A Dosimetric Selectivity Intercomparison of HDR Brachytherapy, IMRT and Helical Tomotherapy in Prostate Cancer Radiotherapy

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1 Strhlentherpie und Onkologie Originl Article A Dosimetric Selectivity Intercomprison of HDR Brchytherpy, IMRT nd Helicl Tomotherpy in Prostte Cncer Rdiotherpy Johnne Hermesse 1, Sylvie Biver 1, Nicols Jnsen 1, Eric Lenerts 2, Nthlie De Ptoul 3, Stefn Vynckier 3, Philippe Coucke 1, Pierre Sclliet 4, Philippe Nickers 5 Bckground nd Purpose: Dose escltion in order to improve the biochemicl control in prostte cncer requires the ppliction of irrdition techniques with high conformlity. The dosimetric selectivity of three rdition modlities is compred: high-dose-rte brchytherpy (HDR-BT), intensity-modulted rdition rdiotherpy (IMRT), nd helicl tomotherpy (HT). Ptients nd Methods: Ten ptients with prostte denocrcinom treted by 10-Gy HDR-BT boost fter externl-bem rdiotherpy were investigted. For ech ptient, HDR-BT, IMRT nd HT theoreticl tretment plns were relized using common contour sets. A 10-Gy dose ws prescribed to the plnning trget volume (PTV). The PTVs nd criticl orgns dose-volume histogrms obtined were compred using Student s t-test. Results: HDR-BT delivers spontneously higher men doses to the PTV with smller cold spots compred to IMRT nd HT. 33% of the rectl volume received men HDR-BT dose of 3.86 ± 0.3 Gy in comprison with men IMRT dose of 6.57 ± 0.68 Gy nd men HT dose of 5.58 ± 0.71 Gy (p < ). HDR-BT lso enbles to better spre the bldder. The hot spots inside the urethr re greter with HDR-BT. The volume of helthy tissue receiving 10% of the prescribed dose is reduced t lest by fctor of 8 with HDR-BT (p < ). Conclusion: HDR-BT offers better conformlity in comprison with HT nd IMRT nd reduces the volume of helthy tissue receiving low dose. Key Words: Prostte cncer IMRT Brchytherpy Tomotherpy Strhlenther Onkol 2009;185: DOI /s Ein dosimetrischer Vergleich von HDR-Brchytherpie, IMRT und helikler Tomotherpie bei der Rdiotherpie des Prosttkrzinoms Hintergrund und Ziel: Eine Dosiseskltion zur Steigerung der biochemischen Kontrollrten beim Prosttkrzinom erfordert die Anwendung von Bestrhlungstechniken, die eine hohe Dosiskonformität ermöglichen. Verglichen wird die dosimetrische Selektivität von drei Bestrhlungsmodlitäten: High-Dose-Rte-Brchytherpie (HDR-BT), intensitätsmodulierte Rdiotherpie (IMRT) und helikle Tomotherpie (HT). Ptienten und Methodik: Zehn Ptienten mit einem Adenokrzinom der Prostt, die im Anschluss n eine perkutne Rdiotherpie einen Boost von 10 Gy in Form einer HDR-BT erhielten, wurden untersucht. Für jeden dieser Ptienten wurden Bestrhlungspläne für eine HDR-BT, eine IMRT und eine HT unter Anwendung gemeinsmer Konturierungsverfhren erstellt. Für ds Plnungszielvolumen (PTV) wurden 10 Gy verordnet. Die ermittelten jeweiligen PTV und Dosis-Volumen-Histogrmme für die kritischen Orgne wurden mittels Student-t-Test miteinnder verglichen. Ergebnisse: Die HDR-BT führt zu höheren mittleren Dosen im PTV mit kleineren Cold Spots ls die IMRT oder HT. 33% des bestrhlten Volumens des Rektums erhielten bei der HDR-BT eine mittlere Dosis von 3,86 ± 0,3 Gy im Vergleich zu 6,57 ± 0,68 Gy bei der IMRT und 5,58 ± 0,71 Gy bei der HT (p < 0,0001). Die HDR-BT ermöglicht eine bessere Schonung der Hrnblse. Die Dosisspitzen (Hot Spots) n der Urethr sind jedoch bei der HDR-BT höher. Ds Volumen des gesunden Gewebes, ds 10% der vorgeschriebenen Dosis erhält, wird bei Anwendung der HDR-BT etw um den Fktor 8 verringert (p < 0,0001). 1 Deprtment of Rdition Oncology, Liège University Hospitl, Belgium, 2 Deprtment of Medicl Physics, Liège University Hospitl, Belgium, 3 Deprtment of Medicl Physics, St Luc University Hospitl, Brussels, Belgium, 4 Deprtment of Rdition Oncology, St Luc University Hospitl, Brussels, Belgium, 5 Deprtment of Rdition Oncology, Oscr Lmbret Center, Lille, Frnce. Received: April 6, 2009; ccepted: July 16, Strhlenther Onkol 2009 No. 11 Urbn & Vogel

2 Schlussfolgerung: Die HDR-BT führt zu einer günstigeren Dosiskonformität im Vergleich zur HT und zur IMRT und reduziert so ds mit einer niedrigen Dosis belstete Volumen gesunden Gewebes. Schlüsselwörter: Prosttkrzinom IMRT Brchytherpie Tomotherpie Introduction Mny rndomized studies hve shown tht in prostte cncer rdiotherpy, dose escltion significntly improves the rte of biochemicl control [24, 27, 28, 39]. Nevertheless, n incresing dose to the prostte is ssocited with certin level of toxicity. Moderte side effects still remin reltively frequent even by using conforml rdition therpy [11, 38]. Different rdition modlities developed in order to improve the conformlity of the rdition tretment nd to decrese the toxicity re under investigtion. High-dose-rte brchytherpy (HDR-BT) is precise hypofrctionted rdition tretment whose efficcy is well estblished in prostte cncer [13, 14, 18, 19]. The α/β rtio of prostte crcinom is still being discussed but well known to be lower thn the typicl vlue of 10 Gy of most other solid tumors [4, 9]. So, hypofrctionted tretment should be ble to increse the therpeutic rtio [8, 35]. This hypofrctiontion ws initilly used in HDR-BT in combintion with externl-bem rdition therpy (EBRT) s demonstrted in recent rndomized phse III tril [14]. Intensity-modulted rdiotherpy (IMRT) is lso ble to sfely chieve high dose to the plnning trget volume (PTV) in prostte cncer. Retrospective studies indicte tht dose distributions of IMRT trnslte into improved rtes of disese control nd/or lower rtes of rectl toxicity [12, 37]. A recent study reported cceptble toxicity nd fvorble biochemicl outcome provided by ultrhigh-dose (86.4 Gy) IMRT for loclized prostte cncer [5]. Helicl tomotherpy (HT) is n dvnced form of continuous helicl IMRT with ccurte integrted imge-guided rdiotherpy (IGRT) [34]. This complex rottionl method of tretment delivery my improve the dose conformity of tretment pln compred with the fixed-bem method of IMRT using limited number of bem directions. First reports encourged this rdition modlity [7, 16, 32]. Improvement of tretment conformlity in order to spre orgns t risk (OARs) sometimes increses the volume of helthy tissues t distnce of the PTV receiving low rdition doses, with possible higher rtes of lte side effects such s secondry cncers [2, 3]. We therefore decided to compre the dosimetric selectivity of HDR-BT, IMRT nd HT on prostte model without tking the impct of frctiontion on tumor control nd side effects into ccount. Ptients nd Methods In the beginning of 2007, ten consecutive ptients with loclized dvnce prostte denocrcinom treted with 10-Gy HDR-BT boost fter EBRT were investigted. HDR-BT ws delivered through eight to ten ctheters plced by the sme well-trined rdition oncologist ccording to method previously reported [23]. Joint slices of 5 mm thickness ech were obtined nd trnsferred to the contouring softwre pltform (Artiview, Aquilb, Lille, Frnce). The clinicl trget volume (CTV) included only the prostte. No further expnsion from CTV ws pplied to generte the PTV. The rectum, bldder nd urethr were contoured entirely. The Brchyvision (version 8, Vrin Medicl System, Chrlottesville, VA, USA) tretment-plnning system (TPS) ws used to clculte the tretment for n HDR 192 Ir stepping source. At lest 95% of the PTV hd to be covered by the 10-Gy isodose while 50% could not receive > 150% of the prescribed dose. Dose constrints for OARs re represented in Tble 1. The dose optimiztion by modeling dwell times ws done step by step by mnully improving theoreticl proposl given t first by the TPS. For this study, we then trnsferred, vi DICOM RT link, the computed tomogrphy (CT) scn imges nd ll contouring informtion performed on the Artiview sttion to the Corvus (Nomos Corp., Pittsburgh, PA, USA) TPS for IMRT nd to Hi-Art (Tomotherpy inc, Mdison, WI, USA) for HT tretment plnning. Concerning IMRT, step-nd-shoot technique ws plnned with five 6-MV photon bems (0, 60, 120, 240, 300 ). The PTV ws defined s the CTV plus 4 mm in the left-right nd nterior-posterior xes nd 10 mm in the cr- Tble 1. First constrints pplied to orgns t risk in the different tretment plns for HDR-BT, IMRT nd HT dosimetry. HDR-BT: high-dose-rte brchytherpy; HT: helicl tomotherpy; IMRT: intensity-modulted rdiotherpy. Tbelle 1. Dosisbereiche für die Risikoorgne bei den unterschiedlichen Bestrhlungsplänen für die HDR-BT-, IMRT- und HT-Dosimetrie. HDR-BT: High-Dose-Rte-Brchytherpie; HT: helikle Tomotherpie; IMRT: intensitätsmodulierte Rdiotherpie. Tolerted Volume Miniml Mximl dose (Gy) bove (%) dose (Gy) dose (Gy) Tissues Rectum Urethr Bldder Strhlenther Onkol 2009 No

3 Figure 1. Axil nd sgittl views show high conformlity of HDR-BT, HT nd IMRT. The 10-Gy isodose lines well surround the PTV considered s the prostte for HDR-BT nd s the prostte with mrgins tking the prostte motion (blue line) for both other techniques into ccount. Abbildung 1. Die Drstellungen in xiler und sgittler Schnittebene belegen eine hohe Konformlität von HDR-BT, HT und IMRT. Die 10-Gy-Isodose, die ds PTV definiert, entspricht dem Prosttvolumen bei der HDR-BT, während für die beiden nderen Bestrhlungstechniken die Bewegungen der Prostt (blue Linie) mitberücksichtigt wurden. Figure 2. Axil nd sgittl views show volume receiving 5 Gy with HDR-BT, IMRT nd HT. Abbildung 2. Mit 5 Gy belstetes Volumen bei der HDR-BT, IMRT und HT (xile und sgittle Schnittebene). Figure 3. Volume of helthy tissues receiving 10% of the prescribed dose with the three irrdition techniques. Abbildung 3. Volumen gesunden Gewebes, ds bei den drei Bestrhlungstechniken mit 10% der verschriebenen Dosis belstet wird. niocudl direction. Dose constrints equl to those used for HDR-BT were first pplied to the PTV nd OARs nd were next modified until the lowest doses to criticl orgns were chieved, while mintining the initil constrints to the PTV. HT plnning ws done ccording to stndrdized clss solution with field width of 25 mm, pitch of 0.215, nd modultion fctor of 2. Preliminry constrints for PTV nd OARs were identicl to those introduced in IMRT nd HDR-BT plnning. The dose clcultion used totl of 18.4 full gntry rottions for the dose spred rry of the incident 6-MV bem. Importnce nd penlty vlues were djusted s the dosimetric prmeters were modified to obtin the lowest doses to criticl orgns without decrese of the PTV coverge initilly plnned. 738 Strhlenther Onkol 2009 No. 11

4 Tble 2. Dose received by 95% of plnning trget volume (PTV), men nd miniml doses delivered to the PTV with HDR-BT, IMRT nd HT modlity. HDR-BT: high-dose-rte brchytherpy; HT: helicl tomotherpy; IMRT: intensity-modulted rdiotherpy. Tbelle 2. Dosis für 95% des Plnungszielvolumens (PTV), mittlere und minimle uf ds PTV eingestrhlte Dosen für ds HDR-BT-, IMRT- und HT-Verfhren. HDR-BT: High-Dose-Rte-Brchytherpie; HT: helikle Tomotherpie; IMRT: intensitätsmodulierte Rdiotherpie. Tble 4. Mximl, men nd miniml doses received by urethr; dose received by 20% of urethr volume with HDR-BT, IMRT nd HT. HDR-BT: high-dose-rte brchytherpy; HT: helicl tomotherpy; IMRT: intensity-modulted rdiotherpy. Tbelle 4. Mximle, mittlere und minimle Dosen n der Urethr; Dosis für 20% des Urethrvolumens für ds HDR-BT-, IMRT- und HT-Verfhren. HDR-BT: High-Dose-Rte-Brchytherpie; HT: helikle Tomotherpie; IMRT: intensitätsmodulierte Rdiotherpie. Men for 10 ptients (Gy) p-vlue Men for 10 ptients (Gy) p-vlue PTV 95% HDR-BT ± 0.02 p = 0.3 HDR-BT vs. IMRT IMRT ± 0.07 p = 0.3 HDR-BT vs. HT HT ± 0 p = 0.6 IMRT vs. HT PTV men dose HDR-BT ± 0.49 p < HDR-BT vs. IMRT IMRT ± 0.18 p < HDR-BT vs. HT HT ± 0.06 p = 0.6 IMRT vs. HT PTV miniml dose HDR-BT 8.97 ± 0.32 p = 0.03 HDR-BT vs. IMRT IMRT 7.93 ± 1.08 p = 0.05 HDR-BT vs. HT HT 8.77 ± 0.31 p = 0.04 IMRT vs. HT double-sided pired t-test Tble 3. Mximl doses delivered to the rectum; doses received by 33%, 20% nd 0.5 ml of rectum volume with HDR-BT, IMRT nd HT. HDR- BT: high-dose-rte brchytherpy; HT: helicl tomotherpy; IMRT: intensity-modulted rdiotherpy. Tbelle 3. Mximle Dosen m Rektum; Dosen für 33%, 20% und 0,5 ml des Rektumvolumens für ds HDR-BT-, IMRT- und HT-Verfhren. HDR-BT: High-Dose-Rte-Brchytherpie; HT: helikle Tomotherpie; IMRT: intensitätsmodulierte Rdiotherpie. Men for 10 ptients(gy) p-vlue Mximl rectl dose HDR-BT ± 0.87 p = 0.3 HDR-BT vs. IMRT IMRT ± 0.22 p = 0.3 HDR-BT vs. HT HT ± 0.24 p = 0.6 IMRT vs. HT D 33% rectum HDR-BT 3.86 ± 0.3 p < HDR-BT vs. IMRT IMRT 6.57 ± 0.68 p < HDR-BT vs. HT HT 5.58 ± 0.71 p = 0.02 IMRT vs. HT D 20% rectum HDR-BT 4.80 ± 0.35 p < HDR-BT vs. IMRT IMRT 8.08 ± 0.58 p < HDR-BT vs. HT HT 6.87 ± 0.69 p = IMRT vs. HT D 0.5 ml rectum HDR-BT 7.99 ± 0.74 p < HDR-BT vs. IMRT IMRT ± 0.38 p < HDR-BT vs. HT HT ± 0.28 p = 0.3 IMRT vs. HT double-sided pired t-test Mximl urethrl dose HDR-BT ± 0.74 p < HDR-BT vs. IMRT IMRT ± 0.27 p < HDR-BT vs. HT HT ± 0.13 p = IMRT vs. HT Men urethrl dose HDR-BT ± 0.05 p = 0.6 HDR-BT vs. IMRT IMRT ± 0.23 p = 0.6 HDR-BT vs. HT HT ± 0.07 p = 0.89 IMRT vs. HT Miniml urethrl dose HDR-BT 5.48 ± 1.56 p = HDR-BT vs. IMRT IMRT 7.90 ± 2.46 p < HDR-BT vs. HT HT 9.93 ± 0.38 p = IMRT vs. HT D 20% urethr HDR-BT ± 0.41 p = 0.1 HDR-BT vs. IMRT IMRT ± 1.07 p = 0.98 HDR-BT vs. HT HT ± 0.12 p = 0.91 IMRT vs. HT double-sided pired t-test Tble 5. Volume of helthy tissues receiving 10% of the prescribed dose. HDR-BT: high-dose-rte brchytherpy; HT: helicl tomotherpy; IMRT: intensity-modulted rdiotherpy. Tbelle 5. Volumen gesunden Gewebes, ds 10% der vorgeschriebenen Dosis erhält. HDR-BT: High-Dose-Rte-Brchytherpie; HT: helikle Tomotherpie; IMRT: intensitätsmodulierte Rdiotherpie. Men volume receiving 10% of prescribed dose for 10 ptients (ml) p-vlue HDR-BT ± p < HDR-BT vs. IMRT IMRT 3, ± 1, p < HDR-BT vs. HT HT 5, ± 1, p < IMRT vs. HT double-sided pired t-test In order to compre the different tretment plnning methods, dose normliztion ws done to ll HDR-BT, IMRT nd HT plns to obtin full coverge of the PTV with the 95% isodose curve. Then, we compred the different PTV nd OARs dose-volume histogrm prmeters of the different tretment options using double-sided pired t-test. Strhlenther Onkol 2009 No

5 Results The three tretment plns were ble to stick to the dosimetric criteri nd the 10-Gy isodose did systemticlly surround 95% of the PTV while spring the criticl orgns. Nevertheless, the dose distribution is different with the three techniques of irrdition (Figures 1 to 3). Tble 2 presents the doses to the PTV with the three different methods. The dose to 95% of the PTV is 10 Gy for ll the tretments (p 0.3) which is in ccordnce with the designed methodology. The men dose to the PTV is significntly incresed with HDR-BT (16.23 ± 0.49 Gy; p < ) in comprison with the other methods while there is no difference between IMRT nd HT (10.47 ± 0.18 Gy nd ± 0.06 Gy, respectively; p = 0.6). Dose distribution inside the PTV is more heterogeneous with HDR-BT. Hot spots re observed round HDR ctheters. Cold spots re slightly less with HDR-BT in comprison with HT (8.97 ± 0.32 Gy nd 8.77 ± 0.31 Gy, respectively; p = 0.05) nd more importnt in the IMRT plnning (7.93 ± 1.08 Gy; p 0.04). Rectl doses re represented in Tble 3. The mximl dose is similr for the three methods (p 0.3). The dose delivered to 0.5 ml of the orgn is significntly reduced from ± 0.38 Gy (IMRT) nd ± 0.28 Gy (HT) to 7.99 ± 0.74 Gy with HDR-BT (p < ). 33% of the rectl volume receives men dose of 3.86 ± 0.3 Gy with HDR-BT compred to 6.57 ± 0.68 Gy with IMRT nd 5.58 ± 0.71 Gy with HT. The difference is in fvor of HDR-BT (p < 0.001) even if the protection rte of the rectum offered by HT is higher thn with IMRT (p = 0.02). Likewise, the bldder is better spred with HDR-BT. The men dose to 20% of the OAR is 3.49 ± 0.65 Gy with HDR-BT compred to 7.11 ± 1.13 Gy with IMRT nd 6.87 ± 1.09 Gy with HT (p < ). Urethr irrdition is more heterogeneous with HDR-BT with mximl dose of ± 0.74 Gy nd miniml dose of 5.48 ± 1.56 Gy. For IMRT, the mximl nd miniml doses re ± 0.27 Gy nd 7.9 ± 2.46 Gy; nd for HT ± 0.13 Gy nd 9.93 ± 0.38 Gy, respectively. The men dose to the urethr is, however, similr for the three pproches (p 0.6; Tble 4). The volume of distnt tissues from the PTV receiving 10% of the prescribed dose (1 Gy) is ± ml, 3, ± 1, ml, nd 5, ± 1, ml for HDR-BT, IMRT, nd HT, respectively (p < ; Tble 5). Discussion This study imed to compre HDR-BT, IMRT nd HT s wy to deliver fixed dose to the PTV while best spring the criticl orgns nd helthy distnt tissues. Hypofrctiontion fvored by low α/β vlue of prosttic denocrcinom ws initilly used in HDR-BT. It is lso pplicble to IMRT nd HT but remins under investigtion [15, 36]. We decided thus to deliver theoreticl normlized dose of 10 Gy for ech of the methods to compre only the dosimetric selectivity of these irrdition techniques without tking the impct of hypofrctiontion into ccount. CTV-PTV Expnsions For IMRT nd HT, the PTV definition hd to consider the intrfrction movements of the prostte nd the setup uncertinties before tretment using the most modern IGRT techniques [21, 26]. These prosttic intrfrction motions required sfety mrgin of 4 mm from the prostte [1, 22]. The longer the tretment durtion, the higher the risk of displcement, minly in the crniocudl direction [17, 20]. We therefore decided to fix 4 mm s the internl mrgin in the left-right nd nterior-posterior xes nd 10 mm in the crniocudl xis. No dditionl mrgin ws dded to tke setup errors into ccount ssuming tht ptient position is corrected dily pplying the most recent IGRT. Considering HDR-BT, no further expnsion from CTV ws utilized to generte the PTV becuse movement of the implnt hs no mrked influence on dose distribution with proper fixtion of ctheters [25]. Moreover, rdition tretment ws performed in the 30 min following the dosimetric CT scn while the ptient ws unble to move. Dose Distribution Inside the PTV The gol ws not to crete dose pinting inside the PTV but to crete fll of the dose outside the PTV s shrp s possible. HDR-BT llows delivering spontneously higher men doses to the PTV with smller cold spots compred to IMRT nd HT. This higher men dose in the centrl prts of the prostte is more likely to hve clinicl consequences for tumor control. Dose Distribution Inside the OARs The rectl dose ws significntly reduced in the HDR-BT pproch compred to IMRT nd HT pproches. Not only mximl doses were decresed but lso the men rectl doses which were recently demonstrted to contribute significntly to the toxicity [31]. HT seems to better spre the rectum s compred to IMRT. If mximl delivered doses re identicl with both techniques, doses to 20% nd 33% of the orgn re lower with HT compred to IMRT (p 0.02). The bldder spring is lso greter with HDR-BT in comprison with IMRT nd HT. The hot spots inside the urethr re more mrked with HDR-BT. This level of dose hs, however, not been demonstrted to contribute to incresed lte toxicity. In phse II studies, Mrtin et l. nd Mrtinez et l. demonstrted the possibility of four 9.5 Gy HDR-BT frctions for the tretment of fvorble-stge prostte cncer (equivlent dose per 2 Gy frction/eqd2 95 Gy or Gy ccording the prostte α/β rtio selected for the clcultion: 3 Gy or 1.5 Gy) [18, 19]. The dose to ny segment of urethr ws limited to 125% of the prescribed dose (EQD2 of 141 Gy). A recent report shows tht 740 Strhlenther Onkol 2009 No. 11

6 doses up to 75.6 Gy nd 86.4 Gy re recommended for intermedite- nd high-risk ptients, respectively [39]. If we considered totl tretment of HDR-BT with three 10-Gy frctions corresponding to EQD2 of 78 Gy or Gy (ccording the prostte α/β rtio selected: 3 Gy or 1.5 Gy), the mximl dose received by urethr would be n EQD2 of 127 Gy. Moreover, in our study, the men urethrl dose is identicl for the three compred methods (p 0.6). Risks of Secondry Cncer Rdition-induced cncers re n uncommon lte compliction of rdition therpy [2]. The risk of developing second primry cncer in irrdited norml tissues increses s rdition dose increses to mximum t doses round 3 5 Gy. The cell kill effect becomes dominnt t higher doses nd cuses reduction in survivl of trnsformed cells [29]. For low- nd intermedite-risk ptients, HDR-BT monotherpy my be mens of sfely delivering higher doses with less secondry rdition-induced cncers in comprison to IMRT or HT. HDR-BT s monotherpy is not widely estblished s stndrd tretment but is still under investigtion [6, 13, 18, 19]. Common schedules of HDR monotherpy proposed three or four frctions of Gy to the prostte. In this study, the volume of helthy tissue receiving 1 Gy is reduced by fctor 8 or 10 when compred to IMRT nd HT dt, respectively (p < ). Schneider et l. showed tht dose escltion for prostte rdition tretments reltes to n incresed risk of secondry tumor induction [30]. Tkm et l. demonstrted tht mong ll rdition tretment techniques for prostte cncer, either LDR- (low-dose-rte) or HDR-BT offers smller risk of crcinogenis thn tretments involving EBRT techniques [33]. These prostte ptients re not the most relevnt when looking t rdition-induced tumors, becuse the verge ge t tretment of these ptients is quite high. Nevertheless, tking the risk of secondry cncer into ccount, HDR should be specilly recommended to younger ptients or those with life expectncy > yers. Conclusion HDR-BT remins thus within the rdition therpy techniques offering the highest dosimetric selectivity. The reltively less impressive performnces of IMRT nd HT re prtilly induced by the need to tke mrgin for setup nd orgn motion, even with the best IGRT. Irrdition offering rel trcking properties such s CyberKnife could perhps compete with HDR-BT tht is more invsive [10]. However, low dose received by helthy tissues t distnce of the PTV should lso be quntified in future CyberKnife trils. References 1. Beltrn C, Hermn MG, Brin D. Plnning trget mrgin clcultions for prostte rdiotherpy bsed on intrfrction nd interfrction motion using four locliztion methods. Int J Rdit Oncol Biol Phys 2008;70: Bhojni N, Jeldres S, D Pozzo LF, et l. Externl-bem rdition therpy increses the rte of secondry mlignncies reltive to rdicl prosttectomy in men with prostte cncer. J Urol 2008;179:Suppl:113.bstrct Brenner DJ, Curtis RE, Hll EJ, et l. Second mlignncies in prostte crcinom ptients fter rdiotherpy compred with surgery. Cncer 2000;88: Brenner DJ, Mrtinez AA, Edmundson GK, et l. Direct evidence tht prostte tumors show high sensitivity to frctiontion (low lph/bet rtio), similr to lte-responding norml tissue. Int J Rdit Oncol Biol Phys 2002;52: Chlon O, Zelefsky MJ, Shippy A, et l. Ultr-high dose (86.4 Gy) IMRT for loclized prostte cncer: toxicity nd biochemicl outcomes. Int J Rdit Oncol Biol Phys 2008;71: Corner C, Rojs AM, Bryn L, et l. A phse II study of high-dose-rte fterloding brchytherpy s monotherpy for the tretment of loclized prostte cncer. Int J Rdit Oncol Biol Phys 2008;72: Cozzrini C, Fiorino C, Di Muzio N, et l. Significnt reduction of cute toxicity following pelvic irrdition with helicl tomotherpy in ptients with loclized prostte cncer. Rdiother Oncol 2007;84: Dsu A. Is the lph/bet vlue for prostte tumours low enough to be sfely used in clinicl trils? Clin Oncol (R Coll Rdiol) 2007;19: Fowler JF. The rdiobiology of prostte cncer including new spects of frctionted rdiotherpy. Act Oncol 2005;44: Fuller DB, Nitoh J, Lee C, et l. Virtul HDR CyberKnife tretment for loclized prosttic crcinom: dosimetry comprison with HDR brchytherpy nd preliminry clinicl observtions. Int J Rdit Oncol Biol Phys 2008;70: Goldner G, Bombosch V, Geinitz H, et l. Moderte risk-dpted dose escltion with three-dimensionl conforml rdiotherpy of loclized prostte cncer from 70 to 74 Gy. Strhlenther Onkol 2009;185: Guckenberger M, Flentje M. Intensity-modulted rdiotherpy (IMRT) of loclized prostte cncer. A review nd future perspectives. Strhlenther Onkol 2007;183: Hoskin PJ, Bownes P, Bryn L, et l. HDR monotherpy brchytherpy for loclised prostte cncer. Clin Oncol (R Coll Rdiol) 2007;19:Suppl:S Hoskin PJ, Motohshi K, Bownes P. High dose rte brchytherpy in combintion with externl bem rdiotherpy in the rdicl tretment of prostte cncer: initil results of rndomised phse three tril. Rdiother Oncol 2007;84: Junius S, Hustermns K, Bussels B, et l. Hypofrctionted intensity modulted irrdition for loclized prostte cncer, results from phse I/II fesibility study. Rdiother Oncol 2007;8: Keiler L, Dobbins D, Kulsekere R, et l. Tomotherpy for prostte denocrcinom: report on cute toxicity. Rdiother Oncol 2007;84: Lngen KM, Willoughby TR, Meeks SL, et l. Observtion on rel-time prostte glnd motion using electromgnetic trcking. Int J Rdit Oncol Biol Phys 2008;71: Mrtin T, Blts D, Kurek R, et l. 3-D conforml HDR brchytherpy s monotherpy for loclized prostte cncer. Strhlenther Onkol 2004;180: Mrtinez AA, Ptki I, Edmundson G, et l. Phse II prospective study of the use of conforml high-dose-rte brchytherpy s monotherpy for the tretment of fvorble stge prostte cncer: fesibility report. Int J Rdit Oncol Biol Phys 2001;49: Meijer GJ, De Klerk J, Bzdusek K, et l. Wht CTV-to-PTV mrgins should be pplied for prostte irrdition? Four-dimensionl quntittive ssessment using model-bsed deformble imge registrtion techniques. Int J Rdit Oncol Biol Phys 2008;72: Nirz O, Merz F, Deutschmnn H, et l. A strtegy for the use of imge-guided rdiotherpy on liner ccelertors nd its impct on tretment mrgins for prostte cncer ptients. Strhlenther Onkol 2008;184: Nedervenn A, Lngedijk J, Hofmn P. Detection of fiducil gold mrkers for utomtic on-line megvoltge position verifiction using mrker extrction kernel (MEK). Int J Rdit Oncol Biol Phys 2000;47: Strhlenther Onkol 2009 No

7 23. Nickers P, Thissen B, Jnsen N, et l. 192 Ir or 125 I prostte brchytherpy s boost to externl bem rdiotherpy in loclly dvnced prosttic cncer: dosimetric point of view. Rdiother Oncol 2006;78: Peeters STH, Heemsbergen WD, Koper PCM, et l. Dose-response in rdiotherpy for loclized prostte cncer: results of the Dutch multicenter rndomized phse III tril compring 68 Gy of rdiotherpy with 78 Gy. J Clin Oncol 2006;24: Pieters BR, Vn der Grient JNB, Blnk LECM, et l. Miniml displcement of novel self-nchoring ctheters suitble for temporry prostte implnts. Rdiother Oncol 2006;80: Pinkw M, Pursch-Lee M, Asdpour B, et l. Imge-guided rdiotherpy for prostte cncer. Strhlenther Onkol 2008;184: Pollck A, Hnlon AL, Horwitz EM, et l. Prostte cncer rdiotherpy dose response: n updte of the fox chse experience. J Urol 2004;171: Roch M. Dose esclted externl bem rdiotherpy versus neodjuvnt ndrogen deprivtion therpy nd conventionl dose externl bem rdiotherpy for cliniclly loclized prostte cncer: do we need both? Strhlenther Onkol 2007:183:Specil Issue 2: Ruben JD, Dvis S, Evns C, et l. The effect of intensity-modulted rdiotherpy on rdition-induced second mlignncies. Int J Rdit Oncol Biol Phys 2008;70: Schneider U, Lomx A, Besserer J, et l. The impct of dose escltion on secondry cncer risk fter rdiotherpy of prostte cncer. Int J Rdit Oncol Biol Phys 2007;48: Söhn M, Alber M, Yn D. Principl component nlysis-bsed pttern nlysis of dose-volume histogrms nd influence on rectl toxicity. Int J Rdit Oncol Biol Phys 2007;69: Sterzing F, Schubert K, Srok-Perez G, et l. Helicl tomotherpy. Experiences of the first 150 ptients in Heidelberg. Strhlenther Onkol 2008;184: Tkm R, Bezk E, Yeoh E. Risk of second primry cncer following prostte cncer rdiotherpy: DVH nlysis using the competitive risk model. Phys Med Biol 2009;54: Tomsej M. The TomoTherpy Hi.Art System for sophisticted IMRT nd IGRT with helicl delivery: recent developments nd clinicl pplictions. Cncer Rdiother 2006;10: Willims SG, Tylor JM, Liu N, et l. Use of individul frction size dt from 3756 ptients to directly determine the lph/bet rtio of prostte cncer Int J Rdit Oncol Biol Phys 2007;68: Yuen J, Rodrigues G, Trenk K, et l. Compring two strtegies of dynmic intensity modulted rdition therpy (dimrt) with 3-dimensionl conforml rdition therpy (3DCRT) in the hypofrctionted tretment of high-risk prostte cncer. Rdiother Oncol 2008;3: Zelefsky MJ, Fuks Z, Hunt M, et l. High-dose intensity modulted rdition therpy for prostte cncer: erly toxicity nd biochemicl outcome in 772 ptients. Int J Rdit Oncol Biol Phys 2002;53: Zelefsky MJ, Fuks Z, Wolfe T, et l. Loclly dvnced prosttic cncer: long-term toxicity outcome fter three-dimensionl conforml rdition therpy: dose-escltion study. Rdiology 1998;209: Zelefsky MJ, Ymd Y, Fuks Z, et l. Long term results of conforml rdiotherpy for prostte cncer: impct of dose escltion on biochemicl control nd distnt metstses-free survivl outcomes. Int J Rdit Oncol Biol Phys 2008;71: Address for Correspondence Johnne Hermesse, MD Deprtment of Rdition Oncology B35 Domine Universitire du Srt Tilmn 4000 Liège Belgium Phone (+32/43) , Fx -952 e-mil: jhermesse@chu.ulg.c.be, johermesse@hotmil.com 742 Strhlenther Onkol 2009 No. 11