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Hyperfractionation compared to standard fractionation in intensity-modulated radiation therapy for patients with locally advanced recurrent nasopharyngeal carcinoma

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Abstract

We prospectively studied the efficacy and safety of hyperfractionated intensity-modulated radiation therapy (HF-IMRT) and compared to a historical cohort treated with standard fractionation (SF-IMRT) in patients with locally advanced recurrent (rT3–T4, rN0–N1, M0) nasopharyngeal carcinoma (NPC). Ten patients were treated with induction chemotherapy followed by HF-IMRT (64.8 Gy/54 fr/5.5 weeks) concurrent with weekly cisplatin. They were compared to another ten patients treated with induction chemotherapy followed by SF-IMRT (60 Gy/30 fr/6 weeks) concurrent with weekly cisplatin. After a median follow-up duration of 44.6 months, we demonstrated that the median local failure-free survival (LFFS) showed a trend in favor of HF-IMRT (28.2 vs. 16.6 months, p = 0.164). Overall survival (OS) (34.8 vs. 35.5 months, p = 0.603) was not different between the two groups. Treatment-related hemorrhage was slightly less with HF-IMRT (30.0 vs. 0 %), reaching marginal significance (p = 0.060). Judging from our study results, HF-IMRT offered a marginally better LFFS and an apparently more favorable toxicity profile compared to SF-IMRT in locally advanced recurrent NPC.

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References

  1. Lee AW, Sze WM, Au JS et al (2005) Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys 61(4):1107–1116

    Article  PubMed  Google Scholar 

  2. Wei WI, Chan JY, Ng RW et al (2011) Surgical salvage of persistent or recurrent nasopharyngeal carcinoma with maxillary swing approach—critical appraisal after 2 decades. Head Neck 33(7):969–975

    Article  PubMed  Google Scholar 

  3. Wei WI, Kwong DLW (2011) Recurrent nasopharyngeal carcinoma: surgical salvage vs. additional chemoradiation. Curr Opin Otolaryngol Head Neck Surg 19(2):82–86

    Article  PubMed  Google Scholar 

  4. Teo PM, Kwan WH, Chan AT et al (1998) How successful is high dose (>60 Gy) reirradiation using many external beams in salvaging local failures of nasopharyngeal carcinoma? Int J Radiat Oncol Biol Phys 40(4):897–913

    Article  CAS  PubMed  Google Scholar 

  5. Chen AM, Phillips TL, Lee NY (2011) Practical considerations in the re-irradiation of recurrent and second primary head-and-neck cancer: who, why, how, and how much? Int J Radiat Oncol Biol Phys 81(5):1211–1219

    Article  PubMed  Google Scholar 

  6. Lee N, Chan K, Bekelman JE et al (2007) Salvage re-irradiation for recurrent head and neck cancer. Int J Radiat Oncol Biol Phys 68(3):731–740

    Article  PubMed  Google Scholar 

  7. Sulman EP, Schwartz DL, Le TT et al (2009) IMRT reirradiation of head and neck cancer-disease control and morbidity outcomes. Int J Radiat Oncol Biol Phys 73(2):399–409

    Article  PubMed  Google Scholar 

  8. Popovtzer A, Gluck I, Chepeha DB et al (2009) The pattern of failure after reirradiation of recurrence squamous cell head and neck cancer: Implications for defining the targets. Int J Radiat Oncol Biol Phys 74(5):1342–1347

  9. Langendijk JA, Kasperts N, Leemans CR et al (2006) A phase II study of primary reirradiation in squamous cell carcinoma of head and neck. Radiother Oncol 78(3):306–312

    Article  PubMed  Google Scholar 

  10. Chen AM, Bucci MK, Singer MI et al (2007) Intraoperative radiation therapy for recurrent head-and-neck cancer: the UCSF experience. Int J Radiat Oncol Biol Phys 67(1):122–129

    Article  PubMed  Google Scholar 

  11. Heron DE, Ferris RL, Karamouzis M et al (2009) Stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: results of a phase I dose-escalation trial. Int J Radiat Oncol Biol Phys 75(5):1493–1500

    Article  PubMed  Google Scholar 

  12. Puthawala A, Nisar Syed AM, Gamie S et al (2001) Interstitial low-dose-rate brachytherapy as a salvage treatment for recurrent head-and-neck cancers: long-term results. Int J Radiat Oncol Biol Phys 51(2):354–362

    Article  CAS  PubMed  Google Scholar 

  13. Roh KW, Jang JS, Kim MS et al (2009) Fractionated stereotactic radiotherapy as reirradiation for locally recurrent head and neck cancer. Int J Radiat Oncol Biol Phys 74(5):1348–1355

    Article  PubMed  Google Scholar 

  14. Perry DJ, Chan K, Wolden S et al (2010) High-dose-rate intraoperative radiation therapy for recurrent head-and-neck cancer. Int J Radiat Oncol Biol Phys 76(4):1140–1146

    Article  PubMed  Google Scholar 

  15. Fu KK, Pajak TF, Trotti A et al (2000) A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 48(1):7–16

    Article  CAS  PubMed  Google Scholar 

  16. Beitler JJ, Zhang Q, Fu KK et al (2014) Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer. Int J Radiat Oncol Biol Phys 89(1):13–20

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bourhis J, Overgaard J, Audry H et al (2006) Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH) Collaborative Group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 368(9538):843–854

    Article  PubMed  Google Scholar 

  18. Spenser SA, Harris J, Wheeler RH et al (2008) Final report of RTOG 96-10, a multi-institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck. Head Neck 30(3):281–288

    Article  Google Scholar 

  19. Langer CJ, Harris J, Horwitz EM et al (2007) Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: results of the Radiation Therapy Oncology Group protocol 9911. J Clin Oncol 25(30):4800–4805

    Article  CAS  PubMed  Google Scholar 

  20. Watkins JM, Shirai KS, Wahlquist AE et al (2009) Toxicity and survival outcomes of hyperfractionated split-course reirradiation and daily concurrent chemotherapy in locoregionally recurrent, previously irradiated head and neck cancers. Head Neck 31(4):493–502

    Article  PubMed  Google Scholar 

  21. Ang KK, Jiang GL, Feng Y et al (2001) Extent and kinetics of recovery of occult spinal cord injury. Int J Radiat Oncol Biol Phys 50(4):1013–1020

    Article  CAS  PubMed  Google Scholar 

  22. Jones B, Grant W (2014) Retreatment of central nervous system tumours. Clin Oncol (R Coll Radiol) 26(7):407–418

    Article  CAS  Google Scholar 

  23. Lu TX, Mai WY, Teh BS et al (2004) Initial experience using intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 58(3):682–687

    Article  PubMed  Google Scholar 

  24. Chua DT, Sham JS, Au GK (2005) Induction chemotherapy with cisplatin and gemcitabine followed by reirradiation for locally recurrent nasopharyngeal carcinoma. Am J Clin Oncol 28(5):464–471

    Article  CAS  PubMed  Google Scholar 

  25. Chua DT, Sham JS, Leung LH et al (2005) Re-irradiation of nasopharyngeal carcinoma with intensity-modulated radiotherapy. Radiother Oncol 77(3):290–294

    Article  PubMed  Google Scholar 

  26. Qiu S, Lin S, Tham IW et al (2012) Intensity-modulated radiation therapy in the salvage of locally recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 83(2):676–683

    Article  PubMed  Google Scholar 

  27. Han F, Zhao C, Huang SM et al (2012) Long-term outcomes and prognostic factors of re-irradiation for locally recurrent nasopharyngeal carcinoma using intensity-modulated radiotherapy. Clin Oncol (R Coll Radiol) 24(8):569–576

    Article  Google Scholar 

  28. Hua YJ, Han F, Lu LX et al (2012) Long-term treatment outcome of recurrent nasopharyngeal carcinoma treated with salvage intensity modulated radiotherapy. Eur J Cancer 48(18):3422–3428

    Article  PubMed  Google Scholar 

  29. Chen HY, Ma XM, Ye M et al (2013) Effectiveness and toxicities of intensity-modulated radiotherapy for patients with locally recurrent nasopharyngeal carcinoma. PLoS One 8(9):e73918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tian YM, Tian YH, Zeng L et al (2014) Prognostic model for survival of local recurrent nasopharyngeal carcinoma with intensity-modulated radiotherapy. Br J Cancer 110(2):297–303

    Article  PubMed  Google Scholar 

  31. Tian YM, Zhao C, Guo Y et al (2014) 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 120(22):3502–3509

    Article  PubMed  Google Scholar 

  32. Tian YM, Guan Y, Xiao WW et al (2016) Long-term survival and late complications in intensity-modulated radiotherapy of locally recurrent T1 to T2 nasopharyngeal carcinoma. Head Neck 38(2):225–231

    Article  PubMed  Google Scholar 

  33. Qiu S, Lu J, Zheng W et al (2014) Advantages of intensity modulated radiotherapy in recurrent T1-2 nasopharyngeal carcinoma: a retrospective study. BMC Cancer 14:797

    Article  PubMed  PubMed Central  Google Scholar 

  34. You R, Zou X, Hua YJ et al (2015) Salvage endoscopic nasopharyngectomy is superior to intensity-modulated radiation therapy for local recurrence of selected T1-T3 nasopharyngeal carcinoma—a case-matched comparison. Radiother Oncol 115(3):399–406

    Article  PubMed  Google Scholar 

  35. Syed AM, Puthawala AA, Damore SJ et al (2000) Brachytherapy for primary and recurrent nasopharyngeal carcinoma: 20 years’ experience at Long Beach Memorial. Int J Radiat Oncol Biol Phys 47(5):1311–1321

    Article  CAS  PubMed  Google Scholar 

  36. Leung TW, Tung SY, Sze WK et al (2000) Salvage radiation therapy for locally recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 48(5):1331–1338

    Article  CAS  PubMed  Google Scholar 

  37. Kwong DL, Wei WI, Cheng AC et al (2001) Long term results of radioactive gold grain implantation for the treatment of persistent and recurrent nasopharyngeal carcinoma. Cancer 91(6):1105–1113

    Article  CAS  PubMed  Google Scholar 

  38. Law SC, Lam WK, Ng MF et al (2002) Reirradiation of nasopharyngeal carcinoma with intracavitary mold brachytherapy: an effective means of local salvage. Int J Radiat Oncol Biol Phys 54(4):1095–1113

    Article  PubMed  Google Scholar 

  39. Koutcher L, Lee N, Zelefsky M et al (2010) Reirradiation of locally recurrent nasopharynx cancer with external beam radiotherapy with or without brachytherapy. Int J Radiat Oncol Biol Phys 76(1):130–137

    Article  PubMed  Google Scholar 

  40. Cheah SK, Lau FN, Yusof MM et al (2014) Treatment outcome with brachytherapy for recurrent nasopharyngeal carcinoma. Asian Pac J Cancer Prev 14(11):6513–6518

    Article  PubMed  Google Scholar 

  41. Shen X, Li Y, Zhang Y et al (2015) An analysis of brachytherapy with computed tomography-guided permanent implantation of Iodine-125 seeds for recurrent nonkeratin nasopharyngeal carcinoma. Onco Targets Ther 8:991–997

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Orecchia R, Redda MG, Ragona R et al (1999) Results of hypofractionated stereotactic re-irradiation on 13 locally recurrent nasopharyngeal carcinomas. Radiother Oncol 53(1):23–28

    Article  CAS  PubMed  Google Scholar 

  43. Ahn YC, Lee KC, Kim DY et al (2000) Fractionated stereotactic radiation therapy for extracranial head and neck tumors. Int J Radiat Oncol Biol Phys 48(2):501–505

    Article  CAS  PubMed  Google Scholar 

  44. Chen HJ, Leung SW, Su CY (2001) Linear accelerator based radiosurgery as a salvage treatment for skull base and intracranial invasion of recurrent nasopharyngeal carcinomas. Am J Clin Oncol 24(3):255–258

    Article  CAS  PubMed  Google Scholar 

  45. Pai PC, Chuang CC, Wei KC et al (2002) Stereotactic radiosurgery for locally recurrent nasopharyngeal carcinoma. Head Neck 24(8):748–753

    Article  PubMed  Google Scholar 

  46. Chua DT, Sham JS, Kwong PW et al (2003) Linear accelerator-based stereotactic radiosurgery for limited, locally persistent, and recurrent nasopharyngeal carcinoma: efficacy and complications. Int J Radiat Oncol Biol Phys 56(1):177–183

    Article  PubMed  Google Scholar 

  47. Low JS, Chua ET, Gao F et al (2006) Stereotactic radiosurgery plus intracavitary irradiation in the salvage of nasopharyngeal carcinoma. Head Neck 28(4):321–329

    Article  PubMed  Google Scholar 

  48. Wu SX, Chua DT, Deng ML 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

    Article  PubMed  Google Scholar 

  49. Leung TW, Wong VY, Tung SY (2009) Stereotactic radiotherapy for locally recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 75(3):734–741

    Article  PubMed  Google Scholar 

  50. Chua DT, Wu SX, Lee V et al (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

    Article  PubMed  PubMed Central  Google Scholar 

  51. Seo Y, Yoo H, Yoo S et al (2009) Robotic system-based fractionated stereotactic radiotherapy in locally recurrent nasopharyngeal carcinoma. Radiother Oncol 93(3):570–574

    Article  PubMed  Google Scholar 

  52. 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

    Article  PubMed  Google Scholar 

  53. Roeder F, Zwicker F, Saleh-Ebrahimi L et al (2011) Intensity modulated or fractionated stereotactic reirradiation in patients with recurrent nasopharyngeal cancer. Radiat Oncol 6:22

    Article  PubMed  PubMed Central  Google Scholar 

  54. Dizman A, Coskun-Breuneval M, Altinisik-Inan G et al (2014) Reirradiation with robotic stereotactic body radiotherapy for recurrent nasopharyngeal carcinoma. Asian Pac J Cancer Prev 15(8):3561–3566

    Article  PubMed  Google Scholar 

  55. Yamazaki H, Ogita M, Himei K et al (2015) Carotid blowout syndrome in pharyngeal cancer patients treated by hypofractionated stereotactic re-irradiation using CyberKnife: a multi-institutional matched-cohort analysis. Radiother Oncol 115(1):67–71

    Article  PubMed  Google Scholar 

  56. Bonner JA, Harari PM, Giralt J et al (2006) Radiothearpy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354(6):567–578

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 1/F, Professorial Block, 102 Pokfulam Road, Pokfulam, Hong Kong

    Victor H. F. Lee, Dora L. W. Kwong, To-Wai Leung, Sherry C. Y. Ng, Ka-On Lam, Chi-Chung Tong & Chun-Kin Sze

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  1. Victor H. F. Lee
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  2. Dora L. W. Kwong
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Correspondence to Victor H. F. Lee.

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Lee, V.H.F., Kwong, D.L.W., Leung, TW. et al. Hyperfractionation compared to standard fractionation in intensity-modulated radiation therapy for patients with locally advanced recurrent nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol 274, 1067–1078 (2017). https://doi.org/10.1007/s00405-016-4339-0

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