A novel nomogram containing acute radiation esophagitis predicting radiation pneumonitis in thoracic cancer receiving radiotherapy

Abstract

Background: Radiation-induced pneumonitis (RP) is a non-negligible and sometimes life-threatening complication among patients with thoracic radiation. We initially aimed to ascertain the predictive value of acute radiation-induced esophagitis (SARE, grade ≥ 2) to symptomatic RP (SRP, grade ≥ 2) among thoracic cancer patients receiving radiotherapy. Based on that, we established a novel nomogram model to provide individualized risk assessment for SRP.

Methods: Thoracic cancer patients who were treated with thoracic radiation from Jan 2018 to Jan 2019 in Shandong Cancer Hospital and Institute were enrolled prospectively. All patients were followed up during and after radiotherapy (RT) to observe the development of esophagitis as well as pneumonitis. Variables were analyzed by univariate and multivariate analysis using the logistic regression model, and a nomogram model was established to predict SRP by "R" version 3.6.0.

Results: A total of 123 patients were enrolled (64 esophageal cancer, 57 lung cancer and 2 mediastinal cancer) in this study prospectively. RP grades of 0, 1, 2, 3, 4 and 5 occurred in 29, 57, 31, 0, 3 and 3 patients, respectively. SRP appeared in 37 patients (30.1%). In univariate analysis, SARE was shown to be a significant predictive factor for SRP (P < 0.001), with the sensitivity 91.9% and the negative predictive value 93.5%. The incidence of SRP in different grades of ARE were as follows: Grade 0-1: 6.5%; Grade 2: 36.9%; Grade 3: 80.0%; Grade 4: 100%. Besides that, the dosimetric factors considering total lung mean dose, total lung V5, V20, ipsilateral lung mean dose, ipsilateral lung V5, and mean esophagus dose were correlated with SRP (all P < 0.05) by univariate analysis. The incidence of SRP was significantly higher in patients whose symptoms of RP appeared early. SARE, mean esophagus dose and ipsilateral mean lung dose were still significant in multivariate analysis, and they were included to build a predictive nomogram model for SRP.

Conclusions: As an early index that can reflect the tissue's radiosensitivity visually, SARE can be used as a predictor for SRP in patients receiving thoracic radiation. And the nomogram containing SARE may be fully applied in future's clinical work.

Keywords: Acute radiation-induced esophagitis; Nomogram; Radiotherapy; Symptomatic radiation-induced pneumonitis; Thoracic cancer.

Fig. 1

Incidence of SRP in different grades of ARE population. Abbreviations: ARE: acute radiation-induced esophagitis; SRP: severe radiation-induced pneumonitis

Fig. 2

Receiver operating characteristic (ROC) curves illustrating the relative predict power of these factors. And SARE seems to be a better predictor for symptomatic radiation-induced pneumonitis (SRP) with areas under the curve (AUC) values of 0.778, P <0.001. Besides that, MED, AUC=0.641 P=0.019; IL-MLD: AUC=0.610 P=0.067; Abbreviations: SARE: severe acute radiation-induced esophagitis; TLMLD:total mean lung dose; ILMLD: ipsilateral mean lung dose; MED: mean esophagus dose; TIME: the time that pneumonia symptoms appear

Fig. 3

Nomogram for the prediction of SRP, based on multivariable model. Instructions: To use the nomogram, an individual patient’s value is located on each variable axis, and a line is drawn upward to determine the number of points received for each variable value. The sum of these numbers is located on the Total Points axis, and a line is drawn downward to the axes to determine the likelihood of SRP. Abbreviations: ARE: acute radiation-induced esophagitis; MED: mean esophagus dose; ILMLD:mean ipsilateral lung dose; SRP: severe radiation-induced pneumonia

Fig. 4

ROC curve of the nomogram model for SRP: the area under the curve is 0.827 (95% CI: 0.746-0.908, P <0.001)

Fig. 5

Calibration Curve. Hosmer and Lemeshow Test: Chi-square=10.975 P=0.203 The predicted probability is almost the same as the actual probability, and the prediction error of the model is acceptable

Fig. 6

This 64-year-old esophageal cancer patient suffered grade 4 severe acute radiation-induced esophagitis (SARE) after only 10 fractions of radiotherapy. And he developed symptomatic radiation-induced pneumonitis (SRP) only 4 days after radiotherapy (RT) and then got infected of pneumocystis carinii during RT treatment. a: Endoscopy reveals diffuse mucosal erosion, sloughing, ulceration, and hemorrhage, and the endoscopic secretion culture revealed the fungal infection. b: Computed tomography (CT) image before radiotherapy; c: CT image that 6 days after radiotherapy; d: CT image that got infected of pneumocystis carinii during RP treatment.