Skip to main content
Top
Published in: Radiation Oncology 1/2020

01-12-2020 | Lung Cancer | Research

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

Authors: 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

Published in: Radiation Oncology | Issue 1/2020

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Auperin A, Le Pechoux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:2181–90.CrossRef Auperin A, Le Pechoux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:2181–90.CrossRef
2.
go back to reference Machtay M, Paulus R, Moughan J, Komaki R, Bradley JE, Choy H, et al. Defining local-regional control and its importance in locally advanced non-small cell lung carcinoma. J Thorac Oncol. 2012;7:716–22.CrossRef Machtay M, Paulus R, Moughan J, Komaki R, Bradley JE, Choy H, et al. Defining local-regional control and its importance in locally advanced non-small cell lung carcinoma. J Thorac Oncol. 2012;7:716–22.CrossRef
3.
go back to reference Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16:187–99.CrossRef Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16:187–99.CrossRef
4.
go back to reference Liao ZX, Komaki RR, Thames HD Jr, Liu HH, Tucker SL, Mohan R, et al. Influence of technologic advances on outcomes in patients with unresectable, locally advanced non-small-cell lung cancer receiving concomitant chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2010;76:775–81.CrossRef Liao ZX, Komaki RR, Thames HD Jr, Liu HH, Tucker SL, Mohan R, et al. Influence of technologic advances on outcomes in patients with unresectable, locally advanced non-small-cell lung cancer receiving concomitant chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2010;76:775–81.CrossRef
5.
go back to reference Li Q-W, Qiu B, Wang B, Zhang J, Chen L, Zhou Y, et al. Comparison of hyper- and hypofractionated radiation schemes with IMRT technique in small cell lung cancer: clinical outcomes and the introduction of extended LQ and TCP models. Radiother Oncol. 2019;136:98–105.CrossRef Li Q-W, Qiu B, Wang B, Zhang J, Chen L, Zhou Y, et al. Comparison of hyper- and hypofractionated radiation schemes with IMRT technique in small cell lung cancer: clinical outcomes and the introduction of extended LQ and TCP models. Radiother Oncol. 2019;136:98–105.CrossRef
6.
go back to reference Mehta N, King CR, Agazaryan N, Steinberg M, Hua A, Lee P. Stereotactic body radiation therapy and 3-dimensional conformal radiotherapy for stage I non-small cell lung cancer: a pooled analysis of biological equivalent dose and local control. Pract Radiat Oncol. 2012;2:288–95.CrossRef Mehta N, King CR, Agazaryan N, Steinberg M, Hua A, Lee P. Stereotactic body radiation therapy and 3-dimensional conformal radiotherapy for stage I non-small cell lung cancer: a pooled analysis of biological equivalent dose and local control. Pract Radiat Oncol. 2012;2:288–95.CrossRef
7.
go back to reference Tai A, Liu F, Gore E, Li XA. An analysis of tumor control probability of stereotactic body radiation therapy for lung cancer with a regrowth model. Phys Med Biol. 2016;61:3903–13.CrossRef Tai A, Liu F, Gore E, Li XA. An analysis of tumor control probability of stereotactic body radiation therapy for lung cancer with a regrowth model. Phys Med Biol. 2016;61:3903–13.CrossRef
8.
go back to reference Liu F, Tai A, Lee P, Biswas T, Ding GX, El Naqa I, et al. Tumor control probability modeling for stereotactic body radiation therapy of early-stage lung cancer using multiple bio-physical models. Radiother Oncol. 2017;122:286–94.CrossRef Liu F, Tai A, Lee P, Biswas T, Ding GX, El Naqa I, et al. Tumor control probability modeling for stereotactic body radiation therapy of early-stage lung cancer using multiple bio-physical models. Radiother Oncol. 2017;122:286–94.CrossRef
9.
go back to reference Ma L, Qiu B, Li Q, Chen L, Wang B, Hu Y, et al. An esophagus-sparing technique to limit radiation esophagitis in locally advanced non-small cell lung cancer treated by simultaneous integrated boost intensity-modulated radiotherapy and concurrent chemotherapy. Radiat Oncol. 2018;13:130.CrossRef Ma L, Qiu B, Li Q, Chen L, Wang B, Hu Y, et al. An esophagus-sparing technique to limit radiation esophagitis in locally advanced non-small cell lung cancer treated by simultaneous integrated boost intensity-modulated radiotherapy and concurrent chemotherapy. Radiat Oncol. 2018;13:130.CrossRef
10.
go back to reference Fowler JF. The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol. 1989;62:679–94.CrossRef Fowler JF. The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol. 1989;62:679–94.CrossRef
11.
go back to reference Lea DE. Actions of radiations on living cells. London: Cambridge University Press; 1946. Lea DE. Actions of radiations on living cells. London: Cambridge University Press; 1946.
12.
go back to reference Sachs RK, Hlatky LR, Hahnfeldt P. Simple ODE models of tumour growth and anti-angiogenic or radiation treatment. Mathl Comput Model. 2001;33:1297–305.CrossRef Sachs RK, Hlatky LR, Hahnfeldt P. Simple ODE models of tumour growth and anti-angiogenic or radiation treatment. Mathl Comput Model. 2001;33:1297–305.CrossRef
13.
go back to reference Brenner DJ, Hlatky LR, Hahnfeldt PJ, Hall EJ, Sachs RK. A convenient extension of the linear-quadratic model to include redistribution and reoxygenation. Int J Radiat Oncol Biol Phys. 1995;32:379–90.CrossRef Brenner DJ, Hlatky LR, Hahnfeldt PJ, Hall EJ, Sachs RK. A convenient extension of the linear-quadratic model to include redistribution and reoxygenation. Int J Radiat Oncol Biol Phys. 1995;32:379–90.CrossRef
14.
go back to reference Speer JF, Petrosky VE, Retsky MW, Wardwell RH. A stochastic numerical model of breast cancer growth that simulates clinical data. Cancer Res. 1984;44:4124–30.PubMed Speer JF, Petrosky VE, Retsky MW, Wardwell RH. A stochastic numerical model of breast cancer growth that simulates clinical data. Cancer Res. 1984;44:4124–30.PubMed
15.
go back to reference Thames HD Jr, Peters LJ, Withers HR, Fletcher GH. Accelerated fractionation vs hyperfractionation: rationales for several treatments per day. Int J Radiat Oncol Biol Phys. 1983;9:127–38.CrossRef Thames HD Jr, Peters LJ, Withers HR, Fletcher GH. Accelerated fractionation vs hyperfractionation: rationales for several treatments per day. Int J Radiat Oncol Biol Phys. 1983;9:127–38.CrossRef
16.
go back to reference Moraru IC, Tai A, Erickson B, Li XA. Radiation dose responses for chemoradiation therapy of pancreatic cancer: an analysis of compiled clinical data using biophysical models. Pract Radiat Oncol. 2014;4:13–9.CrossRef Moraru IC, Tai A, Erickson B, Li XA. Radiation dose responses for chemoradiation therapy of pancreatic cancer: an analysis of compiled clinical data using biophysical models. Pract Radiat Oncol. 2014;4:13–9.CrossRef
17.
go back to reference Bates DM, Watts DG. Nonlinear regression analysis and its applications; 1988.CrossRef Bates DM, Watts DG. Nonlinear regression analysis and its applications; 1988.CrossRef
18.
go back to reference Mauguen A, Le Pechoux C, Saunders MI, Schild SE, Turrisi AT, Baumann M, et al. Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis. J Clin Oncol. 2012;30:2788–97.CrossRef Mauguen A, Le Pechoux C, Saunders MI, Schild SE, Turrisi AT, Baumann M, et al. Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis. J Clin Oncol. 2012;30:2788–97.CrossRef
19.
go back to reference Kaster TS, Yaremko B, Palma DA, Rodrigues GB. Radical-intent hypofractionated radiotherapy for locally advanced non-small-cell lung cancer: a systematic review of the literature. Clin Lung Cancer. 2015;16:71–9.CrossRef Kaster TS, Yaremko B, Palma DA, Rodrigues GB. Radical-intent hypofractionated radiotherapy for locally advanced non-small-cell lung cancer: a systematic review of the literature. Clin Lung Cancer. 2015;16:71–9.CrossRef
20.
go back to reference Kong FM, Ten Haken RK, Schipper M, Frey KA, Hayman J, Gross M, et al. Effect of Midtreatment PET/CT-adapted radiation therapy with concurrent chemotherapy in patients with locally advanced non-small-cell lung cancer: a phase 2 clinical trial. JAMA Oncol. 2017;3:1358–65.CrossRef Kong FM, Ten Haken RK, Schipper M, Frey KA, Hayman J, Gross M, et al. Effect of Midtreatment PET/CT-adapted radiation therapy with concurrent chemotherapy in patients with locally advanced non-small-cell lung cancer: a phase 2 clinical trial. JAMA Oncol. 2017;3:1358–65.CrossRef
21.
go back to reference Withers HR, Taylor JM, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol. 1988;27:131–46.CrossRef Withers HR, Taylor JM, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol. 1988;27:131–46.CrossRef
22.
go back to reference Machtay M, Bae K, Movsas B, Paulus R, Gore EM, Komaki R, et al. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non-small cell lung carcinoma treated with chemoradiation: an analysis of the radiation therapy oncology group. Int J Radiat Oncol Biol Phys. 2012;82:425–34.CrossRef Machtay M, Bae K, Movsas B, Paulus R, Gore EM, Komaki R, et al. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non-small cell lung carcinoma treated with chemoradiation: an analysis of the radiation therapy oncology group. Int J Radiat Oncol Biol Phys. 2012;82:425–34.CrossRef
23.
go back to reference Fowler JF, Chappell R. Non-small cell lung tumors repopulate rapidly during radiation therapy. Int J Radiat Oncol Biol Phys. 2000;46:516–7.CrossRef Fowler JF, Chappell R. Non-small cell lung tumors repopulate rapidly during radiation therapy. Int J Radiat Oncol Biol Phys. 2000;46:516–7.CrossRef
24.
go back to reference Steel GG. Basic clinical radiobiology, 3rd edn. London: Arnold; 2002. Steel GG. Basic clinical radiobiology, 3rd edn. London: Arnold; 2002.
25.
go back to reference Fowler JF. Biological factors influencing optimum fractionation in radiation therapy. Acta Oncol. 2001;40:712–7.CrossRef Fowler JF. Biological factors influencing optimum fractionation in radiation therapy. Acta Oncol. 2001;40:712–7.CrossRef
26.
go back to reference Chun SG, Hu C, Choy H, Komaki RU, Timmerman RD, Schild SE, et al. Impact of intensity-modulated radiation therapy technique for locally advanced non-small-cell lung cancer: a secondary analysis of the NRG oncology RTOG 0617 randomized clinical trial. J Clin Oncol. 2017;35:56–62.CrossRef Chun SG, Hu C, Choy H, Komaki RU, Timmerman RD, Schild SE, et al. Impact of intensity-modulated radiation therapy technique for locally advanced non-small-cell lung cancer: a secondary analysis of the NRG oncology RTOG 0617 randomized clinical trial. J Clin Oncol. 2017;35:56–62.CrossRef
Metadata
Title
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
Authors
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
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2020
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-020-01555-x

Other articles of this Issue 1/2020

Radiation Oncology 1/2020 Go to the issue