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

Purpose: To investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr) and the reduction of the effective doubling time (T-D) 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). Methods: A 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 T-D 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 (H-EGFr and L-EGFr), respectively. By obtaining the TD from the above analysis and the sub-sites' potential doubling time (T-pot) from flow cytometry and immunohistochemical methods, we were able to estimate the average T-D for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (D-prolif), was estimated. Results: The averages of T-D were 77 (27-90)(95%) days in L-EGFr and 8.8 (7.3-11.0)(95%) days in H-EGFr, if an onset of accelerated proliferation T-K at day 21 was assumed. The correspondent H-EGFr sub-sites' T-D 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 T-pot for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The D-prolif for the H-EGFr groups were 0.33 (0.29), 0.33 (0.29), 0.42 (0.31), 0.14 (0.15) Gy/day if a = 0.3 Gy(-1) and alpha/beta = 10 Gy were assumed. Conclusions: A 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 T-D and D-prolif for each head and neck sub-site.