DOCSLIB.ORG

Radiation Therapy for Brain Metastases

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

JUNE 2021 SYSTEMATIC REVIEW Radiation Therapy for Brain Metastases In Partnership with Comparative Effectiveness Review Number 242 Radiation Therapy for Brain Metastases Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 Fishers Lane Rockville, MD 20857 www.ahrq.gov and Patient-Centered Outcomes Research Institute 1828 L Street, NW, Ste. 900 Washington, DC 20036 www.pcori.org Contract No. 290-2015-00010-I Prepared by: Southern California Evidence-based Practice Center Santa Monica, CA Investigators: Adam Garsa, M.D. Julie K. Jang, M.D., Ph.D. Sangita Baxi, M.A.S, M.Phil. Christine Chen, M.D. Olamigoke Akinniranye, M.S. Owen Hall, M.S. Jody Larkin, M.S. Aneesa Motala, B.A. Sydne Newberry, Ph.D. Susanne Hempel, Ph.D. AHRQ Publication No. 21-EHC021 PCORI® Publication No. 2020-SR-02 June 2021 This report is based on research conducted by the Southern California Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2015-00010-I). The Patient-Centered Outcomes Research Institute® (PCORI®) funded the report (No. 2020-SR-02). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ or PCORI. Therefore, no statement in this report should be construed as an official position of PCORI, AHRQ, or the U.S. Department of Health and Human Services. None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report. The information in this report is intended to help healthcare decision makers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of healthcare services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients. This report is made available to the public under the terms of a licensing agreement between the author and the Agency for Healthcare Research and Quality. This report may be used and reprinted without permission except those copyrighted materials that are clearly noted in the report. Further reproduction of those copyrighted materials is prohibited without the express permission of copyright holders. PCORI®, AHRQ, or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied. AHRQ appreciates appropriate acknowledgment and citation of its work. Suggested language for acknowledgment: This work was based on an evidence report, Radiation Therapy for Brain Metastases, by the Evidence-based Practice Center Program at the Agency for Healthcare Research and Quality (AHRQ). Suggested citation: Garsa A, Jang JK, Baxi S, Chen C, Akinniranye O, Hall O, Larkin J, Motala A, Newberry S, Hempel S. Radiation Therapy for Brain Metastases. Comparative Effectiveness Review No. 242. (Prepared by the Southern California Evidence-based Practice Center under Contract No. 290-2015-00001-I.) AHRQ Publication No. 21-EHC021. PCORI Publication No. 2020-SR-02. Rockville, MD: Agency for Healthcare Research and Quality; June 2021. DOI: https://doi.org/10.23970/AHRQEPCCER242, Posted final reports are located on the Effective Health Care Program search page. ii Preface The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-based Practice Centers (EPCs), sponsors the development of systematic reviews to assist public- and private-sector organizations in their efforts to improve the quality of healthcare in the United States. These reviews provide comprehensive, science-based information on common, costly medical conditions, and new healthcare technologies and strategies. The Patient-Centered Outcomes Research Institute® (PCORI®) was established to fund research that helps patients and caregivers make better informed healthcare choices. To fulfill its authorizing mandate, PCORI partners with AHRQ to generate evidence synthesis products and make comparative effectiveness research more available to patients and providers. Systematic reviews are the building blocks underlying evidence-based practice; they focus attention on the strength and limits of evidence from research studies about the effectiveness and safety of a clinical intervention. In the context of developing recommendations for practice, systematic reviews can help clarify whether assertions about the value of the intervention are based on strong evidence from clinical studies. For more information about AHRQ EPC systematic reviews, see www.effectivehealthcare.ahrq.gov/about/epc/evidence-synthesis. AHRQ expects that these systematic reviews will be helpful to health plans, providers, purchasers, government programs, and the healthcare system as a whole. Transparency and stakeholder input are essential to the Effective Health Care Program. Please visit the website (www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join an email list to learn about new program products and opportunities for input. If you have comments on this systematic review, they may be sent by mail to the Task Order Officer named below at: Agency for Healthcare Research and Quality, 5600 Fishers Lane, Rockville, MD 20857, or by email to [email protected]. David Meyers, M.D. Arlene S. Bierman, M.D., M.S. Acting Director Director, Center for Evidence and Practice Agency for Healthcare Research and Quality Improvement Agency for Healthcare Research and Quality Nakela Cook, M.D., M.P.H. William Lawrence, M.D., M.S. Executive Director Senior Clinical Advisor Patient-Centered Outcomes Research Institute Office of the Chief Engagement and Dissemination Officer Patient-Centered Outcomes Research Institute Christine Chang, M.D., M.P.H. Lionel Bañez, M.D. Acting Director Task Order Officer Evidence-based Practice Center Program Center for Evidence and Practice Center for Evidence and Practice Improvement Improvement Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality Michelle Althuis, Ph.D., M.A. Jennie Dalton Bowen, M.P.H. Associate Director Program Officer Patient-Centered Outcomes Research Institute Patient-Centered Outcomes Research Institute iii Acknowledgments The authors gratefully acknowledge the following individuals for their contributions to this project: Lionel Bañez, Jennie Dalton Bowen, Lisa Bradfield, and Ethan Balk for helpful comments. We also thank the authors Paul Brown, Lois Browne, Peter Graham, Siow Ming Lee, Mark Middleton, Alan Nichol, Stephanie Pugh, Srinivas Raman, and Daniel Roos for additional data or clarifications regarding data. In addition, we would like to thank Armenda Bialas and Lea Xenakis for project assistance. Key Informants In designing the study questions, the EPC consulted several Key Informants who represent the end-users of research. The EPC sought the Key Informant input on the priority areas for research and synthesis. Key Informants are not involved in the analysis of the evidence or the writing of the report. Therefore, in the end, study questions, design, methodological approaches, and/or conclusions do not necessarily represent the views of individual Key Informants. Key Informants must disclose any financial conflicts of interest greater than $5,000 and any other relevant business or professional conflicts of interest. Because of their role as end-users, individuals with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any conflicts of interest. The list of Key Informants who provided input to this report follows: Ralph DeVitto Sharon Mesmer American Brain Tumor Association Patient Advocate Chicago, IL Los Angeles, CA Rebecca Kirch, J.D. Hans Messersmith, M.P.H. National Patient Advocate Foundation American Society of Clinical Oncology Washington, DC (ASCO) Alexandria, VA Tim Kruser, M.D. Northwestern Memorial Hospital Debbie Robins, M.S., CFRE Northwestern University Feinberg School of American Brain Tumor Association Medicine Chicago, IL American Society for Radiation Oncology (ASTRO) Nicole Willmarth, Ph.D. Chicago, IL American Brain Tumor Association Chicago, IL iv Technical Expert Panel In designing the study questions and methodology at the outset of this report, the EPC consulted several technical and content experts. Broad expertise and perspectives were sought. Divergent and conflicted opinions are common and perceived as healthy scientific discourse that results in a thoughtful, relevant systematic review. Therefore, in the end, study questions, design, methodologic approaches, and/or conclusions do not necessarily represent the views of individual technical and content experts. Technical Experts must disclose any financial conflicts of interest greater than $5,000 and any other relevant business or professional conflicts of interest. Because of their unique clinical or content expertise, individuals with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any potential
Recommended publications
  • Targeted Radiotherapy of Brain Tumours

    Targeted Radiotherapy of Brain Tumours

    British Journal of Cancer (2004) 90, 1469 – 1473 & 2004 Cancer Research UK All rights reserved 0007 – 0920/04 $25.00 www.bjcancer.com Minireview Targeted radiotherapy of brain tumours ,1 MR Zalutsky* 1Department of Radiology, Duke University Medical Center, PO Box 3808, Durham, NC 27710, USA The utility of external beam radiotherapy for the treatment of malignant brain tumours is compromised by the need to avoid excessive radiation damage to normal CNS tissues. This review describes the current status of targeted radiotherapy, an alternative strategy for brain tumour treatment that offers the exciting prospect of increasing the specificity of tumour cell irradiation. British Journal of Cancer (2004) 90, 1469–1473. doi:10.1038/sj.bjc.6601771 www.bjcancer.com Published online 6 April 2004 & 2004 Cancer Research UK Keywords: glioblastoma multiforme; radiotherapy; radioimmunotherapy; glioma; anaplastic astrocytoma Even with aggressive multi-modality treatment strategies, the life present both on glioma as well as normal neural tissue (Hopkins expectancy for patients with glioblastoma multiforme (GBM), the et al, 1998). However, the vast majority of targeted radiotherapy most common and virulent primary brain tumour, is less than a studies in brain tumour patients have utilised radiolabelled mAbs year from the time of diagnosis (Stewart, 2002). The vast majority reactive with the tenascin molecule (Table 1). of glioma patients experience local recurrence, with a median survival of only 16–24 weeks for those with recurrent disease (Wong et al, 1999). Conventional radiotherapy continues to play a TENASCIN AND ANTI-TENASCIN MABS primary role in brain cancer treatment; however, its lack of tumour Tenascin-C is a hexabrachion polymorphic glycoprotein that is specificity is a severe limitation of this form of therapy.
  • When Cancer Spreads to the Bone

    When Cancer Spreads to the Bone

    When Cancer Spreads to the Bone John U. (pictured) was diagnosed with kidney cancer which metastasized to the bone over 10 years ago. Since then, he has had over a dozen procedures to stabilize his bones. Cancer occurs when cells in your body their cancer has spread to their bones. start growing and dividing faster than is booklet explains: normal. At rst, these cells may form into • Why bone metastases occur small clumps or tumors. But they can • How they are treated also spread to other parts of the body. When cancer spreads, it is said to have • What patients with bone metastases can “metastasized.” do to prevent broken bones and fractures It is possible for many types of cancer to spread to the bones. People with cancer can live for years after they have been told What is Bone? BONE ANATOMY Many people don’t spend much time thinking about their bones. But there’s a lot going on Trabecular Bone inside them. Bone is living, growing tissue, Blood vessels in bone marrow made up of proteins and minerals. Your bones have two layers. The outer layer— called cortical bone— is very thick. The inner layer—the trabecular (truh-BEH-kyoo-ler) bone—is very spongy. Inside the spongy bone is your bone marrow. It contains stem cells that can develop into white blood cells, red blood cells, and platelets. Cortical Bone The cells that make up the bones are always changing. There are three types of cells that are found only in bone: Osteoclasts (OS-tee-oh-klast), which break down the bone LLC, US Govt.
  • QUEST Provider Bulletin

    QUEST Provider Bulletin

    HMSA Provider Bulletin HMS A ’ S P L an fo R Q U E S T M embe R S Bulletin Q08-01 January 15, 2008 A MESSAGE FROM OUR appointments, ensuring the collection and forwarding of MEDICAL DIRECTOR necessary information, obtaining prior authorizations, educating the parents, and following up to ensure appointments are kept is Children with Special Health Care Needs guaranteed to be difficult and time consuming. Children with chronic illnesses are Other examples include children with diabetes, congenital heart challenging for pediatricians and other defects, seizure disorders, asthma, cancer (even if in remission), primary care providers entrusted with and juvenile rheumatoid arthritis. Also included are children their care. This is especially so for with multiple diagnoses, related or otherwise. those children whose management The Hawaii Department of Health has a service dedicated to requires the services of various assisting such children, their families and their caregivers. This medical specialists, allied health care is the Children with Special Health Needs Program, under the providers, organizations, and institutions. A child with Family Health Services Division. Children and youth under 21 a cleft palate, for example, may require the services of years of age residing in Hawaii are eligible if they have chronic an ENT surgeon, oral surgeon, dentist, audiologist, health conditions lasting (or expected to last) at least one year, speech therapist, DME provider (for hearing aids), for which specialized medical care is required. and the Department of Education. Locating these The Children with Special Health Needs Program can assist providers, making the necessary referrals, coordinating QUEST members who are having difficulty in coordinating or obtaining health care services, or who cannot obtain certain Happy New Year 2008 services through QUEST, with the following: IN THIS ISSUE: • Coordination of health care referrals and appointments.
  • ASTRO Bone Metastases Guideline-Full Version

    ASTRO Bone Metastases Guideline-Full Version

    1 Palliative Radiotherapy for Bone Metastases: An ASTRO Evidence-Based Guideline Stephen T. Lutz, M.D.,* Lawrence B. Berk, M.D., Ph.D.,† Eric L. Chang, M.D.,‡ Edward Chow, M.B.B.S.,§ Carol A. Hahn, M.D.,║ Peter J. Hoskin, M.D.,¶ David D. Howell, M.D.,# Andre A. Konski, M.D.,** Lisa A. Kachnic, M.D.,†† Simon S. Lo, M.B. ChB,§§ Arjun Sahgal, M.D.,║║ Larry N. Silverman, M.D.,¶¶ Charles von Gunten, M.D., Ph.D., FACP,## Ehud Mendel, M.D., FACS,*** Andrew D. Vassil, M.D.,††† Deborah Watkins Bruner, R.N., Ph.D.,‡‡‡ and William F. Hartsell, M.D.§§§ * Department of Radiation Oncology, Blanchard Valley Regional Cancer Center, Findlay, Ohio; † Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida; ‡ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; § Department of Radiation Oncology, Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada; ║ Department of Radiation Oncology, Duke University, Durham, North Carolina; ¶ Mount Vernon Centre for Cancer Treatment, Middlesex, UK; # Department of Radiation Oncology, University of Michigan, Mt. Pleasant, Michigan; ** Department of Radiation Oncology, Wayne State University, Detroit, Michigan; †† Department of Radiation Oncology, Boston Medical Center, Boston, Massachusetts; §§ Department of Radiation Oncology, Ohio State University, Columbus, Ohio; ║║ Department of Radiation Oncology, Sunnybrook Odette Cancer Center and the Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada; ¶¶ 21st Century Oncology, Sarasota, Florida; ## The Institute for Palliative Medicine, San Diego Hospice, San Diego, California; *** Neurological Surgery, Ohio State University, Columbus, Ohio; ††† Department of Radiation Oncology, The Cleveland Clinic 2 Foundation, Cleveland, Ohio; ‡‡‡ School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania; §§§ Department of Radiation Oncology, Good Samaritan Cancer Center, Downers Grove, Illinois Reprint requests to: Stephen Lutz, M.D., 15990 Medical Drive South, Findlay, OH 45840.
  • The Predictive Values of Advanced Non-Small Cell Lung

    The Predictive Values of Advanced Non-Small Cell Lung

    ORIGINAL RESEARCH published: 26 August 2021 doi: 10.3389/fonc.2021.646577 The Predictive Values of Advanced Non-Small Cell Lung Cancer Patients Harboring Uncommon EGFR Mutations—The Mutation Patterns, Use of Different Generations of EGFR-TKIs, and Concurrent Edited by: Genetic Alterations Francois X. Claret, University of Texas MD Anderson † † Cancer Center, United States Jiarong Tan , Chengping Hu , Pengbo Deng*, Rongjun Wan, Liming Cao, Min Li, Reviewed by: Huaping Yang, Qihua Gu, Jian An and Juan Jiang Lin Liu, Department of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, China Nankai University, China Hui Guo, First Affiliated Hospital of Xi’an Introduction: Epidermal growth factor receptor (EGFR) 19del and L858R mutation are Jiaotong University, China “ ” Tony Y. Hu, known as common mutations in non-small cell lung cancer (NSCLC) and predict Tulane University, United States sensitivities to EGFR tyrosine kinase inhibitors (TKIs), whereas 20ins and T790M *Correspondence: mutations confer drug-resistance to EGFR-TKIs. The role of the remaining uncommon Pengbo Deng EGFR mutations remains elusive. [email protected] †These authors have contributed Methods: We retrospectively screened a group of NSCLC patients with uncommon equally to this work EGFR mutations other than 20ins and T790M. The mutation patterns, use of different generations of EGFR-TKIs, and concurrent genetic alterations were analyzed. Meanwhile, Specialty section: This article was submitted to a cohort of patients with single 19del or L858R were included for comparison. Cancer Molecular Targets Results: A total of 180/1,300 (13.8%) patients were identified. There were 102 patients and Therapeutics, a section of the journal with advanced or recurrent NSCLC that received first-line therapy of gefitinib/erlotinib/ Frontiers in Oncology icotinib and afatinib and were eligible for analysis.
  • The Brain That Changes Itself

    The Brain That Changes Itself

    The Brain That Changes Itself Stories of Personal Triumph from the Frontiers of Brain Science NORMAN DOIDGE, M.D. For Eugene L. Goldberg, M.D., because you said you might like to read it Contents 1 A Woman Perpetually Falling . Rescued by the Man Who Discovered the Plasticity of Our Senses 2 Building Herself a Better Brain A Woman Labeled "Retarded" Discovers How to Heal Herself 3 Redesigning the Brain A Scientist Changes Brains to Sharpen Perception and Memory, Increase Speed of Thought, and Heal Learning Problems 4 Acquiring Tastes and Loves What Neuroplasticity Teaches Us About Sexual Attraction and Love 5 Midnight Resurrections Stroke Victims Learn to Move and Speak Again 6 Brain Lock Unlocked Using Plasticity to Stop Worries, OPsessions, Compulsions, and Bad Habits 7 Pain The Dark Side of Plasticity 8 Imagination How Thinking Makes It So 9 Turning Our Ghosts into Ancestors Psychoanalysis as a Neuroplastic Therapy 10 Rejuvenation The Discovery of the Neuronal Stem Cell and Lessons for Preserving Our Brains 11 More than the Sum of Her Parts A Woman Shows Us How Radically Plastic the Brain Can Be Appendix 1 The Culturally Modified Brain Appendix 2 Plasticity and the Idea of Progress Note to the Reader All the names of people who have undergone neuroplastic transformations are real, except in the few places indicated, and in the cases of children and their families. The Notes and References section at the end of the book includes comments on both the chapters and the appendices. Preface This book is about the revolutionary discovery that the human brain can change itself, as told through the stories of the scientists, doctors, and patients who have together brought about these astonishing transformations.
  • Tanibirumab (CUI C3490677) Add to Cart

    Tanibirumab (CUI C3490677) Add to Cart

    5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor
  • Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis

    Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis

    cancers Review Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis Justin Kwan * and Uei Pua Department of Vascular and Interventional Radiology, Tan Tock Seng Hospital, Singapore 388403, Singapore; [email protected] * Correspondence: [email protected] Simple Summary: Colorectal cancer liver metastasis occurs in more than 50% of patients with colorectal cancer and is thought to be the most common cause of death from this cancer. The mainstay of treatment for inoperable liver metastasis has been combination systemic chemotherapy with or without the addition of biological targeted therapy with a goal for disease downstaging, for potential curative resection, or more frequently, for disease control. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies including hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are alternative treatment strategies that have shown promising results, most commonly in the salvage setting in patients with chemo-refractory disease. In recent years, their role in the first-line setting in conjunction with concurrent systemic chemotherapy has also been explored. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future. Abstract: The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential Citation: Kwan, J.; Pua, U. Review of curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, Intra-Arterial Therapies for Colorectal major advances in modern chemotherapy and personalized biological agents have improved overall Cancer Liver Metastasis.
  • The Great Brain Race How Global Universities Are Reshaping the World

    The Great Brain Race How Global Universities Are Reshaping the World

    ! Book Review: The Great Brain Race How Global Universities Are Reshaping the World Mary Sullivan April 2019 © Professors Without Borders 2019 Contact [email protected] www.prowibo.com ! In The Great Brain Race: How Global Universities Are Reshaping the World author Ben Wildavsky explores the “globalisation” of higher education. Wildavsky argues that academics and students alike must view the global system of higher education as a form of international trade. Moreover, in this system, nations act in accordance with liberal economic theory entering into agreements to maximize benefits of the global economy. An advocate for academic free trade, Wildavsky explores this thesis through six chapters to outline the processes that have created this new system. Wildavsky examines how Western universities have tried to capitalize on the advancements in academic mobility. Wildavsky dives into the evolution of academic mobility with the early movement of traveling scholars in the 13th century. As students and faculty are able to easily move around the globe, institutions continue to globalise their activities and ambitions. This has compelled Western universities to establish branch institutions throughout the Middle East and Asia. Wildavsky believes that the continuously changing realities of the global system of higher education have led to behavioral change of states themselves. For example, like China, India, Saudi Arabia, Germany and France all have made lofty investments in higher education so that their institutions can compete with Western “World Class Universities”. Moreover, Wildavsky argues that the consequence of the race to achieve “World Class” status has contributed to the explosion of university rankings systems. These lists have increased in popularity since the 1990s and allow students and universities to determine how universities compare at the national and global level.
  • UCSD Moores Cancer Center Neuro-Oncology Program

    UCSD Moores Cancer Center Neuro-Oncology Program

    UCSD Moores Cancer Center Neuro-Oncology Program Recent Progress in Brain Tumors 6DQWRVK.HVDUL0'3K' 'LUHFWRU1HXUR2QFRORJ\ 3URIHVVRURI1HXURVFLHQFHV 0RRUHV&DQFHU&HQWHU 8QLYHUVLW\RI&DOLIRUQLD6DQ'LHJR “Brain Cancer for Life” Juvenile Pilocytic Astrocytoma Metastatic Brain Cancer Glioblastoma Multiforme Glioblastoma Multiforme Desmoplastic Infantile Ganglioglioma Desmoplastic Variant Astrocytoma Medulloblastoma Atypical Teratoid Rhabdoid Tumor Diffuse Intrinsic Pontine Glioma -Mutational analysis, microarray expression, epigenetic phenomenology -Age-specific biology of brain cancer -Is there an overlap? ? Neuroimmunology ? Stem cell hypothesis Courtesy of Dr. John Crawford Late Effects Long term effect of chemotherapy and radiation on neurocognition Risks of secondary malignancy secondary to chemotherapy and/or radiation Neurovascular long term effects: stroke, moya moya Courtesy of Dr. John Crawford Importance Increase in aging population with increased incidence of cancer Patients with cancer living longer and developing neurologic disorders due to nervous system relapse or toxicity from treatments Overview Introduction Clinical Presentation Primary Brain Tumors Metastatic Brain Tumors Leptomeningeal Metastases Primary CNS Lymphoma Paraneoplastic Syndromes Classification of Brain Tumors Tumors of Neuroepithelial Tissue Glial tumors (astrocytic, oligodendroglial, mixed) Neuronal and mixed neuronal-glial tumors Neuroblastic tumors Pineal parenchymal tumors Embryonal tumors Tumors of Peripheral Nerves Shwannoma Neurofibroma
  • The Financial Statism Regime As Scaffolding In

    The Financial Statism Regime As Scaffolding In

    Financial Statism as an Alternative Interventionist Approach in Developing International Financial Centres (IFCs): The Case of Shanghai since the 1990s Thesis submitted for the degree of Doctor of Philosophy University College London Dafeng Xu Development Planning Unit University College London December 2014 - 1 - Declaration I, Dafeng Xu, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. - 2 - Abstract As increasing numbers of developing countries seek to build their own international financial centres, it is critical to take account of this new phenomenon in the realm of development studies. Previous development theories have devoted a great deal of attention to the analysis of industrialisation in the manufacturing sector, but insufficient attention to this new subject. At odds with neoliberal laissez-faire evolution, the financial statism identified in this thesis as (a) state ownership in the financial sector; (b) financial restraint policies; and (c) state control over capital mobility and currency convertibility, suggests an alternative approach adopted by the Chinese state to develop Shanghai into an international financial centre from the 1990s. It is argued that IFCs‘ development is multi-faceted and can only be addressed in a country-specific context. The study demonstrates that due to the imperfection of institutions and infrastructure in China as a transitional economy in the 1990s, financial statism has played an active role in maintaining socio-economic stability at macro level, creating market institutions and urban infrastructure at meso-level and precluding exogenous financial risks at meta-level.
  • 5 Combinations of Hypoxia-Targeting Compounds and Radiation-Activated Prodrugs with Ionizing Radiation

    5 Combinations of Hypoxia-Targeting Compounds and Radiation-Activated Prodrugs with Ionizing Radiation

    Combinations of Hypoxia-Targeting Compounds and Radiation-Activated Prodrugs with Ionizing Radiation 67 5 Combinations of Hypoxia-Targeting Compounds and Radiation-Activated Prodrugs with Ionizing Radiation G-One Ahn and J. Martin Brown CONTENTS 5.1 Targeting Tumor Hypoxia 5.1 Targeting Tumor Hypoxia 67 5.2 Oxygen-Level Enhancers 68 5.3 Hypoxia-Selective Radiosensitizers 69 Tumor hypoxia was first postulated from histo- 5.3.1 Nitroimidazoles 69 logical studies of human lung adenocarcinomas by 5.3.2 Mixed-Function Radiosensitizers 69 Thomlinson and Gray (1955). They reasoned that, 5.3.3 DNA-Affinic Radiosensitizers 71 because of unrestrained growth, tumor cells are 5.3.4 Limitations of HSR 71 forced away from blood vessels beyond the effec- 5.4 Hypoxic Cytotoxins 72 5.4.1 Introduction 72 tive diffusion distance of oxygen (O2) in respiring 5.4.2 Combination of Hypoxic Cytotoxins with Ionizing tissues, hence becoming hypoxic and eventually Radiation 72 necrotic (Fig. 5.1a). Given the typical values for 5.4.3 Nitroimidazoles 73 intracapillary O2 tensions and consumption rates, 5.4.4 Other Nitroaromatics 73 they calculated that O diffusion distances would 5.4.4.1 CB 1954 73 2 be approximately 150 Pm and this was consistent 5.4.4.2 SN 23862 and PR-104 74 Thomlinson 5.4.4.3 RSU 1069 and RB 6145 74 with their histological observations ( 5.4.5 Quinones 75 and Gray 1955). This type of hypoxia has come to be 5.4.5.1 Mitomycin C 75 termed “chronic,” or “diffusion-limited,” hypoxia. 5.4.5.2 Porfiromycin 75 Acute hypoxia also develops in tumors through 5.4.5.3 EO9 75 temporal (reversible) cessation or reduction of 5.4.6 Benzotriene di-N-Oxides 76 5.4.7 Tertiary Amine N-Oxides 78 tumor blood flow resulting from highly disorga- 5.4.7.1 Nitracrine N-Oxides 78 nized tumor vasculature (Fig.