Supplementary Table 1: Clinical characteristics of the 41 ...



Supplementary Table 1: Clinical characteristics of the 41 NPC patients and 21 patients with NPC and unilateral TLNCharacteristicValue for the 41 NPC patientsValue for the 21 NPC patients with unilateral TLNNumber 4121GenderMale3116Female105Age (years)≤ 40138> 402813T stageaT171T291T3173T4816N stageaN064N12012N2115N340Overall stageaI21II111III163IV1216Radiation techniquebVMAT170Static IMRT2421Chemotherapy No63Yes 3518Involved lateralityLeft side13Right side8Abbreviations: 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 methodsDosimetric parametersMethod 1aMethod 2bt Difference PMean differenceP-valuetMean differenceP-valueD0.1ccc6.1510.46<0.0016.0910.40<0.001D0.5cc5.088.03<0.0016.8411.87<0.001D1cc6.9812.84<0.0017.0112.86<0.001D5cc7.1214.28<0.0017.7014.81<0.001D10cc5.9212.91<0.0016.5513.45<0.001D15cc4.7010.09<0.0015.0810.49<0.001D20cc3.807.290.0014.267.77<0.001D25cc3.525.440.0023.965.790.001D30cc3.443.450.0044.184.240.001D35cc2.421.970.0254.423.03<0.001D40cc2.001.310.0493.852.170.001D1d7.0612.54<0.0017.1412.90<0.001D27.2313.82<0.0017.2514.12<0.001D57.8414.89<0.0018.0415.05<0.001D107.1214.66<0.0017.0114.16<0.001D156.1713.02<0.0015.4611.66<0.001D204.9811.33<0.0014.589.12<0.001D254.618.91<0.0014.206.840.001D304.217.050.0014.234.96<0.001D354.625.75<0.0014.813.98<0.001D404.514.19<0.0014.393.00<0.001D454.033.140.0013.982.270.001D503.632.360.0023.741.770.001D553.611.760.0023.671.510.002D603.591.40.0023.711.470.001V10e3.324.880.0033.175.280.005V205.135.86<0.0015.316.15<0.001V255.957.16<0.0016.166.79<0.001V306.978.72<0.0016.957.69<0.001V356.779.71<0.0016.868.18<0.001V406.1810.01<0.0016.488.26<0.001V455.849.89<0.0016.108.03<0.001V502.723.370.0135.817.78<0.001V555.198.61<0.0015.397.02<0.001V604.757.07<0.0014.785.75<0.001V653.884.930.0013.884.010.001V702.852.640.012.872.200.009V752.060.830.0422.190.720.041Volume2.923.620.0092.263.100.035Dmean5.834.98<0.0015.834.36<0.001D1 of PRVf7.3511.48<0.0017.5011.80<0.001D5 of PRV7.8014.19<0.0018.2014.73<0.001D10 of PRV6.8014.18<0.0017.2714.73<0.001D15 of PRV5.9513.14<0.0015.7212.45<0.001D20 of PRV4.9311.02<0.0014.719.59<0.001D25 of PRV4.308.60<0.0014.297.15<0.001D30 of PRV4.016.770.0014.205.25<0.001D35 of PRV3.945.070.0014.263.92<0.001D40 of PRV4.163.88<0.0014.383.06<0.001D45 of PRV3.892.930.0014.132.350.001D50 of PRV3.702.230.0013.911.880.001D55 of PRV3.721.660.0013.761.590.001D60 of PRV3.441.250.0033.571.400.002V20 of PRV5.315.66<0.0015.215.72<0.001V25 of PRV5.736.88<0.0016.016.70<0.001V30 of PRV6.948.77<0.0016.707.73<0.001V35 of PRV6.599.40<0.0016.828.28<0.001V40 of PRV6.229.61<0.0016.528.31<0.001V45 of PRV5.969.92<0.0016.318.06<0.001V50 of PRV5.749.17<0.0016.047.78<0.001V55 of PRV5.538.47<0.0015.767.18<0.001V60 of PRV5.057.16<0.0015.176.08<0.001V65 of PRV4.335,.30<0.0014.384.51<0.001V70 of PRV3.182.990.0053.422.660.003V75 of PRV2.451.100.0242.550.980.019Abbreviations: 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 suf?xes expresses the same meaning, but the suf?x numbers represent the absolute volume.dD1 is the minimum dose received by the ‘‘hottest’’ 1% of the organ, the other D with suf?xes express the same meaning, but the suf?x 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 suf?xes express the same meaning, but the suf?x 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 pre?x parameter represent the percentage of volume or the dose received.Supplementary Table 3: Anatomic boundaries of the organs at risk in anStandard TPS name [20]CranialCaudalAnteriorPosteriorLateralMedialTMJ TMjointaDisappearance of articular cavityAppearance 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 condyleSurface of fossa glenoidLat. edge of mandibular condyle or surface of fossa glenoidBrainstemBrainStemOptic tract or the disappearance of posterior cerebral arteryForamen magnumPost. edge of prepon- tine cistern or basilar arteryAnt. edge of forth ventricle or mesencephalic aqueductPosterior cerebral artery, anterior inferior cerebellar artery, cerebellar peduncleOptic chiasmChiasmOne or two slices superiorlyPituitary or suprasellar cisternOptic canalInfundibulumInternal carotid arteries, middle cerebral arteriesTongue(oral cavity)bTongue Post. edge of the hard palate or soft palateDisappearance of anterior belly of digastric musclePost. edge of mandible or is freePalate, oropharynx, the palatine tonsil, hyoid boneMed. edge of the mandible or inferior alveoli socketLarynx(larynx and laryngopharynx)Larynx Cranial edge of epiglottisCaudal edge of cricoid cartilageAnt. edge of thyroid cartilage or cricoid cartilageIncluding arytenoid cartilage, the superior and inferior horns of thyroid cartilage and post. edge of pharyngeal constrictorMed. edge of hyoid bone, lat. edge of thyroid cartilage and cricoid cartilage， cervical vessels, nerves, and lateral thyroidUpper pharyngeal constrictor [22]Pharyngeal- Const_UpperCaudal edge of pterygoid platesCranial edge of hyoid boneNasopharynx, oropharynx, laryngopharynx, base of tongueLongus capitis m., longus colli m., body of cervical vertebraCarotid sheathMiddle pharyngeal constrictor [22]Pharyngeal- Const_MiddleCranial edge of hyoid boneCaudal edge of hyoid boneLaryngopharynxLongus capitis m., longus colli m., body of cervical vertebraHyoid boneInferior pharyngeal constrictor [22]Pharyngeal- Const_LowerCaudal edge of hyoid boneCaudal edge of cricoid cartilageLaryngopharynx or cricoids cartilageLongus capitis m., longus colli m., body of cervical vertebraThyroid cartilage or thyroid glandTracheaTracheaCaudal edge of cricoid cartilageTwo centimeters below the caudal edge of the clavicular headPost. edge of isthmus of thyroid glandAnt. edge of esophagusLateral thyroid glandOne-two millimeters expanded from the lumen of tracheaSubman-dibular gland SubmandibularaInferior edge of medial pterygoid or the level of C3Appearance of fat space of submandibular triangleLat. 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 platysmaCervical vessels, superior and middle pharyngeal constrictor m., hyoid bone, post. belly of the digastric m., mylohyoid m. or hyoglossus m.Esophagus [22]EsophagusCaudal edge of cricoid cartilageTwo centimeters below the caudal edge of the clavicular headTracheaVertebral body or longus colli m.Fat space or thyroid glandOptic nerve [23]OpticNerveaBelow the superior rectusSuperior the inferior rectusPosterior edge of the center of globeOptic canalTemporal lobeTemporalLobeaCranial edge of the sylvian fissureBase of middle cranial fossaTemporal bone and sylvian fissure， greater wing of sphenoidPetrous part of temporal lobe, tentorium of cerebellum, incisura preoccipitalisTemporal boneCavernous sinus, sphenoid sinus, sella turcica, and sylvian fissure（including parahippocampal gyrus and hippocampusParotid gland [21]ParotidaExternal auditory canal, mastoid process Appearance post. part submandibular spaceMasseter m. post. border mandibular bone, medial pterygoid m.Ant. belly sternocleidomastoid m., lat. side post. belly of the digastric m. (posterior medial)， mastoid processSubmandibular fat, platysmaPost. belly of the digastric m., styloid process, parapharyngeal space， sternocleidomastoidSpinal cordSpinalCordDisappearance of cerebellumTwo centimeters below the inferior edge of the clavicular headExclude the subarachnoid spaceBrachial plexus [24]BrachialPlexusaCaudal edge of C4Caudal edge of T1 at neural foramina and one to two CT slices below the clavicular head as the posterior aspect of the neurovascularbundleAnterior scalene muscleMiddle scalene muscleFat spaceSpinal cordThyroid glandThyroidCaudal edge of pyriform sinus or midpoint of thyroid cartilageBody of fifth to seventh cervical vertebraSternohyoid or sternocleidomastoidCervical vessels or longus colli m.Cervical vessels or sternocleidomastoidThyroid cartilage or cricoids cartilage or esophagus or pharyngeal constrictorMandibleMandibleThe 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 earEar_InneraCochlea and IAC should be individually delineated and named.Middle earEar_MiddleaTympanic cavity, bony part of ET should be individually delineated and named. EyesEyesaEnsure the retina to be contoured completely.LensLensaThe boundary between the lens and the vitreum is obviousPituitaryPituitaryThe 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 thicknessAbbreviations: 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.AbbreviationsFull nameOARorgan at riskTMJtemporomandibular jointNPCnasopharyngeal carcinomaPCpharyngeal constrictorETEustachian tubeROCreceiver operating characteristicTLNtemporal lobe necrosisIACinternal auditory canalRTradiotherapyGTVgross target volumeCTVclinical target volumePTVplanning target volumePRVplanning organ at risk volumeDmeanmean doseDmaxmaximum doseS.E.standard errorSNHLsensorineural hearing lossOMEotitis media with effusionIMRTintensity modulated radiotherapyVMATvolumetric modulated arc therapyAUCArea under the curveDx(xcc)minimum dose received by the ‘‘hottest’’ x% (or x ml) of the organVxvolume percentage of the organ receiving ≥ X GySupplementary 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.Supplementary References 1: The list of literatures relative to OARs contouringBaxi S, Park E, Chong V, Chung HT. Temporal changes in IMRT contouring of organs at risk for nasopharyngeal carcinoma - the learning curve blues and a tool that could help. Technol Cancer Res Treat 2009; 8:131-140.Gondi V, Tome WA, Rowley HA, Mehta MP. Hippocampal Contouring: A Contouring Atlas for RTOG 0933. 2011.Penumetcha N,?HYPERLINK ""Kabadi S,?HYPERLINK ""Jedynak B, et al. 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