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Strahlentherapie und Onkologie

, Volume 194, Issue 5, pp 375–385 | Cite as

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

  • Chawalit LertbutsayanukulEmail author
  • Anussara Prayongrat
  • Danita Kannarunimit
  • Chakkapong Chakkabat
  • Buntipa Netsawang
  • Sarin Kitpanit
Original Article

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.

Keywords

IMRT with simultaneous integrated boost IMRT with sequential boost Nasopharyngeal carcinoma Survival Toxicities 

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

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

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.

Schlüsselwörter

IMRT mit simultan integriertem Boost IMRT mit sequenziellem Boost Nasopharynxkarzinom Überleben Toxizitäten 

Notes

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

Compliance with ethical guidelines

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.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Radiation Oncology, Department of Radiology, Faculty of MedicineKing Chulalongkorn Memorial Hospital, Chulalongkorn UniversityBangkokThailand

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