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Yuxia Deng,1 Ting Qiu,1 Nishant Patel,1 Shi Zhou,1 Tao Xue,2 Haijun Zhang1,3 1Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Cardiothoracic Surgery, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Precision Medical Center, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Haijun ZhangPrecision Medical Center, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, Jiangsu, People’s Republic of ChinaTel|Fax +86 25 8327 2216Email zhanghaijunseu@163.comTao XueDepartment of Cardiothoracic Surgery, Medical School of Southeast University, 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, People’s Republic of ChinaTel|Fax +86 25 8326 2381Email taoxuezdyy@163.comPurpose: Risk of radiation pneumonia (RP) could not be effectively detected due to non-specific clinical symptoms in the early stage. The purpose of this investigation was to evaluate serum biomarkers of cytokines interleukin-6 (IL-6), C-reactive protein (CRP) and procalcitonin (PCT) for its early detection in patients with thoracic malignant tumors receiving radiotherapy.Patients and methods: The clinical data of 105 patients with thoracic malignant tumors (lung cancer, esophageal carcinoma and mediastinal tumors) treated by radiotherapy were retrospectively analyzed. The patients were divided into RP group and non-RP group according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0). The serum level of IL-6 was detected by chemiluminescence, and the level of CRP was measured by nephelometry during radiotherapy. The level of PCT, one of the specific indicators to distinguish infection and non-infectious etiologies, was also detected by chemiluminescence.Results: Among 105 patients treated by radiotherapy, 28 developed RP, and the other 77 had no RP. There was no significant difference in the risk of RP between patients’ factors (age, sex, PS score, smoking, tumor type) and treatment factors (chemotherapy, V5, GTV dose). However, chronic obstructive pulmonary disease (COPD), V20 and mean lung dose (MLD) were significantly different between the two groups (χ2 = 4.131, 3.986, 7.830, P < 0.05). Furthermore, PCT levels were also found to have insignificant differences between RP group and non-RP group (P > 0.05). However, there were significant differences between the groups in the levels of IL-6 and CRP (P < 0.05). The IL-6 levels significantly increased earlier than that of conventional CT imaging when patients suffering from RP and peaked at 6 weeks during radiotherapy. CRP had a similar change as IL-6. Single cytokine and combination of IL-6 and CRP possessed a good ability to predict RP with the AUC of IL-6 of 0.89±0.04 (95% CI, 0.80–0.95, P |