On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy

Radiotherapy and Oncology xxx (2016) xxx–xxx

Contents lists available at ScienceDirect

Radiotherapy and Oncology journal homepage: www.thegreenjournal.com

Original article

On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy Vasiliki Peppa a, Eleftherios Pappas a, Tibor Major b, Zoltán Takácsi-Nagy b, Evaggelos Pantelis a, Panagiotis Papagiannis a,⇑ a

Medical Physics Laboratory, Medical School, National and Kapodistrian University of Athens, Greece; and b National Institute of Oncology, Budapest, Hungary

a r t i c l e

i n f o

Article history: Received 4 November 2015 Received in revised form 18 January 2016 Accepted 18 January 2016 Available online xxxx Keywords: Brachytherapy High dose rate Head and neck Dosimetry Treatment planning

a b s t r a c t Purpose: To study the effect of finite patient dimensions and tissue heterogeneities in head and neck high dose rate brachytherapy. Methods and materials: The current practice of TG-43 dosimetry was compared to patient specific dosimetry obtained using Monte Carlo simulation for a sample of 22 patient plans. The dose distributions were compared in terms of percentage dose differences as well as differences in dose volume histogram and radiobiological indices for the target and organs at risk (mandible, parotids, skin, and spinal cord). Results: Noticeable percentage differences exist between TG-43 and patient specific dosimetry, mainly at low dose points. Expressed as fractions of the planning aim dose, percentage differences are within 2% with a general TG-43 overestimation except for the spine. These differences are consistent resulting in statistically significant differences of dose volume histogram and radiobiology indices. Absolute differences of these indices are however small to warrant clinical importance in terms of tumor control or complication probabilities. Conclusions: The introduction of dosimetry methods characterized by improved accuracy is a valuable advancement. It does not appear however to influence dose prescription or call for amendment of clinical recommendations for the mobile tongue, base of tongue, and floor of mouth patient cohort of this study. Ó 2016 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2016) xxx–xxx

New dosimetry algorithms have recently become clinically available for 192Ir high dose rate (HDR) brachytherapy [1,2]. These algorithms rely on models prepared from patient computed tomography (CT) imaging to account for tissue heterogeneities and the scatter conditions in the finite patient geometry, factors that TG-43 dosimetry disregards due to its inherent assumptions. This has stimulated retrospective studies on the effect of improved dosimetry for specific HDR brachytherapy sites [3–5]. Brachytherapy is indicated for squamous cell carcinoma of the oral cavity and oropharynx, either alone or as a boost after external beam therapy [6,7]. Besides a paucity of prospective studies, HDR challenges low dose rate interstitial brachytherapy which has a long history of excellent results, on account of the lower exposure to medical staff and the potential for dose optimization [6]. It is therefore interesting to study the effect of improved dosimetric accuracy in head and neck HDR brachytherapy, especially since one might intuitively expect this will be significant due to the limited dimensions and the involvement of air and bone tissues in the geometry that mark ⇑ Corresponding author at: Medical Physics Laboratory, Medical School, Mikras Asias 75, 115 27 Athens, Greece. E-mail address: [email protected] (P. Papagiannis).

a significant departure from the radiological properties of water assumed in TG-43 dosimetry. This study compares standard TG-43 dosimetry for a sample of 22 patients treated with HDR brachytherapy for tongue and floor of mouth carcinoma, to corresponding Monte Carlo (MC) simulation results, since the latter is considered the reference method for patient specific dosimetry. Methods Patient cohort This comprised the plans of 22 consecutive head and neck patients treated with HDR brachytherapy at the National Institute of Oncology in Budapest, exported from PLATO v.14.6 in DICOM-RT format. Tumor sites included mobile tongue, base of tongue and floor of mouth. 9 patients had undergone prior surgery. 3D CT image based planning was performed. While dose optimization and dose prescription do not have an impact on results of this study, the following is reported for completeness. The planning aim was 15  3 Gy (definitive brachytherapy) or 7  3 Gy (boost brachytherapy) to be delivered twice daily with a minimum

http://dx.doi.org/10.1016/j.radonc.2016.01.022 0167-8140/Ó 2016 Elsevier Ireland Ltd. All rights reserved.

Please cite this article in press as: Peppa V et al. On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy. Radiother Oncol (2016), http://dx.doi.org/10.1016/j.radonc.2016.01.022

2

Improved dosimetry and HDR brachytherapy

interval of 6 h. Geometrical and graphical optimizations were applied followed by individual dose prescription. Dose was normalized to basal dose points and a reference relative isodose was selected to achieve at least 90% target volume coverage, keeping the dose homogeneity index above 0.55. When the geometry of the implant precluded meeting both objectives, priority was given to target coverage.

described in detail in the literature [9]. Absorbed dose was approximated by collision kerma, and medium kerma in medium was scored using the F6 tally in each voxel of the lattice geometry. The same number of photon histories was simulated for all patients (80  106). Statistical (type A) uncertainty, according to the codes’ relative error estimates, was typically within 4% (less than 2.5% for the OARs and 0.5% for the PTV).

Dosimetry

Comparison of TG-43 and patient specific dosimetry

The structures included in the treatment plans were limited to the PTV and, partly, the mandible. Seeking to augment the number of Organs at Risk (OARs) studied, the patient images were first processed to delineate the skin using a 4 mm contraction of the external patient contour. The plans were then imported into Oncentra Brachy v.4.5 and the parotid glands, spinal cord and mandible were delineated using Treatment Planning System (TPS) embedded tools. Dose was calculated over the whole imaging volume with 1 mm spatial resolution, using the TG-43 based algorithm of the TPS. Patient specific dosimetry, taking into account anatomy and heterogeneities, was performed using version 6.1 of the MCNP general purpose MC code [8] and BrachyGuide [9]. The latter is a software tool for the automated configuration of MCNP input files based on the parsing of information from plans in DICOM-RT format. It is available as freeware via the web (http://www.rdl. gr/downloads) and its second version includes qualitative and quantitative dose distribution comparison besides DICOM-RT viewer and input file generation capabilities. The configuration of input files for MC simulation using BrachyGuide has been

TG-43 data in dicom RT Dose format and the MC output (patient specific dosimetry) for each patient were imported into the BrachyGuide software. After a review of 2D percentage dose difference maps superimposed on the corresponding planes of the CT image series, organ specific spatial information was discarded through the calculation of the relative cumulative Dose–Volume Histograms (DVHs) for the PTV and the OARs using 0.5% relative dose intervals. Comparison of results in the form of DVHs was further reduced to the comparison of single values of merit in common clinical use for each structure (PTV and OARs). These included the percentage of the structure receiving dose greater than given percentages of the planning aim dose (i.e. boost: 21 Gy, definitive: 45 Gy), Vx, the minimum percentage of the planning aim dose delivered at given volumes or percentages of a structure, Dx, the Dose Homogeneity Index (DHI) and the Conformity Index (COIN) for the PTV, and the mean and maximum structure dose (Dmean, Dmax) as percentages of the planning aim dose, where appropriate [10–13]. In view of the different dose prescriptions in the patient sample, relative DVHs were also calculated in terms of the EQD2, the

Fig. 1. TG-43 versus patient specific (MC) dosimetry on the central axial implant plane of an indicative patient. (a) isodose curves (3, 5, 10, 20, 50 and 100%) superimposed on the CT image (b) a colormap of % dose differences relative to MC,%(DTG-43 DMC)/DMC (c) a colormap of % dose differences relative to the planning aim dose,%(DTG-43 DMC)/ DPA.

Please cite this article in press as: Peppa V et al. On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy. Radiother Oncol (2016), http://dx.doi.org/10.1016/j.radonc.2016.01.022

3

V. Peppa et al. / Radiotherapy and Oncology xxx (2016) xxx–xxx

Fig. 2. The median, minimum and maximum cumulative DVHs for the PTV (left) and the mandible (right) calculated from TG-43 and patient specific (MC) dosimetry in the patient sample studied. The upper and lower panels present results in units of relative dose and relative EQD2, respectively.

Table 1 Comparison of PTV and implant-related dosimetry in the form of different indices obtained from TG-43 and patient specific (Monte Carlo) dosimetry in the patient cohort of this study. Dosimetric characteristic

Coverage V100 V150 V200 D90

TG43

Monte Carlo

p-Value

Median

Range

Median

Range

93.02% 53.50% 27.58% 105.32%

78.41–98.78% 43.02–90.04% 19.86–60.86% 85.19–150.12%

92.43% 50.84% 25.29% 103.91%

77.11–98.50% 39.76–88.84% 18.34–57.04% 83.78-147.01%

<0.05 <0.05 <0.05 <0.05

Homogeneity DHI

0.52

0.42–0.63

0.53

0.42–0.65

<0.05

Conformity COIN

0.65

0.41–0.81

0.64

0.43–0.82

<0.05

Abbreviations: Vx, percentage of the PTV volume receiving at least x% of the planning aim dose (definitive: 45 Gy, boost: 21 Gy); D90, minimum percentage of the planning aim dose received by 90% of the PTV; DHI, Dose Homogeneity Index; COIN, Conformity Index.

Equivalent Total Dose delivered in 2-Gy fractions [14], using a/b = 10.5 Gy for the PTV and 3.5 Gy for the mandible [15]. The effect of the difference between TG-43 and patient specific dosimetry in terms of clinical outcome was also evaluated through the reduction of corresponding differential DVH data to radiobiological indices. In view of the inherent inhomogeneity of brachytherapy dose distributions, the Poisson-based model was coupled with the Equivalent Uniform Dose (EUD) concept [16] for the PTV. The mean survival fraction (S), EUD and Tumor Control Probability (TCP) were calculated assuming a/b = 10.5 Gy [15], a = 0.22 Gy 1 [17], tumor cell doubling time, T = 4.5 days [18] and k = 200 [19]. A summary of the model and equations used can be

found in Bovi et al. 2007 [19]. This analysis was further extended to include Equivalent Uniform BED [20] calculations. A considerable underestimation of the actual TCP is expected for patients receiving a brachytherapy boost since the external beam dose component was not taken into account. This however does not bias the comparison performed in this work. For the OARs the standard Lyman–Kutcher–Burman model [21,22] was employed to calculate the Normal Tissue Control Probability (NTCP) and generalized EUD (gEUD) [23] from both the TG43 and MC derived DVHs. Regarding the parotids, the model parameters adopted (n = 1, m = 0.53, TD50 = 31.4 Gy) [24] correspond to the incidence of xerostomia defined as a reduction to 25% of salivary flow within 6 months after

Please cite this article in press as: Peppa V et al. On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy. Radiother Oncol (2016), http://dx.doi.org/10.1016/j.radonc.2016.01.022

4

Improved dosimetry and HDR brachytherapy

Table 2 Comparison of OAR dosimetry in the form of indices appropriate for each organ obtained from TG-43 and patient specific (Monte Carlo) dosimetry in the patient cohort of this study. Dosimetric characteristic

Mandible V100 D30 D50 D0.1 cc D1 cc Dmean Dmax

TG43

Monte Carlo

p-Value

Median (%)

Range (%)

Median (%)

Range (%)

0.00 22.60 16.60 75.48 55.11 18.52 93.15

0.00–0.57 8.45–30.48 5.97–23.89 34.35–123.23 23.73–84.54 7.97–26.76 43.89–124.36

0.00 21.70 15.86 75.82 55.14 17.69 92.59

0.00–0.44 8.08–29.01 5.69–22.47 34.43–122.30 23.33–82.42 7.62–25.38 43.23–121.82

>0.05 <0.05 <0.05 <0.05 <0.05 <0.05 >0.05

Right Parotid D30 D0.1 cc D1 cc Dmean Dmax

3.68 5.71 4.93 3.38 6.25

2.09–12.91 3.08–23.45 2.68–18.51 1.92–11.51 3.24–28.81

3.15 5.20 4.00 2.84 5.85

1.65–11.86 2.70–22.34 2.23–17.36 1.51–10.48 3.01–28.05

<0.05 <0.05 <0.05 <0.05 <0.05

Left Parotid D30 D0.1 cc D1 cc Dmean Dmax

4.17 6.65 5.28 3.75 7.58

2.04–9.22 3.05–17.38 2.44–12.37 1.87–8.32 3.24–22.14

3.61 6.08 4.47 3.24 7.11

1.67–8.35 2.74–16.37 2.11–11.42 1.52–7.47 3.01–28.05

<0.05 <0.05 <0.05 <0.05 <0.05

14.06 12.51 8.32 14.94

5.31–61.26 5.03–35.79 3.69–18.08 5.43–78.21

12.91 11.50 7.31 13.84

4.66–59.72 4.40–33.90 3.16–16.16 5.03–78.39

<0.05 <0.05 <0.05 <0.05

4.78 4.23 4.96

2.79–9.91 2.45–8.15 2.70–10.67

4.37 3.94 4.56

2.47–8.98 2.24–7.28 2.49-9.74

<0.05 <0.05 >0.05

Skin D0.1 cc D1 cc D10 cc Dmax Spinal Cord D0.1 cc D1 cc Dmax

Abbreviations: V100, percentage of the mandible volume receiving at least 100% of the planning aim dose (definitive: 45 Gy, boost: 21 Gy); Dx, minimum percentage of the planning aim dose received by x% of the organ volume; D0.1 cc, D1 cc and D10 cc, minimum percentage of the planning aim dose delivered to 0.1, 1 and 10 cc of the organ volume, respectively; Dmean and Dmax, mean and maximum organ dose, respectively, expressed as a percentage of the planning aim dose.

irradiation. Osteoradionecrosis with marked limitation of the transmandibular joint was the selected endpoint for mandible with corresponding LKB parameters (n = 0.07, m = 0.10, TD50 = 72 Gy) [25,26]. Differences in DVH related metrics and radiobiological indices between TG-43 and patient specific dosimetry were evaluated for statistical significance using a paired sample Wilcoxon signed rank test with a criterion of p 6 0.05. Results Illustrative results of the comparison between TG-43 and MC dosimetry are presented in Fig. 1. Except for the spine where TG43 underestimates dose up to 10% due to the interposition of air in the anatomy, and the spinal cord where differences are within statistical uncertainty, Fig. 1b shows a general TG-43 overestimation which reaches 20% for the skin. Differences are reduced to within 2% in Fig. 1c where they are presented as fractions of the planning aim dose to account for the steep dose gradient with distance from the implant inherent to brachytherapy, and comply with the common use of relative DVHs. Observations in Fig. 1c explain the difference in the comparison of DVH results from TG-43 and MC dosimetry in the patient sample. This comparison is summarized in Fig. 2 for the PTV and the most critical OAR (mandible). The decrease of TG-43 DVH data for the PTV at high relative dose in Fig. 2 is due to the upper dose threshold of the TPS (400%). DVH results in terms of relative EQD2 in the lower panel of Fig. 2 show a similar pattern of differences. The comparison of DVH results for the PTV and all OARs is further elaborated on in Tables 1 and 2. A statistically significant

TG-43 overestimation of all clinically relevant DVH indices can be seen, with the exception of Dmax for the mandible and the spinal cord. Differences however are generally small. The distributions of percentage differences in selected DVH indices are also summarized in Fig. 3 for the PTV and the mandible. The analysis of relative EQD2 DVHs yielded differences between TG43 and MC in close agreement with those from the analysis of relative dose DVHs. Only the PTV D90% overestimation by TG-43 was found 1% higher. The results of radiobiological indices calculated from DVHs for the two dosimetry methods are presented in Table 3 (see Supplementary material). In accordance with the DVH analysis, differences in all indices are small but consistent, and thus statistically significant.

Discussion Noticeable percentage differences exist between dose distributions calculated for 22 head and neck HDR brachytherapy patients using a conventional TG-43 algorithm and MC which constitutes a reference dosimetry method to account for patient specific anatomy information available through imaging. These differences increase with distance from the implant as well as at points close to the patient contour or behind air filled anatomical structures. Their clinical importance must therefore be evaluated in the light of the actual dose delivered at each point. The analysis of relative DVH indices for the PTV shows that differences are statistically significant due to the consistent TG-43 dose overestimation. They are too small in terms of magnitude and range however to warrant any change in treatment planning

Please cite this article in press as: Peppa V et al. On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy. Radiother Oncol (2016), http://dx.doi.org/10.1016/j.radonc.2016.01.022

V. Peppa et al. / Radiotherapy and Oncology xxx (2016) xxx–xxx

5

Fig. 3. Box plots of the distributions of percentage differences in selected PTV (left) and mandible (right) indices of DVHs calculated from TG-43 and patient specific (MC) dosimetry, % (IndiceTG-43 IndiceMC)/IndiceMC.

practice or prove important in terms of clinical outcome, as shown by TCP and EUD results. The same findings apply to mandible dosimetry. Radionecrosis of the mandibular bone is the most serious complication that could arise after brachytherapy for oral cancer [27]. The differences in the median Dmax, and gEUD values are however small and NTCP was found negligible for both methods. The key to minimizing adverse sequelae is strict adherence to clinical recommendations [6] rather than improved dosimetric accuracy. If MC results of this work were dose to water in bone instead of dose to bone, differences from TG-43 dosimetry would be even lower since the effect of bone density on the spectrum of 192Ir photon radiation propagating in the anatomy is counterbalanced by the effect of its composition [28]. Neither of the dose reporting conventions is directly linked to tissue radiation response in the brachytherapy photon energy range [29]. As already acknowledged in the literature however, the clear reporting the dose quantity used in a study is essential [28] and will allow the deduction of aggregate dose response patterns. Due to their relatively increased distance from the implant, the parotids are effectively spared and the consistent TG-43 overestimation within 1% of the planning aim dose is not deemed clinically important. TG-43 dosimetry also overestimates dose to the skin due to the overestimation of the scatter dose component in the finite patient anatomy [30,31]. The skin area subjected to the highest dose is determined from proximity to the implant, as reflected also in the range of maximum dose in the sample of this work. Relying on TG-43 skin dosimetry can therefore be considered a safe side approach that is more accurate as distance from the implant, and the scatter to primary dose ratio, decreases. The significant yet small overestimation of spinal cord D0.1 cc and D1 cc observed in this study for TG-43 dosimetry is not deemed important since a low dose is delivered and partial myelitis is not an ordinary complication of oral cavity brachytherapy. While anatomical changes expected in the course of head and neck brachytherapy were not considered, a corresponding bias to results of this study is unlikely. Overall, results of this work suggest that for the mobile tongue, base of tongue and floor of mouth patient cohort studied, the role of improved dosimetric accuracy might be less important than controlling other potential sources of uncertainty [32].

Conclusions Patient specific dosimetry in head and neck HDR brachytherapy corroborates the advantage of the technique in terms of low

peripheral dose. Statistically significant differences from the standard TG-43 dosimetry exist, but they do not affect the tumor control or complication probabilities. Advanced dose calculation algorithms introduced in clinical practice can be commissioned using local dose differences to highlight underlying assumptions, but the clinical importance of findings should be evaluated taking dose levels and radiobiological analysis into account. Improved dosimetry is a valuable advancement, especially for salvage or boost brachytherapy. For the patient cohort of mobile tongue, base of tongue and floor of mouth HDR brachytherapy studied however, adherence to clinical recommendations for patient selection and good implant quality, followed by optimization and image based planning, remain the decisive elements of treatment quality. Conflict of interest None. Acknowledgments Research co-financed by the European Union (European Social Fund–ESF – Greece) and Greek National Funds through the Operational Program ‘‘Education and Lifelong Learning Investing in Knowledge Society” of the National Strategic Reference Framework (NSRF). Research Funding Program: Aristeia. Elekta Brachytherapy (Veenendaal, The Netherlands) is gratefully acknowledged for providing Oncentra Brachy v.4.5, for research purposes. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.radonc.2016.01. 022. References [1] Davis SD, Rivard MJ, Thomson RM, et al. Report of the Task Group 186 on model-based dose calculation methods in brachytherapy beyond the TG-43 formalism: current status and recommendations for clinical implementation. Med Phys 2012;39:6208–36. http://dx.doi.org/10.1118/1.4747264. [2] Papagiannis P, Pantelis E, Karaiskos P. Current state of the art brachytherapy treatment planning dosimetry algorithms. Br J Radiol 2014;87:20140163. http://dx.doi.org/10.1259/bjr.20140163. [3] Desbiens M, D’Amours M, Afsharpour H, et al. Monte Carlo dosimetry of high dose rate gynecologic interstitial brachytherapy. Radiother Oncol 2013;109:425–9. http://dx.doi.org/10.1016/j.radonc.2013.09.010. [4] Siebert F-A, Wolf S, Kóvacs G. Head and neck (192)Ir HDR-brachytherapy dosimetry using a grid-based Boltzmann solver. J Contemp Brachyther 2013;5:232–5. http://dx.doi.org/10.5114/jcb.2013.39444.

Please cite this article in press as: Peppa V et al. On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy. Radiother Oncol (2016), http://dx.doi.org/10.1016/j.radonc.2016.01.022

6

Improved dosimetry and HDR brachytherapy

[5] Zourari K, Major T, Herein A, Peppa V, Polgár C, Papagiannis P. A retrospective dosimetric comparison of TG43 and a commercially available MBDCA for an APBI brachytherapy patient cohort. Phys Med 2015:1–8. http://dx.doi.org/ 10.1016/j.ejmp.2015.05.010. [6] Mazeron J-J, Ardiet J-M, Haie-Méder C, et al. GEC-ESTRO recommendations for brachytherapy for head and neck squamous cell carcinomas. Radiother Oncol 2009;91:150–6. http://dx.doi.org/10.1016/j.radonc.2009.01.005. [7] Corvò R. Evidence-based radiation oncology in head and neck squamous cell carcinoma. Radiother Oncol 2007;85:156–70. http://dx.doi.org/10.1016/j. radonc.2007.04.002. [8] Goorley T, James M, Booth T, et al. Initial MCNP6 release overview. Nucl Technol 2012;180:298–315. [9] Pantelis E, Peppa V, Lahanas V, Pappas E, Papagiannis P. BrachyGuide: a brachytherapy-dedicated DICOM RT viewer and interface to Monte Carlo simulation software. J Appl Clin Med Phys 2015;16:208–18. [10] Nag S. Inter-society standards for the performance of brachytherapy: a joint report from ABS, ACMP and ACRO. Crit Rev Oncol Hematol 2003;48:1–17. http://dx.doi.org/10.1016/S1040-8428(03)00026-X. [11] Takácsi-Nagy Z, Oberna F, Koltai P, et al. Long-term outcomes with high-doserate brachytherapy for the management of base of tongue cancer. Brachytherapy 2013;12:535–41. http://dx.doi.org/10.1016/j. brachy.2013.07.001. [12] Baltas D, Kolotas C, Geramani K. A conformal index (COIN) to evaluate implant quality and dose specification in brachytherapy. Int J Radiat Oncol Biol Phys 1998;40:515–24. [13] Ebert MA, Gulliford SL, Buettner F. Two non-parametric methods for derivation of constraints from radiotherapy dose-histogram data. Phys Med Biol 2014;59: N101–11. http://dx.doi.org/10.1088/0031-9155/59/13/N101. [14] Fowler JF. Sensitivity analysis of parameters in linear-quadratic radiobiologic modeling. Int J Radiat Oncol Biol Phys 2009;73:1532–7. http://dx.doi.org/ 10.1016/j.ijrobp.2008.11.039. [15] Stuschke M, Thames HD. Fractionation sensitivities and dose-control relations of head and neck carcinomas: analysis of the randomized hyperfractionation trials. Radiother Oncol 1999;51:113–21. http://dx.doi.org/10.1016/S01678140(99)00042-0. [16] Niemierko A. Reporting and analyzing dose distributions: a concept of equivalent uniform dose. Med Phys 1997;24:103. http://dx.doi.org/10.1118/ 1.598063. [17] Qi XS, Yang Q, Lee SP, Li XA, Wang D. An estimation of radiobiological parameters for head-and-neck cancer cells and the clinical implications. Cancers (Basel) 2012;4:566–80. http://dx.doi.org/10.3390/cancers4020566. [18] Rew DA, Wilson GD. Cell production rates in human tissues and tumours and their significance. Part II: clinical data. Eur J Surg Oncol 2000;26:405–17. http://dx.doi.org/10.1053/ejso.1999.0907. [19] Bovi J, Qi XS, White J, Li XA. Comparison of three accelerated partial breast irradiation techniques: treatment effectiveness based upon biological models.

[20]

[21] [22]

[23] [24]

[25] [26] [27]

[28]

[29]

[30]

[31]

[32]

Radiother Oncol 2007;84:226–32. http://dx.doi.org/10.1016/j. radonc.2007.07.004. Dale RG, Coles IP, Deehan C, O’Donoghue JA. Calculation of integrated biological response in brachytherapy. Int J Radiat Oncol Biol Phys 1997;38:633–42. Lyman JT. Complication probability as assessed from dose–volume histograms. Radiat Res Suppl 1985;8:S13–9. Kutcher GJ, Burman C. Calculation of complication probability factors for nonuniform normal tissue irradiation: the effective volume method. Int J Radiat Oncol Biol Phys 1989;16:1623–30. Niemierko A. A generalized concept of equivalent uniform dose ({EUD}). Med Phys 1999;26. Semenenko VA, Li XA. Lyman–Kutcher–Burman NTCP model parameters for radiation pneumonitis and xerostomia based on combined analysis of published clinical data. Phys Med Biol 2008;53:737–55. http://dx.doi.org/ 10.1088/0031-9155/53/3/014. Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109–22. Burman C, Kutcher GJ, Emami B, Goitein M. Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys 1991;21:123–35. Lozza L, Cerrotta A, Gardani G, et al. Analysis of risk factors for mandibular bone radionecrosis after exclusive low dose-rate brachytherapy for oral cancer. Radiother Oncol 1997;44:143–7. Fonseca GP, Tedgren ÅC, Reniers B, et al. Dose specification for 192Ir high dose rate brachytherapy in terms of dose-to-water-in-medium and dose-tomedium-in-medium. Phys Med Biol 2015;60:4565–79. http://dx.doi.org/ 10.1088/0031-9155/60/11/4565. Thomson RM, Tedgren ÅC, Williamson JF. On the biological basis for competing macroscopic dose descriptors for kilovoltage dosimetry: cellular dosimetry for brachytherapy and diagnostic radiology. Phys Med Biol 2013;58:1123–50. http://dx.doi.org/10.1088/0031-9155/58/4/1123. Pantelis E, Papagiannis P, Karaiskos P, et al. The effect of finite patient dimensions and tissue inhomogeneities on dosimetry planning of 192Ir HDR breast brachytherapy: a Monte Carlo dose verification study. Int J Radiat Oncol Biol Phys 2005;61:1596–602. http://dx.doi.org/10.1016/j.ijrobp.2004.12.065. Zourari K, Pantelis E, Moutsatsos A, et al. Dosimetric accuracy of a deterministic radiation transport based (192)Ir brachytherapy treatment planning system. Part III. Comparison to Monte Carlo simulation in voxelized anatomical computational models. Med Phys 2013;40:011712. http://dx.doi.org/10.1118/1.4770275. Kirisits C, Rivard MJ, Baltas D, et al. Review of clinical brachytherapy uncertainties: analysis guidelines of GEC-ESTRO and the AAPM. Radiother Oncol 2014;110:199–212. http://dx.doi.org/10.1016/j.radonc.2013.11.002.

Please cite this article in press as: Peppa V et al. On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy. Radiother Oncol (2016), http://dx.doi.org/10.1016/j.radonc.2016.01.022