Radiation Pneumonitis Following Thoracic Radiotherapy: A Systematic Review

Authors

  • Lionel Sirait Universitas Sumatera Utara

DOI:

https://doi.org/10.47134/phms.v3i3.611

Keywords:

Dosimetric Parameters, Lung Cancer, Pulmonary Toxicity, Radiation Pneumonitis, Thoracic Radiotherapy

Abstract

Radiation pneumonitis (RP) is a clinically significant and dose-limiting complication of thoracic radiotherapy, occurring despite modern delivery techniques. Its incidence and severity are influenced by a complex interplay of dosimetric, clinical, and patient-related factors, particularly in those receiving combined-modality therapies or with pre-existing pulmonary disease.Aim: To systematically summarize the incidence, risk factors, and predictive strategies for RP in patients undergoing thoracic radiotherapy, with emphasis on clinical, dosimetric, and emerging biological predictors. A PRISMA-guided literature search of PubMed/MEDLINE was conducted from inception to January 2026 using MeSH terms related to radiation pneumonitis and thoracic radiotherapy. Original research studies involving adult patients treated with thoracic radiotherapy and reporting RP-related outcomes were included. Owing to substantial heterogeneity across studies, findings were qualitatively synthesized rather than pooled quantitatively.  Twelve studies comprising approximately 1,298 patients were included. All studies demonstrated a strong association between lung dose-volume parameters and RP development. Maintaining lung V20 at approximately 20–23% was associated with lower symptomatic RP, with grade ≥2 incidence ranging from 5.5% to 13.3%. Patients with interstitial lung disease or idiopathic pulmonary fibrosis exhibited substantially higher risk, with RP ≥2 reported in up to 33% and severe RP in up to 42.1%. Emerging predictive models incorporating radiomics and biomarkers achieved AUC values up to 0.87. Lung dose exposure remains a key determinant of RP following thoracic radiotherapy. Limiting V20 to 20–23% may reduce toxicity, but individualized dose optimization, careful patient selection, and advanced risk stratification are essential — particularly in patients with underlying pulmonary disease or those receiving concurrent systemic therapies.

References

Aerts, H. J. W. L. (2016). The potential of radiomic-based phenotyping in precision medicine. JAMA Oncology, 2(12), 1636–1642. DOI: https://doi.org/10.1001/jamaoncol.2016.2631

Aoki, S., Onishi, H., Karube, M., Yamamoto, N., Yamashita, H., & Shioyama, Y. (2023). Comparative analysis of photon stereotactic radiotherapy and carbon-ion radiotherapy for elderly patients with stage I non-small-cell lung cancer. Cancers (Basel), 15(14), 3633. DOI: https://doi.org/10.3390/cancers15143633

Bi, J., Qian, J., Yang, D., Sun, L., Lin, S., & Li, Y. (2022). Dosimetric risk factors for acute radiation pneumonitis in patients with prior receipt of immune checkpoint inhibitors. Frontiers in Immunology, 12, 828858. DOI: https://doi.org/10.3389/fimmu.2021.828858

Bradley, J., & Movsas, B. (2016). Radiation pneumonitis and esophagitis in thoracic irradiation. Cancer Treatment Research, 170, 43–64. DOI: https://doi.org/10.1007/0-387-25354-8_4

Graham, M. V, Purdy, J. A., Emami, B., Harms, W. B., Bosch, W. R., & Lockett, M. A. (1999). Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer. International Journal of Radiation Oncology Biology Physics, 45(2), 323–329. DOI: https://doi.org/10.1016/S0360-3016(99)00183-2

Huang, J. W., Lin, Y. H., Chang, G. C., & Chen, J. J. W. (2023). A novel tool to evaluate and quantify radiation pneumonitis: correlation of dosimetric parameters with pneumonia patch volume. Frontiers in Oncology, 13, 1130406. DOI: https://doi.org/10.3389/fonc.2023.1130406

Hwang, J., Kim, H., Kim, S. M., & Yang, D. S. (2024). Imaging complexity biomarkers for predicting severe radiation pneumonitis in NSCLC patients with idiopathic pulmonary fibrosis. Life (Basel), 14(7), 897. DOI: https://doi.org/10.3390/life14070897

Kim, H., Hwang, J., Kim, S. M., Choi, J., & Yang, D. S. (2024). Computed tomography patterns and clinical outcomes of radiation pneumonitis in non-small-cell lung cancer patients. Acta Radiologica Open, 13(10), 20584601241288504. DOI: https://doi.org/10.1177/20584601241288502

Kong, F.-M., Ten Haken, R. K., Schipper, M. J., Sullivan, M. A., Chen, M., & Lopez, C. (2005). High-dose radiation improved local tumor control and overall survival in patients with inoperable non-small-cell lung cancer. International Journal of Radiation Oncology Biology Physics, 63(2), 324–333. DOI: https://doi.org/10.1016/j.ijrobp.2005.02.010

Kong, F.-M., Zhao, J., Wang, J., & Faivre-Finn, C. (2021). Radiation-induced lung injury: current evidence and future directions. Seminars in Radiation Oncology, 31(2), 155–161. DOI: https://doi.org/10.1016/j.semradonc.2020.11.006

Lambin, P., Leijenaar, R. T. H., Deist, T. M., Peerlings, J., de Jong, E. E. C., & van Timmeren, J. (2017). Radiomics: the bridge between medical imaging and personalized medicine. Nature Reviews Clinical Oncology, 14(12), 749–762. DOI: https://doi.org/10.1038/nrclinonc.2017.141

Liu, L., Gao, C., Yang, Y., Tang, M., Zhao, T., & Chen, D. (2025). Induction immunochemotherapy followed by radiotherapy for unresectable locally advanced NSCLC. Radiation Oncology, 20(1), 37. DOI: https://doi.org/10.1186/s13014-025-02616-9

Marks, L. B., Bentzen, S. M., Deasy, J. O., Kong, F.-M., Bradley, J. D., & Vogelius, I. S. (2010). Radiation dose-volume effects in the lung. International Journal of Radiation Oncology Biology Physics, 76(3 Suppl), S70–S76. DOI: https://doi.org/10.1016/j.ijrobp.2009.06.091

Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., & Mulrow, C. D. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. The BMJ, 372. DOI: https://doi.org/10.31222/osf.io/v7gm2_v1

Palma, D. A., Senan, S., Tsujino, K., Barriger, R. B., Rengan, R., & Moreno, M. (2013). Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. International Journal of Radiation Oncology Biology Physics, 85(2), 444–450. DOI: https://doi.org/10.1016/j.ijrobp.2012.04.043

Sardaro, A., McDonald, F., Bardoscia, L., Lavrenkov, K., Singh, S., & Ashley, S. (2020). Dyspnea in patients receiving radical radiotherapy for non-small cell lung cancer: a prospective study. Frontiers in Oncology, 10, 594590. DOI: https://doi.org/10.3389/fonc.2020.594590

Shen, T., Sheng, L., Chen, Y., Cheng, L., & Du, X. (2020). High incidence of radiation pneumonitis in lung cancer patients with chronic silicosis treated with radiotherapy. Journal of Radiation Research, 61(1), 117–122. DOI: https://doi.org/10.1093/jrr/rrz084

Song, Z., Zhang, X., Ma, Y., Ma, S., Feng, Z., & Liu, X. (2025). Adaptive radiation strategy with V20 limitation associates with survival benefit and lower incidence of symptomatic radiation pneumonitis in stage III NSCLC patients receiving concurrent immunotherapy and thoracic radiation. Translational Oncology, 51, 102184. DOI: https://doi.org/10.1016/j.tranon.2024.102184

Tonison, J. J., Fischer, S. G., Viehrig, M., Welz, S., Boeke, S., & Zwirner, K. (2019). Radiation pneumonitis after intensity-modulated radiotherapy for esophageal cancer: institutional data and a systematic review. Scientific Reports, 9(1), 2255. DOI: https://doi.org/10.1038/s41598-018-38414-5

Tsujino, K., Hashimoto, T., Shimada, T., Yoden, E., Kado, T., & Takada, Y. (2004). Combined analysis of radiation pneumonitis risk factors in patients treated with concurrent chemoradiotherapy for lung cancer. International Journal of Radiation Oncology Biology Physics, 60(1), 152–158. DOI: https://doi.org/10.1016/j.ijrobp.2004.07.501

Vogelius, I. R., & Bentzen, S. M. (2012). A literature-based meta-analysis of clinical risk factors for development of radiation induced pneumonitis. Acta Oncologica, 51(8), 975–983. DOI: https://doi.org/10.3109/0284186X.2012.718093

Walls, G. M., McMahon, M., Moore, N., Nicol, P., Bradley, G., & Whitten, G. (2023). Clinicoradiological outcomes after radical radiotherapy for lung cancer in patients with interstitial lung disease. BJR Open, 5(1), 20220049. DOI: https://doi.org/10.1259/bjro.20220049

Xu, K., Liang, J., Zhang, T., Zhou, Z., Chen, D., & Feng, Q. (2021). Clinical outcomes and radiation pneumonitis after concurrent EGFR-tyrosine kinase inhibitors and radiotherapy for unresectable stage III non-small cell lung cancer. Thoracic Cancer, 12(6), 814–823. DOI: https://doi.org/10.1111/1759-7714.13816

Yang, S., Yao, Y., Dong, Y., Liu, J., Li, Y., & Yi, L. (2021). Prediction of radiation pneumonitis using genome-scale flux analysis of RNA-seq derived from peripheral blood. Frontiers in Medicine (Lausanne), 8, 715961. DOI: https://doi.org/10.3389/fmed.2021.715961

Yekta, Z., Pourali, Ghasemi-rad, M., Ravanyar, & Nezhadrahim. (2011). Clinical and behavioral factors associated with management outcome in hospitalized patients with diabetic foot ulcer. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 371. https://doi.org/10.2147/dmso.s25309 DOI: https://doi.org/10.2147/DMSO.S25309

Downloads

Published

2026-04-04

How to Cite

Sirait, L. (2026). Radiation Pneumonitis Following Thoracic Radiotherapy: A Systematic Review. Health & Medical Sciences, 3(3), 13. https://doi.org/10.47134/phms.v3i3.611

Issue

Section

Articles