Clinical and dosimetric factors of radiation pneumonitis in patients with locally advanced non-small cell lung cancer_West China Medical Journal

Authors：

YIN Jianqiong ¹ , DENG Yifei ² , ZHOU Laiyan ¹ ,  XUE Jianxin ¹

1. Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Medical Oncology, the Seventh People’s Hospital of Chengdu, Chengdu, Sichuan 610044, P. R. China;

Corresponding author：

XUE Jianxin, Email: radjianxin@163.com

Keywords：

Non-small cell lung cancer; thoracic radiotherapy; radiation pneumonitis

DOI：

10.7507/1002-0179.202402159

Video：

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Objective To investigate the clinical factors and dosimetric parameters associated with grade≥2 radiation pneumonitis (RP) after thoracic radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). Methods The clinical factors and dosimetric parameters in patients with locally advanced NSCLC who received thoracic radiotherapy at West China Hospital of Sichuan University between January 2016 and January 2018 were retrospectively analyzed. The potential factors associated with the occurrence of grade≥2 RP were analyzed with logistic regression analysis. Results A total of 104 patients were included, and the incidence rate of grade≥2 RP was 19.2%. Multivariate logistic regression analysis showed that the percentage of the heart volume that received more than 20 Gy (V₂₀) [odds ratio (OR)=1.068, 95% confidence interval (CI) (1.004, 1.137), P=0.036], lung mean dose (D_mean) [OR=1.003, 95%CI (1.000, 1.006), P=0.031] and superior vena cava D_mean [OR=1.001, 95%CI (1.000, 1.001), P=0.041] were associated with grade≥2 RP. Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve combined with heart V₂₀, lung D_mean and superior vena cava D_mean to predict grade≥2 RP was 0.839 [95%CI (0.752, 0.926)]. In addition, the optimal critical values for heart V₂₀, lung D_mean and superior vena cava D_mean to predict grade≥2 RP were 20%, 13 Gy and 38 Gy, respectively. Conclusions Heart V₂₀, lung D_mean and superior vena cava D_mean are associated with grade≥2 RP after thoracic radiotherapy in patients with locally advanced NSCLC. In addition, taking heart V₂₀<20%, lung D_mean<13 Gy and superior vena cava D_mean<38 Gy as normal organ dose limits may reduce the risk of grade≥2 RP after thoracic radiotherapy for locally advanced NSCLC patients.

Citation： YIN Jianqiong, DENG Yifei, ZHOU Laiyan, XUE Jianxin. Clinical and dosimetric factors of radiation pneumonitis in patients with locally advanced non-small cell lung cancer. West China Medical Journal, 2024, 39(8): 1232-1237. doi: 10.7507/1002-0179.202402159 Copy

1.	Toi Y, Sugawara S, Kawashima Y, et al. Association of immune-related adverse events with clinical benefit in patients with advanced non-small-cell lung cancer treated with nivolumab. Oncologist, 2018, 23(11): 1358-1365.
2.	Palumbo B, Capozzi R, Bianconi F, et al. Classification model to estimate MIB-1 (Ki 67) proliferation index in NSCLC patients evaluated with ¹⁸F-FDG-PET/CT. Anticancer Res, 2020, 40(6): 3355-3360.
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5.	Liu F, Qiu B, Xi Y, et al. Efficacy of thymosin α1 in management of radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy: a phase 2 clinical trial (GASTO-1043). Int J Radiat Oncol Biol Phys, 2022, 114(3): 433-443.
6.	Bai L, Zhou BS, Zhao YX. Dynamic changes in T-cell subsets and C-reactive protein after radiation therapy in lung cancer patients and correlation with symptomatic radiation pneumonitis treated with steroid therapy. Cancer Manag Res, 2019, 11: 7925-7931.
7.	Shepherd AF, Iocolano M, Leeman J, et al. Clinical and dosimetric predictors of radiation pneumonitis in patients with non-small cell lung cancer undergoing postoperative radiation therapy. Pract Radiat Oncol, 2021, 11(1): e52-e62.
8.	Huang BT, Lin PX, Wang Y, et al. Developing a prediction model for radiation pneumonitis in lung cancer patients treated with stereotactic body radiation therapy combined with clinical, dosimetric factors, and laboratory biomarkers. Clin Lung Cancer, 2023, 24(8): e323-e331.e2.
9.	Ren C, Ji T, Liu T, et al. The risk and predictors for severe radiation pneumonitis in lung cancer patients treated with thoracic reirradiation. Radiat Oncol, 2018, 13(1): 69.
10.	McFarlane MR, Hochstedler KA, Laucis AM, et al. Predictors of pneumonitis after conventionally fractionated radiotherapy for locally advanced lung cancer. Int J Radiat Oncol Biol Phys, 2021, 111(5): 1176-1185.
11.	Yakar M, Etiz D, Metintas M, et al. Prediction of radiation pneumonitis with machine learning in stage Ⅲ lung cancer: a pilot study. Technol Cancer Res Treat, 2021, 20: 15330338211016373.
12.	Kelsey CR, Light KL, Marks LB. Patterns of failure after resection of non-small-cell lung cancer: implications for postoperative radiation therapy volumes. Int J Radiat Oncol Biol Phys, 2006, 65(4): 1097-1105.
13.	Kong FM, Ritter T, Quint DJ, et al. Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Int J Radiat Oncol Biol Phys, 2011, 81(5): 1442-1457.
14.	Kim H, Hwang J, Kim SM, et al. Risk factor analysis of the development of severe radiation pneumonitis in patients with non-small cell lung cancer treated with curative radiotherapy, with focus on underlying pulmonary disease. BMC Cancer, 2023, 23(1): 992.
15.	Lu X, Wang J, Zhang T, et al. Comprehensive pneumonitis profile of thoracic radiotherapy followed by immune checkpoint inhibitor and risk factors for radiation recall pneumonitis in lung cancer. Front Immunol, 2022, 13: 918787.
16.	Wu Y, Yang S, Liu H, et al. Novel genetic variants of KIR3DL2 and PVR involved in immunoregulatory interactions are associated with non-small cell lung cancer survival. Am J Cancer Res, 2020, 10(6): 1770-1784.
17.	Zhou D, Nakamura M, Mukumoto N, et al. Development of a deep learning-based patient-specific target contour prediction model for markerless tumor positioning. Med Phys, 2022, 49(3): 1382-1390.
18.	de Boer SM, Powell ME, Mileshkin L, et al. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol, 2019, 20(9): 1273-1285.
19.	Bensenane R, Helfre S, Cao K, et al. Optimizing lung cancer radiation therapy: a systematic review of multifactorial risk assessment for radiation-induced lung toxicity. Cancer Treat Rev, 2024, 124: 102684.
20.	Hanania AN, Mainwaring W, Ghebre YT, et al. Radiation-induced lung injury: assessment and management. Chest, 2019, 156(1): 150-162.
21.	Boonyawan K, Gomez DR, Komaki R, et al. Clinical and dosimetric factors predicting grade≥2 radiation pneumonitis after postoperative radiotherapy for patients with non-small cell lung carcinoma. Int J Radiat Oncol Biol Phys, 2018, 101(4): 919-926.
22.	Tang X, Li Y, Tian X, et al. Predicting severe acute radiation pneumonitis in patients with non-small cell lung cancer receiving postoperative radiotherapy: development and internal validation of a nomogram based on the clinical and dose-volume histogram parameters. Radiother Oncol, 2019, 132: 197-203.
23.	Wang H, Wei J, Zheng Q, et al. Radiation-induced heart disease: a review of classification, mechanism and prevention. Int J Biol Sci, 2019, 15(10): 2128-2138.
24.	Huang EX, Hope AJ, Lindsay PE, et al. Heart irradiation as a risk factor for radiation pneumonitis. Acta Oncol, 2011, 50(1): 51-60.
25.	Hahn E, Jiang H, Ng A, et al. Late cardiac toxicity after mediastinal radiation therapy for hodgkin lymphoma: contributions of coronary artery and whole heart dose-volume variables to risk prediction. Int J Radiat Oncol Biol Phys, 2017, 98(5): 1116-1123.
26.	Wong OY, Yau V, Kang J, et al. Survival impact of cardiac dose following lung stereotactic body radiotherapy. Clin Lung Cancer, 2018, 19(2): e241-e246.

1. Toi Y, Sugawara S, Kawashima Y, et al. Association of immune-related adverse events with clinical benefit in patients with advanced non-small-cell lung cancer treated with nivolumab. Oncologist, 2018, 23(11): 1358-1365.
2. Palumbo B, Capozzi R, Bianconi F, et al. Classification model to estimate MIB-1 (Ki 67) proliferation index in NSCLC patients evaluated with ¹⁸F-FDG-PET/CT. Anticancer Res, 2020, 40(6): 3355-3360.
3. Evison M, AstraZeneca UK Limited. The current treatment landscape in the UK for stage III NSCLC. Br J Cancer, 2020, 123(Suppl 1): 3-9.
4. Men Y, Wang L, Zhang Y, et al. Trends of postoperative radiotherapy for completely resected non-small cell lung cancer in China: a hospital-based multicenter 10-year (2005-2014) retrospective clinical epidemiological study. Front Oncol, 2019, 9: 786.
5. Liu F, Qiu B, Xi Y, et al. Efficacy of thymosin α1 in management of radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy: a phase 2 clinical trial (GASTO-1043). Int J Radiat Oncol Biol Phys, 2022, 114(3): 433-443.
6. Bai L, Zhou BS, Zhao YX. Dynamic changes in T-cell subsets and C-reactive protein after radiation therapy in lung cancer patients and correlation with symptomatic radiation pneumonitis treated with steroid therapy. Cancer Manag Res, 2019, 11: 7925-7931.
7. Shepherd AF, Iocolano M, Leeman J, et al. Clinical and dosimetric predictors of radiation pneumonitis in patients with non-small cell lung cancer undergoing postoperative radiation therapy. Pract Radiat Oncol, 2021, 11(1): e52-e62.
8. Huang BT, Lin PX, Wang Y, et al. Developing a prediction model for radiation pneumonitis in lung cancer patients treated with stereotactic body radiation therapy combined with clinical, dosimetric factors, and laboratory biomarkers. Clin Lung Cancer, 2023, 24(8): e323-e331.e2.
9. Ren C, Ji T, Liu T, et al. The risk and predictors for severe radiation pneumonitis in lung cancer patients treated with thoracic reirradiation. Radiat Oncol, 2018, 13(1): 69.
10. McFarlane MR, Hochstedler KA, Laucis AM, et al. Predictors of pneumonitis after conventionally fractionated radiotherapy for locally advanced lung cancer. Int J Radiat Oncol Biol Phys, 2021, 111(5): 1176-1185.
11. Yakar M, Etiz D, Metintas M, et al. Prediction of radiation pneumonitis with machine learning in stage Ⅲ lung cancer: a pilot study. Technol Cancer Res Treat, 2021, 20: 15330338211016373.
12. Kelsey CR, Light KL, Marks LB. Patterns of failure after resection of non-small-cell lung cancer: implications for postoperative radiation therapy volumes. Int J Radiat Oncol Biol Phys, 2006, 65(4): 1097-1105.
13. Kong FM, Ritter T, Quint DJ, et al. Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Int J Radiat Oncol Biol Phys, 2011, 81(5): 1442-1457.
14. Kim H, Hwang J, Kim SM, et al. Risk factor analysis of the development of severe radiation pneumonitis in patients with non-small cell lung cancer treated with curative radiotherapy, with focus on underlying pulmonary disease. BMC Cancer, 2023, 23(1): 992.
15. Lu X, Wang J, Zhang T, et al. Comprehensive pneumonitis profile of thoracic radiotherapy followed by immune checkpoint inhibitor and risk factors for radiation recall pneumonitis in lung cancer. Front Immunol, 2022, 13: 918787.
16. Wu Y, Yang S, Liu H, et al. Novel genetic variants of KIR3DL2 and PVR involved in immunoregulatory interactions are associated with non-small cell lung cancer survival. Am J Cancer Res, 2020, 10(6): 1770-1784.
17. Zhou D, Nakamura M, Mukumoto N, et al. Development of a deep learning-based patient-specific target contour prediction model for markerless tumor positioning. Med Phys, 2022, 49(3): 1382-1390.
18. de Boer SM, Powell ME, Mileshkin L, et al. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol, 2019, 20(9): 1273-1285.
19. Bensenane R, Helfre S, Cao K, et al. Optimizing lung cancer radiation therapy: a systematic review of multifactorial risk assessment for radiation-induced lung toxicity. Cancer Treat Rev, 2024, 124: 102684.
20. Hanania AN, Mainwaring W, Ghebre YT, et al. Radiation-induced lung injury: assessment and management. Chest, 2019, 156(1): 150-162.
21. Boonyawan K, Gomez DR, Komaki R, et al. Clinical and dosimetric factors predicting grade≥2 radiation pneumonitis after postoperative radiotherapy for patients with non-small cell lung carcinoma. Int J Radiat Oncol Biol Phys, 2018, 101(4): 919-926.
22. Tang X, Li Y, Tian X, et al. Predicting severe acute radiation pneumonitis in patients with non-small cell lung cancer receiving postoperative radiotherapy: development and internal validation of a nomogram based on the clinical and dose-volume histogram parameters. Radiother Oncol, 2019, 132: 197-203.
23. Wang H, Wei J, Zheng Q, et al. Radiation-induced heart disease: a review of classification, mechanism and prevention. Int J Biol Sci, 2019, 15(10): 2128-2138.
24. Huang EX, Hope AJ, Lindsay PE, et al. Heart irradiation as a risk factor for radiation pneumonitis. Acta Oncol, 2011, 50(1): 51-60.
25. Hahn E, Jiang H, Ng A, et al. Late cardiac toxicity after mediastinal radiation therapy for hodgkin lymphoma: contributions of coronary artery and whole heart dose-volume variables to risk prediction. Int J Radiat Oncol Biol Phys, 2017, 98(5): 1116-1123.
26. Wong OY, Yau V, Kang J, et al. Survival impact of cardiac dose following lung stereotactic body radiotherapy. Clin Lung Cancer, 2018, 19(2): e241-e246.

West China Medical Journal

Clinical and dosimetric factors of radiation pneumonitis in patients with locally advanced non-small cell lung cancer

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