university of wisconsin-madison

UNIVERSITY OF WISCONSIN-MADISON
TomoTherapy total skin treatment for mycosis fungoides
Mark Geurts, MS DABR CQE; Adam Bayliss, PhD DABR; Bishnu Thapa, PhD; Geoff Nelson, PhD, UW Carbone Cancer Center
T
otal Skin Electron Therapy (TSET, or TSEBT) is considered a primary treatment for late stage (T3) or early stage (T1-2) refractory skin-directed/systemic/combination therapy mycosis fungoides1. The American Association of Physicists in Medicine Task Group 30 provides a thorough review of the history and various implementations of total skin electron therapy 2.
The University of Wisconsin Carbone Cancer Center uses a six dual-field modified Stanford
technique3,4 for total skin treatments. There exists several challenges when performing TSET. The Stanford technique requires the patient to remain still in challenging positions for the duration of treatment,
which can be on the order of 30 minutes or longer depending on positioning, source distance, and accelerator dose rate. Although some authors have proposed techniques that allow the patient to lie down5,6
rather than stand, comfort is still a limitation to improving dosimetry. Extra time is also required to set
up and take down the electron degrader. The use of overlapping electron fields causes dose variations
around 10% for even simple circular phantoms2, with upwards of ±15% when considering self-shielding
and patient motion7. Additionally, treatment of the primary fields is split over two days (three dual fields
per day) with additional follow up “patch” fields to treat areas missed by the primary fields, including
the perineum and scalp apex. This can cause treatments to extend for over two months.
A new set of TLDs and film were placed in the anthropomorphic phantom in the same locations as before. The phantom was then reassembled and set up on a conventional accelerator according to the commissioned TSET protocol. All twelve electron fields were delivered three times to simulate three 2.0 Gy fractions. The TLDs and film were then removed and processed.
Using the phantom MVCT image, the effects of positioning uncertainty were investigated. The
MVCT was loaded into the TomoTherapy Planned Adaptive™ (version 5.0) software. Then, the
phantom was intentionally offset by 0, 5, 10, 15, and 20 mm along IEC-x. For each non-zero offset, the planned dose was re-calculated on the phantom MVCT and compared to the 0 mm dose.
Patient Measurements
Finally, a treatment plan was developed for a patient with Stage IIIB chemotherapy refractory mycosis fungoides. For planning simulation, the patient was immobilized using a full body Vac-Lok
bag, head first supine, arms at sides. The plan was optimized to deliver 3000 cGy in 20 fractions to
90% of the 7.0 mm internal rind target volume. Additional PTVs were generated to deliver 3000
cGy to positive inguinal and axillary nodal chains. The 1 cm external flash rind was also prescribed
to 3000 cGy. A complete block was generated by contracting the Skin PTV by 5.0 cm. A 5.0 cm
fixed field was used with a pitch and planning modulation factor of 0.215 and 3.0, respectively.
The patient’s bones, brain, heart, liver, lungs, and kidneys were contoured and constrained to reduce the dose as low as possible.
Helical tomotherapy radiation delivery offers several potential advantages for total skin treatment. First,
the patient can be positioned comfortably (supine, arms at side) for treatment. Also, no additional equipment is required to set up and take down. If the patient is 160 cm or shorter, the treatment can be delivered in a single position, with the entire skin surface receiving treatment each day. Finally, the plan is
optimized based on the patient anatomy, offering the potential to reduce dosimetric variability. The application of helical tomotherapy to superficial treatments has been investigated by a number of authors812
. In addition, several centers have reported on their success using the TomoTherapy ® Treatment System (Accuray Incorporated, Sunnyvale, CA) to deliver total skin treatments 13,14,15 using different techniques. Leveraging this data, we developed a treatment protocol for TomoTherapy-based total skin treatment and conducted a series of tests to compare the dosimetry and feasibility achievable using this protocol to our existing modified Stanford electron-based technique. To determine feasibility, several requirements were established, described below.
Following optimization, IMRT quality assurance using an in-house protocol in which the treatment
is delivered with the couch out of the bore, the exit detector response is exported, and the measured
leaf open times are compared to the actual leaf open times. The planned dose was then reconstructed using the measured leaf open times and compared to the optimized plan using a 3%/3 mm global
gamma analysis19.
Prior to the first treatment, a new set of TLDs were placed on the patient’s skin and
gown. Following treatment, the TLDs were removed, processed, and compared to the
planned fraction dose at each TLD location. Unfortunately, the patient was in too
much pain to be able to complete the treatment in one sitting, so the TLDs placed on
the feet were not irradiated. These TLDs were removed from analysis. A set of calibration TLDs from the same batch were irradiated to 100 cGy, 200 cGy, and 300 cGy
and used to determine absolute dose. In addition to comparing planned to measured
dose, the posterior TLD measurements that were between the Vac-Lok and patient
were compared to the anterior TLD measurements to determine if the presence of the
Vac-Lok yielded any significant change in measured dose. The two groups were
compared using a Kolmogorov-Smirnov test.
First, the treatment planning system must be able to achieve at least 90% prescription dose coverage to
the planning target volume, defined as the 7 mm “rind” below the skin surface. This prescription depth
was chosen to treat thick plaques in accordance with the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group16, and also to be similar to the effective
R50 for the six dual-field TSET technique reported by AAPM Task Group 302. The maximum planned
dose should be less than 120% of the prescribed dose. In addition, the total immobilized treatment time
goal was 60 minutes (image guidance acquisition, registration, and treatment delivery) or less so as to
make the protocol logistically feasible on two already busy TomoTherapy systems.
Next, the depth dose characteristics, measured using phantoms, must match the planned dose distribution
and be similar to that achievable using TSET. As discussed in more detail under Methods, this requirement is evaluated in the superficial (< 1 mm), penumbra (5-20 mm), and deep tissue (~10 cm) regions.
Finally, Thermo-Luminescent Dosimeters (TLDs) are employed to measure the dose for all TSET patients at the University of Wisconsin. Therefore, using a similar TLD arrangement, the difference between measured and expected dose using total skin helical tomotherapy must be less than or equivalent to results achieved using TSET, as well as results published by other leading institutions17,18.
METHODS
Simulation CT datasets were acquired for a 30 cm diameter cylindrical phantom (TomoPhantom) and an anthropomorphic phantom.
The anthropomorphic phantom was immobilized by taping the phantom sections tightly together and lying the phantom down in a VacLok™ bag (CIVCO Medical Solutions, Coralville, IA). TLDs and Gafchromic® EBT3 film (Ashland Incorporated, Covington, KY)
were placed within the phantom prior to simulation to make phantom setup on the TomoTherapy treatment system as reproducible as
possible. In addition, TLDs were placed along the front, back, and sides of the phantom, as well as inside the phantom within the brain,
bones, and lungs. For all experiments, the film was scanned at 24 hours post-exposure using an Epson® 10000XL scanner (Seiko Epson
Corporation, Long Beach, CA) in transparency mode, 16-bit color, without image correction, and processed using FilmQA™ Pro version
3.0.4777.36538 (Ashland Incorporated, Covington, KY).
RESULTS
Results have been separated into the following three categories based on how they were acquired: using the TomoPhantom (film), anthropomorphic phantom (film and TLD), and patient (TLD). For the TomoPhantom and anthropomorphic phantom measurements, the
TomoTherapy and conventional TSET results are compared.
TomoPhantom Measurements
Superficial dose was evaluated by comparing the four layers of film
along the outside of the phantom. For each film, a region of interest
of approximately 2.0 cm2 was generated using FilmQA Pro. The
mean dose and standard deviation using the red channel were 112.8 ±
4.1 cGy, 128.6 ± 3.7 cGy, 136.4 ± 3.1 cGy, 144.5 ± 3.9 cGy for approximate depths 140 µm, 420 µm, 700 µm, and 980 µm, respectively. Target depth dose and penumbra were evaluated using the film
placed along the radius of the phantom. A red channel line profile was
extracted along the center of the depth dose films using FilmQA Pro.
Next, Gafchromic EBT3 film was placed between the two halves of the TomoPhantom such that the edge of the film was flush with the
external surface of the phantom. In this orientation, the film could be used to measure a depth dose profile. As well, four films were
layered around one side of the phantom. Since each film is nominally 280 mm thick, with the active layer at approximately 125-155
mm depth, the films would measure the dose along the cylindrical surface at 140, 420, 700, and 980 mm depths, respectively. The phantom was placed on the treatment couch, aligned, imaged, registered, and irradiated.
Following measurement, new film was inserted between the phantom halves in the same manner as before. This time, the phantom was
set up according to the commissioned TSET protocol on a conventional C-arm linear accelerator, at 300 cm source to treatment plane
distance with a 1.0 cm thick sheet of acrylic placed 10 cm in front of the phantom to act as an electron degrader and spoiler. The phantom was then irradiated to 150 cGy.
TomoTherapy Measured (Diff)
TSET Measured
Surface
15
566.2 ± 40.8 cGy (-1.9 ± 3.8%)
614.6 ± 150.6 cGy
Brain
3
137.3 ± 7.1 cGy (2.8 ± 6.8%)
35.3 ± 0.1 cGy
Lungs
4
142.5 ± 3.4 cGy (17.2 ± 4.8%)
34.1 ± 0.2 cGy
Pelvic Bones/Femurs 5
165.1 ± 72.8 cGy (5.4 ± 13.9%)
35.3 ± 4.1 cGy
Ribs
4
358.7 ± 43.5 cGy (-2.8 ± 2.4%)
35.1 ± 2.1 cGy
Cervical Vertebrae
4
142.1 ± 5.7 cGy (17.2 ± 5.6%)
34.6 ± 0.5 cGy
Thoracic Vertebrae
7
143.0 ± 8.9 cGy (17.2 ± 2.7%)
33.5 ± 0.6 cGy
Lumbar Vertebrae
3
129.9 ± 3.2 cGy (18.3 ± 1.2%)
33.2 ± 0.1 cGy
Finally, the maximum and minimum deviations at the
surface in the target volume of the phantom when
shifted laterally relative to the planned position were
evaluated, as predicted by the TomoTherapy Planned
Adaptive software. The maximum deviations were
6.5%, 9.5%, 11.0%, and 17.5% for 5, 10, 15, and 20
mm offsets, respectively, and occurred on the side of
the phantom placed further from isocenter relative to
the planned position. The minimum deviations occurred on the side closer to isocenter and were -4.0%,
-11.5%, -28.0%, and –49.5% for 5, 10, 15, and 20
mm offsets, respectively.
Anthropomorphic Phantom Measurements
Next, the anthropomorphic phantom CT was contoured according to the same protocol (7.0 mm internal rind for the target volume, 1.0
cm external “flash” rind overridden to 0.2 g/cm3). A plan was optimized to deliver 600 cGy in 3 fractions to 95% of the target volume.
The flash contour was also prescribed to 600 cGy. A 5.0 cm fixed field width was used with a pitch and planning modulation factor of
0.215 and 2.7, respectively. The planned dose to each TLD was recorded. The phantom was then positioned on the TomoTherapy treatment system, imaged, registered, and all three fractions were delivered. A set of three calibration TLDs from the same batch were exposed to known doses of 500, 600, and 700 cGy. The TLDs and film were removed from the phantom and processed.
In addition, restricting dose delivery to exclusively tangential beamlets (through blocking and constraints on deeper tissues) can provide
adequate superficial doses. Although lower than degraded 6 MeV beams used for conventional TSET, the dose rises to within 10% of
the prescribed dose by approximately 700 µm depth. As expected, the effective depth and penumbra of total skin helical tomotherapy
depends largely on the thickness chosen for the target “rind”; 7.0 mm appeared to yield similar prescription depth dose and falloff to
conventional TSET. The target and flash thicknesses also impact the setup margin; the plan quality began to significantly degrade if the
phantom was offset by more than 10 mm using 7.0 mm and 10 mm target and flash thicknesses, respectively. From our center’s experience positioning total body and total skin patients, this setup margin is reasonably achievable when using Vac-Lok immobilization.
As shown in the included table, the variation in surface dose is significantly less (p < 0.001) than TSET for a phantom (without limbs).
Similar uniformity was confirmed for the (more complex) patient plan. At depth, our helical tomotherapy technique yielded higher doses than conventional TSET. This is apparent even for the basic cylindrical plan, and increases for more complex geometries. TLDs
placed within the anthropomorphic phantom confirmed the predicted doses to various critical organs.
For depths beyond penumbra, the dose appears to be approximately 10% of the prescribed dose. This risk was considered acceptable
for this patient and blood counts were monitored during the course of treatment. It is noteworthy that the marrow dose exceeded the 70
cGy recommended whole body dose limit for conventional treatment for the standard TSET treatment as well16. The measured results
for the femur and long bones indicate a mean dose of 34.2 cGy, which scaled to the total treatment result in 171 cGy or approximately
5.7% of the prescribed dose. It is likely the case that the intervening air and beam spoiler significantly increase the bremsstrahlung contamination delivered to deep, centrally located tissues.
CONCLUSIONS
Helical tomotherapy based total skin radiotherapy is an acceptable alternative to conventional TSET with several advantages: the skin
dose is more homogeneous as shown with phantom studies and compared to published TSET results17,18, the patient is able to lie down
in a comfortable position, and the treatment is easy to deliver without any additional equipment setup or physics support. That said,
these advantages are not without compromise: organs at risk receive higher doses. However, given the higher delivery uniformity and
shorter course, a lower total dose might be possible while maintaining a successful response. This is an opportunity for future research.
WORKS CITED
Of the 46 TLDs placed on the phantom, 15 were placed on the surface
to measure the target dose, while 31 were placed inside the phantom
within various critical structures. The mean and standard deviation results for both the TomoTherapy plan and TSET deliveries are
summarized in the following table. For the TomoTherapy plan, the results are compared to the planned dose at each TLD. The differences are shown in parentheses.
N
For this project, the dosimetric feasibility was evaluated across three successively more complex geometries: first using a simple cylindrical phantom, and ending with an actual patient. As would be expected, the complexity in planning each case also increased. Using
the experience gained from each prior experiment, a planning protocol was developed that meets the criteria established in the Introduction. Using a density override on the flash contour made it easy to achieve 90% coverage without having to retract the target structure
from the patient surface. The time required to develop and validate the patient total skin helical tomotherapy plan was also reasonable,
requiring only a few hours from contour delineation to a treatment ready for delivery.
The authors would like to thank the physics staff at the UW Carbone Cancer Center for their thoughtful insight toward the project, as
well as the UW Radiation Calibration Laboratory (UWRCL) for analyzing the many TLDs needed.
Anthropomorphic Phantom Measurements
Region
DISCUSSION
ACKNOWLEDGEMENTS
TomoPhantom Measurements
Following simulation, a treatment plan was optimized to deliver 150 cGy to a 7.0 mm rind around the cylindrical exterior of the TomoPhantom, while simultaneously minimizing the dose at the center of the phantom. Target prescription coverage was set to 95%. A
separate “flash” rind was added by expanding the external contour by 1.0 cm. The density of the flash structure was overridden to 0.2
g/cm3 and a dose constraint equal to the target was chosen. The purpose of the flash contour was to cause the TomoTherapy optimizer
to open additional leaves beyond the target, while using an artificial density override prevented the optimizer from struggling to deliver
dose to air while minimizing the dosimetric impact to the target. A 5.0 cm fixed field width was chosen with a pitch of 0.215. The
planning modulation factor was set to 2.0.
A total of 46 TLDs were processed from the patient’s first treatment and compared to the planned dose using the calibration
TLD readings. The measured dose ranged from 122.4 cGy to
192.1 cGy, with a mean and standard deviation of 154.2 ± 14.4
cGy. When compared to the planned dose, the differences
ranged from -15.2% to 11.8%, with a mean and standard deviation of -0.8% ± 5.5%. A histogram of differences is provided.
When comparing the TLD measurements obtained from the patient’s anterior (N=26) and posterior (N=19), no statistical significance was found in either the distribution of measured doses
(p = 0.921) or dose differences (p = 0.930).
Patient Measurements
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An illustration of the planned, measured, and difference in leaf open times obtained during IMRT QA using the exit detector is shown to
the right. The mean and standard deviation difference (relative to the projection time) was -0.54% ± 1.83%, while 97.2% of the leaf
events yielded errors less than 5%. When comparing the reconstructed dose to the original plan, the mean dose difference was -0.72%,
while 99.8% of the dose voxels yielded a global gamma value less than one using 3%/3 mm criteria. Only voxels whose planned dose
was less than 20% of the maximum dose were included in analysis.
Copyright © 2014 Board of Regents of the University of Wisconsin System
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