Znt.J. Rodiation Oncology B~ol. Phys.. 1976. Vol. 1. pp. 549-552. Pergamon Press.
??Technical
Printed in the US A.
Innovations TOTAL
ROBERT
BODY IRRADIATION UTILIZING SINGLE @Co SOURCE
J. MILLER, M.S., EDWARD A. LANGDON, and ALAN S. TESLER, M.D..
Division of Radiation Therapy, Department
A M.D.
of Radiological Sciences
and Bone Marrow Transplantation Group University of California, Los Angeles Center for the Health Sciences, Los Angeles, CA90024, U.S.A. A method of total body irradiation (TBI) is described for the treatment of acute leukemia with a single 6oCo source simulating two opposed fields. Thermoluminescent dosimeters (TLDs) in a Rando Phantom indicate that the variation in dose distribution to the patient is 5-l@%. Rectal catheters with TLDs were inserted in 13 patients undergoing TBI. The measured dose rates are compared to the calculated values. Variations are of the order of 12%, consistent with uncertainties in the calculated dose rate, except for the upper pelvis. When it is possible, in oioo measurement of the dose rate is recommended because of this variation. Total body irradiation;
Bone marrow
transplantation;
INTRODUCTION Low dose total body irradiation has been in use for many years in the treatment of a variety of malignant diseases, primarily leukemia and lymphomas.5.6.7P9Recently, total body irradiation has been employed in the treatment of leukemia prior to bone marrow transplantation. The University of Washington Division of Radiation Therapy has reported the use of two opposed -Co sources for total body irradiation.’ The Division of Radiation Therapy at UCLA has been involved in a combined chemotherapy-total body irradiation regimen followed by bone marrow transplantation for patients with acute leukemia who are not responsive to conventional therapeutic modalities.* It is now possible to evaluate the validity of total body irradiation using a single source of radiation from a dosimetric standpoint. IRRADIATION PROCEDUXE A single Atomic Energy of Canada, Ltd. (AECL) Theratron 780,660O Ci Yo unit with a 1.75 cm source diameter is used for the total body irradiation. The patient is positioned
Dosimetry.
lying on his side with the hips and knees flexed on a stretcher adjacent to a wall. The sourcemidplane distance is 330cm. The head and arm of the cobalt unit are rotated so that the beam clears the beam stopper, and the beam axis intersects the patient. With the collimators completely open and rotated 45”, the patient is exposed by a diamond-shaped field with the body lying along the diagonal of the field (Figs. 1 and 2). Before treatment starts, a 26 French Foley catheter containing thermoluminescent dosimeters (TLDs) if the tip is inserted in the rectum. The patient lies facing the Yo unit for the first calculated 200rad. The patient then is turned to face the wall for an additional 200rad. At this time the catheter is removed and the treatment resumed with a calculated time to irradiate the midline to an additional 300rad. While the treatment continues, the TLDs are read and the actual dose rate determined. The calculated treatment time is adjusted to correlate with the actual dose rate. The last portion of the treatment is delivered with the patient facing the -Co unit. In this fashion, the resulting dose distribution is that of two opposed fields.
550
Radiation Oncology 0 Biology 0 Physics
March-April
1976. Vol. 1, Number 5 and Number 6
Fig. 1. Patient in position for total body irradiation with diamond-shaped field. Source-midplane distance is 330 cm. The beam is angled 17”from the horizontal plane.
Fig. 2. Patient receives half the treatment facing the wall. In effect, the patient is irradiated with two 1Popposed fields.
The possibility that certain leukemic cells periodically may sequester and always be “posterior” to the beam has been considered. Although extremely unlikely for any significant group of cells, single cells may, in fact, undergo this unfortuitous sequence of events. Their dose would be at least 650 rad, which appears to be adequate for killing of a single cell or small cluster of cells.’ The clinical results achieved by this procedure (intensive chemotherapy followed by TBI) indicate the leukemic cell population is sufficiently reduced.3
DOSIMETRIC ANALYSIS Dosimetry A dose of 1000 rad is calculated to the midline of the pelvis. The output in air at 330cm is reduced by the appropriate tissueair-ratio (TAR) value. The midplane dose rate is increased 5% to account for the increase in scattered radiation adjacent to the wall (Table 1). In order to obtain an idea of the dose distribution in the body with the set-up we are using, TLDs were placed at a number of locations in each of six levels of a Rando
Total body irradiation utilizing a single To
551
source 0 R. J. MILLER et al.
Table 1. Comparison of measured output @ad/minute) and calculated output at 5 cm depth in phantom. North wall of treatment room is 352 cm from “‘Co source. An increase of 5% in measured dose rates is consistent with the expected magnitude of backscatter from the wall
Measured values Inverse-square
Source-axis distance (cm) 292 309 329 265
336
85
167
141.8
37.40 36.70
14.80 14.60
12.50 12.00
11.20 10.70
10.10 9.50
9.60 9.10
1.02
1.01
1.04
1.05
1.06
1.05
Measurement/calculated
phantom ranging from the pelvis to the head. The phantom was placed on its side, reproducing the geometry of a patient undergoing TBI. The phantom was turned so as to simulate the actual treatment of patients as described in the previous section. The overall variation was of the order of 5% of the normalized dose (Fig. 3). The expected increase in dose to the thinner portions of the body is offset partially by the reduced dose rate at the periphery of the 6oCo beam” where the head, neck and legs are positioned. TLDs IN RAND0 PHANTOM
TLDs in a rectal catheter were inserted in a number of patients receiving total body irradiation. It is assumed that the rectal dose rate is a valid indication of the dose received at the pelvic midplane. As previously stated, the calculated treatment time was adjusted according to the dose rate indicated by the lithium-fluoride dosimeters. Three TLDs were placed at the tip of the catheter and inserted 10-15 cm proximal to the anus just prior to the treatment. With each measurement, a calibration exposure was performed on dosimeters of the same batch in order to determine the magnitude of the supralinearity of the TLDs in the 300-500 rad dose range. For the most part, the measured values agree within 10% of the calculated values (Table 2). The effect of blankets and pillows (to prop the patient) and the Foley catheter on the TLDs were measured and found to be negligiTable 2. Comparison
of measured rectal dose rates with calculated values. Rectal doses were measured with TLDs
Date
Fig. 3. Dose distribution in six levels of a Rando Phantom. Values are percentages of normalized dose in upper pelvis (approximate field center). Within group variation of the TLDs is less than 5%.
Calculated (rad/min)
Measured @ad/mm)
Calculated measured
12174 l/75 l/75 2175 2175 4175 5175 7175 7175 8175
10.6 9.9 10.3 9.0 10.3 8.9 9.5 8.0 8.2 9.0
11.7 10.9 10.5 8.6 10.8 9.0 9.2 7.2 8.6 8.6
0.91 0.91 0.98 1.05 0.95 0.99 1.03 1.11 0.95
8175
9.4
8.4
9175 10/75
8.8 8.8
8.9 7.6
1.12 0.99 1.16+
fOver 12% disagreement
1.05
with calculated values.
552
Radiation Oncology ??Biology 0 Physics
ble (I%), In addition, TLDs in a Foley catheter were inserted in a number of patients receiving routine pelvic AP-PA treatments. The TLDs were in excellent agreement with the computed dose using the Memorial External Beam Program.’ It was felt that the dose that the dosimeters displayed was an accurate assessment of the rectal dose. DISCUSSION A number of problems are encountered when one attempts to calculate accurately the dose received at the patient midplane in total body irradiation. The exact source-patient axis distance changes during treatment as the patient shifts position occasionally. With our present set-up, it is thought that the overall source-axis distance varies from 315 to 345 cm. This produces the largest source of error in attempting to predict the patient dose. Restricting patient movement during an already uncomfortable and lengthy treatment sometimes is difficult. The TLDs in the catheter are not precisely on the midline of the patient, and an uncertainty of 25% consistent with the variation in dose distribution in the patient is expected. In measuring the patient
March-April 1976, Vol. 1, Number 5 and Number 6
Table 3. Uncertainty involved in calculating rectal dose rates with our set-up. Uncertainty was determined by square root of sum of squares of the independent percent errors Calculated vs actual dose Positional (2 15 cm) Dose variation in patient Patient thickness (-Cl cm) Exposure rate
(%) 210 +5 r3 *3 +12.0
contour (in a sterile isolation room), we are accurate to no more than +l cm. This results in an approximate error of 3% accuracy. All of these uncertainties result in an overall error in the calculations of 12% (Table 3). Examination of Table 2 reveals that almost all calculated dose rates were within this margin of error. The use of a single source of radiation appears to be a dosimetrically accurate method for total body irradiation. The use of in vim measurements for verification of the midline dose rate is recommended because of the uncertainty involved in the calculations.
REFERENCES Berry, R.J., Andrews, J.R.: The effect of radiation ionization density (LET) upon the reproductive capacity of mammalian cells irradiated and assayed in vivo. Br. J. Radiol. 36: 49-55, 1%3. DeClemente, A., Mohan, R., Reddy, M.T., Holt, J.G.: Memorial Dose Distribution Service. External Beam Program User Guide (Nov. 1971). Gale, R.: Bone marrow transplantation in man. (Presented 6 Feb. 1975 at the UCLA Conf. Division of Hematology -Oncology, Department of Medicine, UCLA School of Medicine, Martin J. Cline, M.D., Panel Moderator); Ann. Intern. Med. 83: 691-708, 1975. Gale, R.P., Feig. S., Opelz, G., Territo, M., et al.: Bone marrow transplantation in acute leukemia using intensive chemoradiotherapy (SCARI-UCLA). Transplantation Proc. in press.
5. Heublin, A.C.: A preliminary report on continuous irradiation of the entire body. Radiology 18: 1051-1060, 1932. 6. Johnson, R.E.: Evaluation of fractionated total body irradiation in patients with leukemia and disseminated lymphomas. Radiology 86: 10851089, 1966. 7. Johnson, R.E.: Total body irradiation (TBI) as primary therapy for advanced lymphosarcoma. Cancer 35: 242-246, 1975. 8. Thomas, E.D., et al.: Allogeneic marrow grafting for hematologic malignancy using HL-A matched donor-recipient sibling pairs. Blood 38: 267-287, 1971. 9. Thomas, E.D., et al.: Bone marrow transplantation, Part I and Part II. N. Engl. J. Med. 292: 832-843, 895-902, 1975. 10. Webster, E.W., Tsien, K.C.: Atlas of Radiation Dose Distributions, Vol. 1. International Atomic Energy Agency, Vienna, 1%5, pp. 13-21.
??Technical
Printed in the US A.
Innovations TOTAL
ROBERT
BODY IRRADIATION UTILIZING SINGLE @Co SOURCE
J. MILLER, M.S., EDWARD A. LANGDON, and ALAN S. TESLER, M.D..
Division of Radiation Therapy, Department
A M.D.
of Radiological Sciences
and Bone Marrow Transplantation Group University of California, Los Angeles Center for the Health Sciences, Los Angeles, CA90024, U.S.A. A method of total body irradiation (TBI) is described for the treatment of acute leukemia with a single 6oCo source simulating two opposed fields. Thermoluminescent dosimeters (TLDs) in a Rando Phantom indicate that the variation in dose distribution to the patient is 5-l@%. Rectal catheters with TLDs were inserted in 13 patients undergoing TBI. The measured dose rates are compared to the calculated values. Variations are of the order of 12%, consistent with uncertainties in the calculated dose rate, except for the upper pelvis. When it is possible, in oioo measurement of the dose rate is recommended because of this variation. Total body irradiation;
Bone marrow
transplantation;
INTRODUCTION Low dose total body irradiation has been in use for many years in the treatment of a variety of malignant diseases, primarily leukemia and lymphomas.5.6.7P9Recently, total body irradiation has been employed in the treatment of leukemia prior to bone marrow transplantation. The University of Washington Division of Radiation Therapy has reported the use of two opposed -Co sources for total body irradiation.’ The Division of Radiation Therapy at UCLA has been involved in a combined chemotherapy-total body irradiation regimen followed by bone marrow transplantation for patients with acute leukemia who are not responsive to conventional therapeutic modalities.* It is now possible to evaluate the validity of total body irradiation using a single source of radiation from a dosimetric standpoint. IRRADIATION PROCEDUXE A single Atomic Energy of Canada, Ltd. (AECL) Theratron 780,660O Ci Yo unit with a 1.75 cm source diameter is used for the total body irradiation. The patient is positioned
Dosimetry.
lying on his side with the hips and knees flexed on a stretcher adjacent to a wall. The sourcemidplane distance is 330cm. The head and arm of the cobalt unit are rotated so that the beam clears the beam stopper, and the beam axis intersects the patient. With the collimators completely open and rotated 45”, the patient is exposed by a diamond-shaped field with the body lying along the diagonal of the field (Figs. 1 and 2). Before treatment starts, a 26 French Foley catheter containing thermoluminescent dosimeters (TLDs) if the tip is inserted in the rectum. The patient lies facing the Yo unit for the first calculated 200rad. The patient then is turned to face the wall for an additional 200rad. At this time the catheter is removed and the treatment resumed with a calculated time to irradiate the midline to an additional 300rad. While the treatment continues, the TLDs are read and the actual dose rate determined. The calculated treatment time is adjusted to correlate with the actual dose rate. The last portion of the treatment is delivered with the patient facing the -Co unit. In this fashion, the resulting dose distribution is that of two opposed fields.
550
Radiation Oncology 0 Biology 0 Physics
March-April
1976. Vol. 1, Number 5 and Number 6
Fig. 1. Patient in position for total body irradiation with diamond-shaped field. Source-midplane distance is 330 cm. The beam is angled 17”from the horizontal plane.
Fig. 2. Patient receives half the treatment facing the wall. In effect, the patient is irradiated with two 1Popposed fields.
The possibility that certain leukemic cells periodically may sequester and always be “posterior” to the beam has been considered. Although extremely unlikely for any significant group of cells, single cells may, in fact, undergo this unfortuitous sequence of events. Their dose would be at least 650 rad, which appears to be adequate for killing of a single cell or small cluster of cells.’ The clinical results achieved by this procedure (intensive chemotherapy followed by TBI) indicate the leukemic cell population is sufficiently reduced.3
DOSIMETRIC ANALYSIS Dosimetry A dose of 1000 rad is calculated to the midline of the pelvis. The output in air at 330cm is reduced by the appropriate tissueair-ratio (TAR) value. The midplane dose rate is increased 5% to account for the increase in scattered radiation adjacent to the wall (Table 1). In order to obtain an idea of the dose distribution in the body with the set-up we are using, TLDs were placed at a number of locations in each of six levels of a Rando
Total body irradiation utilizing a single To
551
source 0 R. J. MILLER et al.
Table 1. Comparison of measured output @ad/minute) and calculated output at 5 cm depth in phantom. North wall of treatment room is 352 cm from “‘Co source. An increase of 5% in measured dose rates is consistent with the expected magnitude of backscatter from the wall
Measured values Inverse-square
Source-axis distance (cm) 292 309 329 265
336
85
167
141.8
37.40 36.70
14.80 14.60
12.50 12.00
11.20 10.70
10.10 9.50
9.60 9.10
1.02
1.01
1.04
1.05
1.06
1.05
Measurement/calculated
phantom ranging from the pelvis to the head. The phantom was placed on its side, reproducing the geometry of a patient undergoing TBI. The phantom was turned so as to simulate the actual treatment of patients as described in the previous section. The overall variation was of the order of 5% of the normalized dose (Fig. 3). The expected increase in dose to the thinner portions of the body is offset partially by the reduced dose rate at the periphery of the 6oCo beam” where the head, neck and legs are positioned. TLDs IN RAND0 PHANTOM
TLDs in a rectal catheter were inserted in a number of patients receiving total body irradiation. It is assumed that the rectal dose rate is a valid indication of the dose received at the pelvic midplane. As previously stated, the calculated treatment time was adjusted according to the dose rate indicated by the lithium-fluoride dosimeters. Three TLDs were placed at the tip of the catheter and inserted 10-15 cm proximal to the anus just prior to the treatment. With each measurement, a calibration exposure was performed on dosimeters of the same batch in order to determine the magnitude of the supralinearity of the TLDs in the 300-500 rad dose range. For the most part, the measured values agree within 10% of the calculated values (Table 2). The effect of blankets and pillows (to prop the patient) and the Foley catheter on the TLDs were measured and found to be negligiTable 2. Comparison
of measured rectal dose rates with calculated values. Rectal doses were measured with TLDs
Date
Fig. 3. Dose distribution in six levels of a Rando Phantom. Values are percentages of normalized dose in upper pelvis (approximate field center). Within group variation of the TLDs is less than 5%.
Calculated (rad/min)
Measured @ad/mm)
Calculated measured
12174 l/75 l/75 2175 2175 4175 5175 7175 7175 8175
10.6 9.9 10.3 9.0 10.3 8.9 9.5 8.0 8.2 9.0
11.7 10.9 10.5 8.6 10.8 9.0 9.2 7.2 8.6 8.6
0.91 0.91 0.98 1.05 0.95 0.99 1.03 1.11 0.95
8175
9.4
8.4
9175 10/75
8.8 8.8
8.9 7.6
1.12 0.99 1.16+
fOver 12% disagreement
1.05
with calculated values.
552
Radiation Oncology ??Biology 0 Physics
ble (I%), In addition, TLDs in a Foley catheter were inserted in a number of patients receiving routine pelvic AP-PA treatments. The TLDs were in excellent agreement with the computed dose using the Memorial External Beam Program.’ It was felt that the dose that the dosimeters displayed was an accurate assessment of the rectal dose. DISCUSSION A number of problems are encountered when one attempts to calculate accurately the dose received at the patient midplane in total body irradiation. The exact source-patient axis distance changes during treatment as the patient shifts position occasionally. With our present set-up, it is thought that the overall source-axis distance varies from 315 to 345 cm. This produces the largest source of error in attempting to predict the patient dose. Restricting patient movement during an already uncomfortable and lengthy treatment sometimes is difficult. The TLDs in the catheter are not precisely on the midline of the patient, and an uncertainty of 25% consistent with the variation in dose distribution in the patient is expected. In measuring the patient
March-April 1976, Vol. 1, Number 5 and Number 6
Table 3. Uncertainty involved in calculating rectal dose rates with our set-up. Uncertainty was determined by square root of sum of squares of the independent percent errors Calculated vs actual dose Positional (2 15 cm) Dose variation in patient Patient thickness (-Cl cm) Exposure rate
(%) 210 +5 r3 *3 +12.0
contour (in a sterile isolation room), we are accurate to no more than +l cm. This results in an approximate error of 3% accuracy. All of these uncertainties result in an overall error in the calculations of 12% (Table 3). Examination of Table 2 reveals that almost all calculated dose rates were within this margin of error. The use of a single source of radiation appears to be a dosimetrically accurate method for total body irradiation. The use of in vim measurements for verification of the midline dose rate is recommended because of the uncertainty involved in the calculations.
REFERENCES Berry, R.J., Andrews, J.R.: The effect of radiation ionization density (LET) upon the reproductive capacity of mammalian cells irradiated and assayed in vivo. Br. J. Radiol. 36: 49-55, 1%3. DeClemente, A., Mohan, R., Reddy, M.T., Holt, J.G.: Memorial Dose Distribution Service. External Beam Program User Guide (Nov. 1971). Gale, R.: Bone marrow transplantation in man. (Presented 6 Feb. 1975 at the UCLA Conf. Division of Hematology -Oncology, Department of Medicine, UCLA School of Medicine, Martin J. Cline, M.D., Panel Moderator); Ann. Intern. Med. 83: 691-708, 1975. Gale, R.P., Feig. S., Opelz, G., Territo, M., et al.: Bone marrow transplantation in acute leukemia using intensive chemoradiotherapy (SCARI-UCLA). Transplantation Proc. in press.
5. Heublin, A.C.: A preliminary report on continuous irradiation of the entire body. Radiology 18: 1051-1060, 1932. 6. Johnson, R.E.: Evaluation of fractionated total body irradiation in patients with leukemia and disseminated lymphomas. Radiology 86: 10851089, 1966. 7. Johnson, R.E.: Total body irradiation (TBI) as primary therapy for advanced lymphosarcoma. Cancer 35: 242-246, 1975. 8. Thomas, E.D., et al.: Allogeneic marrow grafting for hematologic malignancy using HL-A matched donor-recipient sibling pairs. Blood 38: 267-287, 1971. 9. Thomas, E.D., et al.: Bone marrow transplantation, Part I and Part II. N. Engl. J. Med. 292: 832-843, 895-902, 1975. 10. Webster, E.W., Tsien, K.C.: Atlas of Radiation Dose Distributions, Vol. 1. International Atomic Energy Agency, Vienna, 1%5, pp. 13-21.
