Practical Radiation Oncology (2016) 6, 119-125
CME www.practicalradonc.org
Original Report
Dosimetric comparison of 3-dimensional conformal radiation therapy and intensity modulated radiation therapy and impact of setup errors in lower limb sarcoma radiation therapy Meadhbh Arthurs BSc a , Charles Gillham MD, PhD b , Evelyn O’Shea MSc b , Elaine McCrickard BSc b , Michelle Leech MSc, PG, DIp a,⁎ a
Applied Radiation Therapy Trinity Research Group, Discipline of Radiation Therapy, School of Medicine, Trinity College Dublin, Ireland b St. Luke’s Radiation Oncology Network, Dublin, Ireland Received 15 December 2014; revised 19 March 2015; accepted 30 March 2015
Abstract Purpose: This study compared dosimetric data between 3-dimensional conformal radiation therapy (3DCRT) and intensity modulated radiation therapy (IMRT) plans in a population of patients with lower limb sarcoma immobilized with an in-house device and quantified the impact of systematic and random errors on these techniques. The dosimetric effects of displacements on target coverage and organs at risk (OARs) were considered. Methods and materials: Plans were created for 11 postoperative patients using both 3DCRT and IMRT. The techniques were compared dosimetrically. Population-based systematic and random errors were applied and the results compared with the initial plans. Results: Higher target D95, D2, D98, and D50 and the best homogeneity index resulted with IMRT compared with 3DCRT. Systematic errors increased target D2 in IMRT. Random errors decreased target homogeneity in IMRT. Maximum bone dose was higher in IMRT than in 3DCRT. Neither error type increased OAR dose for either technique. Conclusions: IMRT could become the favored lower limb sarcoma radiation therapy technique because of superior target coverage and homogeneity. Offline imaging can adequately correct for systematic errors in these patients when an in-house immobilization device is used. © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Introduction Note—Earn CME credit by taking a brief online assessment at https:// www.astro.org/JournalCME. Conflicts of interest: None. ⁎ Corresponding author. Discipline of Radiation Therapy, Trinity Centre for Health Sciences, St. James’s Hospital Campus, Dublin 8, Ireland. E-mail address: [email protected] (M. Leech).
Sarcomas account for approximately 1% of adult cancers. 1 Surgery and adjuvant radiation therapy (RT) achieve high tumor control rates. 2 The surgical resection should have negative margins; however, microscopic positive margins may be present when nerves, bone, or
http://dx.doi.org/10.1016/j.prro.2015.03.008 1879-8500/© 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
120
M. Arthurs et al
arteries are kept intact, if followed by RT. 3 Multidisciplinary management of the method of biopsy and excision is crucial, because sarcoma cells have a tendency to seed. Rates of local recurrence are 7% to 15% in specialized sarcoma centers. 4 Patients receiving RT for lower limb sarcomas require careful immobilization, such as by use of vacuum bags, thermoplastic masks, and ankle casts. 5,6 Factors that affect setup include flexibility of the limb and changes in soft tissue and surface contours. 7 RT carries a risk of long-term side effects, including limb fibrosis, joint stiffness, lymphedema, and bone fractures. 8 The risk of late effects increases with postoperative RT because of higher doses and a larger treated volume. 9 Preoperative RT increases the risk of wound complications. 10,11 Radiation dose is usually 50 Gy preoperatively and 60 to 66 Gy postoperatively. 10 Postoperative RT is often delivered in 2 phases, 2,12 with phase 1 including a margin to cover microscopic disease and phase 2 consisting of a boost to the tumor bed. Systematic displacements may cause a shift in the cumulative dose distribution relative to the target, whereas random displacements cause a blurring of the dose distribution. 13 This study aimed to evaluate the dosimetric differences between 3-dimensional conformal RT (3DCRT) and intensity modulated RT (IMRT) plans to compare the dosimetric benefits and limitations of both. To test this, plans were generated for a population of patients. Dose metrics were analyzed from dose-volume histograms (DVHs) and statistically compared between techniques. This study also aimed to determine the effect of systematic and random errors on planning target volume (PTV) dose and dose to organs at risk (OARs). To test this, errors were simulated. Dose metrics were analyzed from DVHs and statistically compared with those from original plans.
Practical Radiation Oncology: March-April 2016
Figure 1 Immobilization device for radiation therapy for lower limb sarcoma.
All patients were positioned supine, immobilized with a non–commercially available immobilization device (Fig 1) that consisted of thermoplastic material and vacuum bags. Anonymous clinical details were acquired subsequently.
Institutional setup error data
Methods and materials
Setup error data were acquired from the clinical institute. The data were previously recorded from a population of patients with lower limb sarcoma to calculate institutionspecific clinical target volume (CTV)-PTV margins for setup uncertainty. Therefore, simulation of population-based rather than patient-specific setup errors was deemed most appropriate. The population standard deviations of systematic setup error (Σ) and random setup error (δ) in each axis were provided from the clinical institute (n = 11) (Table 1). These were calculated by use of van Herk’s methodology, in which the mean displacement and standard deviation in each axis per patient were recorded. 13 The mean of these means determined the overall mean error (M).
Participant population
Treatment planning
Ethical approval was received from the institute’s Research Ethics Committee. Sample size was 11 patients, treated between 2011 and 2013, each given an identification number. Median tumor size was 7.5 cm (range, 1.6-15 cm). Exclusion criteria were data from patients treated palliatively and patients who had received previous RT to the same site. Inclusion criteria were data from patients with a lower limb sarcoma treated radically with RT and planned with computed tomography (CT). Irrevocably anonymized CT data sets were acquired by the lead investigator through the Varian Eclipse treatment planning system at the academic institute. CT slice thickness was 5 mm. Patients had previously been treated with postoperative RT at the clinical institute.
The original PTV and OAR contours were present on each data set. The entire length of bone was contoured on each CT slice. The CTV to PTV expansion was 1 cm in all cases. The PTV was cropped by 5 mm inside the skin surface. 3DCRT and IMRT plans were generated for each patient. Energy used was 6 MV, and the dose was prescribed according to clinical data, at 2 Gy per fraction, to total doses of 60 to 66 Gy. Phase 1 prescription was 50 Gy for 10 patients and 52 Gy for 1 patient. Phase 2 was 10 Gy for 6 patients, 14 Gy for 2 patients, and 16 Gy for 3 patients. Plans included maximal avoidance of the contralateral limb, normal tissue, and bone. Bone dose-volume constraints were V40 b 64%, mean dose b 37 Gy, and Dmax b 59 Gy. The target coverage goal in IMRT was 95% of the PTV to
Practical Radiation Oncology: March-April 2016 Table 1 (n = 11)
Extremity sarcoma radiation therapy
Population SD of systematic and random errors
Variable
Lateral (x) (cm)
Longitudinal (y) (cm)
Vertical (x) (cm)
Systematic SD (Σ) Random SD (δ)
0.169 0.293
0.133 0.224
0.201 0.192
SD, standard deviation.
receive 100% of the dose, whereas in 3DCRT, plans were optimized toward International Commission on Radiation Units & Measurements recommendations (ICRU 50) of between − 5% and + 7% of the prescribed dose. Optimization was based on PTV coverage, thereby ensuring CTV coverage because the CTV in all cases was within the PTV. In 3DCRT, segments and wedges were used as appropriate to optimize the dose distribution. In IMRT, “dummy” structures were created to enable optimization. A corridor of normal tissue represented approximately one-third of the circumference of the treated limb. Dose to this structure was constrained below 30 Gy where feasible. DVHs were examined to ensure adequate PTV coverage, and a visual inspection of the 95% isodose line in each axial slice and in the sagittal and coronal planes was conducted.
Simulation of systematic error For each patient, a unique systematic error in each axis was acquired from a gaussian random number generator. The same error was applied to the same patient’s 3DCRT and IMRT phase 1 plan. The systematic error was applied to 3 fractions of phase 1. The remainder of the phase 1 plan was summed with the 3 systematic error fractions to give the phase 1 plan summary, on which target dose was reported. Phase 1 was added to any subsequent phases to give the overall plan summary, on which OAR dose was reported.
Simulation of random error For each patient, a set of 5 specific random errors in each axis were acquired from a gaussian random number generator. This number was arbitrary and was chosen to represent random errors at some but not all fractions. Random errors were applied to 5 fractions for each patient in their phase 1 3DCRT plans. The same error per patient fraction was applied to the patients’ IMRT phase 1 plans. The remainder of the phase 1 plan was summed with the 5 random error fractions to give the phase 1 plan summary, on which target dose was reported. This was added to any subsequent phases to give the overall plan summary, on which OAR dose was reported.
121
Dosimetric comparison Cumulative DVHs were generated, and the dose covering 95% of the PTV (D95), median dose (D50), near-minimum dose (D98), near-maximum dose (D2), and the homogeneity index (HI) 14 were recorded. The HI was defined as (D2% − D98%)/D50%. The CTV D95, bone volume receiving 40 Gy (V40), bone mean dose (Dmean), and bone maximum dose (Dmax) were also recorded. V30 for the tissue corridor in IMRT plans was recorded. Direct comparisons of dosimetric parameters between 3DCRT and IMRT plans and between plans with and without errors were performed with 2-tailed, pairedsample Student t tests with the Statistical Package for Social Sciences version 20. P values b .05 were considered statistically significant.
Results 3DCRT and IMRT plan comparison Comparisons of dosimetrics between 3DCRT and IMRT plans without setup errors are given in Table 2. Statistically significant higher D95, D2, D98, and D50 values were found for IMRT than for 3DCRT (P b .01). The mean HI value was statistically closer to 0 in IMRT than in 3DCRT (P b .01). CTV D95 was significantly greater in IMRT than in 3DCRT. IMRT bone Dmax was significantly higher than in 3DCRT (P b .0001).
Systematic error No statistically significant differences in PTV D95, D2, D98, D50, CTV D95, or HI were found in 3DCRT original plans compared with plans with systematic errors. There was no significant difference in bone Dmax, Dmean, or V40 in 3DCRT original plans compared with plans with systematic errors. No significant alteration was found in IMRT phase 1 PTV D95, D98, D50, or HI between original plans and plans with systematic errors (Table 3). Systematic errors caused a statistically significant increase in IMRT phase 1 PTV D2 (P b .05) (Table 3). Systematic errors caused no significant difference in IMRT bone Dmax, Dmean, or V40. No significant variation occurred in the IMRT tissue corridor V30 (Table 3).
Random error No statistically significant alteration was found in 3DCRT phase 1 PTV D95, D2, D98, D50, or HI between original plans and plans with random errors (Table 4).
122
M. Arthurs et al
Table 2
Practical Radiation Oncology: March-April 2016
Dosimetric comparison of 3DCRT and IMRT plans
Variable
No. of patients 3DCRT
D95 PTV phase 1, Gy (%) D2 PTV phase 1, Gy (%) D98 PTV phase 1, Gy (%) D50 PTV phase 1, Gy (%) HI PTV phase 1 D95 CTV phase 1, Gy Dmax bone combined phases, Gy V40 bone combined phases, % Dmean bone combined phases, Gy
11 11 11 11 11 10 11 11 11
IMRT
47.12 ± 1.38 (93.9 ± 2.3) 50.26 ± 0.63 (100.2 ± 0.5) 52.81 ± 0.87 (105.2 ± 1.0) 54.36 ± 1.22 (108.3 ± 1.7) 45.54 ± 1.41 (90.7 ± 2.7) 49.00 ± 0.65 (97.6 ± 1.0) 50.39 ± 0.80 (100.4 ± 0.6) 52.83 ± 1.08 (105.3 ± 1.4) 0.1443 ± 0.0277 0.1012 ± 0.0208 44.60 ± 6.27 47.32 ± 6.79 63.57 ± 3.25 67.25 ± 3.22 43.29 ± 18.34 40.12 ± 20.73 28.04 ± 10.40 29.71 ± 10.99
Paired t test P value .000 .000 .000 .000 .002 .003 .000 .354 .266
Values are mean ± SD unless otherwise stated. 3DCRT, 3-dimensional conformal radiation therapy; CTV, clinical target volume; IMRT, intensity modulated radiation therapy; D2, dose received by 2% of the volume; D50, dose received by 50% of the volume; D95, dose received by 95% of the volume; Dmean, mean dose; HI, homogeneity index; PTV, planning target volume; SD, standard deviation; V40, percent of volume receiving 40 Gy.
Significant decreases in bone V40 and bone Dmean were found in 3DCRT plans with random errors (Table 4). No statistically significant dissimilarity was found in IMRT phase 1 PTV D95, D2, D98, or D50 values between original plans and plans with random errors (Table 5). Random errors caused a statistically significant change in IMRT phase 1 PTV HI (Table 5). A significant decrease in bone Dmean was found in IMRT plans with random errors (Table 5).
Discussion This study made dosimetric comparisons between techniques and also questioned whether errors had a dosimetric impact on target coverage and OARs. Systematic errors increased the PTV D2 in IMRT. Random errors decreased the bone V40 and bone Dmean in 3DCRT and decreased the bone Dmean in IMRT. Random errors in IMRT caused the HI value to drift further from 0, which resulted in less target homogeneity. Radiation dose distributions can conform better to large sarcoma tumors with IMRT than with 3DCRT. 15 IMRT has been shown to provide a superior conformity index compared with 3DCRT. 16 Higher D98 and D95 occurred with IMRT, which ensured the PTV received closer to the prescribed dose. However, because the mean prescription dose for phase 1 was 50.18 Gy, an issue that arose in IMRT was the resulting high value for D2 (mean 54.36 ± 1.22 Gy; mean 108.3 ± 1.7%). Because dosimetry is dependent on the operator, the dosimetric results achieved could differ if a different dosimetrist developed the 3DCRT and IMRT plans. In this study, the CTV was not cropped 5 mm inside the skin surface such as the PTV was, which resulted in lower than expected values for CTV D95. The CTV did not extend outside of the PTV in any case. It was necessary to crop the PTV by 5 mm inside the skin surface because the
PTV extended into air, which caused difficulty for the treatment planning system in calculating the dose close to the skin surface. This is referred to as PTV_Eval in Table 5. Reflecting clinical practice and the work of sarcoma specialists, 11 a bolus was not used to increase skin dose. IMRT offers the potential to reduce dose to bone by reducing the circumferential expansion of the target at the soft tissue/bone interface. 15 This is feasible because bone is a natural barrier to local spread. A further advantage of IMRT in the treatment of lower limb sarcoma is highlighted in the study by Folkert et al., 17 in which IMRT was shown to be associated with reduced local recurrence compared with conventional external beam RT. The current study used a 1-cm CTV-PTV margin, and implementation of a reduced CTV-PTV margin, such as 0.5 cm, 11,18 would reasonably require online imaging, such as daily kilovoltage or cone beam CT imaging. Gierga et al 7 also recommend surface imaging as a suitable technique for daily image guidance in extremity sarcoma. 3DCRT enabled exclusion of a strip of normal tissue from the field, whereas in IMRT, the majority of the corridor was kept to Dmax b 30 Gy. These methods could not be compared statistically because the area that was spared differed. In contrast to other studies, 15,19 the present study did not show a reduction in dose to bone with IMRT compared with 3DCRT. Bone was contoured as a whole; therefore, summary statistics did not distinguish which parts of the bone were included in the PTV. The bone dose-volume constraints that were adhered to in the present study were based on those of Dickie et al. 8 Three fractions with a simulated systematic error were planned because this is indicative of most offline correction protocols in clinical practice. A mean increase of 0.03 Gy in D2 PTV in IMRT plans with systematic error was observed but clearly was unlikely to affect clinical outcome. Should the systematic error not be corrected for after 3 fractions, a greater effect would likely be observed. An increase in PTV HI values in IMRT plans with random errors could lead to a greater degree of heterogeneity
Practical Radiation Oncology: March-April 2016 Table 3
Extremity sarcoma radiation therapy
123
Dosimetric comparison of original IMRT plans and IMRT plans with systematic errors simulated for 3 fractions
Variable
No. of patients
Original IMRT plans
IMRT plans with systematic errors
Paired t test P value
D95 PTV phase 1 (Gy) D2 PTV phase 1 (Gy) D98 PTV phase 1 (Gy) D50 PTV phase 1 (Gy) HI PTV phase 1 D95 CTV phase 1 (Gy) Dmax bone combined phases (Gy) V40 bone combined phases (%) Dmean bone combined phases (Gy) V30 tissue corridor combined phases (%)
11 11 11 11 11 10 11 11 11 11
50.26 ± 54.36 ± 49.00 ± 52.83 ± 0.1012 ± 47.32 ± 67.25 ± 40.12 ± 29.71 ± 5.25 ±
50.23 ± 54.39 ± 48.98 ± 52.85 ± 0.1022 ± 47.30 ± 67.25 ± 40.06 ± 29.67 ± 5.27 ±
.400 .020 .606 .064 .151 .836 .966 .486 .301 .725
0.63 1.22 0.65 1.08 0.0208 6.79 3.22 20.73 10.99 5.86
0.67 1.24 0.68 1.02 0.0202 6.83 3.20 20.70 10.96 5.91
Values are mean ± SD unless otherwise stated. V30, percent of volume receiving 30 Gy or more. Other abbreviations as in Table 2.
in the target, causing difficulty in correlating treatment outcome to dose. In opposition to the study hypothesis, random errors caused no increase in dose to bone. A limitation is that random errors were applied only to an arbitrary number of fractions (5) of phase 1. This assumes that the remaining fractions were error free. However, there is always a degree of random error present, and therefore, a study evaluating the effect of random errors present at all fractions would be beneficial in representing a truer clinical scenario. A further limitation is the small sample size; however, this study was similar to sample sizes presented in related studies. 7,19,20 This study did not evaluate the effect of rotational displacements, which may result in large displacements at the end of an elongated target. 21 In 1 IMRT study, rotations of greater than 3° were corrected for by repositioning. 9 Another option is the use of hexapod couches 22 to automatically correct for rotations, but these are not routinely used in many clinical departments. Two multicenter trials, now closed to accrual, are investigating the effect of reducing RT treatment volume in extremity sarcomas. These are the phase 3, 2-armed VORTEX
Table 4
UK trial 23 comparing conventional postoperative RT with reduced-field postoperative RT and the Radiation Therapy Oncology Group (RTOG) 0630 phase 2 trial of preoperative image-guided RT. 18 The results may establish whether a reduction in RT volume can reduce toxicity, and thus side effects, while maintaining tumor control. The majority of patients (71.3%) in RTOG 0630 were treated with IMRT, 18 the advantages of which are reflected in the current study.
Conclusions This study found IMRT to be favorable over 3DCRT in terms of target coverage and homogeneity in soft tissue sarcomas of the lower extremity. Maximum dose to bone was lower in 3DCRT than in IMRT, but mean dose and V40 were comparable between techniques. Simulated systematic errors that were corrected for after 3 fractions had minimal effects on IMRT plans and no significant effects on 3DCRT plans. Random errors simulated at 5 fractions negatively affected target homogeneity in IMRT
Dosimetric comparison of original 3DCRT plans and 3DCRT plans with random errors simulated for 5 fractions
Variable
No. of Patients
Original 3DCRT plans
3DCRT plans with random errors
Paired t test P value
D95 PTV phase 1 (Gy) D2 PTV phase 1 (Gy) D98 PTV phase 1 (Gy) D50 PTV phase 1 (Gy) HI PTV phase 1 D95 CTV phase 1 (Gy) Dmax bone combined phases (Gy) V40 bone combined phases (%) Dmean bone combined phases (Gy)
11 11 11 11 11 10 11 11 11
47.12 ± 1.38 52.81 ± 0.87 45.54 ± 1.41 50.39 ± 0.80 0.1443 ± 0.0277 44.60 ± 6.27 63.57 ± 3.25 43.29 ± 18.34 28.04 ± 10.40
47.10 ± 1.35 52.80 ± 0.88 45.88 ± 1.93 50.40 ± 0.80 0.1375 ± 0.0390 44.70 ± 6.37 63.50 ± 3.22 42.81 ± 18.36 27.89 ± 10.35
.265 .138 .348 .640 .354 .349 .233 .047 .041
Values are mean ± SD unless otherwise stated. Abbreviations as in Table 2.
124
M. Arthurs et al
Table 5
Practical Radiation Oncology: March-April 2016
Dosimetric comparison of original IMRT plans and IMRT plans with random errors simulated for 5 fractions
Variable
No. of patients
Original IMRT plans
IMRT plans with random errors
Paired t test P value
D95 PTV_Eval phase 1 (Gy) D2 PTV_Eval phase 1 (Gy) D98 PTV_Eval phase 1 (Gy) D50 PTV_Eval phase 1 (Gy) HI PTV_Eval phase 1 D95 CTV phase 1 (Gy) Dmax bone combined phases (Gy) V40 bone combined phases (%) Dmean bone combined phases (Gy) V30 tissue corridor combined phases (%)
11 11 11 11 11 10 11 11 11 11
50.26 ± 0.63 54.36 ± 1.22 49.00 ± 0.65 52.83 ± 1.08 0.1012 ± 0.0208 47.32 ± 6.79 67.25 ± 3.22 40.12 ± 20.73 29.71 ± 10.99 5.25 ± 5.86
50.00 54.29 48.77 52.63 0.1048 47.19 67.20 39.94 29.61 5.24
.164 .534 .107 .384 .009 .464 .246 .137 .038 .461
± 0.93 ± 1.36 ± 0.92 ± 1.33 ± 0.0210 ± 6.73 ± 3.20 ± 20.72 ± 10.95 ± 5.89
Values are mean ± SD unless otherwise stated. Abbreviations as in Tables 2 and 3.
and had no statistically significant effect on 3DCRT target dose. A small decrease in mean dose and V40 to bone was observed for 3DCRT plans with random setup errors, and a small decrease in mean dose to bone was observed in IMRT plans with random setup errors. The results could be substantially different if errors were applied to a greater number of fractions or to a larger sample size. Offline verification protocols involving imaging for the initial 3 fractions can adequately correct for systematic translations in these patients when an in-house immobilization device is used. These results would indicate that to maintain target homogeneity in IMRT, daily online imaging would be required to reduce the effects of random displacements and quantifying daily rotations.
9.
10.
11.
12.
References 1. Grimer R, Judson I, Peake D, Seddon B. Guidelines for the management of soft tissue sarcomas. Sarcoma. 2010;2010:506182. 2. McGee L, Indelicato DJ, Dagan R, et al. Long-term results following postoperative radiotherapy for soft tissue sarcomas of the extremity. Int J Radiat Oncol Biol Phys. 2012;84:1003-1009. 3. Biau DJ, Weiss KR, Bhumbra RS, et al. Monitoring the adequacy of surgical margins after resection of bone and soft-tissue sarcoma. Ann Surg Oncol. 2013;20:1858-1864. 4. Dickie CI, Griffin AM, Parent AL, et al. The relationship between local recurrence and radiotherapy treatment volume for soft tissue sarcomas treated with external beam radiotherapy and function preservation surgery. Int J Radiat Oncol Biol Phys. 2012;82:1528-1534. 5. Dickie CI, Parent A, Griffin A, et al. A device and procedure for immobilization of patients receiving limb-preserving radiotherapy for soft tissue sarcoma. Med Dosim. 2009;34:243-249. 6. Zheng X, Dai T, Shu X, et al. A new method of lower extremity immobilization in radiotherapy. Radiat Oncol. 2012;7:27. 7. Gierga DP, Turcotte JC, Tong LW, Chen YL, DeLaney TF. Analysis of setup uncertainties for extremity sarcoma patients using surface imaging. Pract Radiat Oncol. 2014;4:261-266. 8. Dickie CI, Parent AL, Griffin AM, et al. Bone fractures following external beam radiotherapy and limb-preservation surgery for lower
13. 14.
15.
16.
17.
18.
19.
extremity soft tissue sarcoma: relationship to irradiated bone length, volume, tumor location and dose. Int J Radiat Oncol Biol Phys. 2009;75:1119-1124. Dickie CI, Parent AL, Chung PW, et al. Measuring interfractional and intrafractional motion with cone beam computed tomography and an optical localization system for lower extremity soft tissue sarcoma patients treated with preoperative intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2010;78: 1437-1444. O'Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial. Lancet. 2002;359:2235-2241. O'Sullivan B, Griffin AM, Dickie CI, et al. Phase 2 study of preoperative image-guided intensity-modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma. Cancer. 2013;119: 1878-1884. Haas RL, Delaney TF, O'Sullivan B, et al. Radiotherapy for management of extremity soft tissue sarcomas: Why, when, and where? Int J Radiat Oncol Biol Phys. 2012;84:572-580. van Herk M. Errors and margins in radiotherapy. Semin Radiat Oncol. 2004;14:52-64. Kataria T, Sharma K, Subramani V, Karrthick KP, Bisht SS. Homogeneity index: An objective tool for assessment of conformal radiation treatments. J Med Phys. 2012;37:207-213. Hong L, Alektiar KM, Hunt M, Venkatraman E, Leibel SA. Intensity-modulated radiotherapy for soft tissue sarcoma of the thigh. Int J Radiat Oncol Biol Phys. 2004;59:752-759. Griffin AM, Euler CI, Sharpe MB, et al. Radiation planning comparison for superficial tissue avoidance in radiotherapy for soft tissue sarcoma of the lower extremity. Int J Radiat Oncol Biol Phys. 2007;67:847-856. Folkert MR, Singer S, Brennan MF, et al. Comparison of local recurrence with conventional and intensity-modulated radiation therapy for primary soft-tissue sarcomas of the extremity. J Clin Oncol. 2014;32:3236-3241. Wang D, Zhang Q, Kirsch DG, et al. RTOG phase II trial of preoperative image guided radiotherapy (IG-RT) for primary soft tissue sarcoma of the extremity: Acute toxicity report. Int J Radiat Oncol Biol Phys. 2011;81:117. (Suppl). Stewart AJ, Lee YK, Saran FH. Comparison of conventional radiotherapy and intensity-modulated radiotherapy for post-operative radiotherapy for primary extremity soft tissue sarcoma. Radiother Oncol. 2009;93:125-130.
Practical Radiation Oncology: March-April 2016 20. Li XA, Qi XS, Pitterle M, et al. Interfractional variations in patient setup and anatomic change assessed by daily computed tomography. Int J Radiat Oncol Biol Phys. 2007;68:581-591. 21. Guckenberger M, Meyer J, Vordermark D, Baier K, Wilbert J, Flentje M. Magnitude and clinical relevance of translational and rotational patient setup errors: A cone-beam CT study. Int J Radiat Oncol Biol Phys. 2006;65:934-942.
Extremity sarcoma radiation therapy
125
22. Arumugam S, Jameson MG, Xing A, Holloway L. An accuracy assessment of different rigid body image registration methods and robotic couch positional corrections using a novel phantom. Med Phys. 2013;40:031701. 23. Cowie E. The VORTEX trial: QA for target volume delineation of extremity soft tissue sarcoma. Radiother Oncol. 2011;99:588. (Suppl).
CME www.practicalradonc.org
Original Report
Dosimetric comparison of 3-dimensional conformal radiation therapy and intensity modulated radiation therapy and impact of setup errors in lower limb sarcoma radiation therapy Meadhbh Arthurs BSc a , Charles Gillham MD, PhD b , Evelyn O’Shea MSc b , Elaine McCrickard BSc b , Michelle Leech MSc, PG, DIp a,⁎ a
Applied Radiation Therapy Trinity Research Group, Discipline of Radiation Therapy, School of Medicine, Trinity College Dublin, Ireland b St. Luke’s Radiation Oncology Network, Dublin, Ireland Received 15 December 2014; revised 19 March 2015; accepted 30 March 2015
Abstract Purpose: This study compared dosimetric data between 3-dimensional conformal radiation therapy (3DCRT) and intensity modulated radiation therapy (IMRT) plans in a population of patients with lower limb sarcoma immobilized with an in-house device and quantified the impact of systematic and random errors on these techniques. The dosimetric effects of displacements on target coverage and organs at risk (OARs) were considered. Methods and materials: Plans were created for 11 postoperative patients using both 3DCRT and IMRT. The techniques were compared dosimetrically. Population-based systematic and random errors were applied and the results compared with the initial plans. Results: Higher target D95, D2, D98, and D50 and the best homogeneity index resulted with IMRT compared with 3DCRT. Systematic errors increased target D2 in IMRT. Random errors decreased target homogeneity in IMRT. Maximum bone dose was higher in IMRT than in 3DCRT. Neither error type increased OAR dose for either technique. Conclusions: IMRT could become the favored lower limb sarcoma radiation therapy technique because of superior target coverage and homogeneity. Offline imaging can adequately correct for systematic errors in these patients when an in-house immobilization device is used. © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Introduction Note—Earn CME credit by taking a brief online assessment at https:// www.astro.org/JournalCME. Conflicts of interest: None. ⁎ Corresponding author. Discipline of Radiation Therapy, Trinity Centre for Health Sciences, St. James’s Hospital Campus, Dublin 8, Ireland. E-mail address: [email protected] (M. Leech).
Sarcomas account for approximately 1% of adult cancers. 1 Surgery and adjuvant radiation therapy (RT) achieve high tumor control rates. 2 The surgical resection should have negative margins; however, microscopic positive margins may be present when nerves, bone, or
http://dx.doi.org/10.1016/j.prro.2015.03.008 1879-8500/© 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
120
M. Arthurs et al
arteries are kept intact, if followed by RT. 3 Multidisciplinary management of the method of biopsy and excision is crucial, because sarcoma cells have a tendency to seed. Rates of local recurrence are 7% to 15% in specialized sarcoma centers. 4 Patients receiving RT for lower limb sarcomas require careful immobilization, such as by use of vacuum bags, thermoplastic masks, and ankle casts. 5,6 Factors that affect setup include flexibility of the limb and changes in soft tissue and surface contours. 7 RT carries a risk of long-term side effects, including limb fibrosis, joint stiffness, lymphedema, and bone fractures. 8 The risk of late effects increases with postoperative RT because of higher doses and a larger treated volume. 9 Preoperative RT increases the risk of wound complications. 10,11 Radiation dose is usually 50 Gy preoperatively and 60 to 66 Gy postoperatively. 10 Postoperative RT is often delivered in 2 phases, 2,12 with phase 1 including a margin to cover microscopic disease and phase 2 consisting of a boost to the tumor bed. Systematic displacements may cause a shift in the cumulative dose distribution relative to the target, whereas random displacements cause a blurring of the dose distribution. 13 This study aimed to evaluate the dosimetric differences between 3-dimensional conformal RT (3DCRT) and intensity modulated RT (IMRT) plans to compare the dosimetric benefits and limitations of both. To test this, plans were generated for a population of patients. Dose metrics were analyzed from dose-volume histograms (DVHs) and statistically compared between techniques. This study also aimed to determine the effect of systematic and random errors on planning target volume (PTV) dose and dose to organs at risk (OARs). To test this, errors were simulated. Dose metrics were analyzed from DVHs and statistically compared with those from original plans.
Practical Radiation Oncology: March-April 2016
Figure 1 Immobilization device for radiation therapy for lower limb sarcoma.
All patients were positioned supine, immobilized with a non–commercially available immobilization device (Fig 1) that consisted of thermoplastic material and vacuum bags. Anonymous clinical details were acquired subsequently.
Institutional setup error data
Methods and materials
Setup error data were acquired from the clinical institute. The data were previously recorded from a population of patients with lower limb sarcoma to calculate institutionspecific clinical target volume (CTV)-PTV margins for setup uncertainty. Therefore, simulation of population-based rather than patient-specific setup errors was deemed most appropriate. The population standard deviations of systematic setup error (Σ) and random setup error (δ) in each axis were provided from the clinical institute (n = 11) (Table 1). These were calculated by use of van Herk’s methodology, in which the mean displacement and standard deviation in each axis per patient were recorded. 13 The mean of these means determined the overall mean error (M).
Participant population
Treatment planning
Ethical approval was received from the institute’s Research Ethics Committee. Sample size was 11 patients, treated between 2011 and 2013, each given an identification number. Median tumor size was 7.5 cm (range, 1.6-15 cm). Exclusion criteria were data from patients treated palliatively and patients who had received previous RT to the same site. Inclusion criteria were data from patients with a lower limb sarcoma treated radically with RT and planned with computed tomography (CT). Irrevocably anonymized CT data sets were acquired by the lead investigator through the Varian Eclipse treatment planning system at the academic institute. CT slice thickness was 5 mm. Patients had previously been treated with postoperative RT at the clinical institute.
The original PTV and OAR contours were present on each data set. The entire length of bone was contoured on each CT slice. The CTV to PTV expansion was 1 cm in all cases. The PTV was cropped by 5 mm inside the skin surface. 3DCRT and IMRT plans were generated for each patient. Energy used was 6 MV, and the dose was prescribed according to clinical data, at 2 Gy per fraction, to total doses of 60 to 66 Gy. Phase 1 prescription was 50 Gy for 10 patients and 52 Gy for 1 patient. Phase 2 was 10 Gy for 6 patients, 14 Gy for 2 patients, and 16 Gy for 3 patients. Plans included maximal avoidance of the contralateral limb, normal tissue, and bone. Bone dose-volume constraints were V40 b 64%, mean dose b 37 Gy, and Dmax b 59 Gy. The target coverage goal in IMRT was 95% of the PTV to
Practical Radiation Oncology: March-April 2016 Table 1 (n = 11)
Extremity sarcoma radiation therapy
Population SD of systematic and random errors
Variable
Lateral (x) (cm)
Longitudinal (y) (cm)
Vertical (x) (cm)
Systematic SD (Σ) Random SD (δ)
0.169 0.293
0.133 0.224
0.201 0.192
SD, standard deviation.
receive 100% of the dose, whereas in 3DCRT, plans were optimized toward International Commission on Radiation Units & Measurements recommendations (ICRU 50) of between − 5% and + 7% of the prescribed dose. Optimization was based on PTV coverage, thereby ensuring CTV coverage because the CTV in all cases was within the PTV. In 3DCRT, segments and wedges were used as appropriate to optimize the dose distribution. In IMRT, “dummy” structures were created to enable optimization. A corridor of normal tissue represented approximately one-third of the circumference of the treated limb. Dose to this structure was constrained below 30 Gy where feasible. DVHs were examined to ensure adequate PTV coverage, and a visual inspection of the 95% isodose line in each axial slice and in the sagittal and coronal planes was conducted.
Simulation of systematic error For each patient, a unique systematic error in each axis was acquired from a gaussian random number generator. The same error was applied to the same patient’s 3DCRT and IMRT phase 1 plan. The systematic error was applied to 3 fractions of phase 1. The remainder of the phase 1 plan was summed with the 3 systematic error fractions to give the phase 1 plan summary, on which target dose was reported. Phase 1 was added to any subsequent phases to give the overall plan summary, on which OAR dose was reported.
Simulation of random error For each patient, a set of 5 specific random errors in each axis were acquired from a gaussian random number generator. This number was arbitrary and was chosen to represent random errors at some but not all fractions. Random errors were applied to 5 fractions for each patient in their phase 1 3DCRT plans. The same error per patient fraction was applied to the patients’ IMRT phase 1 plans. The remainder of the phase 1 plan was summed with the 5 random error fractions to give the phase 1 plan summary, on which target dose was reported. This was added to any subsequent phases to give the overall plan summary, on which OAR dose was reported.
121
Dosimetric comparison Cumulative DVHs were generated, and the dose covering 95% of the PTV (D95), median dose (D50), near-minimum dose (D98), near-maximum dose (D2), and the homogeneity index (HI) 14 were recorded. The HI was defined as (D2% − D98%)/D50%. The CTV D95, bone volume receiving 40 Gy (V40), bone mean dose (Dmean), and bone maximum dose (Dmax) were also recorded. V30 for the tissue corridor in IMRT plans was recorded. Direct comparisons of dosimetric parameters between 3DCRT and IMRT plans and between plans with and without errors were performed with 2-tailed, pairedsample Student t tests with the Statistical Package for Social Sciences version 20. P values b .05 were considered statistically significant.
Results 3DCRT and IMRT plan comparison Comparisons of dosimetrics between 3DCRT and IMRT plans without setup errors are given in Table 2. Statistically significant higher D95, D2, D98, and D50 values were found for IMRT than for 3DCRT (P b .01). The mean HI value was statistically closer to 0 in IMRT than in 3DCRT (P b .01). CTV D95 was significantly greater in IMRT than in 3DCRT. IMRT bone Dmax was significantly higher than in 3DCRT (P b .0001).
Systematic error No statistically significant differences in PTV D95, D2, D98, D50, CTV D95, or HI were found in 3DCRT original plans compared with plans with systematic errors. There was no significant difference in bone Dmax, Dmean, or V40 in 3DCRT original plans compared with plans with systematic errors. No significant alteration was found in IMRT phase 1 PTV D95, D98, D50, or HI between original plans and plans with systematic errors (Table 3). Systematic errors caused a statistically significant increase in IMRT phase 1 PTV D2 (P b .05) (Table 3). Systematic errors caused no significant difference in IMRT bone Dmax, Dmean, or V40. No significant variation occurred in the IMRT tissue corridor V30 (Table 3).
Random error No statistically significant alteration was found in 3DCRT phase 1 PTV D95, D2, D98, D50, or HI between original plans and plans with random errors (Table 4).
122
M. Arthurs et al
Table 2
Practical Radiation Oncology: March-April 2016
Dosimetric comparison of 3DCRT and IMRT plans
Variable
No. of patients 3DCRT
D95 PTV phase 1, Gy (%) D2 PTV phase 1, Gy (%) D98 PTV phase 1, Gy (%) D50 PTV phase 1, Gy (%) HI PTV phase 1 D95 CTV phase 1, Gy Dmax bone combined phases, Gy V40 bone combined phases, % Dmean bone combined phases, Gy
11 11 11 11 11 10 11 11 11
IMRT
47.12 ± 1.38 (93.9 ± 2.3) 50.26 ± 0.63 (100.2 ± 0.5) 52.81 ± 0.87 (105.2 ± 1.0) 54.36 ± 1.22 (108.3 ± 1.7) 45.54 ± 1.41 (90.7 ± 2.7) 49.00 ± 0.65 (97.6 ± 1.0) 50.39 ± 0.80 (100.4 ± 0.6) 52.83 ± 1.08 (105.3 ± 1.4) 0.1443 ± 0.0277 0.1012 ± 0.0208 44.60 ± 6.27 47.32 ± 6.79 63.57 ± 3.25 67.25 ± 3.22 43.29 ± 18.34 40.12 ± 20.73 28.04 ± 10.40 29.71 ± 10.99
Paired t test P value .000 .000 .000 .000 .002 .003 .000 .354 .266
Values are mean ± SD unless otherwise stated. 3DCRT, 3-dimensional conformal radiation therapy; CTV, clinical target volume; IMRT, intensity modulated radiation therapy; D2, dose received by 2% of the volume; D50, dose received by 50% of the volume; D95, dose received by 95% of the volume; Dmean, mean dose; HI, homogeneity index; PTV, planning target volume; SD, standard deviation; V40, percent of volume receiving 40 Gy.
Significant decreases in bone V40 and bone Dmean were found in 3DCRT plans with random errors (Table 4). No statistically significant dissimilarity was found in IMRT phase 1 PTV D95, D2, D98, or D50 values between original plans and plans with random errors (Table 5). Random errors caused a statistically significant change in IMRT phase 1 PTV HI (Table 5). A significant decrease in bone Dmean was found in IMRT plans with random errors (Table 5).
Discussion This study made dosimetric comparisons between techniques and also questioned whether errors had a dosimetric impact on target coverage and OARs. Systematic errors increased the PTV D2 in IMRT. Random errors decreased the bone V40 and bone Dmean in 3DCRT and decreased the bone Dmean in IMRT. Random errors in IMRT caused the HI value to drift further from 0, which resulted in less target homogeneity. Radiation dose distributions can conform better to large sarcoma tumors with IMRT than with 3DCRT. 15 IMRT has been shown to provide a superior conformity index compared with 3DCRT. 16 Higher D98 and D95 occurred with IMRT, which ensured the PTV received closer to the prescribed dose. However, because the mean prescription dose for phase 1 was 50.18 Gy, an issue that arose in IMRT was the resulting high value for D2 (mean 54.36 ± 1.22 Gy; mean 108.3 ± 1.7%). Because dosimetry is dependent on the operator, the dosimetric results achieved could differ if a different dosimetrist developed the 3DCRT and IMRT plans. In this study, the CTV was not cropped 5 mm inside the skin surface such as the PTV was, which resulted in lower than expected values for CTV D95. The CTV did not extend outside of the PTV in any case. It was necessary to crop the PTV by 5 mm inside the skin surface because the
PTV extended into air, which caused difficulty for the treatment planning system in calculating the dose close to the skin surface. This is referred to as PTV_Eval in Table 5. Reflecting clinical practice and the work of sarcoma specialists, 11 a bolus was not used to increase skin dose. IMRT offers the potential to reduce dose to bone by reducing the circumferential expansion of the target at the soft tissue/bone interface. 15 This is feasible because bone is a natural barrier to local spread. A further advantage of IMRT in the treatment of lower limb sarcoma is highlighted in the study by Folkert et al., 17 in which IMRT was shown to be associated with reduced local recurrence compared with conventional external beam RT. The current study used a 1-cm CTV-PTV margin, and implementation of a reduced CTV-PTV margin, such as 0.5 cm, 11,18 would reasonably require online imaging, such as daily kilovoltage or cone beam CT imaging. Gierga et al 7 also recommend surface imaging as a suitable technique for daily image guidance in extremity sarcoma. 3DCRT enabled exclusion of a strip of normal tissue from the field, whereas in IMRT, the majority of the corridor was kept to Dmax b 30 Gy. These methods could not be compared statistically because the area that was spared differed. In contrast to other studies, 15,19 the present study did not show a reduction in dose to bone with IMRT compared with 3DCRT. Bone was contoured as a whole; therefore, summary statistics did not distinguish which parts of the bone were included in the PTV. The bone dose-volume constraints that were adhered to in the present study were based on those of Dickie et al. 8 Three fractions with a simulated systematic error were planned because this is indicative of most offline correction protocols in clinical practice. A mean increase of 0.03 Gy in D2 PTV in IMRT plans with systematic error was observed but clearly was unlikely to affect clinical outcome. Should the systematic error not be corrected for after 3 fractions, a greater effect would likely be observed. An increase in PTV HI values in IMRT plans with random errors could lead to a greater degree of heterogeneity
Practical Radiation Oncology: March-April 2016 Table 3
Extremity sarcoma radiation therapy
123
Dosimetric comparison of original IMRT plans and IMRT plans with systematic errors simulated for 3 fractions
Variable
No. of patients
Original IMRT plans
IMRT plans with systematic errors
Paired t test P value
D95 PTV phase 1 (Gy) D2 PTV phase 1 (Gy) D98 PTV phase 1 (Gy) D50 PTV phase 1 (Gy) HI PTV phase 1 D95 CTV phase 1 (Gy) Dmax bone combined phases (Gy) V40 bone combined phases (%) Dmean bone combined phases (Gy) V30 tissue corridor combined phases (%)
11 11 11 11 11 10 11 11 11 11
50.26 ± 54.36 ± 49.00 ± 52.83 ± 0.1012 ± 47.32 ± 67.25 ± 40.12 ± 29.71 ± 5.25 ±
50.23 ± 54.39 ± 48.98 ± 52.85 ± 0.1022 ± 47.30 ± 67.25 ± 40.06 ± 29.67 ± 5.27 ±
.400 .020 .606 .064 .151 .836 .966 .486 .301 .725
0.63 1.22 0.65 1.08 0.0208 6.79 3.22 20.73 10.99 5.86
0.67 1.24 0.68 1.02 0.0202 6.83 3.20 20.70 10.96 5.91
Values are mean ± SD unless otherwise stated. V30, percent of volume receiving 30 Gy or more. Other abbreviations as in Table 2.
in the target, causing difficulty in correlating treatment outcome to dose. In opposition to the study hypothesis, random errors caused no increase in dose to bone. A limitation is that random errors were applied only to an arbitrary number of fractions (5) of phase 1. This assumes that the remaining fractions were error free. However, there is always a degree of random error present, and therefore, a study evaluating the effect of random errors present at all fractions would be beneficial in representing a truer clinical scenario. A further limitation is the small sample size; however, this study was similar to sample sizes presented in related studies. 7,19,20 This study did not evaluate the effect of rotational displacements, which may result in large displacements at the end of an elongated target. 21 In 1 IMRT study, rotations of greater than 3° were corrected for by repositioning. 9 Another option is the use of hexapod couches 22 to automatically correct for rotations, but these are not routinely used in many clinical departments. Two multicenter trials, now closed to accrual, are investigating the effect of reducing RT treatment volume in extremity sarcomas. These are the phase 3, 2-armed VORTEX
Table 4
UK trial 23 comparing conventional postoperative RT with reduced-field postoperative RT and the Radiation Therapy Oncology Group (RTOG) 0630 phase 2 trial of preoperative image-guided RT. 18 The results may establish whether a reduction in RT volume can reduce toxicity, and thus side effects, while maintaining tumor control. The majority of patients (71.3%) in RTOG 0630 were treated with IMRT, 18 the advantages of which are reflected in the current study.
Conclusions This study found IMRT to be favorable over 3DCRT in terms of target coverage and homogeneity in soft tissue sarcomas of the lower extremity. Maximum dose to bone was lower in 3DCRT than in IMRT, but mean dose and V40 were comparable between techniques. Simulated systematic errors that were corrected for after 3 fractions had minimal effects on IMRT plans and no significant effects on 3DCRT plans. Random errors simulated at 5 fractions negatively affected target homogeneity in IMRT
Dosimetric comparison of original 3DCRT plans and 3DCRT plans with random errors simulated for 5 fractions
Variable
No. of Patients
Original 3DCRT plans
3DCRT plans with random errors
Paired t test P value
D95 PTV phase 1 (Gy) D2 PTV phase 1 (Gy) D98 PTV phase 1 (Gy) D50 PTV phase 1 (Gy) HI PTV phase 1 D95 CTV phase 1 (Gy) Dmax bone combined phases (Gy) V40 bone combined phases (%) Dmean bone combined phases (Gy)
11 11 11 11 11 10 11 11 11
47.12 ± 1.38 52.81 ± 0.87 45.54 ± 1.41 50.39 ± 0.80 0.1443 ± 0.0277 44.60 ± 6.27 63.57 ± 3.25 43.29 ± 18.34 28.04 ± 10.40
47.10 ± 1.35 52.80 ± 0.88 45.88 ± 1.93 50.40 ± 0.80 0.1375 ± 0.0390 44.70 ± 6.37 63.50 ± 3.22 42.81 ± 18.36 27.89 ± 10.35
.265 .138 .348 .640 .354 .349 .233 .047 .041
Values are mean ± SD unless otherwise stated. Abbreviations as in Table 2.
124
M. Arthurs et al
Table 5
Practical Radiation Oncology: March-April 2016
Dosimetric comparison of original IMRT plans and IMRT plans with random errors simulated for 5 fractions
Variable
No. of patients
Original IMRT plans
IMRT plans with random errors
Paired t test P value
D95 PTV_Eval phase 1 (Gy) D2 PTV_Eval phase 1 (Gy) D98 PTV_Eval phase 1 (Gy) D50 PTV_Eval phase 1 (Gy) HI PTV_Eval phase 1 D95 CTV phase 1 (Gy) Dmax bone combined phases (Gy) V40 bone combined phases (%) Dmean bone combined phases (Gy) V30 tissue corridor combined phases (%)
11 11 11 11 11 10 11 11 11 11
50.26 ± 0.63 54.36 ± 1.22 49.00 ± 0.65 52.83 ± 1.08 0.1012 ± 0.0208 47.32 ± 6.79 67.25 ± 3.22 40.12 ± 20.73 29.71 ± 10.99 5.25 ± 5.86
50.00 54.29 48.77 52.63 0.1048 47.19 67.20 39.94 29.61 5.24
.164 .534 .107 .384 .009 .464 .246 .137 .038 .461
± 0.93 ± 1.36 ± 0.92 ± 1.33 ± 0.0210 ± 6.73 ± 3.20 ± 20.72 ± 10.95 ± 5.89
Values are mean ± SD unless otherwise stated. Abbreviations as in Tables 2 and 3.
and had no statistically significant effect on 3DCRT target dose. A small decrease in mean dose and V40 to bone was observed for 3DCRT plans with random setup errors, and a small decrease in mean dose to bone was observed in IMRT plans with random setup errors. The results could be substantially different if errors were applied to a greater number of fractions or to a larger sample size. Offline verification protocols involving imaging for the initial 3 fractions can adequately correct for systematic translations in these patients when an in-house immobilization device is used. These results would indicate that to maintain target homogeneity in IMRT, daily online imaging would be required to reduce the effects of random displacements and quantifying daily rotations.
9.
10.
11.
12.
References 1. Grimer R, Judson I, Peake D, Seddon B. Guidelines for the management of soft tissue sarcomas. Sarcoma. 2010;2010:506182. 2. McGee L, Indelicato DJ, Dagan R, et al. Long-term results following postoperative radiotherapy for soft tissue sarcomas of the extremity. Int J Radiat Oncol Biol Phys. 2012;84:1003-1009. 3. Biau DJ, Weiss KR, Bhumbra RS, et al. Monitoring the adequacy of surgical margins after resection of bone and soft-tissue sarcoma. Ann Surg Oncol. 2013;20:1858-1864. 4. Dickie CI, Griffin AM, Parent AL, et al. The relationship between local recurrence and radiotherapy treatment volume for soft tissue sarcomas treated with external beam radiotherapy and function preservation surgery. Int J Radiat Oncol Biol Phys. 2012;82:1528-1534. 5. Dickie CI, Parent A, Griffin A, et al. A device and procedure for immobilization of patients receiving limb-preserving radiotherapy for soft tissue sarcoma. Med Dosim. 2009;34:243-249. 6. Zheng X, Dai T, Shu X, et al. A new method of lower extremity immobilization in radiotherapy. Radiat Oncol. 2012;7:27. 7. Gierga DP, Turcotte JC, Tong LW, Chen YL, DeLaney TF. Analysis of setup uncertainties for extremity sarcoma patients using surface imaging. Pract Radiat Oncol. 2014;4:261-266. 8. Dickie CI, Parent AL, Griffin AM, et al. Bone fractures following external beam radiotherapy and limb-preservation surgery for lower
13. 14.
15.
16.
17.
18.
19.
extremity soft tissue sarcoma: relationship to irradiated bone length, volume, tumor location and dose. Int J Radiat Oncol Biol Phys. 2009;75:1119-1124. Dickie CI, Parent AL, Chung PW, et al. Measuring interfractional and intrafractional motion with cone beam computed tomography and an optical localization system for lower extremity soft tissue sarcoma patients treated with preoperative intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2010;78: 1437-1444. O'Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial. Lancet. 2002;359:2235-2241. O'Sullivan B, Griffin AM, Dickie CI, et al. Phase 2 study of preoperative image-guided intensity-modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma. Cancer. 2013;119: 1878-1884. Haas RL, Delaney TF, O'Sullivan B, et al. Radiotherapy for management of extremity soft tissue sarcomas: Why, when, and where? Int J Radiat Oncol Biol Phys. 2012;84:572-580. van Herk M. Errors and margins in radiotherapy. Semin Radiat Oncol. 2004;14:52-64. Kataria T, Sharma K, Subramani V, Karrthick KP, Bisht SS. Homogeneity index: An objective tool for assessment of conformal radiation treatments. J Med Phys. 2012;37:207-213. Hong L, Alektiar KM, Hunt M, Venkatraman E, Leibel SA. Intensity-modulated radiotherapy for soft tissue sarcoma of the thigh. Int J Radiat Oncol Biol Phys. 2004;59:752-759. Griffin AM, Euler CI, Sharpe MB, et al. Radiation planning comparison for superficial tissue avoidance in radiotherapy for soft tissue sarcoma of the lower extremity. Int J Radiat Oncol Biol Phys. 2007;67:847-856. Folkert MR, Singer S, Brennan MF, et al. Comparison of local recurrence with conventional and intensity-modulated radiation therapy for primary soft-tissue sarcomas of the extremity. J Clin Oncol. 2014;32:3236-3241. Wang D, Zhang Q, Kirsch DG, et al. RTOG phase II trial of preoperative image guided radiotherapy (IG-RT) for primary soft tissue sarcoma of the extremity: Acute toxicity report. Int J Radiat Oncol Biol Phys. 2011;81:117. (Suppl). Stewart AJ, Lee YK, Saran FH. Comparison of conventional radiotherapy and intensity-modulated radiotherapy for post-operative radiotherapy for primary extremity soft tissue sarcoma. Radiother Oncol. 2009;93:125-130.
Practical Radiation Oncology: March-April 2016 20. Li XA, Qi XS, Pitterle M, et al. Interfractional variations in patient setup and anatomic change assessed by daily computed tomography. Int J Radiat Oncol Biol Phys. 2007;68:581-591. 21. Guckenberger M, Meyer J, Vordermark D, Baier K, Wilbert J, Flentje M. Magnitude and clinical relevance of translational and rotational patient setup errors: A cone-beam CT study. Int J Radiat Oncol Biol Phys. 2006;65:934-942.
Extremity sarcoma radiation therapy
125
22. Arumugam S, Jameson MG, Xing A, Holloway L. An accuracy assessment of different rigid body image registration methods and robotic couch positional corrections using a novel phantom. Med Phys. 2013;40:031701. 23. Cowie E. The VORTEX trial: QA for target volume delineation of extremity soft tissue sarcoma. Radiother Oncol. 2011;99:588. (Suppl).
