- Email: [email protected]
Perspectives of brachytherapy: Patterns of care, new technologies, and “new biology”
Cancer/Radiothérapie 18 (2014) 434–436
Disponible en ligne sur
ScienceDirect www.sciencedirect.com
Review
Perspectives of brachytherapy: Patterns of care, new technologies, and “new biology” Perspectives de la curiethérapie : conduite thérapeutique, nouvelles technologies et « nouvelle biologie » F. Guedea ∗ Department of Radiation Oncology, Institut Català d’Oncologia (ICO), University of Barcelona (UB), L’Hospitalet del Llobregat, Barcelona, Spain
a r t i c l e Keywords: Brachytherapy Dose escalation Prostate Breast Gynaecological
i n f o
a b s t r a c t Brachytherapy has come a long way from its beginnings nearly a century ago. In recent years, brachytherapy has become ever more sophisticated thanks to a multitude of technological developments, including high-dose rate afterloading machines, image-guidance, and advanced planning systems. One of the advantages of brachytherapy, apart from the well-known capability of delivering highly conformal doses directly to the target, is that it is highly adaptable and can be used as a primary, adjunct, or salvage treatment. However, despite the existence of international treatment guidelines, the clinical practice of brachytherapy varies greatly by region, country, and even institution. In the present article, we provide an overview of recent findings from the Patterns of Care for Brachytherapy in Europe (PCBE) Study and we discuss new technologies used in brachytherapy and the emerging concept of “new biology” that supports the use of high-dose brachytherapy. Compared to the 1990s, the use of brachytherapy has increased substantially and it is expected to continue growing in the future as it becomes ever more precise and efficient. © 2014 Published by Elsevier Masson SAS on behalf of the Société française de radiothérapie oncologique (SFRO).
r é s u m é Mots clés : Curiethérapie Escalade de dose Prostate Sein Gynécologique
La curiethérapie a parcouru un long chemin, depuis ses débuts il y a près d’un siècle. Au cours des dernières années, la curiethérapie est devenue de plus en plus sophistiquée grâce à une multitude de développements technologiques, y compris l’avènement des chargeurs de source de haut débit de dose, du guidage par l’image et des systèmes de planification des doses évolués. Un des avantages de la curiethérapie, mis à part sa capacité bien connue de délivrer une irradiation très conformationnelle dans la cible, est sa grande adaptabilité et la possibilité d’être utilisée comme traitement de première intention, adjuvant ou de rattrapage. Cependant, malgré l’existence de nombreuses recommandations internationales, la pratique clinique de la curiethérapie varie beaucoup selon les régions, les pays et même les institutions. Dans cet article, nous résumons la récente étude Patterns of Care for Brachytherapy in Europe (PCBE) et nous discutons les nouvelles technologies utilisées en curiethérapie ainsi que le concept émergeant de « nouvelle biologie » appliquée à la curiethérapie, qui prend en considération la délivrance de fortes doses. Par comparaison aux années 1990, la curiethérapie a vu son utilisation franchement augmenter, phénomène qui devrait se poursuivre dans les années à venir étant donné ses propriétés reconnues de précision et d’efficacité. © 2014 Publie´ par Elsevier Masson SAS pour la Société française de radiothérapie oncologique (SFRO).
∗ Department of Radiation Oncology, Institut Català d’Oncologia (ICO), University of Barcelona (UB), Gran via s/n, 2.7 km, 08907 L’Hospitalet de Llobregat, Barcelona, Spain. E-mail address: [email protected] http://dx.doi.org/10.1016/j.canrad.2014.07.143 1278-3218/© 2014 Published by Elsevier Masson SAS on behalf of the Société française de radiothérapie oncologique (SFRO).
F. Guedea / Cancer/Radiothérapie 18 (2014) 434–436
1. Introduction Cancer incidence in Western Europe is now about 4000 patients per million per year. Due to the ageing population, a yearly increase of 1–1.5% in cancer cases is to be expected in the next two decades [1]. More than half of cancer patients will receive radiotherapy. In the last two decades, the development of new technologies has led to important advances in radiation oncology. New techniques in external beam radiotherapy, such as intensity-modulated radiotherapy, image-guided radiotherapy, and proton therapy, have made it possible to deliver highly conformal doses of ionizing radiation directly to the target volume. Similarly, brachytherapy technology continues to be refined and improved. Brachytherapy is being increasingly used as treatments become more sophisticated with the spread of high-dose rate afterloading machine, the use of image-guided brachytherapy), and newer, more sophisticated planning systems. Brachytherapy is used either as a primary treatment (e.g., in prostate and gynaecological tumors) or as a boost following surgery or external beam radiotherapy. It is also used as salvage therapy for local recurrence. The clinical practice of brachytherapy, however, is not uniform, and there are regional and country-specific variations [2]. 2. Patterns of care for brachytherapy in Europe To keep abreast of developments in brachytherapy and regional differences in clinical practice, in the year 2001 the Groupe Européen de Curiethérapie European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) decided to undertake a pattern of care study for brachytherapy in Europe (PCBE) to document patterns of clinical practice and to evaluate the brachytherapy-related resources utilized in European radiotherapy centres in the years 1997, 2002 and 2007. The PCBE data collection software was made available online initially in June 2003 and again in 2007 through a single website. The questionnaire was web-based. A national coordinator in each country was assigned to take responsibility for the initial task of co-ordinating the distribution of the questionnaires and to encourage compliance, within the PCBE project. These data have been analysed to search for differences in availability of resources and activity of the centres among countries and European regions to complete data previously published [3–8]. We reported and published the European results for 2007 and compared these to the previously reported 2002 findings [9,10]. In summary, the conclusions were: • gynaecological brachytherapy remains the most common application, although the use of this technique for both prostate and breast has increased; • CT-based dosimetry has become increasingly common since 2002; • the use of high-dose rate and pulsed-dose rate techniques has increased markedly, while both low-dose rate and medium-dose rate have declined. . 3. New technologies for brachytherapy Brachytherapy tends to “fly under the radar” when compared to external beam radiotherapy. However, numerous important – though perhaps under-appreciated – advances in brachytherapy have been made in the last two decades. This therapeutic modality has several important advantages, particularly the fact that it allows for high-doses of radiation to be delivered
435
to with great precision to the tumor, thus minimizing damage to healthy tissue. For this reason, it is important that efforts be made to remind all cancer care professionals of the continuous improvements in this technique and the value of brachytherapy in the cancer treatment toolkit. Functional imaging for brachytherapy is an area in which great improvements have been made. The range of imaging tools, many which can now be used in real-time, have greatly expanded the possibilities of brachytherapy. These include ultrasound, power Doppler imaging, positron emission tomography (PET), and magnetic resonance imaging (MRI) [11]. The combination of functional imaging with intraoperative dose calculation and optimization opens new horizons for brachytherapy. Thanks in large part to advances in computer technology, treatment planning, intraoperative navigation, and dose delivery have all improved. Powerful new computers able to process images in real-time have made image-guided brachytherapy the technique of choice to achieve excellent conformal radiation therapy. Imageguided brachytherapy allows for accurate dose delivery to small volumes under direct image visualization [12,13].
4. “New Biology” with high doses in radiotherapy The concept of high doses in radiotherapy can include essentially three entities: stereotactic body radiotherapy [14,15], high-dose rate image-guided brachytherapy and intraoperative radiotherapy. The aim and approach of these three techniques is similar and can be summarized as follows [16,17]: the accurate delivery of highly conformal, high-dose radiation therapy to limited-volume targets in the body with: • high dose per fraction (> 7–10 Gy); • single or few fractions (one to five) in 1–1.5 weeks (single in intraoperative radiotherapy); • highly precise image-guided radiation delivery; • rapid dose fall-off gradients encompassing target.
Concurrently with these clinical developments of high-dose radiotherapy (stereotactic body radiotherapy, high-dose rate image-guided brachytherapy, and intraoperative radiotherapy), laboratory studies have suggested that at high-dose fractions (> 7–10 Gy) there may be additional biological processes resulting in enhanced tumor cell killing: High radiation doses produce Sphingolipid ceramide, is to say sphingomyelinase-dependent rapid vascular collapse that markedly enhances the antitumor effect of radiation [18,19]. The abscopal or bystander effects of high-dose radiotherapy are consistent with some reports demonstrating T cells (CD8+ T cells) have antitumor effects to tumors outside the treatment field after stereotactic body radiotherapy was delivered [20–22]. Two signalling pathways differentially activated by surgical wound fluids from control and patients receiving intraoperative radiotherapy, namely p70S6 K and STAT3. Their activation is necessary to stimulate local recurrences, and intraoperative radiotherapy can explain at least partially, the very low recurrence rates found in trials with intraoperative radiotherapy in breast and other locations [23,24]. The question is whether some or even all of these biological processes (sphingolipid ceramide, CD8+ T cells, signalling pathways p70S6 K and STAT3, etc.), often referred to as a “new biology”, are required to explain at least partly, the remarkable success of highdose rate image-guided brachytherapy. We face an open question that may be answered in coming years.
436
F. Guedea / Cancer/Radiothérapie 18 (2014) 434–436
5. Conclusions In summary, it is apparent that there exist many differences across European regions and countries in brachytherapy treatments. These differences point to the need for continued investment in resources for brachytherapy in Europe. Compared to the 1990s, brachytherapy use has increased substantially, particularly for radical treatments in prostate and breast cancer. Part of the growth of brachytherapy is due to the increasingly sophisticated treatments made possible by new technological developments such as high-dose rate afterloading machines, image-guided brachytherapy, and, of course, the use of new planning systems. The clinical developments in brachytherapy discussed here, together with the use of high-dose fractions (over 7–10 Gy), may stimulate additional biological processes resulting in enhanced tumor cell killing. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108. [2] Chauvet B, Mahé MA, Maingon P, Mazeron JJ, Mornex F. [White paper on radiation oncology in France. Twelve proposals to improve a major cancer treatment. Société franc¸aise de radiothérapie oncologique]. Cancer Radiother 2013;17 suppl. 1:S2–72. [3] Bentzen SM, Heeren G, Cottier B, Slotman B, Glimelius B, Lievens Y, et al. Towards evidence-based guidelines for radiotherapy infrastructure and staffing needs in Europe: the ESTRO QUARTS project. Radiother Oncol 2005;75:355–65. [4] Heeney C, McClean B, Kelly C. A dosimetric intercomparison of brachytherapy facilities in Ireland, Scotland and the North of England. Radiother Oncol 2005;74:149–56. [5] Esco R, Palacios A, Pardo J, Biete A, Carceller JA, Veiras C, et al. Infrastructure of radiotherapy in Spain: a minimal standard of radiotherapy resources. Int J Radiat Oncol 2003;56:319–27. [6] Ruggieri-Pignon S, Pignon T, Marty M, Rodde-Dunet M-H, Destembert B, Fritsch B. Infrastructure of radiation oncology in France: a large survey of evolution of external beam radiotherapy practice. Int J Radiat Oncol 2005;61: 507–16.
[7] Slotman BJ, Cottier B, Bentzen SM, Heeren G, Lievens Y, van den Bogaert W. Overview of national guidelines for infrastructure and staffing of radiotherapy. ESTRO-QUARTS: Work package 1. Radiother Oncol 2005;75:349.E1–6. [8] Slotman BJ, Leer JWH. Infrastructure of radiotherapy in the Netherlands: evaluation of prognoses and introduction of a new model for determining the needs. Radiother Oncol 2003;66:345–9. [9] Guedea F, Venselaar J, Hoskin P, Hellebust TP, Peiffert D, Londres B, et al. Patterns of care for brachytherapy in Europe: updated results. Radiother Oncol 2010;97:514–20. [10] Guedea F, Ellison T, Venselaar J, Borras JM, Hoskin P, Poetter R, et al. Overview of brachytherapy resources in Europe: a survey of patterns of care study for brachytherapy in Europe. Radiother Oncol 2007;82:50–4. [11] Otahal B, Dolezel M, Cvek J, Simetka O, Klat J, Knybel L, et al. Dosimetric comparison of MRI-based HDR brachytherapy and stereotactic radiotherapy in patients with advanced cervical cancer: a virtual brachytherapy study. Rep Pract Oncol Radiother 2014, http://dx.doi.org/10.1016/j.rpor.2014.04.005. [12] Mazeron J-J. Brachytherapy: a new era. Radiother Oncol 2005;74:223–5. [13] Guedea F. Recent developments in brachytherapy. Rep Pract Oncol Radiother 2011;16:203–6. [14] Janoray G, Chapet S, Ruffier-Loubière A, Bernadou G, Pointreau Y, Calais G. Robotic stereotactic body radiation therapy for tumours of the liver: radiationinduced liver disease, incidence and predictive factors. Cancer Radiother 2014;18:191–7. [15] Feuvret L, Vinchon S, Martin V, Lamproglou I, Halley A, Calugaru V, et al. Stereotactic radiotherapy for large solitary brain metastases. Cancer Radiother 2014;18:97–106. [16] Loo BW. Stereotactic ablative radiotherapy (SABR) for lung cancer: what does the future hold? J Thorac Dis 2011;3:150–2. [17] Loo Jr BW, Chang JY, Dawson LA, Kavanagh BD, Koong AC, Senan S, et al. Stereotactic ablative radiotherapy: what’s in a name? Pract Radiat Oncol 2011;1:38–9. [18] Garcia-Barros M, Paris F, Cordon-Cardo C, Lyden D, Rafii S, Haimovitz-Friedman A, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 2003;300:1155–9. [19] Fuks Z, Kolesnick R. Engaging the vascular component of the tumor response. Cancer Cell 2005;8:89–91. [20] Brown JM, Brenner DJ, Carlson DJ. Dose escalation, not “new biology”, can account for the efficacy of SBRT with NSCLC. Int J Radiat Oncol Biol Phys 2013;85:1159–60. [21] Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys 2004;58:862–70. [22] Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 2012;366:925–31. [23] Belletti B, Vaidya JS, D’Andrea S, Entschladen F, Roncadin M, Lovat F, et al. Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. Clin Cancer Res 2008;14:1325–32. [24] Segatto I, Berton S, Sonego M, Massarut S, Fabris L, Armenia J, et al. p70S6 kinase mediates breast cancer cell survival in response to surgical wound fluid stimulation. Mol Oncol 2014;8:766–80.
Disponible en ligne sur
ScienceDirect www.sciencedirect.com
Review
Perspectives of brachytherapy: Patterns of care, new technologies, and “new biology” Perspectives de la curiethérapie : conduite thérapeutique, nouvelles technologies et « nouvelle biologie » F. Guedea ∗ Department of Radiation Oncology, Institut Català d’Oncologia (ICO), University of Barcelona (UB), L’Hospitalet del Llobregat, Barcelona, Spain
a r t i c l e Keywords: Brachytherapy Dose escalation Prostate Breast Gynaecological
i n f o
a b s t r a c t Brachytherapy has come a long way from its beginnings nearly a century ago. In recent years, brachytherapy has become ever more sophisticated thanks to a multitude of technological developments, including high-dose rate afterloading machines, image-guidance, and advanced planning systems. One of the advantages of brachytherapy, apart from the well-known capability of delivering highly conformal doses directly to the target, is that it is highly adaptable and can be used as a primary, adjunct, or salvage treatment. However, despite the existence of international treatment guidelines, the clinical practice of brachytherapy varies greatly by region, country, and even institution. In the present article, we provide an overview of recent findings from the Patterns of Care for Brachytherapy in Europe (PCBE) Study and we discuss new technologies used in brachytherapy and the emerging concept of “new biology” that supports the use of high-dose brachytherapy. Compared to the 1990s, the use of brachytherapy has increased substantially and it is expected to continue growing in the future as it becomes ever more precise and efficient. © 2014 Published by Elsevier Masson SAS on behalf of the Société française de radiothérapie oncologique (SFRO).
r é s u m é Mots clés : Curiethérapie Escalade de dose Prostate Sein Gynécologique
La curiethérapie a parcouru un long chemin, depuis ses débuts il y a près d’un siècle. Au cours des dernières années, la curiethérapie est devenue de plus en plus sophistiquée grâce à une multitude de développements technologiques, y compris l’avènement des chargeurs de source de haut débit de dose, du guidage par l’image et des systèmes de planification des doses évolués. Un des avantages de la curiethérapie, mis à part sa capacité bien connue de délivrer une irradiation très conformationnelle dans la cible, est sa grande adaptabilité et la possibilité d’être utilisée comme traitement de première intention, adjuvant ou de rattrapage. Cependant, malgré l’existence de nombreuses recommandations internationales, la pratique clinique de la curiethérapie varie beaucoup selon les régions, les pays et même les institutions. Dans cet article, nous résumons la récente étude Patterns of Care for Brachytherapy in Europe (PCBE) et nous discutons les nouvelles technologies utilisées en curiethérapie ainsi que le concept émergeant de « nouvelle biologie » appliquée à la curiethérapie, qui prend en considération la délivrance de fortes doses. Par comparaison aux années 1990, la curiethérapie a vu son utilisation franchement augmenter, phénomène qui devrait se poursuivre dans les années à venir étant donné ses propriétés reconnues de précision et d’efficacité. © 2014 Publie´ par Elsevier Masson SAS pour la Société française de radiothérapie oncologique (SFRO).
∗ Department of Radiation Oncology, Institut Català d’Oncologia (ICO), University of Barcelona (UB), Gran via s/n, 2.7 km, 08907 L’Hospitalet de Llobregat, Barcelona, Spain. E-mail address: [email protected] http://dx.doi.org/10.1016/j.canrad.2014.07.143 1278-3218/© 2014 Published by Elsevier Masson SAS on behalf of the Société française de radiothérapie oncologique (SFRO).
F. Guedea / Cancer/Radiothérapie 18 (2014) 434–436
1. Introduction Cancer incidence in Western Europe is now about 4000 patients per million per year. Due to the ageing population, a yearly increase of 1–1.5% in cancer cases is to be expected in the next two decades [1]. More than half of cancer patients will receive radiotherapy. In the last two decades, the development of new technologies has led to important advances in radiation oncology. New techniques in external beam radiotherapy, such as intensity-modulated radiotherapy, image-guided radiotherapy, and proton therapy, have made it possible to deliver highly conformal doses of ionizing radiation directly to the target volume. Similarly, brachytherapy technology continues to be refined and improved. Brachytherapy is being increasingly used as treatments become more sophisticated with the spread of high-dose rate afterloading machine, the use of image-guided brachytherapy), and newer, more sophisticated planning systems. Brachytherapy is used either as a primary treatment (e.g., in prostate and gynaecological tumors) or as a boost following surgery or external beam radiotherapy. It is also used as salvage therapy for local recurrence. The clinical practice of brachytherapy, however, is not uniform, and there are regional and country-specific variations [2]. 2. Patterns of care for brachytherapy in Europe To keep abreast of developments in brachytherapy and regional differences in clinical practice, in the year 2001 the Groupe Européen de Curiethérapie European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) decided to undertake a pattern of care study for brachytherapy in Europe (PCBE) to document patterns of clinical practice and to evaluate the brachytherapy-related resources utilized in European radiotherapy centres in the years 1997, 2002 and 2007. The PCBE data collection software was made available online initially in June 2003 and again in 2007 through a single website. The questionnaire was web-based. A national coordinator in each country was assigned to take responsibility for the initial task of co-ordinating the distribution of the questionnaires and to encourage compliance, within the PCBE project. These data have been analysed to search for differences in availability of resources and activity of the centres among countries and European regions to complete data previously published [3–8]. We reported and published the European results for 2007 and compared these to the previously reported 2002 findings [9,10]. In summary, the conclusions were: • gynaecological brachytherapy remains the most common application, although the use of this technique for both prostate and breast has increased; • CT-based dosimetry has become increasingly common since 2002; • the use of high-dose rate and pulsed-dose rate techniques has increased markedly, while both low-dose rate and medium-dose rate have declined. . 3. New technologies for brachytherapy Brachytherapy tends to “fly under the radar” when compared to external beam radiotherapy. However, numerous important – though perhaps under-appreciated – advances in brachytherapy have been made in the last two decades. This therapeutic modality has several important advantages, particularly the fact that it allows for high-doses of radiation to be delivered
435
to with great precision to the tumor, thus minimizing damage to healthy tissue. For this reason, it is important that efforts be made to remind all cancer care professionals of the continuous improvements in this technique and the value of brachytherapy in the cancer treatment toolkit. Functional imaging for brachytherapy is an area in which great improvements have been made. The range of imaging tools, many which can now be used in real-time, have greatly expanded the possibilities of brachytherapy. These include ultrasound, power Doppler imaging, positron emission tomography (PET), and magnetic resonance imaging (MRI) [11]. The combination of functional imaging with intraoperative dose calculation and optimization opens new horizons for brachytherapy. Thanks in large part to advances in computer technology, treatment planning, intraoperative navigation, and dose delivery have all improved. Powerful new computers able to process images in real-time have made image-guided brachytherapy the technique of choice to achieve excellent conformal radiation therapy. Imageguided brachytherapy allows for accurate dose delivery to small volumes under direct image visualization [12,13].
4. “New Biology” with high doses in radiotherapy The concept of high doses in radiotherapy can include essentially three entities: stereotactic body radiotherapy [14,15], high-dose rate image-guided brachytherapy and intraoperative radiotherapy. The aim and approach of these three techniques is similar and can be summarized as follows [16,17]: the accurate delivery of highly conformal, high-dose radiation therapy to limited-volume targets in the body with: • high dose per fraction (> 7–10 Gy); • single or few fractions (one to five) in 1–1.5 weeks (single in intraoperative radiotherapy); • highly precise image-guided radiation delivery; • rapid dose fall-off gradients encompassing target.
Concurrently with these clinical developments of high-dose radiotherapy (stereotactic body radiotherapy, high-dose rate image-guided brachytherapy, and intraoperative radiotherapy), laboratory studies have suggested that at high-dose fractions (> 7–10 Gy) there may be additional biological processes resulting in enhanced tumor cell killing: High radiation doses produce Sphingolipid ceramide, is to say sphingomyelinase-dependent rapid vascular collapse that markedly enhances the antitumor effect of radiation [18,19]. The abscopal or bystander effects of high-dose radiotherapy are consistent with some reports demonstrating T cells (CD8+ T cells) have antitumor effects to tumors outside the treatment field after stereotactic body radiotherapy was delivered [20–22]. Two signalling pathways differentially activated by surgical wound fluids from control and patients receiving intraoperative radiotherapy, namely p70S6 K and STAT3. Their activation is necessary to stimulate local recurrences, and intraoperative radiotherapy can explain at least partially, the very low recurrence rates found in trials with intraoperative radiotherapy in breast and other locations [23,24]. The question is whether some or even all of these biological processes (sphingolipid ceramide, CD8+ T cells, signalling pathways p70S6 K and STAT3, etc.), often referred to as a “new biology”, are required to explain at least partly, the remarkable success of highdose rate image-guided brachytherapy. We face an open question that may be answered in coming years.
436
F. Guedea / Cancer/Radiothérapie 18 (2014) 434–436
5. Conclusions In summary, it is apparent that there exist many differences across European regions and countries in brachytherapy treatments. These differences point to the need for continued investment in resources for brachytherapy in Europe. Compared to the 1990s, brachytherapy use has increased substantially, particularly for radical treatments in prostate and breast cancer. Part of the growth of brachytherapy is due to the increasingly sophisticated treatments made possible by new technological developments such as high-dose rate afterloading machines, image-guided brachytherapy, and, of course, the use of new planning systems. The clinical developments in brachytherapy discussed here, together with the use of high-dose fractions (over 7–10 Gy), may stimulate additional biological processes resulting in enhanced tumor cell killing. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108. [2] Chauvet B, Mahé MA, Maingon P, Mazeron JJ, Mornex F. [White paper on radiation oncology in France. Twelve proposals to improve a major cancer treatment. Société franc¸aise de radiothérapie oncologique]. Cancer Radiother 2013;17 suppl. 1:S2–72. [3] Bentzen SM, Heeren G, Cottier B, Slotman B, Glimelius B, Lievens Y, et al. Towards evidence-based guidelines for radiotherapy infrastructure and staffing needs in Europe: the ESTRO QUARTS project. Radiother Oncol 2005;75:355–65. [4] Heeney C, McClean B, Kelly C. A dosimetric intercomparison of brachytherapy facilities in Ireland, Scotland and the North of England. Radiother Oncol 2005;74:149–56. [5] Esco R, Palacios A, Pardo J, Biete A, Carceller JA, Veiras C, et al. Infrastructure of radiotherapy in Spain: a minimal standard of radiotherapy resources. Int J Radiat Oncol 2003;56:319–27. [6] Ruggieri-Pignon S, Pignon T, Marty M, Rodde-Dunet M-H, Destembert B, Fritsch B. Infrastructure of radiation oncology in France: a large survey of evolution of external beam radiotherapy practice. Int J Radiat Oncol 2005;61: 507–16.
[7] Slotman BJ, Cottier B, Bentzen SM, Heeren G, Lievens Y, van den Bogaert W. Overview of national guidelines for infrastructure and staffing of radiotherapy. ESTRO-QUARTS: Work package 1. Radiother Oncol 2005;75:349.E1–6. [8] Slotman BJ, Leer JWH. Infrastructure of radiotherapy in the Netherlands: evaluation of prognoses and introduction of a new model for determining the needs. Radiother Oncol 2003;66:345–9. [9] Guedea F, Venselaar J, Hoskin P, Hellebust TP, Peiffert D, Londres B, et al. Patterns of care for brachytherapy in Europe: updated results. Radiother Oncol 2010;97:514–20. [10] Guedea F, Ellison T, Venselaar J, Borras JM, Hoskin P, Poetter R, et al. Overview of brachytherapy resources in Europe: a survey of patterns of care study for brachytherapy in Europe. Radiother Oncol 2007;82:50–4. [11] Otahal B, Dolezel M, Cvek J, Simetka O, Klat J, Knybel L, et al. Dosimetric comparison of MRI-based HDR brachytherapy and stereotactic radiotherapy in patients with advanced cervical cancer: a virtual brachytherapy study. Rep Pract Oncol Radiother 2014, http://dx.doi.org/10.1016/j.rpor.2014.04.005. [12] Mazeron J-J. Brachytherapy: a new era. Radiother Oncol 2005;74:223–5. [13] Guedea F. Recent developments in brachytherapy. Rep Pract Oncol Radiother 2011;16:203–6. [14] Janoray G, Chapet S, Ruffier-Loubière A, Bernadou G, Pointreau Y, Calais G. Robotic stereotactic body radiation therapy for tumours of the liver: radiationinduced liver disease, incidence and predictive factors. Cancer Radiother 2014;18:191–7. [15] Feuvret L, Vinchon S, Martin V, Lamproglou I, Halley A, Calugaru V, et al. Stereotactic radiotherapy for large solitary brain metastases. Cancer Radiother 2014;18:97–106. [16] Loo BW. Stereotactic ablative radiotherapy (SABR) for lung cancer: what does the future hold? J Thorac Dis 2011;3:150–2. [17] Loo Jr BW, Chang JY, Dawson LA, Kavanagh BD, Koong AC, Senan S, et al. Stereotactic ablative radiotherapy: what’s in a name? Pract Radiat Oncol 2011;1:38–9. [18] Garcia-Barros M, Paris F, Cordon-Cardo C, Lyden D, Rafii S, Haimovitz-Friedman A, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 2003;300:1155–9. [19] Fuks Z, Kolesnick R. Engaging the vascular component of the tumor response. Cancer Cell 2005;8:89–91. [20] Brown JM, Brenner DJ, Carlson DJ. Dose escalation, not “new biology”, can account for the efficacy of SBRT with NSCLC. Int J Radiat Oncol Biol Phys 2013;85:1159–60. [21] Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys 2004;58:862–70. [22] Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 2012;366:925–31. [23] Belletti B, Vaidya JS, D’Andrea S, Entschladen F, Roncadin M, Lovat F, et al. Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. Clin Cancer Res 2008;14:1325–32. [24] Segatto I, Berton S, Sonego M, Massarut S, Fabris L, Armenia J, et al. p70S6 kinase mediates breast cancer cell survival in response to surgical wound fluid stimulation. Mol Oncol 2014;8:766–80.