(RED), between each high dose rate (HDR) brachytherapy (BT) fraction in cervical carcinoma patients. BT using a tandem (T) and two ovoids (O) is included, ...
The British Journal of Radiology, 79 (2006), 504–509
Changes in applicator positions and dose distribution between high dose rate brachytherapy fractions in cervix carcinoma patients receiving definitive radiotherapy 1
˘ AOG˘LU, MD, 1N TUNC¸EL, PhD, 1M G DALMAZ, M GARIPAG ˘ , BSc and 1F G KO ˘ LU, MD ¨ KIZILDAG ¨ SEOG AU
MD,
2
H GU¨LKESEN,
MD,
1
A TOY,
BSc,
1
Akdeniz University School of Medicine, Departments of 1Radiation Oncology and 2Bioistatistics, Antalya, 07070 Turkey ABSTRACT. This study examines the change of applicator geometry and its effect on rectal/rectum (R) and bladder (B) doses, and obtained radiobiological equivalent doses (RED), between each high dose rate (HDR) brachytherapy (BT) fraction in cervical carcinoma patients. BT using a tandem (T) and two ovoids (O) is included, and any discrepancies in applicator positions among the fractions were calculated. Whether the change of applicator position had an effect on the calculated R and B doses was analysed. Furthermore, the relationship between the size of tumour, the magnitude of displacement and the change in R and B doses was also investigated. Lastly, the changes in R and B RED were noted. The average magnitude of displacement was between 2.0 mm and 16.9 mm, showing time trend. There was no relationship between tumour size and the magnitude of discrepancy of Left O, Right O, T, R, B, and neither change in R and B doses (p.0.05). The mean differences of R and B doses were between 49–78 cGy, and 70–84 cGy, respectively. The magnitude of discrepancy and changes in doses showed no correlation (p.0.05). There were no significant differences in REDs for bladder (p50.8) and rectum (p50.2). In conclusion, there were significant differences in the applicator positions R and B and R and B doses among the fractions, which confirm the necessity of treatment planning in each HDR BT fraction. However, the total calculated R and B REDs did not show a remarkable difference.
Radiotherapy consisting of external radiotherapy and brachytherapy (BT) is the only curative treatment method for locally advanced stage cervical carcinoma [1–4]. The natural steep dose gradient of brachytherapy dose distribution allows a higher dose to the target while not exceeding the tolerance limit of normal rectal (R) and bladder (B) tissues. The optimal integration of brachytherapy and external radiotherapy is the main defining factor of radiotherapy treatment characteristics, such as the total point A dose, total paracentral dose and total treatment time which are independent prognostic factors in the treatment of cervical carcinoma as well as tumour and patient related factors [1, 2, 5–7]. It was claimed that in comparison with low dose rate (LDR) BT, high dose rate (HDR) BT has a physical dose distribution advantage. However, some authors claim that HDR BT has a radiobiological disadvantage [8–15], although performing HDR BT with multiple small fractions could alter this radiobiological disadvantage [5, 11, 16, 17]. Critical organs, namely R and B, are very close to the applicators and high dose region of BT. A small change in the distance from a particular point to the active sources may cause a great dose difference due to the BT Address correspondence to: Dr Melahat Garipag˘aog˘lu, Acibadem Oncology and Neurological Science Hospital, Department of Radiation Oncology, Inonu cad. Okur sok. No:20 Kozyatag˘ı 34742 Istanbul, Turkey.
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Received 28 January 2005 Revised 24 October 2005 Accepted 5 December 2005 DOI: 10.1259/bjr/33762931 ’ 2006 The British Institute of Radiology
having a large dose gradient near the region close to the active sources [14, 18]. Therefore, a precise dose calculation of normal tissue as well as the target is critical for successful treatment in HDR BT. The aim of this study is to detect the change of applicator geometry between HDR BT fractions and its effect on the calculated R and B doses, and the given radiobiological effective doses (RED)s, using tandem (T) and ovoid (O) in cervical carcinomas.
Methods The orthogonal radiographs of patients receiving intracavitary brachytherapy using T and two Os were used for this retrospective study. External radiotherapy was administered with a 1.8 Gy fraction size, totalling 46–50.4 Gy to the whole pelvis. BT was done five times using Ir192 Microselectron HDR machine with 6 Gy fraction size, starting after the completion of at least 40 Gy of external radiotherapy in order to achieve enough tumour regression to perform an optimal application, and BT fractions were used twice a week to reduce the total treatment time. The application was done after the patient had fasted for 12 h. Laxatives were used for the elimination of rectal matters, urinary Foley catheter was used to keep the bladder empty during the whole procedure, and the The British Journal of Radiology, June 2006
Position and dose variations among HDR brachytherapy fractions
balloon of the Foley catheter was filled with 7 cm3 of an opaque solution. Before the BT application, the same procedure of sedation and analgesia was given in all fractions of each patient. An extra analgesic was given when it was needed after the applicator placement. After the completion of the application, one tandem and two ovoids were fixed to each other and a specially designed table used until completion of treatment, to ensure the immobilization of the patient during simulation, treatment and transport. In addition, all the applications were given by the same experienced physician using the same kind of packing technique. Orthogonal X-rays were taken for each fraction. A reference volume definition for R and B dose calculations were carried out according to ICRU-38 recommendations. Treatment planning and optimization were applied in each fraction. Special effort was made not to exceed rectal and bladder tolerance levels. In order to determine the changes of applicator positions between the BT fractions, pelvic bone reference points were used as fixed points, applicators (T, left O, right O), B and R reference points were used as non-fixed points (Figure 1). A Cartesian coordinate centre (for x, y and z axes) was chosen using orthogonal radiographs (anterior-posterior (AP) and lateral) (Figure 1). The position of fixed and non-fixed points were measured according to centre of Cartesian coordinate centre in x, y and z axes. The distances between the fixed and nonfixed points were measured on the x and y axes on AP
radiographs and in z axis on lateral radiograms. The differences in the measured distances were calculated between the first fractions and subsequent fractions. Whether the magnitude of displacement showed a time trend was investigated. Furthermore, the magnitudes of the displacements on the x, y and z axes were used to calculate the resultant vector. The relationship between the initial tumour size and the magnitude of resultant vectors was also examined. For this study, to evaluate whether the change of applicator positions to the bony pelvis has an effect on the calculated R and B doses, both active source positions and calculated treatment time of first fraction were repeated for subsequent fractions of each patient, and inferential R and inferential B dose calculations were made. Then the difference between the ICRU-38 recommended R and B doses in the first fraction and the subsequent inferential R and B doses was determined [19]. The relationship between changes in subsequent inferential R and B doses and initial tumour size obtained from MR images was also evaluated. It was assumed that geometric variations might lead to a change in calculated doses. The relationship between the magnitude of displacement of the applicators and the inferential doses were examined. In an effort to determine whether changes in R and B doses have an effect on R and B REDs, R and B REDs of each fraction were calculated using inferential R and B doses, according to the ‘‘linear quadratic model,’’ then added [20]. The chosen alpha/beta value was 3 for B and R, as in previous studies [21]. The change in total REDs
Figure 1. The fixed points, which are pelvic bone reference points; the non-fixed points, namely left ovoid (LO), right ovoid (RO), tandem stopper (S), bladder (B) and rectal (Rg) reference points are shown on (a) anterior-posterior and (b) lateral diagram. The British Journal of Radiology, June 2006
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of R and B calculated in concordance with the linear quadratic model was investigated.
Statistical analysis Statistical analysis was performed using SPSS 10.0 software, the normality of samples was analysed by a Shapiro-Wilk test. Statistical significance of the displacement and dose changes between fractions was tested using the paired t-test or a Wilcoxon signed-rank test. Spearman’s rho test was used for correlations; p,0.05 is considered to be statistically significant.
Results 13 out of 75 total fractions were excluded from the study because of low quality X-rays or the use of the applications other than tandem and ovoids. 15 distances of each fraction were measured on AP and lateral graphs, with a total of 930 distances recorded. The average magnitude of discrepancy in the x, y and z axes and resultant vector are presented in Table 1. The mean discrepancy of left O, right O, T, B and R reference points between the fractions were between 10.0 mm and 19.4 mm. In the first fraction, the distance of the T from the non-fixed point was 37¡3 mm (mean¡standard deviation), and was 31¡3 mm in the fourth fraction (p50.012). In other words, the stopper of T moved 6 mm superior towards the end of the treatment. No other statistically significant time trend or movement to a certain direction of non-fixed points could be determined (data not shown). There was no significant relationship
between the initial tumour size and the magnitude of resultant vectors of left O (r50.239, p50.132), right O (r50.24, p50.13), T (r50.036, p50.821), R (r50.035, p50.834) and B (r50.309, p50.059). The differences calculated between inferential R and B doses and R and B doses in the first fraction are presented in Table 2. The mean differences for B and R were between 78–149 cGy and 70–84 cGy, respectively. A correlation was seen between initial tumour size and changes in inferential R doses (r50.414, p50.005), but no correlation was seen in the B doses (r5–0.075, p50.621). The magnitude of resultant vectors and changes in doses for R (r50.455, p50.005), and B (r5–0.418, p50.007) showed correlation (Figure 2). The difference between inferential dose and administered dose for B was greater than 60 cGy in 15 (100%) of the patients, and 6 (40%) of these patients had a difference greater than 120 cGy. The difference for the R was greater than 60 cGy in 10 (66%) patients; 6 (40%) of them had a difference greater than 120 cGy. The median of differences between total REDs and total inferential REDs for the R for each patient was 11 Gy, whereas it was 4 Gy for the B as BED values. The differences were not statistically significant.
Discussion Significant geometric variations were seen in all three applicators’, namely left O, right O and T positions, between the HDR brachytherapy fractions. As noted previously in either LDR or HDR brachytherapy, these position differences were more than 1 cm in 60% of the applications [22–29].
Table 1. Absolute discrepancy on x, y, z axes and displacement in resultant vector (mean, mm)
Second fraction (n515) Left ovoid Right ovoid Stopper Bladder Rectum Third fraction (n514) Left ovoid Right ovoid Stopper Bladder Rectum Fourth fraction (n511) Left ovoid Right ovoid Stopper Bladder Rectum Fifth fraction (n55) Left ovoid Right ovoid Stopper Bladder Rectum
Delta x
Delta y
Delta z
Resultant vector
95% CI
SD
10.0 11.4 9.8 8.9 8.4
5.5 5.5 7.6 2.0 5.9
8.3 7.3 5.7 4.9 6.8
16.6 17.2 16.9 12.5 13.9
11.0–22.2 11.2–23.2 11.3–22.5 8.1–16.9 9.9–17.9
10.8 11.8 10.9 8.1 7.4
11.3 12.3 10.1 11.0 8.3
6.2 6.4 6.5 4.2 6.8
7.9 6.5 6.4 8.3 5.9
16.9 17.6 16.7 15.8 15.4
10.9–22.9 11.8–23.4 11.7–21.7 7.8–23.8 11.0–19.8
11.1 11.0 9.2 14.3 8.2
9.5 12.7 7.7 10.9 7.2
6.1 6.3 6.8 3.7 6.1
9.9 10.9 9.9 5.8 7.7
16.7 19.4 15.6 15.1 13.1
12.1–21.3 14.0–24.8 8.6–22.6 5.3–24.9 9.5–16.7
7.5 8.8 11.7 15.4 5.6
14.0 16.9 13.7 6.3 9.2
4.2 5.9 8.2 4.3 8.9
5.7 3.2 4.1 8.5 8.1
16.8 17.1 17.6 10.0 17.3
5.6–28.0 6.9–27.3 7.6–27.6 5.4–14.6 11.3–22.9
12.5 11.4 11.1 4.7 6.1
CI, confidence interval; SD, standard deviation.
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Position and dose variations among HDR brachytherapy fractions Table 2. The difference between inferential rectal and bladder doses, calculated using first fraction active sources positions and treatment times
Second fraction (n515) Bladder Rectum Third fraction (n514) Bladder Rectum Fourth fraction (n511) Bladder Rectum Fifth fraction (n55) Bladder Rectum
Mean dose
95% CI
SD
92 77
37–147 35–119
99 73
149 84
79–219 34–135
126 88
78 83
36–119 15–152
69 113
99 70
38–160 24–116
79 55
CI, confidence interval; SD, standard deviation.
Furthermore, in comparison with T and R applications, the magnitude of differences was lower in the present study, compatible with other reports regarding T and O applications [22–26, 29]. Some authors claim that insufficient fixation of applicators both to each other and to the table is a main potential reason for geometric variation [26, 29]. Although the variations were higher in non-fixed applications than in fixed and the changes in O were higher than in T in non-fixed applications, there was still a significant variation in the present study. Research also showed that another reason for displacement was anaesthesia given among the fractions [27, 28]. In the present study, the same kind of anaesthesia was used in all fractions of each patient. However, there were significant geometric variations in the applicator positions among the fractions. In order to achieve enough tumour response to perform an optimal application, brachytherapy was
started after the completion of 40 Gy external radiotherapy. The stopper of tandem moved approximately 6 mm superior towards the end of the treatment. We speculate that this finding supports continuing tumour shrinkage in a period of brachytherapy fractions [24, 27, 29]. In comparison with the magnitude of changes in B position, the changes in R position were higher. The B was kept empty and the ICRU 38 recommended B reference point is related to the balloon of the Foley catheter, therefore showing that the change in B position was small. The ICRU 38 recommended R reference point is defined according to the position of the applicators, so the changes in applicator positions also affected the changes in ICRU 38 recommended R reference point, as expected [28]. The inferential R and B doses were helpful for predicting R and B doses of subsequent fractions when treatment planning and dose calculation were not performed for remaining fractions. In addition, positional differences were seen, and R and B doses differed among the fractions. (This difference was higher than 60 cGy, which is 10% of prescribed dose in 10 out of 15 patients in B doses and 15 out of 15 patients in R doses, and higher than 120 cGy, which is 20% of prescribed dose in 10 out of 15 patients in B doses and 15 out of 15 patients in R doses). The precise physical dose calculation is more important in HDR than LDR brachytherapy because of its claimed radiobiological disadvantage. Therefore, the prescribed dose should be adjusted considering normal tissue doses. This magnitude of differences in normal tissue dose illustrates the necessity of treatment planning and dose calculation in each fraction of HDR brachytherapy, which is in agreement with other studies [24, 25, 27–29]. Furthermore, there was a relationship between the initial tumour size and the change in R dose, as seen in the literature [24, 28]. However, there was no association between the B dose and the initial tumour size. Presumably, the reason is that the ICRU 38 recommended
Figure 2. Simple scatter plot graphics of relationship between resultant vector and dose change in the rectum (r520.418, p50.007). The British Journal of Radiology, June 2006
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R reference point is defined according to Os location, therefore tumour shrinkage has an effect on R point. On the contrary, ICRU 38 recommended B reference point is dependent on Foley catheter balloon position without using the applicators. There were remarkable relationships between the magnitudes of geometric displacement (as a resultant factor) and dose variation for R and B. Both tumour control and radiation injury increased with increasing radiation doses. B and R are the main dose limiting organs in the pelvis. For this reason, brachytherapy is helpful for increasing central tumour doses while external radiotherapy with midline shielding is helpful for increasing parametrial doses without increasing R and B doses. The hypothesis of using brachytherapy to increase central tumour dose and of using external radiotherapy with midline shielding to increase parametrial doses, without increasing R and B doses has many shortcomings, such as the increase of rectal complications, the difficulty of defining vagina location, which kind of block technique (i.e. stepwedge or rectangle) should be used and what percentage of isodose is best to integrate with external radiotherapy successfully [3, 5, 28, 30–35]. Moreover, according to the results of the current study and previous studies, the calculated doses differ among HDR fractions using T and O [26–29]. For these reasons, the design of the midline shield according to isodose distribution of the first BT fraction could result in an inappropriate isodose distribution, due to changes in subsequent fraction’s isodose distribution. The total inferential R and B REDs were relatively similar. However, one should keep in mind that the acceptable R and B doses were calculated ICRU 38 recommended R and B reference points and based on the points, rather than volume. As shown in other studies, these doses do not represent the real R and B doses [36– 39]. On the other hand, volume based three-dimensional planning for each fraction is not possible in most centres using HDR. The results of the current study suggest that proper treatment planning, dose calculation and optimization according to normal tissue doses for each fraction are necessary in cervical carcinoma patients receiving HDR brachytherapy using T and O.
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