Skip to main content
SpringerLink
Log in

Determining the suitability of definitive radiation therapy in patients with metastatic nasopharyngeal carcinoma based on PET/CT: a large cohort study

  • Head and Neck
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To determine patients with de novo metastatic nasopharyngeal carcinoma (mNPC) who would benefit from receiving definitive radiation therapy (DRT) along with their pre-existing palliative chemotherapy (PCT) by evaluating their post-PCT Deauville scores and EBV DNA.

Methods

A total of 570 mNPC patients, treated with PCT or PCT+DRT, were studied. EBV DNA levels, along with post-PCT Deauville scores, were used to stratify risk based on the recursive partitioning analysis (RPA).

Results

Significant differences were observed in the survival rates of patients with Deauville scores of 1–3 and 4–5 (2-year progression-free survival (PFS): 23.4% versus 8.5%, p < 0.001; 2-year overall survival (OS): 56.8% versus 18.8%, p < 0.001). RPA yielded three distinct groups in the increasing order of risk (Deauville scores of all RPA I-II were within the range of 1–3): (1) RPA I: EBV DNA levels at a pretreatment concentration ≤ 4000 copies/mL and undetectable post-PCT; (2) RPA II: EBV DNA levels either at a pretreatment concentration > 4000 copies/mL or at a pretreatment concentration ≤ 4000 copies/mL and detectable post-PCT; (3) RPA III: Deauville scores 4–5. While patients in RPA I and RPA II had significantly PFS rates when treated with PCT+DRT than when treated with PCT alone (RPA I: 72.7% versus 13.4%, RPA II: 37.8% versus 6.3%), those in RPA III did not experience such PFS benefits (6.5% versus 9.7%).

Conclusion

PCT+DRT might improve the survival rates in mNPC patients in the low- and mid-risk strata but not those of patients in the high-risk strata.

Key Points

  • We use the Deauville scores and the concentrations of the Epstein-Barr virus (EBV) DNA to determine those patients with de novo metastatic NPC who would benefit from radiation therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

2-[18F]FDG:

2-deoxy-2-[18F]fluoro-D-glucose

5-fu:

5-Fluorouracil

AJCC:

American Joint Committee on Cancer

AUC:

Area under the receiver operating characteristic curve

CCRT:

Concurrent chemoradiotherapy

CI:

Confidence interval

DDP:

Cisplatin

DRT:

Definitive radiation therapy

EBV DNA:

Epstein-Barr virus DNA

ECOG:

Eastern Cooperative Oncology Group

HR:

Hazard ratio

IMRT:

Intensity-modulated radiotherapy

mNPC:

Metastatic nasopharyngeal carcinoma

MRI:

Magnetic resonance imaging

NCCN:

National Comprehensive Cancer Network

OS:

Overall survival

PCT:

Palliative chemotherapy

PET/CT:

Positron emission tomography/computed tomography

PFS:

Progression-free survival

ROC:

Receiver operator characteristic

RPA:

Recursive partitioning analysis

RT:

Radiation therapy

SUV:

Standardized uptake value

References

  1. Zhang Y, Chen L, Hu GQ et al (2019) Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med. 381:1124–1135

    Article  CAS  Google Scholar 

  2. Zhang LL, Huang MY, Fei-Xu X et al (2020) Risk stratification for nasopharyngeal carcinoma: a real-world study based on locoregional extension patterns and Epstein–Barr virus DNA load. Ther Adv Med Oncol. 12:1758835920932052

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  4. You R, Liu YP, Huang PY, et al (2020) Efficacy and safety of locoregional radiotherapy with chemotherapy vs chemotherapy alone in de novo metastatic nasopharyngeal carcinoma: a multicenter Phase 3 randomized clinical trial. JAMA Oncol. 6:1345–1352

    Article  Google Scholar 

  5. Lee A, Chow JCH, Lee NY (2020) Treatment deescalation strategies for nasopharyngeal cancer: a review. JAMA Oncol. 7:445–453

    Article  Google Scholar 

  6. Sun XS, Liang YJ, Chen QY, et al (2020) Optimizing the treatment pattern for de novo metastatic nasopharyngeal carcinoma patients: a large-scale retrospective cohort study. Front Oncol. 10:543646

    Article  Google Scholar 

  7. Balermpas P (2021) Locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma significantly prolongs survival. Strahlenther Onkol. 197:82–84

    Article  Google Scholar 

  8. Jin Y, Shi YX, Cai XY, et al (2012) Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma. J Cancer Res Clin Oncol. 138:1717–1725

    Article  CAS  Google Scholar 

  9. Bensouda Y, Kaikani W, Ahbeddou N, et al (2011) Treatment for metastatic nasopharyngeal carcinoma. Eur Ann Otorhinolaryngol Head Neck Dis. 128:79–85

    Article  CAS  Google Scholar 

  10. Zhang L, Huang Y, Hong S, et al (2016) Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 388:1883–1892

    Article  CAS  Google Scholar 

  11. Fang W, Yang Y, Ma Y, et al (2018) Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 19:1338–1350

    Article  CAS  Google Scholar 

  12. Paydary K, Seraj SM, Zadeh MZ, Emamzadehfard S, Shamchi SP, Gholami S et al (2019) The evolving role of FDG-PET/CT in the diagnosis, staging, and treatment of breast cancer. Mol Imaging Biol. 21:1–10

    Article  CAS  Google Scholar 

  13. Cheung PK, Chin RY, Eslick GD (2016) Detecting residual/recurrent head neck squamous cell carcinomas using PET or PET/CT: systematic review and meta-analysis. Otolaryngol Head Neck Surg. 154:421–432

    Article  Google Scholar 

  14. Xiao BB, Lin DF, Sun XS, et al (2021) Nomogram for the prediction of primary distant metastasis of nasopharyngeal carcinoma to guide individualized application of FDG PET/CT. Eur J Nucl Med Mol Imaging. 48:2586–2598

    Article  CAS  Google Scholar 

  15. Chang MC, Chen JH, Liang JA, et al (2013) Accuracy of whole-body FDG-PET and FDG-PET/CT in M staging of nasopharyngeal carcinoma: a systematic review and meta-analysis. Eur J Radiol. 82:366–373

    Article  Google Scholar 

  16. Tang LQ, Chen QY, Fan W, et al (2013) Prospective study of tailoring whole-body dual-modality [18F]fluorodeoxyglucose positron emission tomography/computed tomography with plasma Epstein–Barr virus DNA for detecting distant metastasis in endemic nasopharyngeal carcinoma at initial staging. J Clin Oncol. 31:2861–2869

    Article  CAS  Google Scholar 

  17. Itti E, Meignan M, Berriolo-Riedinger A, et al (2013) An international confirmatory study of the prognostic value of early PET/CT in diffuse large B-cell lymphoma: comparison between Deauville criteria and ΔSUVmax. Eur J Nucl Med Mol Imaging. 40:1312–1320

    Article  Google Scholar 

  18. Sjövall J, Bitzén U, Kjellén E, et al (2016) Qualitative interpretation of PET scans using a Likert scale to assess neck node response to radiotherapy in head and neck cancer. Eur J Nucl Med Mol Imaging. 43:609–616

    Article  Google Scholar 

  19. Dai N, Zhou Y, Deng S, Sang S, Wu Y (2021) Prognostic value of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography after autologous hematopoietic stem cell transplantation in lymphoma using Deauville scores. Contrast Media Mol Imaging. 2021:5510825. https://doi.org/10.1155/2021/5510825

    Article  CAS  Google Scholar 

  20. Barrington SF, Eertink JJ, de Vet HCW, George Mikhaeel NG, Hoekstra OS, Zijlstra JM (2021) Not yet time to abandon the Deauville criteria in Diffuse Large B-cell lymphoma. J Nucl Med. 62:1655–1656

    Article  Google Scholar 

  21. Qin W, Jiang X, You J, et al (2021) Deauville score evaluation of interim PET/CT in primary mediastinal large B-cell lymphoma. Eur J Nucl Med Mol Imaging. 48:3347–3350

    Article  Google Scholar 

  22. Huang HL, Ngam PI, Tan KM, et al (2021) The exact Deauville score, NABS score and high SUVmax predicts outcome in extranodal natural killer/T-cell lymphoma. Ann Nucl Med. 35:557–568

    Article  CAS  Google Scholar 

  23. Zwezerijnen GJC, Eertink JJ, Burggraaff CN, et al (2021) Interobserver agreement on automated metabolic tumor volume measurements of Deauville score 4 and 5 lesions at interim 18 F-FDG PET in Diffuse Large B-Cell Lymphoma. J Nucl Med. 62:1531–1536

    Article  CAS  Google Scholar 

  24. Li WZ, Lv SH, Liu GY, et al (2021) Development of a prognostic model to identify the suitable definitive radiation therapy candidates in de novo metastatic nasopharyngeal carcinoma: a real-world study. Int J Radiat Oncol Biol Phys. 109:120–130

    Article  Google Scholar 

  25. Tan R, Phua SKA, Soong YL, et al (2020) Clinical utility of Epstein–Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma. Cancer Commun (Lond). 40:564–585

    Article  Google Scholar 

  26. Lee AW, Tung SY, Ngan RK, et al (2011) Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: combined analyses of NPC-9901 and NPC-9902 Trials. Eur J Cancer. 47:656–666

    Article  CAS  Google Scholar 

  27. Chen FP, Huang XD, Lv JW, et al (2020) Prognostic potential of liquid biopsy tracking in the posttreatment surveillance of patients with nonmetastatic nasopharyngeal carcinoma. Cancer. 126:2163–2173

    Article  CAS  Google Scholar 

  28. Cao Y (2017) EBV based cancer prevention and therapy in nasopharyngeal carcinoma. npj Precis. Oncol. 1:10. https://doi.org/10.1038/s41698-017-0018-x

    Article  Google Scholar 

  29. Lei Y, Li YQ, Jiang W, Hong et al (2021) A gene-expression predictor for efficacy of induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 113:471–480

    Article  Google Scholar 

  30. Kim KY, Le QT, Yom SS, Pinsky BA, Bratman SV, Ng RH et al (2017) Current state of PCR-based Epstein–Barr virus DNA testing for nasopharyngeal cancer. J Natl Cancer Inst. 109(4):djx007. https://doi.org/10.1093/jnci/djx007

    Article  CAS  Google Scholar 

  31. Tian YM, Zeng L, Wang FH, Liu S, Guan Y, Lu TX et al (2013) Prognostic factors in nasopharyngeal carcinoma with synchronous liver metastasis: a retrospective study for the management of treatment. Radiat Oncol. 8:272. https://doi.org/10.1186/1748-717X-8-272

    Article  Google Scholar 

  32. Boellaard R, O’Doherty MJ, Weber WA, et al (2010) FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging 37:181–200

    Article  Google Scholar 

  33. Almuhaideb A, Papathanasiou N, Bomanji J (2011) 18F-FDG PET/CT imaging in oncology. Ann Saudi Med. 31:3–13

    Article  Google Scholar 

  34. Blanchard P, Lee A, Marguet S, et al (2015) Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 16:645–655

    Article  Google Scholar 

  35. Lopci E, Meignan M (2019) Deauville score: the Phoenix rising from ashes. Eur J Nucl Med Mol Imaging. 46:1043–1045

    Article  CAS  Google Scholar 

  36. Bouard L, Bodet-Milin C, Bailly C, et al (2019) Deauville Scores 4 or 5 assessed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography early post-allotransplant is highly predictive of relapse in lymphoma patients. Biol Blood Marrow Transplant. 25:906–911

    Article  Google Scholar 

  37. Li H, Huang C, Chen Q, et al (2020) Lymph-node Epstein–Barr virus concentration in diagnosing cervical lymph-node metastasis in nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol. 277:2513–2520

    Article  Google Scholar 

Download references

Funding

This study was funded by grants from the National Key R&D Program of China(2017YFC0908500, 2017YFC1309003), the National Natural Science Foundation ofChina (No. 81425018, No. 81672868, No.81802775, No. 82073003, No.82002852, No.82003267), the Sci-Tech Project Foundation of Guangzhou City (201707020039), theSun Yat-sen University Clinical Research 5010 Program (No. 2019023), the SpecialSupport Plan of Guangdong Province (No. 2014TX01R145), the Natural ScienceFoundation of Guangdong Province (No. 2017A030312003, No. 2018A0303131004), theNatural Science Foundation of Guangdong Province for Distinguished Young Scholar(No. 2018B030306001), the Sci-Tech Project Foundation of Guangdong Province (No.2014A020212103), the Health and Medical Collaborative Innovation Project ofGuangzhou City (No. 201400000001, No.201803040003), Pearl River S&T NovaProgram of Guangzhou (No. 201806010135), the Planned Science and TechnologyProject of Guangdong Province (2019B020230002), the National Science andTechnology Pillar Program during the Twelfth Five-year Plan Period (No.2014BAI09B10), Natural Science Foundation of Guangdong Province(2017A030312003), and the Fundamental Research Funds for the Central Universities.

Author information

Author notes

  1. Zhen-Chong Yang, Ying-Ying Hu, and Li-Ting Liu have contributed equally to this work.

Authors and Affiliations

  1. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China

    Zhen-Chong Yang, Ying-Ying Hu, Li-Ting Liu, Shan-Shan Guo, Chao-Chao Du, Yu-Jing Liang, Qiu-Yan Chen & Hai-Qiang Mai

  2. Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Zhen-Chong Yang, Li-Ting Liu, Shan-Shan Guo, Chao-Chao Du, Yu-Jing Liang, Qiu-Yan Chen & Hai-Qiang Mai

  3. Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Ying-Ying Hu

Authors
  1. Zhen-Chong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying-Ying Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li-Ting Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shan-Shan Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chao-Chao Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu-Jing Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qiu-Yan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hai-Qiang Mai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Qiu-Yan Chen or Hai-Qiang Mai.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Hai-Qiang Mai.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

Ying-Ying Hu and Ji-Bin Li kindly provided statistical advice for this manuscript.

Informed consent

Written informed consent was obtained from all patients in this study.

Ethics approval

Institutional Review Board approval was obtained.

Methodology

• retrospective

• diagnostic or prognostic study

• performed at one institution

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(DOCX 299 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, ZC., Hu, YY., Liu, LT. et al. Determining the suitability of definitive radiation therapy in patients with metastatic nasopharyngeal carcinoma based on PET/CT: a large cohort study. Eur Radiol 32, 7722–7732 (2022). https://doi.org/10.1007/s00330-022-08814-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-022-08814-3

Keywords

Search

Navigation