PowerPointPrsentation

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Clinical aspects of carbon ion RT Daniela
Schulz-Ertner
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Particle therapy
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Lateral scattering
Protons
Carbon ions
5 cm
LBL data
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Dose distribution in nanometer scale
At Bragg peak
At start of Bragg peak
Entrance Channel
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Definition of RBE
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Calculations for different sensitivities
M. Scholz, GSI
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Which Tumors Are Best For Carbon?
Resistant Tumors
Sensitive Normal Tissues
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Potential indications for carbon ion RT

• Chordoma / low grade chondrosarcoma
• Malignant salivary gland tumors
• Malignant melanoma of the paranasal sinus
• Soft tissue sarcomas and bone tumors
• Lung cancer
• Liver tumors
• Prostate carcinoma

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Potential advantages of carbon ion RT

• precision
• reduced integral dose
• modification of the biological effectiveness
• High-LET effect, less pronounced OER

Clinical benefit ?
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Availability of carbon ion RT
NIRS, Chiba / Japan
Hyogo Ion Beam Medical Center / Japan
GSI, Darmstadt / Germany
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GSI Darmstadt
Availability for clinical applications 3 beam
time blocks / year 20 days
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Rasterscan-Technique
Irradiated volume

-
Isoenergetic levels
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Passive beam application - constant modulation
depth and intensity throughout the field
RBE as depth dependent factor Tsuji 1998
Active beam application (raster scanning) -
Adaption of modulation depth at each point -
Optimization of intensity at each scan spot
RBE calculation at each voxel
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Principle of the Local-Effect-Model (LEM)

• Input parameters
• radial dose distribution
• size of cell nucleus
• x-ray sensitivity (?/? ratio)

Scholz 1996
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Therapy parameters at GSI

• Immobilization
• intensity-controlled raster scanning with pulsed
• energy variation
• 3D treatment planning (CTMRI)
• VIRTUOS
• TRiP
• daily x-ray controls (comparison with DRR)
• PET (beam verification)

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Carbon ion radiotherapy at GSI

• n264, 1998-2005

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15
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131
58
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Results of carbon ion RT at NIRS
Locally advanced head and neck (phase II, n
134, 52.8 - 64.0 GyE / 16 Fx / 4 weeks) 2y-
LC 61 3y- OS 42
Yamamoto 2005
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Combined photon IMRT plus C12 boost total dose 72
CGE (54Gy18CGE)
60 CGE-Isodose line 39 CGE-Isodose line 54
CGE-Isodose line gt 66 CGE
Schulz-Ertner, Cancer 2005
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FSRT / IMRT vs FSRT / IMRTC12 for locally
advanced adenoid cystic carcinoma
OS
LC

• Acute toxicity acceptable
• late toxicity gt CTC Grade 2 lt 5

Schulz-Ertner, Cancer 2005
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Chondrosarcoma G1/2
Prä OP
Post OP
Dosis in
Carbon ion RT Biologically optimized treatment
plan
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Carbon ion RT of skull base chordomas
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Carbon ion RT for skull base chordomas and
chondrosarcomas (phase I/II trial)
Schulz-Ertner, IJROBP 2004
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RT of chordomas and chondrosarcomas
Author, year n RT local control Romero, 1993
18 conv.RT 17 (CH) Debus, 2000 45 FSRT
50 / 5y (CH) Munzenrider, 1999 519 prot. (
phot) 73 / 5y (CH) 98 / 5y (CS) Castro,
1994 223 He 63 / 5y (CH) 78 / 5y
(CS) Noel, 2001 67 prot phot 71 / 3y
(CH) 85 / 3y (CS) Schulz-Ertner,
2004 67 C12 74 / 4y (CH)) 87 / 4y (CS)

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Phantom measurements
Position 2
Max. dose variation myelon 14 / mm for C12 8
/ mm for photon-IMRT
Karger PMB 2003
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Carbon ion RT of inoperable soft tissue sarcomas
Local control
Kamada, JCO 2004
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Stage I NSCLC (phase I/II, inoperable PT) 57.6 -
95.4 GyE, 18 Fx, 6 weeks, n 47, 72 GyE, 9 Fx, 3
weeks, n 34
5y-overall survival 42 5y-cause-specific
survival 60 radiation pneumonitis III 3/81
Miyamato et al. 2003
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Results of carbon ion RT at NIRS
Hepatocellular carcinoma (Protocol liver-2, phase
I/II) n 82 2y-local control 83 3y-overall
survival 45 cause of death mostly related to
progression of associated liver cirrhosis
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Dose escalation for localized prostate cancer
Pollack 2002, MD Anderson
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Zelefsky 2001, Memorial Sloan Kettering
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Dose-response curve for PC
Hanks 2002, Fox Chase
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Rationale for carbon ion RT in locally advanced
prostate cancer

• ?/ß low (1.5 3 Gy)
• hypofractionation ?

Fowler 2003
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Particle therapy for localized prostate cancer

• severe toxicity
• RT Dose n GI GU 5J-NED
• MDACC Conv. RT lt67 Gy 500 54 (4y)
• 67-77Gy 495 14.8 8.5 71 (4y)
• gt77 Gy 132 77 (4y)
• MSKCC IMRT 81.0-86.4 772 4.5 15 86
  (3y,IR) 92 (3y,LR) late 1.5
  II 81 (3y,HR)
• LLUMC Protons 75CGE 1255 1 (III) 1 (III)
  48 (HR)
• NIRS Carbon 66.0GyE 170 1 (II) 6 (II) 79
  (HR)

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Influence of organ motion on carbon ion RT

• Variance for 95 90-coverage / CTV
• 3.6 (SD 3.7) 2.8 (SD 2.8)
• Variance for the clinically relevant Dmin 6.2 Gy
  /GTV, 12.5 Gy /CTV
• Variance of the rectal volume gt 70 Gy lt3cm3
• (Kupelian 2002 rectal volume gt 70 Gy lt15cm3)

Nikoghosyan 2004
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Phase I/II trial Combined photon IMRT carbon
ion boostfor locally advanced prostate cancer

Photon IMRT 60 Gy / median CTV2 (prostate
seminal vesicles5mm individual safety
margin) Carbon ion RT 18 GyE (6 Fx) CTV1 /
prostate individual safety margin
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Photon IMRT and C12
IMRT
C12
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Carbon ion RT trials at GSI
Skull base CHCS ACC Phase I/II spinal/ sacral
CH CS Phase I/II Prostate
30 / year routine
10 / year routine
completed
15 / year
2003
2004
2005
2006
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Heavy Ion Therapy (HIT) in Heidelberg


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Conclusions

• Randomized trials proving the superiority of
  carbon ion RT in comparison to photon IMRT and
  protons are lacking, but several combined
  facilities are planned to be built in Europe and
  will allow phase III trials in the future
• Integration of carbon ion RT into
  interdisciplinary treatment concepts necessary
• First results of clinical phase I and II trials
  performed at NIRS and GSI support the assumption
  that carbon ions provide an enhanced biological
  effectiveness in adenoid cystic carcinomas, H/N
  melanomas, lung and liver tumors, large soft
  tissue sarcomas, chordomas / chondrosarcomas and
  prostate cancer
• radiobiologic research will enable better
  exploitation of the advantages of carbon ion RT
  in future trials