Pathological N2 Non-small Cell Lung Research Articles

EP08.02-28 Do We Have to Offer Postoperative Radiotherapy in Resected Pathologic N2 Non-small Cell Lung Cancer with Extranodal Extension?

EP08.02-28 Do We Have to Offer Postoperative Radiotherapy in Resected Pathologic N2 Non-small Cell Lung Cancer with Extranodal Extension?

P1.28-11 Recurrence Dynamics for Pathological N2 Non-small Cell Lung Cancer depending on the IASLC Residual Tumor Descriptor

P1.28-11 Recurrence Dynamics for Pathological N2 Non-small Cell Lung Cancer depending on the IASLC Residual Tumor Descriptor

Survival outcome of upfront surgery for clinical single-station N2 non-small cell lung cancer.

Pathological N2 (pN2) non-small cell lung cancer (NSCLC) is diverse; its treatment depends on the clinical N (cN) status. We aimed to determine the efficacy of upfront surgery for cN2pN2 NSCLC. The study included 43 cN2pN2 NSCLC patients who underwent upfront surgery at the Shizuoka Cancer Center between 2002 and 2017. Survival outcome, focusing on cN2 status, was retrospectively investigated. Mediastinal lymph nodes were pre-operatively evaluated using computed tomography and positron emission tomography. Surgical eligibility criteria included single-station cN2. N2 with N1 and skip N2 were defined as N2 with and without ipsilateral hilar lymph node metastasis, respectively. A platinum-doublet regimen was used for adjuvant chemotherapy. Survival curves were analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazard regression model. Clinical-skip N2 and cN2 with N1 cases included 22 and 21 patients, respectively. Twenty-three patients received adjuvant chemotherapy. The median follow-up duration was 73months. Clinical-skip N2 had a significantly better 5-year recurrence-free survival (RFS) than cN2 with N1 (58.3 vs 28.6%, P = 0.038) and was an independent favorable RFS predictor. Recurrence within 18 months occurred in 71% of cN2 with N1 cases. Five-year overall survival and RFS rates in patients receiving adjuvant chemotherapy vs those without adjuvant chemotherapy were 82.2 vs 41.9% (P = 0.019) and 56.5 vs 28.0% (P = 0.049), respectively. Clinical-skip N2 had an excellent prognosis, and upfront surgery was acceptable. Conversely, upfront surgery followed by chemotherapy is not recommended for cN2 with N1 patients because of early recurrence.

The association of postoperative radiotherapy with survival in resected N2 non-small cell lung cancer.

The current staging system for completely resected pathologic N2 non-small cell lung cancer (NSCLC) treated with chemotherapy is not suitable for distinguishing those patients most likely to benefit from postoperative radiotherapy (PORT). This study aimed to construct a survival prediction model that will enable individualized prediction of the net survival benefit of PORT in patients with completely resected N2 NSCLC treated with chemotherapy. A total of 3,094 cases from between 2002 and 2014 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patient characteristics were included as covariates, and their association with overall survival (OS) with and without PORT was assessed. Data from 602 patients from China were included for external validation. Age, sex, the number of examined/positive lymph nodes, tumor size, the extent of surgery, and visceral pleural invasion (VPI) were significantly associated with OS (P<0.05). Two nomograms were developed based on clinical variables to estimate individuals' net survival difference attributable to PORT. The calibration curve showed excellent agreement between the OS predicted by the prediction model and that actually observed. In the training cohort, the C-index for OS was 0.619 [95% confidence interval (CI): 0.598-0.641] in the PORT group and 0.627 (95% CI: 0.605-0.648) in the non-PORT group. Results showed that PORT could improve OS [hazard ratio (HR): 0.861; P=0.044] for patients with a positive PORT net survival difference. Our practical survival prediction model can be used to make an individualized estimate of the net survival benefit of PORT for patients with completely resected N2 NSCLC who have been treated with chemotherapy.

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

<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.

Long-term clinical outcomes and prognostic factors of upfront surgery as a first-line therapy in biopsy-proven clinical N2 non-small cell lung cancer.

BackgroundMultimodality therapy offers the best opportunity to improve pathological N2 non-small cell lung cancer (NSCLC) prognosis. This paper aimed to evaluate the long-term clinical outcomes and the prognostic factors of upfront surgery as first-line therapy in biopsy-proven clinical N2.MethodsRetrospective review of biopsy-proven cN2 NSCLC patients operated between 2007 and 2017. Upfront surgery was considered if the primary tumour was deemed completely resectable, with mediastinal nodal involvement confined to a single station and no preoperative evidence of extranodal tumour invasion.ResultsTwo hundred eighty-five patients who underwent radical resections were included. One hundred fifty-nine patients (55.8%) received induction chemotherapy. At follow-up completion, 127 (44.6%) patients had died. For the induction chemotherapy group, the median overall survival (OS) was 49 months [95% confidence interval (CI): 38–70 months], and the 5-year OS was 44.4%. The median and 5-year OS for the up front surgery group was 66 months (95% CI: 40–119 months) and 66.3%, respectively. There were no statistically significant differences between treatment approaches (p = 0.48). One hundred thirty-four patients (47.0%) developed recurrence. The recurrence-free survival (RFS) at 5 years was 17% (95% CI: 11–25%) for induction chemotherapy and 22% (95% CI: 9–32%) for upfront surgery; there were no statistically significant differences between groups (p = 0.93). No significant differences were observed based on the clinical N status (OS, p = 0.36; RFS, p = 0.65).ConclusionsUpfront surgery as first-line therapy for biopsy-proven cN2 NSCLC showed favourable clinical outcomes, similar to those obtained after induction chemotherapy followed by surgery. Therefore, it should be considered one of the multimodality treatment options in resectable N2 NSCLC.

A decision support framework for postoperative radiotherapy in patients with pathological N2 non-small cell lung cancer

IntroductionPostoperative radiotherapy (PORT) plays a highly controversial role in pathological N2 (pN2) non-small cell lung cancer (NSCLC) disease. Recent studies reveal that not all patients can benefit from PORT. Further research is needed to identify predictors of PORT. MethodsA total of 1044 pathologic stage T1-3N2M0 NSCLC patients were analyzed. Risk factors of distant metastasis were identified by the log-rank tests and the multivariable Cox models. We integrated risk factors of distant metastasis and our previously published loco-regional recurrence (LRR) related prognostic index into a decision support framework (DSF) to predict the outcomes of PORT. An independent cohort was used to validate the DSF. ResultsWe defined patients with more than two of three identified LRR-related features (heavy cigarette smoking history, clinical N2 status, and more than four positive lymph nodes) as a high LRR risk group. We found the high-intermediate-risk histological type (with micropapillary and/or solid components) was associated with a higher risk of distant metastasis (HR = 1.207, 95 % CI 1.062 to 1.371, P = 0.0038), but not LRR. We built the DSF by combining these two types of features. Patients were stratified into four groups by using the DSF. PORT significantly improved OS only in the subgroup without high-risk histological features (without micropapillary or solid components) and with a high risk for LRR (three-year OS: 66.7 % in the PORT group vs 50.2 % in the non-PORT group; P = 0.023). ConclusionsA particular pN2 subgroup with a high risk of LRR and without micropapillary or solid components could benefit from PORT.

Optimal positive lymph node ratio showing the benefit of postoperative radiotherapy in pathologic N2 non-small cell lung cancer: an exploratory study using the Surveillance, Epidemiology, and End Results data.

PurposeThis study aimed to identify the clinical parameters having the beneficial effect of postoperative radiotherapy (PORT) in pathologic N2 (pN2) non-small cell lung cancer (NSCLC) using the Surveillance, Epidemiology, and End Results (SEER) data.Materials and methodsAmong non-metastatic NSCLC patients in the SEER data, we included patients who diagnosed after 2002, who confirmed as pN2 after lobectomy or pneumonectomy, and who coded as underwent PORT or observation. Patients who survived less than 4 months of diagnosis were excluded in consideration of the perioperative mortality. After performing propensity score matching (PSM) on the selected patients, we compared PORT group with surgery alone group. We also performed exploratory subgroup analysis to find patients who could benefit from PORT.ResultsAmong the selected 4,456 patients, 1,729 patients received PORT, and 2,727 patients did not. There was no survival benefit of PORT in all patients with pN2 disease (hazard ratio [HR] = 1.03, p = 0.5). In subgroup analyses, the patients with a positive lymph node (LN) ratio of 60%–80% showed the significant benefit of PORT (HR = 0.71, p = 0.002).ConclusionPORT did not show the significant survival benefit in patients with pN2 disease after correcting the confoundedness in the SEER data. However, a specific range of LN ratios can be a potential indicator maximizing the survival benefit of PORT.

Lymph Node Parameters Predict Adjuvant Chemoradiotherapy Efficacy and Disease-Free Survival in Pathologic N2 Non-Small Cell Lung Cancer.

Pathologic N2 non-small cell lung cancer (NSCLC) is prominently intrinsically heterogeneous. We aimed to identify homogeneous prognostic subgroups and evaluate the role of different adjuvant treatments. We retrospectively collected patients with resected pathologic T1-3N2M0 NSCLC from the Shanghai Chest Hospital as the primary cohort and randomly allocated them (3:1) to the training set and the validation set 1. We had patients from the Fudan University Shanghai Cancer Center as an external validation cohort (validation set 2) with the same inclusion and exclusion criteria. Variables significantly related to disease-free survival (DFS) were used to build an adaptive Elastic-Net Cox regression model. Nomogram was used to visualize the model. The discriminative and calibration abilities of the model were assessed by time-dependent area under the receiver operating characteristic curves (AUCs) and calibration curves. The primary cohort consisted of 1,312 patients. Tumor size, histology, grade, skip N2, involved N2 stations, lymph node ratio (LNR), and adjuvant treatment pattern were identified as significant variables associated with DFS and integrated into the adaptive Elastic-Net Cox regression model. A nomogram was developed to predict DFS. The model showed good discrimination (the median AUC in the validation set 1: 0.66, range 0.62 to 0.71; validation set 2: 0.66, range 0.61 to 0.73). We developed and validated a nomogram that contains multiple variables describing lymph node status (skip N2, involved N2 stations, and LNR) to predict the DFS of patients with resected pathologic N2 NSCLC. Through this model, we could identify a subtype of NSCLC with a more malignant clinical biological behavior and found that this subtype remained at high risk of disease recurrence after adjuvant chemoradiotherapy.

The addition of radiotherapy to adjuvant chemotherapy has a combinatorial effect in pN2 non-small cell lung cancer only with extranodal invasion or multiple N2 metastasis

ObjectivesThe benefit of adjuvant therapy for heterogenous group of pathological N2 (pN2) non-small cell lung cancer (NSCLC) remains unclear. We evaluated the prognostic effect of adjuvant therapy after stratifying patients with pN2 according to subdivided N2 descriptors. Materials and MethodsWe performed a retrospective analysis of clinical outcomes in patients with pN2 NSCLC who underwent upfront surgery. N2 descriptors were subdivided as single N2 metastasis without N1 involvement (pN2a1), single N2 with metastasis with N1 involvement (pN2a2), and multiple N2 metastasis (pN2b). ResultsFrom 2005–2017, 838 patients with pN2 NSCLC underwent complete resection. There were 173 (21.0 %), 338 (40.3 %), and 324 (38.7 %) in the pN2a1, pN2a2, and pN2b groups. Patients who received chemoradiotherapy (CRTx; n = 389, 46.4 %) or chemotherapy (CTx; n = 204, 24.3 %) had similar prognoses, which were better than prognoses in patients who received with radiotherapy (RTx; n = 116, 13.8 %) or those who did not receive adjuvant therapy (n = 129, 15.4 %). According to the stratified multivariable Cox analysis, patients with pN2b stage in the CTx group had a significantly poor prognosis than those in the CRTx group (hazard ratio, 1.38; 95 % confidence interval, 1.03–1.98; p = 0.046). The difference in survival outcomes between the CRTx and CTx groups was significant in patients with extranodal invasion (ENI) (p = 0.011), but not in those without ENI (p = 0.527) ConclusionsAdjuvant CTx improves the overall and recurrence-free survival in patients with pN2 NSCLC undergoing upfront surgery with complete resection. RTx with adjuvant chemotherapy has a combinatorial effect on pN2 NSCLC only with ENI or multiple N2 metastasis.

How Effective Is Neoadjuvant Therapy Followed by Surgery for Pathologic Single-Station N2 Non–Small Cell Lung Cancer?

The optimal treatment strategy for pathologic single-station N2 (pN2a1) non-small cell lung cancer (NSCLC)-surgery first followed by adjuvant treatment (SF) or neoadjuvant therapy followed by surgery (NS)-remains unclear. We compared disease-free survival (DFS) and overall survival (OS) after NS versus SF for pN2a1 NSCLC. We retrospectively identified patients with pN2a1 NSCLC resected between 2000 and 2018. Patients in the SF group had cN0 disease and were treated with surgery before adjuvant chemotherapy; patients in the NS group had known preoperative nodal disease, cN2 disease, and were treated with neoadjuvant therapy before surgery. The matching-weights procedure was applied to generate a cohort with similar characteristics between groups. DFS and OS were calculated using the Kaplan-Meier approach and compared between groups using weighted log-rank test and Cox proportional hazards models. We identified 227 patients with pN2a1 disease: 121 treated with SF and 106 with NS. After the matching-weights procedure, 5- and 10-year DFS were 45% and 27% for SF versus 26% and 21% for NS (log-rank P = 0.056; hazard ratio [HR], 1.61; 95% confidence interval [CI], 0.98-2.65); 5- and 10-year OS were 49% and 30% for SF versus 43% and 20% for NS (log-rank P = 0.428; HR, 1.24; 95% CI, 0.67-2.28). SF and NS for pN2a1 NSCLC resulted in similar survival. A study comparing SF for known preresectional pN2a1 with occult pN2a1 disease could be a next step. Further investigation of SF for known N2a1 versus occult pN2a1 disease could power a clinical trial focused on N2a NSCLC.

Propensity-Matched Analysis of Clinical Relevance of the Highest Mediastinal Lymph Node Metastasis

The clinical relevance of the highest mediastinal lymph node (HMLL) metastasis in patients with pathological N2 non-small cell lung cancer (NSCLC) is still controversial. Our study aimed to reassess the effect of HMLL metastasis on survival. Patients with stage pT1-4N2M0 NSCLC who underwent major lung resection and systemic lymphadenectomy at Peking University People's Hospital from 2004 to 2015 were identified. Patients in the HMLL-positive group were matched to patients in the HMLL-negative group using 1:1 propensity score matching analysis. Overall survival was estimated by Kaplan-Meier method and compared using log-rank test, and multivariable Cox proportional hazard regression was constructed to identify risk factors associated with overall survival. The cumulative incidence of cancer specific mortality was evaluated through a competing risk analysis. A total of 266 NSCLC patients with stage pT1-4N2M0 NSCLC were enrolled. Of those, 128 cases were HMLL positive and 138 cases were HMLL negative. A higher proportion of patients in the HMLL-positive group were female (P= .034) and had a higher rate of adenocarcinoma (P= .003). Compared with the HMLL-negative, the HMLL-positive group was not associated with worse survival in unmatched cohorts (adjusted hazard ratio= 1.21; 95% confidence interval, 0.87-1.68). After propensity score matching, 109 pairs were selected. No survival difference remained in matched cohorts (adjusted hazard ratio= 1.00; 95% confidence interval, 0.70-1.42). Highest mediastinal lymph node metastasis does not exhibit worse survival in patients with stage pT1-4N2M0 NSCLC. The clinical relevance of HMLL metastasis needs further examination.

Association of postoperative radiotherapy with survival in patients with completely resected pathologic N2 non-small cell lung cancer treated with chemotherapy.

e21008 Background: The current staging system for completely resected pathological N2 non-small-cell lung cancer (NSCLC) treated with chemotherapy is not suitable for predicting those patients most likely to benefit or not from post-operative radiotherapy (PORT). This study aimed to construct a survival prediction model that will enable individualized predictions of the net survival of PORT. Methods: A total of 3094 cases between 2002 and 2014 were extracted from the Surveillance, Epidemiology, and End Results databases. Patient characteristics were included as covariates, and their association for overall survival (OS) with and witout PORT was assessed. Externally validate data of 602 patients were included from China. Results: A total of 3696 patients were included for analysis. Age, gender, examined lymph node, positive lymph node, tumor size, extent of surgery, and visceral pleural invasion were significantly associated with OS, with P &lt; .05. The calibration curve for OS showed great agreement between prediction by survival prediction model and actual observation.In the training cohort, the C-index for OS was 0.619 (95% CI, 0.598-0.641) in the PORT group and 0.627 (95% CI, 0.605-0.648) in the non-PORT group. In the externally validation cohort, the C-index for OS was 0.599 (95% CI, 0.485- 0.713) in the PORT group and 0.595 (95% CI, 0.544-0.646) in non-PORT group. The two survival prediction models were developed based on clinical variables to estimate an individual's net survival gain or not attributable to PORT. We found that PORT could improve OS (HR, 0.861; P = 0.044) for patients with a positive PORT net survival benefit. Conclusions: We established a practical survival prediction model that can be used to make individualized predictions about the expected survival of PORT or without PORT in patients with completely resected pathological N2 NSCLC, treated with chemotherapy.

Thoracoscopic Surgery Shows Non-Inferiority to Open Surgery for Clinical N0-N2 and Pathologic N2 Non-Small Cell Lung Cancer

Objectives Controversy has remained over the primary surgical management for stage IIIA-N2 non–small cell lung cancer. Minimal or non-bulky N2 disease defined as single-station nodal involvement may still be a candidate of radical surgery. The aim of this study was thus to assess the outcome of thoracoscopic surgery in clinical N0-N2 and pathologic N2 disease. Methods Seventy-nine cases of pathologic N2 diseases without induction therapy (clinical N0, 27; N1, 13; N2, 39) were operated on between September 2003 and December 2010 in our institute. Forty-seven patients underwent thoracoscopic surgery (group T) and 32 patients underwent standard thoracotomy (group S). Perioperative and oncologic outcomes were compared between the 2 groups. Results There were no significant differences between the 2 groups regarding dissected number of lymph nodes, operative time, morbidity, and mortality. However, blood loss in group T was less than in group S (Mean: T, 229 versus S, 534 mL, respectively; P = 0.0004). Although disease-free survival in group T did not differ from that in group S, overall survival in group T was better than in group S after propensity score matching to adjust confounding factors including tumor size and T factor (P = 0.03). Multivariate analysis showed that multinodal stations was significantly worse prognostic factor [hazard ratio (HR) = 4.79; 95% confidence interval (CI) = (1.6–14.3); P = 0.005) in disease-free and overall survivals [HR = 8.21; 95% CI = (1.9–35.4); P = 0.005]. Thoracoscopic surgery was favorable prognostic factor in overall survivals [HR = 0.13; 95% CI = (0.03–0.6); P = 0.009]. Conclusions Our study demonstrated that thoracoscopic surgery for non-bulky N2 disease was feasible and not inferior to standard thoracotomy in terms of oncologic outcome.

EP1.18-09 Analysis of the Role of Postoperative Radiotherapy in Pathological N2 Non-Small Cell Lung Cancer with Propensity Score Matching

N2 non-small cell lung cancer (NSCLC) is a heterogeneous disease. For operable patients with postoperative N2 non-small cell lung cancer, the optimum adjuvant treatment strategy is still in dispute. Our aim was to assess the efficacy of conbine postoperative chemoradiotherapy (POCRT) or postoperative chemotherapy (PCT) alone following surgery in pathological N2 non-small cell lung cancer using propensity score matching, and to explore the factors influencing the prognosis. Between 2004 and 2014, a total of 175 patients fulfilled the inclusion criteria. The initiation of PCT started later than 2 weeks after the operation. The regimens of PCT in the present study included a cisplatin-based regimen and were administered for at least 2 cycles. POCRT was executed sequentially or sandwiched with PCT with three-dimensional conformal radiotherapy(3D-CRT) or intensity-modulated radiotherapy technique(IMRT). The prescription dose to clinical target volume (CTV) was 50 (range 44-60) Gy, Data were analyzed using SPSS version 24.0. Survival curves were produced using the Kaplan-Meier estimator method and compared with the log-rank test. Univariable and multivariable analyses of clinical characteristics. All available patient and tumor variables were compared using the χ2 test. Propensity score matching (PSM) analyses were used to compensate for differences in baseline characteristics between the POCRT and PCT groups to confirm the survival difference. The survival of the two groups was followed up and the effect of postoperative radiotherapy was analyzed. The median survival time was 57 vs 40 months in the POCRT and PCT groups, and the 1, 3 and 5-year OS rates in the POCRT and pCT groups were 98.3 vs. 86.1%, 71.7 vs.53.0% and 45.7 vs. 39.0%, respectively (P=0.019). Exploratory subgroup analysis found that compared with PCT, POCRT improved OS in patients with squamous cell subtype (P=0.010), no lymphovascular invasion (P=0.006), pN2a (P=0.006) or total number of metastatic lymph nodes ≤7 (P=0.016). Following PSM, a total of 113 events were identified in both the POCRT and PCT groups, with 60 and 53 patients in each group, respectively. There was no significant difference in the general clinical data between the two groups after matching. The median survival time was 57 vs 63 months in the POCRT and PCT groups after matching, and the 1, 3 and 5-year OS rates in the POCRT and PCT groups were 98.3 vs. 92.5%, 71.7 vs. 64.2% 和 45.7 vs. 50.7% respectively, with no significant difference (P=0.463). Following PSM, the survival differences between POCRT and PCT in the various subgroups were not statistically significant, except in patients with squamous cell lung cancer (P=0.010), there was also a trend toward an increase in the overall survival of pN2-NSCLC with pN2a (P = 0.196) or total number of metastatic lymph nodes ≤7 (P=0.367). Univariate and multivariate analyses indicated that T stage, total number of MLNs and POCRT were independent factors affecting OS. POCRT following complete resection clearly demonstrated superior survival compared with pCT. And POCRT may be specifically recommended to N2 patients with squamous cell lung cancer, particularly those with limited nodal involvement and T4 disease.

P1.01-123 Recent Clinical Outcomes of Upfront Surgery Followed by Adjuvant Therapy for Resectable Pathological N2 Non-Small Cell Lung Cancer

P1.01-123 Recent Clinical Outcomes of Upfront Surgery Followed by Adjuvant Therapy for Resectable Pathological N2 Non-Small Cell Lung Cancer

Deep-learning Based Automatic Delineation Improves CTV Contouring Quality and Efficiency for Pathological N2 (pN2) Non-small Cell Lung Cancer (NSCLC) Receiving Post-operation Radiation Therapy

Deep-learning Based Automatic Delineation Improves CTV Contouring Quality and Efficiency for Pathological N2 (pN2) Non-small Cell Lung Cancer (NSCLC) Receiving Post-operation Radiation Therapy

P3.01-31 Prognostic Factors in Patients with Resected Pathological N2 Non-Small Cell Lung Cancer

Postoperative outcome for non-small cell lung cancer (NSCLC) patients with mediastinal lymph node metastasis is unfavorable even after complete resection. To identify the subgroup of NSCLC patients with mediastinal lymph node metastasis whom we recommend surgical treatment, we sought to investigate prognostic factors in these patients. We retrospectively reviewed NSCLC patients with pathologically identified mediastinal lymph node metastasis who underwent complete resection with systematic nodal dissection between 2000 and 2016. Demographic, clinical, and pathologic factors (sex, age, Brinkman index, performance status [PS], % vital capacity, forced expiratory volume % in 1 second, preoperative carcinoembryonic antigen [CEA], histological subtype, pathological tumor size, p-T factor [7th edition], pleural invasion, pulmonary metastasis, histological grade, number of positive mediastinal nodal stations [single station vs multiple stations], number of positive mediastinal lymph nodes [1-2 vs ≥3], epidermal growth factor receptor [EGFR] mutation status, and adjuvant chemotherapy) were analyzed using the log-rank test as univariate analyses and a Cox proportional hazards regression model for multivariate analyses to identify independent predictors of favorable overall survival (OS). Of the 54 eligible patients, 38 were male and 16 were female. The median age and CEA were 65 years and 5.3 ng/mL, respectively. Lobectomy, bilobectomy, and pneumonectomy were performed in 49/3/2 patients. Histological subtypes were adenocarcinoma in 29 patients, squamous cell carcinoma in 17, and others in 8. EGFR was inspected in 33 patients, and 10 patients were EGFR mutated. Adjuvant chemotherapy was performed in 26 patients. The details of adjuvant chemotherapy were cisplatin-based combination chemotherapy in 18 patients, and carboplatin-based combination chemotherapy in 8. The 3-year and 5-year OS were 64.9% and 44.7%, respectively, with a median follow-up period of 41 months. The preoperative CEA <5.3 ng/mL (HR: 0.2151) and undergoing adjuvant chemotherapy (HR: 0.3580) were identified as significant predictors of favorable OS. The 3-year and 5-year OS in patients with CEA <5.3 and ≥5.3 ng/mL were 88.3/70.8% vs 41.0/17.9%, respectively (p<0.001). The 3-year and 5-year OS in patients who underwent adjuvant chemotherapy or none were 75.3/70.3% vs 55.3/23.1%, respectively (p = 0.009). Even if NSCLC patients have mediastinal lymph node metastasis, favorable postoperative prognosis may be expected in patients with low preoperative serum CEA. Adjuvant chemotherapy should be considered in patients with mediastinal lymph node metastasis on pathological examination.

P3.01-89 Upfront Surgery Versus Neoadjuvant Treatment Followed by Surgery in Pathologic N2 Non-Small Cell Lung Cancer

P3.01-89 Upfront Surgery Versus Neoadjuvant Treatment Followed by Surgery in Pathologic N2 Non-Small Cell Lung Cancer

Association between clinicopathological factors and postoperative radiotherapy in patients with completely resected pathological N2 non-small cell lung cancer.

The function of postoperative radiotherapy (PORT) in patients with completely resected pathologically N2 (pN2) non-small cell lung cancer (NSCLC) remains controversial due to a lack of prospective studies. The present study aimed to evaluate the efficacy of PORT in completely resected pN2 NSCLC when using modern radiation techniques, and to determine the associations between clinicopathological factors and PORT and survival rates. Following patient selection, 246 out of 269 consecutive patients with pN2 NSCLC were enrolled in the present study, with 88 patients having received postoperative chemotherapy (POCT) and PORT, 90 having received adjuvant chemotherapy, 1 having received adjuvant radiotherapy and the remaining 67 having received no adjuvant therapy. Overall survival (OS), local recurrence-free survival (LRFS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. The median age of the patients was 59 years, overall, 175 (71.1%) of the patients were male and the median radiation dose was 50.4 Gy. The median follow-up duration was 38.3 months. The 1-, 3- and 5-year OS rates were 98.9, 71.3 and 54.9%, and 93.0, 58.4 and 36.7% (P=0.011) in the PORT and non-PORT group, respectively. The 1-, 3- and 5-year LRFS rates were 95.5, 84.6 and 78.0%, and 86.6, 70.6 and 52.8% (P<0.001) in the PORT and non-PORT groups, respectively. The 1-, 3- and 5-year DFS rates were 86.5, 55.2 and 37.9%, and 80.9, 40.3 and 26.8% (P=0.132) in the PORT and non-PORT groups, respectively. Univariate analysis revealed that the OS rate was significantly increased in patients with peripheral tumors (P=0.029), pT1-2 (P=0.015), one N2 lymph node (LN) metastasis (P=0.001), single N2 station metastasis (P=0.030), no bronchial involvement (P=0.025), use of PORT (P=0.011) and POCT (P=0.003). Multivariate analysis revealed that PORT (HR, 0.755; 95% CI, 0.498-0.986; P=0.047), POCT (HR, 0.645; 95% CI, 0.420-0.988; P=0.044), bronchial involvement (HR, 1.453; 95% CI, 1.002-2.107; P=0.049) and ≥2 N2 metastases (HR, 1.969; 95% CI, 1.228-3.157; P=0.005) were significant independent predictors of OS. Subgroup analysis demonstrated an increased OS rate with PORT only in the patients with positive bronchial involvement and ≥2 N2 LN metastases. The results revealed that PORT may improve the LRFS and OS rates in completely resected pN2 NSCLC, and that the patients with positive bronchial involvement and ≥2 N2 LN metastases may receive more benefit from PORT.