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II. TBI-DOSE PRESCRIPTION
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Target volume.
Malignant stem cells, immunocytes and the bone marrow stem cells all are intended to be destroyed with the TBI treatment. These cells are spread out all around the body. Therefore, the target volume has to be the whole body, including the skin. In incomplete remission, or in the later stages of disease, local irradiation may be needed additionally[1,5,24].
Organs at risk.
Therapeutic TBI doses, in combination with chemotherapy, may exceed the tolerance of certain organs (lungs, eye lens, etc). In particular, the lungs are the most critical organ at risk, because interstitial pneumonitis is one of the main causes for fatal complications in TBI treatments.
Specification point for absorbed dose.
In TBI the target volume is very extended so we need at least one representative point to which the prescribed dose can be referred. In most centres, this point is placed at the patient's midline and close to the abdomen or pelvis. The prescription of dose to other points may lead to confusion.
Prescribed dose to target volume. The TBI dose is an essential parameter for the success of treatment. Encouraging results have been obtained with doses ranging from 5 to 14 Gy. However, retrospective studies have not yet cast enough light onto an optimum value regarding all factors relating to TBI and BMT, so that the optimum dose is, as yet, unknown. This is probably due to the variety of existing schemes and techniques which makes the correlation between cause and effect very complex for the isolation of the most significant parameters. Thanks to the present effort, a more concrete protocol of physical parameters will become available.
Prescribed dose to organs at risk.
The main organ at risk is the lung. The low density of the lung implies a delivered dose which is higher than the dose prescribed to the target volume, when no shielding is used. The very steep dose-effect relationship of lung toxicity (20% increase with only 5% higher dose), provides the requirement not to exceed a certain threshold of dose. This is to guarantee that a noticeable part of the lung mantains its function. At the same time, it is not convenient to be too far below this value in order to obtain good treatment results. Unfortunately, there are not yet enough data to be able to specify the maximum allowed dose to be used in combination with chemotherapy and other toxic agents used in BMT treatment (e.g. methotrexate)[22,25-28].
Dose homogeneity.
If a uniform probability of target cell kill is desired, a homogeneous distribution of dose has to be achieved. This can be evaluated by the dose distribution along the patient's midline at several reference points and at the transverse section containing the specification point .
Time dose distribution.
From the beginning of radiobiology, the modifying effect of dose rate has been known to be important. Again, we can not say which quotient of dose/time is the best during the treatments. However, it should be clearly stated which dose rate is being specified: whether the mean value of every session, which means the dose per fraction divided by the time taken, which might be interrupted by the patient positioning or any other cause (i.e. mean dose rate), or the dose rate coming from the machine at a point (i.e. momentaneous dose rate).
The dose rate is probably of less importance in fractionated than in continuous TBI. On the other hand, and according to experimental results, there is no significant relationship between dose-rate and the effect on bone marrow stem cells or other malignant cells while a strong influence is found on late reacting normal tissue treated in a single fraction.
As the mean dose rate has special importance in lungs[29], it seems appropriate to define the TBI dose rate as the mean lung dose rate, the dose to lung per fraction divided by lung irradiation time per fraction.
RECOMMENDATIONS - MEDICAL TREATMENT PLANNING
- As a general rule, the physician should prescribe the dose to the target volume and lung, and the timing schedule of the treatment.
- The target volume is the whole body including the skin, if not prescribed differently.
- A homogenous distribution of dose in the target volume is required.
- The reference dose to the target volume must be specified as the total dose delivered at the mid point of the abdomen at the level of the umbilicus.
- The dose to organs at risk must be specified. It is recommended neither to exceed a certain threshold dose nor to be far below this value.
- The lung dose should be specified at a point which is representative for more than 50% of the lung volume.
- The mean lung dose rate must be specified. Shielding of the lungs must be used in every session in order to have the same mean lung dose rate in each session.
- The estimated relative volume of lung receiving a reduced dose (by partial shielding) must be stated.
- The maximum and minimum values of dose in the transverse section containing the specification point should be within ±10%. The same criterion for dose homogeneity applies to the maximum and minimum values along the patient's midline.
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Due to the large fields used, TBI techniques require a different approach than in standard Radiotherapy.
The particular TBI technique is imposed by the facilities of the Institution. A beam spoiler is recommended when high energy is used, to achieve dose homogeneity at shallow depths.
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