Simultaneous Integrated Boost (SIB) for Nasopharynx Cancer with Helical Tomotherapy

497Strahlenther Onkol 2007 · No. 9 © Urban & Vogel

Strahlentherapie und Onkologie Original Article

Simultaneous Integrated Boost (SIB) for Nasopharynx Cancer with Helical TomotherapyA Planning Study

Claudio Fiorino1, Italo Dell’Oca2, Alessio Pierelli1, Sara Broggi1, Giovanni Mauro Cattaneo1, Anna Chiara2, Elena De Martin1, Nadia Di Muzio2, Ferruccio Fazio2, 3, Riccardo Calandrino1

Purpose: To explore the potential of helical tomotherapy (HT) in the treatment of nasopharynx cancer.Patients and Methods: Six T1–4 N1–3 patients were considered. A simultaneous integrated boost (SIB) technique was planned with inversely optimized conventional intensity-modulated radiotherapy (IMRT; dynamic multileaf collimator using the Eclipse-He-lios Varian system) and HT. The prescribed (median) doses were 54 Gy, 61.5 Gy, and 64.5 Gy delivered in 30 fractions to PTV1 (planning target volume), PTV2, and PTV3, respectively. The same constraints for PTV coverage and for parotids, spinal cord, mandible, optic structures, and brain stem were followed in both modalities. The planner also tried to reduce the dose to other structures (mucosae outside PTV1, larynx, esophagus, inner ear, thyroid, brain, lungs, submental connective tissue, bony struc-tures) as much as possible.Results: The fraction of PTV receiving > 95% of the prescribed dose (V95%) increased from 97.6% and 94.3% (IMRT) to 99.6% and 97% (HT) for PTV1 and PTV3, respectively (p < 0.05); median dose to parotids decreased from 30.1 Gy for IMRT to 25.0 Gy for HT (p < 0.05). Significant gains (p < 0.05) were found for most organs at risk (OARs): mucosae (V30 decreased from 44 cm3 [IMRT] to 18 cm3 [HT]); larynx (V30: 25 cm3 vs. 11 cm3); thyroid (mean dose: 48.7 Gy vs. 41.5 Gy); esophagus (V45: 4 cm3 vs. 1 cm3); brain stem (D1%: 45.1 Gy vs. 37.7 Gy). Conclusion: HT improves the homogeneity of dose distribution within PTV and PTV coverage together with a significantly greater sparing of OARs compared to linac five-field IMRT.

Key Words: Planning optimization · IMRT · Tomotherapy · Head-and-neck radiotherapy

Strahlenther Onkol 2007;183:497–505 DOI 10.1007/s00066-007-1698-x

Simultaner integrierter Boost (SIB) bei Nasopharynxkarzinom mit helikaler Tomotherapie. Eine Planungsstudie

Ziele: Untersuchung des Potentials der helikalen Tomotherapie (HT) beim Nasopharynxkarzinom.Patienten und Methodik: Sechs T1–4 N1–3-Patienten wurden einbezogen. Eine Technik des simultanen integrierten Boost (SIB) wurde geplant mit invers optimierter konventioneller intensitätsmodulierter Radiotherapie (IMRT; dynamischer Multileaf-Kollimator des Eclipse-Helios Varian-Systems) und mit HT. Die verschriebenen (medianen) Strahlungsdosen waren 54 Gy, 61,5 Gy und 64,5 Gy, die in 30 Fraktionen auf die Planungszielvolumina PTV1, PTV2 bzw. PTV3 gegeben wurden. Bei beiden Modalitäten, HT und IMRT, wurden für die PTV-Erfassung sowie für Parotiden, Rückenmark, Kiefer, optischen Apparat und Stammhirn dieselben Begrenzungen eingehalten. Der Planer versuchte auch, die Strahlungsdosis auf andere Regionen (Mukosa außerhalb von PTV1, Larynx, Ösophagus, Innenohr, Schilddrüse, Hirn, Lunge, Bindegewebe und Knochen unterhalb des Kinns) so stark wie möglich zu reduzieren. Ergebnisse: Der PTV-Anteil, der mehr als 95% der verschriebenen Strahlungsdosis (V95%) erhielt, erhöhte sich für PTV1 und PTV3 von 97,6% bzw. 94,3% (IMRT) auf 99,6% bzw. 97% (HT) (p < 0,05); die mediane Dosis der Parotiden verminderte sich von 30,1 Gy bei IMRT auf 25,0 Gy bei HT (p < 0,05). Signifikante Vorteile (p < 0,05) zeigten sich für die meisten Risikoorgane: Mukosa (V30-Verminderung von 44 cm3 [IMRT] auf 18 cm3 [HT]), Larynx (V30: 25 cm3 vs. 11 cm3), Schilddrüse (mittlere Strahlungsdosis: 48,7 Gy vs. 41,5 Gy), Ösophagus (V45: 4 cm3 vs. 1 cm3), Stammhirn (D1%: 45,1 Gy vs. 37,7 Gy).Schlussfolgerung: Verglichen mit der Linac-5-Felder-IMRT verbessert HT die Homogenität der Dosisverteilung innerhalb des PTV und die PTV-Erfassung bei signifkant besserer Schonung von Risikoorganen.

Schlüsselwörter: Planungsoptimierung · IMRT · Tomotherapie · Kopf-Hals-Strahlentherapie

Received: December 18, 2006; accepted: June 1, 2007

1 Medical Physics, S. Raffaele Institute, Milano, Italy,2Department of Radiotherapy, S. Raffaele Institute, Milano, Italy,3IBFM CNR, Milano, Italy.

Fiorino C, et al. Tomotherapy Planning for Nasopharynx Cancer

498 Strahlenther Onkol 2007 · No. 9 © Urban & Vogel

Introduction Nasopharyngeal carcinoma (NPC) has always presented a challenge to the radiation oncologist. Survival depends upon local control with high-dose radiation, yet the nasopharynx is surrounded by critical, dose-limiting normal tissues. Histori-cally, patients with T1/T2 disease had acceptable local control rates (87–100%). Unfortunately, many patients present with locally advanced disease and, even with the introduction of combined-modality therapy, control rates remain approxi-mately 62–73% and 44–50% for T3 and T4 lesions, respec-tively [14, 17, 27, 29].

The most common reason for failure is local recurrence that for radiotherapy alone ranges from 15% to 60%, depend-ing on the initial tumor status [14, 21, 34, 36, 41].

The existence of a dose-response relationship is generally accepted; however, dose escalation with conventional exter-nal-beam radiotherapy is often unfeasible.

Intensity-modulated radiotherapy (IMRT) for NPC and other head-and-neck cancers has been demonstrated to be an effective method for improving the therapeutic ratio [4, 5, 13, 15, 19, 25, 31, 32, 37, 38, 40, 42]; IMRT gives also the possibility to simultaneously deliver different doses to different volumes in a very efficient way: this approach, named simultaneous in-tegrated boost (SIB), has also some potential for improving the local control through a moderate acceleration of the treat-ment [15, 16, 24, 39].

The recent availability of newer advanced IMRT delivery techniques, such as helical tomotherapy (HT), may open new fields of exploration due to the potential of tailoring sharper dose distributions around the target volumes.

A Tomotherapy Unit (HiArt2 Tomotherapy®) was re-cently installed at our institute and has been operative since November 2004.

Current analysis refers to a planning comparison be-tween HT and our conventionally delivered IMRT technique (IMRT linac [22]) with a linear accelerator (Varian 600/CD, 6-MV X-rays) by dynamic MLC (multileaf collimator) IMRT in an SIB approach for the treatment of NPC.

Patients and Methods Patients: Volumes and Doses

Six patients (four males and two females) previously subjected to IMRT with radical intent were considered for this study.

All patients had undifferentiated NPC and received neo-adjuvant chemotherapy; T stage was 1–4 while N stage was 1–3. For each patient two or three different volumes were defined. CTV1 (clinical target volume) included the regional nodes at risk and was defined according to published crite-ria for selection and delineation of the neck nodes [10, 11, 18, 20]. CTV2 included only the macroscopic nodes (defined only for three patients). CTV3 included the GTV (gross tumor volume) and in one patient also the nodes with macroscopic invasion. Each CTV was automatically expanded to generate the corresponding PTV (planning target volume) with an iso-

tropic 0.5-cm margin. An SIB approach was followed with the intent to deliver 54, 61.5, and 64.5 Gy in 30 fractions to PTV1, PTV2, and PTV3 respectively.

These dose levels were equivalent to 54, 64.8, and 70.2 Gy delivered with 1.8 Gy/fraction by calculating 2 Gy equivalent doses (EQD2) through the linear-quadratic model (with an α/� ratio equal to 10) and the repopulation correction suggested by Bentzen et al. [2, 3, 37].

IMRT linac and HT plans were always renormalized at the same median PTV3 dose (i.e., 64.5 Gy). For each pa-tient, both parotids, mandible (including temporomandibular joint), spinal cord, optic structures, brain stem, and brain were

Table 1. Summary of dose and dose-volume constraints followed dur-ing inverse optimization. OARs: organs at risk; PTV: planning target volume.

Tabelle 1. Zusammenfassung der Dosis- und Dosis-Volumen-Begren-zungen, die während der inversen Planung eingehalten wurden. OARs: Risikoorgane; PTV: Planungszielvolumen.

PTVs Constraints

TV 54 Gy (1) V54 ≥ 95%a

Median dose ≤ 56 GyPTV 61.5 Gy (2) Median dose = 61.5 Gya

V95% ≥ 98%a

Dmax ≥ 107%PTV 64.5Gy (3) Median dose = 64.5 Gya

V95% ≥ 95%a

Dmax ≤ 107%a

OARs Constraints

Parotids V15 ≤ 67% V30 ≤ 50% V45 ≤ 25%Mandible Dmax ≤ 65 Gya

V55 ≤ 20%Spinal cord Dmax ≤ 40 Gya

Spinal cord expansion Dmax ≤ 45 GyBrain stem Dmax ≤ 50 Gya

Brain stem expansion V55 ≤ 5%Brain V50 ≤ 5 cm3

Vertebral body Dmax ≤ 65 Gya

V55 < 20%Inner ear Dmax ≤ 50 GyOptic chiasm Dmax ≤ 45 Gya

Optic nerves Dmax ≤ 45 Gya

Eye Dmax ≤ 45 Gya

Lens Dmax ≤ 10 GyMucosae outside target V20 ≤ 50% V30 ≤ 40%Larynx V30 ≤ 50%Thyroid V45 ≤ 50%Esophagus Dmax ≤ 45 GySubmental connective tissue V30 ≤ 50%Pulmonary apexes V30 ≤ 50%

ahard constraints



contoured by the same physician. Spinal cord and brain stem were automatically expanded with a 1-cm margin to generate the “planned” spinal cord/brain stem. This volume helped in avoiding the generation of a too steep dose gradient around the spinal cord.

A number of other structures were also defined: mucosae outside PTV1, larynx, thyroid, inner ear, esophagus, lungs’ apex, bone structures next to PTV3, and submental connec-tive tissue.

In particular, mucosae outside PTV1 included the oral cavity and the pharynx with a 0.5-cm margin from PTV1, quite consistently with a recently suggested definition [30].

Larynx included the portion of pharyngeal constrictor muscle between larynx and vertebral body, partly in agree-ment with the suggestion of Eisbruch et al. [7].

Inverse Planning Optimization with IMRT For IMRT linac, a five-field 6-MV X-ray technique with two oblique anterior fields, two oblique posterior fields and one posterior field was always used. This geometry is routinely used at our institute [22]. The gantry angles were optimized by the planner to be more effective in sparing parotids, mandible, and oral cavity.

The IMRT beams (Varian Linac 600 CD equipped with a Varian Millenium 80-leaves MLC) were optimized by the He-lios inverse planning module incorporated in the Eclipse Var-ian treatment-planning system (version 7.2). A sliding-win-dows dynamic technique was used.

Inverse Planning Optimization with Tomotherapy The dose delivery with HT is performed by translating the pa-tient in a continuously rotating fan beam which is modulated by a binary MLC for a maximum of 51 different configurations during every rotation.

Three main parameters can be set by the operator: the field width, the pitch, and the modulation factor. Briefly, the field width is the fixed field dimension in the cranial-caudal direction (1, 2.5, 5 cm); the pitch is the ratio between the couch translation during one gantry rotation and the field width; the modulation factor is the ratio between maximum and average beam intensity.

In current investigation a field dimension of 2.5 cm, a pitch of 0.3, and a modulation factor equal to 3–3.5 were used. The readers are referred to other published work [12] to bet-ter understand the methods of optimization of the inverse planning.

Optimization Criteria for Target Structures and Organs at Risk (OARs)

Dose-volume constraints were established partly according to the RTOG protocol H-0022 [28], partly according to that of Eisbruch et al. [8], and on our own experience (Table 1).

The highest priority was given to PTV coverage and spinal cord/brain stem/visual pathway constraints (hard constraints):

in any case the planner should also try to improve the homo-geneity of the dose distribution within every PTV as much as possible.

After satisfying PTV coverage and hard constraints, pa-rotids and mandible were considered without compromis-ing PTV coverage. Concerning the remaining structures, the planner tried to spare them as much as possible while keeping an acceptable PTV coverage and satisfying hard constraints while possibly keeping mean parotid dose < 30 Gy.

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Figure 1. The values of PTV1-V95%, CI95% and IV10–20 are shown for each patient for both modalities (tomotherapy and IMRT). See text for the definition of these parameters.

Abbildung 1. Die Werte von PTV1-V95%, CI95% und IV10–20 werden für jeden Patienten für beide Modalitäten gezeigt (Tomotherapie und IMRT). Definition dieser Parameter s. Text.



Dose-Volume Histograms (DVHs) – Dose Statistics-Based Comparisons

The following DVH parameters were chosen for the compari-son: V95%, V107% and D99% for PTV2–3, and Dmax for PTV3. The conformity index (CI) was also considered and defined as:

CI(95%) = VBody (> 95%)/V(PTV),where VBody (> 95%) is the volume of body (including the PTV) receiving a dose > 95% of the prescribed dose; V(PTV) is the volume of PTV.

A number of different dose-volume data were compared for all OARs (see Tables 2 and 3).

In order to assess the low-dose bath to the body, the nor-malized irradiated body (IV) at a dose > 10 and 20 Gy was defined as:

IV10 = VBody (> 10 Gy)/V(PTV); IV20 = VBody (> 20 Gy)/V(PTV),

where VBody (> 10/20 Gy) is the body volume receiving a dose > 10/20 Gy.

Table 2. Summary of the results concerning planning target volumes and a number of important organs at risk. IMRT: intensity modulated radio-therapy; NS: p > 0.2; SD: standard deviation; TOMO: tomotherapy.

Tabelle 2. Zusammenfassung der Ergebnisse hinsichtlich Planungszielvolumina und wichtiger Risikoorgane. IMRT: intensitätsmodulierte Strah-lentherapie; NS: p > 0,2; SD: Standardabweichung; TOMO: Tomotherapie.

IMRT TOMO TOMO – IMRT Mean SD Mean SD Mean p-value

V50 98.5% 0.7% 99.8% 0.2% 1.2 < 0.05 D99% (Gy) 48.8 1.8 52.8 0.8 4.0 < 0.05 V90% 99.1% 0.5% 99.9% 0.1% 0.8 < 0.05PTV 54 Gy V95% 97.6% 1.0% 99.6% 0.3% 2.0 < 0.05 Dmedian (Gy) 57.2 0.6 56.2 0.7 –1.0 < 0.05 Dmean (Gy) 57.3 0.3 56.2 0.6 –1.1 < 0.05 SD (Gy) 2.94 0.32 1.61 0.28 –1.33 < 0.05

D99% (Gy) 55.9 1.2 58.2 0.5 2.4 NS V90% 99.1% 0.5% 99.8% 0.1% 0.7 NSPTV 61.5 Gy V95% 95.4% 2.6% 98.5% 0.9% 3.1 NS(n = 3 patients) V107% 2.4% 2.4% 0.1% 0.1% –2.4 NS Dmedian (Gy) 61.7 0.4 61.7 0.2 0.0 NS Dmean (Gy) 62.0 0.6 61.7 0.3 –0.3 NS SD (Gy) 1.98 0.24 1.37 0.47 –0.61 NS

D99% (Gy) 58.6 1.5 59.3 2.1 0.7 NS V90% 99.3% 0.9% 99.4% 0.8% 0.1 NS V95% 94.3% 2.2% 97.0% 1.5% 2.7 < 0.05PTV 64.5 Gy V107% 0.1% 0.4% 0.0% 0.0% –0.1 NS Dmax (Gy) 68.8 1.2 67.7 0.5 –1.1 0.07 Dmean (Gy) 64.3 0.1 64.1 0.2 –0.2 < 0.05 SD (Gy) 1.84 0.34 1.37 0.29 –0.47 0.07

V15 79.4% 3.2% 69.4% 3.8% –10.0 < 0.05 V30 50.1% 3.0% 43.0% 2.3% –7.1 < 0.05Parotids V45 26.0% 4.5% 25.1% 2.9% –0.9 NS Dmedian (Gy) 30.1 2.1 25.0 1.5 –5.1 < 0.05 Dmean (Gy) 31.5 1.6 29.7 1.4 –1.8 < 0.05

V55 (cm3) 11 13 15 9 4 NSMandible Dmax (Gy) 62.8 3.4 64.7 1.6 1.9 NS Dmean (Gy) 40.1 9.7 41.3 7.3 1.2 NS

Vertebral body V55 (cm3) 34 9 36 9 2 NS Dmax (Gy) 66.8 1.2 67.0 1.2 0.2 NS

Spinal cord D1% (Gy) 38.3 1.0 34.7 1.3 –3.6 < 0.05 Dmax (Gy) 40.9 1.0 37.0 1.8 –3.9 0.14

Spinal cord expansion V45 5.7% 3.2% 1.5% 1.6% –4.2 < 0.05 D1% (Gy) 48.5 1.7 44.8 3.3 –3.7 < 0.05

Brain stem D1% (Gy) 45.1 2.3 37.7 9.1 –7.4 < 0.05 Dmax (Gy) 48.4 2.7 41.7 9.9 –6.7 NS

Brain stem expansion V55 7.3% 4.9% 5.3% 5.1% –2.0 < 0.05 D1% (Gy) 56.5 5.3 53.1 14.3 –3.4 NS



Integral dose was also calculated (in Gy · liter) and was expressed as the mean dose to the body (excluding PTV) mul-tiplied by the considered body volume. IV10–20 was the irra-diated volume receiving a dose between 10 Gy and 20 Gy.

As the dose calculation is performed with two different planning systems, the results have to be considered with cau-tion, especially concerning the low doses received by the body and, consequently, the integral dose.

The statistical significance of the differences between the two techniques was assessed through the Wilcoxon matched pairs test (Statistica StatSoft Inc.).

Results PTVs and Typical OARs

A summary of the results is reported in Table 2 and in Fig-ures 1 and 2. In Figure 3 a typical dose distribution obtained with HT is also shown.

HT significantly improved the coverage and the homoge-neity of the dose distribution within every PTV. An improved sparing of OARs of greater interest was obtained: spinal cord and brain stem D1% decreased by 3.6 Gy and 7.4 Gy, respectively (p < 0.05). Concerning the parotids, Dmedian and Dmean decreased by about 5 Gy and 2 Gy, respectively (p < 0.05); the sparing was greater at low dose levels (V15Gy: 79.4% vs. 69.4%; p < 0.05). Concerning optic structures, the minimum distance between cranial border of PTV and eyes/chiasm/optic nerves was always > 1 cm, so that the data of these structures were not of interest; chiasm Dmax was re-ported showing significantly better result for IMRT (p < 0.05); however, this result concerns very low dose values (< 15 Gy).

Sparing of Mucosae and Other OARs A summary of the results is shown in Table 3 and Figure 2.

Concerning mucosae, V20 decreased from 63 cm3 to 38 cm3, with an average reduction of Dmean of about 12 Gy (p < 0.05). Laryngeal and esophageal Dmean decreased by 21 Gy and 14 Gy, respectively (p < 0.05). Reductions of Dmean of about 4–7 Gy for thyroid (p < 0.05), inner ear (not significant: contoured in only three patients) and connective tissue (p = 0.07) were also found.

IV, CI, and Integral Dose Integral dose values (expressed in Gy · liter; Table 4) were comparable within their standard deviations; the high dose levels were better conformed to target volume, while at low dose levels the irradiated volume was higher with HT: the nor-malized IV between 10 and 20 Gy was raised from about 0.7 to 1.5 (p < 0.05; Figure 1).

Discussion and Conclusion By rigorously applying the same optimization criteria for both delivery techniques, large gains in using HT were found, especially for mucosae, larynx, thyroid, and brain stem, while improving PTV coverage/homogeneity. The dose gradients generated by HT between different PTVs were much steep-er, reducing in this way undesired high-dose regions at the boundary of the higher-dose PTVs. Concerning parotids, HT was able to significantly reduce the median dose (about 5 Gy) and V15–V40 Gy, while no differences were found in the high-dose region, reflecting the higher priority of PTV coverage.

Table 3. Summary of the results concerning “nonconventional” organs at risk. IMRT: intensity-modulated radiotherapy; NS: p > 0.2; SD: standard deviation; TOMO: tomotherapy.

Tabelle 3. Zusammenfassung der Ergebnisse hinsichtlich der „nichtkonventionellen“ Risikoorgane. IMRT: intensitätsmodulierte Strahlentherapie; NS: p > 0,2; SD: Standardabweichung; TOMO: Tomotherapie.


V20 (cm3) 63 18 38 19 –25 < 0.05Mucosae outside target V30 (cm3) 44 15 18 5 –26 < 0.05 Dmean (Gy) 36.9 5.2 24.5 3.5 –12.4 < 0.05

V20 (cm3) 25 17 15 17 –10 < 0.05Larynx V30 (cm3) 25 17 11 17 –14 < 0.05 Dmean (Gy) 48.9 9.1 27.6 9.1 –21.3 < 0.05

Esophagus V45 (cm3) 4 2 1 1 –3 < 0.05 Dmean (Gy) 39.7 7.5 26.1 8.2 –13.6 < 0.05

Thyroid V45 (cm3) 19 12 9 3 –10 < 0.05 Dmean (Gy) 48.7 12.1 41.5 4.4 –7.2 < 0.05

Connective tissue V30 (cm3) 6 5 3 3 –3 0.07(n = 4 patients) Dmean (Gy) 30.3 2.8 24.7 4.8 –5.6 0.07

Inner ear (n = 3 patients) Dmean (Gy) 52.8 9.8 48.6 8.6 –4.2 NS

Pulmonary apexes Dmean (Gy) 24.9 13.1 23.0 9.6 –1.9 NS

Optic chiasm Dmax (Gy) 4.4 1.9 13.2 6.0 4.7 < 0.05



A larger gain in Dmean (around 5–6 Gy) was already re-ported with HT for oropharynx cancer patients [9, 35]; the proximity of the high-dose PTVs to parotids may reduce the potentials of sparing of IMRT compared to oropharynx can-cer patients, due to the relatively large overlap between parot-ids and PTV; moreover, the fact that, once the goals of DVH constraints for parotids reached, the planner tried to spare a number of other OARs may have limited parotid sparing.

A number of investigations reported significant reduction of xerostomia with IMRT compared to conventional/confor-mal techniques [4, 19, 38]. However, the intrinsic limitation of parotid sparing due to the partial overlap with PTV, limits the possibility of sparing these structures so that main series re-

ported a mean dose to parotids generally > 30 Gy, more often around 35–40 Gy [4, 19, 38].

Concerning brain stem and spinal cord protection, HT was able to better cover the targets in proximity of these struc-tures. Very few data are available in the literature about the dose delivered to OARs other than brain stem, spinal cord, chiasm, and parotids.

Concerning inner and middle ears, there is some evidence of a linear relationship between dose and severity of hear-ing loss [26]. On the other hand, few investigations reported quantitative data: Lee et al. [19] reported a median dose to middle and inner ear with IMRT around 49 Gy; in the same NPC population 5/67 grade 4 hearing losses were reported.

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Figure 2. A number of relevant dose volume parameters concerning OARs are plotted for each patient for both modalities (tomotherapy and IMRT).

Abbildung 2. Graphische Darstellung einiger relevanter Dosis-Volu-men-Parameter hinsichtlich OARs für jeden Patienten und beide Mo-dalitäten (Tomotherapie und IMRT).



More recently, Wolden et al. [38] reported a mean dose to cochlea with IMRT around 56 Gy and a 15% incidence of grade 3 hearing loss and 48% of patients with some hearing impairment.

We found a mean dose of 48.6 Gy for HT and 52.8 Gy for IMRT when contouring the “inner ear”, showing some potential of HT in reducing the dose to this structure; in par-ticular, for one patient the mean dose was reduced by > 7 Gy. However, the result was not found to be statistically signifi-cant, due to the fact that the inner ear was contoured only in three patients, as for the remaining ones the inner ear was fully included in PTV1 and was not considered in the opti-mization.

No clear data are available in the literature about the dose received by mucosal structures and larynx in IMRT, excepting sporadic examples [7, 30].

The reported dramatic improvement in the sparing of mucosae outside PTV due to HT may have some clinical im-pact, as acute and late mucositis are one of the major obstacles to dose escalation in radiotherapy of head-and-neck cancers [3, 16, 24].

The potential of “mucosa-sparing” IMRT optimization were rarely reported: Sanguineti et al. [30] showed a drastic reduction of mucositis in the oral cavity in patients treated after “mucosa-sparing” inverse planning compared to a group of patients with “conventional” inverse optimization.

About larynx, the peculiar dose delivery of HT permits the generation of very deep gradients at the border of PTV1 with a much larger sparing of larynx without losing the cover-age of PTV.

Larynx irradiation is known to be associated not only with voice impairment; Eisbruch et al. [7] showed that larynx and pharyngeal constrictor muscle should be spared in order to preserve swallowing, aspiration, and motion of the larynx. In our NPC series, due to the different PTV definition (NPC pa-tients vs. oropharynx cancer patients in the study by Eisbruch et al.), larynx could be much more efficiently spared, so that a direct comparison cannot be done. Anyway, it is important to underline that HT was able to reduce the mean dose to the larynx (including part of the middle constrictor muscle in our definition) from 48.9 Gy to 27.6 Gy, with the potential of clini-cally reducing larynx toxicity in NPC patients.

Thyroid seems to show a significant volume effect so that the possibility of using IMRT to reduce the dose received by fractions of this organ is highly attractive; on the other hand, this is not a simple task as thyroid is partly overlapped with PTV.

Long-term hypothyroidism is a well-known and quite common effect of radiotherapy of head-and-neck cancer [6, 33], even if not particularly frequent in NPC patients [33]. Our

Table 4. Summary of the results concerning conformity index (CI), irradiated volumes (IV), and integral dose. IMRT: intensity modulated radio-therapy; NS: p > 0.2; PTV: planning target volume; SD: standard deviation; TOMO: tomotherapy.

Tabelle 4. Zusammenfassung der Ergebnisse hinsichtlich Konformitätsindex (CI), bestrahlter Volumina (IV) und integraler Dosis. IMRT: intensitäts-modulierte Strahlentherapie; NS: p > 0,2; PTV: Planungszielvolumen; SD: Standardabweichung; TOMO: Tomotherapie.


Body – PTV Integral dose (Gy · liter) 126 20 134 23 8 NSIV10 3.8 0.3 4.7 0.3 1.3 < 0.05IV20 3.3 0.3 3.4 0.3 1.0 < 0.05CI95% (PTV 54 Gy) 1.56 0.12 1.47 0.14 0.95 0.14

Figure 3. Plot of the dose distribution (tomotherapy planning) for one of the patients included in the study (Gy).

Abbildung 3. Darstellung der Dosisverteilung (Tomotherapieplanung) für einen der Studienpatienten.



result confirmed the potential of HT in significantly decreasing the dose to the thyroid (about 7 Gy, mean dose) with a conse-quent decrease of the probability of occurrence of long-term hypothyroidism.

Bony structures represent another important issue, espe-cially mandible and temporomandibular joints, vertebral bod-ies, and occipital bone. The use of slightly hypofractionated regimens like our SIB approach can increase the risk of radio-necrosis of the bones [18, 23, 24], due to the very low α/� value for bone [2, 24]. In our planning study we were very careful in avoiding hot spots in bone structures.

About the integral dose, our findings show a (nonsignifi-cant) 6% increase for HT. This value may be affected by rela-tively large uncertainties due to the different handling of the penumbra and out-of-field dose contributions of the two plan-ning systems and different body volume calculation. Howev-er, it seems to be quite clear that HT does not dramatically increase the integral dose in the treatment of head-and-neck cancer, consistently with few other reports [1, 9].

This result seems to be the consequence of a balancing effect between a dose reduction with HT at high-intermediate dose levels and an increase of the volume irradiated at doses < 20 Gy.

Although it is not a goal of this work, it is important to un-derline that our clinical experience with both IMRT and HT shows a substantial equivalence between the two techniques in terms of time slot for NPC patients, including setup (MVCT and correction with HT) and delivery.

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Address for Correspondence Claudio Fiorino Servizio di Fisica Sanitaria H. S. Raffaele Via Olgettina 60 20132 Milano Italy Phone (+39/02) 2643-2278, Fax -2773

e-mail: [email protected]

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Simultaneous Integrated Boost (SIB) for Nasopharynx Cancer with Helical Tomotherapy