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Can a total body irradiation technique be fast and reproducible?
Int. J. Radiation
Oncology
Pergamon
Biol. Phys.. Vol. 29, No. 5. pp. 1167-l 173. 1994 CopyrIght C 1994 Elsevier Science Ltd Printed m the USA. All rights reserved 0360-30 I6/94 $6.00 + .OO
0360-3016(94)E0095-2
??Technical Innovation and Notes
CAN A TOTAL BODY IRRADIATION TECHNIQUE BE FAST AND REPRODUCIBLE? RAYMOND
MIRALBELL,
PHILIPPE NOUET, PATRICK BOTTERON,
M.D., M.S.,
MICHEL ROUZAUD,
SABINE BIERI, M.D.,
ENG., MANUEL
MONTERO,
M.S.,
EUGENE GROB, ENG.,
SABINE B. MAJNO, M.D.,
ENG. AND JEAN
C. PRECOMA, R.T.
Division de Radio-Oncologic, H6pital Cantonal Universitaire, 1211 Geneva 14, Switzerland Purpose: Total body irradiation (TBI) is frequently a complex and time-consuming technique that significantly overloads Radiation Oncology departments. In an attempt to shorten TBI setup and treatment time we aimed to develop a system where the lung blocks are fixed with optimal precision to the build-up booster lucite screen while the patient is immobilized in a reproducible upright position. Methods and Materials: Fifteen patients diagnosed with leukemia were conditioned before bone marrow transplant since March 1992. Patients were immobilized in a semistanding position in a special stand with arm bars and hand grips. Treatment was delivered with a 6 MV x-ray horizontal beam. Six fractions of 2.25 Gy (mean instantaneous dose rate of 13.8 f 3.8 cGy/min) were delivered twice a day over 3 days (total dose: 13.5 Gy). Each fraction was given in alternating AP (facing the beam) and PA (turning the back) projections. Customized lung blocks (35% transmission) were used to assure a maximum lung dose of 10 f 0.5 Gy. The blocks were taped to a 1 cm thick lucite screen interposed between the source and the patient. Lung shields were checked by port films before each fraction. The reproducibility of the patient’s positioning (and lung shielding) was evaluated by measuring the horizontal and vertical deviations of the infero-external corners of the lung blocks in the port films in relation to the same point in the simulation films. In viva dosimetry (thermoluminiscence and diodes) was performed by placing dosimeters and probes in the central axis and in several off-axis sites. Results: The mean horizontal and vertical deviations were 3.5 f 4.1 mm and 7.5 + 5.9 mm for the anterior fields, and 4.1 + 4.1 mm and 6.9 * 6.4 mm for the posterior fields. An acceptable position of the blocks was considered when deviations were < 5 mm horizontally and/or < 10 mm vertically. The mean time per fraction (i.e., interval between the patient’s entering and leaving the treatment room) was 35 + 5 min. Conclusions: A satisfactory level of reproducibilty can be reached with this technique. The reasonably short treatment time contributes to reproducibility and patient comfort. Bone marrow transplant, Leukemia, Total body irradiation. INTRODUCTION
High dose total body irradiation (TBI) followed or preceded by intensive chemotherapy is an accepted conditioning regimen before bone marrow transplantation (BMT) in treating patients with leukemia. There is no TBI technique that is considered standard, but rather a large number of procedures differing in the total dose, fractionation, dose rate, patient positioning, beam modifiers, and other technical factors. Ideally, an optimal TBI regimen in allografted leukemia patients would result in optimal immunosuppression and bone marrow ablation, a low toxicity rate (particularly pneumonitis) and, in association with chemotherapy, a greater antileukemic effect (6, 21). Unfortunately, the efficacy of different TBI regi-
mens has rarely been studied in comparative trials (12, 17, 18). One common TBI technique is the use of parallel lateral fields with the patient reclining on a stretcher. This technique has important limitations due to inhomogeneities in the dose distribution with frequent overdosages in the less thick anatomical structures or in the lungs, frequently requiring the use of compensation filters or bolus. Anterior and posterior directed fields with the linear accelerator gantry in a lateral position can achieve a more homogeneous dose distribution besides allowing the overall treatment time to be shortened. Shielding the lungs is a widely accepted procedure today (2, 3, 5, 8-l 1, 14). In many of the centers using lung shielding the blocks are in or almost in contact with the patient’s thoracic skin. Thus, the blocks
1993 Swiss Society for Radiobiology and Medical Physics Varian award for radiotherapy. Reprint requests to: Dr. Raymond Miralbell. Division de Ra-
dio-Oncologic, Hbpital Cantonal Universitaire, 14, Switzerland. Accepted for publication 27 January 1994. 1167
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I. J. Radiation Oncology 0 Biology 0 Physics
are carried by the patient himself with or without the use of sophisticated ancillary equipment to hold part of the shield’s weight. This may increase the patient’s discomfort, and prolong the treatment setup if modifications are to be made. Here we present our TBI technique used since March 1992, which has thus far been used for the transplant conditioning of 15 patients. This technique is partly based in the experience of Shank et al. ( 14) and Glasgow et al. (8). We aimed to develop a system where the lung blocks would be fixed with optimal precision to the currently used build-up booster lucite screen with the patient treated in an upright position. Such a system, however, would need a highly reproducible positioning and treatment inmobilisation, which is also tested in our study. This should allow for a reasonably short setup and treatment time, improving patient comfort and avoiding undue overloading of a busy radiation oncology department.
METHODS
AND
MATERIALS
The irradiation technique consists of a set of parallel and opposed anterior and posterior fields using an almost
Volume 29, Number 5. 1994
horizontal (i.e., 272” gantry rotation) 6 MV x-ray beam. The collimator is opened to its maximum field size of 40 X 40 cm at 1 meter from the target and is rotated 45”. The source to skin distance (SSD) is about 400 cm. The distance of the source to the treatment room’s opposite wall is 450 cm. The diagonals (i.e., vertical and horizontal axis) of the diamond-shaped fields measure 220 cm at the above mentioned SSD, with a useful field of 190 cm (i.e., 90% of the dose at the beam center). Patients are treated in a semistanding position alternatively facing and turning the back to the beam (Fig. 1). A total dose of 13.5 Gy (6 X 2.25 Gy) twice-a-day, 9 h apart over 3 days is delivered. The instantaneous dose rate ranges between 12- 15 cGy/ min. Partial transmission (i.e. 35%) lung shields are used allowing for a -25% dose reduction (i.e., 10 -t 0.5 Gy) in the core of both lungs. In viva dosimetry is performed on every patient and treatment session by using simultaneous thermoluminiscence (TLD) and diodes placed on the central axis (abdomen) and off-axis (head-front, neck, mediastinum, bilateral chest, thigh, and leg) anatomical sites. A special homemade stand with a bike-like chair and an additional immobilization system for the head and
04 Fig. 1. TBI treatment
position.
(A) Anterior
(facing the beam) field. (B) Posterior
(turning
the back) field.
Total body irradiation technique 0 R.
thorax helps to position the patient in a reproducible manner. The stand is a modular structure built of aluminium tubes of 4 cm diameter and wood with a plastified surface. Figure 2 presents the technical description of the stand. Its dimensions are: 220 cm high, 105 cm wide, and 85 cm deep. The stand’s floor is elevated 20 cm from the ground and is supported by 4 wheels. The structure is fixed to the treatment room wall with a pair of hooks. A 170 cm high, 95 cm wide, and 1 cm thick removable lucite screen hangs from the front top of the structure to an average distance of 40-50 cm from the patient. This screen has a double purpose: as a “beam spoiler” aiming to reach a skin dose of 2 95%, and as a lung shield holder. An aluminium device screwed to the top of the screen matches exactly the top front bar of the stand allowing for a reproducible positioning. The back of the stand is built with a mobile flat wooden surface that enables a correct positioning of the patient’s back and head. An adjustable film holder is attached to the posterior structure of the support system to obtain lung localization films. Once the patient is sitting, the chair height is adjusted to allow the beam cross-hair to match with the patient’s umbilicus. The immobilization system aims to fix the thorax of the patient in a reproducible manner. This can be ob-
Backmboord
w8t.h cassette-holder
Lung
block
shadow
(x.y adjustable)
PVC~Arn~ho(der//
/
(bl
wth /
Patient
/
brahe seat
Floor-panel _
Fig. 2. Treatment stand: Technical (b) Lateral view. (c) Top view.
(wood,
(plostlfied
Prrc~sion hook and pos,t,omng lucltc panel,
description.
stuffed)
wood)
(a) Anterior view.
MIRALBELL
et ul.
1169
tained with the use of a pair of movable bars that hold the patient’s axillae, and a second pair of adjustable hand holders. The arm and hand holders are made in PVC modeled material. A set of two straps help to prevent the patient from falling down in case of sudden weakness. In addition, the head is immobilized against a flat pillowlike surface with an adjustable strap. Simulation is done the week preceding the treatment. The patient is seated in a comfortable position facing the beam by adjusting the chair height, the axilla-bars, and the hand holders. The head is then fixed. A megavoltage chest x-ray is taken with the treatment beam after taping a 10 cm lead marker on the vertical axis of the lucite screen at a known distance from the beam center projection on the same screen (i.e., 30-35 cm). The same procedure is performed for the posterior (turning the back to the beam) position. The top and the bottom of the projection of the lead marker on the patient’s anterior and posterior midlines are tattoed. The corresponding projection marks are also drawn on the screen. Central axis and off-axis (anatomical sites mentioned above) thicknesses are measured for dosimetric purposes. Lung blocks for the anterior and posterior positions are drawn on the simulation films with a 3.5 cm margin from the diaphragm and the lung apex and a 2.5 cm margin from the lateral rib cage limits and the vertebral body edge. They are manufactured thereafter with 23 mm deep cerrobend material. The blocks are positioned and taped on a 2 mm thin lucite tray bearing drawn points corresponding to the top and bottom of the lead marker used for simulation purposes. The tray with the blocks are fixed to the lucite screen with adjustable screws, allowing for fast up-and-down displacements to match the screen marks with the patient’s midline tattoos. This permits correction of the block positioning if dictated by the port films. Although both anterior and posterior fields are treated in every session, lung blocks are used in an alternative fashion: anterior blocks are used in the first, third, and fifth treatment fractions, while posterior blocks are used during the second, fourth, and sixth fractions. This setup and the 35% block transmission enable to obtain the desired 25% lung dose reduction. If, according to the in vivo dose measurements, a lung dose higher or lower than previously specified is predicted, the lung blocking time is corrected. Port films are taken at the beginning of every session for every treatment position where blocks are used. The port films allowed the reproducibility of the technique to be analyzed by matching the port and simu!ation films and measuring the deviation of the lung blocks. We measured the horizontal and vertical deviations of the infero-external corners of the two anterior and the two posterior lung block images (Fig. 3) and plotted the obtained values on a scattergram. We did not perform corrections in the block positioning if deviations were < 5 mm in the horizontal axis and/or < 10 mm in the vertical
1. J. Radiation
Oncology
0 Biology 0 Physics
Volume
29, Number
5. 1994
TLD dosimeters, and port film implementation and evaluation. Figure 4 displays the deviations of the lung blocks in both horizontal and vertical axes for the anterior and posterior beam projections for all the 15 patients treated. For the anterior fields the mean values for a deviation in the horizontal and vertical axes were 3.5 + 4.1 mm and 7.5 f 5.9 mm, respectively. For the posterior fields, the mean values for the same deviations were 4.1 -t 4.1 mm and 6.9 + 6.4 mm, respectively. Figure 5 presents the graphic representation of the deviations together for the anterior and posterior fields for the first two patients (1 and 2) and last two patients ( 14 and 15) treated. A marked reduction in patient setup errors, especially concerning horizontal deviations, is observed for our last two patients. This is most likely the result of tattooing the patient’s midline, thus allowing for a better alignment in both axes. This procedure was not performed in the first patients. Unfortunately there are still vertical deviations observed despite tattooing the patients, especially for the anterior fields. This may be explained by a tendency of the patient to lean the upper body forward to improve his comfort. This assumption has induced us just recently to immobilize the patient’s head against the stand with an adjustable strap to further improve reproducibility.
DISCUSSION i i
Deviation
Fig. 3. Schematic representation of the lung blocks as drawn in the simulation fields (black contours) and their corresponding images on the port films (shadows). Deviations of the inferoexternal corners of the lung block images are measured in the horizontal and vertical axes.
axis. The 15 patients treated so far with this TBI technique are the subject of this reproducibility study.
RESULTS In viva dosimetry measurements allowed us to calculate the dose uniformity as a ratio of the dose in a specified anatomic site to the dose in the abdomen (central axis). The mean value and standard deviations of these ratios were: 0.976 + 0.053 for the head, 1.048 ? 0.046 for the neck, 1 .O 10 f 0.03 1 for the mediastinum, 1.033 * 0.048 for the thigh, and 1.10 1 + 0.048 for the ankle. The mean lung dose ratio was 0.740 ? 0.016 (i.e., 9.99 + 0.22 Gy). The mean instantaneous dose rate at the abdominal level was 13.8 + 3.8 cGy/min corresponding to a 250 mu/min linear accelerator output rate. The mean duration of each treatment session measured as the interval between the patient’s entering and leaving the treatment room was 35 + 5 min. From this period of time, 16-20 min corresponded to the treatment and 15-20 min to the patient’s setup: positioning, fixation and removal of diodes and
Total body irradiation regimens in the 70s consisted frequently of single dose (i.e., 10 Gy) low dose rate (i.e., 2-8 cGy/min) regimens (1, 16). The wide opinion that fractionation enhanced the repair of cellular radiation damage more efficiently in nontarget cells (i.e., lung cells) than in target cells (i.e., bone marrow, immunocompetent, and leukemic cells) (13), recommended the use of small fractions, usually more than once a day to overcome the accelerated repopulation of the target cells. Furthermore, synchronization effects on the target cells have also been claimed as a reason to prefer the use of hyperfractionated TBI ( 14). Clinical data concerning the engraftment rates of different fractionation schedules, however, suggest a larger-than-expected repair capacity of the bone marrow target cells (20). Using murine bone marrow chimera models as experimental material, Down et al. published recently a study that revealed an appreciable sublethal damage repair and high cell-renewal potential in the stem cell population of the bone marrow after using different TBI schemes with various fractionations, total doses, and dose rates (4). Hence, for a given total dose, hypofractionated doses may be more advantageous than delivering the same dose in smaller fractions, specially if BMT involves T-cell depleted grafts. Pneumonitis is a main conditioning-related complication with a multifactorial dependence (e.g., radiation dose to the lungs, chemotherapy, graft-vs.-host disease). Radiation damage to the lung cells is strongly fractionation dependent. Fractionation will enhance cell repair and de-
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I. J. Radiation Oncology 0 Biology 0 Physics
1172
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Volume 29, Number 5. 1994
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plot of the lung block deviations for the first two patients (I and 2) and the last two patients
(14 and 15).
ducing significantly the duration of each fraction to 35 k 5 min. This time can still be reduced on the average 510 min if higher output rates are used (i.e., 400 mu/min), increasing the instantaneous patient midline dose rate to 17-25 cGy/min. The youngest patient treated so far with this new method is a 6-year-old girl. The midline dose uniformity at all anatomical sites was usually within the ? 10% range of the prescribed dose to the abdomen, and frequently within the + 5% range with a definite trend for the ankles to be overdosed. We did not find this to be a strong enough argument to use compensating filters, as is done by others (5). Several centers using partial transmission lung blocks give an additional electron boost to the shielded segments of rib cage aiming to deliver a uniform dose to the whole bone marrow (5, 8, 9, 11, 14). We did not attempt to follow this attitude based on our former experience in which, despite using partially shielding lung blocks to keep the dose to the lungs within a 9-10 Gy range, the permanent engraftment rate still was close to 95%, while the overall idiopathic pneumonitis rate was 2% ( 10). This results have been reproduced by others using a similar treatment approach (22). We chose the method of measuring the horizontal and vertical deviations of the lung block corners on the port
films by superimposing the anatomical structures of both the simulation and port films. Besides up-and-down and lateral displacements, slight vertical or horizontal rotations of the patient’s trunk would definitely magnify the error of block positioning. Hence, the deviations measured are a good expression of the precision and reproducibility of patient positioning. Initially, our confidence in the immobilization device was such that we did not consider skin marks necessary. We observed, however, that our system allowed for some movements. The most comfortable position for the patient at simulation tended to be different from that shortly after high dose chemotherapy when TBI started. Since we started to tattoo our patients, reproducibility has clearly improved. The tendency of the patients to slightly lean forward in the anterior position has prompted us recently to fix the head against the stand. Corrections are made, if necessary, after checking the port films. Lateral corrections are made by slight changes in the patient positioning (pushing or pulling the arm bars), while vertical corrections are quickly obtained by sliding up or down the block tray screwed to the lucite screen. In summary, we presented an exercise of TBI optimization by using a simple immobilization system with lung blocks fixed to the screen. Although block shifts of 2 cm
Total body irradiation
technique
0 R. MIRALBELLe/ ul.
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were sometimes observed, this happened mainly with the first patients before positioning had been optimized. After some experience with the technique, we reached a satisfactory level of reproducibility in the last patients treated, with an acceptable match (i.e., < 5 mm horizontal or < 10 mm vertical deviations) of the simulation and
ibility and patient comfort. To further reduce toxicity of TBI, especially if large fractions or higher total doses are to be recommended in the future, one should be able to partially shield the kidneys and/or the liver in a reproducible manner. We think that these are additional reasons to use the lucite screen as block holder while the
port films in > 80% of the situations.
patient
treatment
time
for each fraction
The reasonably
contributes
short
is treated
in an upright
position.
to reproduc-
REFERENCES 1. Barrett,
2.
3.
4
5.
6.
7.
A.; Depledge, M. H.; Powles. R. L. Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation. Int. J. Radiat. Oncol. Biol. Phys. 9: 1029-1033; 1983. Breneman, J. C.; Elson, H. R.; Little, R.; Lamba, M.; Foster, A. E.; Aron, B. S. A technique for delivery of total body irradiation for bone marrow transplantation in adults and adolescents. Int. J. Radiat. Oncol. Biol. Phys. 18: 1233- 1236; 1990. Burnett, A. K.; Harm, M. I.; Robertson, A. G.; Alcorn, M.; Gibson, B.; McVicar, I.; Niven, L.; Mckinnon, S.; Hambley, H.; Morrison, A.; Todd, A. Prevention of graft-versus-host disease by ex viva T cell depletion: Reduction in graft failure with augmented total body irradiation. Leukemia 2:300303; 1988. Down, J. D.; Tarbell, N. J.; Thames, H. D.; Mauch, P. M. Syngeneic and allogeneic bone marrow engraftment after total body irradiation: Dependence on dose, dose rate, and fractionation. Blood 77:66 l-669; I99 1. Findley, D. 0.; Skov, D. D.; Blume, K. G. Total body irradiation with a 10 MV linear accelerator in conjunction with bone marrow transplantation. Int. J. Radiat. Oncol. Biol. Phys. 6:695-702; 1980. Gale, R. P.; Butturini, A.; Bortin, M. M. What does total body irradiation do in bone marrow transplants for leukemia? Int. J. Radiat. Oncol. Biol. Phys. 20:631-634; 1991. Giri, P. G. S.; Kimler, B. F.; Giri, U. P.; Cox, G. G.; Reddy, E. K. Comparison of single fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung. Int. J. Radiat. Oncol. Biol. Phys. 11527-534; 1985.
J. A total body irradiation stand for bone marrow transplant patients. Int. J. Radiat. Oncol. Biol. Phys. 16:875-877; 1989. S.; Murray, K. J.; Casper, 9. Lawton, C. A.; Barber-Derus, J. T.; Ash, R. C.; Gillin, M. T.; Wilson, J. F. Technical modifications in hyperfractionated total body irradiation for T-lymphocyte deplete bone marrow transplant. Int. J. Radiat. Oncol. Biol. Phys. 17:319-322; 1989. 10. Miralbell, R.; Chapuis, B.; Nouet, P.; Helg, C.; Delorme, H.; Wacker, P.; Wyss, M.; Kurtz, J. Conditioning the leukemic patient before allogeneic BMT: value of intensifying immunosuppression in the context of different levels of graft T lymphocyte depletion. Bone Marrow Transplant. 11:447451; 1993. A. Physical aspects of total body irradia11. Niroomand-Rad,
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21.
22.
tion of bone marrow transplant patients using 18 MV X rays. Int .J. Radiat. Oncol. Biol. Phys. 20:605-6 11; 1991. Ozsahin, M.; P&e, F.; Touboul, E.; Belkacemi, Y.; Schwartz, L. H.; Rio, B.: Gorin, N. C.; Leblond, V.; Schlienger, M.; Laugier, A. Interstitial pneumonitis and total body irradiation: A randomized comparison of two instantaneous dose rates. Proc. 18th Eur. BMT Meeting 153; 1992. Peters, L. J.; Withers, H. R.; Cundiff, J. C.; Dicke, K. A. Radiobiological considerations in the use of total-body irradiation for bone-marrow transplantation. Radiology 13 1: 243-247; 1979. Shank, B.; O’Reilly, R. J; Cunningham, I.; Kernan, N.; Yaholom, Y.; Brochstein, J.; Castro-Malaspina, H.; Kutcher, G. J.; Mohan, R.; Bon&ho, P. Total body irradiation for bone marrow transplantation: The Memorial Sloan-Kettering Cnacer Center experience. Radiother. Oncol. Suppl. 1:68-81; 1990. Tarbell, N. J.; Guinan, E. C.; Niemeyer, C.; Mauch, P.; Sallan, S. E.; Weinstein, H. J. Late onset of renal dysfunction in survivors of bone marrow transplantation. Int. J. Radiat. Oncol. Biol. Phys. 15:99-104; 1988. Thomas, E. D.; Storb, R.; Buckner, C. D. Total body irradiation in preparation for bone marrow engraftment. Transplant Proc. 8:591-593; 1976. Thomas, E. D.; Clift, R. A.; Hersman, J.; Sanders, J. E.; Stewart, P.; Buckner, C. D.; Fefer, A.; McGuffin, R.; Smith, J. W.; Storb, R. Marrow transplantation for acute nonlymphoblastic leukemia in first remission using fractionated or single-dose irradiation. Int. J. Radiat. Oncol. Biol. Phys. 8: 817-821; 1982. Thomas, E. D. Total body irradiation regimens for marrow grafting. Int. J. Radiat. Oncol. Biol. Phys. 19:1285-1288; 1990. Travis, E. L.; Parkins, C. S.; Down, J. D.; Fowler, J. F.; Thames, H. D. Repair in mouse lung between multiple small doses of X-rays. Radiat.Res. 94:326-339; 1983. Van Bekkum, D. W.; Hagenbeek, A. Immunohematological aspects of total body irradiation and bone marrow transplantation for the treatment ofleukemia. Radiother. Oncol. Suopl. 1:30-36; 1990. Vhesendorp, H. M.; Herman, M. G.; Saral, R. Future analysis of total body irradiation. Int. J. Radiat. Oncol. Biol. Phys. 20:635-637; 199 1. Weshler, Z.; Breuer, R.; Naparstek, E.; Pfeffer, M. R.; Lowental, E.; Slavin, S. Interstitial pneumonitis after total body irradiation: Effect of partial lung shielding. Br. J. Haematol. 74:6 l-64; 1990.
Oncology
Pergamon
Biol. Phys.. Vol. 29, No. 5. pp. 1167-l 173. 1994 CopyrIght C 1994 Elsevier Science Ltd Printed m the USA. All rights reserved 0360-30 I6/94 $6.00 + .OO
0360-3016(94)E0095-2
??Technical Innovation and Notes
CAN A TOTAL BODY IRRADIATION TECHNIQUE BE FAST AND REPRODUCIBLE? RAYMOND
MIRALBELL,
PHILIPPE NOUET, PATRICK BOTTERON,
M.D., M.S.,
MICHEL ROUZAUD,
SABINE BIERI, M.D.,
ENG., MANUEL
MONTERO,
M.S.,
EUGENE GROB, ENG.,
SABINE B. MAJNO, M.D.,
ENG. AND JEAN
C. PRECOMA, R.T.
Division de Radio-Oncologic, H6pital Cantonal Universitaire, 1211 Geneva 14, Switzerland Purpose: Total body irradiation (TBI) is frequently a complex and time-consuming technique that significantly overloads Radiation Oncology departments. In an attempt to shorten TBI setup and treatment time we aimed to develop a system where the lung blocks are fixed with optimal precision to the build-up booster lucite screen while the patient is immobilized in a reproducible upright position. Methods and Materials: Fifteen patients diagnosed with leukemia were conditioned before bone marrow transplant since March 1992. Patients were immobilized in a semistanding position in a special stand with arm bars and hand grips. Treatment was delivered with a 6 MV x-ray horizontal beam. Six fractions of 2.25 Gy (mean instantaneous dose rate of 13.8 f 3.8 cGy/min) were delivered twice a day over 3 days (total dose: 13.5 Gy). Each fraction was given in alternating AP (facing the beam) and PA (turning the back) projections. Customized lung blocks (35% transmission) were used to assure a maximum lung dose of 10 f 0.5 Gy. The blocks were taped to a 1 cm thick lucite screen interposed between the source and the patient. Lung shields were checked by port films before each fraction. The reproducibility of the patient’s positioning (and lung shielding) was evaluated by measuring the horizontal and vertical deviations of the infero-external corners of the lung blocks in the port films in relation to the same point in the simulation films. In viva dosimetry (thermoluminiscence and diodes) was performed by placing dosimeters and probes in the central axis and in several off-axis sites. Results: The mean horizontal and vertical deviations were 3.5 f 4.1 mm and 7.5 + 5.9 mm for the anterior fields, and 4.1 + 4.1 mm and 6.9 * 6.4 mm for the posterior fields. An acceptable position of the blocks was considered when deviations were < 5 mm horizontally and/or < 10 mm vertically. The mean time per fraction (i.e., interval between the patient’s entering and leaving the treatment room) was 35 + 5 min. Conclusions: A satisfactory level of reproducibilty can be reached with this technique. The reasonably short treatment time contributes to reproducibility and patient comfort. Bone marrow transplant, Leukemia, Total body irradiation. INTRODUCTION
High dose total body irradiation (TBI) followed or preceded by intensive chemotherapy is an accepted conditioning regimen before bone marrow transplantation (BMT) in treating patients with leukemia. There is no TBI technique that is considered standard, but rather a large number of procedures differing in the total dose, fractionation, dose rate, patient positioning, beam modifiers, and other technical factors. Ideally, an optimal TBI regimen in allografted leukemia patients would result in optimal immunosuppression and bone marrow ablation, a low toxicity rate (particularly pneumonitis) and, in association with chemotherapy, a greater antileukemic effect (6, 21). Unfortunately, the efficacy of different TBI regi-
mens has rarely been studied in comparative trials (12, 17, 18). One common TBI technique is the use of parallel lateral fields with the patient reclining on a stretcher. This technique has important limitations due to inhomogeneities in the dose distribution with frequent overdosages in the less thick anatomical structures or in the lungs, frequently requiring the use of compensation filters or bolus. Anterior and posterior directed fields with the linear accelerator gantry in a lateral position can achieve a more homogeneous dose distribution besides allowing the overall treatment time to be shortened. Shielding the lungs is a widely accepted procedure today (2, 3, 5, 8-l 1, 14). In many of the centers using lung shielding the blocks are in or almost in contact with the patient’s thoracic skin. Thus, the blocks
1993 Swiss Society for Radiobiology and Medical Physics Varian award for radiotherapy. Reprint requests to: Dr. Raymond Miralbell. Division de Ra-
dio-Oncologic, Hbpital Cantonal Universitaire, 14, Switzerland. Accepted for publication 27 January 1994. 1167
12 11 Gekve
1168
I. J. Radiation Oncology 0 Biology 0 Physics
are carried by the patient himself with or without the use of sophisticated ancillary equipment to hold part of the shield’s weight. This may increase the patient’s discomfort, and prolong the treatment setup if modifications are to be made. Here we present our TBI technique used since March 1992, which has thus far been used for the transplant conditioning of 15 patients. This technique is partly based in the experience of Shank et al. ( 14) and Glasgow et al. (8). We aimed to develop a system where the lung blocks would be fixed with optimal precision to the currently used build-up booster lucite screen with the patient treated in an upright position. Such a system, however, would need a highly reproducible positioning and treatment inmobilisation, which is also tested in our study. This should allow for a reasonably short setup and treatment time, improving patient comfort and avoiding undue overloading of a busy radiation oncology department.
METHODS
AND
MATERIALS
The irradiation technique consists of a set of parallel and opposed anterior and posterior fields using an almost
Volume 29, Number 5. 1994
horizontal (i.e., 272” gantry rotation) 6 MV x-ray beam. The collimator is opened to its maximum field size of 40 X 40 cm at 1 meter from the target and is rotated 45”. The source to skin distance (SSD) is about 400 cm. The distance of the source to the treatment room’s opposite wall is 450 cm. The diagonals (i.e., vertical and horizontal axis) of the diamond-shaped fields measure 220 cm at the above mentioned SSD, with a useful field of 190 cm (i.e., 90% of the dose at the beam center). Patients are treated in a semistanding position alternatively facing and turning the back to the beam (Fig. 1). A total dose of 13.5 Gy (6 X 2.25 Gy) twice-a-day, 9 h apart over 3 days is delivered. The instantaneous dose rate ranges between 12- 15 cGy/ min. Partial transmission (i.e. 35%) lung shields are used allowing for a -25% dose reduction (i.e., 10 -t 0.5 Gy) in the core of both lungs. In viva dosimetry is performed on every patient and treatment session by using simultaneous thermoluminiscence (TLD) and diodes placed on the central axis (abdomen) and off-axis (head-front, neck, mediastinum, bilateral chest, thigh, and leg) anatomical sites. A special homemade stand with a bike-like chair and an additional immobilization system for the head and
04 Fig. 1. TBI treatment
position.
(A) Anterior
(facing the beam) field. (B) Posterior
(turning
the back) field.
Total body irradiation technique 0 R.
thorax helps to position the patient in a reproducible manner. The stand is a modular structure built of aluminium tubes of 4 cm diameter and wood with a plastified surface. Figure 2 presents the technical description of the stand. Its dimensions are: 220 cm high, 105 cm wide, and 85 cm deep. The stand’s floor is elevated 20 cm from the ground and is supported by 4 wheels. The structure is fixed to the treatment room wall with a pair of hooks. A 170 cm high, 95 cm wide, and 1 cm thick removable lucite screen hangs from the front top of the structure to an average distance of 40-50 cm from the patient. This screen has a double purpose: as a “beam spoiler” aiming to reach a skin dose of 2 95%, and as a lung shield holder. An aluminium device screwed to the top of the screen matches exactly the top front bar of the stand allowing for a reproducible positioning. The back of the stand is built with a mobile flat wooden surface that enables a correct positioning of the patient’s back and head. An adjustable film holder is attached to the posterior structure of the support system to obtain lung localization films. Once the patient is sitting, the chair height is adjusted to allow the beam cross-hair to match with the patient’s umbilicus. The immobilization system aims to fix the thorax of the patient in a reproducible manner. This can be ob-
Backmboord
w8t.h cassette-holder
Lung
block
shadow
(x.y adjustable)
PVC~Arn~ho(der//
/
(bl
wth /
Patient
/
brahe seat
Floor-panel _
Fig. 2. Treatment stand: Technical (b) Lateral view. (c) Top view.
(wood,
(plostlfied
Prrc~sion hook and pos,t,omng lucltc panel,
description.
stuffed)
wood)
(a) Anterior view.
MIRALBELL
et ul.
1169
tained with the use of a pair of movable bars that hold the patient’s axillae, and a second pair of adjustable hand holders. The arm and hand holders are made in PVC modeled material. A set of two straps help to prevent the patient from falling down in case of sudden weakness. In addition, the head is immobilized against a flat pillowlike surface with an adjustable strap. Simulation is done the week preceding the treatment. The patient is seated in a comfortable position facing the beam by adjusting the chair height, the axilla-bars, and the hand holders. The head is then fixed. A megavoltage chest x-ray is taken with the treatment beam after taping a 10 cm lead marker on the vertical axis of the lucite screen at a known distance from the beam center projection on the same screen (i.e., 30-35 cm). The same procedure is performed for the posterior (turning the back to the beam) position. The top and the bottom of the projection of the lead marker on the patient’s anterior and posterior midlines are tattoed. The corresponding projection marks are also drawn on the screen. Central axis and off-axis (anatomical sites mentioned above) thicknesses are measured for dosimetric purposes. Lung blocks for the anterior and posterior positions are drawn on the simulation films with a 3.5 cm margin from the diaphragm and the lung apex and a 2.5 cm margin from the lateral rib cage limits and the vertebral body edge. They are manufactured thereafter with 23 mm deep cerrobend material. The blocks are positioned and taped on a 2 mm thin lucite tray bearing drawn points corresponding to the top and bottom of the lead marker used for simulation purposes. The tray with the blocks are fixed to the lucite screen with adjustable screws, allowing for fast up-and-down displacements to match the screen marks with the patient’s midline tattoos. This permits correction of the block positioning if dictated by the port films. Although both anterior and posterior fields are treated in every session, lung blocks are used in an alternative fashion: anterior blocks are used in the first, third, and fifth treatment fractions, while posterior blocks are used during the second, fourth, and sixth fractions. This setup and the 35% block transmission enable to obtain the desired 25% lung dose reduction. If, according to the in vivo dose measurements, a lung dose higher or lower than previously specified is predicted, the lung blocking time is corrected. Port films are taken at the beginning of every session for every treatment position where blocks are used. The port films allowed the reproducibility of the technique to be analyzed by matching the port and simu!ation films and measuring the deviation of the lung blocks. We measured the horizontal and vertical deviations of the infero-external corners of the two anterior and the two posterior lung block images (Fig. 3) and plotted the obtained values on a scattergram. We did not perform corrections in the block positioning if deviations were < 5 mm in the horizontal axis and/or < 10 mm in the vertical
1. J. Radiation
Oncology
0 Biology 0 Physics
Volume
29, Number
5. 1994
TLD dosimeters, and port film implementation and evaluation. Figure 4 displays the deviations of the lung blocks in both horizontal and vertical axes for the anterior and posterior beam projections for all the 15 patients treated. For the anterior fields the mean values for a deviation in the horizontal and vertical axes were 3.5 + 4.1 mm and 7.5 f 5.9 mm, respectively. For the posterior fields, the mean values for the same deviations were 4.1 -t 4.1 mm and 6.9 + 6.4 mm, respectively. Figure 5 presents the graphic representation of the deviations together for the anterior and posterior fields for the first two patients (1 and 2) and last two patients ( 14 and 15) treated. A marked reduction in patient setup errors, especially concerning horizontal deviations, is observed for our last two patients. This is most likely the result of tattooing the patient’s midline, thus allowing for a better alignment in both axes. This procedure was not performed in the first patients. Unfortunately there are still vertical deviations observed despite tattooing the patients, especially for the anterior fields. This may be explained by a tendency of the patient to lean the upper body forward to improve his comfort. This assumption has induced us just recently to immobilize the patient’s head against the stand with an adjustable strap to further improve reproducibility.
DISCUSSION i i
Deviation
Fig. 3. Schematic representation of the lung blocks as drawn in the simulation fields (black contours) and their corresponding images on the port films (shadows). Deviations of the inferoexternal corners of the lung block images are measured in the horizontal and vertical axes.
axis. The 15 patients treated so far with this TBI technique are the subject of this reproducibility study.
RESULTS In viva dosimetry measurements allowed us to calculate the dose uniformity as a ratio of the dose in a specified anatomic site to the dose in the abdomen (central axis). The mean value and standard deviations of these ratios were: 0.976 + 0.053 for the head, 1.048 ? 0.046 for the neck, 1 .O 10 f 0.03 1 for the mediastinum, 1.033 * 0.048 for the thigh, and 1.10 1 + 0.048 for the ankle. The mean lung dose ratio was 0.740 ? 0.016 (i.e., 9.99 + 0.22 Gy). The mean instantaneous dose rate at the abdominal level was 13.8 + 3.8 cGy/min corresponding to a 250 mu/min linear accelerator output rate. The mean duration of each treatment session measured as the interval between the patient’s entering and leaving the treatment room was 35 + 5 min. From this period of time, 16-20 min corresponded to the treatment and 15-20 min to the patient’s setup: positioning, fixation and removal of diodes and
Total body irradiation regimens in the 70s consisted frequently of single dose (i.e., 10 Gy) low dose rate (i.e., 2-8 cGy/min) regimens (1, 16). The wide opinion that fractionation enhanced the repair of cellular radiation damage more efficiently in nontarget cells (i.e., lung cells) than in target cells (i.e., bone marrow, immunocompetent, and leukemic cells) (13), recommended the use of small fractions, usually more than once a day to overcome the accelerated repopulation of the target cells. Furthermore, synchronization effects on the target cells have also been claimed as a reason to prefer the use of hyperfractionated TBI ( 14). Clinical data concerning the engraftment rates of different fractionation schedules, however, suggest a larger-than-expected repair capacity of the bone marrow target cells (20). Using murine bone marrow chimera models as experimental material, Down et al. published recently a study that revealed an appreciable sublethal damage repair and high cell-renewal potential in the stem cell population of the bone marrow after using different TBI schemes with various fractionations, total doses, and dose rates (4). Hence, for a given total dose, hypofractionated doses may be more advantageous than delivering the same dose in smaller fractions, specially if BMT involves T-cell depleted grafts. Pneumonitis is a main conditioning-related complication with a multifactorial dependence (e.g., radiation dose to the lungs, chemotherapy, graft-vs.-host disease). Radiation damage to the lung cells is strongly fractionation dependent. Fractionation will enhance cell repair and de-
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I. J. Radiation Oncology 0 Biology 0 Physics
1172
Patient
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Volume 29, Number 5. 1994
[
boo_...
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plot of the lung block deviations for the first two patients (I and 2) and the last two patients
(14 and 15).
ducing significantly the duration of each fraction to 35 k 5 min. This time can still be reduced on the average 510 min if higher output rates are used (i.e., 400 mu/min), increasing the instantaneous patient midline dose rate to 17-25 cGy/min. The youngest patient treated so far with this new method is a 6-year-old girl. The midline dose uniformity at all anatomical sites was usually within the ? 10% range of the prescribed dose to the abdomen, and frequently within the + 5% range with a definite trend for the ankles to be overdosed. We did not find this to be a strong enough argument to use compensating filters, as is done by others (5). Several centers using partial transmission lung blocks give an additional electron boost to the shielded segments of rib cage aiming to deliver a uniform dose to the whole bone marrow (5, 8, 9, 11, 14). We did not attempt to follow this attitude based on our former experience in which, despite using partially shielding lung blocks to keep the dose to the lungs within a 9-10 Gy range, the permanent engraftment rate still was close to 95%, while the overall idiopathic pneumonitis rate was 2% ( 10). This results have been reproduced by others using a similar treatment approach (22). We chose the method of measuring the horizontal and vertical deviations of the lung block corners on the port
films by superimposing the anatomical structures of both the simulation and port films. Besides up-and-down and lateral displacements, slight vertical or horizontal rotations of the patient’s trunk would definitely magnify the error of block positioning. Hence, the deviations measured are a good expression of the precision and reproducibility of patient positioning. Initially, our confidence in the immobilization device was such that we did not consider skin marks necessary. We observed, however, that our system allowed for some movements. The most comfortable position for the patient at simulation tended to be different from that shortly after high dose chemotherapy when TBI started. Since we started to tattoo our patients, reproducibility has clearly improved. The tendency of the patients to slightly lean forward in the anterior position has prompted us recently to fix the head against the stand. Corrections are made, if necessary, after checking the port films. Lateral corrections are made by slight changes in the patient positioning (pushing or pulling the arm bars), while vertical corrections are quickly obtained by sliding up or down the block tray screwed to the lucite screen. In summary, we presented an exercise of TBI optimization by using a simple immobilization system with lung blocks fixed to the screen. Although block shifts of 2 cm
Total body irradiation
technique
0 R. MIRALBELLe/ ul.
1173
were sometimes observed, this happened mainly with the first patients before positioning had been optimized. After some experience with the technique, we reached a satisfactory level of reproducibility in the last patients treated, with an acceptable match (i.e., < 5 mm horizontal or < 10 mm vertical deviations) of the simulation and
ibility and patient comfort. To further reduce toxicity of TBI, especially if large fractions or higher total doses are to be recommended in the future, one should be able to partially shield the kidneys and/or the liver in a reproducible manner. We think that these are additional reasons to use the lucite screen as block holder while the
port films in > 80% of the situations.
patient
treatment
time
for each fraction
The reasonably
contributes
short
is treated
in an upright
position.
to reproduc-
REFERENCES 1. Barrett,
2.
3.
4
5.
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