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Radiotherapeutic requirements of 14 MeV fast neutron beams with respect to depth-dose and collimation
Europ. 07. Cancer Vol. 7, pp. 129-134. Pergamon Press 1971. Printed in Great Britain
Radiotherapeutic Requirements of 14 MeV Fast Neutron Beams with Respect to Depth-Dose and Collimation W. DUNCAN, D. GREENE and D. MAJOR Christie Hospital and Holt Radium Institute, Manchester, England
Abstract ~ The shielding of 14 M e V neutron generators cannot be as efficient as that of X-ray machines. A method of estimating the level of stray radiation outside the geometric beam is suggested as compared with the stray radiation from telecobalt units and 250 k V X-ray machines. The level of whole body neutron radiation which will have to be tolerated by patients is considered to be within acceptable limits.
THE MOSTimportant requirement of fast neutron beams for radiotherapy is that they should have sufficiently good penetration to treat deepseated tumours. It has been suggested that at a depth of 10 cm the dose should be at least 50% of the surface dose. A more practical criterion is that at least 30% should be obtained at 15 cm depth as this would allow most deepseated tumours to be treated with an arrangement of three fields, whereby the overlying tissues each receive a dose which will not be larger than the total dose received by the tumour. Fig. 1 illustrates the depth-dose curve of 14 MeV neutrons for a 10× 10 cm field at 75 cm SSD and shows that adequate penetration is achieved. Some improvement in depth-dose is obtained by increasing the source to skin distance but unless larger neutron yields can be attained little advantage (Fig. 2) as regards depth-dose is to be gained by going beyond about 75 cm because the reduction in dose rate with distance from a D - T generator quickly increases treatment times to an unacceptable extent. The isodose curves of 1 4 M e V neutrons measured by Greene and Major [1] using a 55 cm thick steel and polythene collimator (Fig. 3) are similar to those for 250 kV X-rays, but do show much better flatness of the beam. Recent preliminary results of Nias and Greene
[2] indicate that these isodose curves are in fact iso-effect curves and that the quality of the beam does not significantly change with attenuation. In profile (Fig. 4) the neutron beam is flat and well defined and compares well with a 250 kV X-ray beam at depth. A serious problem is encountered beyond the edge of the beam where the stray radiation continues at a much higher level than we are accustomed to with megavoltage X-rays. The stray radiation (Fig. 5) at 10 cm depth in a phantom has been measured [3] outside beams of X-rays, gamma-rays and fast neutrons. The upper two curves in Fig. 5 show the stray radiation outside collimated beams of 14 MeV neutrons and are seen to be much less satisfactory. The lower of these two curves was obtained by Marshall at the Radiological Protection Service, Sutton, using a 75 cm collimator and measuring the fast neutron dose with a nuclear emulsion film. The highest curve was measured by Greene and Major [1] for a 55 cm collimator, using an ionisation chamber. Shielding of fast neutron sources can never achieve the standards attained with megavoltage X-ray apparatus. The specification of the shielding and collimators of these machines permits a dose level of no more than 0 . 1 % in air outside the penumbra. The practical 129
130
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Isodose curvesfor a 10 x 10 cm collimated beam of 14 M e V neutrons at 55 cm source to skin distarwe [ 1].
Radiotherapeutic Requirements of 14 Me V Fast Neutron Beams • • o
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Profile of a l O x I0 c m collimated beam of 14 M e V neutrons measured in air and 10 c m deep in a ptmntom [1]. The contribution of stray radiation may be approximated by subtraction.
1M
132
W. Duncan, D. Greene and D. Major
difficulties in terms of thickness of material required in designing collimators for 14 MeV neutrons implies that the comparable curve o f stray radiation has to be much greater. It is important to note, however, that the level of 0"1%, specified for X-ray machines, has not been determined primarily on any clinical consideration but as a reasonable level which can be readily obtained by good engineering design. With fast neutron beam therapy the average whole body dose outside the useful beam will be much greater than with X-rays and one must consider what level of dose is tolerable and acceptable clinically and how one may estimate the whole body dose delivered by stray radiation. The level of whole-body radiation received by a patient treated with X-rays is determined predominantly by scattered radiation from the primary beam, rather than by leakage radiation through the collimator, while the latter is an important factor with fast neutrons from D - T neutron generators. The comparison of the fields of stray radiation, obtained with different types of neutron collimators and X-ray collimators, has to be made in relation to the total dose distribution produced in a phantom, extending over a region comparable to the trunk of a patient, taken as 50 cm in length. T h e following discussion is based on the clinical situation of treating a patient with a tumour at a depth of 10 cm and expressing the wholebody dose as a percentage of the tumour dose at that depth. The dose gradient from the central axis of a 10 X 10 cm field to a distance of 50 cm was plotted on a linear scale for 250 kV X-rays, cobalt gamma-rays and 14 MeV neutrons and the average determined. It is necessary to find a figure which will give a meaningful average whole-body dose for the different qualities of radiation. Three ways of arriving at such a figure have been considered (see Table 1). The first method is to estimate the mean dose from the beam centre to the 50-cm point. This is unsatisfactory because the estimate of whole-body dose is largely determined by the
dose in the main beam and we know in clinical practice that this is only valid when field sizes greater than about 25 cm in length are used. A more relevant approach is to find a reference point somewhere in the penumbra region. With single field treatments the tumour dose is commonly considered to extend to the 80% isodose line and in a sense all radiation outside this is unwanted. The average dose is now taken from the 80% isodose line to a point 50 cm from the tumour centre axis of the beam. For this reference point it is clear that the telecobalt collimation is very much better than the others and that the measure of stray radiation from 250 kV X-rays is similar to that obtained from fast neutrons using the experimental collimators. However, it may be thought that this figure is unduly weighted by the radiation in the penumbra and that a more reasonable figure may be obtained by averaging the dose from the edge of the penumbra. Looking at the 14 MeV neutron beam (Fig. 4) the penumbra ends at 8 cm from the central axis. This point corresponds to the 30% isodose line for fast neutrons, 40% for X-rays and 10% for cobalt gamma-rays. Although one cannot be certain about the most appropriate method of estimating the stray radiation level, it would appear that the most meaningful figure is given by this last method. From Fig. 6 which shows beam collimation of 14 MeV neutrons in air and in a phantom it is possible by subtracting one curve from the other to approximate to the situation pertaining to an "ideal" collimator which allows negligible transmission of neutron radiation. This situation is shown in the last column of the Table and it does make clear that about 40% of the average whole-body dose as defined here is derived from processes of beam scattering and cannot be improved by collimator design. The percentages in this Table refer to the total absorbed dose and it is essential to determine the qualities of radiation contributing to the total dose. When fast neutrons are attenuated in
Table 1. Averagewhole-body dose Percentage of t u m o u r dose at 10 cm d e p t h
B e a m reference
Central axis 80% dose level 8 cm from central axis
S0Co gammarays
14 2.5 1
14 MeV neutrons 250 kV X-rays collimator 1 collimator 2 ideal 12 7.8 4
18 7-8
19 8.7
15 3.8
5.3
6.6
2.3
Radiotherapeutic Requirements of 14 Me V Fast Neutron Beams tissue, slowed-down neutrons and gamma-rays are produced and the biological effectiveness of the absorbed radiation will depend on the proportion of each component. These spectra may be different outside and inside the main beam. We are also aware that the RBE for the very small doses of fast neutrons scattered outside the beam will be much higher than the RBE of the high dose delivered to the tumour volume [4]. Recent measurements made in Manchester indicate that in the penumbra region gammarays contribute almost half the total dose. Their contribution quickly increases with distance and is 100°/0 at the 50 cm point. Bewley and Parnell [5] have also shown that at 1 0 c m from the central axis of the 6 MeV neutron beam under similar conditions the gamma-radiation dose exceeds the neutron dose which then very quickly becomes negligible beyond this point. From the clinical point of view this finding is of great importance. The calculated wholebody dose is mainly due to gamma-radiation and the neutron dose is likely to be not greater than 30% of the total dose. If an RBE for the level of stray radiation is taken as 5 for tolerance of the blood forming organs, as suggested by Field [4] then the effective whole body dose shown in the Table will be no more than twice the calculated v a l u e - about 10°/0 in terms of gamma-radiation. However, RBE values for haemopoietic stem cells have been found to be much closer to unity [6-10]. Assuming for example that a tumour dose of 1600 rods of 14 MeV neutrons is given in 8 exposures in 2-3 weeks, the estimated 'average whole-body dose' would be effectively 10°/0 or equivalent to 160 rads of gamma-rays. There is evidence that this is certainly acceptable in clinical
133
practice, although a drop in the total white blood cell count (WBC) might be expected. Whole-body radiation was given, in the past, to patients suffering from polycythaemia [11]. Two hundred and fifty kV X-rays were used and commonly a whole body dose of 10 rads was given each day for 3-4 weeks, resulting in a total dose of 150-175 rads. It was felt that the total dose should not exceed 250 rads. Consideration of wide field X-ray techniques for abdominal and chest baths and treatment of the whole cerebrospinal axis in patients with medulloblastoma, gives additional evidence about tolerance to whole body doses. In these patients very large volumes of the bone marrow are included in the high dose region, receiving about 9500 rads given in 15 exposures in three weeks. The whole body dose calculated for regions outside the 80% isodose line will deliver at least another 100 rads to the remainder of the bone marrow. A whole body dose of 200 rads is also accepted as tolerable in the treatment of patients with thyroid cancer using iodine-131. Indeed some patients with metastatic thyroid cancer have been treated on a regime which, after an ablative dose of radio-iodine, gives 50 mCi of radio-iodine twice weekly for 6-8 weeks [12]. A fair estimate of the whole body dose in these patients would be 15-20 rads for each treatment dose resulting in a total dose of 250 rads. In radiotherapeutic applications of 14 MeV fast neutrons much higher levels of stray radiation outside the treatment beam will have to be accepted than with high energy X-ray beam therapy and this is a matter of concern. Examined in the way suggested here, it seems however that the hazards should be, at least, not greater than accepted with certain other forms of radiation therapy.
REFERENCES 1. D. GREENE and D. MAJOR, Collimation of 14 MeV neutron beams. Europ 07. Cancer 7, 121 (1971). 2. A. H. W. NL~s and D. GREENE, Changes in the biological parameters for mammalian cells as a function of position in a 14 MeV neutron field. Proc. IVth Int. Congress of Radiation Research, Biology and Medicine, Vol. 1, Gordon and Breach (1970). 3. D . K . BEWLEY, Fast neutron beams for therapy. In Current Topics in Radiation Research (Edited by M. EBERT and A. HOWARD), Vol. VI, p.249. NorthHolland, Amsterdam, (1970). 4. S.B. FmLz~,The relative biological effectiveness of fast neutrons for mammalian tissues. Radiology 93, 915 (1969). 5. D . K . BEWLEY and C. J. PARNELL, The fast neutron beam from the M.R.C. cyclotron. Brit. 07. Radiol. 42, 281 (1969). 6. S. SAWADAand H. YOSmNAOA,The relative biological effectiveness of X-ray, Co 80 gamma-ray, and 14-1 MeV fast neutron for acute death in mice. Nippon Acta Radiol. 23, 1080 (1963).
134
IV. Duncan, D. Greene and D. Major 7.
8. 9.
I0.
11. 12.
M . L . DAVIS,E. B. DARDENand G. E. COSOROV~.,Early hematologic effects of whole-body 14 MeV neutron irradiation in mice. Acta Radiol. 3, 87 (1965). J.J. BROERS~.,Dose-mortality studies for mice irradiated with X-rays, gammarays and 15 MeV neutrons. Int. 3. Radiat. Biol. 15, 115 (1969). W. DUNCAN, D. GREENE, A. H O W A R D and J. B. MASSEY, The R B E of 14 M e V neutrons. Observations on colony-forming units in mouse bone-marrow. Int.3. Radiat. Biol. 15, 397 (1969). J.J. BROERSE, W. DUNCAN, A. C. ENGELS, C. W. GILBERT, D. GREENE, J. H. HENDRY, A. HOWARD, P. LELIEVELD, J. B. MASSEY and L. M. VAN PUTTEN, The survival of colony-forming units in mouse bone-narrow after in vivo irradiation with D - T neutrons, X- and gamma-radiation. To be published in Int. 3. Radiat. Biol. R. PATERSON, The Treatment of Malignant Diseases by Radium and X-rays, p. 454. Arnold, London (1949). K . E . HALNAN, Techniques and dosage in treatment of thyroid cancer. Proc. Roy. Soc. Med. 56~ 723 (1963).
Radiotherapeutic Requirements of 14 MeV Fast Neutron Beams with Respect to Depth-Dose and Collimation W. DUNCAN, D. GREENE and D. MAJOR Christie Hospital and Holt Radium Institute, Manchester, England
Abstract ~ The shielding of 14 M e V neutron generators cannot be as efficient as that of X-ray machines. A method of estimating the level of stray radiation outside the geometric beam is suggested as compared with the stray radiation from telecobalt units and 250 k V X-ray machines. The level of whole body neutron radiation which will have to be tolerated by patients is considered to be within acceptable limits.
THE MOSTimportant requirement of fast neutron beams for radiotherapy is that they should have sufficiently good penetration to treat deepseated tumours. It has been suggested that at a depth of 10 cm the dose should be at least 50% of the surface dose. A more practical criterion is that at least 30% should be obtained at 15 cm depth as this would allow most deepseated tumours to be treated with an arrangement of three fields, whereby the overlying tissues each receive a dose which will not be larger than the total dose received by the tumour. Fig. 1 illustrates the depth-dose curve of 14 MeV neutrons for a 10× 10 cm field at 75 cm SSD and shows that adequate penetration is achieved. Some improvement in depth-dose is obtained by increasing the source to skin distance but unless larger neutron yields can be attained little advantage (Fig. 2) as regards depth-dose is to be gained by going beyond about 75 cm because the reduction in dose rate with distance from a D - T generator quickly increases treatment times to an unacceptable extent. The isodose curves of 1 4 M e V neutrons measured by Greene and Major [1] using a 55 cm thick steel and polythene collimator (Fig. 3) are similar to those for 250 kV X-rays, but do show much better flatness of the beam. Recent preliminary results of Nias and Greene
[2] indicate that these isodose curves are in fact iso-effect curves and that the quality of the beam does not significantly change with attenuation. In profile (Fig. 4) the neutron beam is flat and well defined and compares well with a 250 kV X-ray beam at depth. A serious problem is encountered beyond the edge of the beam where the stray radiation continues at a much higher level than we are accustomed to with megavoltage X-rays. The stray radiation (Fig. 5) at 10 cm depth in a phantom has been measured [3] outside beams of X-rays, gamma-rays and fast neutrons. The upper two curves in Fig. 5 show the stray radiation outside collimated beams of 14 MeV neutrons and are seen to be much less satisfactory. The lower of these two curves was obtained by Marshall at the Radiological Protection Service, Sutton, using a 75 cm collimator and measuring the fast neutron dose with a nuclear emulsion film. The highest curve was measured by Greene and Major [1] for a 55 cm collimator, using an ionisation chamber. Shielding of fast neutron sources can never achieve the standards attained with megavoltage X-ray apparatus. The specification of the shielding and collimators of these machines permits a dose level of no more than 0 . 1 % in air outside the penumbra. The practical 129
130
W. Duncan, D. Greeneand D. Major 100
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Depth--dose curve for a 10 X 10 cm collimated beam of 14 M e V neutrons compared with a telecobalt gamma-ray beam. 12
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neutrons[see.
I I1%__ I //t ,-''.--7___:__Y_-/J)l
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2O
Isodose curvesfor a 10 x 10 cm collimated beam of 14 M e V neutrons at 55 cm source to skin distarwe [ 1].
Radiotherapeutic Requirements of 14 Me V Fast Neutron Beams • • o
14 MeV neutrons, 1.8 cm deep 14 MeV neutrons, lO,cm deep 250 kVX-rays, lOcm deep
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Profile of a I0 × I0 cm collimated beam of 14 M e V neutrons at 1.8 cm and 10 cm depth and a 250 k V X-ray beam at 10 cm depth. 100
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~-~o u
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~
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[depth in a phantom.
20-
~ l
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.o
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40
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Profile of a l O x I0 c m collimated beam of 14 M e V neutrons measured in air and 10 c m deep in a ptmntom [1]. The contribution of stray radiation may be approximated by subtraction.
1M
132
W. Duncan, D. Greene and D. Major
difficulties in terms of thickness of material required in designing collimators for 14 MeV neutrons implies that the comparable curve o f stray radiation has to be much greater. It is important to note, however, that the level of 0"1%, specified for X-ray machines, has not been determined primarily on any clinical consideration but as a reasonable level which can be readily obtained by good engineering design. With fast neutron beam therapy the average whole body dose outside the useful beam will be much greater than with X-rays and one must consider what level of dose is tolerable and acceptable clinically and how one may estimate the whole body dose delivered by stray radiation. The level of whole-body radiation received by a patient treated with X-rays is determined predominantly by scattered radiation from the primary beam, rather than by leakage radiation through the collimator, while the latter is an important factor with fast neutrons from D - T neutron generators. The comparison of the fields of stray radiation, obtained with different types of neutron collimators and X-ray collimators, has to be made in relation to the total dose distribution produced in a phantom, extending over a region comparable to the trunk of a patient, taken as 50 cm in length. T h e following discussion is based on the clinical situation of treating a patient with a tumour at a depth of 10 cm and expressing the wholebody dose as a percentage of the tumour dose at that depth. The dose gradient from the central axis of a 10 X 10 cm field to a distance of 50 cm was plotted on a linear scale for 250 kV X-rays, cobalt gamma-rays and 14 MeV neutrons and the average determined. It is necessary to find a figure which will give a meaningful average whole-body dose for the different qualities of radiation. Three ways of arriving at such a figure have been considered (see Table 1). The first method is to estimate the mean dose from the beam centre to the 50-cm point. This is unsatisfactory because the estimate of whole-body dose is largely determined by the
dose in the main beam and we know in clinical practice that this is only valid when field sizes greater than about 25 cm in length are used. A more relevant approach is to find a reference point somewhere in the penumbra region. With single field treatments the tumour dose is commonly considered to extend to the 80% isodose line and in a sense all radiation outside this is unwanted. The average dose is now taken from the 80% isodose line to a point 50 cm from the tumour centre axis of the beam. For this reference point it is clear that the telecobalt collimation is very much better than the others and that the measure of stray radiation from 250 kV X-rays is similar to that obtained from fast neutrons using the experimental collimators. However, it may be thought that this figure is unduly weighted by the radiation in the penumbra and that a more reasonable figure may be obtained by averaging the dose from the edge of the penumbra. Looking at the 14 MeV neutron beam (Fig. 4) the penumbra ends at 8 cm from the central axis. This point corresponds to the 30% isodose line for fast neutrons, 40% for X-rays and 10% for cobalt gamma-rays. Although one cannot be certain about the most appropriate method of estimating the stray radiation level, it would appear that the most meaningful figure is given by this last method. From Fig. 6 which shows beam collimation of 14 MeV neutrons in air and in a phantom it is possible by subtracting one curve from the other to approximate to the situation pertaining to an "ideal" collimator which allows negligible transmission of neutron radiation. This situation is shown in the last column of the Table and it does make clear that about 40% of the average whole-body dose as defined here is derived from processes of beam scattering and cannot be improved by collimator design. The percentages in this Table refer to the total absorbed dose and it is essential to determine the qualities of radiation contributing to the total dose. When fast neutrons are attenuated in
Table 1. Averagewhole-body dose Percentage of t u m o u r dose at 10 cm d e p t h
B e a m reference
Central axis 80% dose level 8 cm from central axis
S0Co gammarays
14 2.5 1
14 MeV neutrons 250 kV X-rays collimator 1 collimator 2 ideal 12 7.8 4
18 7-8
19 8.7
15 3.8
5.3
6.6
2.3
Radiotherapeutic Requirements of 14 Me V Fast Neutron Beams tissue, slowed-down neutrons and gamma-rays are produced and the biological effectiveness of the absorbed radiation will depend on the proportion of each component. These spectra may be different outside and inside the main beam. We are also aware that the RBE for the very small doses of fast neutrons scattered outside the beam will be much higher than the RBE of the high dose delivered to the tumour volume [4]. Recent measurements made in Manchester indicate that in the penumbra region gammarays contribute almost half the total dose. Their contribution quickly increases with distance and is 100°/0 at the 50 cm point. Bewley and Parnell [5] have also shown that at 1 0 c m from the central axis of the 6 MeV neutron beam under similar conditions the gamma-radiation dose exceeds the neutron dose which then very quickly becomes negligible beyond this point. From the clinical point of view this finding is of great importance. The calculated wholebody dose is mainly due to gamma-radiation and the neutron dose is likely to be not greater than 30% of the total dose. If an RBE for the level of stray radiation is taken as 5 for tolerance of the blood forming organs, as suggested by Field [4] then the effective whole body dose shown in the Table will be no more than twice the calculated v a l u e - about 10°/0 in terms of gamma-radiation. However, RBE values for haemopoietic stem cells have been found to be much closer to unity [6-10]. Assuming for example that a tumour dose of 1600 rods of 14 MeV neutrons is given in 8 exposures in 2-3 weeks, the estimated 'average whole-body dose' would be effectively 10°/0 or equivalent to 160 rads of gamma-rays. There is evidence that this is certainly acceptable in clinical
133
practice, although a drop in the total white blood cell count (WBC) might be expected. Whole-body radiation was given, in the past, to patients suffering from polycythaemia [11]. Two hundred and fifty kV X-rays were used and commonly a whole body dose of 10 rads was given each day for 3-4 weeks, resulting in a total dose of 150-175 rads. It was felt that the total dose should not exceed 250 rads. Consideration of wide field X-ray techniques for abdominal and chest baths and treatment of the whole cerebrospinal axis in patients with medulloblastoma, gives additional evidence about tolerance to whole body doses. In these patients very large volumes of the bone marrow are included in the high dose region, receiving about 9500 rads given in 15 exposures in three weeks. The whole body dose calculated for regions outside the 80% isodose line will deliver at least another 100 rads to the remainder of the bone marrow. A whole body dose of 200 rads is also accepted as tolerable in the treatment of patients with thyroid cancer using iodine-131. Indeed some patients with metastatic thyroid cancer have been treated on a regime which, after an ablative dose of radio-iodine, gives 50 mCi of radio-iodine twice weekly for 6-8 weeks [12]. A fair estimate of the whole body dose in these patients would be 15-20 rads for each treatment dose resulting in a total dose of 250 rads. In radiotherapeutic applications of 14 MeV fast neutrons much higher levels of stray radiation outside the treatment beam will have to be accepted than with high energy X-ray beam therapy and this is a matter of concern. Examined in the way suggested here, it seems however that the hazards should be, at least, not greater than accepted with certain other forms of radiation therapy.
REFERENCES 1. D. GREENE and D. MAJOR, Collimation of 14 MeV neutron beams. Europ 07. Cancer 7, 121 (1971). 2. A. H. W. NL~s and D. GREENE, Changes in the biological parameters for mammalian cells as a function of position in a 14 MeV neutron field. Proc. IVth Int. Congress of Radiation Research, Biology and Medicine, Vol. 1, Gordon and Breach (1970). 3. D . K . BEWLEY, Fast neutron beams for therapy. In Current Topics in Radiation Research (Edited by M. EBERT and A. HOWARD), Vol. VI, p.249. NorthHolland, Amsterdam, (1970). 4. S.B. FmLz~,The relative biological effectiveness of fast neutrons for mammalian tissues. Radiology 93, 915 (1969). 5. D . K . BEWLEY and C. J. PARNELL, The fast neutron beam from the M.R.C. cyclotron. Brit. 07. Radiol. 42, 281 (1969). 6. S. SAWADAand H. YOSmNAOA,The relative biological effectiveness of X-ray, Co 80 gamma-ray, and 14-1 MeV fast neutron for acute death in mice. Nippon Acta Radiol. 23, 1080 (1963).
134
IV. Duncan, D. Greene and D. Major 7.
8. 9.
I0.
11. 12.
M . L . DAVIS,E. B. DARDENand G. E. COSOROV~.,Early hematologic effects of whole-body 14 MeV neutron irradiation in mice. Acta Radiol. 3, 87 (1965). J.J. BROERS~.,Dose-mortality studies for mice irradiated with X-rays, gammarays and 15 MeV neutrons. Int. 3. Radiat. Biol. 15, 115 (1969). W. DUNCAN, D. GREENE, A. H O W A R D and J. B. MASSEY, The R B E of 14 M e V neutrons. Observations on colony-forming units in mouse bone-marrow. Int.3. Radiat. Biol. 15, 397 (1969). J.J. BROERSE, W. DUNCAN, A. C. ENGELS, C. W. GILBERT, D. GREENE, J. H. HENDRY, A. HOWARD, P. LELIEVELD, J. B. MASSEY and L. M. VAN PUTTEN, The survival of colony-forming units in mouse bone-narrow after in vivo irradiation with D - T neutrons, X- and gamma-radiation. To be published in Int. 3. Radiat. Biol. R. PATERSON, The Treatment of Malignant Diseases by Radium and X-rays, p. 454. Arnold, London (1949). K . E . HALNAN, Techniques and dosage in treatment of thyroid cancer. Proc. Roy. Soc. Med. 56~ 723 (1963).