Correlation between egfr expression and accelerated proliferation during radiotherapy of head and neck squamous cell carcinoma

Piernicola Pedicini,Rocchina Caivano,Roberto Orecchia,Marco Salvatore,Francesca Botta,Antonio Nappi,Giovanni Storto,Marcello Benassi,Daniela Alterio,Lidia Strigari,Barbara Alicia Jereczek-Fossa,Alba Fiorentino,Giuseppina Improta,Marta Cremonesi,Barbara Vischioni

doi:10.1186/1748-717x-7-143

Abstract

PurposeTo investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr) and the reduction of the effective doubling time (TD) during radiotherapy treatment and also to determine the dose per fraction to be taken into account when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC).MethodsA survey of the published papers comparing 3-years of local regional control rate (LCR) for a total of 2162 patients treated with conventional and accelerated radiotherapy and with a pretreatment assessment of EGFr expression, was made. Different values of TD were obtained by a model incorporating the overall time corrected biologically effective dose (BED) and a 3-year clinical LCR for high and low EGFr groups of patients (HEGFr and LEGFr), respectively. By obtaining the TD from the above analysis and the sub-sites’ potential doubling time (Tpot) from flow cytometry and immunohistochemical methods, we were able to estimate the average TD for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (Dprolif), was estimated.ResultsThe averages of TD were 77 (27-90)95% days in LEGFr and 8.8 (7.3-11.0)95% days in HEGFr, if an onset of accelerated proliferation TK at day 21 was assumed. The correspondent HEGFr sub-sites’ TD were 5.9 (6.6), 5.9 (6.6), 4.6 (6.1), 14.3 (12.9) days, with respect to literature immunohistochemical (flow cytometry) data of Tpot for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The Dprolif for the HEGFr groups were 0.33 (0.29), 0.33 (0.29), 0.42 (0.31), 0.14 (0.15) Gy/day if α = 0.3 Gy-1 and α/β = 10 Gy were assumed.ConclusionsA higher expression of the EGFr leads to enhanced proliferation. This study allowed to quantify the extent of the effect which EGFr expression has in terms of reduced TD and Dprolif for each head and neck sub-site.

Highlights

head and neck squamous cell carcinoma (HNSCC) accelerates the production of clonogenic cells during radiotherapy, whereby an amount of a given dose of radiation may be used to sterilize cells produced during the treatment [1]
Epidermal Growth Factor receptor (EGFr) is overexpressed in the majority of HNSCC [4] and activation of the receptor leads to phosphorylation of the tyrosine kinase domains on the intracellular part of the receptor, activating downstream cascades which result in altered gene activation and modulation of the cell products
The aim of the present study is to investigate the correlation between EGFr expression and the reduction of TD during radiotherapy treatment and to determine the dose per fraction to be taken into account when the overall treatment time (OTT) is reduced in accelerated radiotherapy of HNSCC

Summary

Introduction

HNSCC accelerates the production of clonogenic cells during radiotherapy, whereby an amount of a given dose of radiation may be used to sterilize cells produced during the treatment [1]. EGFr is overexpressed in the majority of HNSCC [4] and activation of the receptor leads to phosphorylation of the tyrosine kinase domains on the intracellular part of the receptor, activating downstream cascades which result in altered gene activation and modulation of the cell products. This has been related to increased cell proliferation, decreased apoptotic activity, increased angiogenesis, increased invasive and metastatic potential, and increased resistance to anti tumour therapy

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