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INTRODUCTION TO HADRON THERAPY

International Workshop on LHC, Astrophysics, Medical and Environmental Physics. Shkodra , 6-8 October 2014. INTRODUCTION TO HADRON THERAPY. P.R. Altieri , PhD University of Bari and Italian National Institute of Nuclear Physics (INFN). Outline HISTORY OF HADRON THERAPY

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INTRODUCTION TO HADRON THERAPY

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  1. International Workshop on LHC, Astrophysics, Medical and Environmental Physics. Shkodra, 6-8 October 2014 INTRODUCTION TO HADRON THERAPY P.R. Altieri, PhD Universityof Bari and Italian National InstituteofNuclearPhysics (INFN)

  2. Outline • HISTORY OF HADRON THERAPY • PHYSICAL BASICS • BIOLOGICAL BASICS • TECHNICAL ASPECTS • CONCLUSIONS AND FUTURE CHALLENGES

  3. HISTORY OF HADRON THERAPY 1895: discoveryof X rays 1898: discoveryofradioactivity Wilhelm Roentgen Henri Becquerel Pierre and Marie Curie

  4. HISTORY OF HADRON THERAPY 1946: R. Wilson first proposed a possible therapeutic application of proton and ion beams R. Wilson, Radiologial use of fast protons, Radiology 47, 487-491, 1946 Robert Rathbun Wilson 1954: first patient treated with deuteron and helium beams at Lawrence Berkeley Laboratory (LBL)

  5. HISTORY OF HADRON THERAPY The first hadrontherapycentersoperated at the nuclear and subnuclearphysicslaboratories: • 1957: Uppsala (Sweden); • 1961: Massachusetts General Hospital and Harvard CyclotronLaboratory (USA); • 1967: Dubna (Russia); • 1979: Chiba (Japan); • 1985: Villigen (Switzerland). 1990: the first hospital-basedprotontherapyfacility at Loma Linda UniversityMedical Center (LLUMC). LLUMC (California, USA)

  6. PHYSICAL BASICS HadronTherapy Treatment oftumorsthroughexternalirradiationbymeansofacceleratedhadronicparticles: neutrons, protons, pions, antiprotons, helium, lithium, boron, carbon and oxygenions. Protons and heavyions(particleswith mass greaterthanhelium) havephysicalproperties, and so radiobiologicaleffects, suchthat: high and conformal dose isdeliveredto the tumor target; minimazing the irradiation of healthy tissue. Photons Hadrons Ionization density Effect on cellular DNA

  7. PHYSICAL BASICS Interactionsofprotonswithbiologicalmatter Interactionsofprotonswithbiologicalmatter Seo Hyun Park, Jin Oh Kang, Basis of particle therapy I:,physis, Radiat. Onol. J 29(3), 135-146, 2011

  8. PHYSICAL BASICS Interactionsofprotonswithbiologicalmatter Energy transfer reliesmainly on: • Coulomb interactions (Stopping) with the outer-shellelectronsof the target atoms->excitation and ionizationofatoms -> protonsslow down - > energy loss (80 ÷ 90%) • loss per interactionsmall->continuously slow down • secondaryelectronshaverange < 1mm ->dose absorbedlocally Energy loss isgivenbyBethe-Blochequation:

  9. PHYSICAL BASICS Interactionsofprotonswithbiologicalmatter • Nuclearreactions:nonelasticnuclearreactionswith the target nuclei (energy loss 5 ÷ 20%) ->production ofsecondariessuchas • protons, α ,recoils nuclei, γ-rays (nuclei excitation), neutrons ->radiationsafety • radioactiveisotopes (tissueactivation), es. 15O, 11C, 13N (β+- emitters) -> fromisotopesactivity 3D dose verificationwith PET/CT K. Parodi et al., IEEE MIC CR, 2002 Proton beam @ 110 MeV

  10. PHYSICAL BASICS Interactionsofprotonswithbiologicalmatter Angulardeflectionofhadronsis due to • Multiple Coulomb Scattering (MCS):elastic Coulomb interactionswith the target nuclei-> superposition ofsmalldeflections -> beamlateralpenumbra (importantforitseffect on ograns at risk) Proton mass >> electron mass ->deflectionsforelasticcollisions can beneglected MCS iswelldescribedfromMoliéretheory Lateralscatteringcan beapproximatelydescribedwith a Gauss distribution.

  11. dE dm [Gy = J/kg] PHYSICAL BASICS Depth-dose curve Braggpeak Dose = William Bragg Physicalabsorbed dose Dose: [40 Gy, 70 Gy] dE dx the highest dose is released near the end of hadron range giving rise to the “Bragg peak” - V-2 Range: penetrationdepthsuchthat dose absorbedis 80% ofpeakvalue Range and dose distributioncalculationmustbe as accurate aspossible

  12. PHYSICAL BASICS Spread-outofBraggPeak (SOBP) SOBP Totreatanextended target the Braggpeakis spread out to cover the whole volume bymodulating the beamenergy Beamenergymodulation

  13. DX-rays Dparticle BIOLOGICAL BASICS Relative BiologicalEffectiveness (RBE) RBE = RBE depens on manyfactors: • energy; • particletype; • organdimensions; • tissuetype; • presenceofoxygen. hadrons more biologically effective than photons: lower dose is required to cause the same biological effect

  14. dE dl BIOLOGICAL BASICS Linear Energy Transfer (LET) [keV/μm] LET = LET ->ionization density ->qualityofradiation High LET (> 10 keV/μm) -> multiple DNA damages Hadrons are high LET withrespecttophotons Relationshipbetween RBE and LET as a functionofparticletype

  15. BIOLOGICAL BASICS Protons vs photons TC image: dose distributioncalculatedforprotonbeams and X-rays. Physicaladvantages : • finite range and high ionization density; • lowerintegral dose; • smalllateralscattering (largerflexibility). Clinicaladvantages : • treatment ofdeep-seated, irregularshaped and radioresistanttumors; • smallprobabilityof side effects in normaltissue (criticalstructrure); • protontherapysuitableforpediatricdiseases (reducedtoxicity).

  16. TECHNICAL ASPECTS Mainpartsofanhadrontherapyfacility Beam Delivery System ACCELERATOR (cyclotron, synchrotron, linear) B D S B T S Patient BeamTransport System HaHadrontherapyfacilityscheme – IBA (Belgium)

  17. TECHNICAL ASPECTS Particleaccelerators Synchrotron: presents a cycle (spill) thatlastsabout 2 s, beamispresentforabout 0.5 s and itsenergy can bevariedfromspilltospillwithout passive elements. Energy rangefortherapeutichadronbeams: • p: [60, 250] MeV • 12C: [120, 400] MeV/u Cyclotron: high intensity, continuousbeam, itsenergyisfixed and can bedegradedwith passive absorbers in the Energy Selection System (ESS).

  18. TECHNICAL ASPECTS Beam Delivery System – Passive Scattering System Beam is widened and flattened by means of personalized collimators and compensators. Range shifter (rotating wheel with different thickness) is used to irradiate at different penetration depths (SOBP). Passive Scattering System Collimator and compensator RangeModulator

  19. TECHNICAL ASPECTS Beam delivery system – Active Scanning System Active Scanning System • Hadrons can be deflected magnetically -> a narrow mono-energetic “pencil beam” can be scanned magnetically across the target volume in a zigzag pattern in the x-y plane perpendicular to the beam direction (z); • the depth scan is done by means of energy variation.

  20. TECHNICAL ASPECTS Dose delivery system – Active Scanning System Discrete spot scanning: (developed at PSI) dose is delivered to a given spot at a static position (constant magnet settings). Then the pencil beam is switched off and the magnet settings are changed to target the next spot, dose is delivered to the next spot, and so forth. Principleofactive beam scanning Single beam Lateral scanning Scanning in depth 3D dose distribution

  21. TECHNICAL ASPECTS Dose delivery system – Active Scanning System Raster scanning: (developed at GSI - Darmstadt) continuous path, beam dose not switch off between two voxels (except two spot are away from each other). Dynamic spot scanning: beam is scanned fully continuously across the target volume. Intensity modulation can be achieved through a modulation of the output of the source, or the speed of the scan, or both. Principleofactive beam scanning

  22. TECHNICAL ASPECTS Active Scanning System vs Passive Scattering System AdvantagesofActive Scanning technique: No need of compensators and collimators (dependent on patient anatomy), the beam has less nuclear interactions outside the patient, this means less neutron contamination and overdose; great flexibility, arbitrary shapes can be irradiated with a single beam, this allows better target conformation. Disadvantage of Active Scanning technique: Difficulty to treat “moving organs” (organs subject to motion due to respiration) such as lung cancer, it is necessary to develop systems to synchronize the beam and the patient’s respiration.

  23. TECHNICAL ASPECTS Gantry and nozzle Conformalradiationtherapyrequires target irradiationfrom any desired angle. The beam is deflected by the magnetic field in the gantry. Treatment nozzle (final part of the gantry) consists of various components for beam shaping and beam monitoring. Big dimensions(3.5 m diameter) -> veryexpensive Gantry at HidelbergIon-beamTherapy Center (HIT) Treatment room at Boston Northeast Proton Therapy Center (NPTC)

  24. TECHNICAL ASPECTS Imaging and qualityassurance ComputedTomography (CT) / Positron Emission Tomography (PET) essential: • prior to treatment-planning for delineating target volumes and structures of interest; • to position and immobilize the patient reducing errors; • online and offline monitoring (in vivo 3D dose and/or range verification). Homer Simpson CT Allsourcesofuncertaintiesmustbeminimize: • test formechanical and electricalsafety; • test ofbeamcharacteristics (intensity, profile and position mustbestable); • checkoftolerances and geometricmisalignments; • shieldingforsecondaryradiation (speciallyneutrons).

  25. TECHNICAL ASPECTS Monte Carlo Simulations Monte Carlo method: probabilistic method that allows to solve analytically complex problems, stochastic or deterministic, by means of sampling techniques. MCS “gold standard” in radiation therapy for: • dose distribution prediction; • range uncertainties estimation; • radiobilogical studies; • design an commissioning of facilities. treatment planning validation Accurate resultsrequire the simulationof a largenumberofevents (106÷109) -> long executiontime and largecomputationalresources GRID computing

  26. TECHNICAL ASPECTS Hadrontherapyfacility in Itlaly CATANA (Centro di Adroterapia e Applicazioni Nucleari Avanzate) @ LNS (Laboratori Nazionali del Sud) - Catania CATANA treatment room Since 2002 eyetumors are successfullytreatedwithprotonbeamsof 62 MeVproducedby a superconducting cyclotron (SC).

  27. TECHNICAL ASPECTS Hadrontherapyfacility in Itlaly CNAO (Centro Nazionale di Adroterapia Oncologica) @ Pavia • Treatmentswithprotonsstarted in september 2011 • Treatmentswithcarbonionsstarted in november 2012 p E : [60, 250] MeV C6+ E : [120, 400] MeV/u Syncrotron (26 m diameter) 3 Treatmetrooms 3 Horizontalbeamlines 1 Vertical beamline

  28. TECHNICAL ASPECTS Hadrontherapyfacility in Itlaly ATreP (Agenzia Provinciale per la Protonterapia) @ Trento Cyclotron (4.34 m diameter) Proton beamsextracted at 230 MeV Two treatment rooms Inaugurated in July 2013, aftercommissioningit’s starting the clinicalactivity

  29. CONCLUSIONS AND FUTURE CHALLENGES Hadrontherapyreperesentsanimportantinstrumentfor the cure ofcancer; it can beconsidered the directapplicationof high energyphysicsresearch and technologiesdevelopedfor the experiments; it’s a multidisciplinaryfield(medicine, physics, biology, engineering) in continuousevolution. Research and developmentefforts: toimprovecarbonion treatment and introduce newhadrons (helimunions); toimprovebeam delivery techniques and movingorgans treatment; toconstructnewaccelerators (LINAC or laser plasma accelerator).

  30. THANKS FOR YOUR ATTENTION P.R. Altieri: palma.altieri@ba.infn.it PP

  31. BACK UP

  32. dN dA dE dm [Gy = J/kg] [Particles/cm2] PHYSICAL BASICS Absorbed dose Ideal dose distribution: - 100% to the target - 0% tosurroundinghealthytissue Dose = Fluence Range: penetrationdepthsuchthat dose absorbedis 80% ofpeakvalue. Φ = 32

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