The basic tools for the immobilization of patients with head and neck (HN) tumors during radiotherapy are thermoplastic masks with a 5-point pinning system and supporting system for the head. These immobilization aids largely, but not completely, prevent major shifts during irradiation. Due to its regular use, the head support can shrink and deform over time, which leads to deviations in the position of the HN compared to the reference position determined on the computed tomography (CT) simulator (Figure 1). To overcome this problem, patient-specific head supports were introduced (
At the Institute of Oncology Ljubljana, the majority of HN cancer patients are irradiated on two similar treatment units with slightly different imaging capabilities. Commercially available head supports have been used since the 1990s (CIVCO, Coralville, Iowa, USA), whereas patient-specific head supports have never been introduced in routine practice. Until 2015, all patients irradiated on a particular treatment unit shared the same set of head supports (
In the present study, two hypotheses were tested: (1) Deviations recorded by portal imaging system will be smaller in patients using individual head supports compared to those with standard ones; (2) The treatment unit with a more advanced portal imaging system will allow for a more accurate positioning of patients.
Between January 2014 and October 2017, 120 HN cancer patients irradiated with curative intent were included in this retrospective non-interventional study. Patients were irradiated on either of the two low-energy linear accelerators equipped with MV imaging systems: unit A - Unique Performance Edition; and unit B - Clinac DBX (both: Varian Medical Systems, Palo Alto, California, USA). Depending on the treatment unit (A or B), the time of irradiation, and the type of head support used, patients were divided into 6 groups of 20 patients. Because individual head supports were introduced into routine practice in 2015, the consistency of results related to their use over time was verified in two time periods (2015 and 2017) and, consequently, in two independent groups of patients:
Group 1 – linear accelerator A, 2014 (standard head support)
Group 2 – linear accelerator B, 2014 (standard head support)
Group 3 – linear accelerator A, 2015 (individual head support)
Group 4 – linear accelerator B, 2015 (individual head support)
Group 5 – linear accelerator A, 2017 (individual head support)
Group 6 – linear accelerator B, 2017 (individual head support)
Variations in the position of the isocenter (IC) relative to the reference point determined on the CT simulator (
At the CT simulator, the most appropriate head support was selected from the commercially available set of items of various heights and contours, offering a comprehensive range of neck angulations (CIVCO, Coralville, Iowa, USA), according to the curvature of patient’s neck and occiput. The Kneefix™ and the Armaflex™ cushion were placed under the knees and the back and pelvis, respectively, and the head was additionally fixed with a thermoplastic 5-point Posicast® mask (all: CIVCO, Coralville, Iowa, USA). Radio-opaque markers (Beekley Medical, Bristol, Connecticut, USA) were used for three-point marking of the IC origin. CT scanning from 2 cm above the top of the head to the tracheal bifurcation (slice thickness: 2 mm) was accomplished using an intravenous administration of iodine contrast medium by power injector, followed by tattooing the thoracic skin for the central alignment of the patient.
Patients on the treatment units were pre-positioned into the IC, based on the room lasers before the set up imaging. Portal images were taken according to the Extended No Action Level (eNAL) protocol.5 The PortalVision computer program with the AutoMatching registration procedure (Varian Medical Systems, Palo Alto, California, USA) was used to calculate the size and direction of the displacement. Electronic portal images acquired with gantry at 0° (anteroposterior projection) and 90° (or 270°, lateral projection) were compared with digitally reconstructed radiographs (DRRs). Portal images were obtained using the Varian’s EPID PortalVision using an amorphous silicon plane detector aS1000 (resolution of 1024 × 768 pixels, unit A) or aS500 (resolution 512 × 384 pixels, unit B). Whereas unit A allows simultaneous patient position alignment in all three directions using 2D/2D image matching, unit B requires the radiographers to combine the position corrections obtained from two separate orthogonal 2D image matchings.
The study protocol was approved by the Protocol Review Board of the Institute of Oncology Ljubljana on April 4, 2017.
Testing set-up error distributions for normality was done using the Shapiro-Wilk test. As Shapiro-Wilk test did not support the normality hypothesis in any of the distribution, non-parametric Mann-Whitney U-test (two-sample rank-sum test) was employed for comparing median values in distributions instead of two-sided Student’s t-test. For the same reason, non-parametric modified Levene’s test (using median instead of mean) was used to test the equality of variances in set-up error distributions. Statistical calculations were performed using the GNU R statistical program.7 The sample size of 350 measurements per time period was calculated with the G*Power software, considering a = 0.05, b = 0.8 and the effect size of 0.267, which was calculated on the basis of averages and standard deviations of similar studies.1,2,6,8 For comparison with published studies, the clinical target volume (CTV) – planning target volume (PTV) safety margin was calculated according to the formula proposed by Van Herk.,9 The differences at p < 0.05 were considered statistically significant.
In total, 2454 portal images and 3681 set-up errors were analysed: 828, 832, and 794 portal images obtained in 2014, 2015, and 2017, respectively. We first analysed the data sets for the presence of large setup errors. The proportion of displacements smaller than 3 mm and smaller than 5 mm were 85% and 99.1%, respectively in the 2014 set, when standard head supports were employed. The introduction of individual head supports in 2015 increased these figures to 89% and 99.6%, respectively, and in a most recent data set from 2017 they were further increased to 90% and 99.6%, respectively.
Inter-fraction set-up errors registered in units A and B at different periods are shown in Table 1 and Figure 2. The difference in distribution of interfraction displacements were tested using Mann-Whitney U-test. In four cases, the test showed that the distribution obtained in one year differ significantly (p < 0.05) from those obtained in the other two years. For unit A, set-up error distributions in the vertical direction obtained in 2014 and in the longitudinal direction obtained in 2017 differ from the other two years. For unit B, set-up error distributions in the vertical direction in the year 2014 and in the lateral direction in the year 2014 differ from the other two years. Comparing the vertical shift distribution for the unit A in the years 2014 and 2015 shows significant difference (Mann-Whitney U = 16293, n1 = 187, n2 = 201, p = 0.02, Hodges-Lehmann estimator (HLΔ) = -0.000012, 95% confidence interval (CI) is (-0.999974, -0.000010)). The difference in distributions is even more pronounced between the sets for the year 2014 and 2017 (U = 12918.5, n1 = 187, n2 = 175, p < 0.001, HLΔ = -0.999982, 95% CI (-0.999989, -0.000059). Comparing the distributions for the years 2015 and 2017 did not show a significant difference. Comparing the longitudinal shift distributions for the unit A also doesn’t show a significant difference; however, comparing the distributions for the years 2014 and 2017 does show a significant difference (U = 11230, n1 = 187, n2 = 175, p < 0.001, HLΔ = -0.999982, 95% CI (-1.000066, -0.999956)), and so does the comparison for the years 2015 and 2017 (U = 10171.5, n1 = 201, n2 = 175, p < 0.001, HLΔ = -1.000006, 95% CI (-1.000032, -0.999955)). Neither comparison for the lateral shifts for the unit A showed significance. Comparing the vertical shift distributions for the unit B also shows significant difference between the sets for the years 2014 and 2015 (U = 19637.5, n1 = 227, n2 = 215, p < 0.001, HLΔ = -0.999931, 95% CI (-1.000049, -0.000042)), as well as between the sets for the years 2014 and 2017 (U = 21674, n1 = 227, n2 = 222, p < 0.01, HLΔ = -0.000046, 95% CI (-0.999990, -0.000025)), while the difference between data sets for the years 2015 and 2017 is not significant. In unit B, none of the differences in the longitudinal shift distribution is considered significant. Comparing the lateral shift distributions shows significance between the data sets for the years 2014 and 2015 (U = 18998, n1 = 227, n2 = 215, p < 0.01, HLΔ = -0.999942, 95% CI (-0.999980, -0.000042)) and for the years 2014 and 2017 (U = 22030, n1 = 227, n2 = 222, p < 0.02, HLΔ = -0.000058, 95% CI (-0.999953, -0.000040)), while the distributions of lateral shifts between 2015 and 2017 is not considered significant. Comparing the variances of the distributions (which correspond to the systematic error Σ and the random error σ combined) only shows significant differences in five cases: in unit A the vertical shift distributions for the years 2015 and 2017 differ significantly (Levene’s F = 6.3082, DF = 386, p < 0.02), as well as longitudinal shift distributions for the years 2014 and 2017 (F = 9.2817, DF = 360, p < 0.01). In unit B, all three comparisons of longitudinal shift distributions show significant difference: between the sets for 2014 and 2015 (F = 24.5077, DF = 440, p < 0.001), between the sets for 2014 and 2017 (F = 9.1372, DF = 447, p < 0.01), and between the sets for 2015 and 2017 (F = 4.5802, DF = 435, p = 0.03). In Table 2, the number of IC displacements for both units together at different periods are presented, as well as the number of recorded gross errors (> 5 mm). Most of the IC shifts were made in the posterior, inferior and in the left direction. With the implementation of individual head supports, their number decreased, except for the lateral direction, and the number of gross errors was also reduced.
Inter-fraction displacements recorded on units A and B at different periods
2014 Standard head support | 2015 Individual support | 2017 Individual support | |||||||
---|---|---|---|---|---|---|---|---|---|
VRT | LNG | LAT | VRT | LNG | LAT | VRT | LNG | LAT | |
- 0.86 | 0.05 | 0.05 | - 0.47* | - 0.24* | - 0.05 | - 0.16* | 0.88 | 0.18 | |
0.66 | 1.04 | 0.88 | 0.91 | 0.79 | 0.95 | 0.82 | 0.59 | 0.83 | |
1.49 | 1.21 | 1.37 | 1.56 | 1.28 | 1.38 | 1.28 | 1.14 | 1.2 | |
- 0.60 | 0.46 | - 0.43 | - 0.02* | 0.51 | 0.25 | - 0.18* | 0.46 | - 0.02 | |
1.09 | 0.80 | 0.82 | 0.92 | 0.74 | 0.94 | 0.93 | 0.69 | 0.88 | |
1.77 | 1.83 | 1.47 | 1.77 | 1.22 | 1.41 | 1.71 | 1.56 | 1.44 |
LAT = lateral (medial-lateral); LNG = longitudinal (superior-inferior); VRT = vertical (anterior-posterior)
*p < 0.05 (2014 vs. 2015 or 2014
Number of IC displacements and of gross errors at treatment units in relation to time for both units. In the brackets, the most prevalent direction of applied movements is indicated
Isocenter movements | ||||
---|---|---|---|---|
VRT | LNG | LAT | Gross errors | |
Regression errors | ||||
Unit A / unit B (direction) | Unit A / unit B (direction) | Unit A / unit B (direction) | ||
11 / 15 (P) | 5 / 15 (I) | 4 / 5 (L) | 2 / 5 | |
12 / 13 (P) | 3 / 6 (I) | 9 / 8 (R) | 0 / 1 | |
5 / 14 (P) | 7 / 10 (I) | 6 / 7 (L) | 0 / 1 |
I = inferior; L = left; LAT = lateral (medial-lateral); LNG = longitudinal (superior-inferior); P = posterior; R = right; VRT = vertical (anterior-posterior)
The CTV-PTV safety margins calculated from the population set-up errors for units A and B at different periods are shown in Table 3. In unit A, the largest reduction of the safety margin after implementation of individual head supports was calculated in the longitudinal direction (2014
Clinical target volume - planning target volume (CTV-PTV) safety margins for units A and B at different periods (calculated according to van Herk8)
CTV-PTV safety margin [mm] | |||
---|---|---|---|
VRT | LNG | LAT | |
2.7 | 3.4 | 3.2 | |
3.4 | 2.9 | 3.3 | |
2.9 | 2.3 | 2.9 | |
4.0 | 3.3 | 3.1 | |
3.5 | 2.7 | 3.3 | |
3.5 | 2.8 | 3.2 |
LAT = lateral (medial-lateral); LNG = longitudinal (superior-inferior); VRT = vertical (anterior-posterior)
In the present study, individual head supports were found to significantly reduce inter-fraction displacements in the vertical direction, specifically in the posterior direction, compared to the standard head supports. Reduction of average displacement in vertical direction recorded between 2014 and 2017 on units A and B was 0.70 mm and 0.42 mm, respectively. This observation pointed to the shrinkage of material,
Comparing the three periods, the systematic error did not change significantly for either unit. In the vertical direction, the systematic error recorded on unit A increased by an average of 0.15 mm, while on unit B it decreased by approximately the same extent. A negligible increase over the time was observed in the lateral direction, on average by less than 0.1 mm. It seems that the use of head supports and the shrinkage of the material they are made of influenced mainly the rotational set-up errors of the head in the sagittal plane, rather than the head displacements to the left or to the right.1 In the longitudinal direction, the systematic error was reduced over time on both treatment units. Similarly, by abolishing the standard head supports, a statistically non-significant decrease in the size of the random error was recorded on unit A in all three directions. On unit B, the random error remained practically unchanged in two directions; in the longitudinal direction, its change was negligible.
Our observations are in line with those of other authors. A reduction of systematic and random errors in all directions was calculated by Van Lin
Furthermore, our calculations of the estimated margins from CTV to PTV were also comparable to those reported in the literature. Humphreys
Humphreys
In addition, there were some differences across the study groups recorded in the size of inter-fraction displacements (unit A: longitudinal displacement, 2014
When compared to standard head supports, the introduction of individual head supports reduced inter-fraction set-up errors in the vertical direction and the number of gross errors; in some directions, also the number of IC displacements and the size of the CTV-PTV safety margin were reduced. A more advanced imaging system with a better spatial resolution contributed to a reduction in the systematic and random errors.