Outline
2
• Radioterapiae“particletherapy”• Iconcettidibase• Alcunielementidiradiobiologia• Particletherapynelmondo• Ricerca&Sviluppo:alcuniitemssucuifisicanucleareedelleparticellepossonocontribuire
HistoryofRadiotherapy31945, R. Wilson: first proposal to use hadrons for radiotherapy
Hadron RT proposed by Robert Wilson in 1946
First hadron therapy in the sixties in US (Protons) 1954–Berkeleytreatsthefirstpatientandbeginsextensivestudieswithvariousions1957–firstpatienttreatedwithprotonsinEuropeatUppsala1961–collaborationbetweenHarvardCyclotronLab.andMassachusettsGeneralHospital1993–patientstreatedatthefirsthospital-basedfacilityatLomaLinda1994–firstfacilitydedicatedtocarbonionsoperationalatHIMAC,Japan2009–firstEuropeanproton-carbonionfacilitystartstreatmentinHeidelberg
Modulazionedellaprofonditàecapacita’diconformazione
muovendo il fascio in X,Y e variandone l’energia (profondità raggiunta) tutto il bersaglio puo’ essere efficacemente irradiato
Fasci di energia diversa depositano energia a profondità diverse nel tessuto→ rilascio di dose modulato lungo la
direzione del fascio
Conformazione:ilconcettodiSpreadOutBraggPeak(SOBP)
Size of the tumor region
PTV = Planned Treatement Volume
This plot is in physical dose for a constant biogical
effectiveness
SingleFieldUniformDose(SFUD)
MultiFieldOptimisation(MFO)or
IntensityModulatedProtonTherapy(IMPT)
Combinationofindividuallyoptimisedfields,eachofwhichdeliverahomogenousdoseacrossthetarget
SimultaneousoptimisationofallBraggpeaksfromallfields:thesumofthebeamscoversthetargetuniformlywithdose.Itprovidesmoredegreeoffreedomandbetternormaltissuesparing,especiallyforOARsontheproximalsideofthetarget.
ProtonTherapy:ScanningBeams
2DIMPT:deliveryofintensitymodulatedprotonfieldswithfixedrangemodulation.thedepth–dosedistributionischaracterizedbyafixedextentSOBP,whosedistaledgeismatchedtothedistaledgeofthetargetvolumebyafixedandfieldspecificrangecompensator.deliveryofa2Dmatrixofintensities,witheachintensitybeingassignedtoanarrow,fixedextentSOBPpencilbeam.
homogeneousdosedistributionscanbeachievedthroughtheuseofsingleBraggpeaksandinwhichtheratioofenergydepositedinthetargetvolumetothatdepositedelsewherecanbemaximized.amono-energeticprotonbeamwhoseBraggpeakismatchedtothedistaledgeofthetarget.intensityvariationofthemono-energeticBraggpeakpencilbeamswithafixeddepth–dosecharacteristicinwater
2.5DIMPTintensitymodulationofvariable,asopposedtofixed,extentSOBPs.theextentofSOBPsoriginatingfromdifferentpointsinthetransversalplanearematchedtothethicknessofthetargetinthebeamdirection,reducingunnecessarydoseproximaltothetargetvolume.althoughthefreemodulationofpencilbeamsstilltakesplaceonlyinthetransversalplane,thedepth–dosecharacteristicsoftheindividualpencilbeamsalsovaryacrossthetransversalplane.Thiscanbethoughtofasalimitedformofdepthmodulation,eventhoughthedepth–dosecharacteristicsofindividualpencilbeamsarefixed,andassucharenotmodifiedbytheoptimizationprocess.
exploitsthe3DlocalizationofdoseintheBraggpeakbyintensitymodulatingindividualnarrowbeamBraggpeaksinthreedimensions.Braggpeaksaredistributedthroughoutthetargetvolumeinthree-dimensions,witheachindividualBraggpeakpencilbeam,regardlessofitspositionindepth,beingtreatedasafreeparameterintheoptimization.
IMPT
Magneti deflettono lateralmente il fascio incidente di energia variabile allo scopo di irraggiare tutto il bersaglio che è suddiviso in volumi cubici(voxel) raggruppati in sezioni longitudinali (slices, la cui posizione dipende dall’energia)
Ilconcettodirasterscanning(scanningattivo)
Non e’ conveniente utilizzare ioni piu’ pesanti del Carbonio: producono troppi frammenti nucleari che vanno piu’ lontano di quello che serve
Ione (nucleo di Carbonio): 6 protoni + 6 neutroni
A causa della maggior efficacia radiobiologica, è meno probabile la capacità della cellula irradiata di autoripararsi: mediamente potrebbero bastare 8-10 sedute di radioterapia contro le 20-30 della terapia con raggi X o con protoni
Rangedienergiautile:
Protoni: 50-250MeV12C: 60-400MeV/u
CiclotronioSincrotroni
soprattuttoSincrotroni
Particletherapyconnuclei(ioni):ilcasodelcarbonio
Profilo di dose conforme in profondità È facilmente assorbibile dai tessuti biologici VANTAGGI Elevata efficacia biologica “a fine corsa” Possibilità verifica in-beam mediante PET
Tecnologie di produzione costose (>100 milioni di €) SVANTAGGI Frammentazione nucleare
Attuamente la terapia con ioni carbonio è effettuata a • Dopo l’esperienza pionieristica al GSI/Germania, con beam scanning attivo, ora sono in funzione Heidelberg e CNAO (Italia, sperim. Clinica) • HIMAC,HIBMC/Giappone, con fascio diffuso
48clinicalcentersinoperationUnderconstruction:25proton/4heavyioncentersOnlyinUSA27newcentersexpectedby2017
~2014:137179treatedpatients:118195withp,mainlyinUSA,5353215736with12C,mainlyinJapan,10993;+46,000inthepast5years≈10,000patientsperyear
ChargedParticleTherapyintheworld
Robert R. Wilson (left) designedthe cyclotron but joined Cornellbeforeitwasbuilt.
Earlier, Wilson wrote the shortpaper that launched protonradiotherapy (‘Radiological use offast protons,’ Radiology 47 (1946)487)
ThesecondHarvardCyclotronwasdedicatedon15June1949.The first treatments, by Dr. Ray Kjellberg, were single fraction‘radiosurgery’ofintracranialtargets.Thelastpatient,aoneyearoldinfant,wastreated10April2002.
Pioneers
2308/06/2015G.Battistoni
CarbonIonTherapy
Exp. Data (points) from Haettner et al, Rad. Prot. Dos. 2006 Simulation: A. Mairani PhD Thesis, 2007, Nuovo Cimento C, 31, 2008
Bragg peak in a water phantom 400 MeV/A C beam: The importance of fragmentation
Braggpeaksvsexp.data:12C@270&330MeV/n
25G.Battistoni08/06/2015
Exp.DataJpn.J.Med.Phys.18,1,1998
Dosevsdepthdistributionfor270and330MeV/n12Cionsona
waterphantom.Thefullgreenand
dashedbluelinesaretheFLUKApredictionsThesymbolsareexp
datafromGSI