The Radiobiological Four "R"S of Hypofractionation
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Time, Dose and Fractionation in Radiotherapy
2/25/2013 The introduction of Fractionation 2-13/13 Radiobiology lecture Time, Dose and Fractionation in Radiotherapy The Four Rs of Radiobiology Repair of Sublethal Damage • Cells exposed to sparse radiation experience • Efficacy of fractionation based on the 4 Rs: sublethal injury that can be repaired – Repair of sublethal damage • Cell killing requires a greater total dose when given –Repopulation in several fractions – Reassortment of cells within the cell cycle • Most tissue repair occurs in about 3 hours and up –Reoxygenation to 24 hours post radiation • Allows for repair of injured normal tissue and gives a potential therapeutic advantage over tumor cells Reoxygenation Redistribution • Oxygen stabilizes free radicals • Position in cell cycle at time of radiation • Hypoxic cells require more radiation to kill determines sensitivity •Hypoxic tumors • S phase is radioresistant – Temporary vessel constriction •G2 phase delay results in increased radiation – Outgrowth of blood supply and capillary collapse resistance • Tumor shrinkage reduces hypoxic areas • Fractionated RT redistributes cells • Reinforces fractionated dosing • Rapidly cycling cells like mucosa, skin are more sensitive • Slower cyclers like connective tissue, brain are spared 1 2/25/2013 Repopulation • Increased regeneration of surviving fraction Basics of Fractionation • Rapidly proliferating tumors regenerate faster • Determines the length and timing of therapy course • Dividing a dose into several fractions spares normal tissues • Accelerated Repopulation – Repair -
Reduced Fractionation in Lung Cancer Patients Treated with Curative-Intent Radiotherapy During the COVID-19 Pandemic
This document was published on 2 April 2020. Please check www.rcr.ac.uk/cancer-treatment-documents to ensure you have the latest version. This document is the collaborative work of oncologists and their teams, and is not a formal RCR guideline or consensus statement. Reduced fractionation in lung cancer patients treated with curative-intent radiotherapy during the COVID-19 pandemic Corinne Faivre-Finn1,2, John D Fenwick3,4, Kevin N Franks5,6, Stephen Harrow7,8, Matthew QF Hatton9, Crispin Hiley10,11, Jonathan J McAleese12, Fiona McDonald13, Jolyne O’Hare12, Clive Peedell14, Ceri Powell15,16, Tony Pope17, Robert Rulach7,8, Elizabeth Toy18 1The Christie NHS Foundation Trust, Manchester 2The University of Manchester 3Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool 4Department of Physics, Clatterbridge Cancer Centre, Liverpool 5Leeds Cancer Centre 6University of Leeds 7Beatson West of Scotland Cancer Centre, Glasgow 8University of Glasgow 9Weston Park Hospital, Sheffield 10CRUK Lung Cancer Centre of Excellence, University College London 11Department of Clinical Oncology, University College London Hospitals NHS Foundation Trust, London 12Northern Ireland Cancer Centre, Belfast 13The Royal Marsden NHS Foundation Trust, London 14James Cook University Hospital, Middlesbrough 15South West Wales Cancer Centre 16Velindre Cancer Centre 17Clatterbridge Cancer Centre, Liverpool 18Royal Devon and Exeter NHS Foundation Trust 1 This document was published on 2 April 2020. Please check www.rcr.ac.uk/cancer-treatment-documents to ensure you have the latest version. This document is the collaborative work of oncologists and their teams, and is not a formal RCR guideline or consensus statement. Introduction The World Health Organisation (WHO) declared COVID-19, the disease caused by the 2019 novel coronavirus SARS-CoV-2, a pandemic on the 11th of March 2020. -
Hypo-Fractionated FLASH-RT As an Effective Treatment Against Glioblastoma That Reduces Neurocognitive Side Effects in Mice
Author Manuscript Published OnlineFirst on October 15, 2020; DOI: 10.1158/1078-0432.CCR-20-0894 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Hypo-fractionated FLASH-RT as an effective treatment against glioblastoma that reduces neurocognitive side effects in mice Pierre Montay-Gruel1*, Munjal M. Acharya2*, Patrik Gonçalves Jorge1, 3, Benoit Petit1, Ioannis G. Petridis1, Philippe Fuchs1, Ron Leavitt1, Kristoffer Petersson1, 3, Maude Gondre1, 3, Jonathan Ollivier1, Raphael Moeckli3, François Bochud3, Claude Bailat3, Jean Bourhis1, Jean-François Germond3°, Charles L. Limoli2° and Marie-Catherine Vozenin1° 1 Department of Radiation Oncology/DO/Radio-Oncology/CHUV, Lausanne University Hospital and University of Lausanne, Switzerland. 2 Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA. 3 Institute of Radiation Physics/CHUV, Lausanne University Hospital, Switzerland. *, ° contributed equally to the work Running title Sparing the cognition, not the tumor with FLASH-RT Key words FLASH radiation therapy, glioblastoma, neurocognition Financial support The study was supported by a Synergia grant from the FNS CRS II5_186369 (M-C.V. and F.B.), a grant from lead agency grant FNS/ANR CR32I3L_156924 (M-C.V. and C.B.), ISREC Foundation thank to Biltema donation (JB and MCV) and by NIH program project grant PO1CA244091 (M-C.V. and C.L.L.), NINDS grant NS089575 (C.L.L.), KL2 award KL2TR001416 (M.M.A.). P.M.-G. was supported by Ecole Normale Supérieure de Cachan fellowship (MESR), FNS N°31003A_156892 and ISREC Foundation thank to Biltema donation, K.P. by FNS/ANR CR32I3L_156924 and ISREC Foundation thank to Biltema donation; P.J.G. -
Time, Dose and Fractionation: Accounting for Hypoxia in the Search for Optimal Radiotherapy Treatment Parameters
!"#$ #"%"" &&' ( )(' * % ( + % , , %- .( (, , , % , . . % . %* . , . ( . %- ( . (, , , . . % / , 012( , . % 3 , % / , ( , , ( ( % . % , . ( . % , . + ( . , %%1 % - ( . , . 4 #)-*56 . ( . %1 , . ( + , , . % . , % !"#$ 788 %% 8 9 : 77 7 7 #6);"# <1=>$)>#$$>$";#? <1=>$)>#$$>$";!; ! (#"?># TIME, DOSE AND FRACTIONATION: ACCOUNTING FOR HYPOXIA IN THE SEARCH FOR OPTIMAL RADIOTHERAPY TREATMENT PARAMETERS Emely Kjellsson Lindblom Time, dose and fractionation: accounting for hypoxia in the search for optimal radiotherapy treatment parameters Emely Kjellsson Lindblom ©Emely Kjellsson Lindblom, Stockholm University 2017 ISBN print 978-91-7797-031-6 -
Radiobiology Is a Young Science and Is Solely Concerned with the Study Of
The Rockefeller Foundation and its support of Radiobiology up to the 1970s By Sinclair Wynchank Senior Lecturer University of Cape Town Rondebosch, South Africa [email protected] © 2011 by Sinclair Wynchank Radiation biology, or radiobiology, is a very young science, solely concerned with the study of the interactions between ionizing radiation and living matter. This science slowly became a recognized field of study after the discovery of ionizing radiation (i.e., X rays) in 1895. A broadly varied and evolving terminology has been applied to aspects of radiobiology and therefore, archival searches concerning it are complex. This report is a work in progress, which mainly recounts support given by the Rockefeller Foundation (RF) to radiobiology. The RF was a most important player in the early history of radiobiology and a crucial influence in ensuring that the science steadily matured during its first six decades. Time constraints prevented all relevant items from being accessed, but a clear idea of the RF‟s strong influence on radiobiology‟s early history has resulted. Examples of RF activities to verify this assertion are given below, in by and large chronological order. After a brief analysis of RF aid, there is a short account of why its support so strongly benefitted the young science. To my knowledge there is very little written about the history of radiobiology and nothing about the role that the RF or other philanthropic bodies played in this history. Inevitably, for an extensive time, individual radiobiologists first studied other fields of science before radiobiology. Even in 2011 there are only five universities in the U.S. -
Single-Dose Versus Fractionated Radioimmunotherapy of Human Colon Carcinoma Xenografts Using 131I-Labeled Multivalent CC49 Single-Chain Fvs1
Vol. 7, 175–184, January 2001 Clinical Cancer Research 175 Single-Dose versus Fractionated Radioimmunotherapy of Human Colon Carcinoma Xenografts Using 131I-labeled Multivalent CC49 Single-chain Fvs1 Apollina Goel, Sam Augustine, labeled systemic toxicity was observed in any treatment Janina Baranowska-Kortylewicz, David Colcher, groups. The results show that radioimmunotherapy delivery for sc(Fv) and [sc(Fv) ] in a fractionated schedule clearly Barbara J. M. Booth, Gabriela Pavlinkova, 2 2 2 2 presented a therapeutic advantage over single administration. Margaret Tempero, and Surinder K. Batra The treatment group receiving tetravalent scFv showed a sta- Departments of Biochemistry and Molecular Biology [A. G., tistically significant prolonged survival with both single and S. K. B.], Pathology and Microbiology [S. A., B. J. M. B., G. P., fractionated administrations suggesting a promising prospect S. K. B.], and Radiation Oncology [J. B-K.], College of Pharmacy [S. A.], Eppley Institute for Research in Cancer and Allied Diseases of this reagent for cancer therapy and diagnosis in MAb-based [S. K. B.], University of Nebraska Medical Center, Omaha, Nebraska radiopharmaceuticals. 68198; Coulter Pharmaceutical Incorporated, San Francisco, California 94080 [D. C.]; and University of California San Francisco Cancer Center, San Francisco, California 94115 [M. T.] INTRODUCTION RIT3 is a rapidly developing therapeutic modality for the treatment of a wide variety of carcinomas (1). Numerous anti- ABSTRACT body-radionuclide combinations have been evaluated in clinical The prospects of radiolabeled antibodies in cancer detec- studies (2–9). RIT has yielded complete responses in hemato- tion and therapy remain promising. However, efforts to logical diseases like Hodgkin and non-Hodgkin lymphoma (10, achieve cures, especially of solid tumors, with the systemic 11); however, for solid tumors only a partial clinical response administration of radiolabeled monoclonal antibodies (MAbs) has been observed (12–14). -
Low Dose and Low Dose-Rate Radiation Effects and Models
Forty-Fourth Annual Meeting Program Low Dose and Low Dose-Rate Radiation Effects and Models April 14–15, 2008 Bethesda North Marriott Hotel & Conference Center 5701 Marinelli Road North Bethesda, MD 20852 On the cover: • top: Two nuclei have each been “hit” by three alpha particles from a microbeam and show activated γH2AX foci at the site of the traversal. • center: Chromosome painting technology makes it possible to identify each human chromosome and characterize the number, location and types of aberrations produced by ionizing radiation. • bottom: Measuring the frequency of micronuclei provides a rapid measure of cytogenetic damage, which increases as a function of radiation dose. Introduction Low Dose and Low Dose-Rate Radiation Effects and Models Forty-Fourth Annual Meeting of the National Council on Radiation Protection and Measurements (NCRP) Potential human health effects of low doses of ionizing models of the biological responses and human health radiation such as those experienced in occupational impacts of exposure to low doses of radiation. The and medical exposures are of great contemporary meeting will feature presentations by international interest. Considerable debate exists over the applica- experts on the topics of (1) molecular, cellular, tissue, bility of a linear-nonthreshold model for characterizing and laboratory animal studies on the effects of expo- the biological responses and health effects of expo- sure to low dose and low dose-rate radiation, (2) sure to low radiation doses, and alternative models results of epidemiological studies on human health have been proposed. A related subject of interest and effects of low radiation doses in occupational, medical debate is the effect of the rate of delivery of radiation and other exposure scenarios, (3) potential impacts of doses on the biological and health outcomes of expo- these findings on future regulatory guidance and pub- sure. -
Radioresistance of Brain Tumors
cancers Review Radioresistance of Brain Tumors Kevin Kelley 1, Jonathan Knisely 1, Marc Symons 2,* and Rosamaria Ruggieri 1,2,* 1 Radiation Medicine Department, Hofstra Northwell School of Medicine, Northwell Health, Manhasset, NY 11030, USA; [email protected] (K.K.); [email protected] (J.K.) 2 The Feinstein Institute for Molecular Medicine, Hofstra Northwell School of Medicine, Northwell Health, Manhasset, NY 11030, USA * Correspondence: [email protected] (M.S.); [email protected] (R.R.); Tel.: +1-516-562-1193 (M.S.); +1-516-562-3410 (R.R.) Academic Editor: Zhe-Sheng (Jason) Chen Received: 17 January 2016; Accepted: 24 March 2016; Published: 30 March 2016 Abstract: Radiation therapy (RT) is frequently used as part of the standard of care treatment of the majority of brain tumors. The efficacy of RT is limited by radioresistance and by normal tissue radiation tolerance. This is highlighted in pediatric brain tumors where the use of radiation is limited by the excessive toxicity to the developing brain. For these reasons, radiosensitization of tumor cells would be beneficial. In this review, we focus on radioresistance mechanisms intrinsic to tumor cells. We also evaluate existing approaches to induce radiosensitization and explore future avenues of investigation. Keywords: radiation therapy; radioresistance; brain tumors 1. Introduction 1.1. Radiotherapy and Radioresistance of Brain Tumors Radiation therapy is a mainstay in the treatment of the majority of primary tumors of the central nervous system (CNS). However, the efficacy of this therapeutic approach is significantly limited by resistance to tumor cell killing after exposure to ionizing radiation. This phenomenon, termed radioresistance, can be mediated by factors intrinsic to the cell or by the microenvironment. -
General Guidelines for the Estimation of Committed Effective Dose from Incorporation Monitoring Data
Forschungszentrum Karlsruhe in der Helmholtz-Gemeinschaftt Wissenschaftliche Berichte FZKA 7243 General Guidelines for the Estimation of Committed Effective Dose from Incorporation Monitoring Data (Project IDEAS – EU Contract No. FIKR-CT2001-00160) H. Doerfel, A. Andrasi, M. Bailey, V. Berkovski, E. Blanchardon, C.-M. Castellani, C. Hurtgen, B. LeGuen, I. Malatova, J. Marsh, J. Stather Hauptabteilung Sicherheit August 2006 Forschungszentrum Karlsruhe in der Helmholtz-Gemeinschaft Wissenschaftliche Berichte FZKA 7243 GENERAL GUIDELINES FOR THE ESTIMATION OF COMMITTED EFFECTIVE DOSE FROM INCORPORATION MONITORING DATA (Project IDEAS – EU Contract No. FIKR-CT2001-00160) H. Doerfel, A. Andrasi 1, M. Bailey 2, V. Berkovski 3, E. Blanchardon 6, C.-M. Castellani 4, C. Hurtgen 5, B. LeGuen 7, I. Malatova 8, J. Marsh 2, J. Stather 2 Hauptabteilung Sicherheit 1 KFKI Atomic Energy Research Institute, Budapest, Hungary 2 Health Protection Agency, Radiation Protection Division, (formerly National Radiological Protection Board), Chilton, Didcot, United Kingdom 3 Radiation Protection Institute, Kiev, Ukraine 4 ENEA Institute for Radiation Protection, Bologna, Italy 5 Belgian Nuclear Research Centre, Mol, Belgium 7 Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France 8 Electricité de France (EDF), Saint-Denis, France 9 National Radiation Protection Institute, Praha, Czech Republic Forschungszentrum Karlsruhe GmbH, Karlsruhe 2006 Für diesen Bericht behalten wir uns alle Rechte vor Forschungszentrum Karlsruhe GmbH Postfach 3640, 76021 Karlsruhe Mitglied der Hermann von Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF) ISSN 0947-8620 urn:nbn:de:0005-072434 IDEAS General Guidelines – June 2006 Abstract Doses from intakes of radionuclides cannot be measured but must be assessed from monitoring, such as whole body counting or urinary excretion measurements. -
Radiation and Cell Cycle
High Yield Summary Reviews in Radiation Oncology Radiation and Cancer Biology Gayle E. Woloschak, PhD Tuesday, June 18, 2019 11:00 a.m. – 1:00 p.m. Eastern Daylight Time June 25, 2019 Gayle E. Woloschak PhD Professor of Radiation Oncology, Radiology, and Cell & Molecular Biology Associate Dean for Graduate Student and Postdoctoral Affairs Northwestern University Feinberg School of Medicine June 25, 2019 Definitions • Bq-2.7x10-11 Ci—equal to one disintegration per sec • Ci—3.7x1010 disintegrations per sec • Gy—absorbed radiation dose, the quantity which deposits 1 Joule of energy per kg—1Gy=100rad • Sievert—dose equivalence—multiply absorbed dose in Gy by the Quality Factor (Q)— 1Sv=100rem • LET—measure of the rate of energy transfer from an ionizing radiation to the target material—keV of energy lost/micron track length Unit Conversion Factors: SI and Conventional Units • 1 Bq = 2.7 × 10–11 Ci = 27 pCi • 1 Ci = 3.7 × 1010 Bq = 37 GBq • 1 Sv = 100 rem • 1 rem = 0.01 Sv • 1 Gy = 100 rad • 1 rad = 0.01 Gy • 1 Sv Bq–1 = 3.7 × 106 rem μCi–1 • 1 rem μCi–1 = 2.7 × 10–7 Sv Bq–1 • 1 Gy Bq–1 = 3,7 × 106 rad μCi–1 • 1 rad μCi–1 = 2,7 × 10–7 Gy Bq–1 Biomolecular Action of Ionizing Radiation; Editor:Shirley Lehnert, 2007 Units Used in Radiation Protection • Equivalent dose—average dose x radiation weighting factor—Sv • Effective dose—sum of equivalent doses to organs and tissues exposed, each multiplied by the appropriate tissue weighting factor—Sv • Committed equivalent dose—equivalent dose integrated over 50 years (relevant to incroporated radionuclides)—Sv -
Collection of Recorded Radiotherapy Seminars
IAEA Human Health Campus Collection of Recorded Radiotherapy Seminars http://humanhealth.iaea.org WHOLE BODY IRRADIATION Dr. Fuad Ismail Dept. of Radiotherapy & Oncology Universiti Kebangsaan Malaysia Medical Centre WHOLE BODY IRRADIATION (WBI) • WBI may be : – Accidental – Deliberate • Medical – Bone marrow transplant • Non-medical ACCIDENTAL WBI • Usually as a result of radiation disaster or accident – May also be due to medical accidents • Dislodged or stuck sources • Results in WBI by photon and particles eg neutron, heavy ions. Chernobyl ACCIDENTAL WBI • Radiation disasters – Chenobyl – Long Island New York • Radiation accidents – “Stolen” radioactive sources – Malfunction industrial sources ACCIDENTAL WBI • Compared to medical irradiation – Dose is non-uniform – Dose level is not known – Dose may be due to mixed particle and non- particle radiation – Exposure time is not known Acute Radiation Syndrome (ARS) • Acute illness with course over hours to weeks. • Stages – Prodromal symptoms – Latent period – Symptomatic illness – Recovery / sequelae DOSE RANGES FOR ARS • Sequelae of ARS is dependant on dose – < 100 cGy - asymptomatic – 100 - 200 cGy - minor symptoms – 250 – 500 cGy - haematopoietic syndrome – 800 – 3000 cGy - gastro-intestinal syndrome – > 2000 cGy - cerebro-vascular syndrome Prodromal radiation syndrome • Initial reaction to irradiation – – immediate response • Characterized by – Nausea – Vomiting – Diarrhea • Lasts from a few minutes to few days • Happens at low doses but increases with dose Prodromal radiation syndrome -
Human Radiosensitivity and Radiosusceptibility: What Are the Differences?
International Journal of Molecular Sciences Review Human Radiosensitivity and Radiosusceptibility: What Are the Differences? Laura El-Nachef 1, Joelle Al-Choboq 1, Juliette Restier-Verlet 1, Adeline Granzotto 1, Elise Berthel 1,2, Laurène Sonzogni 1,Mélanie L. Ferlazzo 1, Audrey Bouchet 1 , Pierre Leblond 3, Patrick Combemale 3, Stéphane Pinson 4, Michel Bourguignon 1,5 and Nicolas Foray 1,* 1 Inserm, U1296 unit, Radiation: Defense, Health and Environment, Centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France; [email protected] (L.E.-N.); [email protected] (J.A.-C.); Juliette.Restier–[email protected] (J.R.-V.); [email protected] (A.G.); [email protected] (E.B.); [email protected] (L.S.); [email protected] (M.L.F.); [email protected] (A.B.); [email protected] (M.B.) 2 Neolys Diagnostics, 67960 Entzheim, France 3 Centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France; [email protected] (P.L.); [email protected] (P.C.) 4 Hospices Civils de Lyon, Quai des Célestins, 69002 Lyon, France; [email protected] 5 Université Paris Saclay Versailles St Quentin en Yvelines, 78035 Versailles, France * Correspondence: [email protected]; Tel.: +33-4-78-78-28-28 Abstract: The individual response to ionizing radiation (IR) raises a number of medical, scientific, and societal issues. While the term “radiosensitivity” was used by the pioneers at the beginning Citation: El-Nachef, L.; Al-Choboq, of the 20st century to describe only the radiation-induced adverse tissue reactions related to cell J.; Restier-Verlet, J.; Granzotto, A.; death, a confusion emerged in the literature from the 1930s, as “radiosensitivity” was indifferently Berthel, E.; Sonzogni, L.; Ferlazzo, used to describe the toxic, cancerous, or aging effect of IR.