JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS, VOLUME 16, NUMBER 1, 2015

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1 JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS, VOLUME 16, NUMBER 1, 2015 Technicl Note: Dosimetric evlution of Monte Crlo lgorithm in ipln for stereotctic bltive body rdiotherpy (SABR) for lung cncer ptients using RTOG 0813 prmeters Dmodr Pokhrel, Rjeev Bdkul, Hongyu Jing, Prvesh Kumr, Fen Wng Deprtment of Rdition Oncology, The University of Knss Cncer Center, Knss City, KS, USA Received 30 April, 2014; ccepted 26 September, 2014 For stereotctic bltive body rdiotherpy (SABR) in lung cncer ptients, Rdition Therpy Oncology Group (RTOG) protocols currently require rdition dose to be clculted using tissue heterogeneity corrections. Dosimetric criteri of RTOG 0813 were estblished bsed on the results obtined from non-monte Crlo (MC) lgorithms, such s superposition/convolutions. Cliniclly, MC-bsed lgorithms re now routinely used for lung SABR dose clcultions. It is essentil to confirm tht MC clcultions in lung SABR meet RTOG guidelines. This report evlutes ipln MC plns for SABR in lung cncer ptients using dose-volume histogrm normliztion per current RTOG 0813 complince criteri. Eighteen Stge I-II non-smll cell lung cncer (NSCLC) ptients with centrlly locted tumors, who underwent MC-bsed lung SABR with heterogeneity correction using X-ry Voxel Monte Crlo (XVMC) lgorithm (BrinLAB ipln version 4.1.2), were nlyzed. Totl dose of 60 Gy in 5 frctions ws delivered to plnning trget volume (PTV) with t lest V100% = 95%. Internl trget volumes (ITVs) were delineted on mximum intensity projection (MIP) imges of 4D CT scns. PTV (ITV + 5 mm mrgin) volumes rnged from 10.0 to 99.9 cc (men = 36.8 ± 20.7 cc). Orgns t risk (OARs) were delineted on verge imges of 4D CT scns. Optiml clinicl MC SABR plns were generted using combintion of non-coplnr conforml rcs nd bems for the Novlis-TX consisting of high definition multilef collimtors (MLCs) nd 6 MV-SRS (1000MU/min) mode. All plns were evluted using the RTOG 0813 high nd intermedite dose spillge criteri: conformity index (R100%), rtio of 50% isodose volume to the PTV (R50%), mximum dose 2 cm wy from PTV in ny direction (D 2cm ), nd percent of norml lung receiving 20 Gy (V 20 ) or more. Other orgns-t-risk (OARs) doses were tbulted, including the volume of norml lung receiving 5 Gy (V 5 ), mximum cord dose, dose to < 15 cc of hert, nd dose to <5 cc of esophgus. Only six out of 18 ptients met ll RTOG 0813 complince criteri. Eight of 18 ptients hd minor devitions in R100%, four in R50%, nd nine in D 2cm. However, only one ptient hd minor devition in V 20. All other OARs doses, such s mximum cord dose, dose to < 15 cc of hert, nd dose to < 5 cc of esophgus, were stisfctory for RTOG criteri, except for one ptient, for whom the dose to < 15 cc of hert ws higher thn RTOG guidelines. The preliminry results for our limited ipln XVMC dose clcultions indicte tht the mjority (i.e., 2/3) of our ptients hd minor devitions in the dosimetric guidelines set by RTOG 0813 protocol in one wy or nother. When using n exclusive highly sophisticted XVMC lgorithm, the RTOG 0813 dosimetric complince criteri such s R100% nd D 2cm my need to be revisited. Corresponding uthor: Dmodr Pokhrel, Deprtment of Rdition Oncology, The University of Knss Cncer Center, 3901 Rinbow Boulevrd, Knss City, KS 66160, USA; phone: (913) ; fx: (913) ; emil: dpokhrel@kumc.edu

2 350 Pokhrel et l.: Dosimetric evlution of ipln Monte Crlo lgorithm 350 Bsed on our limited number of ptient dtsets, in generl, bout 6% for R100% nd 9% for D 2cm corrections could be pplied to pss the RTOG 0813 complince criteri in most of those ptients. More ptient plns need to be evluted to mke recommendtion for R50%. No djustment is necessry for OAR dose tolernces, including norml lung V 20. In order to estblish new MC specific dose prmeters, further investigtion with lrge cohort of ptients including centrl, s well s peripherl lung tumors, is nticipted nd strongly recommended. PACS number: 8087 Key words: lung cncer, SBRT, heterogeneity, Monte Crlo, XVMC lgorithm, RTOG 0813 I. INTRODUCTION SABR with hypofrctionted dose schemt hs emerged vible lterntive tretment for mediclly inoperble erly-stge lung cncer ptients. (1) Tretment plnning for the SABR lung cse is chllenging due to the involvement of smll fields nd low-density lung medium (ir), which could result in electronic disequilibrium in the regions ner low-density heterogeneity interfce. (2) Dose clcultion lgorithms in commercil tretment plnning systems (TPS) must hve ccurte modeling for the tissue heterogeneity corrections in order to void inccurte delivery of the monitor units (MUs) of rdition during the ptient tretment. Rdition Therpy Oncology Group (RTOG) 0813 SABR lung protocol requires the prticipting institutions to generte the tretment plns using dose clcultion lgorithms tht cn compute the dose pplying tissue heterogeneity corrections. Dosimetric criteri of RTOG 0813 were estblished bsed on the results obtined from non-monte Crlo (MC) lgorithms, such s superposition/convolutions. (3,4) Recently, severl commercil TPS hve employed MC-bsed dose clcultion lgorithms, nd mny reserchers hve investigted whether MC-bsed dose clcultion lgorithms cn meet the dosimetric criteri of RTOG (5,6) For instnce, Li et l. (5) evluted the MC lgorithm employed in Monco TPS (Computerized Medicl System, St. Louis, MO) for SBRT lung plns nd compred the results ginst the superposition lgorithm in XiO TPS (Computerized Medicl System, St. Louis, MO). In one of the most recent studies, Rn et l. (6) evluted the MC-bsed Acuros XB employed in Eclipse TPS (Vrin Medicl Systems, Plo Alto, CA) for the SBRT lung cses, nd compred the results ginst the nisotropic nlyticl lgorithm (AAA) in Eclipse TPS. Li et l. (5) reported tht dosimetric results from MC lgorithm in Monco hd lrger vlues compred to the ones from superposition lgorithm in XiO TPS. In the study by Rn et l., (6) it ws found tht Acuros XB resulted in lower mgnitudes of R100%, R50%, nd D 2cm by 5%, 1.2%, nd 1.6%, respectively, on verge, thn the AAA, except for the norml lung tissue (V 20 ) where it ws higher by 1.1%. In ddition to the vrition in dose clcultion lgorithms nd TPS used between these two studies the tretment plnning techniques were different s well. Specificlly, Li et l. (5) used intensity modulted rdition therpy (IMRT) nd Rn et l. (6) used volumetric modulted rc therpy (VMAT), which is referred s RpidArc in Eclipse TPS. MC is more complex nd ccurte in hndling of tissue heterogeneities. This is becuse of their bility to more ccurtely simulte rdition trnsport of ) secondry sctter photons, nd b) lterl electron equilibrium in the MC lgorithms, nd therefore, more ccurtely predict dose distribution, specificlly, t the low-density lung nd heterogeneous tissues interfces. Tht could ctully emulte ctul mesured doses. Cliniclly, MC-bsed lgorithms re now routinely used for lung SABR dose clcultions. It is essentil to confirm tht MC clcultions in lung SABR meet RTOG guidelines. At our institution, we currently use X-ry Voxel Monte Crlo (XVMC) lgorithm (7) (BrinLAB ipln, Feldkirchen, Germny) for dose clcultions for our lung SABR ptients. To our best knowledge, dosimetric evlution of ipln MC lung

3 351 Pokhrel et l.: Dosimetric evlution of ipln Monte Crlo lgorithm 351 SABR pln using RTOG 0813 criteri is yet to be reported. One of the requirements of RTOG 0813 protocol is the pln normliztion to be done to single point (e.g., n isocenter or point inside the plnning trget volume (PTV)). (3, 4) Since, dose-volume (DV) normliztion is one of the most populr methods used to report the clinicl dosimetric results, the min purpose of this pper ws to investigtes whether those RTOG 0813 dosimetric criteri cn be met or not. The results were presented by pplying ipln XVMC lgorithm dose clcultion nd DV normliztion method for the clinicl SABR lung plns. II. MATERIALS AND METHODS A. Dose clcultion lgorithm Both the pencil bem (PB) nd XVMC lgorithms were commissioned nd cliniclly implemented in the BrinLAB ipln RT (version 4.1.2) TPS in our institution. The XVMC ws bsed on the X-ry Voxel Monte Crlo lgorithm (7) which consists of source modeling, bem collimting system modeling, nd ptient dose computtion. The dose clcultion prmeters for XVMC in ipln re sptil resolution, men vrince, dose result type, nd MLC model. The sptil resolution defines the size of the dose clcultion grid, wheres the men vrince estimtes the sttisticl uncertinty of the MC dose clcultion. Choosing smller vrince, the dose clcultions would be more ccurte t the cost of computtion time. Dose to wter nd to medium re the two options in the dose type; in this clcultion it ws set to dose to the medium. Reders re dvised to refer to the BrinLAB Technicl Reference Guide (8) for more detils for XVMC lgorithm nd its clinicl implementtion. B. Verifiction of XVMC lgorithm There hve been severl studies focused on verifying Monte Crlo dose clcultions in both homogenous nd heterogeneous mediums. These studies utilized ipln RT dose plnning system. For instnce, using 6 MV photon bem with micro-mlc, n experimentl vlidtion of the XVMC lgorithm (9) ws performed. The vlidtion utilized film, ion chmbers, wter phntoms, nd heterogeneous solid wter slbs. These solid wter slbs contined bone nd lung density equivlent mterils. The experiment demonstrted tht the clculted dose greed with the mesured dose within ± 2% in high-dose regions, nd 2 mm in high-grdient regions. (9, 10) The verge 1D gmm vlues did not exceed 0.3 with 2%/2 mm cretion when compring clculted nd mesured dose distributions. (11) Another experimentl investigtion of XVMC lgorithm ws presented by Fippel et l., (12) utilizing dimond detector nd film mesurements on homogenous nd inhomogeneous phntoms, nd 6 MV photons. Fippel nd collegues lso demonstrted tht the mesured nd clculted doses greed within experimentlly uncertinty (within ± 2%). Dobler et l., (13) using GAFCHROMIC EBT films, reveled tht XVMC predicted the mesured dose more ccurtely with mximum difference of -3%. However, the PB lgorithm overestimted the dose by up to 15% compred to the mesurement, suggesting tht PB lgorithms re limited t the tissue/lung interfces, nd MC is the most ccurte lgorithm for dose prediction. Another dosimetric study reported by Chen et l. (14) suggested tht XVMC lgorithm greed well with film mesurements when using 15 MV photons (< 1% difference in lterl profile). Wheres the devition between the PB lgorithm nd film mesurements ws gin up to 15%, this is consistent with other studies. In the sme study using 35 lung cncer ptients, the lrgest differences were reported for smll lung tumors circumferentilly encompssed by the lung tissues. The PTV men dose difference between PB nd XVMC ws in excess of 4 Gy (prescription dose, 30 Gy). The volume covered by the 9 Gy isodose of lung dose ws 8% higher when clculted by XVMC compred with PB in one ptient. In ddition, Chen nd collegues reported tht the dose clcultion ccurcy is lso dependent on tumor size nd loction. In most recent studies by Sethi et l., (15) XVMC lgorithm ws benchmrk using ion chmber nd

4 352 Pokhrel et l.: Dosimetric evlution of ipln Monte Crlo lgorithm 352 EDR films in vrious depth in five different phntoms with four different density mterils. These include tissue-equivlent plstic wter, lung-equivlent (low- nd high-density) corks, nd bone, nd irrdited with 6 MV photons. For heterogeneous lung phntoms, there ws n excellent greement (< 3%) between mesured nd clculted dose profiles. However, PB clcultions significntly overestimted men PTV mesured dose by up to 34%. Mesured nd PB clculted dose difference incresed with decresing field size, decresing density, nd incresing depth within heterogeneity (however similr results beyond heterogeneity). In contrst, lrge underestimted dose (up to 50%) ws observed in the penumbr region while using PB lgorithm. (15) Using virtul phntom nd ptients dtsets, Miur et l. (16) hve lso presented similr results in which the men PTV dose ws nerly 20% higher on both the phntom nd ptients with PB lgorithm compred to XVMC. Our own clinicl experience (17) on vlidting nd cliniclly implementing ipln XVMC lgorithm using Qusr (Modus Medicl Devices Inc., London, Cnd) phntom study hd shown n excellent greement (within ± 2%) between doses clculted using XVMC versus ion chmber mesurements for 6 MV-SRS bem in lung-equivlent mteril. In our phntom study, (17) the dose devition between heterogeneities-corrected PB nd mesured vlue ws s lrge s 9%. MC lgorithm not only predicted ccurte dose t isocenter, but lso t borders of tumors where heterogeneities-corrected PB overestimted the doses. Tht is due to the lck of electronic equilibrium in the regions ner low-density tissues heterogeneities interfce. In our most recent clinicl study (18) with 10 lung cncer ptients, the men PTV dose ws s high s 13%, on verge, when using heterogeneities-corrected PB lgorithm compred to XVMC using sme bem configurtions, MLCs, nd the sme number of MUs. However, the volume covered by 5 Gy, 10 Gy, nd 20 Gy isodose lines of the norml lung were comprble (within 3.0%), on verge, when clculted by heterogeneities-corrected PB compred to XVMC. All the peer reviewed litertures cited in this pper hve well-documented the fct tht PB clcultion overestimtes the PTV nd OARs doses significntly, s reported bove. C. Ptient simultion nd trget contouring Eighteen centrlly locted Stge I-II non-smll cell lung cncer (NSCLC) ptients who underwent MC-bsed lung SABR t the University of Knss Hospitl, Knss City, KS were included in this retrospective study. The simultion ws performed on 16 slice Phillips Brillince Big Bore CT Scnner (Philips Helthcre, Andover, MA) nd ptient in the supine position ws immobilized using BlueBAG BodyFIX system (Medicl Intelligence, Schwbmuenchen, Germny) with n bdominl compression. Motion mngement ws done using PHILIPS bellows (Clevelnd, OH) for 4D CT scns. The 4D CT imges were cquired with pixels t 2 mm slice thickness nd 2 mm slice spcing. All phses of DICOM 4D CT dtsets were then electroniclly trnsferred to the BrinLAB ipln TPS for contouring purposes. Mximum intensity projection (MIP) nd men intensity projection (verge) imges were then creted in ipln TPS nd uto-fused with ech phse of 4D CT imges. Internl trget volume (ITV) ws delineted on MIP imges of the 4D CT scns. PTV ws generted from ITV with 5 mm uniform mrgin with men volume 36.8 ± 20.7 cc (rnged from 10.0 to 99.9 cc). The criticl structures, such s bilterl lungs excluding the ITV (ipsi-lung), hert, esophgus, nd spinl cord, were delineted on the verge imges of 4D CT scns. D. Tretment plnning nd dose clcultion Optiml clinicl MC SABR tretment plns were generted using combintion of non-coplnr 3D conforml rcs nd bems for the Novlis TX liner ccelertor (Vrin Plo Alto, CA) with BrinLAB system consisting of high definition MLCs nd 6 MV-SRS (1000MU/min) mode (see Fig. 1). All tretment plns were clculted using XVMC lgorithm for heterogeneity corrections with cm 3 dose grid sizes, 2% vrince (reltive stndrd devition of the men), dose to medium, nd ccurcy optimized for MLC modeling. All plns hd dose delivery schem of 60 Gy in 5 frctions with t lest 95% of the PTV volume received

5 353 Pokhrel et l.: Dosimetric evlution of ipln Monte Crlo lgorithm 353 Fig.1. Demonstrtion of coronl view of noncoplnr conforml rcs nd sttic bems setup with respect to ptient ntomy. 100% of the prescription dose DV normliztion. For smll PTV volume ( 10 cc), liberl bem mrgin ws used to stisfy the protocol s recommendtions to tret t lest 3.5 cm bem perture while keeping the originl PTV volume. In cses where the PTV ws butting criticl orgns, the plns were re-optimized such tht there ws no hot spot within the orgn tht receiving more thn 105% of the prescribed dose. E. Pln evlution The DVHs of ll tretment plns were generted in the BrinLAB ipln TPS nd evluted for the following RTOG 0813 high nd intermedite dose spillge dose prmeters: (4) ) R100%: rtio of prescription isodose volume to the PTV (conformlity index), b) R50%: rtio of 50% prescription isodose volume to the PTV, c) D 2cm : mximl dose 2 cm wy from PTV in ny direction s percentge of prescription dose, nd d) V 20 : percentge of ipsilterl lung receiving dose equl to or lrger thn 20 Gy. Furthermore, ll the clinicl MC plns were evluted for the reltive volume of norml lung receiving 5 Gy dose, mximum spinl cord dose, dose to < 15 cc of hert, nd dose to < 5 cc of esophgus, s well. A clinicl MC computed DVH for one representtive ptient is shown in Fig. 2 nd MC dose distribution (xil, coronl nd sgittl views) for the sme ptient is shown in Fig. 3.

6 354 Pokhrel et l.: Dosimetric evlution of ipln Monte Crlo lgorithm 354 Fig. 2. A MC DVH showing 95% of the PTV is conformlly covered by the prescription dose (60 Gy). R100% = 1.18, men PTV dose = 68.3 Gy, mximum dose = 76.6 Gy. Fig. 3. MC Isodose distributions on xil (left), coronl (center) nd sgittl (right) views for SABR lung pln. Lines indicte ITV (innermost), followed by PTV. Higher isodose lines, such s 100%, 95%, nd 80%, hd shrp flloff, hotspot ws within 128%; 20 Gy isodose line restricted minly in the ipsilterl lung. Pink color ring ws contoured to clculte D 2cm (%). III. RESULTS & DISCUSSION Tbles 1-5 present the results of dosimetric prmeters from 18 SABR lung plns correspond to RTOG 0813 dosimetry evlution criteri. Only six out of 18 ptients met ll the RTOG 0813 complince criteri. Eight of 18 ptients hd minor devitions in R100%, four in R50%, nd nine in D 2cm. However, only one ptient (# XIII) ssocited with the lrgest PTV volume hd minor violtion in V 20. All of the OAR doses, such s mximum cord dose, dose to < 15 cc of hert, nd dose to < 5 cc of esophgus, were stisfctory for RTOG 0813 criteri, except in ptient # X, where the dose to < 15 cc of hert which hd tumor volume butting hert ws higher with minor devition on RTOG 0813 requirement.

7 355 Pokhrel et l.: Dosimetric evlution of ipln Monte Crlo lgorithm 355 Tble 1 shows tht eight out of 18 ptients hd minor devitions in R100%. The men vlue of R100% ws 1.22 ± 0.07, resulting in stndrd devition of bout 6% from the men vlue. However, no mjor devition ws observed. Minor devitions in R100% were cliniclly ccepted by the physicins. The devitions cn be explined, primrily, due to underlying chrcteristic behviors of the XVMC lgorithm for dose distribution prediction, or it my be during initil pln review physicin subjective in selecting tretment pln bsed on clinicl decisions. The underlying chrcteristic behviors of XVMC could be explined by more ccurte modeling of ) secondry sctter photons, nd b) lterl electron equilibrium, specificlly t the lung nd tumor interfces. In Tble 2 it will be seen tht only four out of 18 ptients did not meet the RTOG 0813 R50% criteri. The men vlue of R50% ws 4.1 ± 0.7. However, one ptient who ws ner the tolernce vlue (# XIII with the lrgest PTV volume of nerly 100 cc, which ws in the border line rnge of SABR tretment volume) ws deemed cliniclly cceptble by the physicin nd treted. Other three ptients (# XII, # XIV, nd # XVII) who hd minor devitions in R50% were cliniclly ccepted by the physicins nd were treted. In those three cses, the minor devitions in R50% could be explined by subjectivity of the physicin-dependent initil tretment pln review bsed on clinicl decisions. Also, it could be due to ptient geometry nd tumor loction preventing optiml bem rrngements or some contributions from underlying chrcteristic behviors of the XVMC lgorithm for dose prediction s discussed erlier. As reported in Tble 3, nine out of 18 ptients hd minor devitions in RTOG 0813 D 2cm criteri. The men vlue of D 2cm ws 58.9 ± 8.1, resulting in stndrd devition of bout 9% from the men vlue. However, no mjor devition ws observed. Those devitions could be justified by numerous resons: ) primrily, due to underlying chrcteristic behviors of the XVMC lgorithm depending in predicting more ccurte dose distribution in surrounding low-density lung nd heterogeneous tumor interfces; b) those minor devitions in D 2cm were mostly ssocited to lrge/medium size tumors with suboptiml conformlity index; in generl, the lrger the tumor volume gets, the hrder it is to meet the D 2cm criteri; c) ptient-specific clinicl restrictions preventing optiml bem rrngements; d) or during the initil subjective tretment pln review by the physicin to respect criticl structures dose tolernce. Tble 1. Evlution of R100% in SABR lung plns clculted by ipln XVMC lgorithm. PTV Vol. RTOG 0813 R100% Ptient # (cc) Minor Devition ipln MC I II III IV V VI VII VIII IX X XI XII XIII XIV XV XVI XVII XVIII AVG STDEV Dt tht hve minor devitions from RTOG 0813 criteri. PTV = plnning trget volume; R100% = rtio of prescription isodose volume to PTV; AVG = Averge; STDEV = stndrd devition.

8 356 Pokhrel et l.: Dosimetric evlution of ipln Monte Crlo lgorithm 356 Tble 2. Evlution of R50% in SABR lung plns clculted by ipln XVMC lgorithm. PTV Vol. RTOG 0813 R50% Ptient # (cc) Minor Devition ipln MC I II III IV V VI VII VIII IX X XI XII XIII XIV XV XVI XVII XVIII AVG STDEV Dt tht hve minor devitions from RTOG 0813 criteri. PTV = plnning trget volume; R50% = rtio of 50% prescription isodose volume to PTV; AVG = Averge; STDEV = stndrd devition. Tble 3. Evlution of D 2cm in SABR lung plns clculted by ipln XVMC lgorithm. PTV Vol. RTOG 0813 D 2cm Ptient # (cc) Minor Devition ipln MC I II III IV V VI VII VIII IX X XI XII XIII XIV XV XVI XVII XVIII AVG STDEV Dt tht hve minor devitions from RTOG 0813 criteri. PTV = plnning trget volume; D 2cm = mximl dose 2 cm from PTV in ny direction s percentge of prescription dose; AVG = Averge; STDEV = stndrd devition. Tbles 4 nd 5 report the dosimetric evlution of norml lung, V 20 (Tble 4) nd V 5, s well s other OARs doses (Tble 5) such s dose to hert, mximum cord dose, nd esophgus doses in SABR lung plns clculted by ipln XVMC lgorithm respectively. The results of this study showed tht the RTOG 0813 high-dose spillge criteri, such s R100%, ws met only in 10 out of 18 ptients, with 8 minor devitions. The stndrd devition

9 357 Pokhrel et l.: Dosimetric evlution of ipln Monte Crlo lgorithm 357 Tble 4. Evlution of norml lung V 20 in SABR lung plns clculted by ipln XVMC lgorithm. PTV Vol. RTOG 0813 V 20 (%) Ptient # (cc) Minor Devition ipln MC I II III IV V VI VII VIII IX X XI XII XIII b XIV XV XVI XVII XVIII AVG STDEV Norml lung V 20 vlues rnged from 1.1% to 13.8% (men = 5.3 ± 3.0%). b No minor devition in V 20 from the RTOG 0813 criteri ws observed; except for one ptient (ptient # XIII) whose PTV volume ws bout 100 cc nd whose V 20 = 13.8%. PTV = plnning trget volume; Ipsi-lung = Ipsilterl lung; V 20 = percentge of ipsilterl lung receiving dose equl to or lrger thn 20 Gy; AVG = Averge; STDEV = stndrd devition. of R100% from the men vlue ws bout 6%. However, there ws no mjor devition in R100%. One of the intermedite dose spillge criteri, R50% pssed the RTOG guidelines for 14 ptients, with only three minor devitions nd one mjor devition, ner the tolernce vlue. It ws observed tht the mjor devition ws due to the lrgest PTV volume tht ws outside or ner the recommended tolernce of SABR tretment volume. Other three ptients (ptient # XII, # XIV, nd # XVII) who hd minor devitions in R50% hd suboptiml bem rrngements due to ptient geometry nd tumor loctions. All those plns were cliniclly ccepted by the physicins nd were treted. However, 50% of our ptients hd minor devitions in D 2cm, but no mjor devition ws observed. The men vlue of D 2cm ws 58.9 ± 8.1, with stndrd devition resulting from the men vlue of bout 9%. Only one ptient, who hd the lrgest PTV volume, hd minor devition from RTOG 0813 criteri in norml lung V 20. No minor devitions from RTOG 0813 criteri were observed for ll other OAR dose tolernces such s mximum cord dose, dose to < 15 cc of hert, nd dose to < 5 cc of esophgus, except for one ptient (ptient #X) whose tumor ws next to the hert. Minor devitions from RTOG complince criteri were lso reported in previous studies. (5,6) For instnce, Rn et l. (6) compred the tretment plns computed by nlytic nisotropic lgorithm (AAA) nd Acuros XB for the sme number of MUs. It ws reported tht AAA plns hd higher R100%, R50%, nd D 2cm when compred to the Acuros XB plns. However, V 20 of lung ws found to be lower in AAA plns. Rn nd collegues lso reported minor devitions in R100%, R50%, nd D 2cm for both the AAA nd Acuros XB plns, with Acuros XB showing minor devition in fewer cses when compred to AAA. In tht study, it ws lso reported lower PTV coverge using Acuros XB when compred to AAA. On the other dosimetric study reported by Li et l. (5) using Monco MC lgorithm in XiO TPS lso observed minor devitions from RTOG 0813 complince criteri on R50%, R100%, nd D 2cm. Our findings were consistent with those previous reports. One of the differences between our study nd Rn et l. (6) is the pln normliztion method. Dosimetric results from their study were bsed on the normliztion t single point per RTOG

10 358 Pokhrel et l.: Dosimetric evlution of ipln Monte Crlo lgorithm 358 Tble 5. Evlution of norml lung V 5, dose to hert, mximum cord dose, nd esophgus doses in SABR lung plns clculted by ipln XVMC lgorithm. Mximum Dose to Dose to Norml Lung Dose to <15cc of <5cc of PTV Vol. V 5 Spinl Cord b Hert c Esophgus d Ptient # (cc) (%) (Gy) (Gy) (Gy) I II III IV V VI VII VIII IX X e 5.2 XI XII XIII XIV XV XVI XVII XVIII AVG STDEV Norml lung V 5 vlues rnged from 3.9% to 28% (men = 15.7 ± 7.8%). b RTOG minor devition criteri for mximum cord dose > 30 Gy. c RTOG minor devition criteri for dose to < 15cc of hert > 32 Gy, d RTOG minor devition criteri for dose to < 5cc of esophgus >27.5 Gy. e No minor devition from RTOG 0813 criteri ws observed; except for one ptient (ptient # X) whose tumor ws butting hert. PTV = plnning trget volume; V 5 = percentge of ipsilterl lung receiving dose equl to or lrger thn 5 Gy; AVG = Averge; STDEV = stndrd devition. requirement, wheres our results re bsed on DV normliztion technique. In this preliminry study, we hve demonstrted the fesibility of using DV normliztion technique to replicte/ stisfy RTOG 0813 criteri. More cliniclly relevnt DV normliztion techniques hve llowed us to investigte the dosimetric impct of the tumor size-dependent rdiobiologicl effectiveness of the delivered MC dose to 99% of PTV volume versus locl control. (19) We pln to continue building MC lung SABR ptient s dtbse in our clinic nd further investigte RTOG 0813 dosimetric prmeters, s well s it s rdiobiologicl effectiveness. In the future, further studies involving lrge cohort of ptients, including centrl s well s peripherl lung tumors, re needed. This will help to estblish new prmeters specific for the MC-bsed dose clcultions in the lung SABR plnning. Also, the dosimetric impct of vrious pln normliztion techniques on RTOG 0813 complince criteri need to be further investigted. IV. CONCLUSIONS The preliminry dosimetric results for our limited ipln XVMC dose clcultions lgorithm indictes tht not ll ptient s plns could meet the dosimetric guidelines set by RTOG 0813 protocol. Minor devitions in R100%, R50%, nd D 2cm were observed in the mjority of the ptients (i.e., 2/3) in one wy or nother. When using n exclusive highly sophisticted ipln XVMC lgorithm for dose clcultions, the RTOG 0813 dosimetric complince criteri, such s R100% nd D 2cm, my need to be reexmined. Bsed on our limited number of ptient dtsets, in generl, R100% nd D 2cm criteri could be relxed by bout 6% nd 9%, respectively, to

11 359 Pokhrel et l.: Dosimetric evlution of ipln Monte Crlo lgorithm 359 pss the RTOG 0813 dosimetric criteri in most of those ptients. More ptient plns need to be studied to mke recommendtion for R50% criteri. No djustment is required for norml lung V 20, nd other OAR dose tolernces such s mximum cord dose, dose to < 15 cc of hert, nd dose to < 5 cc of esophgus when exclusively using MC-bsed dose clcultions. In order to estblish new MC-specific dose prmeters, further investigtion with lrge number of ptients, including peripherl lung tumors, is nticipted nd highly recommended. ACKNOWLEDGMENTS The first uthor of this pper would like to express his sincere grtitude to Suresh Rn, MS, of ProCure Proton Therpy Center, Oklhom City, for mny stimulus discussions while working on this reserch project nd lso for his editoril help in prepring this mnuscript. REFERENCES 1. Zimmermnn FB, Geinitz H, Schill S, et l. Stereotctic hypofrctionted rdition therpy for stge I non-smll cell lung cncer. Lung Cncer. 2005;48(1): Rn S. Clinicl dosimetric impct of Acuros XB nd nlyticl nisotropic lgorithm (AAA) on rel lung cncer tretment plns: review. Int J Cncer Ther Oncol. 2014;2(1): Rdition Therpy Oncology Group [website Home Pge]. Avilble t: Accessed on 31 Mrch ROTG. Semless phse I/Ii study of stereotctic lung rdiotherpy (SBRT) for erly stge, centrlly locted, nonsmll cell lung cncer (NSCLC) in mediclly inoperble ptients. RTOG Phildelphi, PA: ROTG; Li J, Glvin J, Hrrison A, Timmermn R, Yu Y, Xio Y. Dosimetric verifiction using Monte Crlo clcultions for tissue heterogeneity-corrected conforml tretment plns following RTOG 0813 dosimetric criteri for lung cncer stereotctic body rdiotherpy. Int J Rdit Oncol Biol Phys. 2012;84(2): Rn S, Rogers K, Pokhrel S, Cheng C. Evlution of Acuros XB lgorithm bsed on RTOG 0813 dosimetric criteri for SBRT lung tretment with RpidArc. J Appl Clin Med Phys. 2014;15(1): Fippel M. Fst Monte Crlo dose clcultion for photon bems bsed on the VMC electron lgorithm. Med Phys. 1999;26(8): BrinLAB Technicl Reference Guide, rev Munich, Germny: BrinLAB AG; Frgoso M, Wen N, Kumr S, et l. Dosimetric verifiction nd clinicl evlution of new commercilly vilble Monte Crlo-bsed dose lgorithm for ppliction in stereotctic body rdition therpy (SBRT) tretment plnning. Phys Med Biol. 2010;55(16): Petoukhov AL, vn Wingerden K, Wiggenrd RG, et l. Verifiction mesurements nd clinicl evlution of the ipln RT Monte Crlo dose lgorithm for 6MV photon energy. Phys Med Biol. 2010;55(16): Kunzler T, Fotin I, Stock M, Georg D. Experimentl verifiction of commercil Monte Crlo-bsed dose clcultion module for high-energy photon bems. Phys Med Biol. 2009;54(24): Fippel M, Lub W, Huber B, Nusslin F. Experimentl investigtion of fst Monte Crlo photon bem dose clcultion lgorithm. Phys Med Biol. 1999;44(12): Dobler B, Wlter C, Knopg A, et l. Optimiztion of extrcrnil stereotctic rdition therpy of smll lung lesions using ccurte dose clcultion lgorithms. Rdit Oncol. 2006;1: Chen H, Lohr F, Fritz P, et l. Stereotctic, single-dose irrdition of lung tumors: comprison of bsolute dose nd dose distribution between pencil bem nd Monte Crlo lgorithms bsed on ctul ptient CT scns. Int J Rdit Oncol Biol Phys. 2010;78(3): Sethi A, Leo P, Kbt C, Cecilio P. Vlidtion of Monte Crlo dose lgorithm in heterogeneous medium [bstrct]. Med Phys. 2013;40(6): Miur H, Msi N, Oh RJ, et l. Clinicl introduction of Monte Crlo tretment plnning for lung stereotctic body rdiotherpy. J Appl Clin Med Phys. 2014;15(1): Bdkul R, Pokhrel D, Jing H, Wng F, Kumr P. Dosimetric evlution nd clinicl implementtion of ipln Monte Crlo lgorithm for lung stereotctic bltive rdiotherpy (SABR) [bstrct]. Med Phys. 2013;40(6): Pokhrel D, Bdkul R, Jing H, et l. Dosimetric evlution of centrlly locted lung tumors: Monte Crlo (MC) study of lung SBRT plnning [bstrct]. Med Phys. 2014;41(6): Pokhrel D, Bdkul R, Jing H, et l. BED vs. locl control: rdiobiologicl effect of tumor volume in Monte Crlo (MC) lung SBRT plnning [bstrct]. Med Phys. 2014;41(6):94.