Radiation dose intensity and local tumour control of non-small cell lung cancer: A radiobiological modelling perspective

Abstract

Several clinical situations call for the use of radiobiological principles as powerful clinical tools. The aim of this project is to examine the effect of radiotherapy dose intensity on local tumour control for non-small cell lung cancer (NSCLC) using the biological effective dose (BED) concept. A two-year tumour control probability (TCP) model was developed based on the linear-quadratic cell concept combined with Poisson statistics. The two-year local control outcome was analysed for the radiotherapy dose using the BEDs. The BED calculations and the TCP model were fitted to a series of NSCLC patients drawn from the literature. The investigation is based on the two-year local tumour control rate for stage I-II NSCLC for a dose fractionation size that varied from 1.5-20 Gy per fraction delivered via three radiotherapy treatments: 3D-conformal radiation therapy (3D-CRT), continuous hyperfractionated accelerated radiotherapy (CHART) and stereotactic ablative body radiotherapy (SABR). The BED values of 2,280 patients were computed and analysed as a function of local tumour control. To quantitatively assess the correlation between the BED and local tumour control, a residuals analysis and linear regression were performed. Higher radiotherapy doses were associated with improved local tumour control and survival rates for NSCLC, as suggested by the coefficient of the correlation R2 statistical test: 0.83 for the 3D-CRT and 0.91 for the SABR treatment.

Locally advanced non-small cell lung cancer: current issues and recent trends

“…encompasses main bronchus irrespective of distance from the carina but without including the carina invades visceral pleura associated with atelectasis or obstructive pneumonitis that extends to the hilar region, including part or the entire lung T3 Tumour > 5 cm but ≤ 7 cm in the greatest dimension that meets either of the following particular conditions: invades either of the following particular organs; chest wall, phrenic nerve, and parietal pericardium associated with separate tumour nodule(s) in the same lobe as the primary tumour T4 Tumour > 7 cm in the greatest dimension that meets either of the following particular conditions: invades either of the following particular organs; diaphragm, mediastinum, great vessels, heart, recurrent laryngeal nerve, esophagus, carina or vertebral body associated with separate tumour nodule(s) in a different ipsilateral lobe than that of the primary tumour tionately with the expanding tumour size and that the radiation dose required to attain local tumour curability relies on the logarithm of surviving clonogenic cells to be deactivated. Zips [19] observed a linear diminution of clonogenic density as radiotherapy doses increase, corroborating the results of Alaswad et al [20,21]. It is also evident that tumours become more radioresistant under hypoxic states, and hypoxia is more prevalent in large tumours than in small tumours [22,23].…”

A theoretical cell-killing model to evaluate oxygen enhancement ratios at DNA damage and cell survival endpoints in radiation therapy

“…In these regards, to consider the progression of oxygen effects, a more biologically detailed model based on DNA damage yield than the conventional LQ model 13 is necessary. When compared to many available models for hypoxia, 10,11,28,29 the integrated microdosimetric-kinetic (IMK) model [30][31][32][33] has unique features such as involvement of DNA damage kinetics 34,35 and the cell-cycle phase. 31 The model is suitable for estimating radio-sensitivity under chronic lower oxygen pressure.…”