Radiotherapy and Oncology 89 (2008) 89–96www.thegreenjournal.com

Treatment of NPC

Dosimetric comparisons of helical tomotherapyand step-and-shoot intensity-modulated radiotherapy

in nasopharyngeal carcinoma

Tsair-Fwu Leea,b,1, Fu-Min Fangb,1, Pei-Ju Chaoa,c, T.-J. Sua,Luke K. Wanga, Stephen W. Leungc,d,*

aNational Kaohsiung University of Applied Sciences, Kaohsiung, Taiwan, ROC, bDepartment of Radiation Oncology, Chang Gung MemorialHospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan, ROC, cDepartment of Radiation Oncology,

Kaohsiung Yuan’s General Hospital, Taiwan, ROC, dDepartment of Radiological Technology,Central Taiwan University of Science and Technology, Taiwan, ROC

Abstract

Purpose: The study evaluates and quantifies the potential dosimetric gains of helical tomotherapy (HT) versus step-and-shoot intensity-modulated radiotherapy (SaS-IMRT) for nasopharyngeal carcinoma (NPC).Materials and methods: Twenty consecutive NPC patients curatively treated by HT were examined. Each case was

planned by HT and SaS-IMRT (ADAC Pinnacle3) planning system, respectively. Dose plans were compared using dosevolume histograms (DVH), conformity index (CI), homogeneity index (HI), and minimal dose to 1 cc (Dmin_1cc) of theplanned target volume (PTV) and a comprehensive quality index (CQI) of ten organs at risk (OARs). The prescribed dose/fractionation was 72 Gy to the PTV, 64.8 Gy to the elective PTV, and 54 Gy to the clinically negative neck region. Theplan of 54 Gy to the PTV (PTV54) was used to evaluate the CI and HI in the target. The cumulative doses of the three PTVplans to the OARs were calculated.Results: We observed the HT plans significantly improved the CI (improvement ratio: 11.9 ± 5.5%) and HI (improvement

ratio: 8.8 ± 1.5%) of the PTV54 compared with SaS-IMRT plans. In addition, the mean/maximal dose of most of the OARsexcept chiasm was significantly reduced in HT plans, with the CQI of 0.92 ± 0.08. A negative result of HT in chiasm wasobserved but only significantly revealed in cases without skull base infiltration.Conclusions: A dosimetric gain in CI and HI of PTV and sparing of OARs was significantly obtained in HT versus SaS-IMRT

plans in NPC patients. Whether such dosimetric superiority in HT could transfer into clinical advantages needs furtherinvestigation.

�c 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 89 (2008) 89–96.

Keywords: Dosimetric comparisons; Helical tomotherapy; Intensity-modulated radiotherapy; Nasopharyngeal carcinoma

Over the past decade, much progress has been made inimproving the therapeutic index of radiotherapy (RT)against nasopharyngeal carcinoma (NPC). The advances ofRT techniques for treating NPC have emerged with thedevelopment of three-dimensional conformal RT (3D-CRT)and, more recently, intensity-modulated RT (IMRT). IMRTemploys inverse planning algorithms and iterative com-puter-driven optimization to generate treatment fields withvarying beam intensity. Combinations of intensity-modu-lated fields produce custom-tailored conformal dose distri-butions around the tumor, with steep dose gradients atthe transition to adjacent normal tissues [1].

Currently, a step-and-shoot IMRT (SaS-IMRT) delivered bylinear accelerators (linacs) is used in most centers, and

1 These authors contributed equally to this work.

0167-8140/$ - see front matter �c 2008 Elsevier Ireland Ltd. All rights re

approximately five to nine beams are usually sufficient toachieve acceptable dose homogeneity within the targetand for normal tissue sparing. A small increase in the beamnumbers does not seem to improve the dose distribution[2,3]. The recent availability of Hi-Art Helical Tomotherapy(HT) (TomoTherapy, Madison, WI) capable of calculating themultileaf collimator (MLC) position every 7 deg of rotationmight have opened a new field of exploration in creating amore uniform target dose [4].

The HT for cancer patients has been widely used in Tai-wan. The first unit was installed at the Yuan’s general hos-pital at Kaohsiung in southern Taiwan in April, 2006. It hasbeen reported that HT provided improved dose homogeneityin the target and normal structures compared with SaS-IMRTin the treatment of oropharyngeal cancer [5,6]. Here, weprospectively quantified the potential gains of HT in

served. doi:10.1016/j.radonc.2008.05.010

90 Dosimetric comparisons in nasopharyngeal carcinoma

dosimetry for patients with NPC against the SaS-IMRTplanned by ADAC Pinnacle planning system (ADACPinnacle3).

Materials and methodsStudy population

Twenty newly diagnosed and consecutive patients withpathology-proven NPC treated with curative RT by HT inthe Department of Radiation Oncology, Kaohsiung Yuan’sGeneral Hospital between May 2006 and December 2007were enrolled. The patients’ characteristics were demon-strated on Table 1. The median age was 48 years (range28–79 years). The distributions of clinical stages accordingto the American Joint of Cancer Committee (AJCC) stagingsystem published in 1997 were II: 1 (5%), III: 7 (35%), andIV: 12 (60%). Twelve (60%) of them were treated with a com-bination of chemotherapy.

Treatment plans in HT and SaS-IMRTAll patients were immobilized in a tailor-made thermo-

plastic cast from head to shoulders, and 3 mm-thicknessPET/CT (Siemens Biograph LSO PET/CT) scan slices of thehead and neck were obtained to be used for localizationof targets and organs at risk (OARs). The PET/CT image setswere then transferred to and fused in the SaS-IMRT (ADACPinnacle3) planning systems. After delineating all of theessential targets and OARs, we transferred these contoursto HT and ADAC, respectively, for IMRT inverse planning.

Table 1Patient characteristics (n = 20)

Variables Number

Age, median years (range) 48 (28–79)

GenderMale 17 (85%)Female 3 (15%)

AJCC stageI–II 1 (5%)III 7 (35%)IVa–b 12 (60%)

T stageT1 6 (30%)T2 4 (20%)T3 4 (20%)T4 6 (30%)

N stageN0 2 (10%)N1 3 (15%)N2 9 (45%)N3 6 (30%)

Combination with chemotherapyYes 12 (60%)No 8 (40%)

Abbreviation: AJCC, American Joint of Cancer Committee in1997.

The targets delineated included the gross tumor volume(GTV), clinical target volume (CTV), and planning target vol-ume (PTV). The GTV covered the visible primary tumor andneck nodes of NPC shown on the image studies. The CTVencompassed the GTV with a 1.5 cm margin, the micro-scopic spread of disease and the prophylactic area of neck.The PTV included the CTV with 3-mm extensions in alldimensions to account for patient setup error and motionuncertainties, except for situations where the GTV or theCTV is adjacent to the brain stem, where the margin canbe as small as 1 mm [7]. The OARs concerned at the discre-tion of the treating oncologist including seven serial-type oforgans (serial OARs), e.g., brainstem, spinal cord, lenses,eyes, optic nerves, chiasm, and mandible; and three paral-lel-type of organs (parallel OARs), e.g., parotids, subman-dibular glands, and oral cavity.

The prescribed dose/fractionation was 72 Gy to thePTV, 64.8 Gy to the elective PTV, and 54 Gy to the clini-cally negative neck region with a daily fraction size of1.8 Gy and five fractions per week. Three sequential planswere made for the three different PTV in the individualcase. The plan of 54 Gy to the PTV (PTV54) was used toevaluate the dose conformity and homogeneity in the tar-get. The cumulative doses of the three PTV plans to theOARs were calculated and evaluated. In ADAC plans, astandard coplanar 7-field gantry arrangement was designedin all cases and delivered on an Elekta PreciseTM Linacequipped with an 80-leaf 1-cm MLC in SaS-IMRT mode. InHT plans, three main parameters must be chosen by theoperator that are unique to HT. Briefly, the field width isdefined as the slice thickness of the radiation field pro-jected at the isocenter along the gantry rotation axis.The pitch is defined as the couch movement relative tothe field width during one gantry rotation. The modulationfactor is defined as the ration of the maximum number ofthe opening leaves and the average number of openingleaves in active gantry rotations [6,8]. A 2.5 cm fieldwidth, pitch of 0.3, and modulation factor of 2.5 wereused in all HT plans of this study. Both planning systemsuse least-square minimization as cost function. OARs wereoptimized on an individual basis by maximum and doseconstraints set without compromising the PTV coveragewith at least 95% of the PTV receiving the minimum pre-scribed dose. To sculpt the dose to the target and avoidOARs, penalties were given to the PTV that were receivinglower than the prescription dose and OARs that werereceiving higher dose than the constraints. The inverseplanning systems perform iterations during optimizationprocess, which are continuous annealing for SaS-IMRT butalgebraic iteration for HT.

Nomenclature of the dosimetric endpoints

1. Conformity index (CI): a ratio to evaluate the good-ness of fit of the PTV to the prescription isodose vol-ume in treatment plans. CI ¼ V PTV � V TV

TV PV2. [VTV: the

treatment volume of the prescribed isodose lines;VPTV: the volume of PTV; TVPV: the volume of V PTV

within the V TV]. The smaller value of CI, the betterconformal PTV fitting will be presented [9,10].

T.-F. Lee et al. / Radiotherapy and Oncology 89 (2008) 89–96 91

2. Conformity improvement ratio (DCI%): a ratio to eval-uate the improvement or reduction CI of in HT plans

over SaS-IMRT plans. DCI% ¼ CIht�CISaS-imrt

CISaS-imrt� 100%. [CIht

and CISaS-imrt are CI values in the HT and the SaS-IMRTplans, respectively].

3. Homogeneity index (HI): a ratio to evaluate the homo-

geneity of PTV. HI ¼ D5%

D95%; [D5% and D95% are the mini-

mum doses delivered to 5% and 95% of the PTV]. Thegreater HI indicates the poorer homogeneity [11,12].

4. Homogeneity improvement ratio (DHI%): a ratio toevaluate the improvement of HI in HT plans over

SaS-IMRT plans. DHI% ¼ HIht�HISaS-imrt

HISaS-imrt� 100%. [HIht and

HISaS-imrt are the HI values in HT and SaS-IMRT plans,respectively.]

5. Dmin_1cc: minimal dose to 1 cc of the PTV.6. Dmin_1cc improvement ratio (DDmin_1cc%): the relative

difference of Dmin_1cc between HT and SaS-IMRT plans.

DDmin 1cc% ¼ Dmin 1cc;ht�Dmin 1cc;SaS-imrt

Dmin 1cc;SaS-imrt� 100%. [Dmin_1cc,ht

and Dmin_1cc,SaS-imrt are Dmin_1cc values in the HT andthe SaS-IMRT plans, respectively.]

7. Quality index (QI): an index to evaluate the differ-ence of the maximal or mean absorbed dose at serialor parallel OARs, respectively, between HT and SaS-

IMRT plans [11]. QISerial ¼DHTmax

DSaS-imrtmax

; QIParallel ¼DHTmean

DSaS-imrtmean

,

8. Comprehensive quality index (CQI): the average qual-ity index for the OARs analyzed. CQI ¼ 1

N

PNi¼1

ðQISerial j QIParallelÞi; N ¼ 1; . . . ; 10: where i is theindex of the critical structures and ‘|’ means ‘or’.

9. CQISerial: the comprehensive quality index for serial

organs. CQI ¼ 1N

PNi¼1

DHTmax

DSaS-imrtmax

� �i;Serial

; N ¼ 1; . . . ; 7:

10. CQIParallel: the comprehensive quality index for

parallel organs. CQIParallel ¼ 1N

PNi¼1

DHTmean

DSaS-imrtmean

� �i;Parallel

;

N ¼ 1; 2; 3:

Statistical analysisPaired t-test was used to compare the dosimetric differ-

ences between HT and SaS-IMRT. A two-tailed value ofp < 0.05 was defined as having statistical significance. Thesoftware, SPSS-12.0, was used for data processing.

ResultsConformity of PTV54

The isodose distributions of the plan PTV54 in axial planesin one NPC patient by the two planning systems are shown inFig. 1. A steeper dose gradient of the dose–volume histo-gram (DVH) of PTV54 in HT plan was observed. Table 2 liststhe CI values of PTV54 for each patient in SaS-IMRT and HTplans. Nineteen of the 20 patients had a lower CI in HTplans. The mean values of CI were 1.44 ± 0.08 (range1.33–1.66) in SaS-IMRT and 1.27 ± 0.08 (range 1.09–1.47)in HT plans, respectively, indicating a significantly betterconformity in HT (p < 0.001). The mean value of DCI was(�11.9 ± 5.5)% in HT versus SaS-IMRT plans. Thirteenpatients (65%) had a reduction of DCI with at least 10%. A

significantly negative correlation between the CI value andthe PTV54 volume was observed in the both plans, withthe correlation coefficients of �0.26 and �0.28 in SaS-IMRTand HT plans, respectively (p < 0.05). The superiority of CIin HT was not changed in the subgroups of our cohort.

Homogeneity of PTV54

All the 20 patients had better HI in HT plans. The mean HIvalues were 1.15 ± 0.02 (range 1.12–1.19) in SaS-IMRTplans, and 1.05 ± 0.01 (range 1.03 –1.07) in HT plans,respectively, indicating a significantly better homogeneityin HT (p < 0.001, Table 2). The mean value of DHI was(�8.8 ± 1.5)% in HT versus SaS-IMRT plans. Seventeen pa-tients (85%) had an improvement between 6% and 10%. Nosignificant correlation between the HI value and the PTV54volume was observed in the both plans, with the correlationcoefficients of 0.09 and �0.18 in SaS-IMRT and HT plan,respectively. The superiority of HI in HT was not changedin the subgroups of our cohort.

Dmin_1cc of PTV54

The mean values of Dmin_1cc were 60.3 ± 4.6 Gy (range52.3–67.8) in HT and 59.0 ± 2.8 Gy (range 51.9–62.5) inSaS-IMRT plans (Table 2). The mean value of D Dmin_1cc%was (2.0 ± 5.3)% in HT versus SaS-IMRT plans, without signif-icant difference observed (p = 0.10).

Dosimetry of OARsThe mean dose, maximal dose, and QI of the ten OARs

are summarized in Tables 3 and 4. The mean dose was sig-nificantly lower in eight OARS (including brainstem, spinalcord, lenses, eyes, optic nerves, parotids, submandibularglands, and oral cavity) by HT plans, so was seven OARs inmaximal dose (including brainstem, spinal cord, lenses, op-tic nerves, parotids, submandibular glands, and mandible).On the contrast, the mean (28.9 ± 8.7 vs. 18.2 ± 8.3 Gy)and maximal dose (37.2 ± 5.8 vs. 23.7 ± 12.3 Gy) in chiasmwas significantly higher by HT plans. The mean value ofCQI is 0.92 ± 0.08 for the ten OARs. Of the seven serial OARs,the value of is [(0.97 ± 0.12) (range 0.84–1.24)]. The lensesshow the most notable improvement [QI = 0.80 ± 0.15(range 0.65–1.17)], followed by optic nerves[QI = 0.90 ± 0.26 (range 0.48–1.65)], brain stem [QI =0.92 ± 0.03 (range 0.86–0.96)], spinal cord [QI = 0.92 ±0.04 (range 0.83–1.00)], mandible [QI = 0.94 ± 0.10 (range0.86–1.02)], and eyes [QI = 0.94 ± 0.20 (range 0.53–1.52)], indicating an approximately 20% reduction of maxi-mal dose in lenses, 10% in optic nerves and 8% in spinal cord,respectively, by HT versus SaS-IMRT plan. Conversely, the QIvalue in chiasm was 1.44 ± 0.64 (range 0.89–2.98) indicatingan approximately 44% increase of maximal dose in chiasm.Of the three parallel organs, the value of CQIParallel is�[(0.80 ± 0.08) (range 0.64–0.97)]. The parotids show themost evident improvement [QI = 0.72 ± 0.07 (range 0.61–0.87)], followed by oral cavity [QI = 0.83 ± 0.14 (range0.66–1.24)], and submandibular glands [QI = 0.86 ± 0.09(range 0.75–1.10)], indicating an approximately mean dosereduction of 28% in the parotid glands, 17% in oral cavity,and 14% in submandibular glands, respectively, by HT versusSaS-IMRT plan.

Fig. 1. The comparisons of isodose distributions of planned target volume (PTV) and organs at risk (OAR) in three axial planes in one NPCpatient planed by step-and-shoot intensity-modulated radiotherapy (SaS-IMRT, ADAC Pinnacle3) versus Helical tomotherapy (HT) planningsystem.

92 Dosimetric comparisons in nasopharyngeal carcinoma

Dosimetry of OARs for T1-2 versus T3-4 casesThe QI of the ten OARs for T1-2 versus T3-4 cases are

shown in Table 4. There was no significant difference of

the QI between HT and SaS-IMRT plans in most OARs forcases with T1-2 versus T3-4 cases. The only exception wasin chiasm. We observed for patients with skull base infiltra-

Table 2The dosimetric comparisons of PTV between HT and SaS-IMRT plans for each patient

Patient CI HI Dmin_1cc

HT SaS-IMRT DCI(%) HT SaS-IMRT DHI(%) HT SaS-IMRT D Dmin_1cc (%)

1 1.26 1.50 �16.6 1.06 1.15 �7.8 61.9 60.4 2.62 1.47 1.66 �11.3 1.06 1.17 �9.2 54.2 59.3 �8.63 1.23 1.41 �13.3 1.05 1.17 �10.2 56.7 59.3 �4.44 1.13 1.35 �16.3 1.06 1.16 �9.0 58.4 59.1 �1.25 1.37 1.49 �7.9 1.05 1.19 �12.4 54.0 53.8 0.46 1.40 1.51 �7.9 1.04 1.12 �7.0 65.5 61.4 6.77 1.28 1.36 �5.6 1.05 1.13 �6.9 56.8 57.7 �1.58 1.25 1.34 �6.9 1.03 1.12 �8.0 66.8 58.2 14.79 1.25 1.42 �12.1 1.03 1.12 �8.2 65.3 62.5 4.510 1.20 1.40 �14.4 1.04 1.14 �9.0 67.8 62.3 8.811 1.28 1.33 �4.1 1.06 1.13 �6.1 63.2 60.8 4.012 1.36 1.35 0.4 1.05 1.15 �9.2 60.5 60.5 �0.113 1.28 1.43 �10.5 1.06 1.16 �8.6 61.0 60.9 0.214 1.31 1.44 �9.1 1.04 1.18 �11.4 52.3 51.9 0.815 1.19 1.46 �18.0 1.06 1.15 �8.0 62.3 58.0 7.416 1.25 1.55 �18.9 1.05 1.16 �9.3 60.8 59.0 3.117 1.23 1.46 �15.5 1.05 1.16 �9.6 63.2 60.5 4.418 1.23 1.47 �16.3 1.05 1.15 �8.6 63.8 60.5 5.419 1.31 1.49 �12.1 1.06 1.15 �7.9 58.2 59.0 �1.420 1.09 1.39 �21.5 1.07 1.17 �9.2 53.4 56.4 �5.3Mean 1.27 ± 0.09 1.44 ± 0.08 �11.9 ± 5.5a 1.05 ± 0.01 1.15 ± 0.02 �8.8 ± 1.5a 60.3 ± 4.6 59.1 ± 2.6 2.0 ± 5.3�

Abbreviations: HT, helical tomotherapy; SaS-IMRT, step-and-shoot intensity-modulated radiotherapy; PTV, planning target volume; CI,conformity index; HI, homogeneity index; DCI(%), the CI improvement ratio; D HI(%), the HI improvement ratio; D Dmin_1cc (%), the relativeDmin_1cc differences between HT and ADAC SaS-IMRT plans.a p < 0.05; �: p = 0.10.

Table 3The comparison of mean and maximum doses of ten OARs between HT and SaS-IMRT plans

Maximum dose in Gy Mean dose in Gy

OARs HT SaS-IMRT p-values HT SaS-IMRT p-values

SerialBS 51.3 ± 1.1 (49.1–59.9) 55.7 ± 1.3 (53.3–57.6) <0.05 29.3 ± 3.8 (21.8–34.9) 35.6 ± 3.4 (26.4–39.3) <0.05SC 42.4 ± 1.5 (38.5–44.3) 46.0 ± 1.2 (43.5–47.8) <0.05 27.7 ± 3.1 (21.4–34.7) 36.8 ± 1.3 (35.0–38.8) <0.05Lenses 3.5 ± 0.5 (2.6–4.1) 4.5 ± 0.7 (2.5–5.6) <0.05 3.1 ± 0.5 (2.4–3.8) 3.7 ± 0.5 (2.7–4.4) <0.05Eyes 11.3 ± 2.5 (6.8–17.7) 12.2 ± 2.3 (9.2–18.3) 0.09 4.6 ± 0.8 (3.5–6.1) 5.5 ± 0.8 (4.2–7.4) <0.05ON 30.8 ± 12.9 (16.8–60.9) 36.3 ± 15.7 (11.0–67.4) <0.05 12.6 ± 6.2 (5.2–31.2) 16.4 ± 9.4 (6.1–40.3) <0.05Chiasm 37.2 ± 5.8 (27.4–48.3) 23.7 ± 12.3 (11.6–46.5) <0.05 28.9 ± 8.7 (12.9–43.0) 18.2 ± 8.3 (8.0–35.5) <0.05MB 64.0 ± 1.7 (60.2–67.0) 68.0 ± 1.8 (64.5–70.3) <0.05 31.9 ± 5.1 (23.4–39.5) 33.3 ± 5.4 (25.0–46.5) 0.24

ParallelParotids 66.4 ± 3.1 (55.2–69.7) 68.7 ± 2.1 (63.4–70.9) <0.05 21.3 ± 1.8 (18.2–25.0) 29.7 ± 1.1 (26.9–31.0) <0.05SM 69.2 ± 2.9 (61.5–71.6) 66.2 ± 2.8 (59.6–69.8) <0.05 31.6 ± 2.5 (27.8–37.1) 36.8 ± 2.7 (32.9–41.1) <0.05Oral 65.8 ± 4.7 (51.7–70.5) 66.5 ± 2.6 (59.1–70.0) 0.50 33.0 ±5.2 (22.2–41.1) 42.2 ± 6.6 (27.7–52.2) <0.05

Abbreviations: HT, helical tomotherapy; SaS-IMRT, step-and-shoot intensity-modulated radiotherapy; OAR, organ at risk; BS, brain stem;SC, spinal cord; ON, optic nerves; MB, mandible; SM, submandibular glands; Oral, oral cavity. The two-tailed p-values were obtained frompaired t-tests.

T.-F. Lee et al. / Radiotherapy and Oncology 89 (2008) 89–96 93

tion, the QI between HT and SaS-IMRT plans was signifi-cantly lower (better) than those without skull base infiltra-tion (1.03 ± 0.07 vs. 1.86 ± 0.69, p = 0.01).

Treatment timeThe mean value of the actual treatment time (not includ-

ing patient set-up time) for the 20 patients in HT is8.1 ± 0.6 min (range 6.7–10.5 min) compared with the sim-ulated treatment time of 13.9 ± 1.3 min (range 11.2–

16.7 min) in SaS-IMRT plans (p < 0.001, see Table 5). Thesimulated treatment time was calculated by running forall plans in the Linac’s treatment room.

DiscussionThe treatment fields of conventional two-dimensional RT

for NPC are usually large and some normal structures such as

Table 4The dosimetric comparisons of ten OARs between HT and SaS-IMRT plans

Variables of OARs QI values QI values of T1-2 QI values of T3-4 p-values

QI of serial organsBrain stem 0.92 ± 0.03 (0.86–0.96) 0.93 ± 0.02 (0.90–0.96) 0.92 ± 0.03 (0.86–0.96) 0.51Spinal cord 0.92 ± 0.04 (0.83–1.00) 0.93 ± 0.03 (0.90–0.97) 0.92 ± 0.05 (0.83–1.00) 0.81Lenses 0.80 ± 0.15 (0.65–1.17) 0.78 ± 0.16 (0.65–1.17) 0.81 ± 0.14 (0.65–1.07) 0.51Eyes 0.94 ± 0.20 (0.53–1.52) 0.93 ± 0.04 (0.86–0.98) 0.95 ± 0.03 (0.90–1.02) 0.34Optic nerves 0.90 ± 0.26 (0.48–1.65) 0.99 ± 0.33 (0.48–1.65) 0.80 ± 0.09 (0.70–0.99) 0.10Chiasm 1.44 ± 0.64 (0.89–2.98) 1.86 ± 0.69 (1.04–2.98) 1.03 ± 0.07 (0.89–1.13) 0.01Mandible 0.94 ± 0.04 (0.86–1.02) 0.93 ± 0.04 (0.86–0.98) 0.95 ± 0.03 (0.90–1.02) 0.34

QI of parallel organsParotids 0.72 ± 0.07 (0.61–0.87) 0.70 ± 0.08 (0.61–0.86) 0.74 ± 0.06 (0.65–0.87) 0.24Submandibular 0.86 ± 0.09 (0.75–1.10) 0.85 ± 0.09 (0.75–1.02) 0.88 ± 0.10 (0.80–1.10) 0.51Oral cavity 0.83 ± 0.14 (0.66–1.24) 0.83 ± 0.14 (0.75–1.02) 0.83 ± 0.12 (0.66–1.02) 0.97

CQI valuesCQISerial 0.97 ± 0.12 (0.84–1.24)CQIParallel 0.80 ± 0.08 (0.64–0.97)CQI of ten OARs 0.92 ± 0.08 (0.80–1.10)

Abbreviations: HT, helical tomotherapy; SaS-IMRT, step-and-shoot intensity-modulated radiotherapy; OAR, organ at risk; T1-2, subgroup ofstages T1 and T2; T3-4, subgroup of stages T3 and T4; QI, quality index; CQI, comprehensive quality index; CQISerial, comprehensive qualityindex for serial OARs; CQIParallel, comprehensive quality index for parallel OARs.

94 Dosimetric comparisons in nasopharyngeal carcinoma

the parotids are exposed to almost the same irradiated doseas the gross tumor sites. The dosimetric limitations of con-ventional RT can now be overcome with conformal RT.Growing reports have shown that the dosimetric superiorityof IMRT applied in NPC patients can not only preserve paro-tid functions [13–15], but also improve local control[14,16,17] and even patient survival [18,19]. However, stud-ies comparing HT and SaS-IMRT in NPC are still rare in theliterature. This study quantified the potential dosimetricgains of HT against SaS-IMRT in treating NPC.

We demonstrated that HT plans significantly improved CIand HI of the PTV54 compared with SaS-IMRT, but the poten-tial cold spot, as revealed by Dmin_1cc, was not found to havestatistical significant difference in both plans. In addition,the mean/maximal dose of most of the OARs except chiasmwas significantly reduced in HT plans.

We observed the impact of the dose penumbra betweenHT and SaS-IMRT above the cranial border of the PTV be-came remarkable if the OAR located on this level. A sharpercraniocaudal dose fall-off in SaS-IMRT was seen comparedwith HT plans, in which a field width of 2.5 cm and pitchof 0.3 was used, making the contiguous OAR and PTV ex-posed in the same field. Thus, the negative result of HT inchiasm was observed but only significantly revealed in the

Table 5Actual treatment time in HT and simulated treatment time in SaS-IMRT

HT

PTV (cm3) Couch travellength (cm)

Tx time(min)

MU

Mean ± SD 633.7 ± 136.6 23.0 ± 1.3 8.1 ± 0.9 9481 ± 1060(range) (372.3–894.4) (19.9–25.0) (6.7–10.5) (7878–1234

Abbreviations: PTV, planning target volume; HT, helical tomotherapy;treatment time; MU, monitor units used; Patient setup time was not in

T1-2 cases, in which the chiasm was outside but near thecranial border of the PTV, rather than the T3-4 cases, inwhich the chiasm was usually within the PTV.

Our results are compatible with those reported for the in-ter-comparisons between HT and SaS-IMRT in treating theother sites of head-and-neck cancers [5,6,11,20]. All ofthem observed HT provided dosimetric superiority overIMRT delivered by either SaS or dynamic MLC. A dosimetriccomparison of noncoplanar SaS-IMRT versus HT, which lacksnoncoplanar capability, for nasal cavity and paranasal sinuscancer also revealed HT had equivalent or slightly betterdosimetry in normal tissue sparing. Recently, Fiorino et al.made a dosimetric comparison in six NPC patients betweenHT and five-field coplanar IMRT delivered by dynamic MLC.They observed HT improves the homogeneity of dose distri-bution within PTV and PTV coverage together with a signif-icantly greater sparing of OARs [21].

The noncoplanar beams were not used in SaS-IMRT forthis comparison. In our previous experience comparingcoplanar and noncoplanar beams in SaS-IMRT for cases withskull base infiltration, especially with paracavernous sinusor ethmoid invasion, we found the noncoplanar beams cre-ated a better dose distribution in PTV and less dose expo-sure to eyeball, optic nerves, and chiasm (data not

plans

SaS-IMRT

PTV (cm3) Segments Tx time (min) MU

634 ± 136.8 113.3 ± 28.4 13.9 ± 1.3 1063 ± 1236) (373.3–894.8) (76–187) (11.2–16.7) (871–1361)

SaS-IMRT, step-and-shoot intensity-modulated radiotherapy; Tx,cluded. p < 0.001.

T.-F. Lee et al. / Radiotherapy and Oncology 89 (2008) 89–96 95

shown). However, if the noncoplanar beams were chosen,the beams from the vertex would easily cause unavoidablehair loss at the parietal scalp area and created the cosmeticproblems for patients.

Based on the different radiobiological effect influencedby maximal or mean doses, respectively, the OARs were di-vided into the serial and parallel type in our patients. Weobserved the order of the six out of seven serial OARsobtaining an improvement in HT plan is lenses followed byoptic nerves, brain stem, spinal cord, and mandible, so isthe parotids followed by oral cavity, and submandibularglands in the three parallel OARs. HT offers a higher degreeof freedom than SaS-IMRT and thus it might provide a higherspatial resolution of dose computation for the smaller or-gans such as the lens. However, we could not concludewhich OAR was spared more by HT in treating NPC. Theoret-ically, the amount of gains by comparing one planning sys-tem with the other is affected by many factors e.g., thedelineation guidelines used for the OARs, the contours ofthe PTV, the priority of sparing one organ more than theother, and an inevitable bias imposed by different operatorsof the treatment planning systems.

As for the parotids, considered to have the most impacton patients’ quality of life, the mean dose was reduced by8.3 Gy in our cases. This reduction is slightly higher thantwo previously reported studies with around a 6 Gy reduc-tion in parotids by comparing HT with SaS-IMRT in oropha-ryngeal cancer [6,20]. Whether such dosimetric superiorityin parotids could preserve more salivary function and im-prove patients’ quality of life deserves further evaluation.A prospective study using the European Organization forthe Research and Treatment of Cancer Core Quality of LifeQuestionnaire (EORTC QLQ-C30) and the Head and NeckQuality of Life Questionnaire (QLQ-H&N35) to compare theoutcome of quality of life for NPC patients treated by thetwo techniques is under investigation in our institute.

The treatment time by HT was significantly shorter in ourcohort. It was affected by different parameters for HT andSaS-IMRT. In SaS-IMRT, the treatment time is mostly deter-mined by the number of treatment fields and the number ofsegments. In HT, the treatment time depends on the couchmovement speed and travel length, which relies on the lon-gitudinal dimension of the target. The average treatmentfield in our cases was as long as 23 cm, thus, the time con-sumption by the field width of 2.5 cm in HT would becomemore efficient. Therefore, it is not surprising that our resultwas contrast to that comparing HT and SaS-IMRT treatmentplans in intracranial stereotactic radiosurgery [9].

In principle, decreasing the field width and pitch value inHT would provide more degrees of freedom for beam mod-ulation, create better dosimetry, and reduce the chiasmdose exposure in some cases, but at the expense of thetreatment time [22]. Also, the values of modulation factorcould be optimized during the planning process. However,all of our HT plans were assigned with the same values offield width, modulation factor, and pitch value. Our studywas not designed to compare the two planning systems un-der strictly equivalent conditions. Thus, the comparison oftreatment plans between HT and SaS-IMRT is subject tosome degree of bias imposed by different operators, thatis, different dosimetrists may achieve different results.

ConclusionsDosimetric comparisons were made in 20 NPC patients

between HT and ADAC SaS-IMRT plans delivered by 7-fieldcoplanar SaS-IMRT. Both planning systems satisfied the re-quired PTV prescription but a dosimetric gain in CI and HIof PTV and sparing of most OARs was significantly obtainedin HT. Whether the dosimetric superiority in HT could trans-fer into clinical advantages needs further investigation.

AcknowledgementsThe authors would like to thank the anonymous reviewers for

helpful comments on the original manuscript and to Mr. T.-L. Huangand Ms. Y.-C. Chang for their assistance of data collection.

* Corresponding author. Stephen W. Leung, Department ofRadiation Oncology, Kaohsiung Yuan’s General Hospital, 162 Cheng-Kung 1st Road, Kaohsiung 80249, Taiwan, ROC. E-mail addresses:tflee@byte.ec.kuas.edu.tw, jack.york@msa.hinet.net, alf@adm.cgmh.org.tw.

Received 1 March 2008; received in revised form 2 May 2008;accepted 3 May 2008; Available online 2 June 2008

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