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Arc therapy for total body irradiation – A robust novel treatment technique for standard treatment rooms
Radiotherapy and Oncology 110 (2014) 553–557
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Radiotherapy and Oncology journal homepage: www.thegreenjournal.com
TBI arc therapy
Arc therapy for total body irradiation – A robust novel treatment technique for standard treatment rooms Anika Jahnke a,b,⇑, Lennart Jahnke b, Flavia Molina-Duran a,b, Michael Ehmann b, Steffi Kantz c, Volker Steil b, Frederik Wenz b, Gerhard Glatting a, Frank Lohr b, Martin Polednik b a Medical Radiation Physics/Radiation Protection; b Department of Radiation Oncology, Universitätsmedizin Mannheim, Heidelberg University, Mannheim; and c Department of Radiation Oncology, Klinikum der Ludwig-Maximilians-Unversität München, Germany
a r t i c l e
i n f o
Article history: Received 1 July 2013 Received in revised form 5 November 2013 Accepted 15 December 2013 Available online 16 January 2014 Keywords: Total body irradiation TBI Arc therapy
a b s t r a c t Background and purpose: We developed a simple and robust total body irradiation (TBI) method for standard treatment rooms that obviates the need for patient translation devices. Methods and materials: Two generic arcs with rectangular segments for a patient thickness of 16 and 20 cm (arc16/arc20) were generated. An analytical fit was performed to determine the weights of the arc segments depending on patient thickness and gantry angle. Stability and absolute dose for both arcs were measured using EBT3 films in a range of solid water slab phantom thicknesses. Additionally ionization chamber measurements were performed every 10 cm at a source surface distance (SSD) of 200 cm. Results: The measured standard deviation for arc16 is ±3% with a flatness 69.0%. Arc20 had a standard deviation of ±3% with a flatness 67.3% for all measured thicknesses. The theoretical curves proved to be accurate for the prediction of the segment weightings for the two arcs. In vivo measurements for the first 22 clinical patients showed a dose deviation of less than 3%. Conclusions: Arc therapy is a convenient and stable method for TBI. This cost-effective approach has been introduced clinically, obviating the need for field patches and to physically move the patient. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 110 (2014) 553–557
For decades, total body irradiation (TBI) has successfully been part of an interdisciplinary treatment regimen for ‘‘conditioning’’ of patients undergoing bone marrow transplantation for leukemia and lymphoma. The purpose of conditioning is to suppress the immune system to allow engraftment of donor cells, to kill malignant cells and to eradicate cell populations with genetic disorders [1,2]. TBI has been used in conjunction with chemotherapy as a conditioning regimen, for bone marrow transplantation or peripheral blood stem cell transplantation [3,4]. The challenge in TBI is the creation of a relatively uniform dose distribution along all of the patient’s body, therefore necessitating the use of large treatment fields and extended SSD. Two additional dosimetric challenges are different anatomical thicknesses of the patient and the introduction of local dose inhomogeneities to spare critical organs. The predominant critical organ is the lung, which is at risk of developing pneumonitis as a serious, potentially lethal side effect [5,6]. TBI techniques typically comprise a combination of various opposing field setups in a sitting or lying patient position at very ⇑ Corresponding author. Address: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer Ufer 1–3, 68167 Mannheim, Germany. E-mail address: [email protected] (A. Jahnke). 0167-8140/$ - see front matter Ó 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.radonc.2013.12.009
extended SSDs [7–10]. Another technique utilizes a translation couch, where the patient is moved through the field at a constant speed at SSD 200 cm [11–14]. A modification of this approach is the ‘‘sweeping-field’’ technique, where the patient lies on the floor at a distance of 200 cm to the accelerator head and the gantry is sweeping over him. The dosimetric requirements for TBI are described in the AAPM report 17 [15] which defines a prescription point and recommends a dose homogeneity within ±10%. Conventional treatment planning systems (TPS) have been extensively used to optimize TBI/TMI plans [16,17]. We propose a treatment technique that has been implemented clinically and provides optimal dose homogeneity without extra resources in standard treatment rooms, based on the arc paradigm and present first measurements for 22 clinically treated patients.
Materials and methods Patient setup and clinical treatment technique A total body CT of the patient is taken in prone and supine position two weeks before treatment to assess patient thickness and to provide a basis for contouring of lung blocks for patients that are to receive a total dose of >8 Gy. Clinical delivery is performed twice daily with 2 Gy per fraction. Total dose ranges between 4–12 Gy,
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Arc therapy for total body irradiation
delivered in 2–6 fractions on the morning and evening of 1–3 consecutive days with at least 7 h in between the fractions. The patient is treated with two arcs, one in supine and one in prone position, with a source to couch distance of 219 cm. For the alignment point the belly button directly below the isocenter was chosen. To provide optimal skin coverage, a buildup ‘‘spoiler’’ plate is introduced between the accelerator head and the patient. The spoiler consists of 1 cm transparent polycarbonate screen and can be adjusted in height between 29 and 49 cm from the couch surface approximately 20 cm above the patient. Fig. 1 depicts the whole treatment setup. To limit the lung dose below 10 Gy, specially manufactured lung blocks were positioned directly on the patient’s skin. They consist of stacked lead (Pb) plates cut to the desired shape of the individual patient. Prior to treatment the position of the lung blocks is verified by digitally readable and X-ray sensitive film cassettes. When designing the blocks the divergence of the beam including its movement component is taken into account and the isocenter was set to the lower end of the lungs to reduce dose blurring caused by the arc delivery. For 12 Gy prescription dose and 18 cm phantom thickness a required thickness of 12 mm was found corresponding to 12 plates. For 10 Gy prescription 8 mm lead plates are used. The lead thickness was determined by measurements with an inhomogeneous lung phantom and therefore took into account the inhomogeneity of the lung. This resulted in a dose reduction to a maximum of 8–9 Gy midline dose in the lungs. The maximum dose rate in the middle of the body is about 100 cGy/min and in the lung, under the lung blocks, between 60 and 80 cGy/min. Even for single dose/hypofractionated TBI, Sampath et al. [5] could not detect a dose rate effect in treatment series with dose rates up to 41 cGy/min. Recently, three clinical TMI/TBI tomotherapy manuscripts reported the successful use of dose rates 100 cGy/min [18–20]. Before the first treatment of a new patient, the arc is calibrated for absolute dose. During patient treatment, in vivo dosimetry is performed with one in vivo ion chamber and nine semi-conductor detectors (T60010MP, T60010RO, PTW, Freiburg, DE). Diodes are an established tool for in vivo dosimetry [21–23]. Calibration for the diodes is done during the QA measurements. Standard detector positions are head, neck, lung, blocks, isocenter, chest and abdomen.
Development of a theoretical model for arc TBI The basic condition was one arc between gantry angles of 320° and 60° with 10 40 cm field size with a homogeneous dose area that extends over a length of 200 cm. In addition the arc was then
split into ten segments which were weighted according to their gantry angle (see Table 1). The weighted MUs per degree can be fitted using a straight forward approach from the inverse square law and the known polystyrene (RW3, slab phantom material) and polycarbonate (MakrolonÒ, spoiler material) attenuation coefficients. This provides a starting point and thus reduces measurement steps necessary for individual patient thicknesses. The relative weighting factors can be obtained by the ratio of the radiation intensities at 0° segment to the radiation intensity at angle a Þ . segment wf ðaÞ ¼ Ið0 IðaÞ The attenuation coefficients were determined with an energy spectrum obtained by Monte Carlo simulations [24] from an Elekta SynergyÒ 6 MV beam. They were calculated as lp 0.0707 cm1 for RW3 and ls 0.0797 cm1 for MakrolonÒ. The other relevant parameters are of geometrical nature. The functions p(a) and s(a) are the distances the beam has to travel through the phantom and the spoiler, respectively. The initial intensity is I0 and the radii at gantry angle 0° and gantry angle a are r(0) and r(a).
wf ðaÞ ¼
I0 rð0Þ2 I0 rðaÞ2
eðlp pð0ÞÞ eðls sð0ÞÞ eðlp pðaÞÞ eðls sðaÞÞ
ð1Þ
For the inverse square law the distances to the plane with the flat profile have to be known. Here the variable dI denotes the distance from source to isocenter and is fixed to 100 cm, dIPC is the distance from isocenter to the center of the phantom, s0 is the thickness of the spoiler and p0 is half the phantom thickness. The angle alpha denotes the gantry angle of a given segment. In Eq. p0 s0 (2) sðaÞ ¼ cos a and pðaÞ ¼ cos a have been inserted. Using simple geometric arguments, it can be shown that r(0) = dI + dIPC and dIPC rðaÞ ¼ dI þ cos a which has been used in the final Eq. (2).
wf ðaÞ ¼
2 dIPC dI þ cos a 2
ðdI þ dIPC Þ
1 1 eðlp p0 ð1cos aÞÞ eðls s0 ð1cos aÞÞ
ð2Þ
Using this formula, a starting point has been determined for arcs with larger or smaller phantom thicknesses. The calculated arc always needs to be experimentally verified since only relative and no absolute dosimetry is included in the equation. Dose verification measurements To get a DICOM compliant plan the tel.file of MONACOÒ v2.04 (Elekta, Crawley, UK) was modified with the theoretical segment weightings. Two reference measurements for a patient thickness of 16 and 20 cm (arc16 and arc20) were performed using an ionization chamber which was positioned at a depth of 8 and 10 cm, respectively, in a solid water slab phantom (30 90 16/ 20 cm3) with the spoiler in place. The phantom consisted of three stacks with the measurement chamber in the middle in order to simulate patient scatter. Moving the phantom across the irradiation field of the two arcs a measurement point was acquired every Table 1 Normalized weighting factors for each segment for arc16 and arc20.
Fig. 1. Patient setup.
Segment number
Angle (°)
1 2 3 4 5 6 7 8 9 10
320–330 330–340 340–350 350–10 10–20 20–30 30–40 40–50 50–55 55–60
Normalized weighting factor Arc16 (MU/°)
Arc20 (MU/°)
1.424 1.184 1.060 1.000 1.060 1.184 1.424 1.907 2.645 3.562
1.464 1.199 1.065 1.000 1.065 1.199 1.464 2.008 2.869 3.562
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A. Jahnke et al. / Radiotherapy and Oncology 110 (2014) 553–557
10 cm. The total MUs were rescaled to deliver 1 Gy at the reference point (below the isocenter) at 8 and 10 cm depths respectively. Additionally, absolute film measurements using GafchromicÒ EBT3 films were performed. The films were cut into narrow stripes and were positioned for the arc16 at a depth of 2, 8 and 14 cm and for arc20 at a depth of 2, 10 and 18 cm depth. A total length of 240 cm ranging from 150 to 90 cm (with 0 cm being the isocenter) was measured to cover at least part of the dose fall off on one side. The films were scanned using an Epson Expression 10000XL flatbed scanner and calibrated with a multiple point calibration curve and an off axis correction [25] for the peripheral parts of the film. To reduce the noise of the film measurements the mean value of the central 1 cm of each film was analyzed. Finally, as a patient specific QA method, a slab phantom resembling the patient anatomy was built with RW3 slabs and cork plates which emulated lung tissue. In order to determine the phantom thickness the anterior–posterior dimensions of the prone and supine CT were averaged. The dose was measured in 6 different points (head, neck, chest, abdomen, upper leg, lower leg) in the middle of the phantom.
Results The total beam on time was approximately 18 min. The MU weightings for arc16 and arc20 are shown in Table 1. The last segment of arc20 was artificially weighted lower to avoid over dosage
of the feet. Fig. 2(a) demonstrates the flatness (F = (Dmax Dmin)/ (Dmin + Dmax) 100) of arc16 irradiated on the 14 cm phantom. Moreover the results for arc20 irradiated on the 22 cm phantom are depicted in Fig. 2(b). Finally, the reference ionization chamber measurements and the film measurements for the profiles are depicted in Fig. 2(c) and (d). To validate the robustness for different phantom thicknesses, film measurements for 14, 16 and 18 cm thickness for the arc16 as well as measurements for 18, 20, 22 and 24 cm thickness for the arc20 are shown in Table 2. To obtain meaningful results only the central 200 cm were analyzed to determine the statistical values. The standard deviation of the 16 cm arc irradiated on a 14 cm phantom is 3% and therefore the same as for the intended thickness. For arc20, no more than 3% standard deviation was measured for the additional thicknesses. The flatness was acceptable (below 10%) for all given thicknesses. Especially the flatness near the patient surface can only be evaluated by adding up the shallower and the lower film result which is shown in the last columns of Table 2. A measured combined depth dose curve in anterior–posterior and posterior–anterior direction for 30 cm phantom thickness showed a maximum deviation of 9.9 % to the reference point in 15 cm depth. We would therefore suggest a patient thickness of 30 cm as the maximum acceptable thickness for the described technique. In Table 3 patient specific QA results are shown for arc16 and arc20. For these measurements the lung dose is acquired with 12 mm lead plates on the top. All measured doses are within 1.2
1.2
b
1.0
1.0
0.8
0.8
dose [Gy]
dose [Gy]
a
0.6
0.4
0.4
ionization chamber film
ionization chamber film
0.2
0.2
0.0 -150
0.6
-100
-50
0
50
0.0 -150
100
-100
-50
0
50
100
length [cm]
length [cm] 2.0
c
1.5
d
1.0
dose [Gy]
dose [Gy]
1.5
1.0
0.5 0.5
depth 2cm depth 7cm depth 12cm 0.0 -150
-100
-50
length [cm]
0
50
100
0.0 -150
depth 2cm depth 11cm depth 20cm -100
-50
0
50
100
length [cm]
Fig. 2. Measured profiles for different arcs and patient thicknesses with film and ionization chamber (a) film and ionization chamber profiles for arc16 in a 16 cm phantom at a depth of 8 cm, (b) film and ionization chamber profiles for arc20 in a 20 cm phantom at a depth of 10 cm, (c) film profiles for arc16 in 14 cm phantom at a depth of 2, 7 and 12 cm, (d) film profiles for arc20 in a 22 cm phantom at a depth of 2, 11 and 20 cm.
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Arc therapy for total body irradiation
Table 2 Absolute dose and flatness for arc16 and arc20 for different phantom thicknesses in the phantom center measured with film and ionization chamber. The last two columns show the summarized results from the entrance (2 cm from the top of the phantom) and exit (2 cm from the bottom of the phantom) film profiles. Arc
Phantom diameter (cm)
MU
Ionization chamber dose (Gy)
Film in phantom center
Film (entrance + exit)/2
Mean dose (Gy)
Flatness (%)
Mean dose (Gy)
Flatness (%)
16
14 16 18
5884
1.01 1.00 0.99
1.02 ± 0.03 1.01 ± 0.03 0.97 ± 0.03
8.4 8.8 9.0
1.04 ± 0.02 1.05 ± 0.02 1.03 ± 0.02
6.2 6.5 5.2
20
18 20 22 24
6250
1.02 1.00 0.99 0.98
1.05 ± 0.02 1.02 ± 0.02 1.01 ± 0.02 0.97 ± 0.03
6.7 7.2 5.3 7.3
1.08 ± 0.04 1.08 ± 0.04 1.09 ± 0.05 –
9.6 9.1 8.4 –
Table 3 Dose measurements for different phantom sizes and arcs with variable thicknesses measured in the middle of the phantom for 6 different positions. Head
Neck
Chest with 12 mm blocks
Abdomen
Upper leg
Lower leg
Arc 16 for ø 18 cm Thickness (cm) Dose (Gy)
15 0.96
11 1.03
18 0.68
18 1.0
12 1.04
9 1.07
Arc 20 for ø 22 cm Thickness (cm) Dose (Gy)
16 1.04
14 1.05
24 0.69
22 1.0
17 1.03
12 1.10
±10% except the intentionally blocked lung which received around 70% of the prescribed 12 Gy. To date, 22 patients have been treated with this technique. In vivo dosimetry was performed as required by the German technical guideline for TBI [26]. Within this framework, for two female patients in vivo intra-vaginal measurements were carried out and showed a deviation from calculated midbody doses of less than 3%. For all patients the mean exit doses measured daily with an in vivo ionization chamber was within 3% of the predicted exit dose. Discussion TBI has proven to be an important element of the conditioning process before bone marrow or peripheral blood stem cell transplantation. However, long treatment times and the need for meticulous setup and dosimetry to yield delivery with optimal dose homogeneity throughout the body can put a considerable strain on departmental resources. The application of TBI is also limited by local constraints such as small treatment rooms that do not offer the possibility to treat with one field at extended SSDs. Originally the problem was solved by fixed treatment beams [8]. Translational treatment couches that move the patient through a fixed treatment beam have offered another solution to this problem, further improving on dose homogeneity. More advanced techniques include Rapid Arc dose distributions for total marrow irradiation (TMI) [27] and an inverse planned modulated arc TBI method [28]. The VMAT fixed jaw opening method was first theoretically described by [29] with an optimizer for a rotating gantry with fixed patient position. Shortcomings of the reported methods are that field gaps, large treatment rooms or moving couches are needed. This is not the case in the fixed field size arc TBI approach as described in this report. Furthermore this solution proves that segment weighting optimization is unnecessary. Rather than optimizing weightings, an analytical approach to segment weightings is given. Out of the measurements one can conclude that the robustness toward changes in thickness is remarkable whereas the insensitivity toward patient misalignment cranial caudal and left right is due to
the open field approach. A limitation is that the calculated weightings are given for a fixed patient thickness, not accounting for the real patient anatomy with different thicknesses. This can mainly be attributed to the high SSD at which the patient is treated. The dosimetric results demonstrate that arc TBI plans can be achieved with clinically acceptable quality and that they can be delivered with a flatness of 9% for patients with a thickness of up to 30 cm which we would suggest as the upper limit for patient thickness when the reported technique is applied. In our series of 22 patients, this thickness has not been exceeded. No special planning systems, no additional new basic data had to be measured and no inverse methods had to be used. The technique is not vendor specific and it can be implemented on any modern accelerator with flattening filter and rotational therapy option. Future improvements will include the varying patient thickness in the theoretical model. This would increase the homogeneity but at the same time would be less robust against misalignments. It might be possible to decrease the treatment time by using larger beam openings and potentially flattening filter free accelerators, within the limits of clinically acceptable instantaneous dose rates. In summary, arc therapy is a convenient method for total body irradiation. Conflict of interest None. Acknowledgment A research grant by Elekta, Inc. funded part of this work. References [1] Bruno B, Rotta M, Patriarca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 2007;356:1110–20. [2] Stein A, Forman SJ. Allogeneic transplantation for ALL in adults. Bone Marrow Transplant 2008;41:439–46. [3] Appelbaum FR. The influence of total dose, fractionation, dose rate, and distribution of total body irradiation on bone marrow transplantation. Semin Oncol 1993;20:3–10.
A. Jahnke et al. / Radiotherapy and Oncology 110 (2014) 553–557 [4] Gilson D, Taylor RE. Total body irradiation. Report on a meeting organized by the BIR Oncology Committee, held at The Royal Institute of British Architects, London, 28 November 1996. Br J Radiol 1997;70:1201–3. [5] Sampath S, Schultheiss TE, Wong J. Dose response and factors related to interstitial pneumonitis after bone marrow transplant. Int J Radiat Oncol Biol Phys 2005;63:876–84. [6] Lohr F, Wenz F, Schraube P, et al. Lethal pulmonary toxicity after autologous bone marrow transplantation/peripheral blood stem cell transplantation for hematological malignancies. Radiother Oncol 1998;48:45–51. [7] Onal C, Sonmez A, Arslan G, Sonmez S, Efe E, Oymak E. Evaluation of field-infield technique for total body irradiation. Int J Radiat Oncol Biol Phys 2012;83:1641–8. [8] Yao R, Bernard D, Turian J, et al. A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity. Med Phys 2012;39: 2239–48. [9] Hui SK, Das RK, Thomadsen B, Henderson D. CT-based analysis of dose homogeneity in total body irradiation using lateral beam. J Appl Clin Med Phys 2004;5:71–9. [10] Quast U. Total body irradiation – review of treatment techniques in Europe. Radiother Oncol 1987;9:91–106. [11] Quast U. Physical treatment planning of total-body irradiation: patient translation and beam-zone method. Med Phys 1985;12:567–74. [12] Gerig LH, Szanto J, Bichay T, Genest P. A translating-bed technique for totalbody irradiation. Phys Med Biol 1994;39:19–35. [13] Sarfaraz M, Yu C, Chen DJ, Der L. A translational couch technique for total body irradiation. J Appl Clin Med Phys 2001;2:201–9. [14] Umek B, Zwitter M, Habic H. Total body irradiation with translation method. Radiother Oncol 1996;38:253–5. [15] Van Dyk J, Galvin JM, Glasgow GW, Podgorsak E, AAPM report No. 17. The physical aspects of total and half body photon irradiation; 1986. [16] Abraham D, Colussi V, Shina D, Kinsella T, Sibata C. TBI treatment planning using the ADAC pinnacle treatment planning system. Med Dosim 2000;25: 219–24. [17] Han C, Schultheisss TE, Wong JYC. Dosimetric study of volumetric modulated arc therapy fields for total marrow irradiation. Radiother Oncol 2012;102: 315–20.
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[18] Penagaricano JA, Chao M, Van Rhee F, Moros EG, Corry PM, Ratanatharathorn V. Clinical feasibility of TBI with helical tomotherapy. Bone Marrow Transplant 2011;46:929–35. [19] Gruen A, Ebell W, Wlodarczyk W, et al. Total Body Irradiation (TBI) using helical tomotherapy in children and young adults undergoing stem cell transplantation. Radiat Oncol 2013;8:92. [20] Wong JY, Rosenthal J, Liu A, Schultheiss T, Forman S, Somlo G. Image-guided total-marrow irradiation using helical tomotherapy in patients with multiple myeloma and acute leukemia undergoing hematopoietic cell transplantation. Int J Radiat Oncol Biol Phys 2009;73:273–9. [21] Mangili P, Fiorino C, Rosso A, et al. In-vivo dosimetry by diode semiconductors in combination with portal films during TBI: reporting a 5-year clinical experience. Radiother Oncol 1999;52:269–76. [22] Ribas M, Jornet N, Eudaldo T, et al. Midplane dose determination during total body irradiation using in vivo dosimetry. Radiother Oncol 1998;49:91–8. [23] Jornet N, Ribas M, Eudaldo T. Calibration of semiconductor detectors for dose assessment in total body irradiation. Radiother Oncol 1996;38:247–51. [24] Fleckenstein J, Jahnke L, Lohr F, Wenz F, Hesser J. Development of a Geant4 based Monte Carlo Algorithm to evaluate the MONACO VMAT treatment accuracy. Z Med Phys 2013;23:33–45. [25] Menegotti L, Delana A, Martignano A. Radiochromic film dosimetry with flatbed scanners: a fast and accurate method for dose calibration and uniformity correction with single film exposure. Med Phys 2008;35:3078–85. [26] Quast U, Sack H, et al. DGMP-Bericht Nr. 18: Ganzkörper-Strahlenbehandlung; 2003. [27] Surucu M, Yeginer M, Kavak GO, Fan J, Radosevich JA, Aydogan B. Verification of dose distribution for volumetric modulated arc therapy total marrow irradiation in a humanlike phantom. Med Phys 2012;39:281–8. [28] Kirby N, Held M, Morin O, Fogh S, Pouliot J. Inverse-planned modulated-arc total-body irradiation. Med Phys 2012;39:2761–4. [29] Zhuang T, Wu Q. Generating arbitrary one-dimensional dose profiles using rotational therapy. Phys Med Biol 2010;55:6263–77.
Contents lists available at ScienceDirect
Radiotherapy and Oncology journal homepage: www.thegreenjournal.com
TBI arc therapy
Arc therapy for total body irradiation – A robust novel treatment technique for standard treatment rooms Anika Jahnke a,b,⇑, Lennart Jahnke b, Flavia Molina-Duran a,b, Michael Ehmann b, Steffi Kantz c, Volker Steil b, Frederik Wenz b, Gerhard Glatting a, Frank Lohr b, Martin Polednik b a Medical Radiation Physics/Radiation Protection; b Department of Radiation Oncology, Universitätsmedizin Mannheim, Heidelberg University, Mannheim; and c Department of Radiation Oncology, Klinikum der Ludwig-Maximilians-Unversität München, Germany
a r t i c l e
i n f o
Article history: Received 1 July 2013 Received in revised form 5 November 2013 Accepted 15 December 2013 Available online 16 January 2014 Keywords: Total body irradiation TBI Arc therapy
a b s t r a c t Background and purpose: We developed a simple and robust total body irradiation (TBI) method for standard treatment rooms that obviates the need for patient translation devices. Methods and materials: Two generic arcs with rectangular segments for a patient thickness of 16 and 20 cm (arc16/arc20) were generated. An analytical fit was performed to determine the weights of the arc segments depending on patient thickness and gantry angle. Stability and absolute dose for both arcs were measured using EBT3 films in a range of solid water slab phantom thicknesses. Additionally ionization chamber measurements were performed every 10 cm at a source surface distance (SSD) of 200 cm. Results: The measured standard deviation for arc16 is ±3% with a flatness 69.0%. Arc20 had a standard deviation of ±3% with a flatness 67.3% for all measured thicknesses. The theoretical curves proved to be accurate for the prediction of the segment weightings for the two arcs. In vivo measurements for the first 22 clinical patients showed a dose deviation of less than 3%. Conclusions: Arc therapy is a convenient and stable method for TBI. This cost-effective approach has been introduced clinically, obviating the need for field patches and to physically move the patient. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 110 (2014) 553–557
For decades, total body irradiation (TBI) has successfully been part of an interdisciplinary treatment regimen for ‘‘conditioning’’ of patients undergoing bone marrow transplantation for leukemia and lymphoma. The purpose of conditioning is to suppress the immune system to allow engraftment of donor cells, to kill malignant cells and to eradicate cell populations with genetic disorders [1,2]. TBI has been used in conjunction with chemotherapy as a conditioning regimen, for bone marrow transplantation or peripheral blood stem cell transplantation [3,4]. The challenge in TBI is the creation of a relatively uniform dose distribution along all of the patient’s body, therefore necessitating the use of large treatment fields and extended SSD. Two additional dosimetric challenges are different anatomical thicknesses of the patient and the introduction of local dose inhomogeneities to spare critical organs. The predominant critical organ is the lung, which is at risk of developing pneumonitis as a serious, potentially lethal side effect [5,6]. TBI techniques typically comprise a combination of various opposing field setups in a sitting or lying patient position at very ⇑ Corresponding author. Address: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer Ufer 1–3, 68167 Mannheim, Germany. E-mail address: [email protected] (A. Jahnke). 0167-8140/$ - see front matter Ó 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.radonc.2013.12.009
extended SSDs [7–10]. Another technique utilizes a translation couch, where the patient is moved through the field at a constant speed at SSD 200 cm [11–14]. A modification of this approach is the ‘‘sweeping-field’’ technique, where the patient lies on the floor at a distance of 200 cm to the accelerator head and the gantry is sweeping over him. The dosimetric requirements for TBI are described in the AAPM report 17 [15] which defines a prescription point and recommends a dose homogeneity within ±10%. Conventional treatment planning systems (TPS) have been extensively used to optimize TBI/TMI plans [16,17]. We propose a treatment technique that has been implemented clinically and provides optimal dose homogeneity without extra resources in standard treatment rooms, based on the arc paradigm and present first measurements for 22 clinically treated patients.
Materials and methods Patient setup and clinical treatment technique A total body CT of the patient is taken in prone and supine position two weeks before treatment to assess patient thickness and to provide a basis for contouring of lung blocks for patients that are to receive a total dose of >8 Gy. Clinical delivery is performed twice daily with 2 Gy per fraction. Total dose ranges between 4–12 Gy,
554
Arc therapy for total body irradiation
delivered in 2–6 fractions on the morning and evening of 1–3 consecutive days with at least 7 h in between the fractions. The patient is treated with two arcs, one in supine and one in prone position, with a source to couch distance of 219 cm. For the alignment point the belly button directly below the isocenter was chosen. To provide optimal skin coverage, a buildup ‘‘spoiler’’ plate is introduced between the accelerator head and the patient. The spoiler consists of 1 cm transparent polycarbonate screen and can be adjusted in height between 29 and 49 cm from the couch surface approximately 20 cm above the patient. Fig. 1 depicts the whole treatment setup. To limit the lung dose below 10 Gy, specially manufactured lung blocks were positioned directly on the patient’s skin. They consist of stacked lead (Pb) plates cut to the desired shape of the individual patient. Prior to treatment the position of the lung blocks is verified by digitally readable and X-ray sensitive film cassettes. When designing the blocks the divergence of the beam including its movement component is taken into account and the isocenter was set to the lower end of the lungs to reduce dose blurring caused by the arc delivery. For 12 Gy prescription dose and 18 cm phantom thickness a required thickness of 12 mm was found corresponding to 12 plates. For 10 Gy prescription 8 mm lead plates are used. The lead thickness was determined by measurements with an inhomogeneous lung phantom and therefore took into account the inhomogeneity of the lung. This resulted in a dose reduction to a maximum of 8–9 Gy midline dose in the lungs. The maximum dose rate in the middle of the body is about 100 cGy/min and in the lung, under the lung blocks, between 60 and 80 cGy/min. Even for single dose/hypofractionated TBI, Sampath et al. [5] could not detect a dose rate effect in treatment series with dose rates up to 41 cGy/min. Recently, three clinical TMI/TBI tomotherapy manuscripts reported the successful use of dose rates 100 cGy/min [18–20]. Before the first treatment of a new patient, the arc is calibrated for absolute dose. During patient treatment, in vivo dosimetry is performed with one in vivo ion chamber and nine semi-conductor detectors (T60010MP, T60010RO, PTW, Freiburg, DE). Diodes are an established tool for in vivo dosimetry [21–23]. Calibration for the diodes is done during the QA measurements. Standard detector positions are head, neck, lung, blocks, isocenter, chest and abdomen.
Development of a theoretical model for arc TBI The basic condition was one arc between gantry angles of 320° and 60° with 10 40 cm field size with a homogeneous dose area that extends over a length of 200 cm. In addition the arc was then
split into ten segments which were weighted according to their gantry angle (see Table 1). The weighted MUs per degree can be fitted using a straight forward approach from the inverse square law and the known polystyrene (RW3, slab phantom material) and polycarbonate (MakrolonÒ, spoiler material) attenuation coefficients. This provides a starting point and thus reduces measurement steps necessary for individual patient thicknesses. The relative weighting factors can be obtained by the ratio of the radiation intensities at 0° segment to the radiation intensity at angle a Þ . segment wf ðaÞ ¼ Ið0 IðaÞ The attenuation coefficients were determined with an energy spectrum obtained by Monte Carlo simulations [24] from an Elekta SynergyÒ 6 MV beam. They were calculated as lp 0.0707 cm1 for RW3 and ls 0.0797 cm1 for MakrolonÒ. The other relevant parameters are of geometrical nature. The functions p(a) and s(a) are the distances the beam has to travel through the phantom and the spoiler, respectively. The initial intensity is I0 and the radii at gantry angle 0° and gantry angle a are r(0) and r(a).
wf ðaÞ ¼
I0 rð0Þ2 I0 rðaÞ2
eðlp pð0ÞÞ eðls sð0ÞÞ eðlp pðaÞÞ eðls sðaÞÞ
ð1Þ
For the inverse square law the distances to the plane with the flat profile have to be known. Here the variable dI denotes the distance from source to isocenter and is fixed to 100 cm, dIPC is the distance from isocenter to the center of the phantom, s0 is the thickness of the spoiler and p0 is half the phantom thickness. The angle alpha denotes the gantry angle of a given segment. In Eq. p0 s0 (2) sðaÞ ¼ cos a and pðaÞ ¼ cos a have been inserted. Using simple geometric arguments, it can be shown that r(0) = dI + dIPC and dIPC rðaÞ ¼ dI þ cos a which has been used in the final Eq. (2).
wf ðaÞ ¼
2 dIPC dI þ cos a 2
ðdI þ dIPC Þ
1 1 eðlp p0 ð1cos aÞÞ eðls s0 ð1cos aÞÞ
ð2Þ
Using this formula, a starting point has been determined for arcs with larger or smaller phantom thicknesses. The calculated arc always needs to be experimentally verified since only relative and no absolute dosimetry is included in the equation. Dose verification measurements To get a DICOM compliant plan the tel.file of MONACOÒ v2.04 (Elekta, Crawley, UK) was modified with the theoretical segment weightings. Two reference measurements for a patient thickness of 16 and 20 cm (arc16 and arc20) were performed using an ionization chamber which was positioned at a depth of 8 and 10 cm, respectively, in a solid water slab phantom (30 90 16/ 20 cm3) with the spoiler in place. The phantom consisted of three stacks with the measurement chamber in the middle in order to simulate patient scatter. Moving the phantom across the irradiation field of the two arcs a measurement point was acquired every Table 1 Normalized weighting factors for each segment for arc16 and arc20.
Fig. 1. Patient setup.
Segment number
Angle (°)
1 2 3 4 5 6 7 8 9 10
320–330 330–340 340–350 350–10 10–20 20–30 30–40 40–50 50–55 55–60
Normalized weighting factor Arc16 (MU/°)
Arc20 (MU/°)
1.424 1.184 1.060 1.000 1.060 1.184 1.424 1.907 2.645 3.562
1.464 1.199 1.065 1.000 1.065 1.199 1.464 2.008 2.869 3.562
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10 cm. The total MUs were rescaled to deliver 1 Gy at the reference point (below the isocenter) at 8 and 10 cm depths respectively. Additionally, absolute film measurements using GafchromicÒ EBT3 films were performed. The films were cut into narrow stripes and were positioned for the arc16 at a depth of 2, 8 and 14 cm and for arc20 at a depth of 2, 10 and 18 cm depth. A total length of 240 cm ranging from 150 to 90 cm (with 0 cm being the isocenter) was measured to cover at least part of the dose fall off on one side. The films were scanned using an Epson Expression 10000XL flatbed scanner and calibrated with a multiple point calibration curve and an off axis correction [25] for the peripheral parts of the film. To reduce the noise of the film measurements the mean value of the central 1 cm of each film was analyzed. Finally, as a patient specific QA method, a slab phantom resembling the patient anatomy was built with RW3 slabs and cork plates which emulated lung tissue. In order to determine the phantom thickness the anterior–posterior dimensions of the prone and supine CT were averaged. The dose was measured in 6 different points (head, neck, chest, abdomen, upper leg, lower leg) in the middle of the phantom.
Results The total beam on time was approximately 18 min. The MU weightings for arc16 and arc20 are shown in Table 1. The last segment of arc20 was artificially weighted lower to avoid over dosage
of the feet. Fig. 2(a) demonstrates the flatness (F = (Dmax Dmin)/ (Dmin + Dmax) 100) of arc16 irradiated on the 14 cm phantom. Moreover the results for arc20 irradiated on the 22 cm phantom are depicted in Fig. 2(b). Finally, the reference ionization chamber measurements and the film measurements for the profiles are depicted in Fig. 2(c) and (d). To validate the robustness for different phantom thicknesses, film measurements for 14, 16 and 18 cm thickness for the arc16 as well as measurements for 18, 20, 22 and 24 cm thickness for the arc20 are shown in Table 2. To obtain meaningful results only the central 200 cm were analyzed to determine the statistical values. The standard deviation of the 16 cm arc irradiated on a 14 cm phantom is 3% and therefore the same as for the intended thickness. For arc20, no more than 3% standard deviation was measured for the additional thicknesses. The flatness was acceptable (below 10%) for all given thicknesses. Especially the flatness near the patient surface can only be evaluated by adding up the shallower and the lower film result which is shown in the last columns of Table 2. A measured combined depth dose curve in anterior–posterior and posterior–anterior direction for 30 cm phantom thickness showed a maximum deviation of 9.9 % to the reference point in 15 cm depth. We would therefore suggest a patient thickness of 30 cm as the maximum acceptable thickness for the described technique. In Table 3 patient specific QA results are shown for arc16 and arc20. For these measurements the lung dose is acquired with 12 mm lead plates on the top. All measured doses are within 1.2
1.2
b
1.0
1.0
0.8
0.8
dose [Gy]
dose [Gy]
a
0.6
0.4
0.4
ionization chamber film
ionization chamber film
0.2
0.2
0.0 -150
0.6
-100
-50
0
50
0.0 -150
100
-100
-50
0
50
100
length [cm]
length [cm] 2.0
c
1.5
d
1.0
dose [Gy]
dose [Gy]
1.5
1.0
0.5 0.5
depth 2cm depth 7cm depth 12cm 0.0 -150
-100
-50
length [cm]
0
50
100
0.0 -150
depth 2cm depth 11cm depth 20cm -100
-50
0
50
100
length [cm]
Fig. 2. Measured profiles for different arcs and patient thicknesses with film and ionization chamber (a) film and ionization chamber profiles for arc16 in a 16 cm phantom at a depth of 8 cm, (b) film and ionization chamber profiles for arc20 in a 20 cm phantom at a depth of 10 cm, (c) film profiles for arc16 in 14 cm phantom at a depth of 2, 7 and 12 cm, (d) film profiles for arc20 in a 22 cm phantom at a depth of 2, 11 and 20 cm.
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Arc therapy for total body irradiation
Table 2 Absolute dose and flatness for arc16 and arc20 for different phantom thicknesses in the phantom center measured with film and ionization chamber. The last two columns show the summarized results from the entrance (2 cm from the top of the phantom) and exit (2 cm from the bottom of the phantom) film profiles. Arc
Phantom diameter (cm)
MU
Ionization chamber dose (Gy)
Film in phantom center
Film (entrance + exit)/2
Mean dose (Gy)
Flatness (%)
Mean dose (Gy)
Flatness (%)
16
14 16 18
5884
1.01 1.00 0.99
1.02 ± 0.03 1.01 ± 0.03 0.97 ± 0.03
8.4 8.8 9.0
1.04 ± 0.02 1.05 ± 0.02 1.03 ± 0.02
6.2 6.5 5.2
20
18 20 22 24
6250
1.02 1.00 0.99 0.98
1.05 ± 0.02 1.02 ± 0.02 1.01 ± 0.02 0.97 ± 0.03
6.7 7.2 5.3 7.3
1.08 ± 0.04 1.08 ± 0.04 1.09 ± 0.05 –
9.6 9.1 8.4 –
Table 3 Dose measurements for different phantom sizes and arcs with variable thicknesses measured in the middle of the phantom for 6 different positions. Head
Neck
Chest with 12 mm blocks
Abdomen
Upper leg
Lower leg
Arc 16 for ø 18 cm Thickness (cm) Dose (Gy)
15 0.96
11 1.03
18 0.68
18 1.0
12 1.04
9 1.07
Arc 20 for ø 22 cm Thickness (cm) Dose (Gy)
16 1.04
14 1.05
24 0.69
22 1.0
17 1.03
12 1.10
±10% except the intentionally blocked lung which received around 70% of the prescribed 12 Gy. To date, 22 patients have been treated with this technique. In vivo dosimetry was performed as required by the German technical guideline for TBI [26]. Within this framework, for two female patients in vivo intra-vaginal measurements were carried out and showed a deviation from calculated midbody doses of less than 3%. For all patients the mean exit doses measured daily with an in vivo ionization chamber was within 3% of the predicted exit dose. Discussion TBI has proven to be an important element of the conditioning process before bone marrow or peripheral blood stem cell transplantation. However, long treatment times and the need for meticulous setup and dosimetry to yield delivery with optimal dose homogeneity throughout the body can put a considerable strain on departmental resources. The application of TBI is also limited by local constraints such as small treatment rooms that do not offer the possibility to treat with one field at extended SSDs. Originally the problem was solved by fixed treatment beams [8]. Translational treatment couches that move the patient through a fixed treatment beam have offered another solution to this problem, further improving on dose homogeneity. More advanced techniques include Rapid Arc dose distributions for total marrow irradiation (TMI) [27] and an inverse planned modulated arc TBI method [28]. The VMAT fixed jaw opening method was first theoretically described by [29] with an optimizer for a rotating gantry with fixed patient position. Shortcomings of the reported methods are that field gaps, large treatment rooms or moving couches are needed. This is not the case in the fixed field size arc TBI approach as described in this report. Furthermore this solution proves that segment weighting optimization is unnecessary. Rather than optimizing weightings, an analytical approach to segment weightings is given. Out of the measurements one can conclude that the robustness toward changes in thickness is remarkable whereas the insensitivity toward patient misalignment cranial caudal and left right is due to
the open field approach. A limitation is that the calculated weightings are given for a fixed patient thickness, not accounting for the real patient anatomy with different thicknesses. This can mainly be attributed to the high SSD at which the patient is treated. The dosimetric results demonstrate that arc TBI plans can be achieved with clinically acceptable quality and that they can be delivered with a flatness of 9% for patients with a thickness of up to 30 cm which we would suggest as the upper limit for patient thickness when the reported technique is applied. In our series of 22 patients, this thickness has not been exceeded. No special planning systems, no additional new basic data had to be measured and no inverse methods had to be used. The technique is not vendor specific and it can be implemented on any modern accelerator with flattening filter and rotational therapy option. Future improvements will include the varying patient thickness in the theoretical model. This would increase the homogeneity but at the same time would be less robust against misalignments. It might be possible to decrease the treatment time by using larger beam openings and potentially flattening filter free accelerators, within the limits of clinically acceptable instantaneous dose rates. In summary, arc therapy is a convenient method for total body irradiation. Conflict of interest None. Acknowledgment A research grant by Elekta, Inc. funded part of this work. References [1] Bruno B, Rotta M, Patriarca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 2007;356:1110–20. [2] Stein A, Forman SJ. Allogeneic transplantation for ALL in adults. Bone Marrow Transplant 2008;41:439–46. [3] Appelbaum FR. The influence of total dose, fractionation, dose rate, and distribution of total body irradiation on bone marrow transplantation. Semin Oncol 1993;20:3–10.
A. Jahnke et al. / Radiotherapy and Oncology 110 (2014) 553–557 [4] Gilson D, Taylor RE. Total body irradiation. Report on a meeting organized by the BIR Oncology Committee, held at The Royal Institute of British Architects, London, 28 November 1996. Br J Radiol 1997;70:1201–3. [5] Sampath S, Schultheiss TE, Wong J. Dose response and factors related to interstitial pneumonitis after bone marrow transplant. Int J Radiat Oncol Biol Phys 2005;63:876–84. [6] Lohr F, Wenz F, Schraube P, et al. Lethal pulmonary toxicity after autologous bone marrow transplantation/peripheral blood stem cell transplantation for hematological malignancies. Radiother Oncol 1998;48:45–51. [7] Onal C, Sonmez A, Arslan G, Sonmez S, Efe E, Oymak E. Evaluation of field-infield technique for total body irradiation. Int J Radiat Oncol Biol Phys 2012;83:1641–8. [8] Yao R, Bernard D, Turian J, et al. A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity. Med Phys 2012;39: 2239–48. [9] Hui SK, Das RK, Thomadsen B, Henderson D. CT-based analysis of dose homogeneity in total body irradiation using lateral beam. J Appl Clin Med Phys 2004;5:71–9. [10] Quast U. Total body irradiation – review of treatment techniques in Europe. Radiother Oncol 1987;9:91–106. [11] Quast U. Physical treatment planning of total-body irradiation: patient translation and beam-zone method. Med Phys 1985;12:567–74. [12] Gerig LH, Szanto J, Bichay T, Genest P. A translating-bed technique for totalbody irradiation. Phys Med Biol 1994;39:19–35. [13] Sarfaraz M, Yu C, Chen DJ, Der L. A translational couch technique for total body irradiation. J Appl Clin Med Phys 2001;2:201–9. [14] Umek B, Zwitter M, Habic H. Total body irradiation with translation method. Radiother Oncol 1996;38:253–5. [15] Van Dyk J, Galvin JM, Glasgow GW, Podgorsak E, AAPM report No. 17. The physical aspects of total and half body photon irradiation; 1986. [16] Abraham D, Colussi V, Shina D, Kinsella T, Sibata C. TBI treatment planning using the ADAC pinnacle treatment planning system. Med Dosim 2000;25: 219–24. [17] Han C, Schultheisss TE, Wong JYC. Dosimetric study of volumetric modulated arc therapy fields for total marrow irradiation. Radiother Oncol 2012;102: 315–20.
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[18] Penagaricano JA, Chao M, Van Rhee F, Moros EG, Corry PM, Ratanatharathorn V. Clinical feasibility of TBI with helical tomotherapy. Bone Marrow Transplant 2011;46:929–35. [19] Gruen A, Ebell W, Wlodarczyk W, et al. Total Body Irradiation (TBI) using helical tomotherapy in children and young adults undergoing stem cell transplantation. Radiat Oncol 2013;8:92. [20] Wong JY, Rosenthal J, Liu A, Schultheiss T, Forman S, Somlo G. Image-guided total-marrow irradiation using helical tomotherapy in patients with multiple myeloma and acute leukemia undergoing hematopoietic cell transplantation. Int J Radiat Oncol Biol Phys 2009;73:273–9. [21] Mangili P, Fiorino C, Rosso A, et al. In-vivo dosimetry by diode semiconductors in combination with portal films during TBI: reporting a 5-year clinical experience. Radiother Oncol 1999;52:269–76. [22] Ribas M, Jornet N, Eudaldo T, et al. Midplane dose determination during total body irradiation using in vivo dosimetry. Radiother Oncol 1998;49:91–8. [23] Jornet N, Ribas M, Eudaldo T. Calibration of semiconductor detectors for dose assessment in total body irradiation. Radiother Oncol 1996;38:247–51. [24] Fleckenstein J, Jahnke L, Lohr F, Wenz F, Hesser J. Development of a Geant4 based Monte Carlo Algorithm to evaluate the MONACO VMAT treatment accuracy. Z Med Phys 2013;23:33–45. [25] Menegotti L, Delana A, Martignano A. Radiochromic film dosimetry with flatbed scanners: a fast and accurate method for dose calibration and uniformity correction with single film exposure. Med Phys 2008;35:3078–85. [26] Quast U, Sack H, et al. DGMP-Bericht Nr. 18: Ganzkörper-Strahlenbehandlung; 2003. [27] Surucu M, Yeginer M, Kavak GO, Fan J, Radosevich JA, Aydogan B. Verification of dose distribution for volumetric modulated arc therapy total marrow irradiation in a humanlike phantom. Med Phys 2012;39:281–8. [28] Kirby N, Held M, Morin O, Fogh S, Pouliot J. Inverse-planned modulated-arc total-body irradiation. Med Phys 2012;39:2761–4. [29] Zhuang T, Wu Q. Generating arbitrary one-dimensional dose profiles using rotational therapy. Phys Med Biol 2010;55:6263–77.