International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma

Published:November 15, 2017DOI:



      Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome.


      A review of the available literature addressing the natural behaviour of NPC and correlation between clinical and pathological aspects of the disease was conducted. Existing international guidelines as well as published protocols specified by clinical trials on contouring of clinical target volumes (CTV) were compared. This information was then summarized into a preliminary draft guideline which was then circulated to international experts in the field for exchange of opinions and subsequent voting on areas with the greatest controversies.


      Common areas of uncertainty and variation in practices among experts experienced in radiation therapy for NPC were elucidated. Iterative revisions were made based on extensive discussion and final voting on controversial areas by the expert panel, to formulate the recommendations on contouring of CTV based on optimal geometric expansion and anatomical editing for those structures with substantial risk of microscopic infiltration.


      Through this comprehensive review of available evidence and best practices at major institutions, as well as interactive exchange of vast experience by international experts, this set of consensus guidelines has been developed to provide a practical reference for appropriate contouring to ensure optimal target coverage. However, the final decision on the treatment volumes should be based on full consideration of individual patients’ factors and facilities of an individual centre (including the quality of imaging methods and the precision of treatment delivery).


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        • Ng W.T.
        • Lee M.C.
        • Chang A.T.
        • et al.
        The impact of dosimetric inadequacy on treatment outcome of nasopharyngeal carcinoma with IMRT.
        Oral Oncol. 2014; 50: 506-512
        • Wang T.J.
        • Riaz N.
        • Cheng S.K.
        • Lu J.J.
        • Lee N.Y.
        Intensity-modulated radiation therapy for nasopharyngeal carcinoma: a review.
        J Radiat Oncol. 2012; 1: 129-146
      1. DAHANCA Radiotherapy Guidelines 2013 (English version 2.0, 2015). Available from: <>.

        • Gregoire V.
        • Langendijk J.A.
        • Nuyts S.
        Advances in radiotherapy for head and neck cancer.
        J Clin Oncol. 2015; 33: 3277-3284
        • Hansen C.R.
        • Johansen J.
        • Samsøe E.
        • et al.
        Consequences of introducing geometric GTV to CTV margin expansion in DAHANCA contouring guidelines for head and neck radiotherapy.
        Radiother Oncol. 2018; 126: 43-47
        • Gregoire V.
        • Evans M.
        • Le Q.-T.
        • et al.
        Delineation of the primary tumour Clinical Target Volumes (CTV-P) in laryngeal, hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: AIRO, CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC CTG, NRG Oncology, PHNS, SBRT, SOMERA, SRO, SSHNO, TROG consensus guidelines.
        Radiother Oncol. 2018; 126: 3-24
        • Lee N.
        • Harris J.
        • Garden A.S.
        • et al.
        Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: Radiation Therapy Oncology Group Phase II trial 0225.
        J Clin Oncol. 2009; 27: 3684-3690
        • Lee N.Y.
        • Zhang Q.
        • Pfister D.G.
        • et al.
        Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial.
        Lancet Oncol. 2012; 13: 172-180
        • Ng W.T.
        • Lee M.C.
        • Hung W.M.
        • et al.
        Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma.
        Int J Radiat Oncol Biol Phys. 2011; 79: 420-428
        • Gilbeau L.
        • Octave-Prignot M.
        • Loncol T.
        • Renard L.
        • Scalliet P.
        • Gregoire V.
        Comparison of setup accuracy of three different thermoplastic masks for the treatment of brain and head and neck tumors.
        Radiother Oncol. 2001; 58: 155-162
        • Hatt M.
        • Lee J.A.
        • Schmidtlein C.R.
        • et al.
        Classification and evaluation strategies of auto-segmentation approaches for PET: report of AAPM task group No. 211.
        Med Phys. 2017; 44: e1-e42
        • Dubrulle F.
        • Souillard R.
        • Hermans R.
        Extension patterns of nasopharyngeal carcinoma.
        Eur Radiol. 2007; 17: 2622-2630
        • Liang S.B.
        • Sun Y.
        • Liu L.Z.
        • et al.
        Extension of local disease in nasopharyngeal carcinoma detected by magnetic resonance imaging: improvement of clinical target volume delineation.
        Int J Radiat Oncol Biol Phys. 2009; 75: 742-750
        • Li W.F.
        • Sun Y.
        • Chen M.
        • et al.
        Locoregional extension patterns of nasopharyngeal carcinoma and suggestions for clinical target volume delineation.
        Chin J Cancer. 2012; 31: 579-587
      2. NRG-HN001: Randomized phase II and phase III studies of individualized treatment for nasopharyngeal carcinoma based on biomarker Epstein Barr Virus (EBV) Deoxyribonucleic Acid (DNA). Available from: <>.

      3. 2010 Nasopharyngeal Carcinoma Intensity Modulated Radiotherapy Target and Dose Design Guidelines. Expert consensus. Chin J Radiat Oncol 2011;20:267–69 [in Chinese]. Available from: <>.

        • Merlotti A.
        • Alterio D.
        • Vigna-Taglianti R.
        • et al.
        Technical guidelines for head and neck cancer IMRT on behalf of the Italian association of radiation oncology – head and neck working group.
        Radiat Oncol. 2014; 9: 264
        • Chan J.Y.
        • Wong S.T.
        • Wei W.I.
        Whole-organ histopathological study of recurrent nasopharyngeal carcinoma.
        Laryngoscope. 2014; 124: 446-450
        • Campbell S.
        • Poon I.
        • Markel D.
        • et al.
        Evaluation of microscopic disease in oral tongue cancer using whole-mount histopathologic techniques: implications for the management of head-and-neck cancers.
        Int J Radiat Oncol Biol Phys. 2012; 82: 574-581
        • Yuen P.W.
        • Lam K.Y.
        • Chan A.C.
        • Wei W.I.
        • Lam L.K.
        Clinicopathological analysis of local spread of carcinoma of the tongue.
        Am J Surg. 1998; 175: 242-244
        • Fleury B.
        • Thariat J.
        • Barnoud R.
        • et al.
        Microscopic extensions of head and neck squamous cell carcinomas: impact for clinical target volume definition.
        Cancer Radiother. 2014; 18: 666-671
        • Daisne J.F.
        • Duprez T.
        • Weynand B.
        • et al.
        Tumor volume in pharyngolaryngeal squamous cell carcinoma: comparison at CT, MR imaging, and FDG PET and validation with surgical specimen.
        Radiology. 2004; 233: 93-100
        • Ligtenberg H.
        • Jager E.A.
        • Caldas-Magalhaes J.
        • et al.
        Modality-specific target definition for laryngeal and hypopharyngeal cancer on FDG-PET, CT and MRI.
        Radiother Oncol. 2017; 123: 63-70
        • Sham J.S.
        • Wei W.I.
        • Kwan W.H.
        • Chan C.W.
        • Choi P.H.
        • Choy D.
        Fiberoptic endoscopic examination and biopsy in determining the extent of nasopharyngeal carcinoma.
        Cancer. 1989; 64: 1838-1842
        • King A.D.
        • Vlantis A.C.
        • Bhatia K.S.
        • et al.
        Primary nasopharyngeal carcinoma: diagnostic accuracy of MR imaging versus that of endoscopy and endoscopic biopsy.
        Radiology. 2011; 258: 531-537
        • McHanwell S.
        in: Standring S. Gleeson M. Gray’s anatomy. 41st ed. Elsevier, 2016: 572-575
        • Lai S.Z.
        • Li W.F.
        • Chen L.
        • et al.
        How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients?.
        Int J Radiat Oncol Biol Phys. 2011; 80: 661-668
        • Peng G.
        • Wang T.
        • Yang K.Y.
        • et al.
        A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma.
        Radiother Oncol. 2012; 104: 286-293
        • Lin S.
        • Pan J.
        • Han L.
        • Zhang X.
        • Liao X.
        • Lu J.J.
        Nasopharyngeal carcinoma treated with reduced volume intensity modulated radiation therapy: report on the 3 year outcome of a prospective series.
        Int J Radiat Oncol Biol Phys. 2009; 75: 1071-1078
        • Joshi C.P.
        • Darko J.
        • Vidyasagar P.B.
        • Schreiner L.J.
        Dosimetry of interface region near closed air cavities for Co-60, 6 MV and 15 MV photon beams using Monte Carlo simulations.
        J Med Phys. 2010; 35: 73-80
        • Waldron J.N.
        • O'Sullivan B.
        • Warde P.
        • et al.
        Ethmoid sinus cancer: twenty-nine cases managed with primary radiation therapy.
        Int J Radiat Oncol Biol Phys. 1998; 41: 361-369
        • Waldron J.N.
        • O'Sullivan B.
        • Gullane P.
        • et al.
        Carcinoma of the maxillary antrum: A retrospective analysis of 110 cases.
        Radiother Oncol. 2000; 57: 167-173
        • Schmidt-Ullrich R.
        • Buck D.
        • Dogan N.
        • et al.
        IMRT for carcinomas of the oropharynx and oral cavity.
        in: Bortfeld T. Schmidt-Ullrich R. De Neve W. Image-guided IMRT. Springer, 2006: 305
        • Studer G.
        • Huguenin P.U.
        • Davis J.B.
        • Kunz G.
        • Lütolf U.M.
        • Glanzmann C.
        Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas: II–clinical results.
        Int J Radiat Oncol Biol Phys. 2004; 60: 374-387
        • Paganetti H.
        • Parodi K.
        • Jiang H.
        • Adams J.A.
        • Kooy H.M.
        Comparison of pencil-beam and Monte Carlo calculated dose distributions for proton therapy of skull-base and para-spinal tumors.
        in: Magjarevic R. Nagel J.H. World congress on medical physics and biomedical engineering 2006. IFMBE proceedings. Springer, Berlin, Heidelberg2007: 2219-2221
        • Liu Z.P.
        • Tian Y.
        • Wang H.Z.
        • et al.
        Dosimetric effects of air cavity on target volume and organs at risk during intensity-modulated radiation therapy for nasopharyngeal carcinoma.
        Chin J Radiat Oncol. 2017; 26: 862-866
        • Lian J.
        • Fried D.
        • Lehman-Davis M.
        • Chang S.
        • Chera B.
        Influence of patient setup and target delineation on air cavity tomotherapy dosimetry.
        Int J Radiat Oncol Biol Phys. 2012; 84: 3352
        • Gregoire V.
        • Mackie T.R.
        State of the art on dose prescription, reporting and recording in Intensity-Modulated Radiation Therapy (ICRU report No. 83).
        Cancer Radiother. 2011; 15: 555-559
        • Gregoire V.
        • Levendag P.
        • Ang K.K.
        • et al.
        CT-based delineation of lymph node levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC, NCIC, RTOG consensus guidelines.
        Radiother Oncol. 2003; 69: 227-236
        • Grégoire V.
        • Ang K.
        • Budach W.
        • et al.
        Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines.
        Radiother Oncol. 2014; 110: 172-181
        • Gregoire V.
        • Eisbruch A.
        • Hamoir M.
        • Levendag P.
        Proposal for the delineation of the nodal CTV in the node-positive and the post-operative neck.
        Radiother Oncol. 2006; 79: 15-20
        • Lee A.W.
        • Sze H.
        • Ng W.T.
        Is selective neck irradiation safe for node-negative nasopharyngeal carcinoma?.
        Int J Radiat Oncol Biol Phys. 2013; 85: 902-903
        • Chen J.Z.
        • Le Q.T.
        • Han F.
        • et al.
        Results of a phase 2 study examining the effects of omitting elective neck irradiation to nodal levels IV and Vb in patients with N(0–1) nasopharyngeal carcinoma.
        Int J Radiat Oncol Biol Phys. 2013; 85: 929-934
        • Li J.G.
        • Yuan X.
        • Zhang L.L.
        • et al.
        A randomized clinical trial comparing prophylactic upper versus whole-neck irradiation in the treatment of patients with node-negative nasopharyngeal carcinoma.
        Cancer. 2013; 119: 3170-3176
        • van den Brekel M.W.
        • Stel H.V.
        • Castelijns J.A.
        • et al.
        Cervical lymph node metastasis: assessment of radiologic criteria.
        Radiology. 1990; 177: 379-384
        • Vellayappan B.A.
        • Soon Y.Y.
        • Earnest A.
        • et al.
        Accuracy of 18F-flurodeoxyglucose-positron emission tomography/computed tomography in the staging of newly diagnosed nasopharyngeal carcinoma: a systematic review and meta-analysis.
        Radiol Oncol. 2014; 48: 331-338
        • Apisarnthanarax S.
        • Elliott D.D.
        • El-Naggar A.K.
        • et al.
        Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes.
        Int J Radiat Oncol Biol Phys. 2006; 64: 678-683
        • Wei W.I.
        • Ho W.K.
        • Cheng A.C.
        • et al.
        Management of extensive cervical nodal metastasis in nasopharyngeal carcinoma after radiotherapy: a clinicopathological study.
        Arch Otolaryngol Head Neck Surg. 2001; 127: 1457-1462
        • Wang X.S.
        • Yan C.
        • Hu C.S.
        • et al.
        Study of the medial group retropharyngeal node metastasis from nasopharyngeal carcinoma based on 3100 newly diagnosed cases.
        Oral Oncol. 2014; 50: 1109-1113
        • Liu L.Z.
        • Zhang G.Y.
        • Xie C.M.
        • Liu X.W.
        • Cui C.Y.
        • Li L.
        Magnetic resonance imaging of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma: patterns of spread.
        Int J Radiat Oncol Biol Phys. 2006; 66: 721-730
        • Wang X.S.
        • Hu C.S.
        • Ying H.M.
        • et al.
        Patterns of retropharyngeal node metastasis in nasopharyngeal carcinoma.
        Int J Radiat Oncol Biol Phys. 2009; 73: 194-201
        • Hua Q.F.
        • Zheng J.J.
        • Hu B.
        • Shu M.
        • Shen L.
        • Chen J.
        Patterns of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma.
        Biomed Res. 2017; (Available from:
        • King A.D.
        • Ahuja A.T.
        • Leung S.F.
        • et al.
        Neck node metastases from nasopharyngeal carcinoma: MR imaging of patterns of disease.
        Head Neck. 2000; 22: 275-281
        • Ho F.C.
        • Tham I.W.
        • Earnest A.
        • Lee K.M.
        • Lu J.J.
        Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: a meta-analysis of clinical evidence.
        BMC Cancer. 2012; 12: 98
        • Zhang F.
        • Cheng Y.K.
        • Li W.F.
        • et al.
        Investigation of the feasibility of elective irradiation to neck level Ib using intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma: a retrospective analysis.
        BMC Cancer. 2015; 15: 709
        • Ou X.
        • Miao Y.
        • Wang X.
        • Ding J.
        • He X.
        • Hu C.
        The feasibility analysis of omission of elective irradiation to level IB lymph nodes in low-risk nasopharyngeal carcinoma based on the 2013 updated consensus guideline for neck nodal levels.
        Radiat Oncol. 2017; 12: 137
        • Poon I.
        • Fischbein N.
        • Lee N.
        • Akazawa P.
        • et al.
        A population-based atlas and clinical target volume for the head-and-neck lymph nodes.
        Int J Radiat Oncol Biol Phys. 2004; 59: 1301-1311
        • Wang X.
        • Hu C.
        • Ying H.
        • et al.
        Patterns of lymph node metastasis from nasopharyngeal carcinoma based on the 2013 updated consensus guidelines for neck node levels.
        Radiother Oncol. 2015; 115: 41-45
        • Wang X.
        • Li L.
        • Hu C.
        • et al.
        Patterns of level II node metastasis in nasopharyngeal carcinoma.
        Radiother Oncol. 2008; 89: 28-32
      4. J.J. Pan W.T. Ng J.F. Zong et al. Proposal for the 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy Cancer 2016 122 546 558.

        • Ng W.T.
        • Lee A.W.
        • Kan W.K.
        • et al.
        N-staging by magnetic resonance imaging for patients with nasopharyngeal carcinoma: pattern of nodal involvement by radiological levels.
        Radiother Oncol. 2007; 82: 70-75
        • Ribassin-Majed L.
        • Marguet S.
        • Lee A.W.
        • et al.
        What is the best treatment of locally advanced nasopharyngeal carcinoma? An individual patient data network meta-analysis.
        J Clin Oncol. 2017; 35: 498-505
        • Hui E.P.
        • Ma B.B.
        • Leung S.F.
        • et al.
        Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma.
        J Clin Oncol. 2009; 27: 242-249
        • Cao S.M.
        • Yang Q.
        • Guo L.
        • et al.
        Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase III multicentre randomised controlled trial.
        Eur J Cancer. 2017; 75: 14-23
        • Sun Y.
        • Li W.F.
        • Chen N.Y.
        • et al.
        Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial.
        Lancet Oncol. 2016; 17: 1509-1520
        • Salama J.K.
        • Haddad R.I.
        • Kies M.S.
        • et al.
        Clinical practice guidance for radiotherapy planning after induction chemotherapy in locoregionally advanced head-and-neck cancer.
        Int J Radiat Oncol Biol Phys. 2009; 75: 725-733
        • Yang H.
        • Chen X.
        • Lin S.
        • et al.
        Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a prospective, multi-center, randomized clinical trial.
        Radiother Oncol. 2018; 126: 37-42