Tumor-Therapy

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Tumour Therapy with Particle Beams Claus Grupen Merida, Mexico, March 1st, 2000  Radiobiology of Ionising Radiation  Production, Measurement and Control of Heavy Ion Beams  Application in Tumour Therapy  biological effects  raster scan technique  safety systems  treatment facilities

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Radiobiology of Ionising Radiation  photons  electrons  neutrons  protons  heavy ions  the radiation dose is proportional to the energy loss dE/dx  dose D = = [Joule/kg] 1 Gray [Gy] = 1 Joule/kg (old unit 1 rad = 10 m Gy)  the cell kill rate for fixed dE/dx increases with ionisation density absorbed energy  E mass m E m

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 equivalent dose H =  biological effectiveness (RBE) H [Sievert] = 1 Joule/kg  RBE (old unit: 1 rem = 10 mSv) some doses for comparison :  lethal whole body dose  50 % mortality within 30 days without medical treatment  natural annual exposure by  cosmic rays 0.4 mSv  terrestrial radiation 0.6 mSv 2.5 mSv  incorporation 1.5 mSv (inhalation & ingestion)  average annual man-made exposure  1 mSv (medical diagnostics, nuclear power plants, technology, ...) absorbed energy mass

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Photons  X-rays 10 keV - 1000 keV  bremsstrahlung of electron accelerators (up to 10 MeV)  -rays from radioacitve sources (~ MeV) example 60 Co  - 60 Ni** 60 Ni* 60 Ni 1.17 MeV 1.33 MeV absorber x I 0 I(x) = I 0 e - x  - mass attenuation coefficient absorption of photons

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x I 0 I(x)  = f (E  , absorber material)  large dE/dx (  large dose) close to the surface  low penetration  RBE = 1  other effects:  Compton scattering  electron pair production

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Electrons  from radioactive sources  from linear accelerators  dE/dx by ionisation and bremsstrahlung  ionisation: à la Bethe Bloch ~  bremsstrahlung: ( X 0 - radiation length)  low ionisation density  RBE = 1  low penetration for typical energies (4 MeV  ~ 2.5 cm tissue)  large angular scattering (poor aiming)

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Neutrons  no electromagnetic interactions  collisions with cell nuclei  energy deposition I(x) similar to photons  RBE = 3 - 10 depending on the neutron energy Protons  maximum energy deposit at the end of the range  RBE = 10 dE/dx photons protons Bragg-peak x

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Bethe-Bloch Formula charge of the projectile (z=1 for protons) velocity of the projectile energy of the projectile Heavy Ions  energy loss increased by factor z 2  RBE = 20

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dE/dx x E 2 > E 1 E 2 E 1 variation of energy  variation of penetration depth magnetic deflection  variation of position of incidence  destruction of tisssue in a three-dimensional volume  inside the body  at low surface dose  protection of healthy tissue

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Brain Tumour Treatment with Neutrons  the tumour is sensitized with a boron compound before neutron treatment  the boron compound is preferentially deposited in the tumour region  then tumour treatment starts  the -particles have a very short range (several m)  best results with epithermal neutrons (1 keV) produced by 5 MeV protons on light targets (e.g. Be).

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Production, Measurement and Control of Ion Beams ion source 12 C ions stripper foils 12 C nuclei accelerating cavity quadrupoles dipole magnet kicker magnet beam extraction beam monitors veto counters treatment room

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Detectors for measurement and control (beam steering)  magnets for beam steering  accelerating cavities for energy settings  ionisation chambers for dE/dx-measurement for beam intensity measurement  multi-wire proportional chambers for beam position measurement  veto counter, scintillation counter as interlock  will switch off accelerator if beam position is off by a preselected margin

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Applications in Tumour Therapy  the target for cell killing is the DNA in the cell nucleus  a single strand break will be repaired easily (by copying)  a double strand break cannot be repaired correctly  cell division (mitosis) is stopped when the DNA has a major deficiency  again: RBE =  cell killing rate  dE/dx  RBE dose with X-rays dose by heavy ions for the same biological effect

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Raster scan method  thin pencil beam of heavy ions (Ø  1mm)  subdivision of the tumor in three-dimensional pixels  calculation of the required dose (beam intensity) per pixel  for a fixed depth in tissue  areal scan by magnetic deflection (similar to producing a TV image)  “filling” of the tumour volume by energy (  range) variation of the beam 2 cm - 30 cm tissue corresponds to 80 MeV/n - 430 MeV/n  typical: 50 energy steps, starting at the rear plane  treatment time  12 minutes  fixation of patient is necessary

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Safety Systems  in addition to ionisation nuclear fragments are produced by heavy ions 12 C + tissue   11 C, 10 C are positron emitters  the annihilation -rays are emitted back-to-back and detected by a PET-system (positron-emission tomography)  on-line monitoring of dose distribution in tissue ionisation (dE/dx) 11 C, 10 C-production 11 C e +  

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Treatment facilities  first experimental irradiation with protons in Berkeley  later in Dubna (near Moscow), Harvard, Loma Linda in California  about 25 treatment facilities throughout the world  up to now 20 000 patients treated  costs per treatment  20 000,- US $  success rate (brain tumour, eye tumour, ..... (well localized tumours)) >> 50 %

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Outlook  heavy ions are an ideal projectile for tumour treatment  expensive accelerator complex required  suitable for well localized tumours  availability is increasing  construction of dedicated multi-treatment room facilities planned  X-rays and -rays have helped to increase the imaging quality for diagnostic purposes  beam steering and control requires sophisticated particle detectors and interlock systems