Skip to main content

Advertisement

SpringerLink
Log in

A randomized phase III study between sequential versus simultaneous integrated boost intensity-modulated radiation therapy in nasopharyngeal carcinoma

Eine randomisierte Phase-III-Studie für den Vergleich zwischen intensitätsmodulierter Strahlentherapie mit sequenziell oder mit simultan integriertem Boost bei Nasopharynxkarzinom

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Purpose

This study was performed to compare the acute and late toxicities between sequential (SEQ) and simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC).

Materials and methods

Stage I-IVB NPC patients were randomized to receive SEQ-IMRT or SIB-IMRT. SEQ-IMRT consisted of two plans: 2 Gy × 25 fractions to low-risk planning target volume (PTV) followed by a sequential boost (2 Gy × 10 fractions) to high-risk PTV, while SIB-IMRT treated low- and high-risk PTVs with doses of 56 and 70 Gy in 33 fractions. Toxicities and survival outcomes were analyzed.

Results

Between October 2010 and September 2015, of the 209 patients who completed treatment, 102 in the SEQ and 107 in the SIB arm were analyzed. The majority had undifferentiated squamous cell carcinoma (82%). Mucositis and dysphagia were the most common grade 3–5 acute toxicities. There were no statistically significant differences in the cumulative incidence of grade 3–4 acute toxicities between the two arms (59.8% in SEQ vs. 58.9% in SIB; P = 0.892). Common grade 3–4 late toxicities for SEQ and SIB included hearing loss (2.9 vs. 8.4%), temporal lobe injury (2.9 vs. 0.9%), cranial nerve injury (0 vs. 2.8%), and xerostomia (2 vs. 0.9%). With the median follow-up of 41 months, 3‑year progression-free and overall survival rates were 72.7 vs. 73.4% (P = 0.488) and 86.3 vs. 83.6% (P = 0.938), respectively.

Conclusion

SEQ and SIB provide excellent survival outcomes with few late toxicities. According to our study, SIB with a satisfactory dose–volume constraint to nearby critical organs is the technique of choice for NPC treatment due to its convenience.

Zusammenfassung

Zielsetzung

Diese Studie wurde durchgeführt, um die akuten und späten Toxizitäten zwischen intensitätsmodulierter Strahlentherapie (IMRT) mit sequenziell (SEQ) und simultan integriertem Boost (SIB) bei Nasopharynxkarzinom (NPK) zu vergleichen.

Methoden und Material

Patienten mit NPK im Stadium I–IV B wurden randomisiert einer SEQ-IMRT- oder SIB-IMRT-Therapie zugewiesen. Die SEQ-IMRT-Therapie bestand aus 2 Plänen: 2 Gy × 25 Fraktionen für das Planungszielvolumen (PZV) mit geringem Risiko, gefolgt von einem sequenziellen Boost (2 Gy × 10 Fraktionen) für das Hochrisiko-PZV, während PZV mit geringem und hohem Risiko mit SIB-IMRT mit Dosen von 56 und 70 Gy in 33 Fraktionen behandelt wurden. Es wurden Toxizitäten und Überlebensergebnisse analysiert.

Ergebnisse

Zwischen Oktober 2010 und September 2015 wurden von den 209 Patienten, die die Behandlung abschlossen, 102 im SEQ- und 107 im SIB-Arm analysiert. Die Mehrzahl der Patienten (82 %) wies ein undifferenziertes Plattenepithelkarzinom auf. Mukositis und Dysphagie waren die am häufigsten vorkommenden akuten Toxizitäten der Grade 3–5. Es gab keine statistisch signifikanten Unterschiede bei der kumulativen Inzidenz akuter Toxizitäten der Grade 3–4 zwischen den beiden Armen (59,8 % im SEQ- vs. 58,9 % im SIB-Arm; P = 0,892). Häufig auftretende Toxizitäten der Grade 3–4 für SEQ bzw. SIB umfassten Hörverlust (2,9 % bzw. 8,4 %), Temporallappenverletzung (2,9 % bzw. 0,9 %), Hirnnervenverletzung (0 % bzw. 2,8 %) und Xerostomie (2 % bzw. 0,9 %). Bei der Nachbeobachtung mit einer medianen Länge von 41 Monaten betrugen die Raten für 3 Jahre Progressionsfreiheit und die Gesamtüberlebensraten 72,7 % versus 73,4 % (P = 0,488) bzw. 86,3 % versus 83,6 % (P = 0,938).

Schlussfolgerung

SEQ und SIB bieten hervorragende Überlebensergebnisse mit nur wenigen späten Toxizitäten. Laut unserer Studie ist SIB mit einer zufriedenstellenden Dosis-Volumen-Beschränkung für nahegelegene kritische Organe aufgrund seiner Annehmlichkeit die Technik der Wahl für die NPK-Behandlung.

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

Similar content being viewed by others

Abbreviations

2D-RT:

two-dimensional RT

5-FU:

5-fluorouracil

AJCC:

American Joint Committee on Cancer

CRT:

conventional radiation therapy

CT:

computed tomography

CTCAE:

Common Terminology Criteria for Adverse Events

DMFS:

distant metastasis-free survival

Dmax :

maximum dose

DNA:

deoxyribonucleic acid

D1cc :

dose to 1 cc

D50% :

median dose

EBV:

Epstein–Barr virus

IMRT:

intensity-modulated radiation therapy

LPFS:

local progression-free survival

MRI:

magnetic resonance imaging

NPC:

nasopharyngeal carcinoma

OS:

overall survival

PET:

positron-emission tomography

PTV-LR:

low-risk planning target volume

PTV-HR:

high-risk planning target volume

PFS:

progression-free survival

RECIST:

Response Evaluation Criteria in Solid Tumors

RPFS:

regional progression-free survival

RTOG:

Radiation Therapy Oncology Group

SEQ-IMRT:

sequential intensity-modulated radiation therapy

SIB-IMRT:

simultaneous integrated boost intensity-modulated radiation therapy

SPSS:

Statistical Packages for Social Sciences

TLI:

temporal lobe injury

WHO:

World Health Organization

References

  1. Imsamran W, Chaiwerawattana A, Wiangnon S, et al (2015) Cancer in Thailand: Vol. VIII, 2010–2012. National Cancer Institute, Thailand

    Google Scholar 

  2. Eisbruch A, Ten Haken RK, Kim HM et al (1999) Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys 45:577–587

    Article  CAS  PubMed  Google Scholar 

  3. Xia P, Fu KK, Wong GW et al (2000) Comparison of treatment plans involving intensity-modulated radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 48:329–337

    Article  CAS  PubMed  Google Scholar 

  4. Hunt MA, Zelefsky MJ, Wolden S et al (2001) Treatment planning and delivery of intensity-modulated radiation therapy for primary nasopharynx cancer. Int J Radiat Oncol Biol Phys 49:623–632

    Article  CAS  PubMed  Google Scholar 

  5. Kam MK, Leung SF, Zee B et al (2007) Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol 25:4873–4879

    Article  PubMed  Google Scholar 

  6. Pow EH, Kwong DL, McMillan AS et al (2006) Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys 66:981–991

    Article  PubMed  Google Scholar 

  7. Peng G, Wang T, Yang KY 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 104:286–293

    Article  PubMed  Google Scholar 

  8. Lertbutsayanukul C, Khorprasert C, Shotelersuk K, et al (2006) Intensity-modulated radiation therapy in head-and-neck cancer, first report in Thailand. J Med Assoc Thai 89:2068–2076

    PubMed  Google Scholar 

  9. Songthong A, Chakkabat C, Kannarunimit D, et al (2015) Efficacy of intensity-modulated radiotherapy with concurrent carboplatin in nasopharyngeal carcinoma. Radiol Oncol 49:155–162

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lee N, Harris J, Garden AS et al (2009) Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial 0225. J Clin Oncol 27:3684–3690

    Article  PubMed  PubMed Central  Google Scholar 

  11. Wang R, Wu F, Lu H et al (2013) Definitive intensity-modulated radiation therapy for nasopharyngeal carcinoma: long-term outcome of a multicenter prospective study. J Cancer Res Clin Oncol 139:139–145

    Article  CAS  PubMed  Google Scholar 

  12. Butler EB, Teh BS, Grant WH et al (1999) Smart (simultaneous modulated accelerated radiation therapy) boost: a new accelerated fractionation schedule for the treatment of head and neck cancer with intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys 45:21–32

    Article  CAS  PubMed  Google Scholar 

  13. Chen SW, Yang SN, Liang JA et al (2005) Comparative dosimetric study of two strategies of intensity-modulated radiotherapy in nasopharyngeal cancer. Med Dosim 30:219–227

    Article  PubMed  Google Scholar 

  14. Dogan N, King S, Emami B et al (2003) Assessment of different IMRT boost delivery methods on target coverage and normal-tissue sparing. Int J Radiat Oncol Biol Phys 57:1480–1491

    Article  PubMed  Google Scholar 

  15. Wong FC, Ng AW, Lee VH et al (2010) Whole-field simultaneous integrated-boost intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 76:138–145

    Article  PubMed  Google Scholar 

  16. Wolden SL, Chen WC, Pfister DG et al (2006) Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: update of the Memorial Sloan-Kettering experience. Int J Radiat Oncol Biol Phys 64:57–62

    Article  PubMed  Google Scholar 

  17. Sun X, Su S, Chen C et al (2014) Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol 110:398–403

    Article  PubMed  Google Scholar 

  18. Tao H, Wei Y, Huang W et al (2016) Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma. Onco Targets Ther 9:1865–1873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Songthong AP, Kannarunimit D, Chakkabat C, et al (2015) A randomized phase II/III study of adverse events between sequential (SEQ) versus simultaneous integrated boost (SIB) intensity modulated radiation therapy (IMRT) in nasopharyngeal carcinoma; preliminary result on acute adverse events. Radiat Oncol 10:166

    Article  PubMed  PubMed Central  Google Scholar 

  20. Zheng Y, Han F, Xiao W et al (2015) Analysis of late toxicity in nasopharyngeal carcinoma patients treated with intensity modulated radiation therapy. Radiat Oncol 10:17

    Article  PubMed  PubMed Central  Google Scholar 

  21. Tang JM, Ma XM, Hou YL et al (2014) Analysis of simultaneous modulated accelerated radiotherapy (SMART) for nasopharyngeal carcinomas. J Radiat Res 55:794–802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Vlacich G, Stavas MJ, Pendyala P et al (2017) A comparative analysis between sequential boost and integrated boost intensity-modulated radiation therapy with concurrent chemotherapy for locally-advanced head and neck cancer. Radiat Oncol 12:13

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kuang WL, Zhou Q, Shen LF (2012) Outcomes and prognostic factors of conformal radiotherapy versus intensity-modulated radiotherapy for nasopharyngeal carcinoma. Clin Transl Oncol 14:783–790

    Article  PubMed  Google Scholar 

  24. Ou X, Zhou X, Shi Q et al (2015) Treatment outcomes and late toxicities of 869 patients with nasopharyngeal carcinoma treated with definitive intensity modulated radiation therapy: new insight into the value of total dose of cisplatin and radiation boost. Oncotarget 6:38381–38397

    PubMed  PubMed Central  Google Scholar 

  25. Blanco AI, Chao KS, El Naqa I et al (2005) Dose-volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy. Int J Radiat Oncol Biol Phys 62:1055–1069

    Article  PubMed  Google Scholar 

  26. Petsuksiri J, Sermsree A, Thephamongkhol K et al (2011) Sensorineural hearing loss after concurrent chemoradiotherapy in nasopharyngeal cancer patients. Radiat Oncol 6:19

    Article  PubMed  PubMed Central  Google Scholar 

  27. Su SF, Huang Y, Xiao WW et al (2012) Clinical and dosimetric characteristics of temporal lobe injury following intensity modulated radiotherapy of nasopharyngeal carcinoma. Radiother Oncol 104:312–316

    Article  PubMed  Google Scholar 

  28. 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 53:12–22

    Article  PubMed  Google Scholar 

  29. Tan WL, Tan EH, Lim DW et al (2016) Advances in systemic treatment for nasopharyngeal carcinoma. Chin Clin Oncol 5:21

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This research article is made possible through the help and support from significant advisors and industrious colleges. Thank you for Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society for providing the resources and funding for quantitative measurement of plasma EBV DNA level.

Funding

Grant no. RA 8/54, Ratchadapisek Sompoch Endowment Fund, Chulalongkorn University

Author information

Authors and Affiliations

  1. Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Rama IV Rd., Pathumwan, 1873, 10330, Bangkok, Thailand

    Chawalit Lertbutsayanukul Assoc. Prof., MD., Anussara Prayongrat MD, Danita Kannarunimit MD, Chakkapong Chakkabat MD, Buntipa Netsawang B.Sc. & Sarin Kitpanit MD

Authors
  1. Chawalit Lertbutsayanukul Assoc. Prof., MD.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anussara Prayongrat MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danita Kannarunimit MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chakkapong Chakkabat MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Buntipa Netsawang B.Sc.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sarin Kitpanit MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chawalit Lertbutsayanukul Assoc. Prof., MD..

Ethics declarations

Conflict of interest

C. Lertbutsayanukul, A. Prayongrat, D. Kannarunimit, C. Chakkabat, B. Netsawang, and S. Kitpanit declare that they have no competing interests.

Ethical standards

This study was approved by the institutional review board. Informed consent was obtained from every patient before entry into the study.

All participants gave their written consent.

Additional information

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors’ contributions

C. Lertbutsayanukul conceived of the study, participated in carrying out the study design and data acquisition, and drafted the manuscript. AP participated in its design and coordination together with C. Lertbutsayanukul and helped to draft and revise the manuscript. B. Netsawang and C. Lertbutsayanukul performed the statistical analysis. All authors participated in radiotherapy planning, treatment, evaluation, and follow-up. All authors read and approved the final manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lertbutsayanukul, C., Prayongrat, A., Kannarunimit, D. et al. A randomized phase III study between sequential versus simultaneous integrated boost intensity-modulated radiation therapy in nasopharyngeal carcinoma. Strahlenther Onkol 194, 375–385 (2018). https://doi.org/10.1007/s00066-017-1251-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-017-1251-5

Keywords

Schlüsselwörter

Search

Navigation