Machine Learning to Build and Validate a Model for Radiation Pneumonitis Prediction in Patients with Non–Small Cell Lung Cancer

Abstract

Purpose: Radiation pneumonitis is an important adverse event in patients with non-small cell lung cancer (NSCLC) receiving thoracic radiotherapy. However, the risk of radiation pneumonitis grade ! 2 (RP2) has not been well predicted. This study hypothesized that inflammatory cytokines or the dynamic changes during radiotherapy can improve predictive accuracy for RP2. Experimental Design: Levels of 30 inflammatory cytokines and clinical information in patients with stages I-III NSCLC treated with radiotherapy were from our prospective studies. Statistical analysis was used to select predictive cytokine candidates and clinical covariates for adjustment. Machine learning algorithm was used to develop the generalized linear model for predicting risk RP2. Results: A total of 131 patients were eligible and 17 (13.0%) developed RP2. IL8 and CCL2 had significantly (Bonferroni) lower expression levels in patients with RP2 than without RP2. But none of the changes in cytokine levels during radiotherapy was significantly associated with RP2. The final predictive GLM model for RP2 was established, including IL8 and CCL2 at baseline level and two clinical variables. Nomogram was constructed based on the GLM model. The model's predicting ability was validated in the completely independent test set (AUC ¼ 0.863, accuracy ¼ 80.0%, sensitivity ¼ 100%, specificity ¼ 76.5%). Conclusions: By machine learning, this study has developed and validated a comprehensive model integrating inflammatory cytokines with clinical variables to predict RP2 before radiotherapy that provides an opportunity to guide clinicians.

A Novel Nomogram Containing Acute Radiation Esophagitis Predicting Radiation Pneumonitis in Thoracic Cancer Receiving Radiotherapy

“…Secondly, the esophagus and lung are both radiosensitive organs, and the early occurrence of SARE may further indicate the high radiosensitivity of the body tissue. More than this, Previous studies have con rmed multiple in ammatory cytokines were closely related to SARE as well as SRP [10,26,28,29] , so it may be a signal of activation of the systemic in ammatory system. And we look forward to more basic experiments to better explain this relationship.…”

“…Numerous dosimetric indicators of the lung have been widely veri ed in previous studies for RP, such as total or ipsilateral lung V5, V10, V13, V20 [6][7][8][9][10][11][12][13][14] . Furthermore, the dosimetric indicators about esophagus, which may have not been previously well established as predictors, were also considered in this study.…”

“…Previous studies have shown the importance of clinical characteristics, dosimetric parameters factors as well as laboratory indicators, such as pack-years, baseline pulmonary function, a history of lung resection, mean lung dose (MLD), total or ipsilateral lung volume receiving more than 2000 cGy (V20), total lung V10, total lung V13, ipsilateral lung V5, interleukin-8, recombinant human eotaxin-2, recombinant human eotaxin-22, recombinant human eotaxin-17 and so on [6][7][8][9][10][11][12][13] . In addition, genetic variants of pulmonary surfactant-associated glycoprotein D, homeodomain interacting protein kinase 2 and interleukin-4 were also reported to be associated with risk of RP development [14][15][16] .…”

“…In addition, genetic variants of pulmonary surfactant-associated glycoprotein D, homeodomain interacting protein kinase 2 and interleukin-4 were also reported to be associated with risk of RP development [14][15][16] . And the combination of chemotherapy has also been implicated in increasing chances of developing RP [10,17,18] .…”

Efficacy and Safety Aiming at the Combined-Modality Therapy of External Beam Radiotherapy (40Gy) and Iodine-125 Seed Implantation for Locally Advanced NSCLC in the Elderly

“…As a matter of fact, the effective dose of radiotherapy for the diameter of tumor > 5 cm should be more than 100 Gy according to the report of Reveizi (6). As is known to us, radiation pneumonitis is a dose limiting adverse effect which may decline QOL and become life-threatening (26). If patients received so high radiation dose, the adjacent normal tissues would be seriously damaged with increasing the occurrence of severe complications and mortality.…”