Cancer Res Treat.  2022 Jan;54(1):96-108. 10.4143/crt.2020.1349.

Re-irradiation with Moderate Hypo-fractionation Using Intensity Modulated Photon or Proton Radiation Therapy in Locally Recurrent Squamous Cell Carcinoma of Nasopharynx

• Nam H
• Ahn YC
• Yang K
• Oh D
• Noh JM

• KMID: 2524591
• DOI: http://doi.org/10.4143/crt.2020.1349

Abstract

Purpose
This study aimed to analyze the treatment outcomes of locally recurrent nasopharyngeal cancer (NPC) patients following moderate hypo-fractionation re-irradiation (re-RT).
Materials and Methods
Sixty locally recurrent NPC patients underwent hypo-fractionation re-RT. Forty-eight point three percentage had rT3-4, and 30.0% did keratinizing squamous cell carcinoma. Intensity-modulated radiation therapy (IMRT), with or without intensity-modulated proton therapy (IMPT), was used in 66.7% of patients.
Results
With the median follow-up of 22 months (range, 2 to 254 months), 31 patients (51.7%) died, 38 (63.3%) developed further treatment failure, and 30 (50.0%) developed ≥ grade 3 toxicity (including seven grade 5) at time of analysis. The 2- and 5-year rates of overall survival, local failure-free survival, and ≥ grade 3 toxicity-free survival were 57.9% and 45.8%, 64.1% and 52.5%, and 54.8% and 44.9%, respectively. In multivariate analyses, worse factors for overall survival (OS) were iT3-4 (p=0.010) and age at re-RT ≥ 53 years (p=0.003), those for local failure-free survival (LFFS) were rT3-4 (p=0.022) and rN0-1 (p=0.035), and those for toxicity-free survival (TFS) were iT3-4 (p=0.020) and re-IMRT/IMPT (p=0.030), respectively. Cumulative dose or fraction size ≥ 3 Gy at re-RT, however, showed no significance for OS, LFFS and TFS.
Conclusion
Current re-RT with modern RT techniques by moderate hypo-fractionation scheme seemed feasible in treating locally recurrent NPC patients.

Keyword

Nasopharyngeal carcinoma; Re-irradiation; Hypo-fractionation; Histology; Radiation therapy; Proton therapy; Intensity-modulated radiation therapy

Figure

• 

  Fig. 1 Kaplan-Meier plot for overall survival, local failure-free survival (B) and ≥ grade 3 toxicity-free survival (C). The 2- and 5-year overall survival, local failure-free survival, and toxicity-free survival rates were 57.9% and 45.8%, 64.1% and 52.5%, and 54.8% and 44.9%, respectively.

• 

  Fig. 2 Patterns of failure. After a median follow-up of 22 months, second local recurrence occurred in 27 patients (45.0%). Regional recurrence was reported in 17 patients (28.3%), while distant metastasis developed in 19 patients (31.7%).

Reference

References

1. Lee AW, Ma BB, Ng WT, Chan AT. Management of nasopharyngeal carcinoma: current practice and future perspective. J Clin Oncol. 2015; 33:3356–64.

2. Coatesworth AP, Tsikoudas A, MacLennan K. The cause of death in patients with head and neck squamous cell carcinoma. J Laryngol Otol. 2002; 116:269–71.

3. Lee AWM, Ng WT, Chan JYW, Corry J, Makitie A, Mendenhall WM, et al. Management of locally recurrent nasopharyngeal carcinoma. Cancer Treat Rev. 2019; 79:101890.

4. Chan OS, Sze HC, Lee MC, Chan LL, Chang AT, Lee SW, et al. Reirradiation with intensity-modulated radiotherapy for locally recurrent T3 to T4 nasopharyngeal carcinoma. Head Neck. 2017; 39:533–40.

5. Dionisi F, Croci S, Giacomelli I, Cianchetti M, Caldara A, Bertolin M, et al. Clinical results of proton therapy reirradiation for recurrent nasopharyngeal carcinoma. Acta Oncol. 2019; 58:1238–45.

6. Hua YJ, Han F, Lu LX, Mai HQ, Guo X, Hong MH, et al. Long-term treatment outcome of recurrent nasopharyngeal carcinoma treated with salvage intensity modulated radiotherapy. Eur J Cancer. 2012; 48:3422–8.

7. Ng WT, Lee MC, Fung NT, Wong EC, Cheung AK, Chow JC, et al. Dose volume effects of re-irradiation for locally recurrent nasopharyngeal carcinoma. Head Neck. 2020; 42:180–7.

8. Yue Q, Zhang M, Chen Y, Zheng D, Chen Y, Feng M. Establishment of prognostic factors in recurrent nasopharyngeal carcinoma patients who received salvage intensity-modulated radiotherapy: a meta-analysis. Oral Oncol. 2018; 81:81–8.

9. Leong YH, Soon YY, Lee KM, Wong LC, Tham IWK, Ho FCH. Long-term outcomes after reirradiation in nasopharyngeal carcinoma with intensity-modulated radiotherapy: a meta-analysis. Head Neck. 2018; 40:622–31.

10. Alfonso JCL, Berk L. Modeling the effect of intratumoral heterogeneity of radiosensitivity on tumor response over the course of fractionated radiation therapy. Radiat Oncol. 2019; 14:88.

11. Quan K, Xu KM, Zhang Y, Clump DA, Flickinger JC, Lalonde R, et al. Toxicities following stereotactic ablative radiotherapy treatment of locally-recurrent and previously irradiated head and neck squamous cell carcinoma. Semin Radiat Oncol. 2016; 26:112–9.

12. Cho WK, Oh D, Lee E, Kim TG, Lee H, Nam H, et al. Feasibility of selective neck irradiation with lower elective radiation dose in treating nasopharynx cancer patients. Cancer Res Treat. 2019; 51:603–10.

13. Zhang B, Mo Z, Du W, Wang Y, Liu L, Wei Y. Intensity-modulated radiation therapy versus 2D-RT or 3D-CRT for the treatment of nasopharyngeal carcinoma: a systematic review and meta-analysis. Oral Oncol. 2015; 51:1041–6.

14. Li YQ, Tian YM, Tan SH, Liu MZ, Kusumawidjaja G, Ong EHW, et al. Prognostic model for stratification of radioresistant nasopharynx carcinoma to curative salvage radiotherapy. J Clin Oncol. 2018; 36:891–9.

15. Lin R, Slater JD, Yonemoto LT, Grove RI, Teichman SL, Watt DK, et al. Nasopharyngeal carcinoma: repeat treatment with conformal proton therapy: dose-volume histogram analysis. Radiology. 1999; 213:489–94.

16. Hu J, Bao C, Gao J, Guan X, Hu W, Yang J, et al. Salvage treatment using carbon ion radiation in patients with locoregionally recurrent nasopharyngeal carcinoma: Initial results. Cancer. 2018; 124:2427–37.

17. Schwaibold F, Scariato A, Nunno M, Wallner PE, Lustig RA, Rouby E, et al. The effect of fraction size on control of early glottic cancer. Int J Radiat Oncol Biol Phys. 1988; 14:451–4.

18. Le QT, Fu KK, Kroll S, Ryu JK, Quivey JM, Meyler TS, et al. Influence of fraction size, total dose, and overall time on local control of T1–T2 glottic carcinoma. Int J Radiat Oncol Biol Phys. 1997; 39:115–26.

19. Lee AW, Foo W, Law SC, Peters LJ, Poon YF, Chappell R, et al. Total biological effect on late reactive tissues following reirradiation for recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2000; 46:865–72.

20. Tian YM, Zhao C, Guo Y, Huang Y, Huang SM, Deng XW, et al. Effect of total dose and fraction size on survival of patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: a phase 2, single-center, randomized controlled trial. Cancer. 2014; 120:3502–9.

21. Leung TW, Wong VY, Tung SY. Stereotactic radiotherapy for locally recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2009; 75:734–41.

22. Ozyigit G, Cengiz M, Yazici G, Yildiz F, Gurkaynak M, Zorlu F, et al. 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. 2011; 81:e263–8.

23. Seo Y, Yoo H, Yoo S, Cho C, Yang K, Kim MS, et al. Robotic system-based fractionated stereotactic radiotherapy in locally recurrent nasopharyngeal carcinoma. Radiother Oncol. 2009; 93:570–4.

24. Stelow EB, Wenig BM. Update from the 4th edition of the World Health Organization classification of head and neck tumours: nasopharynx. Head Neck Pathol. 2017; 11:16–22.

25. Ou SI, Zell JA, Ziogas A, Anton-Culver H. Epidemiology of nasopharyngeal carcinoma in the United States: improved survival of Chinese patients within the keratinizing squamous cell carcinoma histology. Ann Oncol. 2007; 18:29–35.

26. Fandi A, Cvitkovic E. Biology and treatment of nasopharyngeal cancer. Curr Opin Oncol. 1995; 7:255–63.

27. Reddy SP, Raslan WF, Gooneratne S, Kathuria S, Marks JE. Prognostic significance of keratinization in nasopharyngeal carcinoma. Am J Otolaryngol. 1995; 16:103–8.

28. Yang K, Ahn YC, Nam H, Hong SD, Oh D, Noh JM. Clinical features of post-radiation nasopharyngeal necrosis and their outcomes following surgical intervention in nasopharyngeal cancer patients. Oral Oncol. 2021; 114:105180.

29. Li XY, Sun XS, Liu SL, Chen QY, Guo SS, Liu LT, et al. The development of a nomogram to predict post-radiation necrosis in nasopharyngeal carcinoma patients: a large-scale cohort study. Cancer Manag Res. 2019; 11:6253–63.

30. Shin SS, Ahn YC, Lim DH, Park W, Huh SJ. High dose 3-dimensional re-irradiation for locally recurrent nasopharyngeal cancer. Yonsei Med J. 2004; 45:100–6.