Top

Published in:

01-03-2021 | Radiotherapy | Original Article

Long-term outcomes and safety after reirradiation in locally recurrent nasopharyngeal carcinoma in a non-endemic area

Authors: J. Boustani, A. Ruffier, A. Moya-Plana, Y. Tao, F. Nguyen, C. Even, C. Berthold, O. Casiraghi, S. Temam, P. Blanchard

Published in: Strahlentherapie und Onkologie | Issue 3/2021

Abstract

Purpose

To determine outcomes and toxicities after reirradiation for locally recurrent nasopharyngeal carcinoma (rNPC) and to apply a prognostic index in a non-endemic region.

Methods

We retrospectively reported progression-free survival (PFS), overall survival (OS), and treatment-related toxicities in patients treated with curative intent for locally rNPC. We applied the prognostic model for OS and grade 5 radiotherapy (RT)-related toxicities published by Li et al. and evaluated its prognostic accuracy by receiver operating characteristic (ROC) curve analysis.

Results

Between 2005 and 2018, 33 patients were treated for rNPC in our institution. Median follow-up was 60 months. The mean time to local recurrence was 75 months. Six (18%) patients had a persistent grade 3 toxicity from a previous RT course. The median re-RT dose was 66 Gy. After re-RT, 13 patients had local failure and 3 patients had metastatic recurrence. Median PFS was 18 months with a 5-year PFS rate of 29%. Median OS was 35 months with a 5-year OS rate of 37%. Grade 3 or higher toxicities rate was 74%. There were 21% grade 5 toxicities. The median time to a grade 5 toxicity was less than 6 months following re-RT. The prognostic nomogram was not predictive for OS or grade 5 toxicities.

Conclusion

Reirradiation of rNPC is an effective treatment but is associated with a high rate of life-threatening toxicity. Stratification of patients based on their risk of developing severe toxicity is needed to select patients who will most likely benefit from re-RT.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492CrossRef

Ferlay J, Colombet M, Soerjomataram I et al (2019) Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 144(8):1941–1953. https://doi.org/10.1002/ijc.31937CrossRefPubMed

Colevas AD, Yom SS, Pfister DG et al (2018) NCCN guidelines insights: head and neck cancers, version 1.2018. J Natl Compr Canc Netw 16(5):479–490. https://doi.org/10.6004/jnccn.2018.0026CrossRefPubMed

Peng G, Wang T, Yang K‑Y et al (2012) 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 104(3):286–293. https://doi.org/10.1016/j.radonc.2012.08.013CrossRefPubMed

Zhang B, Mo Z, Du W, Wang Y, Liu L, Wei Y (2015) Intensity-modulated radiation therapy versus 2D-RT or 3D-CRT for the treatment of nasopharyngeal carcinoma: a systematic review and meta-analysis. Oral Oncol 51(11):1041–1046. https://doi.org/10.1016/j.oraloncology.2015.08.005CrossRefPubMed

Mao Y‑P, Tang L‑L, Chen L et al (2016) Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy. Chin J Cancer. https://doi.org/10.1186/s40880-016-0167-2CrossRefPubMedPubMedCentral

Zhang M‑X, Li J, Shen G‑P et al (2015) Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy: a 10-year experience with a large cohort and long follow-up. Eur J Cancer 51(17):2587–2595. https://doi.org/10.1016/j.ejca.2015.08.006CrossRefPubMed

Chang JT, See LC, Liao CT et al (2000) Locally recurrent nasopharyngeal carcinoma. Radiother Oncol 54(2):135–142CrossRef

Perri F, Della Vittoria Scarpati G, Caponigro F et al (2019) Management of recurrent nasopharyngeal carcinoma: current perspectives. Onco Targets Ther 12:1583–1591. https://doi.org/10.2147/OTT.S188148CrossRefPubMedPubMedCentral

10.

Li YQ, Tian YM, Tan SH et al (2018) Prognostic model for stratification of radioresistant nasopharynx carcinoma to curative salvage radiotherapy. J Clin Oncol 36(9):891–899. https://doi.org/10.1200/JCO.2017.75.5165CrossRef

11.

Lee N, Xia P, Quivey JM et al (2002) Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys 53(1):12–22. https://doi.org/10.1016/s0360-3016(02)02724-4CrossRefPubMed

12.

Kwong DLW, Sham JST, Leung LHT et al (2006) Preliminary results of radiation dose escalation for locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 64(2):374–381. https://doi.org/10.1016/j.ijrobp.2005.07.968CrossRefPubMed

13.

Ma BBY, Kam MKM, Leung SF et al (2012) A phase II study of concurrent cetuximab-cisplatin and intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma. Ann Oncol 23(5):1287–1292. https://doi.org/10.1093/annonc/mdr401CrossRefPubMed

14.

Leong YH, Soon YY, Lee KM, Wong LC, Tham IWK, Ho FCH (2018) Long-term outcomes after reirradiation in nasopharyngeal carcinoma with intensity-modulated radiotherapy: a meta-analysis. Head Neck 40(3):622–631. https://doi.org/10.1002/hed.24993CrossRefPubMed

15.

Lee AW, Law SC, Foo W et al (1993) Retrospective analysis of patients with nasopharyngeal carcinoma treated during 1976–1985: survival after local recurrence. Int J Radiat Oncol Biol Phys 26(5):773–782. https://doi.org/10.1016/0360-3016(93)90491-dCrossRefPubMed

16.

Teo PM, Kwan WH, Chan AT, Lee WY, King WW, Mok CO (1998) How successful is high-dose (> or = 60 Gy) reirradiation using mainly external beams in salvaging local failures of nasopharyngeal carcinoma? Int J Radiat Oncol Biol Phys 40(4):897–913. https://doi.org/10.1016/s0360-3016(97)00854-7CrossRefPubMed

17.

Pryzant RM, Wendt CD, Delclos L, Peters LJ (1992) Re-treatment of nasopharyngeal carcinoma in 53 patients. Int J Radiat Oncol Biol Phys 22(5):941–947. https://doi.org/10.1016/0360-3016(92)90792-gCrossRefPubMed

18.

Caudell JJ, Ward MC, Riaz N et al (2018) Volume, dose, and fractionation considerations for IMRT-based reirradiation in head and neck cancer: a multi-institution analysis. Int J Radiat Oncol Biol Phys 100(3):606–617. https://doi.org/10.1016/j.ijrobp.2017.11.036CrossRefPubMed

19.

Dornoff N, Weiß C, Rödel F et al (2015) Re-irradiation with cetuximab or cisplatin-based chemotherapy for recurrent squamous cell carcinoma of the head and neck. Strahlenther Onkol 191(8):656–664. https://doi.org/10.1007/s00066-015-0854-yCrossRefPubMed

20.

Tanvetyanon T, Padhya T, McCaffrey J et al (2009) Prognostic factors for survival after salvage reirradiation of head and neck cancer. J Clin Oncol 27(12):1983–1991. https://doi.org/10.1200/JCO.2008.20.0691CrossRefPubMed

21.

Mavroidis P, Grimm J, Cengiz M et al (2018) Fitting NTCP models to SBRT dose and carotid blowout syndrome data. Med Phys 45(10):4754–4762. https://doi.org/10.1002/mp.13121CrossRefPubMed

22.

Kim YS (2017) Reirradiation of head and neck cancer in the era of intensity-modulated radiotherapy: patient selection, practical aspects, and current evidence. Radiat Oncol J 35(1):1–15. https://doi.org/10.3857/roj.2017.00122CrossRefPubMedPubMedCentral

23.

Tuan JKL, Ha TC, Ong WS et al (2012) Late toxicities after conventional radiation therapy alone for nasopharyngeal carcinoma. Radiother Oncol 104(3):305–311. https://doi.org/10.1016/j.radonc.2011.12.028CrossRefPubMed

24.

Karam I, Yao M, Heron DE et al (2016) Survey of current practices from the International Stereotactic Body Radiotherapy Consortium (ISBRTC) for head and neck cancers. Future Oncol 13(7):603–613. https://doi.org/10.2217/fon-2016-0403CrossRefPubMed

25.

Dizman A, Coskun-Breuneval M, Altinisik-Inan G, Olcay GK, Cetindag MF, Guney Y (2014) Reirradiation with robotic stereotactic body radiotherapy for recurrent nasopharyngeal carcinoma. Asian Pac J Cancer Prev 15(8):3561–3566. https://doi.org/10.7314/apjcp.2014.15.8.3561CrossRefPubMed

26.

Ozyigit G, Cengiz M, Yazici G et al (2011) A retrospective comparison of robotic stereotactic body radiotherapy and three-dimensional conformal radiotherapy for the reirradiation of locally recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 81(4):e263–e268. https://doi.org/10.1016/j.ijrobp.2011.02.054CrossRefPubMed

27.

Wu S‑X, Chua DTT, Deng M‑L et al (2007) Outcome of fractionated stereotactic radiotherapy for 90 patients with locally persistent and recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 69(3):761–769. https://doi.org/10.1016/j.ijrobp.2007.03.037CrossRefPubMed

28.

Chua DTT, Wu S‑X, Lee V, Tsang J (2009) Comparison of single versus fractionated dose of stereotactic radiotherapy for salvaging local failures of nasopharyngeal carcinoma: a matched-cohort analysis. Head Neck Oncol 1:13. https://doi.org/10.1186/1758-3284-1-13CrossRefPubMedPubMedCentral

29.

Vargo JA, Ward MC, Caudell JJ et al (2018) A multi-institutional comparison of SBRT and IMRT for definitive reirradiation of recurrent or second primary head and neck cancer. Int J Radiat Oncol Biol Phys 100(3):595–605. https://doi.org/10.1016/j.ijrobp.2017.04.017CrossRefPubMed

30.

Ward MC, Riaz N, Caudell JJ et al (2018) Refining patient selection for reirradiation of head and neck squamous carcinoma in the IMRT era: a multi-institution cohort study by the MIRI collaborative. Int J Radiat Oncol Biol Phys 100(3):586–594. https://doi.org/10.1016/j.ijrobp.2017.06.012CrossRefPubMed

31.

Chang ET, Adami H‑O (2006) The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 15(10):1765–1777. https://doi.org/10.1158/1055-9965.EPI-06-0353CrossRefPubMed

32.

Ming X, Oei RW, Zhai R et al (2019) MRI-based radiomics signature is a quantitative prognostic biomarker for nasopharyngeal carcinoma. Sci Rep 9(1):10412. https://doi.org/10.1038/s41598-019-46985-0CrossRefPubMedPubMedCentral

33.

Chen W‑S, Li J‑J, Hong L, Xing Z‑B, Wang F, Li C‑Q (2016) Comparison of MRI, CT and 18F-FDG PET/CT in the diagnosis of local and metastatic of nasopharyngeal carcinomas: an updated meta analysis of clinical studies. Am J Transl Res 8(11):4532–4547PubMedPubMedCentral

34.

Peng H, Chen L, Tang L‑L et al (2017) Significant value of 18F-FDG-PET/CT in diagnosing small cervical lymph node metastases in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy. Chin J Cancer. https://doi.org/10.1186/s40880-017-0265-9CrossRefPubMedPubMedCentral

35.

Wei J, Pei S, Zhu X (2016) Comparison of 18F-FDG PET/CT, MRI and SPECT in the diagnosis of local residual/recurrent nasopharyngeal carcinoma: a meta-analysis. Oral Oncol 52:11–17. https://doi.org/10.1016/j.oraloncology.2015.10.010CrossRefPubMed

36.

Comoretto M, Balestreri L, Borsatti E, Cimitan M, Franchin G, Lise M (2008) Detection and restaging of residual and/or recurrent nasopharyngeal carcinoma after chemotherapy and radiation therapy: comparison of MR imaging and FDG PET/CT. Radiology 249(1):203–211. https://doi.org/10.1148/radiol.2491071753CrossRefPubMed

37.

Xiao W, Liu S, Tian Y et al (2015) Prognostic significance of tumor volume in locally recurrent nasopharyngeal carcinoma treated with salvage intensity-modulated radiotherapy. PLoS One 10(4):e125351. https://doi.org/10.1371/journal.pone.0125351CrossRefPubMedPubMedCentral

38.

Yue Q, Zhang M, Chen Y, Zheng D, Chen Y, Feng M (2018) Establishment of prognostic factors in recurrent nasopharyngeal carcinoma patients who received salvage intensity-modulated radiotherapy: a meta-analysis. Oral Oncol 81:81–88. https://doi.org/10.1016/j.oraloncology.2018.04.017CrossRefPubMed

39.

Lo YM, Chan LY, Lo KW et al (1999) Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res 59(6):1188–1191PubMed

40.

Chan ATC, Lo YMD, Zee B et al (2002) Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J Natl Cancer Inst 94(21):1614–1619. https://doi.org/10.1093/jnci/94.21.1614CrossRefPubMed

41.

Chan ATC, Hui EP, Ngan RKC et al (2018) Analysis of plasma Epstein-Barr virus DNA in nasopharyngeal cancer after chemoradiation to identify high-risk patients for adjuvant chemotherapy: a randomized controlled trial. J Clin Oncol 36(31):3091–3100. https://doi.org/10.1200/JCO.2018.77.7847CrossRef

42.

Chan ATC, Ma BBY, Lo YMD et al (2004) Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA. J Clin Oncol 22(15):3053–3060. https://doi.org/10.1200/JCO.2004.05.178CrossRefPubMed

43.

Zhu Q, Cai M‑Y, Chen C‑L et al (2017) Tumor cells PD-L1 expression as a favorable prognosis factor in nasopharyngeal carcinoma patients with pre-existing intratumor-infiltrating lymphocytes. OncoImmunology 6(5):e1312240. https://doi.org/10.1080/2162402X.2017.1312240CrossRefPubMedPubMedCentral

44.

Larbcharoensub N, Mahaprom K, Jiarpinitnun C et al (2018) Characterization of PD-L1 and PD‑1 expression and CD8+ tumor-infiltrating lymphocyte in Epstein-Barr virus-associated nasopharyngeal carcinoma. Am J Clin Oncol 41(12):1204–1210. https://doi.org/10.1097/COC.0000000000000449CrossRefPubMed

45.

Lee VHF, Lo AWI, Leung C‑Y et al (2016) Correlation of PD-L1 expression of tumor cells with survival outcomes after radical intensity-modulated radiation therapy for non-metastatic nasopharyngeal carcinoma. PLoS One 11(6):e157969. https://doi.org/10.1371/journal.pone.0157969CrossRefPubMedPubMedCentral

46.

Hsu C, Lee S‑H, Ejadi S et al (2017) Safety and antitumor activity of pembrolizumab in patients with programmed death-ligand 1‑positive nasopharyngeal carcinoma: results of the KEYNOTE-028 study. J Clin Oncol 35(36):4050–4056. https://doi.org/10.1200/JCO.2017.73.3675CrossRefPubMed

47.

Ma BBY, Lim W‑T, Goh B‑C et al (2018) Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma: an international, multicenter study of the Mayo Clinic phase 2 consortium (NCI-9742). J Clin Oncol 36(14):1412–1418. https://doi.org/10.1200/JCO.2017.77.0388CrossRefPubMedPubMedCentral

48.

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(10):1338–1350. https://doi.org/10.1016/S1470-2045(18)30495-9CrossRefPubMed

49.

Liu J, Yu H, Sun X et al (2017) Salvage endoscopic nasopharyngectomy for local recurrent or residual nasopharyngeal carcinoma: a 10-year experience. Int J Clin Oncol 22(5):834–842. https://doi.org/10.1007/s10147-017-1143-9CrossRefPubMed

50.

Tsang RK, To VS, Ho AC, Ho W‑K, Chan JY, Wei WI (2015) Early results of robotic assisted nasopharyngectomy for recurrent nasopharyngeal carcinoma. Head Neck 37(6):788–793. https://doi.org/10.1002/hed.23672CrossRefPubMed

51.

Chan JYW, Wei WI (2012) Recurrent nasopharyngeal carcinoma after salvage nasopharyngectomy. Arch Otolaryngol Head Neck Surg 138(6):572–576. https://doi.org/10.1001/archoto.2012.832CrossRefPubMed

Title: Long-term outcomes and safety after reirradiation in locally recurrent nasopharyngeal carcinoma in a non-endemic area
Authors: J. Boustani
A. Ruffier
A. Moya-Plana
Y. Tao
F. Nguyen
C. Even
C. Berthold
O. Casiraghi
S. Temam
P. Blanchard
Publication date: 01-03-2021
Publisher: Springer Berlin Heidelberg
Keyword: Radiotherapy
Published in: Strahlentherapie und Onkologie / Issue 3/2021
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-020-01647-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Long-term outcomes and safety after reirradiation in locally recurrent nasopharyngeal carcinoma in a non-endemic area

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2021

Parotid sparing and quality of life in long-term survivors of locally advanced head and neck cancer after intensity-modulated radiation therapy

Kardioonkologie: Herzdosis während einer Radiotherapie im Thoraxbereich

Präoperative Radiotherapie plus Resektion vs. Operation allein bei Patienten mit primärem retroperitonealem Sarkom (EORTC-62092: STRASS): eine multizentrische, randomisierte Phase-III-Studie

Implementation of a dedicated 1.5 T MR scanner for radiotherapy treatment planning featuring a novel high-channel coil setup for brain imaging in treatment position

A randomized in vitro evaluation of transient and permanent cardiac implantable electronic device malfunctions following direct exposure up to 10 Gy

Routine restaging after primary non-surgical treatment of laryngeal squamous cell carcinoma—a review

Implementation of a dedicated 1.5 T MR scanner for radiotherapy treatment planning featuring a novel high-channel coil setup for brain imaging in treatment position

A randomized in vitro evaluation of transient and permanent cardiac implantable electronic device malfunctions following direct exposure up to 10 Gy