmunoTherapy
Resected MAGE-A3 (+) NSCLC
Pathological stage IB, II, IIIA
No chemo
Chemo
Randomization
Up to 4 cycles of
platinum-based chemo
MAGE-A3 ASCI
Placebo
Randomization
Powered for efficacy
MAGE-A3 ASCI
Powered for efficacy
>6000 screened for MAGE-A3 to enroll > 2000
Results expected 2H2014
-5-
Placebo
6. Stimuvax (L-BLP25, Tecemotide)
Mucinous glycoprotein overexpressed or
abnormally glycosylated in epithelial
malignancies
MUC1 mucin
GSTAPPAHGVTSAPDTRPAP
S T A P P A H G V T S A P D T R P A P G S T A P P - Lys (PAL) G
Antigen = BLP25 lipopeptide
The amino acids of the lipopeptide provide antigenic epitopes for T cells
Adjuvant = Monophosphoryl lipid A (MPL®)
The adjuvant supports T-cell response by inducing pro-inflammatory cytokines (via TLR4 stimulation)
Structural lipids = cholesterol, DPPC, and DMPG
Further enhancement of antigen delivery/uptake into APCs and immune reaction
6
Presented by: Charles Butts, M.D.
7. Rand Phase 2 of BLP-25 vs. Placebo
N = 171, stage IIIB or IV NSCLC
Prior chemo CR/PR/SD
Overall, median OS 17.4 vs. 13 mo, HR .739, p = 0.112
MPE/Stage IV
Stage IIIB (no MPE)
7
Butts,Presented by: Charles Butts, M.D.
J Clin Oncol, 2005
8. Study design of EMR 63325-001 (START)
Screening
Weekly treatment
6-weekly treatment
Survival
follow-up
Day −3 i.v.
cyclophosphamide /
saline
Unresectable
NSCLC
stage IIIA/B
No progression
following
chemo/RT*
L-BLP25
+ BSC
s.c. administrations L-BLP25/placebo
Randomize
2:1
Placebo
+ BSC
Disease
progression
Randomization strata:
• Stage IIIA vs. IIIB at first diagnosis
• CR/PR vs. SD to initial chemo/RT
• Concurrent vs. sequential chemo/RT
• Geographical region
The primary analysis (OS) was adjusted for
these four variables.
Primary endpoint: Overall survival
Key secondary endpoints:
• Time to symptom progression (TTSP)
as measured by the Lung Cancer
Symptom Scale (LCSS)
• Time to progression (TTP, investigator assessment)
• Safety
*Chemo/RT ≥2 cycles of platinum-based chemotherapy and radiation ≥50 Gy
Presented by: Charles Butts, M.D.
9. Primary endpoint: Overall survival
L-BLP25
(N=829)
Placebo
(N=410)
Median OS
25.6 mo
22.3 mo
Adjusted HR
0.88 (95% CI 0.75‒1.03)
p=0.123*
OS rate (%)
Median
follow-up
39.9 mo
37.7 mo
*Two-sided, strata and multiplicity adjusted
At risk (N)
Placebo
L-BLP25
9
410
829
353
757
285
617
Presented by: Charles Butts, M.D.
188
429
127
301
108
255
88
204
59
128
33
73
18
33
4
8
0
0
10. Secondary endpoint: Time to progression
Placebo
(N=410)
Median TTP
10.0 mo
8.4 mo
Hazard ratio
TTP rate (%)
L-BLP25
(N=829)
0.87 (95% CI 0.75‒1.00)
p=0.053*
*Two-sided, adjusted for strata
Imaging intervals according to institutional standards
At risk (N)
Placebo
L-BLP25
10
410
829
226
513
144
329
Presented by: Charles Butts, M.D.
90
205
58
144
49
122
42
96
25
60
15
30
9
13
3
5
0
0
11. OS: Subgroup analyses by randomization strata
Median OS (months)
L-BLP25 vs. Placebo
HR* (95% CI)
Stage IIIA (N=487)
23.7 vs. 20.9
0.90 (0.74, 1.09)
NA and Aus. (N=321)
34.1 vs. 21.7
0.79 (0.58, 1.09)
24.2 vs. 22.3
0.91 (0.71, 1.17)
Rest of world (N=443)
Response
to chemo/
RT
0.86 (0.67, 1.11)
W. Europe (N=475)
Region
27.6 vs. 23.1
Stage IIIB (N=752)
Stage
21.8 vs. 22.7
0.95 (0.73, 1.22)
Stable disease (N=396) 20.4 vs. 17.8
0.85 (0.65, 1.11)
Obj. response (N=843) 27.8 vs. 23.9
0.91 (0.75, 1.10)
Chemo/ RT Concurrent (N=806)
type
Sequential (N=433)
*Not adjusted for strata
11
Presented by: Charles Butts, M.D.
30.8 vs. 20.6
0.78 (0.64, 0.96)
19.4 vs. 24.6
1.11 (0.86, 1.43)
Favors L-BLP25
Favors placebo
12. Overall survival: Concurrent chemo/RT
Placebo
(N=268)
Median OS
30.8 mo
20.6 mo
Hazard ratio
0.78 (95% CI 0.64‒0.95)
p=0.016*
OS rate (%)
L-BLP25
(N=538)
*Two-sided, adjusted for strata
At risk (N)
Placebo
L-BLP25
12
268
538
227
499
186
412
Presented by: Charles Butts, M.D.
118
295
73
205
62
176
54
147
40
89
26
51
16
24
4
7
0
0
13. Overall survival: Sequential chemo/RT
Placebo
(N=142)
Median OS
19.4 mo
24.6 mo
Hazard ratio
1.12 (95% CI 0.87‒1.44)
p=0.38*
OS rate (%)
L-BLP25
(N=291)
*Two-sided, adjusted for strata
At risk (N)
Placebo
L-BLP25
13
142
291
126
258
99
205
Presented by: Charles Butts, M.D.
70
134
54
96
46
79
34
57
19
39
7
22
2
9
0
1
0
0
14. Overview of adverse events
Preferred term
AE
L-BLP25
N=1,024
n (%)
Placebo
N=477
n (%)
Any
938 (91.6)
432 (90.6)
Any serious
303 (29.6)
151 (31.7)
Any grade 3/4
342 (33.4)
171 (35.8)
46 (4.5)
35 (7.3)
L-BLP25
(N=1,024)
Placebo
(N=477)
Any
176 (17.3)
56 (11.9)
0 (0)
0 (0)
L-BLP25
(N=1,024)
Placebo
(N=477)
391 (38.2)
8 (1.7)
Any Grade 3/4
Flu-like symptoms
Any
Any Grade 3/4
14
Cough
338 (33.0)
133 (27.9)
Dyspnea
238 (23.2)
112 (23.5)
Fatigue
197 (19.2)
102 (21.4)
146 (14.3)
53 (11.1)
140 (13.7)
39 (8.2)
Chest pain
135 (13.2)
45 (9.4)
Nasopharyngitis
128 (12.5)
44 (9.2)
Headache
124 (12.1)
54 (11.3)
Decreased
appetite
109 (10.6)
44 (9.2)
Arthralgia
108 (10.5)
34 (7.1)
158 (33.1)
15 (1.5)
Placebo
N=477
n (%)
Nausea
Injection site
reactions
L-BLP25
N=1,024
n (%)
Back pain
Any leading to death
Most frequent
adverse events
(>10 % in
L-BLP25 arm)
Presented by: Charles Butts, M.D.
Injection-site reactions and flu-like symptoms
were identified by MedDRA PT search.
15. INSPIRE Trial (Asia)
• N = 500
Stage III
unresectable NSCLC
CR/PR/SD after >2
cycles platinum-based
doublet chemotherapy
with concurrent or
sequential RT
15
Presented by: Charles Butts, M.D.
2
R
A
N
D
1
Tecemotide
Placebo
• Primary endpoint: overall survival
16. START2 Trial, just being initiated
• N = 1002
Stage III
unresectable NSCLC
CR/PR/SD after >2
cycles platinum-based
doublet chemotherapy
with concurrent RT
2
R
A
N
D
1
Tecemotide
Placebo
• Primary endpoint: overall survival
16
Presented by: Charles Butts, M.D.
17. Belagenpumatucel-L: Allogeneic whole tumor cell vaccine
– Four irradiated, cryopreserved NSCLC tumor cell lines
– Each gene-modified to block TGF-β2 secretion
1.0
Survival
All
N
Median
(months)
1-yr
2-yr
5-yr
75
14.5
55%
35%
20%
1
25
10.4
42%
21%
17%
2
26
21.8
67%
46%
21%
3
24
15.8
57%
39%
0.8
Survival
Cohort
Cohort 1
Cohort 2
Cohort 3
0.6
22%
2 stage II patients
12 stage IIIA patients
15 stage IIIB patients
46 stage IV patients
0.4
0.2
0.0
0
12/71 patients (17%) alive (Mar, 2009)
Survival range: 48 - 76 months
4 lost to follow up
12
24
36
48
60
72
Months
Orig data - Nemunaitis, JCO 2006
Data from March 2009
18. Overall survival of phase III-eligible patients
N
Median
(months)
1-yr
2-yr
5-yr
SD, PR, or
CR
18
44
65%
59%
50%
PD
11
1.0
14
64%
36%
14%
BSC-SD,
PR, or CR
11
35%
8%
<5%
BSC-PD
5
0.8
8%
<5%
<5%
Patients received one front-line, combination
chemotherapy regimen:
• with or without adjuvant chemotherapy
• with or without radiation therapy
Survival
Patients who enrolled with SD/PR/CR
8/16 patients (50%) currently alive
Survival range: 51 - 68 months
BSC = best standard of care
SD = stable disease; PR = partial response; CR = complete response
PD = progressive disease
0.6
0.4
Patients who enrolled with PD
0.2
0.0
0
12
24
36
Months
Time (Months)
48
60
Orig data - Nemunaitis, JCO 2006
March 2009
19. STOP trial of Belagenpumatucel vs. Placebo as Maintenance Therapy
• N = 532, 42 with stage IIIA, 490 stage IIIB/IV (NOT all “wet” IIIB)
Stage IIIA/IIIB/IV
NSCLC
CR/PR/SD after 4
cycles platinum-based
doublet chemotherapy
1
R
A
N
D
1
start Rx 4-17 wks
after chemo
Belagenpumatucel-L
Placebo
• Primary endpoint: overall survival
20. STOP trial of Belagenpumatucel vs. Placebo as Maintenance Therapy
• Overall results negative for OS benefit
– med OS 20.3 vs. 17.8 mo (HR 0.94)
– Minimal toxicity (grade 2 rash at most)
• Cox regression analysis (post hoc)
– Stage IIIB/IV pts starting within 12 weeks of prior chemo
med OS 20.7 vs. 13.4 mo (HR = 0.75, p = 0.083)
– Prior RT: med OS 40.1 vs. 10.3 mo (HR = 0.45, p = 0.014)
– Non-adeno, starting within 12 weeks of prior chemo >
med OS 19.9 vs. 12.3 mo (HR 0.55, p = 0.036)
• FDA notes interest in continued study in subgroups
Giaccone, ESMO 2013
21. Conclusions: Vaccines Have Potential for
Efficacy with Excellent Therapeutic Index
• MAGE-A3: MAGRIT trial results awaited this year; have
potential to change standard of care for MAGE-A3
antigen-positive NSCLC in adjuvant setting
• START trial with tecemotide showed promising results
for patients who received concurrent chemo/RT
– Await results of INSPIRE trial (Asia, START design)
– START2 trial of tecemotide after concurrent CT/RT being
initiated (N = 1002)
• Belagenpumatucel: Subsets identified as beneficiaries
– Subsequent study? TBD