The technique of brachytherapy 

Context in source publication

Context 1

... (BT) is a well established treatment for the early stages of tongue cancer. BT is as effective as surgery for tumor control with better functional and cosmetic results in the majority of cases. In comparison with external beam radiotherapy brachytherapy allows the delivery of higher doses of radiation over a shorter period of time with reduced volume of irradiated healthy tissues. The tumor control is improved and postradiation xerostomia and soft tissue fibro- sis are less frequent. Most of experiences with BT to treat tongue cancer was achieved with the manual afterloading technique and iridium wires with continuous low dose rate (LDR) irradiation. Con- tinuous LDR BT favors normal tissue repair during irradiation and results in a beneficial therapeutic ratio between tumor control probability and normal tissue complication probability. High dose rate (HDR) afterloading devices have replaced LDR brachytherapy in many radiotherapy departments. HDR BT is biologically more effective in comparison with LDR BT, which is more profound for the normal late reacting tissues than for the tumor. The consequence is a less beneficial therapeutic ratio. HDR brachytherapy must be fractionated and numerous small fractions are recommended to allow the repair of healthy tissues and to achieve biological equivalence with LDR brachytherapy. As regards the use of HDR BT in tongue cancer there are only controversial results of limited values available to date [1]. HDR is often considered to be dangerous for interstitial implants due to the higher risk of complications. In our institution we started HDR BT to treat oral cancer in 2001 and our preliminary clinical findings were published [2]. Since 2005 we have used CT-based planning of brachytherapy implants. The aim of our radiobiological study was to use the geometry of performed brachytherapy applications and dose volume histiograms for radiobiological modelling of the complication risk of HDR and LDR BT in the treatment of tongue cancer. The brachytherapy technique. HDR BT without external beam radiotherapy is used for patients with T1-2N0M0 tongue carcinoma after excisional biopsy in our institution. The technique of brachytherapy is based on the use of plastic tubes applied in double planes 1 cm apart. The distribution of catheters in the central plane is either in equilateral triangles or in squares. The catheters are secured by plastic buttons located on the surface of the tongue and the submandibular region. The catheters protrude 10 mm above the tongue to ensure a sufficient dose is applied to the tongue surface (Fig. 1). The prescription points are set at 5 mm away from the catheters. Dose distribution is calculated using the Abacus – GammaMed planning system; as of 2005 the calculation is based on CT planning and Brachyvision planning system (Varian, USA). For irradiation delivery we use HDR device (Gammamed, MDS Nordion, Hahn, Germany). The prescribed dose is 54 Gy in 18 fractions, 3 Gy twice daily with an interval of at least 6 hours between fractions and with a gap during weekends. For our radiobio- logical study we have used data from 8 patients planned using the Brachyvision planning system. The details of brachytherapy are presented in Table 1. Method of HDR and LDR implants comparison . We compared the risk of complications of our HDR regime 18 x 3 Gy twice daily/ 11 days and of HDR regime 10 x 6 Gy twice daily/6 days frequently used in the literature [3, 4, 5] with LDR doses biologically equivalent for the tumor. To calculate the biologically equivalent doses we used the formula BED (Biologically Effective Dose) = Nd [1+d/( α / β )] for fractionated HDR BT, where N = number of fractions, d = dose per fraction. For continuous LDR brachytherapy BED = D [1+2R/ μ ( α / β )], where D = R.T, R = 0.5 Gy/hr, T = total time of continuous irradiation, μ = 0.5 Gy -1 /hr. We the assumed ratio α / β = 10 Gy for tumor and early reacting tissues and α / β = 3 Gy for late reacting tissues [6] . We have chosen acute mucositis, late mucosal necrosis and late osteonecrosis of the mandible as the most relevant complications of brachytherapy of the tongue. Planning CT scans were performed with a separation of 3 mm between slices. We delineated the contours of the clini- cal target volume (CTV – tumor with 1 cm margin), mucosa in risk (CTV with 2 cm margin) and mandible (Fig. 2). Differential and cumulative dose volume histiograms (DVH) (Fig. 3) (Fig. 3) were obtained and used to calculate BED, LQED2 (biologically equivalent dose for fractionated radiotherapy 2 Gy/day, 5 fractions/week), tumor control probability (TCP) and normal tissue complication probability (NTCP) for each patient. The effective volume method of Kutcher and Burman was used to reduce non – uniform tissue irradiation to a uniformly irradiated dose equivalent, where a fraction of the organ, V , receives the maximum organ dose [7]. NTCP eff was calculated using Lyman’s model [8] and tolerance parameters according to Emami et al. [9] were applied (Table 2). The risk of acute mucositis was assessed according to Fowler’s model based on analysis of clinical data about acute mucosal reactions from clinical trials with altered fracionation [10]. For TCP calculation we used a model based on Poisson statistics incorporating the parameters of a linear quadratic model [11]. Calculation was performed with the program BioGray [12]. The output of the simulta- neous display of these radiobiological parameters for one patient is shown in Fig. 4. The statistical significance of the differences between HDR and LDR was assessed using a two-tailed Student’s test. For HDR scheme 18 x 3 Gy bid/11 days BED = 70.2 Gy 10 (LQED = 58.5 Gy) and the corresponding LDR dose the biologically equivalent for tumor is 58.5 Gy/115.4 hr (dose rate R = 0.5 Gy/hr). TCP is 88.8% and 74.5% for T1N0M0 and T2N0M0 respectively. Table 3 shows the NTCP values for individual applications. NTCP of HDR BT 18 x 3 Gy bid/11 days was 51.2 ± 1.1%, 4.7 ± 1.9% and 0% for acute mucositis, late mucosal necrosis and osteoradionecrosis respectively. For LDR it was 34.5 ± 1.5%, 2.84 ± 1.4 % and 0%. The risk of acute mucositis was 1.48 times higher and the risk of late mucosal necrosis was 1.66 times higher for HDR in comparison with LDR. This difference was statistically significant (p = 0.011 and p = 0.0001 for acute mucositis and late mucosal necrosis, respectively). For HDR scheme 10 x 6 Gy bid/6 days BED = 96 Gy 10 (LQED = 65 Gy) and the corresponding LDR the dose is 2 80 Gy/160 hr (dose rate R = 0.5 Gy/hour). TCP is 99.6% and 98.7% for T1N0M0 and T2N0M0 respectively. The NTCP values for individual patients are shown in table 4. NTCP of HDR BT 10 x 6 Gy bid/6 days was 100%, 74.4 ± 8.4% and 14.5 ± 4.4% for acute mucositis, late mucosal necrosis and osteoradionecrosis respectively. For the equivalent LDR it was 96.9 ± 0.7%, 21.6 ± 5.6% and 1.1 ± 0.6%. The risk of acute mucositis was 1.3 times higher, the risk of late mucosal necrosis was 3.44 times higher and the risk of osteonecrosis was 13.18 times higher for HDR in comparison with LDR. These differences were statistically significant (p < 0.0001 for both acute and late reactions). Iridium 192 interstitial BT with a low dose rate has been reported as a successful treatment modality for oral cancer in a number of studies. The miniaturization of high activity of radioisotopes along with sophisticated computer technology has led to the establishment of remote afterloading HDR BT. The advantages of HDR compared with LDR are: greater ability to conform the ...