Download PDF
J Neurol Surg B Skull Base
DOI: 10.1055/a-2708-2656
Original Article

Proton Versus Photon Radiation Therapy for Nasopharyngeal Carcinoma

Authors

  • Arash Abiri 

    1   Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine, Orange, California

  • Derek H. Liu

    1   Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine, Orange, California

  • Jonathan C. Pang 

    1   Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine, Orange, California

  • Theodore V. Nguyen

    1   Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine, Orange, California

  • Benjamin F. Bitner

    1   Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine, Orange, California

  • Sina J. Torabi

    1   Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine, Orange, California

  • Edward C. Kuan 

    1   Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine, Orange, California
    2   Department of Neurological Surgery, University of California, Irvine, Orange, California
Further Information
Also available at
   Permissions and Reprints
Preview

Abstract

Objectives

Local treatment for nasopharyngeal carcinoma (NPC) commonly entails a regimen of radiotherapy. Due to its proximity to critical neurovascular structures, radiotoxicity presents a challenge. Proton radiotherapy (PRT) is associated with reduced toxicity and shows promise as an alternative to photon radiotherapy (XRT). Herein, we evaluated the therapeutic efficacies of PRT and XRT in NPC patients.

Study Design

Retrospective database study.

Methods

The 2004–2017 National Cancer Database was queried for patients with NPC who were treated with PRT or XRT. Using propensity score matching (PSM), patients who received XRT were matched in demographics and clinical characteristics with those who received PRT. Overall survival (OS) was assessed with Cox proportional-hazards regression and Kaplan-Meier analysis.

Results

Of 7,003 patients (6,953 XRT, 50 PRT), 1,946 (27.8%) were female with a mean age of 55.7 ± 14.0 years. PSM resulted in 96 patients, with a large representation of T4 (57.3%), M0 (91.7%), and WHO type I (54.2%) tumors. Patients who underwent PRT were, on average, farther away from their treatment facility than XRT patients (101.7 versus 14.0 miles; p < 0.001). The 2-year OS rates for the PRT and XRT cohorts were 83.9 and 53.9%, respectively (p = 0.002). Additionally, PRT was associated with significantly reduced mortality compared with XRT (HR 0.338; p = 0.002).

Conclusion

NPC patients demonstrated higher OS following PRT compared with XRT. Prospective trials consisting of larger and more heterogeneous patient populations are warranted to better delineate the therapeutic efficacy of PRT and direct its appropriate use as a primary radiation modality for NPC patients.

Keywords

nasopharyngeal cancer - radiotherapy - proton therapy - photon therapy - survival

Note

Portions of this work were presented as a talk at the 2023 Triological Society at Combined Otolaryngology Spring Meetings, Boston, MA.




Publication History

Received: 14 February 2025

Accepted: 22 September 2025

Accepted Manuscript online:
24 September 2025

Article published online:
07 October 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Chang ET, Ye W, Zeng YX, Adami HO. The evolving epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 2021; 30 (06) 1035-1047
    Search in Google Scholar
  • 2 Argirion I, Zarins KR, Ruterbusch JJ. et al. Increasing incidence of Epstein-Barr virus-related nasopharyngeal carcinoma in the United States. Cancer 2020; 126 (01) 121-130
    Search in Google Scholar
  • 3 Sinha S, Gajra A. Nasopharyngeal Cancer. In: StatPearls. StatPearls Publishing; 2023. . Accessed April 21, 2023 at: http://www.ncbi.nlm.nih.gov/books/NBK459256/
    Search in Google Scholar
  • 4 Wei WI, Sham JST. Nasopharyngeal carcinoma. Lancet 2005; 365 (9476): 2041-2054
    Search in Google Scholar
  • 5 Goshtasbi K, Lehrich BM, Birkenbeuel JL, Abiri A, Harris JP, Kuan EC. A comprehensive analysis of treatment management and survival outcomes in nasopharyngeal carcinoma. Otolaryngol Head Neck Surg 2021; 165 (01) 93-103
    Search in Google Scholar
  • 6 Wong KCW, Hui EP, Lo KW. et al. Nasopharyngeal carcinoma: an evolving paradigm. Nat Rev Clin Oncol 2021; 18 (11) 679-695
    Search in Google Scholar
  • 7 Gordon KB, Smyk DI, Gulidov IA. Proton therapy in head and neck cancer treatment: state of the problem and development prospects (review). Sovrem Tekhnologii Med 2021; 13 (04) 70-80
    Search in Google Scholar
  • 8 Mohamed N, Lee A, Lee NY. Proton beam radiation therapy treatment for head and neck cancer. Precis Radiat Oncol 2022; 6 (01) 59-68
    Search in Google Scholar
  • 9 Romesser PB, Cahlon O, Scher E. et al. Proton beam radiation therapy results in significantly reduced toxicity compared with intensity-modulated radiation therapy for head and neck tumors that require ipsilateral radiation. Radiother Oncol 2016; 118 (02) 286-292
    Search in Google Scholar
  • 10 National Cancer Database. American College of Surgeons. Published 2020. Accessed at: https://www.facs.org/Quality-Programs/Cancer/NCDB
  • 11 Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat 2011; 10 (02) 150-161
    Search in Google Scholar
  • 12 Colevas AD, Yom SS, Pfister DG. et al. NCCN guidelines ® insights: head and neck cancers, version 1.2018 featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2018; 16 (05) 479-490
    Search in Google Scholar
  • 13 Zhi-Qiang W, Qi M, Ji-Bin L. et al. The long-term survival of patients with III–IVb stage nasopharyngeal carcinoma treated with IMRT with or without Nimotuzumab: a propensity score-matched analysis. BMC Cancer 2019; 19 (01) 1122
    Search in Google Scholar
  • 14 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
    Search in Google Scholar
  • 15 Zhang Y, Chen L, Hu GQ. et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med 2019; 381 (12) 1124-1135
    Search in Google Scholar
  • 16 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 (01) 17
    Search in Google Scholar
  • 17 Smith AR. Proton therapy. Phys Med Biol 2006; 51 (13) R491-R504
    Search in Google Scholar
  • 18 McDonald MW, Liu Y, Moore MG, Johnstone PAS. Acute toxicity in comprehensive head and neck radiation for nasopharynx and paranasal sinus cancers: cohort comparison of 3D conformal proton therapy and intensity modulated radiation therapy. Radiat Oncol 2016; 11 (01) 32
    Search in Google Scholar
  • 19 Lewis GD, Holliday EB, Kocak-Uzel E. et al. Intensity-modulated proton therapy for nasopharyngeal carcinoma: decreased radiation dose to normal structures and encouraging clinical outcomes. Head Neck 2016; 38 (Suppl. 01) E1886-E1895
    Search in Google Scholar
  • 20 Holliday EB, Garden AS, Rosenthal DI. et al. Proton therapy reduces treatment-related toxicities for patients with nasopharyngeal cancer: a case-match control study of intensity-modulated proton therapy and intensity-modulated photon therapy. Int J Part Ther 2015; 2 (01) 19-28
    Search in Google Scholar
  • 21 Lee A, Kitpanit S, Chilov M, Langendijk JA, Lu J, Lee NY. A systematic review of proton therapy for the management of nasopharyngeal cancer. Int J Part Ther 2021; 8 (01) 119-130
    Search in Google Scholar
  • 22 Beddok A, Feuvret L, Noel G. et al. Efficacy and toxicity of proton with photon radiation for locally advanced nasopharyngeal carcinoma. Acta Oncol 2019; 58 (04) 472-474
    Search in Google Scholar
  • 23 Dionisi F, Croci S, Giacomelli I. et al. Clinical results of proton therapy reirradiation for recurrent nasopharyngeal carcinoma. Acta Oncol 2019; 58 (09) 1238-1245
    Search in Google Scholar
  • 24 Park SG, Ahn YC, Oh D. et al. Early clinical outcomes of helical tomotherapy/intensity-modulated proton therapy combination in nasopharynx cancer. Cancer Sci 2019; 110 (09) 2867-2874
    Search in Google Scholar
  • 25 Sanford NN, Lau J, Lam MB. et al. Individualization of clinical target volume delineation based on stepwise spread of nasopharyngeal carcinoma: outcome of more than a decade of clinical experience. Int J Radiat Oncol Biol Phys 2019; 103 (03) 654-668
    Search in Google Scholar
  • 26 Alterio D, D'Ippolito E, Vischioni B. et al. Mixed-beam approach in locally advanced nasopharyngeal carcinoma: IMRT followed by proton therapy boost versus IMRT-only. Evaluation of toxicity and efficacy. Acta Oncol 2020; 59 (05) 541-548
    Search in Google Scholar
  • 27 Jiří K, Vladimír V, Michal A. et al. Proton pencil-beam scanning radiotherapy in the treatment of nasopharyngeal cancer: dosimetric parameters and 2-year results. Eur Arch Otorhinolaryngol 2021; 278 (03) 763-769
    Search in Google Scholar
  • 28 Li X, Kitpanit S, Lee A. et al. Toxicity profiles and survival outcomes among patients with nonmetastatic nasopharyngeal carcinoma treated with intensity-modulated proton therapy vs intensity-modulated radiation therapy. JAMA Netw Open 2021; 4 (06) e2113205
    Search in Google Scholar
  • 29 Chou YC, Fan KH, Lin CY. et al. Intensity modulated proton beam therapy versus volumetric modulated arc therapy for patients with nasopharyngeal cancer: a propensity score-matched study. Cancers (Basel) 2021; 13 (14) 3555
    Search in Google Scholar
  • 30 Slevin F, Pan S, Mistry H. et al. A multicentre UK study of outcomes of nasopharyngeal carcinoma treated with intensity-modulated radiotherapy ± chemotherapy. Clin Oncol (R Coll Radiol) 2020; 32 (04) 238-249
    Search in Google Scholar
  • 31 Setton J, Han J, Kannarunimit D. et al. Long-term patterns of relapse and survival following definitive intensity-modulated radiotherapy for non-endemic nasopharyngeal carcinoma. Oral Oncol 2016; 53: 67-73
    Search in Google Scholar
  • 32 Reddy SP, Raslan WF, Gooneratne S, Kathuria S, Marks JE. Prognostic significance of keratinization in nasopharyngeal carcinoma. Am J Otolaryngol 1995; 16 (02) 103-108
    Search in Google Scholar
  • 33 Engbang JP, Njifou A, Tjomb TD, Mpessa M, Njock LR. Prognosis and Survival of Nasopharyngeal Cancer in Cameroon. Int J Otolaryngol Head Neck Surg 2021; 10 (01) 6-19
    Search in Google Scholar
  • 34 Hutajulu SH, Howdon D, Taroeno-Hariadi KW. et al. Survival outcome and prognostic factors of patients with nasopharyngeal cancer in Yogyakarta, Indonesia: a hospital-based retrospective study. PLoS One 2021; 16 (02) e0246638
    Search in Google Scholar
  • 35 Farias TP, Dias FL, Lima RA. et al. Prognostic factors and outcome for nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 2003; 129 (07) 794-799
    Search in Google Scholar