CRT保留腮腺后的复发

Recurrences after conformal parotid-sparing radiotherapy for headand neck cancerBarbara Bussels a,*,Annelies Maes b ,Robert Hermans c ,Sandra Nuyts a ,Caroline Weltens a ,Walter Van den Bogaert aaDepartment of Radiation Oncology,University Hospital Gasthuisberg,Herestraat 49,B-3000Leuven,BelgiumbLimburgs Oncologisch Centrum,Virga Jesse Hospital,Stadsomvaart 11,B-3500Hasselt,Belgium cDepartment of Radiology,University Hospital Gasthuisberg,Herestraat 49,B-3000Leuven,BelgiumReceived 5June 2003;received in revised form 25February 2004;accepted 12March 2004Available online 19June 2004AbstractBackground and purpose :Evaluation of loco-regional failure patterns and survival after parotid-sparing three-dimensional conformal and intensity modulated radiotherapy (IMRT)for head and neck cancer.Patients and methods :From June 1999to July 2002,seventy-two patients with lateralised head and neck tumours,excluding nasopharyngeal tumours and patients with bilateral or contralateral neck disease,were irradiated with a parotid-sparing technique.Three-dimensional conformal planning was used in 68patients,4patients were treated with dynamic IMRT.Bilateral neck node irradiation was performed in all patients,the junctional (or high level II)nodes,contralateral to the tumour,however,were excluded from the clinical target volume to spare the adjacent parotid from irradiation.In 20patients with persistent or recurrent loco-regional disease,the localisation and volume of the treatment failure,as determined by computed tomography (CT),was copied on the pre-treatment CT-study used for treatment planning.Minimum,mean and maximum doses administered to the region of the failure were calculated and dose–volume histograms were computed of each failure.The failures were divided in three groups depending on the percentage of their volume receiving 95%of the prescribed dose.Recurrences were defined to be in-field (IF)if .95%of their volume received 95%of the prescribed dose and out-field (OF)if ,20%of their volume received 95%of the prescribed dose.When 20–95%of the volume of the recurrence received 95%of the prescribed dose,this recurrence was defined as extending outside the field (EOF).Results :With a median follow-up time of 19months,the 2-year loco-regional control rate was 69%with primary radiotherapy and 63.5%with surgery followed by irradiation ðP ¼0:77Þ:The 2-year overall survival rate for the entire patient population was 67.4%.At the time of analysis,20of the 72patients had developed a loco-regional failure;2patients (2/20)presented with a loco-regional relapse combined with distant metastasis.Fifteen of the 20loco-regional failures (15/20)occurred within the high dose region (IF).Five patients (5/20)developed a failure of which the bulky tumour mass was located within the high dose region but extending outside the treatment volume (EOF).No relapses were seen out-field (OF)and no patients relapsed in the spared junctional area contralateral to the tumour.Conclusions :The selection of patients treated with parotid-sparing radiotherapy,by omitting irradiation to the junctional nodes contralateral to the tumour,proved to be safe in our hands,since no recurrences developed in the spared area.As this parotid-sparing technique reduces significantly the dose to the contralateral parotid and is easy to perform,it should be considered for all selected patients.q 2004Elsevier Ireland Ltd.All rights reserved.Keywords:Parotid-sparing radiotherapy;Xerostomia;Junctional nodes;Intensity modulated radiotherapy;Conformal radiotherapy;Head and neck cancer1.IntroductionUntil recently,the most widely used radiation technique for the treatment of head and neck cancer consisted of twolateral opposed fields and an anterior lower neck field.By using this field set-up,an adequate irradiation of the primary tumour or tumour resection bed and all the neck node levels can be obtained but meanwhile a broad variety of normal tissues are irradiated to high doses.The most hampering long term side effect resulting from this high dose0167-8140/$-see front matter q 2004Elsevier Ireland Ltd.All rights reserved.doi:10.1016/j.radonc.2004.03.014Radiotherapy and Oncology 72(2004)119–127/locate/radonline*Corresponding author.irradiation of normal tissues in the head and neck area is xerostomia[1,14].Xerostomia results from radiation induced dysfunction of the salivary glands and causes disturbances in chewing, swallowing and talking.Due to the lack of saliva,patients are at a higher risk of dental decay,caries and oral candidiasis.Xerostomia is,however,a subjectivefinding, not always well correlated with objectivefindings of salivary gland dysfunction[16].To prevent xerostomia and improve the quality of life of patients irradiated for head and neck cancer,efforts are made—by means of conformal radiation techniques—to reduce the radiation dose to the parotid salivary glands as they produce the majority(60%) of the saliva.The parotid salivary glands are,however,closely related to the junctional(high level II)lymph nodes.Shielding the parotids from irradiation results in a reduced dose to these nodal areas which may be involved by tumour cells.The level II nodes ipsilateral to the tumour are thefirst echelon for nodal involvement of most head and neck cancers. Therefore these nodes are usually included in the clinical target volume[2–4,17,20,23].Data concerning the incidence of nodal invasion of the high level II nodes contralateral to the tumour are very scarce.A detailed literature review concerning the risk of nodal invasion of these contralateral high level II nodes is the subject of a paper by Maes et al.(submitted to Radiotherapy and Oncology).From this scarce literature information it seems that for a subgroup of patients it may be safe to omit the contralateral high level II nodes from the target volume in order to spare the parotid salivary gland contralateral to the tumour.Since June1999,a three-dimensional conformal radi-ation technique is implemented in the Radiotherapy Department of the University Hospitals Leuven(Belgium) with the aim of sparing the parotid gland contralateral to the tumour from irradiation in order to reduce the risk of permanent xerostomia[18].To further improve dose distributions,this technique was optimised by the implementation of intensity modulated radiotherapy since January2002.As the contralateral high level II nodes were omitted from the target volume(to allow sparing of the contralateral parotid),this technique was only taken in consideration for selected patients:patients with lateralised tumours and without clinical evidence of contralateral neck disease. Patients with nasopharyngeal tumours were excluded.While the application of these modern irradiation techniques in order to prevent xerostomia was an exciting idea,the crucial question remained whether these tech-niques would compromise local control.To assess this issue,we investigated the pattern of loco-regional failure of 72patients treated with the parotid-sparing technique. Special attention was given to the nodal area adjacent to the parotid gland contralateral to the tumour,since this region was excluded from the elective nodal volume.2.Methods and materials2.1.Patient characteristicsBetween June1999and July2002,72head and neck cancer patients were treated using conformal parotid-sparing radiotherapy[18].All patients had histological proven head and neck cancer and did not have any evidence for distant metastasis.The diagnostic work up consisted of a chest X-ray,a CT of the head and neck region,a MRI of the head and neck region and an esophagoscopy.Patients with tumours originating from the midline or crossing the mid-line were excluded.So were patients with nasopharyngeal cancer and patients with clinical or radiological evidence of contralateral neck node metastasis.Patients with patho-logical diagnosis or radiological suspicion of involvement of the contralateral nodes at the jugulo-digastric level were also excluded from parotid-sparing radiotherapy.The characteristics of the patients are summarised in Table1.The primary tumour was located in the majority of the cases in the oropharynx(57%),the second most important primary site was the oral cavity(26.5%).The majority of the tumours(93%)were squamous cell carcinoma.Table2represents the stage distribution of all patients according to the TNM classification[24].The majority of the patients(72%)presented with a locally advanced stage (stage III or IV).More than two thirds(49/72)of the patients Table1Patient characteristicsAge:mean(min–max)58years(21–75years) SexMale56Female16Tumour localisationOropharynx41Oral cavity19Larynx6Hypopharynx4Salivary gland1Unknown1PathologySquamous cell carcinoma67 Undifferentiated carcinoma2Poorly differentiated carcinoma2Adenoid cystic carcinoma1Primary RT49RTþCT1RTþporfiromycin1RTþbrachytherapy boost2RT standard schedule(70Gy/2Gy)28RT accelerated schedule17Post-operative RT23B.Bussels et al./Radiotherapy and Oncology72(2004)119–127 120received radiotherapy alone,the remaining one third of the patients(23/72)were treated by primary surgery followed by irradiation.The majority of the patients(15/23)treated post-operatively had a squamous cell carcinoma of the oral cavity.All operated patients underwent a neck dissection,in 4patients a bilateral modified radical neck dissection was performed,19patients underwent an unilateral modified radical neck dissection.The cranial border of level II was defined by our local ENT-surgeons at the base of skull as proposed by Robbins et al.[22].One patient received four cycles of chemotherapy(Cisplatin and5-Fluoro-Uracyl) before radiotherapy and one patient received two intra-venous administrations of40mg/m2Porfiromycin during radiotherapy(within the framework of a randomised phase III trial).All patients were submitted to a regular clinical follow-up at the outpatient clinic:every two months thefirst two years after treatment,every three months the third year after treatment,every four months the fourth year,every six months thefifth year and thereafter every year.CT-studies were performed four months after irradiation and thereafter yearly or earlier in case of symptomatic disease.2.2.Determination and delineation of the target volumesIn all patients a computed tomography study(slice thickness5mm)of the head and neck region was performed in treatment position with an individualised neck support and a thermoplasticfive points mask.On this CT-study primary tumour,post-operative tumour bed,pathological nodes and elective nodal regions were outlined.In the presence of a primary tumour,GTV1was outlined as the visible CT-graphic tumour volume taking into account the clinical presentation of the tumoural lesion.If nodal regions were clinically or radiologically suspect for tumoural invasion these lesions were determined as GTV2. Both GTV’s were extended by1cm in all directions,except in air or bone if there was no evidence for tumoural invasion,to constitute CTV1and CTV2.The third CTV(CTV3)consisted of the elective nodal volume.All nodal regions that would have been irradiated using standard lateral opposed radiationfields in combin-ation with an anterior lower neckfield,were delineated and included in the CTV of the elective neck,except for the contralateral junctional(or high level II)nodes.The junctional or high jugular(high level II)nodal area was defined cranially by the base of skull,caudally by the crossing of the internal jugular vein with the posterior belly of the digastric muscle,laterally by the pterygoid muscle and the parotid gland and medially by the pharyngeal wall and the lateral retropharyngeal nodes.This region corre-sponds to the definition proposed by Eisbruch et al.[8]and consists of the post-styloid portion of the parapharyngeal space,below the jugular fossa and cranially to the jugulo-digastric nodes.The delineation of the neck nodal levels was performed according to the different proposals available in the literature at that moment(1999–2000):Som[25],Martinez-Monge et al.[19],Nowak et al.[21],Wijers et al.[26]and Gre´goire et al.[10].Recently the so-called Brussels guidelines from Gre´goire et al.[10]and the so-called Rotterdam guidelines from Nowak et al.[21]were reviewed and resulted in a common set of recommendations for the delineation of lymph node levels in the node-negative neck [11].The main differences between the delineation of the nodal levels in our series and the consensus guidelines[11] are the cranial limits of level II and level V.In our series the cranial limit of level II was defined at the base of skull in the ipsilateral neck and at the crossing of the internal jugular vein with the posterior belly of the digastric muscle in the contralateral neck(consensus guidelines: caudal edge of lateral process of C1[11]).The cranial limit of level V was defined in our series at the most cranial plane through C1(consensus guidelines:cranial edge of body of hyoid bone[11]).Post-operatively,the CTV of the tumour resection bed was determined as the theoretical reconstruction of the pre-operative gross tumour volume(derived from the pre-operative diagnostic CT-study)with1.5cm margin includ-ing the resection bed with surgical clips and taking into account the potential sites of local tumour extension, excluding air and bone when there was no invasion of the bone.To all these CTV’s a margin of5mm(automatic3D-expansion)was added for inaccuracies in patient set-up and beam placements to create the different PTV’s.As organs at risk both parotids,the brain stem and the spinal cord were outlined on the CT-images.The spinal cord was defined as the structure within the bony edges of the vertebra and a maximal dose of48–50Gy was tolerated. The maximal tolerated dose to the brain stem was50Gy. The goal of the parotid-sparing RT was to administer a mean dose#26Gy to the parotid contralateral to the tumour,no dose constraints were applied to the parotid ipsilateral to the tumour.In patients treated with intensity modulated radiotherapy, the oropharynx and the larynx were also contoured as organs at risk.The dose to these organs was kept as low as possibleTable2Stage distribution of patientsTx T1T2T3T4TotalN0331410838(53%)N10186116(22%)N2a022329(12%)N2b000202(3%)N2c001102(3%)N3030205(7%)Total3(4%)9(12.5%)25(35%)24(33.5%)11(15%)72B.Bussels et al./Radiotherapy and Oncology72(2004)119–127121without compromising irradiation to the elective nodal volumes.2.3.Radiation techniques and dose prescriptionSixty-eight patients were treated using a three-dimensional irradiation technique and4patients underwent dynamic intensity modulated radiotherapy(IMRT).The three-dimensional parotid-sparing technique used at the Leuven department is based on the technique described by Eisbruch et al.[8]and further specified in a publication by Maes et al.[18].This technique consists of a three-field set-up plus an anterior lower neckfield followed by two oblique opposed boostfields.Thefirst28patients,treated with primary parotid-sparing irradiation,received a dose of70Gy to the primary tumour and the involved nodes and a dose of46–50Gy(depending on the dose to the spinal cord)to the elective nodal regions. All patients were treated once daily,five times a week.From January2001to July2002,17patients with locally advanced tumours treated with primary irradiation received an accelerated irradiation schedule consisting of20 fractions of2Gy(once daily)followed by4fractions of 1.6Gy(twice daily)at the level of the primary tumour and the elective nodal regions.A boost irradiation was given to the primary tumour and the involved nodes in16fractions of 1.6Gy(twice daily).All patients were treatedfive times a week.In our study population,two patients received a brachy-therapy boost of respectively20and25Gy low dose rate, both after external irradiation to a dose of46Gy to the primary tumour and the elective nodal regions.When radiation was considered in the post-operative setting,patients were irradiated to a total dose of50–66Gy (in daily fractions of2Gy)depending on the risk to develop relapses.This risk was assessed through a combination of parameters concerning the degree of differentiation of the tumour,the number of invaded nodes,the presence or absence of perineural or vascular invasion and the presence or absence of positive section margins.2.4.Determination of doses to the failure volumesAll patients with persistent or recurrent loco-regional disease underwent a diagnostic contrast enhanced computed tomography study(slice thickness3mm)after histological confirmation.The radiological image of the failure was transposed from the diagnostic CT-scan to the pre-treatment CT-scan used for treatment planning with the help of a radiologist experienced in head and neck oncology.By means of the planning system,minimum,mean and maximum doses at the level of the recurrent or persistent tumoural focus were calculated.Dose–volume histograms were computed of each failure.The failures were defined in-field(IF),extending outside the treated volume(EOF)and out-field(OF)depending on the percentage of their volume—respectively more than95%,between20and 95%and less than20%—receiving95%of the prescribed dose.For all patients with failures extending outside the treated volume,beams-eye-views were displayed of the differentfields to visualise the location of the failure in relation to thefield edges and the blocks.By reviewing the beams-eye-views the probable epicentre of the tumoural relapse was defined.2.5.Statistical analysisThe loco-regional control and overall survival rates were estimated according to the Kaplan–Meier product-limit method.Any local control difference between treat-ments was assessed using the log-rank test.All analyses were performed using a commercial statistical program: Statistica w.3.Results3.1.Local control and overall survival ratesAt the time of analysis,the minimal time from the end of the radiation treatment to last follow-up was six months. The median follow-up time was19months.At two years, the loco-regional control rate was63.5%with surgery followed by radiotherapy and69%with primary irradiation (Fig.1).The difference in local control between the two treatments was not statistically significantðP¼0:77Þ:Fig.2 represents an overview of the number of patients developing loco-regional failures and/or distant metastasis.For the patients with a loco-regional recurrence,the treatment option is also shown.Eighteen of the seventy-two patients(18/72)were diagnosed with loco-regional persistent or recurrent disease without distant metastasis.Two patients(2/72)had a loco-regional recurrence and distant metastasis at the same time. For the analysis of the loco-regional failure patterns all20 patients were taken intoaccount.Fig.1.Loco-regional control.B.Bussels et al./Radiotherapy and Oncology72(2004)119–127 122Five of the seventy-two (5/72)patients developed distant metastasis without a loco-regional recurrence:all patients had lung metastasis (one patient had also bone metastasis).The 2-year overall survival rate for the entire patient population was 67.4%(Fig.3).At the time of analysis 22patients had died:13of a loco-regional recurrence,5patients due to distant metastasis,3patients of a second primary tumour and one patient because of a pneumonia.3.2.Local failure patternsTwenty patients developed a loco-regional failure,thirteen after primary radiotherapy (13/49)and seven afterpost-operative irradiation (7/23).Table 3displays infor-mation about the failures:the primary site,the location of the relapsed volume and the type of relapse.After primary radiotherapy,the majority of the loco-regional failures (12/13)occurred in field (IF):.95%of their volume received 95%of the prescribed dose.One patient (no 4)had a recurrence categorised as extending out-field (EOF):20–95%of the failure volume received 95%of the prescribed dose.This patient presented with a tumoural relapse of which the epicentre was located within the high dose region,but one edge of the failure was in one of the three lateral fields covered by a block.The nodal recurrence was located at the level of the match line of the lateral fields and the anterior lower neck field.Within the group of patients presenting with a loco-regional failure after post-operative radiotherapy,three (3/7)patients presented with an in-field failure while four (4/7)patients had a failure originating in the high dose region but extending outside the borders of the treated volume (EOF).The first of these 4patients (no 15)—21-years old—was treated with post-operative radiation for a primary tumour of the oral tongue.He presented with a recurrence extending from the floor of mouth to the base of skull.The edges of the failure extended to the borders of the radiation fields.When reviewing the beams-eye-views of this patient the epicentre of the tumoural relapse was within the high dose region and the extension outside the irradiated field was probably the result of the aggressive growth oftheFig.2.Fig.3.Overall survival.B.Bussels et al./Radiotherapy and Oncology 72(2004)119–127123tumour.The failure of the second patient (no 16)was located at the match line of the lateral and the anterior lower neck field with a small part of this volume situated under the laryngeal block in the anterior lower neck field.The third patient (no 17)presented with a tumoural invaded abcedation (located in the high dose region)with fistulisation to the skin.The skin was located at the border of the irradiation fields.The fourth and last patient (no 18)was diagnosed with an extensive tumoural recurrence at the level of the tumour resection bed at the oropharynx with extension to the retropharyngeal nodal area in combination with necrotic adenopathies at level Ib ipsilateral and level III ipsi-and contralateral to the tumour.This 48-years old patient,treated with post-operative radiotherapy to a dose of 56Gy,relapsed less than two months after finishing radiotherapy illustrating the aggressive behaviour of this tumour.No out-field recurrences—originating from outside theTable 3Loco-regional recurrence NoSite of primaryLocation of relapse Type of relapsePrimary radiotherapy 1Tonsil LOropharynx L IF T4N0N þlevel II L IF 2Base of tongue RN þlevel II–III R IF T1N33Tonsil LN þlevel II–III L IF T2N14Vallecula LVallecula-floor of mouth L EOF T2N0N þlevel III L EOF 5Supraglottis RHemilarynx RIF T3N16Tonsil LTrigonum retromolare L IF T4N1N þlevel II–III IF 7Vallecula RVallecula RIF T1N08Oral tongue LAnterior tonsillar pillar L IF T2N19Supraglottis RSupraglottis R IF T3N010Supraglottis LAry-epiglottic fold L IF T2N1N þlevel III LIF 11Tonsil LOropharyngeal wall L IF T3N012Buccal mucosa LBuccal mucosa L IF T2N013Base of tongue LBase of tongue LIFT4N0Post-operative radiotherapy 14Tonsil RParapharyngeal space RIF T3N015Oral tongue LParapharyngeal space L from base of skull to floor of mouth EOF T2N016Retromolar trigone LMass from hyoid to larynx EOF T4N0N þlevel III REOF 17Oral tongue RTongue R extension into skin R EOF T3N018Oral tongue ROropharyngeal wall EOF T3N1N þlevel Ib L IF N þlevel III L EOF N þlevel III REOF 19Retromolar trigone L N þretropharyngeal L IF T4N0LUNGMETASTASIS 20Oral tongue L Submandibular L IF T1N2N þlevel IV LIFLUNGMETASTASISAbbreviations used:L,left;R,right;N þ,tumoural invaded node;IF,in-field relapse ¼.95%of the volume of the relapse received 95%of the prescribed dose;EOF,extending outside field ¼20–95%of the volume of the relapse received 95%of the prescribed dose;OF,out-field relapse ¼,20%of the volume of the relapse received 95%of the prescribed dose.B.Bussels et al./Radiotherapy and Oncology 72(2004)119–127124borders of the treatmentfields—were seen in any of the patients.No recurrences were seen at the high level II or junctional nodes contralateral to the tumour,which were omitted from the target volume in order to facilitate sparing of the adjacent parotid salivary gland.4.DiscussionPreventing normal tissue complications after radio-therapy is a priority when new radiation treatment techniques are used,the most important goal of irradiation remains,however,to cure the patient from his cancer.This has to be kept in mind when changing policies in terms of target volume definitions to prevent normal tissue complications.To confirm the choice of target volumes,based on scarce reports in the literature,the most important analysis is the one concerning patterns of loco-regional failure.This study analysed the loco-regional failure patterns of72head and neck cancer patients treated with parotid-sparing radio-therapy.In order to spare from irradiation the parotid gland contralateral to the tumour,the adjacent junctional(or high level II)nodes were omitted from the irradiation volume.As our definitions concerning the margins of the neck node levels derived mainly from the nodal classification by Som [25],the cranial limit of level II was defined at the base of skull in the ipsilateral neck.The region between the base of skull and the crossing of the posterior belly of the digastric muscle with the jugular vein was called the junctional nodal area and the region between this crossing and the caudal edge of the body of the hyoid bone was defined as the jugulo-digastric nodal area.Both the cranial limit of level II and the division of level II into two subareas(junctional and jugulo-digastric nodes) are points of discussion in the literature[2,15].Several authors reported in their papers the base of skull as the cranial limit of level II[6,8,9].Gregoire et al.[10]however, defined the cranial limit of level II at the bottom edge of the body of C1.In the recently developed consensus guidelines for CT-based delineation of lymph node levels in the node-negative neck[11]the cranial border of level II was defined at the caudal edge of the lateral process of C1.This cranial margin is slightly more cranial than the most cranial limit of our clinical target volume in the contralateral neck.Our choice of nodal target volumes was conducted with the aim to include all nodal levels that would have been irradiated by the standardfield set-up,consisting of two lateral opposedfields and a lower anterior neckfield(except for the contralateral high jugular or junctional nodes in the selected patient population).As this standardfield set-up resulted in acceptable loco-regional control rates in our department[12,13],our primary goal was to validate a new treatment technique that allows sparing of the contralateral parotid from irradiation with minimal changes to the target volumes used in the past.Therefore omitting the high junctional nodes contralateral to the tumour from the treatment volume was only thefirst step in creating the ideal target volume.Our future work will consist in a more comprehensive irradiation of the neck nodal levels depend-ing on their risk on microscopic tumoural invasion.Twenty of the72patients developed a loco-regional failure,eighteen of them presented at the time of loco-regional failure without and two of them with distant metastasis.For the loco-regional failure analysis the patient population was divided into two subgroups:primary radiotherapy and post-operative radiotherapy.We are, however,aware of the impact this subgroup analysis has on the power of this study.Therefore,no real conclusions can be made concerning the observation that the majority of the recurrences after primary irradiation occurred in-field while half of the recurrences after post-operative irradiation occurred within the high dose region but extended outside the borders of the treated volume.When analysing both the primary irradiated and the post-operative irradiated patients presenting a failure extending outside thefield(EOF),these patients could be divided into two subgroups:Thefirst subgroup consists of two patients(no4and no 16)with a failure at the level of the match line of the two lateralfields and the anterior lower neckfield.Thisfinding prompted us to retrospectively perform dosimetry within a phantom to check thefield set-up.This check did not show any over-or underdosage at the level of the match lines and ruled out the suspicion of a zone of underdosage increasing the incidence of a local failure.It appeared that the problem of the low doses at the level of the match line was due to the inability of the planning system to calculate precisely the dose at the match line level.These two recurrences can therefore be interpreted as in-field misses.Recently we changed our technique into a one-isocenter conformal technique(with half beams)or to an intensity modulated technique with extendedfields,in order to avoid possible dosage problems at the match line.The second group of patients(no4,no15,no17and no 18)had a loco-regional relapse situated within the high dose region but extending with one edge to the border of this high dose region.This was due to the growth of the tumoural lesion(especially patient no15and patient no18had very aggressive recurrences)and these recurrences would probably not have been prevented by changing the target volumes or using other irradiationfields.We can therefore conclude that all the failures defined as extending outside thefield are rather due to incorrect calculations of the planning system,tumoural growth and aggressive behaviour of the tumour and do not result from wrong target volume definitions or treatment techniques.The most important and reassuring observation was that there were no out-field failures or failures at the level of the junctional(high level II)nodes contralateral to the tumour, adjacent to the spared parotid salivary gland.B.Bussels et al./Radiotherapy and Oncology72(2004)119–127125。