1. RELATIVE BIOLOGICAL EFFECTIVENESS IN ION BEAM THERAPY ........ 1
1.1. Introduction 1
1.1.1. Role of radiation therapy in the treatment
of cancer ........................................ 1
1.1.2. Present situation and future trends .............. 2
1.1.3. Rationale for ion therapy ........................ 3
2. BIOLOGICAL WEIGHTING OF ABSORBED DOSE: THE SPECIFIC
ISSUE OF RBE IN ION BEAM THERAPY ............................. 8
2.1. Absorbed dose ........................................... 8
2.2. Need for weighting factors .............................. 9
2.3. Reference irradiation conditions ....................... 10
2.3.1. Radiation quality ............................... 10
2.3.2. Reference fractionation scheme .................. 10
2.4. Fractionated external photon therapy ................... 11
2.4.1. Weighting factor for differences in dose per
fraction ........................................ 11
2.4.2. Example ......................................... 12
2.5. Brachytherapy and differences in dose rate ............. 12
2.6. Influence of overall time .............................. 13
2.7. Radiation quality and RBE .............................. 14
2.7.1. The RBE concept ................................. 14
2.7.2. Application of the RBE concept in radiation
therapy ......................................... 14
2.7.2.1. RBE and dose prescription .............. 15
2.7.2.2. Selection of the most clinically
relevant RBE or weighting factors
for ions ............................... 18
2.7.2.3. Selection of Wlon based on the linear
quadratic model ........................ 19
2.7.2.4. Evaluation of WIsoE from clinical
considerations or outcomes ............. 22
2.7.3. Ion RBE in therapy applications: Summary ........ 23
3. QUANTITIES AND UNITS ........................................ 26
3.1. Absorbed dose, D ....................................... 26
3.2. Biological weighting factor, WB ........................ 27
3.2.1. Fractionated photon beam therapy ................ 27
3.2.2. Brachythcrapy ................................... 28
3.2.3. External beam therapy with non-conventional
radiation quality ............................... 28
3.3. Biologically weighted absorbed dose, DB ................ 29
3.4. Recommendations lor reporting .......................... 30
3.4.1. Reporting the isoeffective dose weighting
factor, WIsol ................................... 30
3.4.2. General recommendations for reporting
radiation therapy ............................... 31
3.4.3. Review of some current practices for weighting
and reporting weighted dose and isoeffective
dose in centres using particle irradiations ..... 31
3.4.3.1. Proton beam therapy .................... 31
3.4.3.2. The Darmstadt-Heidelberg approach
in carbon ion therapy .................. 32
3.4.3.3. The Chiba approach in carbon ion
therapy ................................ 32
3.4.3.4. Equivalent dose ........................ 32
3.4.4. ICRU/IAEA recommendations for reporting the
isoeffective dose, DIsol ........................ 33
4. RADIOBIOLOGY OF HIGH LET RADIATION:
NEUTRONS AND IONS ........................................... 36
4.1. Radiobiological rationale for the use of high LET
radiation .............................................. 36
4.1.1. Increased RBE ................................... 36
4.1.2. Reduction in the oxygen enhancement ratio
with increasing LET ............................. 39
4.1.3. Reduction of the variation in radiosensiti-
vily related to the position of the cell
in the mitotic cycle ............................ 40
4.1.4. Reduced repair with high LET radiation .......... 41
4.1.5. Effect of tumour differentiation and
growth rate ..................................... 43
4.2. Patient selection for high LET radiotherapy ............ 45
4.3. Rationale for ion therapy .............................. 46
5. CLINICAL EXPERIENCE WITH NEUTRONS AND IONS .................. 51
5.1. Clinical experience with fast neutrons ................. 51
5.1.1. Salivary gland tumours .......................... 51
5.1.2. Prostatic adenocarcinomas ....................... 52
5.1.3. Other tumour sites or types ..................... 54
5.2. Clinical experience with ion beams ..................... 55
5.2.1. llie Berkeley ion programme ..................... 55
5.2.2. The Chiba programme ............................. 56
5.2.3. The Darmstadt programme ......................... 58
5.2.3.1. Chordomas and low grade chondro-
sarcomas of the base of the skull ...... 58
5.2.3.2. Sacrococcygeal and spinal
chordomas and low grade
chondrosarcomas ........................ 59
5.3. Conclusions from clinical experience with high LET
radiations ............................................. 60
5.3.1. Summary of clinical experience .................. 60
5.3.2. Clinical and biological considerations for
selecting patients for ion therapy .............. 62
6. RECOMMENDATIONS FOR REPORTING ION BEAM THERAPY .............. 65
6.1. Reporting: An essential tool for exchanging
information ............................................ 65
6.1.1. Three levels for reporting ...................... 65
6.1.2. Reporting radiation treatment ................... 65
6.1.3. Reporting versus prescribing .................... 66
6.1.4. Points and volumes used for reporting ........... 66
6.1.4.1. Gross target volume .................... 67
6.1.4.2. Clinical target volume ................. 67
6.1.4.3. Planning target volume ................. 67
6.1.4.4. Anatomical volumes relating to normal
tissues ................................ 68
6.1.4.5. Treated volume ......................... 68
6.1.4.6. Reference volume ....................... 69
6.2. Specific recommendations for reporting a therapeutic
ion beam irradiation ................................... 69
6.2.1. Irradiation conditions .......................... 69
6.2.2. Quantities and factors to be reported ........... 69
6.2.2.1. Absorbed dose .......................... 69
6.2.2.2. Isoeffective dose weighting factor
in radiation therapy ................... 70
6.2.2.3. Isoeffective dose in radiation
therapy ................................ 70
6.2.3. Reference points and volumes for reporting ...... 71
6.2.3.1. Reference points ....................... 71
6.2.3.2. Volumes for reporting .................. 71
ANNEX I: RESPONSE IN VIVO TO HIGH LET RADIATION .............. 75
ANNEX II: MODELLING THE INCREASED BIOLOGICAL EFFECTIVENESS
OF HEAVY CHARGED PARTICLES FOR TUMOUR THERAPY
TREATMENT PLANNING .................................. 93
ANNEX III: MEASUREMENT OF RBE OF CARBON IONS FOR CELLS,
TUMOUR RESPONSE AND TISSUE REACTIONS IN
EXPERIMENTAL SYSTEMS ............................... 120
ANNEX IV: CLINICAL RBE DETERMINATION SCHEME AT NIRS-HIMAC .... 135
CONTRIBUTORS TO DRAFTING AND REVIEW ........................... 153
|
