Investigating the loco-regional control of simultaneous integrated boost intensity-modulated radiotherapy with different radiation fraction sizes for locally advanced non-small-cell lung cancer: clinical outcomes and the application of an extended LQ/TCP model

Bo Qiu, Qi Wen Li, Xin Lei Ai, Bin Wang, Jian Huan, Zheng Fei Zhu, Gen Hua Yu, Ming Ji, Hai Hang Jiang, Cheng Li, Jun Zhang, Li Chen, Jin Yu Guo, Yin Zhou, Hui Liu, Bo Qiu, Qi Wen Li, Xin Lei Ai, Bin Wang, Jian Huan, Zheng Fei Zhu, Gen Hua Yu, Ming Ji, Hai Hang Jiang, Cheng Li, Jun Zhang, Li Chen, Jin Yu Guo, Yin Zhou, Hui Liu

Abstract

Background: To investigate the loco-regional progression-free survival (LPFS) of intensity-modulated radiotherapy (IMRT) with different fraction sizes for locally advanced non-small-cell lung cancer (LANSCLC), and to apply a new radiobiological model for tumor control probability (TCP).

Methods: One hundred and three LANSCLC patients treated with concurrent radiochemotherapy were retrospectively analyzed. Factors potentially predictive of LPFS were assessed in the univariate and multivariate analysis. Patients were divided into group A (2.0 ≤ fraction size<2.2Gy), B (2.2 ≤ fraction size<2.5Gy), and C (2.5 ≤ fraction size≤3.1Gy) according to the tertiles of fraction size. A novel LQRG/TCP model, incorporating four "R"s of radiobiology and Gompertzian tumor growth, was developed to predict LPFS and compared with the classical LQ/TCP model.

Results: With a median follow-up of 22.1 months, the median LPFS was 23.8 months. Fraction size was independently prognostic of LPFS. The median LPFS of group A, B and C was 13.8, 35.7 months and not reached, respectively. Using the new LQRG/TCP model, the average absolute and relative fitting errors for LPFS were 6.9 and 19.6% for group A, 5.5 and 8.8% for group B, 6.6 and 9.5% for group C, compared with 9.5 and 29.4% for group A, 16.6 and 36.7% for group B, 24.8 and 39.1% for group C using the conventional LQ/TCP model.

Conclusions: Hypo-fractionated IMRT could be an effective approach for dose intensification in LANSCLC. Compared with conventional LQ model, the LQRG model showed a better performance in predicting follow-up time dependent LPFS.

Keywords: Fraction size; Hypo-fractionation; Locally advanced non-small-cell lung cancer; Loco-regional progression-free survival; Tumor control probability model.

Conflict of interest statement

The authors declare that they have no competing financial interests.

Figures

Fig. 1
Fig. 1
Model fitting to LPFS data using (a) the classical LQ and TCP models, or (b) the new LQRG and TCP
Fig. 2
Fig. 2
Model fitting to the LPFS data versus BED. The classical LQ and TCP models fitting to LPFS data at (a) 13th month and at (c) 48th month. The new LQRG and TCP model fitting to LPFS data at (b) 13th month and at (d) 48th month

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