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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. -
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. -
For Acute Myeloid Leukemia
Published OnlineFirst September 21, 2010; DOI: 10.1158/1078-0432.CCR-10-0382 Published OnlineFirst on September 21, 2010 as 10.1158/1078-0432.CCR-10-0382 Clinical Therapy Clinical Cancer Research Sequential Cytarabine and α-Particle Immunotherapy with Bismuth-213–Lintuzumab (HuM195) for Acute Myeloid Leukemia Todd L. Rosenblat1, Michael R. McDevitt1, Deborah A. Mulford1, Neeta Pandit-Taskar1, Chaitanya R. Divgi1, Katherine S. Panageas1, Mark L. Heaney1, Suzanne Chanel1, Alfred Morgenstern2, George Sgouros1, Steven M. Larson1, David A. Scheinberg1, and Joseph G. Jurcic1 Abstract Purpose: Lintuzumab (HuM195), a humanized anti-CD33 antibody, targets myeloid leukemia cells and has modest single-agent activity against acute myeloid leukemia (AML). To increase the potency of the antibody without the nonspecific cytotoxicity associated with β-emitters, the α-particle–emitting ra- dionuclide bismuth-213 (213Bi) was conjugated to lintuzumab. This phase I/II trial was conducted to determine the maximum tolerated dose (MTD) and antileukemic effects of 213Bi-lintuzumab, the first targeted α-emitter, after partially cytoreductive chemotherapy. Experimental Design: Thirty-one patients with newly diagnosed (n = 13) or relapsed/refractory (n = 18) AML (median age, 67 years; range, 37-80) were treated with cytarabine (200 mg/m2/d) for 5 days followed by 213Bi-lintuzumab (18.5-46.25 MBq/kg). Results: The MTD of 213Bi-lintuzumab was 37 MB/kg; myelosuppression lasting >35 days was dose limiting. Extramedullary toxicities were primarily limited to grade ≤2 events, including infusion-related reactions. Transient grade 3/4 liver function abnormalities were seen in five patients (16%). Treatment- related deaths occurred in 2 of 21 (10%) patients who received the MTD. -
Patient Resource Free
PATIENT RESOURCE FREE Third Edition CancerUnderstanding Immunotherapy Published in partnership with CONTENT REVIEWED BY A DISTINGUISHED PRP MEDICAL PATIENT ADVISORY RESOURCE BOARD PUBLISHING® Understanding TABLE OF CONTENTS Cancer Immunotherapy Third Edition IN THIS GUIDE 1 Immunotherapy Today 2 The Immune System 4 Immunotherapy Strategies 6 Melanoma Survivor Story: Jane McNee Chief Executive Officer Mark A. Uhlig I didn’t look sick, so I didn’t want to act sick. Publisher Linette Atwood Having and treating cancer is only one part of your life. Co-Editor-in-Chief Charles M. Balch, MD, FACS Jane McNee, melanoma survivor Co-Editor-in-Chief Howard L. Kaufman, MD, FACS Senior Vice President Debby Easum 7 The Road to Immunotherapy Vice President, Operations Leann Sandifar 8 Cancer Types Managing Editor Lori Alexander, MTPW, ELS, MWC™ 14 Side Effects Senior Editors Dana Campbell Colleen Scherer 15 Glossary Graphic Designer Michael St. George 16 About Clinical Trials Medical Illustrator Todd Smith 16 Cancer Immunotherapy Clinical Trials by Disease Production Manager Jennifer Hiltunen 35 Support & Financial Resources Vice Presidents, Amy Galey Business Development Kathy Hungerford 37 Notes Stephanie Myers Kenney Account Executive Melissa Amaya Office Address 8455 Lenexa Drive CO-EDITORS-IN-CHIEF Overland Park, KS 66214 For Additional Information [email protected] Charles M. Balch, MD, FACS Advisory Board Visit our website at Professor of Surgery, The University of Texas PatientResource.com to read bios of MD Anderson Cancer Center our Medical and Patient Advisory Board. Editor-in-Chief, Patient Resource LLC Editor-in-Chief, Annals of Surgical Oncology Past President, Society of Surgical Oncology For Additional Copies: To order additional copies of Patient Resource Cancer Guide: Understanding Cancer Immunotherapy, Howard L. -
Targeted Radiotherapeutics from 'Bench-To-Bedside'
RadiochemistRy in switzeRland CHIMIA 2020, 74, No. 12 939 doi:10.2533/chimia.2020.939 Chimia 74 (2020) 939–945 © C. Müller, M. Béhé, S. Geistlich, N. P. van der Meulen, R. Schibli Targeted Radiotherapeutics from ‘Bench-to-Bedside’ Cristina Müllera, Martin Béhéa, Susanne Geistlicha, Nicholas P. van der Meulenab, and Roger Schibli*ac Abstract: The concept of targeted radionuclide therapy (TRT) is the accurate and efficient delivery of radiation to disseminated cancer lesions while minimizing damage to healthy tissue and organs. Critical aspects for success- ful development of novel radiopharmaceuticals for TRT are: i) the identification and characterization of suitable targets expressed on cancer cells; ii) the selection of chemical or biological molecules which exhibit high affin- ity and selectivity for the cancer cell-associated target; iii) the selection of a radionuclide with decay properties that suit the properties of the targeting molecule and the clinical purpose. The Center for Radiopharmaceutical Sciences (CRS) at the Paul Scherrer Institute in Switzerland is privileged to be situated close to unique infrastruc- ture for radionuclide production (high energy accelerators and a neutron source) and access to C/B-type labora- tories including preclinical, nuclear imaging equipment and Swissmedic-certified laboratories for the preparation of drug samples for human use. These favorable circumstances allow production of non-standard radionuclides, exploring their biochemical and pharmacological features and effects for tumor therapy and diagnosis, while investigating and characterizing new targeting structures and optimizing these aspects for translational research on radiopharmaceuticals. In close collaboration with various clinical partners in Switzerland, the most promising candidates are translated to clinics for ‘first-in-human’ studies. -
Particle Accelerators and Detectors for Medical Diagnostics and Therapy Arxiv:1601.06820V1 [Physics.Med-Ph] 25 Jan 2016
Particle Accelerators and Detectors for medical Diagnostics and Therapy Habilitationsschrift zur Erlangung der Venia docendi an der Philosophisch-naturwissenschaftlichen Fakult¨at der Universit¨atBern arXiv:1601.06820v1 [physics.med-ph] 25 Jan 2016 vorgelegt von Dr. Saverio Braccini Laboratorium f¨urHochenenergiephysik L'aspetto pi`uentusiasmante della scienza `eche essa incoraggia l'uomo a insistere nei suoi sogni. Guglielmo Marconi Preface This Habilitation is based on selected publications, which represent my major sci- entific contributions as an experimental physicist to the field of particle accelerators and detectors applied to medical diagnostics and therapy. They are reprinted in Part II of this work to be considered for the Habilitation and they cover original achievements and relevant aspects for the present and future of medical applications of particle physics. The text reported in Part I is aimed at putting my scientific work into its con- text and perspective, to comment on recent developments and, in particular, on my contributions to the advances in accelerators and detectors for cancer hadrontherapy and for the production of radioisotopes. Dr. Saverio Braccini Bern, 25.4.2013 i ii Contents Introduction 1 I 5 1 Particle Accelerators and Detectors applied to Medicine 7 2 Particle Accelerators for medical Diagnostics and Therapy 23 2.1 Linacs and Cyclinacs for Hadrontherapy . 23 2.2 The new Bern Cyclotron Laboratory and its Research Beam Line . 39 3 Particle Detectors for medical Applications of Ion Beams 49 3.1 Segmented Ionization Chambers for Beam Monitoring in Hadrontherapy 49 3.2 Proton Radiography with nuclear Emulsion Films . 62 3.3 A Beam Monitor Detector based on doped Silica Fibres . -
Guide to Treatment Role of Antibodies in Acute Leukemia: Focus on Transplant-Eligible Populations
PRACTICE AID Guide to Treatment Role of Antibodies in Acute Leukemia: Focus on Transplant-Eligible Populations Acute Myeloid Leukemia DRUG STATUS TARGET DOSE EU EMA approved: In combination with daunorubicin and Induction: 3 mg/m2 (up to 5 mg/m2 in EU and 4.5 mg/m2 in US) cytarabine for pts aged ≥15 y with previously untreated, on d 1, 4, and 7 in combination with daunorubicin and cytarabine de novo CD33+ AML, except APL CD33 Consolidation: 3 mg/m2 (up to 5 mg/m2 in EU and 4.5 mg/m2 in US) Gemtuzumab US FDA approved: Newly diagnosed CD33+ AML in adults and 1,2 on d 1 in combination with daunorubicin and cytarabine ozogamicin pediatric pts aged ≥1 month; R/R CD33+ AML in adults and Please consult label for single-agent dosing and dosing in R/R AML. pediatric pts aged 2 y Phase 3 SIERRA study CD45 Adults aged ≥55 y with active R/R AML, adequate organ Dosimetry directed (SIERRA study) Iomab-B3 function, and related/unrelated matched donor (BC8 mAb linked to radioisotope iodine-131) Acute Lymphoblastic Leukemia EU EMA approved: Adults with R/R CD22+ B-cell ALL; adults Cycle 1 dose: 0.8 mg/m2 on d 1; 0.5 mg/m2 on days 8 and 15 for 21 d 2 Inotuzumab with Ph+ R/R B-cell ALL who failed treatment with at least one TKI CD22 Patients in CR/CRi: 0.5 mg/m on days 1, 8, and 15 for 28 d ozogamicin4,5 US FDA approved: Adults with R/R CD22+ B-cell ALL Patients not in CR/CRi: Use cycle 1 dose for 28 d EU Dose: By patient’s weight (≥45 kg = 9 mcg/d on d 1-7 and 28 mcg/d on EU EMA approved: Adults with B-cell ALL who are in d 8-28; <45 kg = 5 mcg/m2/d on -
Whither Radioimmunotherapy: to Be Or Not to Be? Damian J
Published OnlineFirst April 20, 2017; DOI: 10.1158/0008-5472.CAN-16-2523 Cancer Perspective Research Whither Radioimmunotherapy: To Be or Not To Be? Damian J. Green1,2 and Oliver W. Press1,2,3 Abstract Therapy of cancer with radiolabeled monoclonal antibodies employing multistep "pretargeting" methods, particularly those has produced impressive results in preclinical experiments and in utilizing bispecific antibodies, have greatly enhanced the thera- clinical trials conducted in radiosensitive malignancies, particu- peutic efficacy of radioimmunotherapy and diminished its toxi- larly B-cell lymphomas. Two "first-generation," directly radiola- cities. The dramatically improved therapeutic index of bispecific beled anti-CD20 antibodies, 131iodine-tositumomab and 90yttri- antibody pretargeting appears to be sufficiently compelling to um-ibritumomab tiuxetan, were FDA-approved more than a justify human clinical trials and reinvigorate enthusiasm for decade ago but have been little utilized because of a variety of radioimmunotherapy in the treatment of malignancies, particu- medical, financial, and logistic obstacles. Newer technologies larly lymphomas. Cancer Res; 77(9); 1–6. Ó2017 AACR. "To be, or not to be, that is the question: Whether 'tis nobler in the pembrolizumab (anti-PD-1), which are not directly cytotoxic mind to suffer the slings and arrows of outrageous fortune, or to take for cancer cells but "release the brakes" on the immune system, arms against a sea of troubles, And by opposing end them." Hamlet. allowing cytotoxic T cells to be more effective at recognizing –William Shakespeare. and killing cancer cells. Outstanding results have already been demonstrated with checkpoint inhibiting antibodies even in far Introduction advanced refractory solid tumors including melanoma, lung cancer, Hodgkin lymphoma and are under study for a multi- Impact of monoclonal antibodies on the field of clinical tude of other malignancies (4–6). -
TRUNCATED EPIDERIMAL GROWTH FACTOR RECEPTOR (Egfrt)
(19) TZZ _T (11) EP 2 496 698 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07K 14/71 (2006.01) C12N 9/12 (2006.01) 09.01.2019 Bulletin 2019/02 (86) International application number: (21) Application number: 10829041.2 PCT/US2010/055329 (22) Date of filing: 03.11.2010 (87) International publication number: WO 2011/056894 (12.05.2011 Gazette 2011/19) (54) TRUNCATED EPIDERIMAL GROWTH FACTOR RECEPTOR (EGFRt) FOR TRANSDUCED T CELL SELECTION VERKÜRZTER REZEPTOR FÜR DEN EPIDERMALEN WACHSTUMSFAKTOR-REZEPTOR ZUR AUSWAHL UMGEWANDELTER T-ZELLEN RÉCEPTEUR DU FACTEUR DE CROISSANCE DE L’ÉPIDERME TRONQUÉ (EGFRT) POUR LA SÉLECTION DE LYMPHOCYTES T TRANSDUITS (84) Designated Contracting States: • LI ET AL.: ’Structural basis for inhibition of the AL AT BE BG CH CY CZ DE DK EE ES FI FR GB epidermal growth factor receptor by cetuximab.’ GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO CANCER CELL vol. 7, 2005, pages 301 - 311, PL PT RO RS SE SI SK SM TR XP002508255 • CHAKRAVERTY ET AL.: ’An inflammatory (30) Priority: 03.11.2009 US 257567 P checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral (43) Date of publication of application: tissues.’ JEM vol. 203, no. 8, 2006, pages 2021 - 12.09.2012 Bulletin 2012/37 2031, XP008158914 • POWELL ET AL.: ’Large-Scale Depletion of (73) Proprietor: City of Hope CD25+ Regulatory T Cells from Patient Duarte, CA 91010 (US) Leukapheresis Samples.’ J IMMUNOTHER vol. 28, no. -
Multiple Myeloma and Engineered Cell Therapy
Multiple Myeloma and Engineered Cell Therapy Sarah M. Larson, MD Assistant Professor of Medicine September 2018 Spectrum of Disease Morgan GJ Nat Cancer Rev 2012 SMM: Janssen SMM3001 • Patients randomized to dara sc vs active monitoring •Study duration 8 years • Primary endpoint PFS • Prior SMM treatment is an exclusion • NCT03301220 Van de Donk NWCJ Immunol Rev 2016 Multiple Myeloma • Second most common heme malignancy • 33,000 new cases 2017 • >100,000 people with multiple myeloma • Increasing number of patients • Incidence • Improved survival SEER database Treatment Treatment of Initial Consolidation/ ASCT relapsed Therapy Maintenance disease Supportive Care Minimal Residual Disease (MRD) Undetectable MRD: The Goal of Frontline Therapy? PFS OS Landgren O BMT 2016 IFM2009 • Newly diagnosed patients eligible for transplant • Patients <65 years of age PFS 50 mos (p<0.001) CR 59% Transplant MRD neg 79% (p<0.001) R 2 cycles A Len Main RVD N 3 D Cycles O RVD M PFS 36 mos I CR 48% Z MRD neg 65% E 5 Cycles D RVD Len Main Attal M NEJM 2017 Response at Each Treatment Phase Treatment Arm Induction Consolidation Maintenance (%) (%) (%) RVD 45 69 76 Transplant 47 78 85 Attal M NEJM 2017 Conclusions • Transplant remains a standard therapy • Delayed transplant is reasonable • Collection and storage of stem cell frequently not covered • Following second line of treatment • Trials to improve the transplant course Stem Cell Mobilization Trial • BL-8040 Phase III, randomized, double-blinded, placebo controlled trial of BL-8040 and G-CSF vs G- CSF and -
Protocol for Heavy Charged-Particle Therapy Beam Dosimetry
AAPM REPORT NO. 16 PROTOCOL FOR HEAVY CHARGED-PARTICLE THERAPY BEAM DOSIMETRY Published by the American Institute of Physics for the American Association of Physicists in Medicine AAPM REPORT NO. 16 PROTOCOL FOR HEAVY CHARGED-PARTICLE THERAPY BEAM DOSIMETRY A REPORT OF TASK GROUP 20 RADIATION THERAPY COMMITTEE AMERICAN ASSOCIATION OF PHYSICISTS IN MEDICINE John T. Lyman, Lawrence Berkeley Laboratory, Chairman Miguel Awschalom, Fermi National Accelerator Laboratory Peter Berardo, Lockheed Software Technology Center, Austin TX Hans Bicchsel, 1211 22nd Avenue E., Capitol Hill, Seattle WA George T. Y. Chen, University of Chicago/Michael Reese Hospital John Dicello, Clarkson University Peter Fessenden, Stanford University Michael Goitein, Massachusetts General Hospital Gabrial Lam, TRlUMF, Vancouver, British Columbia Joseph C. McDonald, Battelle Northwest Laboratories Alfred Ft. Smith, University of Pennsylvania Randall Ten Haken, University of Michigan Hospital Lynn Verhey, Massachusetts General Hospital Sandra Zink, National Cancer Institute April 1986 Published for the American Association of Physicists in Medicine by the American Institute of Physics Further copies of this report may be obtained from Executive Secretary American Association of Physicists in Medicine 335 E. 45 Street New York. NY 10017 Library of Congress Catalog Card Number: 86-71345 International Standard Book Number: 0-88318-500-8 International Standard Serial Number: 0271-7344 Copyright © 1986 by the American Association of Physicists in Medicine All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of the publisher. Published by the American Institute of Physics, Inc., 335 East 45 Street, New York, New York 10017 Printed in the United States of America Contents 1 Introduction 1 2 Heavy Charged-Particle Beams 3 2.1 ParticleTypes ......................... -
Immunoscintigraphy and Radioimmunotherapy in Cuba: Experiences with Labeled Monoclonal Antibodies for Cancer Diagnosis and Treatment (1993–2013)
Review Article Immunoscintigraphy and Radioimmunotherapy in Cuba: Experiences with Labeled Monoclonal Antibodies for Cancer Diagnosis and Treatment (1993–2013) Yamilé Peña MD PhD, Alejandro Perera PhD, Juan F. Batista MD ABSTRACT and therapeutic tools. The studies conducted demonstrated the good INTRODUCTION The availability of monoclonal antibodies in Cuba sensitivity and diagnostic precision of immunoscintigraphy for detect- has facilitated development and application of innovative techniques ing various types of tumors (head and neck, ovarian, colon, breast, (immunoscintigraphy and radioimmunotherapy) for cancer diagnosis lymphoma, brain). and treatment. Obtaining different radioimmune conjugates with radioactive isotopes OBJECTIVE Review immunoscintigraphy and radioimmunotherapy such as 99mTc and 188Re made it possible to administer radioimmuno- techniques and analyze their use in Cuba, based on the published lit- therapy to patients with several types of cancer (brain, lymphoma, erature. In this context, we describe the experience of Havana’s Clini- breast). The objective of 60% of the clinical trials was to determine cal Research Center with labeled monoclonal antibodies for cancer pharmacokinetics, internal dosimetry and adverse effects of mono- diagnosis and treatment during the period 1993–2013. clonal antibodies, as well as tumor response; there were few adverse effects, no damage to vital organs, and a positive tumor response in a EVIDENCE ACQUISITION Basic concepts concerning cancer and substantial percentage of patients. monoclonal antibodies were reviewed, as well as relevant inter- national and Cuban data. Forty-nine documents were reviewed, CONCLUSIONS Cuba has experience with production and radiola- among them 2 textbooks, 34 articles by Cuban authors and 13 by beling of monoclonal antibodies, which facilitates use of these agents.