Dosimetric analysis of isocentrically shielded volumetric modulated arc therapy for locally recurrent nasopharyngeal cancer
Dosimetric analysis of isocentrically shielded volumetric modulated arc therapy for locally recurrent nasopharyngeal cancer
Daniel T. Chang
OPEN This study aimed to investigate the dosimetric characteristics of an isocentrically shielded RapidArc (IS-RA) technique for treatment of locally recurrent nasopharyngeal cancer (lrNPC). In IS-RA, the isocenter was placed at the center of the pre-irradiated brainstem (BS)/spinal cord (SC) and the jaws were set to shield the BS/SC while ensuring the target coverage during the whole gantry rotation. For fifteen patients, the IS-RA plans were compared with the conventional RapidArc (C-RA) regarding target coverage, organ-at-risk (OAR) sparing and monitor units (MUs). The relationship between the dose reduction of BS/SC and some geometric parameters including the angle extended by the target with respect to the axis of BS/SC (Ang_BSSC), the minimum distance between the target and BS/SC (Dist_Min) and the target volume were evaluated. The IS-RA reduced the BS/SC doses by approximately 1-4 Gy on average over the C-RA, with more MUs. The IS-RA demonstrated similar target coverage and sparing of other OARs except for slightly improved sparing of optic structures. More dose reduction in the isocentric region was observed in the cases with larger Ang_BSSC or smaller Dist_Min. Our results indicated that the IS-RA significantly improves the sparing of BS/SC without compromising dosimetric requirements of other involved structures for lrNPC.
Radiotherapy is the main treatment paradigm for nasopharyngeal carcinoma (NPC)1. Though loco-regional
control rate of NPC has been improved significantly in the past decade, local recurrence remains a major problem2
with an incidence of 10?36%3. Re-irradiation with a tumoricidal dose above 60 Gy is commonly used as a main
treatment for locally recurrent NPC (lrNPC) patients4,5. Clinically, an important factor affecting the local control
of lrNPC radiotherapy is the dose administered to the target. In the era of 3D conformal radiotherapy (3D CRT),
Wang3,6 reported lrNPC is clearly dose responsive. The 5 year survival rate was 45% when ?60 Gy was delivered,
but no patient survived in the <60 Gy group. Lu et al.7 reported an excellent local control rate after high dose
intensity-modulated radiotherapy (IMRT) of 68?70 Gy for lrNPC. Similarly, a better local control and survival
with escalated dose was observed by Li et al.8. However, delivery of higher-dose radiation is clinically challenging
due to the pre-irradiated condition of the surrounding organs at risk (OARs), such as the brainstem (BS) and
spinal cord (SC)9. Myelitis and BS necrosis, which are rare but devastating, may occur if the doses delivered to BS
and SC exceed the tolerance in the management of NPC patients10,11. The fact that, in most cases, the BS/SC are
proximal to the locally recurrent lesion and have reached the threshold doses in the primary treatment course,
aggravates the situation and makes it a challenging task to deliver an adequate dose to the target without causing
any correlated damage.
Volumetric modulated arc therapy (VMAT) provides a viable solution for re-irradiation of nasopharyngeal
carcinoma in clinical practice12. Up to this point, however, little effort has been devoted to optimally utilizing
the technical capability of VMAT for lrNPC. In this work, a proposed RapidArc (RA) strategy, referred to as
?isocentrically shielded RA (IS-RA)?, was investigated for substantially improved dose sparing of the BS/SC while
maintaining the target coverage. A detailed planning study was performed to demonstrate the dosimetric benefits
of the IS-RA technique.
Ethics Statement. The protocol was approved by the Ethical Commission of the Cancer Hospital of Shantou
University Medical College. Because this was not a treatment-based study, our institutional review board waived
the need for written informed consent from the participants. The patient information was anonymized and
de-identified to protect patient confidentiality. The methods were carried out in accordance with the approved
Patient characteristics. Fifteen lrNPC patients with Stage rT1?rT4, N0-1, M0 were included in this study,
staged according to the American Joint Committee on Cancer (AJCC) 7th edition staging system. Eleven were
male and four were female, with the median age of 49 (range, 17?70) years. All the patients received radical
chemoradiation in the first treatment and the median time to treatment failure was 16 months (range, 13?22
CT simulation and target/OAR delineation. All of the patients were immobilized in the supine position
in a tailor-made thermoplastic cast from head to shoulders. CT scans with intravenous contrast using a 3 mm
slice thickness from the head to 2 cm below the sternoclavicular joint were performed by a CT scanner (Philips
Brilliance CT Big Bore Oncology Configuration, Cleveland, OH). The CT images were then transferred to the
Eclipse (version 10.0) treatment planning system (Varian Medical System, Inc., Palo Alto, CA) for target and OAR
delineation and treatment planning.
The gross tumor volume (GTV) included the recurrent primary lesions and positive lymph nodes, which
were determined by the CT, MRI, Positron Emission Tomography (PET) and endoscopic findings. Clinical target
volume (CTV) encompassing microscopic disease was defined as the GTV plus margins of 8?10 mm, allowing
smaller margins close to critical intracranial structures or the SC. Planning target volume (PTV) was generated
to account for setup variability and internal motion by adding 3 mm margins to the CTV. The median volume of
the PTV (Vol_PTV) was 89 cm3 with the range of 38?209 cm3.
The OARs, including the SC, BS, lenses, optic nerves, optic chiasm, temporomandibular (T-M) joints,
temporal lobes, oral cavity and parotids were contoured. Planning organ-at-risk volumes (PRVs) were created by adding
5 mm margins to the SC and 3 mm margins to the BS, denoted as PRV-SC and PRV-BS, respectively. Normal
tissue was defined as the body subtracting the PTV.
Treatment planning. Three different plans were created for each patient in Eclipse using the three
different techniques, IS-RA, conventional RA (C-RA) and RA with the same gantry and collimator angles as those of
IS-RA (RA-SGC). 6-MV photon beams from the TrueBeam linear accelerator (Varian Medical System, Inc., Palo
Alto, CA) were employed for all the plans. The Progressive Resolution Optimizer (PRO, version 10.0.28)
algorithm was used for RA optimization. The prescribed dose to the PTV was 60?69.9 Gy (2.00?2.33 Gy/fraction)
administered in 30 fractions. All the treatment plans were normalized to achieve the goal of 95% of the PTVs
covered by 100% of the prescription dose, except for 4 advanced cases where compromises were necessary to
protect the critical OARs.
The planning goals of the PTVs and OARs used in this dosimetric study are shown in Table?1. Dx represents
the dose which is reached or exceeded in x of the volume. V100% represents the % volume covered by 100% of the
prescription dose. The planning constraints were fine-tuned, balancing the tradeoffs between the lowest dose to
the BS/SC and the acceptable PTV coverage.
In generating an IS-RA plan, the isocenter was set at the center of the BS (13 cases) or SC (2 cases), to which
the PTV was adjacent. Four or six coplanar partial arcs were placed in two gantry rotations (two or three partial
arcs in clockwise gantry rotation, and the other two or three in counter-clockwise rotation). The collimators
rotated to angles approximately parallel to the BS and SC during the gantry rotation, generally 1??20?. The jaw
positions were set individually for each partial arc, with the priority of shielding the PRVs of BS and SC, followed
by the partial coverage of PTV, but ensuring full PTV coverage if possible during the whole gantry rotation. The
geometry settings of a representative IS-RA plan are shown in Fig.?1. There were some overlaps between the
adjacent partial arcs in the cases where the PTV was large and more arc length was required to irradiate every
portion of the PTV. One partial arc irradiated one side of the PTV near the BS/SC from the beam?s eye view (BEV)
while the other partial arc irradiated the opposite side of the PTV. The gantry start and stop angles for each partial
arc were individually determined using the BEV. For the cases in which the PTVs were in proximity to the optic
structures, two non-coplanar arcs (gantry 45??90?) with couch 90? were used to bypass the optic structures and
deliver sufficient doses to the PTVs.
For each C-RA plan, the isocenter was set at the center of the PTV. Two coplanar full arcs (gantry angle:
181??179? and 179??181?) with the same non-coplannar arcs settings as IS-RA were used. The collimator angles
were set to 30? aiming at minimizing the tongue and groove effect. The optimization objectives of the C-RA plans
were set the same as those of the IS-RA plans.
In order to discriminate the effects of the isocenter placement in the BS/SC and the prolonged arc length with
different collimator rotation (1??20?), the RA-SGC plans were generated, in which the only differences from
IS-RA were that the isocenter was placed at the center of the PTV (but not in the BS/SC) and the jaws were
automatically set to fit to the whole PTV (but not manually fixed to irradiate the partial PTV). The same optimization
objectives were used. All the plans were conducted by a medical physicist.
Plan evaluation. To compare the three plans, dose-volume statistics, isodose distributions and cumulative
dose-volume histograms (DVHs) were calculated. According to the International Commission on Radiation
Units and Measurements (ICRU) report 83, D2% and D98% were selected as near-maximal and near-minimal
doses for the PTV, respectively. Homogeneity index (HI) was employed to assess the target dose homogeneity13:
The target dose conformality was measured by the conformity index (CI) introduced by Paddick14 accounting
for the overlap between the prescription isodose volume (PIV) and the target volume (TV):
D2% ? D98%
(TV within PIV )2
TV ? PIV
The CI and HI values were both between 0 and 1, with 1 and 0 indicating the ideal conformity and
homogeneity, respectively. D5% was used to evaluate the dose received by the most heavily irradiated 5% volume of
the organ9,15,16. The D2%, D5% and mean dose (Dmean) were used for evaluating the doses delivered to the OARs.
The geometric parameters of the PTV and its geometric relationship with other structures, including the angle
extended by the PTV with respect to the axis of BS/SC (Ang_BSSC) (Fig.?2), the minimum distance between PTV
and BS/SC (Dist_Min) and the Vol_PTV were measured and their effects on the BS/SC sparing were investigated.
In addition, monitor units (MUs) per fraction were recorded for all plans.
Statistical analysis. Statistical analyses were performed using the SPSS (version 19.0) software (SPSS, Inc.,
Chicago, IL). The comparison among the IS-RA, C-RA and RA-SGC plans were tested with two-sided Wilcoxon
signed rank test. The effect of the geometric parameters of the PTV (Ang_BSSC, Dist_Min and Vol_PTV) on the
BS/SC sparing was investigated using linear regression analysis. P-value of <0.05 was considered to be statistically
A systematic approach referred to as IS-RA was established for the treatment of lrNPC. In most plans (33 out of
45 plans), the V100% of PTV was equal to 95%. In the remaining 4 advanced cases (12 plans), the V100% of PTV
was less than 95%, with the lowest value of 88.4%. The doses of all the OARs were limited to the tolerable levels.
Target coverage. Data of target coverage for all 45 plans is summarized in Table?2. No statistically significant
difference was observed with regard to the dose-volume parameters of PTV between the IS-RA and C-RA plans.
The RA-SGC plans demonstrated inferior HI, CI and D2%. Figure?3 shows the dose distributions of the three plans
for a representative case.
OAR sparing and MUs. The IS-RA spared the BS and SC better than the C-RA and RA-SGC. As shown in
Table?2 and Fig.?3, compared to C-RA and RA-SGC, the IS-RA reduced the D2%/D5%/Dmean of the (PRV of ) BS
by 3.3?3.8 Gy/3.5?3.7 Gy/2.4?2.6 Gy on average. The D2%/D5%/Dmean of the (PRV of) SC was reduced by 2.4?2.8
Gy/2.2?2.5 Gy/0.9?1.1 Gy on average with IS-RA technique. These reductions of BS/SC doses were statistically
significant (P < 0.05, as indicated in Table?2).
The relationship between the Ang_BSSC/Dist_Min/Vol_PTV and the dose reductions of the (PRVs of) BS/SC
by IS-RA are demonstrated in Table?3 and Fig.?4, which displays the selected results of geometrical effects with
Left optic nerve
Right optic nerve
Left T-M joint
Right T-M joint
Left temporal lobe
Right temporal lobe
It is also noticed that IS-RA exhibited slightly superior sparing of the optic structures, by up to 1.26 Gy in
terms of D2% when compared to C-RA. IS-RA also reduced Dmean to the normal tissue by up to 0.16 Gy compared
to both C-RA and RA-SGC (P < 0.05). The doses to most other OARs were comparable among the three plans.
Additionally, the IS-RA produced 40.1 ? 18.9% and 34.9 ? 20.1% more MUs than the C-RA and RA-SGC
The proposed IS-RA addresses an unmet need in treatment of lrNPC, as it substantially reduces the doses to the
BS and SC while adequately covering the PTV. In general, the BS and SC are proximal to the locally recurrent
lesions and their threshold doses have often been reached in the primary treatment course, making it challenging
to irradiate the recurrent tumor(s) without exceeding the dose limit of the BS and SC. It is technically difficult to
IS-RA vs. C-RA
IS-RA vs. RA-SGC
improved if the jaw position and collimator angle could be optimized for each gantry angle. With the emergence
of a new generation of digital linacs, a more general type of treatment planning and delivery techniques referred
to as Station Parameter Optimized Radiation Therapy (SPORT)23?26, which optimizes the angular sampling of the
control points of VMAT either in coplanar or noncoplanar space, may further improve the dosimetric
characteristics of IS-RA in the future.
The proposed isocentrically shielded RapidArc technique takes advantages of desirable features of rotational arc
delivery and central sensitive structure blocking strategy and provides much better sparing of the pre-irradiated
brainstem and spinal cord without compromising dosimetric requirements of other organs at risk and the PTV.
The technique provides a viable choice for the re-irradiation of locally recurrent nasopharyngeal cancer.
This study was supported by the grants from Shantou Medical Science and Technology Planning Project 
62 (M Li),  123 (JY Lu) and NIH 1R01 CA 133474 (L Xing). We also wish to thank the support from the
Stanford University Asia-Medical Fund (SAMFUND), Ho Tim-Stanley Ho-Li Ka Shing Fellowship Training Fund
and Li Ka Shing Foundation.
J.-Y.L. and M.L. conceived and designed the experiments. J.-Y.L. and B.-T.H. performed the experiments. J.-Y.L.
and M.L. analyzed the data. J.-Y.L., B.-T.H. and M.L. contributed materials/analysis tools. J.-Y.L. and B.-T.H.
wrote the paper. L.X., D.T.C., Z.-X.L., L.-X.X. and X.P. revised the paper.
Competing financial interests: The authors declare no competing financial interests.
How to cite this article: Lu, J.-Y. et al. Dosimetric analysis of isocentrically shielded volumetric modulated arc
therapy for locally recurrent nasopharyngeal cancer. Sci. Rep. 6, 25959; doi: 10.1038/srep25959 (2016).
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