The evolution of prophylactic neck irradiation in nasopharyngeal carcinoma: Changing concepts and irradiation ranges

Wenjun Liao , Yue Zhao , Shichuan Zhang

Precision Radiation Oncology ›› 2025, Vol. 9 ›› Issue (1) : 61 -68.

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Precision Radiation Oncology ›› 2025, Vol. 9 ›› Issue (1) : 61 -68. DOI: 10.1002/pro6.70007
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The evolution of prophylactic neck irradiation in nasopharyngeal carcinoma: Changing concepts and irradiation ranges

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Abstract

The approach to prophylactic neck irradiation in nasopharyngeal carcinoma (NPC) has undergone significant changes. For decades, prophylactic whole-neck irradiation has been the standard for all patients with NPC; however, it is linked to a high risk of late complications. Advances in imaging modalities have deepened understanding of the metastatic characteristics of the cervical lymph nodes (LN), prompting a shift towards sparing the uninvolved lower neck and medial retropharyngeal nodal region. This targeted approach has proven effective in controlling cervical LN recurrence as whole-neck irradiation while significantly reducing adverse effects. Currently, contouring of the neck lymphatic drainage clinical target volume (CTV) is being explored to eliminate the use of uniform cervical LN levels as a delineation boundary. Instead, the inferior boundary of the neck CTV is determined either by the distance from the lowest positive LN or two cervical vertebrae below the lowest positive LN, facilitating more individualized CTV delineation and prophylactic neck irradiation. Additionally, omitting lower-risk neck lymphatic drainage CTVs and irradiating only visible LNs in these areas are also being explored. This review examines the evolution of prophylactic neck irradiation for NPC, providing key insights into these advancements.

Keywords

head and neck squamous cell carcinoma / nasopharyngeal carcinoma / neck irradiation / radiotherapy

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Wenjun Liao, Yue Zhao, Shichuan Zhang. The evolution of prophylactic neck irradiation in nasopharyngeal carcinoma: Changing concepts and irradiation ranges. Precision Radiation Oncology, 2025, 9(1): 61-68 DOI:10.1002/pro6.70007

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References

[1]

Chen YP, Chan ATC, Le QT, Blanchard P, Sun Y, Ma J. Nasopharyngeal carcinoma. Lancet. 2019; 394(10192): 64-80.

[2]

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(1): 172-181.

[3]

Lee N, Harris J, Garden AS, 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(22): 3684-3690.

[4]

Zheng Y, Han F, Xiao W, et al. Analysis of late toxicity in nasopharyngeal carcinoma patients treated with intensity modulated radiation therapy. Radiat Oncol. 2015; 10: 17.

[5]

Miller JA, Beadle BM, Gensheimer MF, Le QT. De-escalating elective nodal irradiation for nasopharyngeal carcinoma. Lancet Oncol. 2022; 23(4): 441-443.

[6]

Martin H. The case for prophylactic neck dissection. Cancer. 1951; 4(1): 92-97.

[7]

Poh SS, Wee JTS. Commentary on “Elective upper-neck versus whole-neck irradiation of the uninvolved neck in patients with nasopharyngeal carcinoma: an open-label, non-inferiority, multicentre, randomised phase 3 trial”. Chin Clin Oncol. 2022; 11(5): 35.

[8]

Million RR, Fletcher GH, Jesse RHJR. Evaluation of Elective Irradiation of the Neck for Squamous-Cell Carcinoma of the Nasopharynx, Tonsillar Fossa, and Base of Tongue. Radiology 1963; 8(6).

[9]

Fletcher GH. Elective irradiation of subclinical disease in cancers of the head and neck. Cancer. 1972; 29(6): 1450-1454.

[10]

Jesse RH, Fletcher GH. Treatment of the neck in patients with squamous cell carcinoma of the head and neck. Cancer. 1977; 39(Suppl 2): 868-872.

[11]

Goffinet DR, Gilbert EH, Weller SA, Bagshaw MA. Irradiation of clinically uninvolved cervical lymph nodes. Can J of Otolaryngol. 1975; 4(5): 927-933.

[12]

Berger DS, Fletcher GH, Lindberg RD, Jesse RH, Elective irradiation of the neck lymphatics for squamous cell carcinomas of the nasopharynx and oropharynx. Am J Roentgenol Radium Ther Nucl Med. 1971; 111(1): 66-72.

[13]

Rabuzzi DD, Chung CT, Sagerman RH. Prophylactic neck irradiation. Arch Otolaryngol. 1980; 106(8): 454-455.

[14]

Lee AW, Sham JS, Poon YF, Ho JH. Treatment of stage I nasopharyngeal carcinoma: analysis of the patterns of relapse and the results of withholding elective neck irradiation. Int J Radiat Oncol, Biol, Phys. 1989; 17(6): 1183-1190.

[15]

Lee AW, Poon YF, Foo W, et al. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985: overall survival and patterns of failure. Int J Radiat Oncol, Biol, Phys. 1992; 23(2): 261-270.

[16]

Hoppe RT, Goffinet DR, Bagshaw MA. Carcinoma of the nasopharynx. Eighteen years' experience with megavoltage radiation therapy. Cancer. 1976; 37(6): 2605-2612.

[17]

Yamashita S, Kondo M, Inuyama Y, Hashimoto S. Improved survival of patients with nasopharyngeal squamous cell carcinoma. Int J Radiat Oncol, Biol, Phys. 1986; 12(3): 307-312.

[18]

Rahima M, Rakowsky E, Barzilay J, Sidi J. Carcinoma of the nasopharynx. An analysis of 91 cases and a comparison of differing treatment approaches. Cancer. 1986; 58(4): 843-849.

[19]

Qin DX, Hu YH, Yan JH, et al. Analysis of 1379 patients with nasopharyngeal carcinoma treated by radiation. Cancer. 1988; 61(6): 1117-1124.

[20]

Sham JS, Choy D, Wei WI. Nasopharyngeal carcinoma: orderly neck node spread. Int J Radiat Oncol, Biol, Phys. 1990; 19(4): 929-933.

[21]

Sham JS, Cheung YK, Choy D, Chan FL, Leong L. Computed tomography evaluation of neck node metastases from nasopharyngeal carcinoma. Int J Radiat Oncol, Biol, Phys. 1993; 26(5): 787-792.

[22]

Ng SH, Chang TC, Ko SF, et al. Nasopharyngeal carcinoma: MRI and CT assessment. Neuroradiology. 1997; 39(10): 741-746.

[23]

Zhang GY, Hu WH, Liu LZ, et al. Comparison between PET/CT and MRI in diagnosing lymph node metastasis and N staging of nasopharyngeal carcinoma. Chin J Oncol. 2006; 28(5): 381-384.

[24]

Tang L, Mao Y, Liu L, et al. The volume to be irradiated during selective neck irradiation in nasopharyngeal carcinoma: analysis of the spread patterns in lymph nodes by magnetic resonance imaging. Cancer. 2009; 115(3): 680-688.

[25]

Ho FC, Tham IW, Earnest A, Lee KM, Lu JJ. Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: a meta-analysis of clinical evidence. BMC cancer. 2012; 12: 98.

[26]

Li WF, Sun Y, Chen M, et al. Locoregional extension patterns of nasopharyngeal carcinoma and suggestions for clinical target volume delineation. Chin J Cancer. 2012; 31(12): 579-587.

[27]

Puri A. Is elective irradiation to the lower neck necessary for N0 nasopharyngeal carcinoma?: in regard to Macmillan MS et al. (Int J Radiat Oncol Biol Phys 2010;77:1397-1402). Int J Radiat Oncol, Biol, Phys. 2011; 81(5): 1591.

[28]

He X, Pan Z, Guo X, et al. The pattern of relapse and survival of elective irradiation of the upper neck for stage N0 nasopharyngeal carcinoma. Radiat Oncol. 2012; 7: 35.

[29]

Xie FY, Peng M, Hu WH, Han F, Wang X, Xu HM. Prophylactic irradiation of cervical lymph nodes for Stage-N0 nasopharyngeal carcinoma. Chin J Cancer. 2010; 29(1): 106-110.

[30]

Li JG, Yuan X, Zhang LL, 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(17): 3170-3176.

[31]

Chen JZ, Le QT, 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(4): 929-934.

[32]

Ou X, Shen C, Kong L, et al. Treatment outcome of nasopharyngeal carcinoma with retropharyngeal lymph nodes metastasis only and the feasibility of elective neck irradiation. Oral Oncol. 2012; 48(10): 1045-1050.

[33]

Chen M, Tang LL, Sun Y, et al. Treatment outcomes and feasibility of partial neck irradiation for patients with nasopharyngeal carcinoma with only retropharyngeal lymph node metastasis after intensity-modulated radiotherapy. Head & neck. 2014; 36(4): 468-473.

[34]

Tang LL, Tang XR, Li WF, et al. The feasibility of contralateral lower neck sparing intensity modulation radiated therapy for nasopharyngeal carcinoma patients with unilateral cervical lymph node involvement. Oral Oncol. 2017; 69: 68-73.

[35]

Tang LL, Huang CL, Zhang N, et al. Elective upper-neck versus whole-neck irradiation of the uninvolved neck in patients with nasopharyngeal carcinoma: an open-label, non-inferiority, multicentre, randomised phase 3 trial. Lancet Oncol. 2022; 23(4): 479-490.

[36]

Huang CL, Zhang N, Jiang W, et al. Reduced-Volume Irradiation of Uninvolved Neck in Patients With Nasopharyngeal Cancer: Updated Results From an Open-Label, Noninferiority, Multicenter, Randomized Phase III Trial. J Clin Oncol. 2024; 42(17): 2021-2025.

[37]

Tang SQ, Mao YP, Xu C, et al. The evolution of the nasopharyngeal carcinoma staging system over a 10-year period: implications for future revisions. Chin Med J. 2020; 133(17): 2044-2053.

[38]

Huang CL, Qiu YY, Du XJ, et al. Upper-Neck Versus Whole-Neck Irradiation at the Contralateral Uninvolved Neck in Patients With Unilateral N3 Nasopharyngeal Carcinoma. Int J Radiat Oncol, Biol, Phys. 2023; 116(4): 788-796.

[39]

Tang L, Li L, Mao Y, et al. Retropharyngeal lymph node metastasis in nasopharyngeal carcinoma detected by magnetic resonance imaging: prognostic value and staging categories. Cancer. 2008; 113(2): 347-354.

[40]

Wang XS, Yan C, Hu CS, et al. Study of the medial group retropharyngeal node metastasis from nasopharyngeal carcinoma based on 3100 newly diagnosed cases. Oral Oncol. 2014; 50(11): 1109-1113.

[41]

Gibb AG. Nasopharyngeal carcinoma: Chinese University Press. 1999.

[42]

Lee NY, Zhang Q, Pfister DG, 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(2): 172-180.

[43]

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(3): 721-730.

[44]

Lin L, Lu Y, Wang XJ, et al. Delineation of Neck Clinical Target Volume Specific to Nasopharyngeal Carcinoma Based on Lymph Node Distribution and the International Consensus Guidelines. Int J Radiat Oncol Biol Phys. 2018; 100(4): 891-902.

[45]

ZG Pan, ZQ Liu, SX Wang, et al. Feasibility analysis of non-prophylactic irradiation of retropharyngeal lymph nodes in medial group of nasopharyngeal carcinoma. Oncol Prog. 2022; 10: 20.

[46]

Sun R, Blanchard P. Benefit of medial retropharyngeal nodal region sparing in nasopharyngeal carcinoma patients: the final answer? Asia Pac J Clin Oncol. 2023; 19(6): 579-580.

[47]

Fransen MF, Schoonderwoerd M, Knopf P, et al. Tumor-draining lymph nodes are pivotal in PD-1/PD-L1 checkpoint therapy. JCI insight. 2018; 3(23): e124507.

[48]

Darragh LB, Gadwa J, Pham TT, et al. Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors. Nat Commun. 2022; 13(1): 7015.

[49]

Zhu GL, Zhang XM, Yang KB, Tang LL, Ma J. Metastatic patterns of level II-V cervical lymph nodes assessed per vertebral levels in nasopharyngeal carcinoma. Radiother Oncol. 2023; 179: 109447.

[50]

Liu Y, Yan W, Hu C, et al. Optimizing Cervical Target Volume in Patients with Nasopharyngeal Cancer Based On Nodal Drainage Distance. Clin Cancer Res. 2024; 30(9): 1801-1810.

[51]

Robbins KT, Medina JE, Wolfe GT, Levine PA, Sessions RB, Pruet CW. Standardizing neck dissection terminology. Official report of the Academy's Committee for Head and Neck Surgery and Oncology. Arch Otolaryngol Head Neck Surg. 1991; 117(6): 601-605.

[52]

Reinders FCJ, de Ridder M, Doornaert PAH, P J Raaijmakers C, Philippens MEP. Individual elective lymph node irradiation for the reduction of complications in head and neck cancer patients (iNode): A phase-I feasibility trial protocol. Clin Transl Radiat Oncol. 2023; 39: 100574.

[53]

Sher DJ, Moon DH, Vo D, et al. Efficacy and Quality-of-Life Following Involved Nodal Radiotherapy for Head and Neck Squamous Cell Carcinoma. The INRT-AIR Phase II Clinical Trial. Clin Cancer Res. 2023; 29(17): 3284-3291.

[54]

Chen L, Zhou Z, Sher D, et al. Combining many-objective radiomics and 3D convolutional neural network through evidential reasoning to predict lymph node metastasis in head and neck cancer. Phys Med Biol. 2019; 64(7): 075011.

[55]

Chen L, Dohopolski M, Zhou Z, et al. Attention Guided Lymph Node Malignancy Prediction in Head and Neck Cancer. Int J Radiat Oncol Biol Phys. 2021; 110(4): 1171-1179.

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2025 The Author(s). Precision Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Shandong Cancer Hospital & Institute.

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