Využití jaderných technologíí

Využití jaderných technologíí

Zdravotnictv - terapie chorobn se dlc buky se astji dl a mly by proto bt na zen citlivj ne buky zdrav - nemus to bt ale zcela pravda (nen v nich nkdy tolik kyslku) pravdpodobnost bunn inaktivace vzrst s energi pedvanou jednotlivm bukm - pro rzn druhy bunk me bt tato pravdpodobnost znan rozdln lze pout: elektromagnetick zen (g, RTG) radioterapie tk nabit stice hadronov terapie elektrony - nepouv se (radioaktivn lzn - zven pirozen aktivita pomh lit zejmna nemoci pohybovho stroj - Jchymov,...) Vskyt ndor a spnost lby Ndorov onemocnn jsou 2. nejastj pinou mrt (Evropa, R) lze oekvat, e v nejblich letech bude ve vysplch zemch postien tmto onemocnnm bhem svho ivota kad tet oban. v 58% ppad je ndorov proces v dob jeho diagnostikovn v lokalizovanm stadiu a pi lb se uplatuj pedevm chirurgick a radioterapeutick postupy R: odhaleno tm 60.000 ppad/rok (2005)

umr 28.000 osob/rok (asi 25% vech mrt) Celkem ije tm 285 tisc osob, u kterch byl novotvar zjitn Evropa - da se vylit 45% pacient vylenm se rozum ptilet peit bez pznak tto choroby. https://www.irozhlas.cz/zpravy-domov/rakovina-nemusi-byt-desiva-podivejte-se-jaka-je-prognoza-u-konkretnich-diagnoz_201508310540_jbocek mrtnost na zhoubn ndory vykazuje v absolutnch slech stagnaci, v relativnch ukazatelch, pedevm po standardizaci k vkov struktue obyvatelstva Incidence a mrtnost na 100000 osob v R Vvoj incidence zhoubnch ndor a novotvar in situ u mu a en Rostouc poet hlench ppad meme sten dvat do souvislosti se strnutm populace. Dalmi monmi vlivy jsou vy vskyt fyziklnch a chemickch kancerogen, kter je zpsoben mimo jin zneitnm ivotnho prosted a

zmnami ivotnho stylu, zlepen diagnostika zhoubnch novotvar a celkov kvalita lkask pe, kter znamen, e stle vce osob se dov vyho vku, kdy je riziko ndorovho onemocnn nejvy. V rmci zlepen diagnostiky mohou bt pinou vyho potu hlench ZN mimo jin programy celoplonch onkologickch Vvoj mrtnosti na ZN u mu a en Klesajc mru mrtnosti navzdory rostouc incidenci ovlivuje zvyujc se kvalita lkask pe, dostupnost novch diagnostickch a terapeutickch prostedk nebo asnj diagnostika ndorovch onemocnn. Vzhledem k vazb ndorovch onemocnn na vk byly pi zemnm nebo esk republika a rakovina v slech (2010) Kad tet obyvatel R v prbhu svho ivota onemocn rakovinou a kad tvrt na ni zeme Kadoron onemocn v R rakovinou vce ne 77 000 lid (2010) Kad rok zeme v R na rakovinu pes 27 000 lid (2010) eny: plicn ndory (18 %), ndory prsu (18 %), ndory tlustho steva (15 %) mui: plicn ndory (35 %), ndory tlustho steva (12 %), ndory prostaty (10 %)

V roce 2008 celkem ilo 418 887 osob, u kterch bylo v danm roce nebo dve diagnostikovno onkologick onemocnn. Nejastjm zhoubnm onemocnnm u mu je karcinom plic; vrazn pibylo i karcinom tl. steva, konenku a prostaty. Sniuje se vskyt karcinomu aludku. Nejastjm zhoubnm onemocnnm u en je karcinom prsu; zarejc je vrazn nrst novch ppad karcinomu plic, pokles vskytu karcinomu aludku a nezvyujc se nlezy karcinomu dlonho pku (dvodem jsou pedevm zdokonalen preventivn prohldky) U vech hlavnch diagnz, tedy zhoubnch ndor tlustho steva a konenku, prsu, plic a ledvin setrvale narst meziron incidence o 2 4 % V poslednm desetilet nejrychleji roste poet ndor plic (u en), a ndor tl. steva a konenku. Zvyuje se i vskyt ndor prsu, ke, ledvin, moovho mche a ttn lzy. U mu je vy vskyt ndor jater, prostaty, varlat a mnohoetnho myelomu. esk republika a rakovina v slech (2010)

Kad tet obyvatel R v prbhu svho ivota onemocn rakovinou a kad tvrt na ni zeme Kadoron onemocn v R rakovinou vce ne 77 000 lid (2010) Kad rok zeme v R na rakovinu pes 27 000 lid (2010) eny: plicn ndory (18 %), ndory prsu (18 %), ndory tlustho steva (15 %) mui: plicn ndory (35 %), ndory tlustho steva (12 %), ndory prostaty (10 %) V roce 2008 celkem ilo 418 887 osob, u kterch bylo v danm roce nebo dve diagnostikovno onkologick onemocnn. Nejastjm zhoubnm onemocnnm u mu je karcinom plic; vrazn pibylo i karcinom tl. steva, konenku a prostaty. Sniuje se vskyt karcinomu aludku. Nejastjm zhoubnm onemocnnm u en je karcinom prsu; zarejc je vrazn nrst novch ppad karcinomu plic, pokles vskytu karcinomu aludku a nezvyujc se nlezy karcinomu dlonho pku (dvodem jsou pedevm zdokonalen preventivn prohldky) U vech hlavnch diagnz, tedy zhoubnch ndor tlustho steva a konenku, prsu,

plic a ledvin setrvale narst meziron incidence o 2 4 % V poslednm desetilet nejrychleji roste poet ndor plic (u en), a ndor tl. steva a konenku. Zvyuje se i vskyt ndor prsu, ke, ledvin, moovho mche a ttn lzy. U mu je vy vskyt ndor jater, prostaty, varlat a mnohoetnho myelomu. esk republika a rakovina v slech (2016) Nejastji diagnostikovanm onkologickm onemocnnm je jin zhoubn novotvar ke, piem pod tuto diagnzu spadaj histologicky pedevm bazaliomy a spinocelulrn karcinomy. Dky prognosticky relativn pzniv povaze onemocnn a obvykle vasn diagnze je mrtnost na tento typ ZN stabiln velmi nzk. Pro tato sv specifika je bn vyazovna z dalch analz, aby nezkreslovala informace o onkologickch onemocnnch jako celku. Mezi dal nejpoetnj diagnzy ZN v roce 2016 patily: zhoubn ndory kolorekta, zhoubn ndory prostaty u mu, zhoubn ndory prsu u en a zhoubn ndory prdunice, prduek a plic. Tyto diagnzy tvoily v roce 2016 zhruba tetinu nov zjitnch ppad ZN a po vylouen novotvar ke pedstavovaly tyto vybran diagnzy novotvar necelou polovinu nov zachycench ppad ZN ve sledovanm roce. Radioterapie ndorovch onemocnn pouv se pi kurativn lb (vede k plnmu vylen pacienta) ndorovch onemocnn v lokalizovanm stadiu u pokroilejch stadi se vyuv (nkdy v kombinaci s chemoterapi) jako paliativn prostedek (jen lba nsledk)

Podl na lb (asi polovina pacient podstoup, dnes 40% vylench ppad) se mon zv nov radioterapeutick metody pi zavdn novch diagnostickch procedur a screeningovch metod bude vce ndorovch onemocnn odhaleno ji v inicilnm stadiu (radioterapie velmi inn) Clem je likvidace ndorovho loiska pi co nejmenm souasnm pokozen okolnch zdravch tkn - nesm se pekroit tolerann dvka zdravch tkn Pokozen zdravch tkn lze vznamn snit ozaovnm z vce smr. frakcionovan ozaovn, - celkov dvka se rozdl do vtho potu fraknch dvek, kter se aplikuj piblin v dennch intervalech zpravidla po dobu t a pti tdn - vyuv pznivho pomru tzv. kumulativnho biologickho inku na ndorovou tk a na tk zdravou, kter m vt regeneran schopnost Radioterapie, Extern svazek vyuv se ozaovn pomoc g (60Co) nebo RTG (brzdn) zen (z LINACu) msta lec ped clovou oblast jsou jednotlivmi svazky ozena zpravidla vce ne

vlastn loisko. Pro mnoh ndory lec v tsn blzkosti kritickch orgn vede radioterapie konvennmi svazky k vysokmu riziku neppustnho pokozen tchto struktur Evropa: 20 000 pacient na 10 000 000 obyvatel ron ozaovno radioterapi Typy ozen: zdroj zen mimo tlo (extern svazek, g n, IMRT) zdroj zen uvnit tla (brachyterapie) Extern svazek radioizotopy - aplikuj se tam, kde je vhodn pout jejich pesn danou energii zen

pirozen spolehlivost a mal nroky na drbu Stav v roce 2002 u ns a v EU linac obyv/linac 60Co linac/Co Linern urychlova - zdroj RTG zen sprvn innost se mus kontrolovat denn paprsek lze pesnji zamit a mnit jeho energii pstroj mimo dobu pouvn nez EU 1460 254 000 448 3,26 R 24 425 000 25

0,9 Intensity Modulated Radiation Therapy (IMRT) e- produkovan LINACem interaguj s terkem z tkho kovu a produkuj RTG (brzdn) zen - to je kolimovno a ozauje ndor svazek e- lze pomoc EM pole rzn vychylovat ozen RTG zenm zkm svazkem z mnoha stran dovoluje ozen ndoru vt dvkou typicky 6-10 svazk Pouiteln na:

rakovina prostaty mozkov ndory (glioblastomas, gliomas,...) i metastatick ndory slinivky ndory jater (metastases, hepatocellular carcinoma) rakovina hlavy a krku (hrtan, jazyk, dutiny, sta,...) rakovina plic R Fakultn nemocnice Ostrava (FNO) CyberKnife (2010) Cena za CyberKnife Cena za pstroj Zem Cena (v milionech dolar)

Rok transakce Fakultn nemocnice Ostrava esko 10 2009 Overlook Hospital New Jersey USA 5 2004 Philadelphia CyberKnife, Havertown USA 5

2009 El Camino Hospital, Los Altos USA 5 2009 Apollo Hospital, Chennai Indie 5 2009 St. Anthony Hospital, Oklahoma City USA 4 2003

CyberKnife Center of Palm Beach USA 4 2005 St. Louis University Hospital USA 4 2005 The Seattle CyberKnife Center USA 4 2006

Virginia Hospital Center USA 4 2008 Harley Street Clinic London Anglie 4 2009 Ottawa Hospital Kanada 4 2009 Northeast Medical Center North Carolina

USA 3,53 2008 West Jefferson Medical Center, New Orleans USA 3,53 2006 Georgtown University Hospital USA 3 2001 Kaiser Permanente, San Francisco

USA 3 2009 Fakultn nemocnice Ostrava esko 12 2009 CyberKnife Zentrum Gstrow Nmecko 10 2009 St. Louis University Hospital University of Louisville Harley Street Clinic London

USA USA Anglie 8 7-8 7-8 2005 2008 2009 Apollo Hospital, Chennai Indie 7-8 2009 Europische Cyberknife Zentrum Mnchen Nmecko

7 2006 Erlanger Hospital Chattanooga USA 7 2010 The Seattle CyberKnife Center USA 6-7 2006 Mt. Carmel Hospital Ohio USA 6-7

2010 Frederick Memorial Hospital Maryland USA 6 2007 St. Joseph's/Candler Hospital Georgia USA 6 2010 Cena za budovu a pstroj Leksellv gama n 1. v roce 1967 ve Stockholmu (idea od Larse Leksella - stereotactic radiosurgery) pouv se k len mozkovch ndor

skld se z pohyblivho operanho stolu a z velk ocelov ozaovac hlavice, kter obsahuje 201 zi 60Co ve form proutk systm clon zajist kolimaci zen do jednoho msta s pesnost 0.1 mm dvka zen g zni v krtkm okamiku pesn vymezen a oste ohranien kousek tkn terapie trv 5 a 30 minut (cel procedura vetn pedchozho zobrazen tkn a cv v mozku a radiofyziklnch vpot asi 3 a 5 hodin) dky penn sbrce m R v nemocnici Na Homolce pouit pro zhoubn i nezhoubn ndory Omezen: nen vhodn pro velk terky (3-4 cm) ztrc schopnost etit okoln tk pro velk mnostv terk nen pouvn mimo hlavu (symetrie) Leksellv gamma-n v R pracovit Leksellova gama noe v Nemocnici Na Homolce funguje od r. 1992 Na svt je asi 260 (v 70 nemocnicch?) na svt vtinou v USA a v Japonsku. V Evrop jich je zatm mn ne deset. v roce 2002 a pot i 2006 proel n kompletn modernizac za 20 mil. K a 50 mil. K v letech 1992 2012 zde bylo provedeno pes 13 300 ozaovacch vkon

v poslednch letech kolem 800 zkrok ron spnost lby je kolem 90% lebn zkrok g noem je v R hrazen zdravotnm pojitnm - platba in zhruba 44 000 K za vkon (?) Od r. 2010 nahrazen zcela novm noem (cena 150 mil. K) Brachyradioterapie (ozaovn zblzka) brachy = ecky mal vzdlenost je to typ radioterapie je pouvno u relativn malch a dobe pstupnch ndorovch loisek zdroj zen se zavd do bezprostedn blzkosti ndoru nap. do pochvy pi ozaovn ndor dlonho hrdla nebo do prduek pi ndorech, kter zuuj prduku a znesnaduj dchn) nebo ve form jehel i drt pmo do ndorovho loiska nap. do ndoru prsu nebo konenku zdokonalen pedstavuje tzv. afterloading: do clov oblasti i tlesn dutiny se nejprve zavede hadika, kter se pesn nastav; do n se pak na stanovenou dobu zavd vlastn zi

pouvaj se zie: 60Co, 137Cs, 192Ir (dve i 226Ra - nevhoda - vznik Rn) zie maj tvar jehel, nebo tub u ns vce nemocnic (Masarykv onkol. stav v Brn,) Dvky na jednotliv orgny Minimln tolerann dvka TD5/5 je dvka zen, kter nezpsob vce ne 5% zvanch komplikac bhem 5 let po lb. Maximln tolerann dvka TD50/5 zpsob 50% pacient zvan postien bhem 5 let. RBE a OER Dleitmi veliinami pro popis ink zen na tk jsou i Relative Biological Effectiveness (RBE) podl dvky referennho typu zen (obvykle 250 keV g) vi dvce zen, je ns zajm, pi stejnm biologickm inku pro stejn pouit zen je RBE funkc vyetovanho biologickho systmu a referennho zen RBE pro g i p velice podobn

Oxygen enhancement ratio (OER) pomr dvek v tkni bez O2 vi tkni s O2 vedouc ke stejnmu biologickm inku asi 10% ndor je hipoxidnch relativn vi fotonm RBE a OER (vt obrzek) RBE Data for CHO-K1 cell line irradiated by photons (blue curve) and carbon ions (red curve). Vztah RBE a jakostnho faktoru Q Ta sam veliina (jen v jinch jednotkch) (jedna se pouv pro dozimetrii a druh v lkastv) RBE - m je vt hustota ionizace tm je vt hustota pokozen DNA a reparan mechanizmy nejsou schopny fungovat v dostaten me (je to ve skutenosti troku sloitj) LET by a charged particle in water

ve vod (keV/mm) vztah mezi aQ Q 3.5 a mn 1 7 2 23 5 53 10

175 a vce 20 ? OER Ptomnost molekulrnho kyslku siln ovlivuje biologick efekt nkterch typ zen kyslk mus bt ptomen bhem expozice, nebo nejmn bhem ivota volnch radikl (10-5 s) kyslk fixuje (vytv trval) pokozen zpsoben radikly - pi absenci kyslku mohou bt tato pokozen opravena (nem vliv na pm inky zen) u mal mnostv kyslku m velk vliv - 0.5% kyslku zpsobuje polovin citlivost mezi hypoxickou oblast a pln okyslienou tkn v ndorech jsou msta s nedostatkem kyslku - je to dno nedostaten prokrvenou tkn OER (RTG) 3 pi velkch dvkch a zejm mn ( 2) pi dvce 0.5 to 2 Gy OER kles s rostoucmi ionizanmi ztrtami (LET)

- roste vliv pm interakce zen s DNA OER se pibliuje k jednice (dn efekt) pro LET 160 keV/mm OER pro n je 1.6 Hadronov terapie Most patients are treated by X-rays. World-wide there are 10,000 linacs and 4 million patients a year treated. Hadron therapy (Bragg peak) suggested by Bob Wilson in Radiology 47, 487 (1946) Pioneered in Berkeley and Harvard. Hadronov terapie (II) p a lehk ionty odevzdaj nejvt st energie v zk oblasti tzv. Braggova vrcholu Poloha Braggova maxima dna energi stic. jeho ka asto men ne rozmr ndoru lze rozit pouitm specilnch filtr, nebo ozenm

meandrovitm zpsobem navc minimln bon rozptyl hadronov terapie je lep ne IMRT asi 1% pacient ozaovanch radioterapi (200 pacient/10 mil. obyvatel) pro dalch 10% lep kontrola ozaovn Hadronov terapie (III) pro dobh 25 cm: Ep = 200 MeV, E12C = 4500 MeV nejvt vhoda lze pout v blzkosti citlivch orgn p a g interaguj s DNA spe nepmo pomoc radikl x pro 12C u je dleit i pm interakce s DNA (vt LET) C zanech 23x vce energie ne p se stejnm dobhem pm interakce s DNA je vznamn pro LET > 20 keV/mm C m tuto ionizaci na poslednch 5 cm drhy (He na poslednm 1 mm) m vt ionizan ztrty, tm hor reparace DNA lze sledovat ozen pomoc PET (dopadajc kladn ionty dvaj

vzniknout b+ radioaktivnm jdrm) Hadronov radioterapie vs. IMRT vhodou hadronov terapie je, e nedochz k ozen za objektem a tm k men zti zdrav tkn Hadronov terapie Svt As of August 2013, there were 43 particle therapy facilities in the world, representing a total of 121 treatment rooms available to patients on a regular basis. They are located in Canada, China, Czech Republic, France, Germany, Italy, Japan, South Korea, Poland, Russia, South Africa, Sweden, Switzerland, the UK and the US. 28% of the proton therapy facilities are located in the US and 23% are located in Japan and more than 96,537 patients had been treated R Protonov centrum Na Bulovce (www.ptc.cz) je vybaveno pikovou technologi belgick spolenosti IBA (Ion Beam Application) Pracovit m k dispozici cyklotron (230 MeV protony) a 5 ozaoven, ti z nich pracuj s pohyblivm svazkem (tzv. gantry), jedna se svazkem pevnm a jedna mstnost je urena pro ozaovn ndor oka. K dispozici je CT, NMR, PET/CT Pouit 12C

vhody pouit 12C lep kyslkov pomr ne u p pi ozaovn lze snit poet frakc, do kterch je celkov aplikovan dvka rozdlena (20-30 sezen pro g, pro 12C sta mn ne 10) sniuj se ekonomick nklady zvyuje kapacita pslunho centra sniuje se celkov lebn nronost z pohledu pacienta (men celkov aplikovan dvka) to give 12 Gy in a single stage (three entry points) and so treat a patient in simply one visit (as is done at HIMAC). This should be contrasted with X-rays where the dose delivered in one location, and in one visit, is only 1/3 Gy. nevhody 12C vt magnetick rigidita vy cena Ionizan ztrty v zvisosti na energii stice - popsny Bethe-Blochovou formul SOBP = Spread Out Bragg Peak cel ndor by ml dostat dostatenou dvku, aby se pedelo rediciv Ionizan ztrty tkch nabitch

stic (12C) v zvislosti na energii Zazen na hadronovou terapii - foto zazen pro lbu onch ndor (Villigen - project OPTIS) vce ne 3000 pacient Zazen na hadronovou terapii - foto (II) schma gantry Cummulative plot Total numbers of patients for facilities in and out of operation: http://ptcog.web.psi.ch/patient_statistics.html http://www.klinikum.uni-heidelberg.de Protonov centrum Praha (PTC) Protonov centrum Praha (www.ptc.cz)

4500 pacient (2019) VZP 2018: Celkem 75,4 milion korun stla v loskm roce lba onkologickch pacient za pomoci protonovho ozaovn celkem 159 pacient Vlastnkem centra je spolenost IMMORENT PTC, s.r.o. ze skupiny Erste Group Immorent Projekt za 4,2 miliardy K financovala Erste Group Immorent, kter do nj vstoupila pot, co se bratrm Latovkovm v roce 2006 podailo zskat smlouvu o smlouv budouc s nucenm sprvcem VZP V dubnu 2006 uzavel tehdej nucen sprvce VZP Antonn Peenka za pojiovnu smlouvu o smlouv budouc, kter VZP zavazuje po dobu 15 let hradit Protonovmu centru lbu 1650 jejch klient ron pi cen 26 tisc K za jedno ozen... (trest dva roky vzen s podmnenm odkladem na ti roky - verdikt potvrdil tak Nejvy soud) Nucenou sprvu, kter trvala od listopadu 2005 do kvtna 2006, na VZP uvalil tehdej ministr zdravotnictv David Rath a do funkce nucenho sprvce dosadil svho nmstka Peenku, kter ml provit a zlepit hospodaen pojiovny. Peenka pozdji v Protonovm centru nkolik let psobil. Spory s VZP urovnny a v r. 2016 (jeden pacient cena prmrn 500 000 K, vtinou kolem 20 jednotlivch ozaovn)

Radioterapie mezony p p- maj vrazn Braggovo maximum krom obvyklho mechanismu jsou p--mezony na konci drhy zachyceny v jdrech atom (v tkni nap. v 12C, 16O, 14N) pi zchytu p- jdrem dojde k reakci s p (p- + p+ n + 140MeV) a uvoln se energie 140MeV (vy ne BN) excitovan jdro se roztp zpravidla na a-stice, d, n a p (u tch jader se mezi fragmenty vyskytuj i 6Li nebo 12C) nap. u C dochz k reakci p- + 12C 2a + 3n + p, piem stice a odnej kinetickou energii cca 30MeV a neutrony cca 70MeV (zbylch 40MeV se spotebuje na pekonn vazbov energie jdra). zabrzdnm tchto fragment se v danm mst ped znan ionizan energie p- vznikaj pi ostelovn jader terku (nap. C, Be) p urychlenmi na energie vt ne asi 500MeV dosah p- o energich 50-100MeV v tkni in cca 10-25cm.

zazen v Los Alamos, Vancouveru, Villigenu - celkem asi 1200 pacient nedoshlo se lepch vsledk ne u konvenn terapie zastaveno Cena Leksellv gamma n poizovac cena 3-7x106 USD cena vyeten 7 500 - 9 500 USD (na jednoho pacienta) IMRT poizovac cena 3-10x106 USD za CyberKnife (USA,Anglie,Indie) cena vyeten 10 000-30 000 USD (na jednoho pacienta) Hadronov terapie poizovac cena 3 - 5 mld K (protony) viz dve ron provoz 200 mil K jeden pacient je asi 500 000 K u ns pedpoklad 1200 pacient/rok realita asi o dost jin HIMAC (12C) - poizovac cena 350 mil. USD (10 mld. K) A p facility costs $100M to $200M to construct, and costs of treatment range up to

$100,000 per patient, twice as much as contemporary radiation therapy, and up to four times as much as surgery, brachytherapy, and other options. (wikipedia) comparison probably depends on the type of tumor Poty schvlench dost a nklady VZP na protonovou terapii (PTC) Problmem je, e doposud nebyly publikovny dn zsadn vdeck studie, kter by dokzaly, e mra peit u pacient po protonov lb je ve srovnn s ostatnmi typy lby vy. Nepochybn je vak kvalita jejich ivota lep. Za mnohem vy cenu, nutno ct investice do protonov lby jsou vy jak pi samotn stavb centra, tak pi jeho vyuvn k terapii. Jak to vlastn je? Osobn nzor MK: v blzkosti citlivch orgn to smysl urit Cena Na zdravotnictv ron padne pes 200 miliard korun.

Prv o posouzen nklad pitom pedevm jde. Vdaje na zdravotnictv narostly od roku 1990 o 190 miliard korun, pjmy pitom budou v souvislosti se strnutm populace spe klesat. Podle propot Komern banky m v roce 2025 na tech zdravotnch pojioven oproti nynjku chybt 56 miliard korun. Nadstandard, kter to ml eit, se pitom nerozjel. Stt mus stanovit, jakou cenu je za lidsk ivot mon platit. Podobn to ostatn udlala u ada jinch stt, a Svtov zdravotnick organizace k tomu dokonce vydv i nvod: medicnsk technologie by vmnou za rok kvalitnho ivota nemla stt vce ne trojnsobek HDP na hlavu pslun zem. To je v kontextu esk ekonomiky nco pes milion korun. Dvka kvalitativn obrzek zvislosti nkterch proces v zvislosti na aplikovan dvce Pravdpodobnost [%] 100 90 80 70 odstrann ndoru (a)

60 pokozen zdrav tkn (b) 50 40 bez komplikac (c) odstrann ndoru bez komplikac (d) 30 20 10 0 Aplikovan dvka D mnostv peivch bunk v zvislosti na aplikovan dvce Aplikace - dvka Celkov dvka For curative (radical) cases, the typical dose for a solid epithelial tumor ranges

from 60 to 80 Gy, while lymphoma tumors are treated with 20 to 40 Gy. Preventative (adjuvant) doses are typically around 45 - 60 Gy in 1.8 - 2 Gy fractions (for Breast, Head and Neck cancers respectively.) Rozdlovn dvky The total dose is fractionated (spread out over time) in order to give normal cells time to recover. In the USA and Europe, the typical fractionation schedule for adults is 1.8 to 2 Gy per day, five days a week. (In the northern United Kingdom, fractions are more commonly 2.67 to 2.75 Gy per day, which eases the burden on thinly spread resources.) For children, a typical fraction is 1.5 to 1.7 Gy per day, reducing the chance and severity of late-onset side effects. Boron Neutron Capture Therapy (BNCT) izotop 10B m oproti ostatnm (pirozenm) izotopm vyskytujcm se v tle vrazn vt prez pro zchyt tepelnch neutron navc pi zchytu tepelnho n v 10B dochz k reakci (n,a), zatmco v ostatnch izotopech k reakci (n,g)

Isotop sR (b) H 0.332 H 0.53 B 3837 B 5.5 C 3.4

14 N 1.81 16 O 0.178 S 0.53 1 2 inn prezy nkterch izotop pro zchyt tepelnch

neutron 10 11 12 32 Boron Neutron Capture Therapy (BNCT) do ndorovho loiska se pomoc vhodn sloueniny, kter se pednostn vychytv a akumuluje v ndorov tkni, nav vhodn atomy, jejich jdra maj vysok s pro zchyt n pouv se 10B - velk s pro tepeln n, resp. jeho sloueniny BSH (merkaptododekarbort sodn), i BPA (dihydroxyboralfenylalanin) pipraven ndorov loisko se oz svazkem epitermlnch n ( 1 eV - 1 keV), kter se pi prchodu tkn zpomaluj a jsou zachycovny v jdrech 10B pi reakci n + 10B 7Li (0.84 MeV) + 4He (1.45 Me7) + g (0.48 MeV) vznikl ionty maj v tkni velmi mal dobh - Li 5 mm a He 9 mm, take ionizan energie je pedvna prakticky pouze pslunm ndorovm bukm metoda je zatm zkouena u

mozkovch ndor glioblastom, s pomrn slibnmi vsledky Japonsko, USA, Petten, Studsvik, Finsko, R Sloueniny 10 B 4-Borono-L-fenylalanin (BPA) 10 B merkaptododekabort sodn (BSH) BNCT - foto schma zazen na men mnostv 10B v ltce - PGNAA Stav metody BNCT ve svt zatm (s vjimkou Japonska) ve fzi klinickch test (vdsko a Finsko - jsou po formln (legislativn) strnce dle) Spolen projekt EU (Petten) : asi 30 pacient a Finsko: asi 200+ pacient jedin pracovit v provozu Japonsko: asi 100 pacient (pracovit zavena)

USA: asi 80 pacient a na R - e ozaovno 5 pacient kolem r. 2000 (+ na 5 studovna farmakokinetika) vechno ndory na mozku (gliblastoma multiforme - nejmalignej ndorov onemocnn s malou dobou preit), u kterch nelze pout jin metody ve svt se zkouela i pro ndory ke z fyzikalnho hlediska jsou vhodnj pro tuto metodu ne mozkov ndory ale zde existuj vcemn spn alternativn monosti poteba novch slouenin Krom B se uvaovalo i Gd ozaovn dky konverznm e K dispozici jsou zejm lep sloueniny ne pro B; obrovsk s pro zchyt Aktuln pehled teba na https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006699/ NCT s rychlmi n rychl n s energi 20-50 MeV mohou bt kolimovny pesn na terk - dva mon zpsoby vyuit bhem zpomalovn je 5 - 10 % rychlch n zpomaleno natolik, e mohou bt zachyceny 10B pomoc gantry lze provdt ozaovn z rznch stran a doshnou nejvt dvky v ndoru i bez pidn B

vliv na zdravou tk? rakovina prostaty a plic University of Washington Medical Center Karmanos Cancer Center/Wayne State University (KCC/WSU) in Detroit Radioizotopov terapie aplikujeme-li do organismu RA ltku, vstoup do metabolickho procesu zpsobem, kter je dn chemickou formou ltky - jej farmakokinetikou; poda-li se oznait vhodnm radionuklidem ltku, kter se selektivn vychytv a akumuluje v ndorov tkni, meme dostat velmi efektivn zpsob radian likvidace tumoru "zevnit". pro vtinu ndorovch proces bohuel takovou vhodnou ltku zatm nemme vznamnou vjimkou je karcinom ttn lzy - thyroidln ndorov buky si zpravidla zachovvaj schopnost vychytvat a akumulovat jd aplikujeme-li tedy radioaktivn jd 131I (perorln ve form jodidu sodnho), vychytv se tento radionuklid v ndorovch bukch ttn lzy (stejn jako neaktivn jd), a to i ve vzdlench metastzch. zen beta 131I (t1/2 = 8d), m v tkni dolet 3-4 mm, a likviduje ndorovou

tk "zevnit", a tedy selektivn, pi minimln radian zti okolnch zdravch tkn pro terapii karcinomu ttn lzy se aplikuje aktivita cca 7 GBq radiojdu Radioisotope therapy (RIT) Not used very often nowadays but very progressive future will show Radioisotopes are given by mouth as a drink or capsules, or injected into a vein (intravenous injection). Targeting can be due to the chemical properties of the isotope such as radioiodine which is specifically absorbed by the thyroid gland a thousandfold better than other bodily organs. Targeting can also be achieved by attaching the radioisotope to another molecule or antibody to guide it to the target tissue. Examples are the infusion of metaiodobenzylguanidine (MIBG) to treat neuroblastoma, of oral 131I to treat thyroid cancer or thyrotoxicosis, and of hormone-bound 177Lu and 90Y to treat neuroendocrine tumors (peptide receptor radionuclide therapy). Radioisotope therapy (RIT) Another example is the injection of 90Y radioactive glass or resin microspheres into the hepatic artery to radioembolize liver tumors or liver metastases. These microspheres are used for the treatment approach known as selective internal radiation therapy. The microspheres are approximately 30 m in diameter (about one-third of a human hair) and

are delivered directly into the artery supplying blood to the tumors. These treatments begin by guiding a catheter up through the femoral artery in the leg, navigating to the desired target site and administering treatment. The blood feeding the tumor will carry the microspheres directly to the tumor enabling a more selective approach than traditional systemic chemotherapy. There are currently two different kinds of microspheres: SIRSpheres and TheraSphere. 177 177 Lu production: Lu production (1) leads to carrier added (c.a.) 177Lu and consequently to a lower product quality. In addition, the unwanted long-lived radionuclide 177m Lu is produced (T = 160.1 d) with up to 0.1% of the overall 177Lu activity - this contaminant has to been seen very critically. Due to the long half-life of the nuclide a continuing risk of its release into the environment exists. Furthermore, the user in the hospital faces the problem of safe-handling and

radioactive waste management of the remaining quantities of 177mLu. More reasonable alternative seen from a medical and commercial approach is the production of 177Lu via the indirect nuclear reaction (2). By irradiating highly enriched 176 Yb (> 99%) the short-lived radioisotope 177Yb (T = 1.9 h) is produced and decays to 177 Lu. In this case, Lu can be chemically isolated from Yb in its non carrier added form. No 177mLu is generated through the decay of 177Yb. A drawback of this strategy is the mandatory radiochemical procedure to separate macro quantities of Yb from micro quantities of 177Lu. As the desired radionuclide and the target nuclide represent two adjacent elements of the lanthanide series the separation poses a great challenge because of their high chemical similarity. Lzn Jchymov :-) Lzn Jchymov jsou prvn radonov lzn na svt. I dnes mezi ostatnmi vynikaj svm vysokm obsahem radonu ve vod. Podle oficilnch daj lzn je tato koncentrace dokonce nejvt na svte. Tm pdem je na veker ozdravn procedury pohybovho stroj poteba mnohem men mnostv vody a krat as. Radonov voda blahodrn psob pedevm na nemoci pohybovho stroj,

revmatick bolesti, Bechtrevovu chorobu (tuhnut ptee) a porazov stavy. Radon je ve zdej vod ve vysokm mnostv, skvle pronik k a ozauje klouby a vechna problematick msta, m startuje lebn procesy. pramen vkon teplota vody obsah radonu akademika Bhounka 294 l /min 36,8 C 9 kBq /l C1 30 l /min 30 C

10 kBq /l Currie 30 l /min 28 C 5 kBq /l Agricola 8 l /min 28 C 20 kBq /l Trocha historie radian terapie The concept of therapeutic radiation was invented by Wilhelm Conrad Rontgen when he discovered that the x-ray (discovered 1895) was a powerful and effective tool with which to treat cancer.

The field of radiation therapy began to grow in the early 1900s largely due to the work of Marie Curie, who discovered the radioactive elements Po and Ra. This began a new era in medical treatment and research. Ra was used in various forms until the mid-1900s when Co and Cs units came into use. Medical linear accelerators have been developed since the late 1940s. With Godfrey Hounsfields discovery of computed tomography (CT), three-dimensional planning became a possibility and created a shift from 2-D to 3-D radiation delivery; CTbased planning allowed physicians to directly measure the dose delivered to the patient's anatomy based on axial tomographical images. In the last few decades, the advent of new imaging technologies, e.g., magnetic resonance imaging (MRI) in the 1970s and PET in the 1980s, as well as new radiation delivery and visualization products has moved radiation therapy from 3-D conformal to IMRT and eventually to IGRT (4-D) - Image-guided radiation therapy = the process of frequent imaging, during a course of radiation treatment - in the near future. These advances have

resulted in better treatment outcomes and less side effects. THE END 600 Vskyt zhoubnch ndor (na 100 000 obyvatel) 550 500 450 R Evropa 400 350 300 250 200 1965 1970 1975 1980 1985 1990 1995 1999 280 270

260 250 R Evropa 240 230 mrtnost na zhoubn ndory (na 100 000 obyvatel) 220 210 1965 1970 1975 1980 1985 1990 1995 1999

Prices for Conventional, Natural, Alternative or Holistic Tumour / Tumor / Cancer Therapy / Treatment in Germany The following prices are presented to give you a clear and (almost) definite idea of the costs you would be facing if you decide to have an operation or other medical treatment done in Germany. They are based on the assumption that there will be no serious complications and that there are no serious risk factors involved (e.g. extreme obesity, underlying other diseases, very old age etc.) that might create additional potentially costly challenges for the German doctors and hospitals. Prices do include our organisational fees, but they do not cover travel expenses, costs for hotels, costs for hiring translators etc. Please note that not all of our German partners will be able to offer these prices, which is why all price quotations should be regarded as "starting from". If you decide to go to one particular hospital, we will have to confirm for you if that prticulr hospital is able to perform the required procedure at the quoted price or if it might charge a slightly higher price. This price list is currently under preparation. Quotes will be available shortly. BRAIN TUMOUR SURGERY Gamma Knife Surgery: 11500 EUR or USD (? 7360)

At present, Cost studies IMRT have is applied shown primarily that when to prostate, compared head andtoneck, conventional breast, and neurosurgery, esophageal cancersthe andGamma to those brain Knife tumors is much close less to sensitive

expensive. structures It such as eliminates the eye. Its availability lengthy ispost-surgical expanding rapidly: hospital whereas stays in 1998, andonly expensive 4% of radiation 15 medication. oncology facilities In addition, provided IMRT, thereinare 2003, virtually 38% did.no

Also, post-surgical considerable work is disability being devoted and to make convalescent IMRT usable costs in other with cancers this procedure. such as those in the lung and abdomen, where motion is a problem. Hadronov terapie ve svt www.particle.cz/medicine Modulace svazku: Pasivn rozptyl

www.particle.cz/medicine Modulace svazku: Aktivn skenovn www.particle.cz/medicine Technick poadavky dosah ve tkni protony ionty 220-250 MeV

a 400 MeV/u posun Braggova maxima (1-3 mm) kroky zmny energie (0,5-1 MeV) velikost ozaovacho pole dvkov rychlost tok stic urychlovae 2-3,5 cm 2-10 cm 2-25 cm potebn maximln energie ndory o oblast hlavy a krku

uvnit tla cyklotron (IBA, Accel) synchrotron (PIMMS, PRAMES, Optivus) gantry aktivn skenovn www.particle.cz/medicine Lehk ionty radiobiologie vysok ionizan hustota (LET) hust radiklov shluky komplexn pokozen DNA vy biologick innost

Braggv peak vy RBE nepzniv kyslkov efekt potlaen ni poet frakc ndory v blzkosti kritickch orgn hypoxick radioresistentn ndory on-line monitoring pedvan dvky - PET Aktivity v rmci R interdisciplinrn pracovn skupina Vyuit ionizujcch stic v lkastv a biologii

neutronov zchytov terapie (BNCT) 1.LF UK, FZ, JF AVR, JV klinick testy - JV e , JF AV R, Nemocnice Na Homolce, Onkologick klinika 1.LF UK a VFN hadronov radioterapie vzkumn zprvy, studie PRAMES (1996-2000) Onkologie 2000 PIMMS (gantry) studie Onkologick centrum s hadronovou radioterapi, FZ AVR, kvten 2002 http://weber.fzu.cz/projekty/medicine/studie.pdf od r.2002 ENLIGHT

ENLIGHT http://www.estro.be/estro/Index.html European Network for LIGht Ion Hadron Therapy (grant EC, 2002-2005) vyuit iontovch svazk v radioterapii fyzikln technick aspekty, indikace, vbr pacient, ekonomick otzky European Society for Therapeutic Radiology and Oncology (ESTRO) European Organization for Nuclear Research (CERN)

European Organisation for Research and Treatment of Cancer (EORTC) Gesellschaft fr Schwerionenforschung GmbH, Darmstadt (GSI) German Cancer Research Center (DKFZ Heidelberg), German Heavy Ion Project (GHIP) Fondazione per Adroterapia Oncologica (TERA) Karolinska Institutet ETOILE Project, Universit Claude Bernard Lyon 1 Med-Austron, Wien FZR - Project Forschungszentrum Rossendorf Linkping University Hospital Virgen de la Macarena Charles University Praha Radiofarmaka UJV e produkuje Liv ppravek indikace 131 I Natrium Iodhipuricum diagnostika funkce ledvin 131

I jodid sodn roztok diagnostick aplikace ttn lzy Chlorid thaln 201Tl diagnostika poruch prokrven srdce Gallium citricum 67Ga lokalizace ndor mkkch tkn (vetn Hodgkinovy choroby, zhoubnch ndor vajenk, ndor jater), 111 In chlorid indit znaen komplexotvornch ltek, protiltek a bunnch sloek krve Sm paliativn lba bolestivch kostnch metastz pi

ndorovch onemocnnch, pedevm karcinomu prostaty, prsu, plic a jinch 153 Radioterapie (II) Radioterapie je zaloena na schopnosti ionizujcch stic inaktivovat (usmrtit) jednotliv buky. Bukm (jejich jdrm) je pi ozen pedna urit energie, kter vede k jejich pokozen. Mnoh takto vznikl pokozen je buka schopna opravit, nkter vak vedou k jejmu znien. Pravdpodobnost bunn inaktivace vzrst s energi pedvanou jednotlivm bukm. Pro rzn druhy bunk me bt tato pravdpodobnost znan rozdln. Biologick inek na buku danho typu zvis krom pedan dvky jet na dalch faktorech, z nich za nejdleitj lze oznait tzv. linern penos energie (linear energy transfer - LET): inaktivan inek na jednotliv buky je tm vt, m vce energie pedvaj stice ozaovacho svazku tkni na jednotku dlky sv drhy. Dalm dleitm faktorem je tzv. kyslkov pomr: inaktivan inek je ni, pokud buka obsahuje men mnostv molekulrnho kyslku. Tento rozdl se vak postupn zmenuje pro zen s vym linernm penosem energie.

Aby bylo mon pln vyut monost radioterapie a rozhodnout o jej optimln aplikaci, je nutn znt vechny zkonitosti, kter se pi radiobiologickm mechanismu uplatuj. Tk se to jak inku na jednotliv bunn jdra, tak i celkovho inku na pslunou ozaovanou tk i organismus. PSI The displacement of the spot position in the body is always performed with the beam switched off. For the fastest varying spot motion we use a deflecting magnet (the sweeper magnet ). The motion along the second axis of scanning is realized with a range shifter system , which scans the dose spot in depth. The third direction is covered by the motion of the patient table itself, which is the slowest and the least frequently used motion. The beam is a parallel beam with about 7mm FWHM (full width at half maximum) and is scanned in an orthogonal matrix in steps of 4 or 5 mm. For a one litre target volume typically 10'000 spots are deposited in less than 5 minutes. Proton radiotherapy of ocular tumors The OPTIS project The first proton therapy facility in Western Europe Over 3000 patients treated Interoperative Radiotherapy is a method of delivering radiation

during surgery by directly exposing cancers to electron beam radiation with normal structures being removed from the treatment field. It is used to treat gynecologic cancers, colorectal tumors, biliary tract tumors, retroperitoneal tumors, and certain recurrent head and neck tumors. This treatment is coordinated by boardcertified radiation oncologists and surgeons, with consultation from other medical specialties as needed. Protecting the Embryo/Fetus The only way to protect the embryo/fetus from excess radiation is to protect the mother Belly badge for the baby is issued Bioassay for radioactive material intake is initiated and repeated monthly Dose to baby is measured/ estimated and reported

Historically, pregnant women were not allowed to work with radiation Loss of position and Loss of pay To protect her baby, a mother must voluntarily, in writing, declare herself pregnant Present to Principal User/Supervisor and to the Radiation Control Office Additional information is available through the Radiation Control Office Confidential discussions with RSO about radiation risks to embryo/fetus Even if just planning to get pregnant Relative Biological Effectiveness (RBE) ( Biological effect of radiation Y at dose X Biological effect of 250 kVp x-rays at dose X Both produce the same biological effect. Quality factor (Q) radiation Q photon, b 1

proton, neutron 10 alpha 20 ) Ln (S) Shoulder of curve indicates cell repair at low doses Ne u Effect Same Biological Effect Different Dose from 2 types of radiation No shoulder - no cell repair Ga m

tr o ns Dn ma Dg Dos e Ph o to n s Occupational Dose to the Lens of the Eye Dose must not exceed 15 rem/ yr Occupational Dose Limit for Declared

Pregnant Mothers and Occupational Minors Dose must not exceed 0.5 rem or 500 mrem during the gestation period for declared pregnant mothers. Occupational minors must not exceed this dose in a year long period Radiation Effects for Embryo Declaration of Pregnancy for Occupational Mothers Rapidly dividing and nonspecialized cells are more sensitive to radiation Birth defects have been observed Dose limit to embryo / fetus is 500 mrem for the Hadronov terapie ve svt

p: asi 35000 pacient 12 C: asi 1600 pacient (HIMAC - Japonsko, GSI) asi 25 center dalch asi 20 plnovno (USA, Evropa, Japonsko) pro ionty plnovno zazen TERA v Itlii Loma Linda (USA) jedin komern zazen, jinak ve na zazench pro zkladn vzkum

energie 60 MeV sta pro lbu ndor oka dolet 3-4 cm (Villigen) situace na zatku roku 2003 Fungujc zazen Na potku roku 2008 fungovalo asi 30 zazen WHO, WHERE ITEP, Moscow St.Petersburg PSI, Villigen Dubna Uppsala Clatterbridge Loma Linda Nice Orsay COUNTRY Russia Russia Switzerland Russia

Sweden England CA.,USA France France South iThemba Labs Africa MPRI(2) IN.,USA UCSF CA.,USA HIMAC, Chiba Japan TRIUMF, Canada Vancouve r PSI, Villigen Switzerland G.S.I. Germany Darmstadt HMI, Berlin Germany

MAX. CLINICAL PARTICLE ENERGY (MeV) p 250 p 1000 p 72 p 200*** p 200 p 62 p 250 p 65 p 200

BEAM DIRECTION WHO, WHERE horiz. horiz. horiz. horiz. horiz. horiz. gant ry,ho riz. horiz. horiz. NCC, Kashiwa HIBMC,Hyogo HIBMC,Hyogo PMRC(2), Tsukuba NPTC, MGH Boston INFN-LNS, Catania

Shizuoka Wakasa WERC,Tsurug a WPTC, Zibo MD Ande rson Cancer Center, Houston, TX FPTI, Jacksonville, FL p 200 horiz. p p ion 200 60

800/u horiz. horiz. horiz.,vertical p 72 horiz. p** 250* gant ry ion** 430/u horiz. p

72 horiz. COUNTRY Japan Japan Japan MAX. CLINICAL PARTICLE ENERGY (MeV) p 235 p 230 ion 320 BEAM DIRECTION

gant ry gant ry horiz.,vertical Japan p 250 gant ry USA p 235 gant ry,ho riz. Italy p

60 horiz. Japan p 235 gant ry, ho riz. Japan p 200 horiz.,vertical China p 230

gant ry, ho riz. USA p 250 gant ry, ho riz. USA p 230 gant ry, ho riz. As of June 2012, there were a total of 41 proton therapy centers in Canada, China, England, France, Germany, Italy, Japan, Korea, Poland, Russia, South Africa, Sweden, Switzerland, and USA and more than 83,667 patients had been treated. [ Loma Linda

HIMAC The Japanese two proton ion synchrotrons at HIMAC. The pulse of ions is synchronized with the respiration of the patient so as to minimize the effect of organ movement. The facility is being reconditioned. A new one could be 1/3 as large. Zazen na hadronovou terapii - foto (II) schma gantry In summary (spring 2008): Present facilities (roughly): Sub-atomic physics labs doing some therapy: 12 Hospital based proton therapy centers: 10

Under construction:14 Patients treated: To date about 50,000 patients have been treated with hadrons. (mostly with protons) At HIMAC 3,000 patients treated with carbon beams At GSI 300 patients treated with ions

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