open access

Vol 71, No 2 (2021)
Review paper
Published online: 2021-04-06
Get Citation

Has fractionation in head and neck cancer radiotherapy reached a summit or is there still room for novel therapeutic strategies?

Bogusław Maciejewski, Leszek Miszczyk, Krzysztof Składowski
DOI: 10.5603/NJO.2021.0022
·
Nowotwory. Journal of Oncology 2021;71(2):94-102.

open access

Vol 71, No 2 (2021)
Review article
Published online: 2021-04-06

Abstract

The aim of this paper is to answer to the question whether various dose fractionation regimens are highly effective up to the summit of normal tissue tolerance. Data from 45 trials on altered fractionation, radio-response of the HPV(+) oropharyngeal cancer (OPC) and concurrent chemoradiation (11 533 data) have been selected from the published papers and re-analysed.

Altered fractionation regimens showed an average therapeutic gain (TG) of local tumour control (LTC) of about 2.7% per each 1 izoGy2.0 above 65 Gy. For HPV(+) OPC, TG increased by 3–3.5%/1izoGy2.0. Concurrent chemoradiation for locally advanced H&N cancer produced about 60% LTC using 65 Gy (about 20% more than altered RT). Despite randomization, data sets in the trials remain clinically and biologically heterogeneous. It is not possible to separate the TG rate as the result of change in dose per fraction from that caused by changing the overall treatment time. This is major weakness of the trials.

Moreover, the results are presented as an average value of the LTC or survival. The overstepped tolerance summit is very rarely precisely presented. It likely seems that the tolerance summit is not a single value and is only partly related to dose fractionation intensity, it mainly depends on radiosensitivity and the irradiation volume of normal tissue(s) and their potential repair capacity, and an activation of immunological defense. Finally, it is difficult to accept average trial’ results as evidence based guidelines for personalized radiotherapy for individual patients; what is more the individual tolerance summit is not universal and well quantified.

Abstract

The aim of this paper is to answer to the question whether various dose fractionation regimens are highly effective up to the summit of normal tissue tolerance. Data from 45 trials on altered fractionation, radio-response of the HPV(+) oropharyngeal cancer (OPC) and concurrent chemoradiation (11 533 data) have been selected from the published papers and re-analysed.

Altered fractionation regimens showed an average therapeutic gain (TG) of local tumour control (LTC) of about 2.7% per each 1 izoGy2.0 above 65 Gy. For HPV(+) OPC, TG increased by 3–3.5%/1izoGy2.0. Concurrent chemoradiation for locally advanced H&N cancer produced about 60% LTC using 65 Gy (about 20% more than altered RT). Despite randomization, data sets in the trials remain clinically and biologically heterogeneous. It is not possible to separate the TG rate as the result of change in dose per fraction from that caused by changing the overall treatment time. This is major weakness of the trials.

Moreover, the results are presented as an average value of the LTC or survival. The overstepped tolerance summit is very rarely precisely presented. It likely seems that the tolerance summit is not a single value and is only partly related to dose fractionation intensity, it mainly depends on radiosensitivity and the irradiation volume of normal tissue(s) and their potential repair capacity, and an activation of immunological defense. Finally, it is difficult to accept average trial’ results as evidence based guidelines for personalized radiotherapy for individual patients; what is more the individual tolerance summit is not universal and well quantified.

Get Citation

Keywords

radiotherapy and chemoradiation regimens; weaknesses and benefits; tolerance summits

About this article
Title

Has fractionation in head and neck cancer radiotherapy reached a summit or is there still room for novel therapeutic strategies?

Journal

Nowotwory. Journal of Oncology

Issue

Vol 71, No 2 (2021)

Article type

Review paper

Pages

94-102

Published online

2021-04-06

DOI

10.5603/NJO.2021.0022

Bibliographic record

Nowotwory. Journal of Oncology 2021;71(2):94-102.

Keywords

radiotherapy and chemoradiation regimens
weaknesses and benefits
tolerance summits

Authors

Bogusław Maciejewski
Leszek Miszczyk
Krzysztof Składowski

References (28)
  1. Thames H. On the origin of dose fractionation regimens in radiotherapy. Seminars in Radiation Oncology. 1992; 2(1): 3–9.
  2. Suit H. The Gray Lecture 2001: coming technical advances in radiation oncology. Int J Radiat Oncol Biol Phys. 2002; 53(4): 798–809.
  3. Dragun AE. Altered fractionation schedules. in Principles and Practice of Radiation Oncology. 7th ed. Wolter Kluwer, Philadelphia 2018: 308–328.
  4. Ang KK. Altered fractionation schedules. In: Perez CA, Brady LW. ed. Principles and Practice of Radiation Oncology. Lippincot. Raven Publ 1998: 119–142.
  5. Lacas B, Bourhis J, Overgaard J, et al. MARCH Collaborative Group, MARCH Collaborative Group, 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. 2006; 368(9538): 843–854.
  6. Lucas SB, Bourhis J, Overgaard J, et al. Role of radiotherapy fractionation in head and neck cancer (MARCH): an updated meta-analyses. Lancet Oncol. 2017; 18(9): 1–17.
  7. Glatstein E. Personal thoughts on statistics, or lies, damn lies, and (oncologic) statistics. Int J Radiat Oncol Biol Phys. 2004; 58(5): 1329–1333.
  8. Glatstein E. The return of the snake oil salesmen. Int J Radiat Oncol Biol Phys. 2003; 55(3): 561–562.
  9. Glatstein E. Black, White, or Shades of Gray? Int J Radiat Oncol Biol Phys. 2008; 72(5): 1307.
  10. Saunders MI, Rojas AM, Parmar MKB, et al. CHART Trial Collaborators. Mature results of a randomized trial of accelerated hyperfractionated versus conventional radiotherapy in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2010; 77(1): 3–8.
  11. O'Sullivan B, Huang SH, Perez-Ordonez B, et al. Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy alone using altered fractionation. Radiother Oncol. 2012; 103(1): 49–56.
  12. Huang SH, O'Sullivan B, Waldron J. The Current State of Biological and Clinical Implications of Human Papillomavirus-Related Oropharyngeal Cancer. Semin Radiat Oncol. 2018; 28(1): 17–26.
  13. Maciejewski B, Składowski K. A review of combined treatment strategies for HPV(+), p16(+) oropharyngeal cancer – is de-escalated radiotherapy a convincing and promising paradigm? Nowotwory. Journal of Oncology. 2020; 70(6): 236–243.
  14. Chera BS, Amdur RJ, Tepper J, et al. Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. Int J Radiat Oncol Biol Phys. 2015; 93(5): 976–985.
  15. Brizel D. Radiotherapy and concurrent chemotherapy for the treatment of locally advanced head and neck squamous cell carcinoma. Semin Radiat Oncol. 1998; 8(4): 237–246.
  16. Bernier J, Bentzen SM. Altered fractionation and combined radio-chemotherapy approaches: pioneering new opportunities in head and neck oncology. Eur J Cancer. 2003; 39(5): 560–571.
  17. Bernier J. Current state-of-the-art for concurrent chemoradiation. Semin Radiat Oncol. 2009; 19(1): 3–10.
  18. Denis F, Garaud P, Bardet E, et al. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 2004; 22(1): 69–76.
  19. Brizel DM, Vokes EE. Induction chemotherapy: to use or not to use? That is the question. Semin Radiat Oncol. 2009; 19(1): 11–16.
  20. Pignon JP, Bourhis J, Domenge C, et al. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 2000; 355(9208): 949–955.
  21. Kaanders JH, van der Kogel AJ, Ang KK. Altered fractionation: limited by mucosal reactions? Radiother Oncol. 1999; 50(3): 247–260.
  22. Blanchard P, Baujat B, Holostenco V. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol. 2011; 100(1): 33–40.
  23. Glatstein E. The omega on alpha and beta. Int J Radiat Oncol Biol Phys. 2011; 81(2): 319–320.
  24. Fowler J, Chappell R, Ritter M. Is α/β for prostate tumors really low? Int J Radiat Oncol Biol Phys. 2001; 50(4): 1021–1031.
  25. Fowler JF, Tomé WA, Fenwick JD, et al. A challenge to traditional radiation oncology. Int J Radiat Oncol Biol Phys. 2004; 60(4): 1241–1256.
  26. De La. Proton radiation therapy. Semin Radiat Oncol. 2018; 28: 75–160.
  27. Maciejewski B, Suwiński R. Blamek S. Hipofrakcjonowana radiochirurgia stereotaktyczna. w. Radiobiologia kliniczna w radioonkologii. Medycyna Praktyczna. ; 2019: 99–103.
  28. Składowski K. Personal communication.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Wydawcą serwisu jest VM Media sp. z o.o. VM Group sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl