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Supplementary Table 1: Clinical characteristics of the 41 NPC patients and 21 patients with NPC and unilateral TLN
Characteristic Value for the 41 NPC patients Value for the 21 NPC patients with unilateral TLNNumber 41 21
Gender
Male 31 16
Female 10 5
Age (years)
≤ 40 13 8
> 40 28 13
T stagea
T1 7 1
T2 9 1
T3 17 3
T4 8 16
N stagea
N0 6 4
N1 20 12
N2 11 5
N3 4 0
Overall stagea
I 2 1
II 11 1
III 16 3
IV 12 16
Radiation techniqueb
VMAT 17 0
Static IMRT 24 21
Chemotherapy
No 6 3
Yes 35 18
Involved laterality
Left side 13
Right side 8
Abbreviations: TLN, temporal lobe necrosis; IMRT, intensity modulated radiotherapy; VMAT, volumetric modulated arc therapyaAccording to the 7th AJCC/UICC staging system.bAll the patients were treated with IMRT including 17 with VMAT and 24 with static IMRT.
Supplementary Table 2: Comparison of dosimetric parameters between temporal lobes with and without TLN using the two contouring methods
Dosimetric parameters
Method 1a Method 2b
t Mean difference P-value t Mean difference P-valueD0.1ccc 6.15 10.46 <0.001 6.09 10.40 <0.001D0.5cc 5.08 8.03 <0.001 6.84 11.87 <0.001D1cc 6.98 12.84 <0.001 7.01 12.86 <0.001D5cc 7.12 14.28 <0.001 7.70 14.81 <0.001
D10cc 5.92 12.91 <0.001 6.55 13.45 <0.001D15cc 4.70 10.09 <0.001 5.08 10.49 <0.001D20cc 3.80 7.29 0.001 4.26 7.77 <0.001D25cc 3.52 5.44 0.002 3.96 5.79 0.001D30cc 3.44 3.45 0.004 4.18 4.24 0.001D35cc 2.42 1.97 0.025 4.42 3.03 <0.001D40cc 2.00 1.31 0.049 3.85 2.17 0.001
D1d 7.06 12.54 <0.001 7.14 12.90 <0.001D2 7.23 13.82 <0.001 7.25 14.12 <0.001D5 7.84 14.89 <0.001 8.04 15.05 <0.001D10 7.12 14.66 <0.001 7.01 14.16 <0.001D15 6.17 13.02 <0.001 5.46 11.66 <0.001D20 4.98 11.33 <0.001 4.58 9.12 <0.001D25 4.61 8.91 <0.001 4.20 6.84 0.001D30 4.21 7.05 0.001 4.23 4.96 <0.001D35 4.62 5.75 <0.001 4.81 3.98 <0.001D40 4.51 4.19 <0.001 4.39 3.00 <0.001D45 4.03 3.14 0.001 3.98 2.27 0.001D50 3.63 2.36 0.002 3.74 1.77 0.001D55 3.61 1.76 0.002 3.67 1.51 0.002D60 3.59 1.4 0.002 3.71 1.47 0.001V10e 3.32 4.88 0.003 3.17 5.28 0.005V20 5.13 5.86 <0.001 5.31 6.15 <0.001V25 5.95 7.16 <0.001 6.16 6.79 <0.001V30 6.97 8.72 <0.001 6.95 7.69 <0.001V35 6.77 9.71 <0.001 6.86 8.18 <0.001V40 6.18 10.01 <0.001 6.48 8.26 <0.001V45 5.84 9.89 <0.001 6.10 8.03 <0.001V50 2.72 3.37 0.013 5.81 7.78 <0.001V55 5.19 8.61 <0.001 5.39 7.02 <0.001V60 4.75 7.07 <0.001 4.78 5.75 <0.001V65 3.88 4.93 0.001 3.88 4.01 0.001V70 2.85 2.64 0.01 2.87 2.20 0.009V75 2.06 0.83 0.042 2.19 0.72 0.041
Volume 2.92 3.62 0.009 2.26 3.10 0.035Dmean 5.83 4.98 <0.001 5.83 4.36 <0.001
D1 of PRVf 7.35 11.48 <0.001 7.50 11.80 <0.001D5 of PRV 7.80 14.19 <0.001 8.20 14.73 <0.001D10 of PRV 6.80 14.18 <0.001 7.27 14.73 <0.001D15 of PRV 5.95 13.14 <0.001 5.72 12.45 <0.001
D20 of PRV 4.93 11.02 <0.001 4.71 9.59 <0.001D25 of PRV 4.30 8.60 <0.001 4.29 7.15 <0.001D30 of PRV 4.01 6.77 0.001 4.20 5.25 <0.001D35 of PRV 3.94 5.07 0.001 4.26 3.92 <0.001D40 of PRV 4.16 3.88 <0.001 4.38 3.06 <0.001D45 of PRV 3.89 2.93 0.001 4.13 2.35 0.001D50 of PRV 3.70 2.23 0.001 3.91 1.88 0.001D55 of PRV 3.72 1.66 0.001 3.76 1.59 0.001D60 of PRV 3.44 1.25 0.003 3.57 1.40 0.002V20 of PRV 5.31 5.66 <0.001 5.21 5.72 <0.001V25 of PRV 5.73 6.88 <0.001 6.01 6.70 <0.001V30 of PRV 6.94 8.77 <0.001 6.70 7.73 <0.001V35 of PRV 6.59 9.40 <0.001 6.82 8.28 <0.001V40 of PRV 6.22 9.61 <0.001 6.52 8.31 <0.001V45 of PRV 5.96 9.92 <0.001 6.31 8.06 <0.001V50 of PRV 5.74 9.17 <0.001 6.04 7.78 <0.001V55 of PRV 5.53 8.47 <0.001 5.76 7.18 <0.001V60 of PRV 5.05 7.16 <0.001 5.17 6.08 <0.001V65 of PRV 4.33 5,.30 <0.001 4.38 4.51 <0.001V70 of PRV 3.18 2.99 0.005 3.42 2.66 0.003V75 of PRV 2.45 1.10 0.024 2.55 0.98 0.019
Abbreviations: PRV=planning organ at risk volume; D mean= mean dose; TLN=temporal lobe necrosis;aTemporal lobe including the basal ganglia and insula, excluding parahippocampal gyrus and hippocampusbTemporal lobe including parahippocampal gyrus and hippocampus, excluding basal ganglia and insula.cD0.1cc is the minimum dose received by the ‘‘hottest’’ 0.1ml of the organ, the other D with suffixes
expresses the same meaning, but the suffix numbers represent the absolute volume.dD1 is the minimum dose received by the ‘‘hottest’’ 1% of the organ, the other D with suffixes express the same meaning, but the suffix numbers represent the percentage of volume.eV10 is the percentage of volume of temporal lobe that receives more than 10 Gy, the other V with suffixes express the same meaning, but the suffix numbers represent the doses received.f D1of PRV is the minimum dose received by the ‘‘hottest’’ 1% of the planning organ at risk volume of temporal lobe volume, the other Dx of PRV, Vx of PRV express the same meaning, but the prefix parameter represent the percentage of volume or the dose received.
Supplementary Table 3: Anatomic boundaries of the organs at risk in NPC.
Organ Standard TPS name [20]
Cranial Caudal Anterior Posterior Lateral Medial
TMJ TMjointa Disappearance of articular cavity
Appearance of the head of mandible or one slice superior to the sigmoid notch of the neck of mandible
Articular condyle of the temporal bone, ant. edge of mandibular condyle
Surface of fossa glenoid
Lat. edge of mandibular condyle or surface of fossa glenoid
Brainstem BrainStem Optic tract or the disappearance of posterior cerebral artery
Foramen magnum Post. edge of prepon- tine cistern or basilar artery
Ant. edge of forth ventricle or mesencephalic aqueduct
Posterior cerebral artery, anterior inferior cerebellar artery, cerebellar peduncle
Optic chiasm Chiasm One or two slices superiorly
Pituitary or suprasellar cistern
Optic canal Infundibulum Internal carotid arteries, middle cerebral arteries
Tongue(oral cavity)b
Tongue Post. edge of the hard palate or soft palate
Disappearance of anterior belly of digastric muscle
Post. edge of mandible or is free
Palate, oropharynx, the palatine tonsil, hyoid bone
Med. edge of the mandible or inferior alveoli socket
Larynx(larynx and laryngopharynx)
Larynx Cranial edge of epiglottis
Caudal edge of cricoid cartilage
Ant. edge of thyroid cartilage or cricoid cartilage
Including arytenoid cartilage, the superior and inferior horns of thyroid cartilage and post. edge of pharyngeal constrictor
Med. edge of hyoid bone, lat. edge of thyroid cartilage and cricoid cartilage, cervical vessels, nerves, and lateral thyroid
Upper Pharyngeal- Caudal edge of Cranial edge of hyoid Nasopharynx, Longus capitis m., Carotid sheath
pharyngeal constrictor [22]
Const_Upper pterygoid plates bone oropharynx, laryngopharynx, base of tongue
longus colli m., body of cervical vertebra
Middle pharyngeal constrictor [22]
Pharyngeal- Const_Middle
Cranial edge of hyoid bone
Caudal edge of hyoid bone
Laryngopharynx Longus capitis m., longus colli m., body of cervical vertebra
Hyoid bone
Inferior pharyngeal constrictor [22]
Pharyngeal- Const_Lower
Caudal edge of hyoid bone
Caudal edge of cricoid cartilage
Laryngopharynx or cricoids cartilage
Longus capitis m., longus colli m., body of cervical vertebra
Thyroid cartilage or thyroid gland
Trachea Trachea Caudal edge of cricoid cartilage
Two centimeters below the caudal edge of the clavicular head
Post. edge of isthmus of thyroid gland
Ant. edge of esophagus
Lateral thyroid gland One-two millimeters expanded from the lumen of trachea
Subman-dibular gland
Submandibulara Inferior edge of medial pterygoid or the level of C3
Appearance of fat space of submandibular triangle
Lat. surface of mylohyoid m. or hyoglossus m.
Parapharyngeal space, cervical vessels and post. belly of digastric m., sternocleidomastoid m.
Ramus of the mandible, subcutaneous fat or platysma
Cervical vessels, superior and middle pharyngeal constrictor m., hyoid bone, post. belly of the digastric m., mylohyoid m. or hyoglossus m.
Esophagus [22] Esophagus Caudal edge of cricoid cartilage
Two centimeters below the caudal edge of the clavicular head
Trachea Vertebral body or longus colli m.
Fat space or thyroid gland
Optic nerve [23] OpticNervea Below the superior rectus
Superior the inferior rectus
Posterior edge of the center of globe
Optic canal
Temporal lobe TemporalLobea Cranial edge of the Base of middle cranial Temporal bone and Petrous part of Temporal bone Cavernous sinus,
sylvian fissure fossa sylvian fissure, greater wing of sphenoid
temporal lobe, tentorium of cerebellum, incisura preoccipitalis
sphenoid sinus, sella turcica, and sylvian fissure(including parahippocampal gyrus and hippocampus
Parotid gland [21]
Parotida External auditory canal, mastoid process
Appearance post. part submandibular space
Masseter m. post. border mandibular bone, medial pterygoid m.
Ant. belly sternocleidomastoid m., lat. side post. belly of the digastric m. (posterior medial), mastoid process
Submandibular fat, platysma
Post. belly of the digastric m., styloid process, parapharyngeal space, sternocleidomastoid
Spinal cord SpinalCord Disappearance of cerebellum
Two centimeters below the inferior edge of the clavicular head
Exclude the subarachnoid space
Brachial plexus [24]
BrachialPlexusa Caudal edge of C4 Caudal edge of T1 at neural foramina and one to two CT slices below the clavicular head as the posterior aspect of the neurovascularbundle
Anterior scalene muscle Middle scalene muscle
Fat space Spinal cord
Thyroid gland Thyroid Caudal edge of pyriform sinus or midpoint of thyroid
Body of fifth to seventh cervical vertebra
Sternohyoid or sternocleidomastoid
Cervical vessels or longus colli m.
Cervical vessels or sternocleidomastoid
Thyroid cartilage or cricoids cartilage or esophagus or
cartilage pharyngeal constrictor
Mandible Mandible The mandible be contoured as whole organ but not be divided into the left and the right. Contouring of the mandible should include alveolar bone and exclude the teeth.
Inner ear Ear_Innera Cochlea and IAC should be individually delineated and named.
Middle ear Ear_Middlea Tympanic cavity, bony part of ET should be individually delineated and named.
Eyes Eyesa Ensure the retina to be contoured completely.
Lens Lensa The boundary between the lens and the vitreum is obvious
Pituitary Pituitary The pituitary is located in the hypophysial fossa. Insure the organ be contoured completely but not beyond the surrounding bone. The pituitary is ovoid and can be visualized on 1-2 slices on CT scans of 3 mm thickness
Abbreviations: TMJ, temporomandibular joint; ET, Eustachian tube; IAC, internal auditory canal; m., muscle.a The organs should be divided into left and right, and the standard TPS name of laterality is indicated by appending an underscore character ( _ ), followed by L or R, respectively. For example, the left parotid is named Parotid_L; the right parotid is named Parotid_R.b include the base of the tongue, body of tongue and mouth floor.
Supplementary table 4: Abbreviations mentioned in the manuscript.
Abbreviations Full name
OAR organ at risk
TMJ temporomandibular joint
NPC nasopharyngeal carcinoma
PC pharyngeal constrictor
ET Eustachian tube
ROC receiver operating characteristic
TLN temporal lobe necrosis
IAC internal auditory canal
RT radiotherapy
GTV gross target volume
CTV clinical target volume
PTV planning target volume
PRV planning organ at risk volume
Dmean mean dose
Dmax maximum dose
S.E. standard error
SNHL sensorineural hearing loss
OME otitis media with effusion
IMRT intensity modulated radiotherapy
VMAT volumetric modulated arc therapy
AUC Area under the curve
Dx(xcc) minimum dose received by the ‘‘hottest’’ x% (or x ml) of the organ
Vx volume percentage of the organ receiving ≥ X Gy
Supplementary Figure 1. Receiver operating characteristic (ROC) curve analysis for the D1 of
the PRV using two different temporal lobe contouring methods in 21 NPC patients with
unilateral TLN.
Supplementary Figure 2. Recommended atlas of the tympanic cavity, Eustachian tube (ET), cochlea, IAC,
TMJ, temporal lobe, brainstem, parotid gland, spinal cord, optic nerve, chiasm, submandibular gland,
pituitary, mandible, eyes, lens, brachial plexus, tongue(oral cavity), larynx, pharyngeal constrictors and
trachea as OARs based on CT-MRI fusion in NPC patients.
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