Advertisement
Original Article| Volume 177, P205-213, December 2022

Download started.

Ok

Neck level Ib-sparing versus level Ib-irradiation in intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma with high-risk factors: A propensity score-matched cohort study

  • Author Footnotes
    1 These authors contributed equally to this work.
    Gaoyuan Wang
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Center for Precision Medicine of Sun Yat-sen University, Guangzhou, People’s Republic of China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Chenglong Huang
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Center for Precision Medicine of Sun Yat-sen University, Guangzhou, People’s Republic of China
    Search for articles by this author
  • Kaibin Yang
    Affiliations
    Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Center for Precision Medicine of Sun Yat-sen University, Guangzhou, People’s Republic of China
    Search for articles by this author
  • Rui Guo
    Affiliations
    Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Center for Precision Medicine of Sun Yat-sen University, Guangzhou, People’s Republic of China
    Search for articles by this author
  • Youyu Qiu
    Affiliations
    Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Center for Precision Medicine of Sun Yat-sen University, Guangzhou, People’s Republic of China
    Search for articles by this author
  • Wenfei Li
    Affiliations
    Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Center for Precision Medicine of Sun Yat-sen University, Guangzhou, People’s Republic of China
    Search for articles by this author
  • Yanping Mao
    Affiliations
    Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Center for Precision Medicine of Sun Yat-sen University, Guangzhou, People’s Republic of China
    Search for articles by this author
  • Author Footnotes
    2 The senior authors contributed equally to this work.
    Linglong Tang
    Footnotes
    2 The senior authors contributed equally to this work.
    Affiliations
    Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Center for Precision Medicine of Sun Yat-sen University, Guangzhou, People’s Republic of China
    Search for articles by this author
  • Author Footnotes
    2 The senior authors contributed equally to this work.
    Jun Ma
    Correspondence
    Corresponding author at: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Center for Precision Medicine of Sun Yat-sen University, 651 Dongfeng Road East, Guangzhou 510060, People’s Republic of China.
    Footnotes
    2 The senior authors contributed equally to this work.
    Affiliations
    Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Center for Precision Medicine of Sun Yat-sen University, Guangzhou, People’s Republic of China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    2 The senior authors contributed equally to this work.
Published:November 11, 2022DOI:https://doi.org/10.1016/j.radonc.2022.11.005
Neck level Ib-sparing versus level Ib-irradiation in intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma with high-risk factors: A propensity score-matched cohort study
Previous ArticlePrognostic value of the cervical lymph node necrosis ratio in nasopharyngeal carcinoma
Next ArticleTrends and variation in the use of radiotherapy in non-metastatic prostate cancer: A 12-year nationwide overview from the Netherlands

      Highlights

      • •
        Clinical neck level Ib lymph node involvement is rare (1.4%)
      • •
        Level 1b sparing is safe even with the presence of ENE or large (>2 cm) level II node(s) without positive level Ib lymph nodes.
      • •
        Level 1b sparing provides long-term reduction of dry mouth symptom.

      Abstract

      Aim

      Level Ib lymph nodes metastasis is rare in nasopharyngeal carcinoma (NPC). We aimed to evaluate the feasibility of sparing level Ib-irradiation in NPC patients with high-risk factors.

      Materials and methods

      Four hundred forty-three NPC patients with radiologic extranodal extension (rENE) or level II lymph node maximal axial diameter (MAD) ≥ 20 mm treated by intensity-modulated radiotherapy (IMRT) between 2009 and 2012 were included in this study. Propensity score matching (PSM) was applied to balance potential prognostic factors (including age, sex, T and N stage, pretreatment EBV DNA level, and level II rENE and MAD) between patients who received and omitted level Ib irradiation. Kaplan–Meier analysis and the log-rank test were used to compare regional survival outcomes.

      Results

      PSM resulted in 169 matched pairs of eligible patients. The median follow-up period was 119 months in the matched cohort. The number of level Ib failure in the level Ib-sparing and level-Ib irradiation groups were 3/169 (1.8 %) vs 2/169 (1.2 %), P > 0.999. And the 5-year regional relapse-free survival (RRFS) rates of the two groups were 88.4 % vs 92.6 %, respectively. After PSM, RRFS (hazard ratio [HR]: 1.508, 95 % confidence interval [CI]: 0.762–2.986, P = 0.239), OS (HR: 1.219, 95 % CI: 0.754–1.972, P = 0.418), distant metastasis-free survival (DMFS) (HR: 1.605, 95 % CI: 0.900–2.863, P = 0.109), and local relapse-free (LRFS) (HR: 0.956, 95 % CI: 0.436–2.095, P = 0.910) were similar in the two arms. The incidence of grade ≥ 1 dry mouth after 5 years was higher in the level Ib-irradiation group (27.5 % vs 16.5 %, P = 0.029). However, the incidences of grade 3–4 late toxicities were similar between the two groups.

      Conclusion

      Neck level Ib-sparing appears to be safe and feasible in NPC patients with rENE or level II MAD ≥ 20 mm and negative level Ib lymph nodes. Compared with cervical level Ib-irradiation, omission of irradiation to level Ib provides less dry mouth symptom.

      Keywords

      Abbreviations:

      CI (confidence interval), CT (computed tomography), CTV (clinical target volume), DMFS (distant metastasis-free survival), EBV (Epstein–Barr virus), EORTC (European Organization for Research and Treatment of Cancer), GTV (gross tumor volume), HR (hazard ratio), IMRT (intensity-modulated radiotherapy), LRFS (local relapse-free survival), MRI (magnetic resonance imaging), MAD (maximal axial diameter), NPC (nasopharyngeal carcinoma), OS (overall survival), PET/CT (positron emission tomography/computed tomography), PG (parotid gland), PSM (propensity score matching), PTV (planning target volume), RCT (randomized controlled trial), rENE (radiologic extranodal extension), RRFS (regional relapse-free survival), RTOG (Radiation Therapy Oncology Group), SMG (submandibular gland), UICC/AJCC (Union for International Cancer/American Joint Committee on Cancer)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Radiotherapy and Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • Cao S.M.
        • Qian M.J.
        • Simons C.N.
        The prevalence and prevention of nasopharyngeal carcinoma in China.
        Chin J Cancer. 2011; 30: 114-119https://doi.org/10.5732/cjc.010.10377
        View in Article
        • Su S.F.
        • Han F.
        • Zhao C.
        • Huang Y.
        • Chen C.Y.
        • Xiao W.W.
        • et al.
        Treatment outcomes for different subgroups of nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy.
        Chin J Cancer. 2011; 30: 565-573https://doi.org/10.5732/cjc.010.10547
        View in Article
        • Yi J.L.
        • Gao L.
        • Huang X.D.
        • Li S.Y.
        • Luo J.W.
        • Cai W.M.
        • et al.
        Nasopharyngeal carcinoma treated by radical radiotherapy alone: ten-year experience of a single institution.
        Int J Radiat Oncol Biol Phys. 2006; 65: 161-168https://doi.org/10.1016/j.ijrobp.2005.12.003
        View in Article
        • Murdoch-Kinch C.A.
        • Kim H.M.
        • Vineberg K.A.
        • Ship J.A.
        • Eisbruch A.
        Dose-effect relationships for the submandibular salivary glands and implications for their sparing by intensity modulated radiotherapy.
        Int J Radiat Oncol Biol Phys. 2008; 72: 373-382https://doi.org/10.1016/j.ijrobp.2007.12.033
        View in Article
        • Saibishkumar E.P.
        • Jha N.
        • Scrimger R.A.
        • MacKenzie M.A.
        • Daly H.
        • Field G.
        • et al.
        Sparing the parotid glands and surgically transferred submandibular gland with helical tomotherapy in post-operative radiation of head and neck cancer: a planning study.
        Radiother Oncol. 2007; 85: 98-104https://doi.org/10.1016/j.radonc.2007.09.014
        View in Article
        • Saarilahti K.
        • Kouri M.
        • Collan J.
        • Kangasmaki A.
        • Atula T.
        • Joensuu H.
        • et al.
        Sparing of the sub- mandibular glands by intensity modulated radiotherapy in the treatment of head and neck cancer.
        Radiother Oncol. 2006; 78: 270-275
        View in Article
        • Tang L.
        • Mao Y.
        • Liu L.
        • Liang S.
        • Chen Y.
        • Sun Y.
        • et al.
        The volume to be irradiated during selective neck irradiation in nasopharyngeal carcinoma.
        Cancer. 2009; 115: 680-688https://doi.org/10.1002/cncr.24049
        View in Article
        • Ho F.C.H.
        • Tham I.W.K.
        • Earnest A.
        • Lee K.
        • Lu J.J.
        Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: a meta-analysis of clinical evidence.
        BMC Cancer. 2012; 12: 98https://doi.org/10.1186/1471-2407-12-98
        View in Article
        • Li W.F.
        • Sun Y.
        • Chen M.
        • Tang L.L.
        • Liu L.Z.
        • Mao Y.P.
        • et al.
        Locoregional extension patterns of nasopharyngeal carcinoma and suggestions for clinical target volume delineation.
        Chin J Cancer. 2012; 31: 579-587https://doi.org/10.5732/cjc.012.10095
        View in Article
        • Li W.F.
        • Sun Y.
        • Mao Y.P.
        • Chen L.
        • Chen Y.Y.
        • Chen M.
        • et al.
        Proposed lymph node staging system using the international consensus guidelines for lymph node levels is predictive for nasopharyngeal carcinoma patients from endemic areas treated with intensity modulated radiation therapy.
        Int J Radiat Oncol Biol Phys. 2013; 86: 249-256https://doi.org/10.1016/j.ijrobp.2012.09.003
        View in Article
        • Wang X.S.
        • Hu C.S.
        • Ying H.M.
        • He X.Y.
        • Zhu G.P.
        • Kong L.
        • 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: 41-45https://doi.org/10.1016/j.radonc.2015.02.017
        View in Article
        • Kam M.K.
        • Teo P.M.
        • Chau R.M.
        • Cheung K.Y.
        • Choi P.H.
        • Kwan W.H.
        • et al.
        Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy: the Hong Kong experience.
        Int J Radiat Oncol Biol Phys. 2004; 60: 1440-1450https://doi.org/10.1016/j.ijrobp.2004.05.022
        View in Article
        • Wolden S.L.
        • Chen W.C.
        • Pfister D.G.
        • Kraus D.H.
        • Berry S.L.
        • Zelefsky M.J.
        • et al.
        Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: update of the Memorial Sloan-Kettering experience.
        Int J Radiat Oncol Biol Phys. 2006; 64: 57-62https://doi.org/10.1016/j.ijrobp.2005.03.057
        View in Article
        • Lee N.
        • Harris J.
        • Garden A.S.
        • Straube W.
        • Glisson B.
        • Xia P.
        • 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
        View in Article
        • Ou X.
        • Zhou X.
        • Shi Q.
        • Xing X.
        • Yang Y.
        • Xu T.
        • et al.
        Treatment outcomes and late toxicities of 869 patients with nasopharyngeal carcinoma treated with definitive intensity modulated radiation therapy: new insight into the value of total dose of cisplatin and radiation boost.
        Oncotarget. 2015; 6: 38381-38397https://doi.org/10.18632/oncotarget.5420
        View in Article
        • Ng W.T.
        • Lee M.C.
        • Hung W.M.
        • Choi C.W.
        • Lee K.C.
        • Chan O.S.
        • et al.
        Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma.
        Int J Radiat Oncol Biol Phys. 2011; 79: 420-428https://doi.org/10.1016/j.ijrobp.2009.11.024
        View in Article
        • Lee N.Y.
        • Zhang Q.
        • Pfister D.G.
        • Kim J.
        • Garden A.S.
        • Mechalakos J.
        • 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: 172-180https://doi.org/10.1016/S1470-2045(11)70303-5
        View in Article
        • Zeng L.
        • Zhang Q.
        • Ao F.
        • Jiang C.
        • Xiao Y.
        • Xie H.
        • et al.
        Risk factors and distribution features of level IB lymph nodes metastasis in nasopharyngeal carcinoma.
        Auris Nasus Larynx. 2019; 46: 457-464https://doi.org/10.1016/j.anl.2018.10.012
        View in Article
        • Yi W.
        • Li X.
        • Liu Z.
        • Jiang C.
        • Niu D.
        • Xia Y.
        • et al.
        A risk score model for the metastasis of level Ib lymph node based on the clinicopathological features of nasopharyngeal carcinoma in a large sample.
        Mol Clin Oncol. 2014; 2: 789-797https://doi.org/10.3892/mco.2014.315
        View in Article
        • Lee A.W.
        • Ng W.T.
        • Pan J.J.
        • Poh S.S.
        • Ahn Y.C.
        • AlHussain H.
        • et al.
        International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma.
        Radiother Oncol. 2018; 126: 25-36https://doi.org/10.1016/j.radonc.2017.10.032
        View in Article
        • Peng H.
        • Guo R.
        • Chen L.
        • Zhang Y.
        • Li W.F.
        • Mao Y.P.
        • et al.
        Prognostic impact of plasma Epstein-Barr Virus DNA in patients with nasopharyngeal carcinoma treated using intensity-modulated radiation therapy.
        Sci Rep. 2016; 6https://doi.org/10.1038/srep22000
        View in Article
        • American A.MB.
        Joint Committee on Cancer. AJCC cancer staging manual.
        8th ed. Springer, New York2017
        View in Article
        • Tang L.
        • Li L.
        • Mao Y.
        • Liu L.
        • Liang S.
        • Chen Y.
        • et al.
        Retropharyngeal lymph node metastasis in nasopharyngeal carcinoma detected by magnetic resonance imaging.
        Cancer. 2008; 113: 347-354https://doi.org/10.1002/cncr.23555
        View in Article
        • Mao Y.
        • Wang S.
        • Lydiatt W.
        • Shah J.P.
        • Colevas A.D.
        • Lee A.W.
        • et al.
        Unambiguous advanced radiologic extranodal extension determined by MRI predicts worse outcomes in nasopharyngeal carcinoma: potential improvement for future editions of N category systems.
        Radiother Oncol. 2021; 157: 114-121https://doi.org/10.1016/j.radonc.2021.01.015
        View in Article

      25. Grégoire V, Ang K, Budach W, Grau C, Hamoir M, Langendijk JA, 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;110:172-81. https://doi.org/10.1016/j.radonc.2013.10.010.

        View in Article
        • Sun Y.
        • Guo R.
        • Yin W.J.
        • Tang L.L.
        • Yu X.L.
        • Chen M.
        • et al.
        Which T category of nasopharyngeal carcinoma may benefit most from volumetric modulated arc therapy compared with step and shoot intensity modulated radiation therapy.
        PLoS ONE. 2013; 8: e75304
        View in Article
      27. Edge S.B. Byrd D.R. Compton C.C. Fritz A.G. Greene F.L. Trotti A. AJCC cancer staging manual. Springer, New York2010
        View in Article

      28. Sobin LH, Gospodarowicz MK, Wittekind C, O’Sullivan B, Goldstraw P, Groome P, editors. Union for International Cancer Control (UICC). TNM Classification of Malignant Tumours. 7th ed. Chichester: Wiley-Blackwell; 2010.

        View in Article
        • Sturmer T.
        • Joshi M.
        • Glynn R.J.
        • Avorn J.
        • Rothman K.J.
        • Schneeweiss S.
        A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods.
        J Clin Epidemiol. 2006; 59: 437-447https://doi.org/10.1016/j.jclinepi.2005.07.004
        View in Article
        • Chen J.
        • Ou D.
        • He X.
        • Hu C.
        Sparing level Ib lymph nodes by intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma.
        Int J Clin Oncol. 2014; 19: 998-1004https://doi.org/10.1007/s10147-013-0650-6
        View in Article
        • Li M.
        • Huang X.G.
        • Yang Z.N.
        • Lu J.Y.
        • Zhan Y.Z.
        • Xie W.J.
        • et al.
        Effects of omitting elective neck irradiation to nodal Level IB in nasopharyngeal carcinoma patients with negative Level IB lymph nodes treated by intensity-modulated radiotherapy: a Phase 2 study.
        Br J Radiol. 2016; 89: 1065https://doi.org/10.1259/bjr.20150621
        View in Article
        • Zhang F.
        • Cheng Y.K.
        • Li W.F.
        • Guo R.
        • Chen L.
        • Sun Y.
        • 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: 709https://doi.org/10.1186/s12885-015-1669-z
        View in Article
        • 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: 137https://doi.org/10.1186/s13014-017-0869-x
        View in Article
        • Guo Q.
        • Xiao N.
        • Xu H.
        • Zong J.
        • Xiao Y.
        • Lu T.
        • et al.
        Level Ib sparing intensity-modulated radiation therapy in selected nasopharyngeal carcinoma patients based on the International Guideline.
        Radiother Oncol. 2022; 167: 239-243https://doi.org/10.1016/j.radonc.2021.12.032
        View in Article
        • Tang L.
        • Huang C.
        • Zhang N.
        • Jiang W.
        • Wu Y.
        • Huang S.
        • 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: 479-490https://doi.org/10.1016/S1470-2045(2)00058-4
        View in Article
        • Houweling A.C.
        • Dijkema T.
        • Roesink J.M.
        • Terhaard C.H.J.
        • Raaijmakers C.P.J.
        Sparing the contralateral submandibular gland in oropharyngeal cancer patients: a planning study.
        Radiother Oncol. 2008; 89: 64-70https://doi.org/10.1016/j.radonc.2008.04.008
        View in Article
        • Wang Z.H.
        • Yan C.
        • Zhang Z.Y.
        • Zhang C.P.
        • Hu H.S.
        • Tu W.Y.
        • et al.
        Impact of salivary gland dosimetry on post-IMRT recovery of saliva output and xerostomia grade for head-and-neck cancer patients treated with or without contralateral submandibular gland sparing: a longitudinal study.
        Int J Radiat Oncol Biol Phys. 2011; 81: 1479-1487https://doi.org/10.1016/j.ijrobp.2010.07.1990
        View in Article

      Article info

      Publication history

      Published online: November 11, 2022
      Accepted: November 5, 2022
      Received in revised form: November 2, 2022
      Received: August 7, 2022

      Identification

      DOI: https://doi.org/10.1016/j.radonc.2022.11.005

      Copyright

      © 2022 Elsevier B.V. All rights reserved.

      ScienceDirect

      Access this article on ScienceDirect

      The content on this site is intended for healthcare professionals.


      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the Cookie Preference Center for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties.


      RELX