The role of hypofractionated radiotherapy in the management of head and neck cancer - a modelling approach

Loredana G Marcu; David Marcu

doi:10.1016/j.jtbi.2019.109998

The role of hypofractionated radiotherapy in the management of head and neck cancer - a modelling approach

J Theor Biol. 2019 Dec 7:482:109998. doi: 10.1016/j.jtbi.2019.109998. Epub 2019 Sep 4.

Authors

Loredana G Marcu¹, David Marcu²

Affiliations

¹ Faculty of Science, University of Oradea, Oradea 410087, Romania; Division of Health Sciences, University of South Australia, SA 5005, Australia. Electronic address: loredana@marcunet.com.
² Faculty of Science, University of Oradea, Oradea 410087, Romania.

PMID: 31493484
DOI: 10.1016/j.jtbi.2019.109998

Abstract

Introduction: Cancer stem cells (CSCs) and hypoxia are key contributors towards radioresistance and they influence the choice of radiotherapy schedule for optimal tumour control. Since hypofractionation is becoming more popular in head and neck cancer (HNC) management, the aim of this work is to use a modelling approach to evaluate the efficacy of hypofractionated radiotherapy on both early stage and advanced tumours.

Methods: An in silico HNC was developed starting from one CSC. For a biologically indorsed tumour, CSCs generate all heterogeneous cell lineages with a 1.9% probability of symmetrical division, 33 h mean cell cycle time and 52 days volume doubling time. The simulated schedules include conventional, hyperfractionated, and hypofractionated radiotherapy and they target tumours with various oxygenation levels.

Results: Oxic and mildly hypoxic tumours can benefit from hypofractionation, which reduces treatment time without increasing adverse events. Advanced tumours are only controlled by hyperfractionation, however a tumour with oxygen levels below 6 mmHg and 5.9% pre-treatment CSCs, needs either a dose greater than 81.6 Gy to be eradicated or the addition of adjuvant therapies.

Conclusions: Hypofractionation is suited for early stage tumours, whereas aggressive HNC require hyperfractionation. The interplay between CSCs and hypoxia dictates the optimal treatment strategy.

Keywords: Cancer stem cells; Hypoxia; In silico model; Radioresistance; Treatment regimen.

MeSH terms

Cell Proliferation / radiation effects*
Computer Simulation
Head and Neck Neoplasms / pathology
Head and Neck Neoplasms / radiotherapy*
Humans
Models, Biological*
Monte Carlo Method
Neoplasm Recurrence, Local / pathology
Neoplasm Recurrence, Local / radiotherapy
Neoplastic Stem Cells / pathology
Neoplastic Stem Cells / physiology
Neoplastic Stem Cells / radiation effects
Radiation Dose Hypofractionation*
Radiation Tolerance / physiology
Squamous Cell Carcinoma of Head and Neck / pathology
Squamous Cell Carcinoma of Head and Neck / radiotherapy*
Tumor Burden / radiation effects
Tumor Cells, Cultured