Development and Validation of a Decision Support Framework to Evaluate the Role of Postoperative Radiotherapy in Patients with Pathological N2 Non-Small Cell Lung Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Postoperative radiotherapy (PORT) plays a highly controversial role in pN2 NSCLC disease. Recent study revealed that not all patients can benefit from PORT. Further study is needed to identify predictors for PORT. <h3>Materials/Methods</h3> A total of 1044 patients with completely resected pathologic stage T1-3N2M0 NSCLC were analyzed. Risk factors of distant metastasis were identified by the log-rank tests and the multivariable Cox models. The decision support framework (DSF) was built based on the previously published PI model and risk factors of distant metastasis. An independent dataset was used to validate the DSF. <h3>Results</h3> Clinical N2 status (HR=1.227, 95% CI 1.036 to 1.453, P=0.0178) and >4 involved lymph nodes (HR=1.272, 95% CI 1.071 to 1.510, P=0.0058) were identified as independent risk factors of distant metastasis and were also found to be associated with locoregional recurrence (LRR) in our previous work. The high-intermediate-risk histological type (micropapillary or solid positive adenocarcinomas) was found to be associated with distant metastasis (HR=1.207, 95% CI 1.062 to 1.371, P=0.0129), but not associated with LRR. We built an DSF accordingly and stratify patients into four groups: high LRR risk and high-intermediate histological risk (HHR) group, high LRR risk and low histological risk (HLR) group, low LRR risk and high-intermediate histological risk (LHR) group, and low LRR risk and low histological risk (LLR) group. PORT significantly improved OS only in the subgroup with a high risk of LRR and low-risk histological type (3-year OS rates: 66.7% for PORT vs. 50.2% for non-PORT, respectively; P=0.023). In the HHR group, PORT was associated with a not significant increase in OS. In the LLR and the LHR groups, no significant differences in OS were observed between PORT and non-PORT. <h3>Conclusion</h3> This study developed and validated a DSF combining two types of clinicopathological characteristics to predict the outcome of PORT in patients with completely resected pN2 NSCLC individually.