A simple-to-use nomogram for predicting the risk of radiation pneumonitis in patients with thoracic segment esophageal squamous cell carcinoma

Abstract

Background: Radiation pneumonitis (RP) is one of the most severe complications of radiotherapy (RT) or concurrent chemoradiotherapy for thoracic segment esophageal squamous cell carcinoma (TSESCC) with delayed diagnose by conventional computed tomography (CT). The study aimed to develop a nomogram to predict the risk of RP early.

Methods: Data was collected from 174 patients with clinicopathologically confirmed TSESCC from October 2013 to June 2020. Procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) levels in serum were dynamically monitored during radiotherapy. Lasso analysis was used for feature screening before multivariate logistic regression analysis to reduce the multicollinearity of variables. A nomogram combined with biological factors and clinical signs for individualized risk assessment and precise prediction of RP was developed and assed the performance with respect to its calibration, discrimination.

Results: Of the 174 patients, 30 patients developed RP (grade ≥2) while 144 patients did not. After variable screening by Lasso analysis and logistics multivariate regression analysis, the predictor variables that were finally retained in the nomogram prediction model included IL-6, CRP, and radiotherapy techniques. The model displayed good discrimination with an area under the curve (AUC) of 0.898 (95% CI: 0.849-0.947), with the sensitivity and specificity of 0.967 and of 0.736, respectively. This model also shows good calibration and clinical practical value. In addition, the study provided a web-based version of the dynamic nomogram to facilitate clinical application.

Conclusions: The study provides a nomogram model containing IL-6, CRP, RT techniques, which could be conveniently used for individualized prediction of RP in patients with TSESCC during radiotherapy or concurrent chemoradiotherapy.

Keywords: C-reactive protein (CRP); Radiation pneumonitis (RP); esophageal cancer (EC); interleukin-6 (IL-6); nomogram.

Figure 1

Changes in the levels of IL-6, CRP and PCT in plasma of patients during treatment and follow-up. (A) The serum levels of IL-6 were statistically different after 2 weeks between RP group and non-RP group (P<0.05). (B) The CRP levels in the plasma of the RP group showed a significant difference from those of the non-RP group after 2 weeks (P<0.05). (C) The levels of PCT showed no significant difference comparing the RP group to non-RP groups (P>0.05) during radiotherapy or concurrent chemoradiotherapy. *P<0.05. IL-6, interleukin-6; CRP, C-reactive protein; PCT, procalcitonin; RP, radiation pneumonitis.

Figure 2

The correlation of biomarkers cytokines, dosimetric performance, and clinical signs. Blue indicates positive correlation, red indicates negative correlation, and the shade of color represents the strength of the correlation. For the P value of correlation analysis, “*”, “**” and “***” are used to represent “P<0.05, P<0.01, P<0.001”, respectively. COPD, chronic obstructive pulmonary disease; V20, percentage of total lungs volume receiving 20 Gy; IL-6, interleukin-6; CRP, C-reactive protein; W, week; RT, radiotherapy.

Figure 3

A simple-to-use nomogram for prediction the risk of RP. (A) The nomogram was developed incorporating the IL-6 at 2 weeks, CRP at 6 weeks, and RT techniques. (B) Operation interface of nomogram on the web page. The corresponding probability of RP can be obtained by inputting IL-6_2W, CRP_6W and RT techniques (IMRT or 3DCRT) on the left side of the patient. RP, radiation pneumonitis; IL-6, interleukin-6; CRP, C-reactive protein; W, week; RT, radiotherapy; IMRT, intensity modulated radiotherapy; 3DCRT, three-dimensional conformal radiotherapy.

Figure 4

Predictive performance of the nomogram. (A) ROC curves of IL-6_2W, CRP_6W, RT techniques. (B) Calibration curve of the nomogram predicting the risk of radiation pneumonitis. The x-axis and y-axis indicate the predicted and actual probabilities of radiation pneumonitis, respectively. (C) Decision curves of IL-6_2W, CRP_6W, RT techniques and the prediction model predicting RP. The x-axis represents the threshold probability, and the y-axis represents the net benefit rate after the benefit minus the hazard. ROC, receiver operating characteristic curve.

Figure 5

A typical case of the chest CT imaging and interleukin-6 dynamic changes in patients with TSESCC after radiotherapy. (A-C) Lung imaging when cytokines were altered; (D-F) scattered interstitial changes in both lungs at the onset of radiation pneumonitis; (G-I) interstitial changes after glucocorticoid treatment are more absorbed than before. Dynamic changes of IL-6 and CRP in plasma. CT, computed tomography; IL-6, interleukin-6; CRP, C-reactive protein; PCT, procalcitonin.