Assessment of radiation pneumonitis and predictive factors in patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy
DOI:
https://doi.org/10.2340/1651-226X.2024.40576Keywords:
radiation pneumonitis, Non-Small Cell Lung Cancer, chemoradiotherapy, predictive factors, recovery rateAbstract
Purpose: Radiation pneumonitis (RP) is a dose-limiting toxicity associated with increased mortality for patients with non-small cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT). This study aims to assess the incidence of symptomatic RP (grade 2–5), rate of recovery and associated predictive factors.
Material and methods: We performed a retrospective population-based study including 602 patients with NSCLC who were treated with CRT between 2002 and 2016. RP and rate of recovery were analysed using Common Terminology Criteria for Adverse Events version 4.0. Stepwise logistic regression was performed to analyse potential predictive factors for the two endpoints RP grade ≥ 2 and RP grade ≥ 3.
Results: A total of 136 (23%) patients developed symptomatic RP and 37 (6%) developed RP grade ≥ 3. A total of 67 (71%) recovered, whereas the remaining 27 (29%), with the major proportion of patients belonging to the RP grade ≥ 3 group, suffered from prevailing sequelae. On multivariable analysis, the selected model for predicting RP grade ≥ 2 included the factors V20, smoking status, average fractions per week and chemotherapy agent. V20 and age were selected factors for RP grade ≥ 3.
Interpretation: The results suggest that regardless of all proposed factors predictive for RP, the most important influenceable significant factor still is dose to the lung. The main aim should be to avoid RP grade ≥ 3, where a substantial proportion of patients suffer from prevailing sequalae. Consequently, the technical improvement and precision of radiotherapy delivery should continue to focus on lung sparing techniques also in the ongoing immunotherapy-containing schedules where the risk of pneumonitis may be increased.
e factor still is dose to the lung. Consequently, the technical improvement and precision of radiotherapy delivery should continue to focus on lung sparing techniques also in the ongoing immunotherapy-containing schedules where the risk of pneumonitis may be increased.
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Yoon SM, Shaikh T, Hallman M. Therapeutic management options for stage III non-small cell lung cancer. World J Clin Oncol. 2017;8(1):1.
https://doi.org/10.5306/wjco.v8.i1.1 DOI: https://doi.org/10.5306/wjco.v8.i1.1
Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. N Engl J Med. 2017;377(20):1919–29.
https://doi.org/10.1056/NEJMoa1709937 DOI: https://doi.org/10.1056/NEJMoa1709937
Stervik L, Pettersson N, Scherman J, Behrens CF, Ceberg C, Engelholm S, et al. Analysis of early respiratory-related mortality after radiation therapy of non-small-cell lung cancer: feasibility of automatic data extraction for dose–response studies. Acta Oncol. 2020;59(6):628–35.
https://doi.org/10.1080/0284186X.2020.1739331 DOI: https://doi.org/10.1080/0284186X.2020.1739331
Shi A, Zhu G, Wu H, Yu R, Li F, Xu B. Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy. Radiat Oncol. 2010;5(1):35.
https://doi.org/10.1186/1748-717X-5-35 DOI: https://doi.org/10.1186/1748-717X-5-35
Institute UDoHaHSNIoHNC. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 2009 [updated May 28, 2009 (v4.03: June 14, 2010)]. [Cited date: 17 Sep 2023] Available from: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
Palma DA, Senan S, Tsujino K, Barriger RB, Rengan R, Moreno M, et al. Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2013;85(2):444–50.
https://doi.org/10.1016/j.ijrobp.2012.04.043 DOI: https://doi.org/10.1016/j.ijrobp.2012.04.043
Park YH, Kim J-S. Predictors of radiation pneumonitis and pulmonary function changes after concurrent chemoradiotherapy of non-small cell lung cancer. Radiat Oncol J. 2013;31(1):34.
https://doi.org/10.3857/roj.2013.31.1.34
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(2):187–99. DOI: https://doi.org/10.1016/S1470-2045(14)71207-0
https://doi.org/10.3857/roj.2013.31.1.34 DOI: https://doi.org/10.3857/roj.2013.31.1.34
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(1):56–62.
https://doi.org/10.1200/JCO.2016.69.1378 DOI: https://doi.org/10.1200/JCO.2016.69.1378
Marks LB, Bentzen SM, Deasy JO, Kong FM, Bradley JD, Vogelius IS, et al. Radiation dose-volume effects in the lung. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S70–6.
https://doi.org/10.1016/j.ijrobp.2009.06.091 DOI: https://doi.org/10.1016/j.ijrobp.2009.06.091
Mehta V. Radiation pneumonitis and pulmonary fibrosis in non–small-cell lung cancer: pulmonary function, prediction, and prevention. Int J Radiat Oncol Biol Phys. 2005;63(1):5–24.
https://doi.org/10.1016/j.ijrobp.2005.03.047 DOI: https://doi.org/10.1016/j.ijrobp.2005.03.047
Vogelius IR, Bentzen SM. A literature-based meta-analysis of clinical risk factors for development of radiation induced pneumonitis. Acta Oncol. 2012;51(8):975–83.
https://doi.org/10.3109/0284186X.2012.718093 DOI: https://doi.org/10.3109/0284186X.2012.718093
Torre-Bouscoulet L, Muñoz-Montaño WR, Martínez-Briseño D, Lozano-Ruiz FJ, Fernández-Plata R, Beck-Magaña JA, et al. Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer. Respir Res. 2018;19(1):72. DOI: https://doi.org/10.1186/s12931-018-0775-2
Tsujino K, Hashimoto T, Shimada T, Yoden E, Fujii O, Ota Y, et al. Combined analysis of V20, VS5, pulmonary fibrosis score on baseline computed tomography, and patient age improves prediction of severe radiation pneumonitis after concurrent chemoradiotherapy for locally advanced non–small-cell lung cancer. J Thorac Oncol. 2014;9(7):983–90. DOI: https://doi.org/10.1097/JTO.0000000000000187
Heinze G, Wallisch C, Dunkler D. Variable selection–a review and recommendations for the practicing statistician. Biom J. 2018;60(3):431–49.
https://doi.org/10.1002/bimj.201700067 DOI: https://doi.org/10.1002/bimj.201700067
Wang S, Liao Z, Wei X, Liu HH, Tucker SL, Hu C-s, et al. Analysis of clinical and dosimetric factors associated with treatment-related pneumonitis (TRP) in patients with non–small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT). Int J Radiat Oncol Biol Phys. 2006;66(5):1399–407.
https://doi.org/10.1016/j.ijrobp.2006.07.1337 DOI: https://doi.org/10.1016/j.ijrobp.2006.07.1337
Graham MV, Purdy JA, Emami B, Harms W, Bosch W, Lockett MA, et al. Clinical dose–volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys. 1999;45(2):323–9.
https://doi.org/10.1016/S0360-3016(99)00183-2 DOI: https://doi.org/10.1016/S0360-3016(99)00183-2
Hernando ML, Marks LB, Bentel GC, Zhou S-M, Hollis D, Das SK, et al. Radiation-induced pulmonary toxicity: a dose-volume histogram analysis in 201 patients with lung cancer. Int J Radiat Oncol Biol Phy. 2001;51(3):650–9.
https://doi.org/10.1016/S0360-3016(01)01685-6 DOI: https://doi.org/10.1016/S0360-3016(01)01685-6
Dang J, Li G, Zang S, Zhang S, Yao L. Risk and predictors for early radiation pneumonitis in patients with stage III non-small cell lung cancer treated with concurrent or sequential chemoradiotherapy. Radiat Oncol. 2014;9:172.
https://doi.org/10.1186/1748-717X-9-172 DOI: https://doi.org/10.1186/1748-717X-9-172
Wang JY, Chen KY, Wang JT, Chen JH, Lin JW, Wang HC, et al. Outcome and prognostic factors for patients with non-small-cell lung cancer and severe radiation pneumonitis. Int J Radiat Oncol Biol Phys. 2002;54(3):735–41.
https://doi.org/10.1016/S0360-3016(02)02994-2 DOI: https://doi.org/10.1016/S0360-3016(02)02994-2
Kuang Y, Pierce CM, Chang HC, Sosinsky AZ, Deitz AC, Keller SM et al. Chemoradiation-induced pneumonitis in patients with unresectable stage III non-small cell lung cancer: A systematic literature review and meta-analysis. Lung Cancer. 2022 Dec;174:174-185. doi: 10.1016/j.lungcan.2022.06.005. Epub 2022 Jun 11. PMID: 35717343. DOI: https://doi.org/10.1016/j.lungcan.2022.06.005
Dang J, Li G, Ma L, Diao R, Zang S, Han C, et al. Predictors of grade ≥ 2 and grade ≥ 3 radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with three-dimensional conformal radiotherapy. Acta Oncol (Stockholm, Sweden). 2013;52(6):1175–80.
https://doi.org/10.3109/0284186X.2012.747696 DOI: https://doi.org/10.3109/0284186X.2012.747696
Gao RW, Day CN, Yu NY, Bush A, Amundson AC, Prodduturvar P, et al. Dosimetric predictors of pneumonitis in locally advanced non-small cell lung cancer patients treated with chemoradiation followed by durvalumab. Lung Cancer. 2022;170:58–64.
https://doi.org/10.1016/j.lungcan.2022.06.003 DOI: https://doi.org/10.1016/j.lungcan.2022.06.003
Diamond BH, Belani N, Masel R, DeCarli K, DiPetrillo T, Hepel JT, et al. Predictors of pneumonitis in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiation followed by consolidative Durvalumab. Adv Radiat Oncol. 2023;8(2):101130.
https://doi.org/10.1016/j.adro.2022.101130 DOI: https://doi.org/10.1016/j.adro.2022.101130
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Copyright (c) 2023 Kerstin Gunnarsson, Louise Mövik, Niclas Pettersson, Anna Bäck, Jan Nyman, Andreas Hallqvist
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