Significance Of Clinicopathological Features Of PN2 Non-small Cell Lung Cancer For Prognosis Prediction And Postoperative Radiotherapy Selection

Objective To find appropriate indicators to predict the risk of postoperative recurrence and survival of patients with pN2 non-small cell lung cancer(NSCLC),to understand its failure pattern and recurrence characteristics,and to explore the role of postoperative radiotherapy and to screen patients who potentially benefit from postoperative radiotherapy.Methods Eligible patients with pN2 NSCLC were collected from 2009 to 2016 in Zhejiang cancer hospital.All patients did not receive neoadjuvant therapy and received at least 4 cycles of adjuvant chemotherapy.The failure pattern and locoregional recurrence location of the whole group of patients were counted.Survival analysis was performed using the Kaplan-Meier method and the log-rank test was performed to compare the survival outcomes.Cox regression was used to determine whether variables were significant prognostic factors.Subsequently,stratified analysis was performed according to the mediastinal lymph node metastasis status of patients to compare the survival outcomes between radiotherapy group and non-radiotherapy group in different subgroups.Results A total of 253 patients were included,153 in the radiotherapy group and 100 in the non-radiotherapy group,respectively.162 patients had experienced progression,41 with local recurrence and 140 with distant metastasis.Multivariate regression suggested that adenocarcinoma was significantly associated with brain metastasis(P=0.045).The proportion of patients with contralateral mediastinal recurrence in left and right lung cancer was 47.1%and 31.3%in the whole group,and 54.5%and 36.4%in the non-radiotherapy group.In the whole group of patients,independent risk factors associated with disease-free survival(DFS)included higher The International Association for the Study of Lung Cancer(IASLC)restaging(P=0.005),log ratio of positive lymph nodes(LODDS)>-0.85(P=0.008),and visceral pleural invasion(P=0.005);independent prognostic factors associated with overall survival(OS)included IASLC restaging(P=0.023).For all the 253 pN2 patients,postoperative radiotherapy significantly improved local-regional control rate(LCR)(P<0.01),but did not improve DFS(P=0.256)and distant metastasis-free survival(DMFS)(P=0.742).Moreover,patients received adjuvant radiotherapy had statistically better OS compared with who had not(P=0.008).Further analysis revealed that the survival after progression was significantly better in the radiotherapy group than in the non-radiotherapy group(P=0.005).Stratified analysis according to mediastinal lymph node metastasis status showed that adjuvant radiotherapy did not improve LCR(P=0.238)and DFS(P=0.822)in patients with N2a1(single-station skip metastasis),improved LCR(P<0.001),DFS(P=0.047)and OS(P=0.005)in patients with N2a2(single-station non-skip metastasis),and improved LCR(P=0.005)but not DFS(P=0.103)in patients with N2b(multi-station metastasis).Besides,it was found that the distant metastasis rate was higher in patients with multi-station metastasis than in patients with single-station metastasis(P<0.001).Conclusion LODDS and visceral pleural invasion can effectively predict the risk of disease progression.IASLC restaging is significantly related to the DFS and OS.Patients with adenocarcinoma are more likely to develop brain metastases.Left lung cancer was more likely to have contralateral mediastinal recurrence.Adjuvant radiotherapy is not suitable for the whole group of pN2 patients,but it may benefit N2a2 patients.