Abstract
Purpose
Severe acute radiation pneumonitis (SARP) is a life-threatening complication of thoracic radiotherapy. Pre-treatment pulmonary function (PF) may influence its incidence. We have previously reported on the incidence of SARP among patients with moderate pulmonary dysfunction who received definitive concurrent chemoradiotherapy (dCCRT) for non-small cell lung cancer (NSCLC).
Methods
The clinical outcomes, dose–volume histograms (DVH), and PF parameters of 122 patients (forced expiratory volume in 1 s [FEV1%]: 60–69%) receiving dCCRT between 2013 and 2019 were recorded. SARP was defined as grade ≥3 RP occurring during or within 3 months after CCRT. Logistic regression, receiver operating characteristics curves (ROC), and hazard ratio (HR) analyses were performed to evaluate the predictive value of each factor for SARP.
Results
Univariate and multivariate analysis indicated that the ratio of carbon monoxide diffusing capacity (DLCO%; odds ratio [OR]: 0.934, 95% confidence interval [CI] 0.896–0.974, p = 0.001) and mean lung dose (MLD; OR: 1.002, 95% CI 1.001–1.003, p = 0.002) were independent predictors of SARP. The ROC AUC of combined DLCO%/MLD was 0.775 (95% confidence interval [CI]: 0.688–0.861, p = 0.001), with a sensitivity and specificity of 0.871 and 0.637, respectively; this was superior to DLCO% (0.656) or MLD (0.667) alone. Compared to the MLD-low/DLCO%-high group, the MLD-high/DLCO%-low group had the highest risk for SARP, with an HR of 9.346 (95% CI: 2.133–40.941, p = 0.003).
Conclusion
The DLCO% and MLD may predict the risk for SARP among patients with pre-treatment moderate pulmonary dysfunction who receive dCCRT for NSCLC. Prospective studies are needed to validate our findings.
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References
Sause W, Kolesar P, Taylor S et al (2000) Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest 117:358–364. https://doi.org/10.1378/chest.117.2.358
Aupérin A, Le Péchoux C, Rolland E et al (2010) Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 28:2181–2190. https://doi.org/10.1200/JCO.2009.26.2543
Semrau S, Bier A, Thierbach U et al (2003) Concurrent radiochemotherapy with vinorelbine plus cisplatin or carboplatin in patients with locally advanced non-small-cell lung cancer (NSCLC) and anincreased risk of treatment complications. Strahlenther Onkol 179:823–831. https://doi.org/10.1007/s00066-003-1127-8
Kong F‑M, Hayman JA, Griffith KA et al (2006) Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC): Predictors for radiation pneumonitis and fibrosis. Int J Radiat Oncol Biol Phys 65:1075–1086. https://doi.org/10.1016/j.ijrobp.2006.01.051
Kong F‑M, Wang S (2015) Nondosimetric risk factors for radiation-induced lung toxicity. Semin Radiat Oncol 25:100–109. https://doi.org/10.1016/j.semradonc.2014.12.003
Tsujino K, Hashimoto T, Shimada T et al (2014) 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 9:983–990. https://doi.org/10.1097/JTO.0000000000000187
Wang J, Cao J, Yuan S et al (2013) Poor baseline pulmonary function may not increase the risk of radiation-induced lung toxicity. Int J Radiat Oncol Biol Phys 85:798–804. https://doi.org/10.1016/j.ijrobp.2012.06.040
Palma DA, Senan S, Tsujino K et al (2013) Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys 85:444–450. https://doi.org/10.1016/j.ijrobp.2012.04.043
Zhang X‑J, Sun J‑G, Sun J et al (2012) Prediction of radiation pneumonitis in lung cancer patients: a systematic review. J Cancer Res Clin Oncol 138:2103–2116. https://doi.org/10.1007/s00432-012-1284-1
Shi A, Zhu G, Wu H et al (2010) 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 5:35. https://doi.org/10.1186/1748-717X-5-35
Torre-Bouscoulet L, Muñoz-Montaño WR, Martínez-Briseño D et al (2018) Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung cancer. Respir Res 19:72. https://doi.org/10.1186/s12931-018-0775-2
Jin H, Tucker SL, Liu HH et al (2009) Dose-volume thresholds and smoking status for the risk of treatment-related pneumonitis in inoperable non-small cell lung cancer treated with definitive radiotherapy. Radiother Oncol 91:427–432. https://doi.org/10.1016/j.radonc.2008.09.009
Papi A, Casoni G, Caramori G et al (2004) COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma. Thorax 59:679. https://doi.org/10.1136/thx.2003.018291
Skillrud DM, Offord KP, Miller RD (1986) Higher risk of lung cancer in chronic obstructive pulmonary disease. A prospective, matched, controlled study. Ann Intern Med 105:503–507. https://doi.org/10.7326/0003-4819-105-4-503
Vogelmeier CF, Criner GJ, Martinez FJ et al (2017) Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med 195:557–582. https://doi.org/10.1164/rccm.201701-0218PP
National Clinical Guideline C (2010) National Institute for Health and Clinical Excellence: Guidance. In: Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care. Royal College of Physicians (UK) National Clinical Guideline Centre—Acute and Chronic Conditions, London
Dehing-Oberije C, De Ruysscher D, van Baardwijk A et al (2009) The importance of patient characteristics for the prediction of radiation-induced lung toxicity. Radiother Oncol 91:421–426. https://doi.org/10.1016/j.radonc.2008.12.002
Chen S, Zhou S, Zhang J et al (2007) A neural network model to predict lung radiation-induced pneumonitis. Med Phys 34:3420–3427. https://doi.org/10.1118/1.2759601
Ferrero C, Badellino S, Filippi AR et al (2015) Pulmonary function and quality of life after VMAT-based stereotactic ablative radiotherapy for early stage inoperable NSCLC: a prospective study. Cancer Treat Res 89:350–356. https://doi.org/10.1016/j.lungcan.2015.06.019
Laszlo G (2006) Standardisation of lung function testing: helpful guidance from the ATS/ERS Task Force. Thorax 61:744–746. https://doi.org/10.1136/thx.2006.061648
Seppenwoolde Y, De Jaeger K, Boersma LJ et al (2004) Regional differences in lung radiosensitivity after radiotherapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 60:748–758. https://doi.org/10.1016/j.ijrobp.2004.04.037
Hope AJ, Lindsay PE, El Naqa I et al (2006) Modeling radiation pneumonitis risk with clinical, dosimetric, and spatial parameters. Int J Radiat Oncol Biol Phys 65:112–124. https://doi.org/10.1016/j.ijrobp.2005.11.046
Morgan-Fletcher SL (2001) Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50), ICRU Report 62. ICRU, pp. ix+52, 1999 (ICRU Bethesda, MD) $65.00 ISBN 0‑913394-61‑0. Brit J Radiol 74:294–294. https://doi.org/10.1259/bjr.74.879.740294
Hodapp N (2012) The ICRU Report 83: prescribing, recording and reporting photon-beam intensity-modulated radiation therapy (IMRT). Strahlenther Onkol 188:97–99. https://doi.org/10.1007/s00066-011-0015-x
Jiang X, Li T, Liu Y et al (2011) Planning analysis for locally advanced lung cancer: dosimetric and efficiency comparisons between intensity-modulated radiotherapy (IMRT), single-arc/partial-arc volumetric modulated arc therapy (SA/PA-VMAT). Radiat Oncol 6:140. https://doi.org/10.1186/1748-717x-6-140
Xiao J, Zhang H, Gong Y et al (2010) Feasibility of using intravenous contrast-enhanced computed tomography (CT) scans in lung cancer treatment planning. Radiother Oncol 96:73–77. https://doi.org/10.1016/j.radonc.2010.02.029
Ettinger DS, Wood DE, Aisner DL et al (2017) Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 15:504–535. https://doi.org/10.6004/jnccn.2017.0050
National Cancer Institute (2010) Common terminology criteria for adverse events (CTCAE) version 4.03. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed 14 June 2010
Martel MK, Ten Haken RK, Hazuka MB et al (1994) Dose-volume histogram and 3‑D treatment planning evaluation of patients with pneumonitis. Int J Radiat Oncol Biol Phys 28:575–581. https://doi.org/10.1016/0360-3016(94)90181-3
Graham MV, Purdy JA, Emami B et al (1999) Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 45:323–329. https://doi.org/10.1016/s0360-3016(99)00183-2
Hernando ML, Marks LB, Bentel GC et al (2001) Radiation-induced pulmonary toxicity: a dose-volume histogram analysis in 201 patients with lung cancer. Int J Radiat Oncol Biol Phys 51:650–659. https://doi.org/10.1016/s0360-3016(01)01685-6
Claude L, Perol D, Ginestet C et al (2004) A prospective study on radiation pneumonitis following conformal radiation therapy in non-small-cell lung cancer: clinical and dosimetric factors analysis. Radiother Oncol 71:175–181. https://doi.org/10.1016/j.radonc.2004.02.005
Rancati T, Ceresoli GL, Gagliardi G et al (2003) Factors predicting radiation pneumonitis in lung cancer patients: a retrospective study. Radiother Oncol 67:275–283. https://doi.org/10.1016/s0167-8140(03)00119-1
Fay M, Tan A, Fisher R et al (2005) Dose-volume histogram analysis as predictor of radiation pneumonitis in primary lung cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys 61:1355–1363. https://doi.org/10.1016/j.ijrobp.2004.08.025
Lee HJ Jr., Zeng J, Vesselle HJ et al (2018) Correlation of functional lung heterogeneity and dosimetry to radiation pneumonitis using perfusion SPECT/CT and FDG PET/CT imaging. Int J Radiat Oncol Biol Phys 102:1255–1264. https://doi.org/10.1016/j.ijrobp.2018.05.051
Videtic GM, Stitt LW, Ash RB et al (2004) Impaired diffusion capacity predicts for decreased treatment tolerance and survival in limited stage small cell lung cancer patients treated with concurrent chemoradiation. Cancer Treat Res 43:159–166. https://doi.org/10.1016/j.lungcan.2003.08.026
Lopez Guerra JL, Gomez D, Zhuang Y et al (2012) Change in diffusing capacity after radiation as an objective measure for grading radiation pneumonitis in patients treated for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 83:1573–1579. https://doi.org/10.1016/j.ijrobp.2011.10.065
Guckenberger M, Kestin LL, Hope AJ et al (2012) Is there a lower limit of pretreatment pulmonary function for safe and effective stereotactic body radiotherapy for early-stage non-small cell lung cancer? J Thorac Oncol 7:542–551. https://doi.org/10.1097/JTO.0b013e31824165d7
Chen H, Senan S, Nossent EJ et al (2017) Treatment-related toxicity in patients with early-stage non-small cell lung cancer and coexisting interstitial lung disease: a systematic review. Int J Radiat Oncol Biol Phys 98:622–631. https://doi.org/10.1016/j.ijrobp.2017.03.010
Plummer AL (2008) The carbon monoxide diffusing capacity: clinical implications, coding, and documentation. Chest 134:663–667. https://doi.org/10.1378/chest.07-1771
Fleckenstein K, Zgonjanin L, Chen L et al (2007) Temporal onset of hypoxia and oxidative stress after pulmonary irradiation. Int J Radiat Oncol Biol Phys 68:196–204. https://doi.org/10.1016/j.ijrobp.2006.12.056
Vujaskovic Z, Anscher MS, Feng QF et al (2001) Radiation-induced hypoxia may perpetuate late normal tissue injury. Int J Radiat Oncol Biol Phys 50:851–855. https://doi.org/10.1016/s0360-3016(01)01593-0
Lopez Guerra JL, Gomez DR, Zhuang Y et al (2012) Changes in pulmonary function after three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, or proton beam therapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 83:e537–543. https://doi.org/10.1016/j.ijrobp.2012.01.019
Stanic S, Paulus R, Timmerman RD et al (2014) No clinically significant changes in pulmonary function following stereotactic body radiation therapy for early- stage peripheral non-small cell lung cancer: an analysis of RTOG 0236. Int J Radiat Oncol Biol Phys 88:1092–1099. https://doi.org/10.1016/j.ijrobp.2013.12.050
Guckenberger M, Klement RJ, Kestin LL et al (2013) Lack of a dose-effect relationship for pulmonary function changes after stereotactic body radiation therapy for early-stage non-small cell lung cancer. Int J Radiat Oncol Biol Phys 85:1074–1081. https://doi.org/10.1016/j.ijrobp.2012.09.016
Schroder C, Engenhart-Cabillic R, Vorwerk H et al (2017) Changes in pulmonary function and influencing factors after high-dose intrathoracic radio(chemo)therapy. Strahlenther Onkol 193:125–131. https://doi.org/10.1007/s00066-016-1067-8
Cella L, D’Avino V, Palma G et al (2015) Modeling the risk of radiation-induced lung fibrosis: Irradiated heart tissue is as important as irradiated lung. Radiother Oncol 117:36–43. https://doi.org/10.1016/j.radonc.2015.07.051
Yorke ED, Jackson A, Kuo LC et al (2017) Heart dosimetry is correlated with risk of radiation pneumonitis after lung-sparing hemithoracic pleural intensity modulated radiation therapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 99:61–69. https://doi.org/10.1016/j.ijrobp.2017.04.025
Tucker SL, Liao Z, Dinh J et al (2014) Is there an impact of heart exposure on the incidence of radiation pneumonitis? Analysis of data from a large clinical cohort. Acta Oncol 53:590–596. https://doi.org/10.3109/0284186x.2013.831185
Bradley JD, Paulus R, Komaki R et al (2015) 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 16:187–199. https://doi.org/10.1016/s1470-2045(14)71207-0
Kong FM, Frey KA, Quint LE et al (2007) A pilot study of [18F] fluorodeoxyglucose positron emission tomography scans during and after radiation-based therapy in patients with non small-cell lung cancer. J Clin Oncol 25:3116–3123. https://doi.org/10.1200/jco.2006.10.3747
Mahasittiwat P, Yuan S, Xie C et al (2013) metabolic tumor volume on PET reduced more than gross tumor volume on ct during radiotherapy in patients with non-small cell lung cancer treated with 3DCRT or SBRT. J Radiat Oncol 2:191–202. https://doi.org/10.1007/s13566-013-0091-x
Kong FM, Ten Haken RK, Schipper M et al (2017) 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 3:1358–1365. https://doi.org/10.1001/jamaoncol.2017.0982
Liang J, Bi N, Wu S et al (2017) Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol 28:777–783. https://doi.org/10.1093/annonc/mdx009
Funding
This project was supported by a grant from Sichuan Provincial Science and Technology Funding to Youling Gong (2018SZ0184). This work has been selected to be presented partly in digital poster form at the American Society for Radiation Oncology Annual Meeting, 2019.
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Youling Gong conceived and designed the study. Yin Zhou, Tiansheng Yan, Xiaojuan Zhou, Peng Cao, Chunli Luo, and Youling Gong collected the data. Yin Zhou, Tiansheng Yan, and Youling Gong analyzed and interpreted the data and drafted the article. Lin Zhou, Yong Xu, Yongmei Liu, Jianxin Xue, Jin Wang, Yongsheng Wang, You Lu, and Binmiao Liang critically revised the paper. All of the authors approved the final submitted version.
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Y. Zhou, T. Yan, X. Zhou, P. Cao, C. Luo, L. Zhou, Y. Xu, Y. Liu, J. Xue, J. Wang, Y. Wang, Y. Lu, B. Liang, and Y. Gong declare that they have no competing interests.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee (West China Hospital of Sichuan University Biomedical Research Ethics Committee) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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The authors Ying Zhou and Tiansheng Yan contributed equally to the manuscript.
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Zhou, Y., Yan, T., Zhou, X. et al. Acute severe radiation pneumonitis among non-small cell lung cancer (NSCLC) patients with moderate pulmonary dysfunction receiving definitive concurrent chemoradiotherapy: Impact of pre-treatment pulmonary function parameters. Strahlenther Onkol 196, 505–514 (2020). https://doi.org/10.1007/s00066-019-01552-4
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DOI: https://doi.org/10.1007/s00066-019-01552-4