pN2 Non-small Cell Lung Cancer Research Articles

Disparities in Guideline-Concordant Treatment for Pathologic N1 Non-Small Cell Lung Cancer

Socioeconomic status (SES) disparities in the surgical management of patients with non-small cell lung cancer (NSCLC) are well described. Disparities in the receipt of adjuvant chemotherapy are poorly understood. We assessed the influence of SES on adjuvant chemotherapy after resection in patients with pN1 NSCLC. The National Cancer Database was queried for cN0/N1 NSCLC patients who underwent surgical resection and had demonstrated pN1 disease. This cohort was further divided into those who received multiagent adjuvant chemotherapy (MAAC) vs surgery-only treatment. Factors associated with treatment assignment were examined, and long-term survival was compared. Of the 14,892 patients who underwent resection for pN1 disease, 8061 (54.1%) received MAAC. Patients were less likely to receive MAAC if they resided in rural areas (odds ratio, 1.23; 95% confidence interval [CI], 1.11-1.37; P < .001), or were uninsured or on Medicaid (odds ratio, 1.23; 95% CI, 1.07-1.41; P= .004). The propensity score-weighted 5-year survival was significantly higher for those receiving MAAC compared with surgery only (53.6% vs 39.5%, log-rank P < .001). Lower income (hazard ratio, 1.06; 95% CI, 1.00-1.12; P= .044) and uninsured or Medicaid insurance status (hazard ratio, 1.22; 95% CI, 1.13-1.31; P < .001) were independently associated with increased mortality by Cox regression in the propensity score-weighted cohort. pN1 NSCLC patients living in rural areas or who are uninsured or on Medicaid insurance are at increased risk of not receiving MAAC. Treatment with MAAC significantly improves long-term survival of pN1 patients. Efforts should be made to ensure these at-risk groups receive guideline-concordant care.

Local failure patterns after radical resection and adjuvant chemotherapy in patients with pN2 nonsmall-cell lung cancer: A retrospective analysis.

The patterns of local failure in stage pN2 nonsmall-cell lung cancer (NSCLC) patients undergoing radical resection and adjuvant chemotherapy are controversial. The sites of local failure were compared in subgroups of patients with relevant clinicopathologic features (e.g., location and size of primary lesions). Totally 75 patients with local failure after radical resection and adjuvant chemotherapy for pN2 NSCLC were included in the analysis. Thirty-seven (49.3%) patients had distant metastasis. The median duration from surgical resection to local failure was 11 months (range: 3-45 months). Sites with ≥10% failure rate in all subgroups based on the location of the primary lesions included 4R, 7, the ipsilateral hilum, and the stump. Additional sites with ≥10% failure rate included 2R, 2L, 4L, and 5 for lesions in the left upper lobe; 4L and 5 for lesions in the left lower lobe; and 2R and 3P for lesions in the right upper-middle lobe. Squamous cell carcinoma affected the stump failure rate compared to adenocarcinoma (56.3% vs. 18.0%, P = 0.003). Tumor diameter ≥5 cm affected the stump failure rate compared to tumor diameter < 5 cm (44.0% vs. 18.0%, P = 0.016). Skip N2 metastasis affected the ipsilateral hilum failure rate compared to nonskip N2 metastasis (7.5% vs. 31.4%, P = 0.008). For pN2 NSCLC patients undergoing radical resection and adjuvant chemotherapy, different lung lobes had different high-risk failure sites. Left lung cancer is prone to bilateral mediastinal lymph nodes recurrence, while right lung cancer mainly recurs with ipsilateral mediastinal lymph nodes. Moreover, the local failure patterns are influenced by pathological type, tumor size, and skip N2 metastasis.

Survival benefit of skip metastases in surgically resected N2 non-small cell lung cancer: A multicenter observational study of a large cohort of the Chinese patients

IntroductionN2 non-small cell lung cancer (NSCLC) without N1 involvement, also known as skip metastases (pN0N2), has been suggested as a subgroup of heterogeneous N2 disease with better survival. This real-world observational study aimed to elucidate the prognostic impacts of skip N2 metastases using a large number of pathologic N2 NSCLC from 10 participating centers in China. Materials and methodsMedical records of pN2 NSCLC patients after surgical resection at 10 thoracic surgery centers between January 2014 and September 2017 were retrospectively reviewed based on the LinkDoc database. Clinical data on patient demographics, tumor characteristics, treatments and clinical outcomes were collected. Overall survival of patients with and without skip metastases was evaluated and compared by Kaplan-Meier method and Log-rank test. Cox proportional hazard model was established to identify potential prognostic predictors. Subgroup analysis was carried out to further explore the prognostic significance of skip metastases. ResultsAmong 2653 surgically resected N2 patients, 881 (33.2%) had skip metastases. Patients with skip N2 had a significant better overall survival (P = 0.0019). Multivariate COX regression analysis showed borderline significance of skip metastases (HR = 0.81, 95%CI: 0.645–1.017, P = 0.0698) after adjustment for other covariates. Other independent prognostic predictors included smoking history, tumor location, stage and N2 station involved (P < 0.05). Subgroup analysis demonstrated significant survival benefits of skip N2 in most subpopulations. ConclusionsThis study suggested a prognostic benefit of skip N2 metastases in real world practice. Further subdivision of N2 disease is warranted for better patient management and prognostic prediction (NCT 03429192).

Prognostic relevance of regional lymph-node distribution in patients with N1-positive non-small cell lung cancer: A retrospective single-center analysis

ObjectiveLymph node (LN) metastases predict survival in patients with non-small cell lung cancer (NSCLC) treated with curative surgery. Nevertheless, prognostic differences within the same nodal (N) status have been reported. Consequently, the International Association for the Study of Lung Cancer (IASLC) proposed to stratify patients with limited nodal disease (pN1) from low (pN1a) to high (pN1b) nodal tumor burden. This study aimed to validate the IASLC proposal in a large single-center surgical cohort of patients with pN1 NSCLC. Material and MethodsData from 317 patients with pN1 NSCLC treated between January 2012 and December 2016, were retrospectively analyzed. Associations between distribution of LN metastases and survival were analyzed for different classification models—toward nodal extension (pN1a: one station involved; pN1b: multiple stations involved) and toward location (pN1 in the hilar [LN#10/11] or peripheral zone [LN#12-14]). ResultsTumor-specific survival (TSS) in the entire pN1 cohort was 67.1% at five years. Five-year TSS rates for pN1a and pN1b patients were comparable (67.6% vs. 66.5%, p = 0.623). Significant survival differences from pN1a to pN1b were observed only in patients with adenocarcinoma histology and completed adjuvant chemotherapy (5-year TSS: pN1a, 80.4% vs. pN1b, 49.6%; p = 0.005). TSS for LN metastases in the hilar zone/peripheral zone or in both zones was 68.2% and 59.9%, respectively (p = 0.068). In multivariate analysis, adjuvant chemotherapy, squamous cell histology, and nodal disease limited to one zone nodal disease were identified as independent beneficial prognostic factors (p < 0.05). ConclusionpN1 in only one region (hilar or lobar) was associated with better outcome than metastatic affection of both regions after surgery and adjuvant therapy. A stratification towards single (pN1a) and multiple (pN1b) N1-metastases was found of prognostic relevance only in adenocarcinoma. Prospective multicenter analysis of prognostic subgroups in N1 NSCLC is required to evaluate its clinical impact for consideration in future TNM classification.

MS06.04 Approaches to Overcoming the Nodal Staging Quality Gap

MS06.04 Approaches to Overcoming the Nodal Staging Quality Gap

Postoperative Radiotherapy (PORT) Improves Survivals of Resected pN2 Non-Small Cell Lung Cancer (NSCLC): A Propensity Score-Matched (PSM) Analysis

To evaluate the effect of PORT on survivals as well as tumor control in patients with pN2 NSCLC after complete resection. From Jan. 2003 to Dec. 2015, patients with resected pN2 NSCLC at our institution were retrospectively studied. PSM analysis was conducted to generate comparable study arms. The effect of PORT on survivals (OS, DFS, LRFS, and DMFS) were evaluated using the Kaplan–Meier method and log-rank tests. Cox’s proportional hazards model was used for multivariate analysis. A statistically significant difference was set as p＜0.05. Totally 1434 patients were enrolled, including 341 (23.8%) in the PORT group and 1093 (76.2%) in the non-PORT group. The median follow-up time was 41.8 months. Patients treated with PORT had significantly longer OS (p＜0.001) and DFS (p=0.001) when compared with the control, as well as LRFS (p＜0.001) and DMFS (p=0.015). Multivariate analyses showed that PORT was an independent prognostic factor associating with better OS (HR=0.756, p=0.012). Moreover, we analyzed the effect of PORT on survivals for pⅢA–N2 NSCLC patients who received adjuvant chemotherapy using PSM to balance several covariates. After adjustment, PORT also significantly improved the survivals. The 3- and 5-year OS rates were 72.9% and 56.1%, respectively in the PORT group and were 62.6% and 41.7%, respectively in the control group (p=0.01). The 3- and 5-year DFS rates were 38.9% and 29.5%, respectively in the PORT group and were 21.6% and 13.2%, respectively in the control group (p＜0.001). The 3- and 5-year LRFS rates were 59.0% and 43.8% versus 38.3% and 20.5% in the PORT versus control group, respectively(p＜0.001). The 3- and 5-year DMFS rates were 44.5% and 33.2% versus 30.6% and 15.0% in the PORT versus control group, respectively (p＜0.0001). For NSCLC patients with resected pN2 or pⅢA-N2 receiving adjuvant chemotherapy, PORT can significantly improve the rates of OS, DFS, LRFS and DMFS. A prospective randomized multicenter clinical trial led by our institution is ongoing now.

Impact of Radiotherapy on Predictive Value of Systematic Inflammation-immune Score in Patients with pN2 Non-Small Cell Lung Cancer

Impact of Radiotherapy on Predictive Value of Systematic Inflammation-immune Score in Patients with pN2 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

Visceral pleural invasion in T1 tumors (≤3 cm), particularly T1a, in the eighth tumor-node-metastasis classification system for non-small cell lung cancer: a population-based study.

We aimed to validate the tumor (T) descriptors of visceral pleural invasion (VPI) for T1 tumors (<3 cm) in the 8th edition of the tumor-node-metastasis (TNM) classification system and the prognostic value of VPI for resected T1a tumors. The external cohort consisted of 23,501 patients with resected pN0 non-small cell lung cancer (NSCLC) selected from the Surveillance, Epidemiology, and End Results (SEER) database (2010 to 2013). The classification of T1 tumors with VPI was investigated using survival curves. The internal cohort consisted of patients diagnosed with pN0 NSCLC between 2011 and 2013 at Guangdong Lung Cancer Institute. The prognostic value of VPI for T1a tumors (<1 cm) was further assessed in these two cohorts. The overall survival (OS) and lung cancer-specific survival (LCSS) of the T1-VPI group and groups of each T stage (size only) were compared in the external (SEER) cohort. There were no significant survival differences between the T1-VPI and T2a groups (OS: P=0.706; LCSS: P=0.792) and T1-VPI and T2b groups, although the latter showed a trend toward lower P-values (OS: P=0.117; LCSS: P=0.094). In the internal cohort, a significant difference in OS was observed between patients with T1-VPI and those with T2b (P=0.049). Among patients with T1a tumors and VPI in the SEER database, the prognosis of the non-sub-lobectomy group was superior to that of the sub-lobectomy group, with intrathoracic recurrence as the predominant relapse pattern of T1 tumors with VPI (69.2%). T1 tumors (<3 cm) with VPI can be staged as T2a in the 8th TNM staging system and surgical resection of T1a tumors is a concern when VPI is present.

Role of Skip Mediastinal Lymph Node Metastasis for Patients With Resectable Non–small-cell Lung Cancer: A Propensity Score Matching Analysis

BackgroundN2 disease represents a heterogeneous group of non–small-cell lung cancer (NSCLC) with varying 5-year overall survival (OS) rates. The skip N2 phenomenon is quite frequent, and its prognostic impact remains a matter of debate. The aim of this study is to further assess the clinical significance and prognostic value of skip N2 disease using propensity score matching. Patients and MethodsThe study cohort included 437 patients with stage pN2 NSCLC who underwent resection from 2005 to 2011. Differences in clinicopathologic characteristics were identified in the overall cohort. The effect of skip N2 on OS was assessed, stratified by histology, tumor size, N2 involved stations, and T stage after propensity score matching. ResultsA total of 130 patients had skip N2 diseases in our study. Skip N2 metastasis was associated with age, tumor size, histology, and number of involved N2 stations. Matching of 130 pairs of patients showed that skip N2 was associated with a significantly better 5-year OS rate when compared with non-skip N2 disease (42.7% vs. 25.3%; P = .004), and OS is significantly better in the patients with tumor size of ≤ 3 cm (P = .014) or patients with single N2 station involvement (P = .002). Skip N2 conferred a significantly better OS in stage IIIA (P = .026) and IIIB (P = .029) disease. ConclusionThe presence of skip N2 metastasis was a good prognostic factor of resectable N2 disease. N2 disease may be classified into more subgroups in the revision of the current tumor-lymph node-metastasis (TNM) system.

Adjuvant therapy for resected pN2 non-small cell lung cancer: sequence is not all that matters.

We appreciate the comments from Zhao and Ng (1) regarding our recent National Cancer Database (NCDB) study comparing survival outcomes after postoperative adjuvant concurrent chemoradiotherapy (CRT) versus sequential chemotherapy followed by postoperative radiotherapy (C→PORT) for locally advanced or incompletely resected non-small cell lung cancer (NSCLC).

Clinical characteristics of patients with lymph skip metastases and prognoses of Chinese patients with pN2 non-small cell lung cancer.

e20524Background: Given that the prognoses of patients with pN2 non-small cell lung cancer (NSCLC) are heterogeneous, the optimal patient management remains controversial. The real-world study was ...

Prognostic Significance of the Number of Removed Lymph Nodes in Pathologic Node-Negative Non-small Cell Lung Cancer

Major lung resection combined with mediastinal lymph node dissection is the standard operation for early-stage non-small cell lung cancer (NSCLC), and lymph node staging is the main predictor of long-term survival. This study aims to identify the prognostic significance of the number of removed lymph nodes in patients with pathologic node-negative (pN0) non-small cell lung cancer (NSCLC). Five hundred thirty-six stage pN0 NSCLC patients, received curative resection between January 2004 and July 2011, were enrolled in this retrospective study. The prognostic factors including the number of removed lymph nodes and clinicopathological characteristics were analyzed. Increasing number of removed lymph nodes was associated with better overall survival (OS) (p = 0.009) of stage pN0 NSCLC patients. The number (p < 0.001) and stations (p = 0.011) of removed lymph nodes, tumor stage (p < 0.001), as well as tumor size (p = 0.017), were independent prognostic factors of stage pN0 NSCLC patients. Overall, patients with more than three stations of examined mediastinal lymph node (p = 0.001) owned better 5-year OS. In subgroup analyses, patients of stage T1 and T2 with more than 11 removed lymph nodes (p = 0.033 and p = 0.011, respectively), and patients of stage T3 with more than 16 removed lymph nodes (p < 0.001) obtained improvements of 5-year OS. The number of removed lymph nodes was not correlated with the incidence of postoperative complications (p = 0.130). The number of removed lymph nodes is an independent prognostic factor for stage pN0 NSCLC patients. Sufficient lymph node dissection is recommended to improve the prognosis of patients with pN0 NSCLC.

Clinical significance of skipping mediastinal lymph node metastasis in N2 non-small cell lung cancer.

Lymph node metastasis is critical for the prognosis of non-small cell lung cancer (NSCLC) patients, and understanding of the pattern of lymph node metastasis is key to the treatment. We aim to investigate the N2 NSCLC patients without N1 lymph node involvement. From 1999 to 2005, a total of 803 patients with pN2 NSCLC were enrolled in this study. Among them, 137 pN2 patients with no metastasis at the hilar (N1) lymph nodes [skip (+) group] were compared with the other 666 patients [skip (-) group]. The percentage of male, smoker and squamous cell carcinoma patients were significantly higher in the skip (+) group, (83.21% vs. 64.11%, P<0.001; 76.64% vs. 53.60%, P<0.001; 50.36% vs. 37.54%, P=0.007, respectively). Also, the primary tumor of skip (+) group patients were significantly more often located in the right upper and middle lobe (43.07% vs. 23.42%, 10.95% vs. 4.05%, P=0.001), and metastasis more frequently involved one lymph node station (75.18% vs. 49.55%, P<0.001). There was no significant difference in the number of total and N2 lymph node dissected. The postoperative survival of patients in both groups were also similar (P=0.379). Skipping mediastinal lymph node metastasis happens in about 17% of NSCLC patients with mediastinal lymph nodes metastasis but it is not a prognostic factor.

Prognostic Impact of Extracapsular Lymph Node Invasion on Survival in Non-small-Cell Lung Cancer: A Systematic Review and Meta-analysis.

The extracapsular tumor extension (ECE) of nodal metastasis is an important prognostic factor in different types of malignancies. However, there is a lack of recent data in patients with non-small-cell lung cancer (NSCLC). In addition, the TNM staging system does not include ECE status as a prognostic factor. This systematic review and meta-analysis has been conducted to summarize and pool existing data to determine the prognostic role of ECE in patients with lymph node-positive NSCLC. Two authors performed an independent search in PubMed using a predefined keyword list, without language restrictions with publication date since 1990. Prospective or retrospective studies reporting data on prognostic parameters in subjects with NSCLC with positive ECE or with only intracapsular lymph node metastasis were retrieved. Data were summarized using risk ratios (RR) for the survival with 95% confidence intervals (CI). The data was analyzed using Mix 2 (ref: Bax L: MIX 2.0 - Professional software for meta-analysis in Excel. Version 2.015. BiostatXL, 2016. https://www.meta-analysis-made-easy.com ). There 2,105 studies were reviewed. Five studies covering a total of 828 subjects met the inclusion criteria and were included in the meta-analysis. Two hundred and ninety-eight (35.9%) patients were categorized as ECE+, of whom 54 (18.1%) survived at the end of follow-up. In the ECE-negative group, 257 patients (48.4%) survived by the end of follow-up. Thus, ECE status is associated with a significantly decreased survival rate: pooled RR 0.45 (95% CI 0.35-0.59), Q (4)=4.06, P value=0.39, and I 2=68.00% (95 CI 0.00-79.55%). In conclusion, ECE has a significant impact on survival in NSCLC patients and should be considered in diagnostic and therapeutic decisions in addition to the current TNM staging. Postoperative radiotherapy may be an option in ECE-positive pN1 NSCLC patients.

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.

Choice of postoperative radiation for stage IIIA pathologic N2 non-small cell lung cancer: impact of metastatic lymph node number

BackgroundPostoperative radiation (PORT) is an option for non-small cell lung cancer (NSCLC) patients with resectable stage IIIA pathological N2 status (pN2). For patients with PORT, this study aims to investigate the impact of the exact number of positive lymph nodes (LNs) on overall survival (OS) and lung cancer-specific survival (LCSS).MethodsWithin the Surveillance, Epidemiology, and End Results database, we identified 3373 patients with stage IIIA pathological N2 status (pN2) NSCLC who underwent a lobectomy or pneumonectomy from 2004 to 2013. OS and LCSS were compared among patients coded as receiving PORT or observation. The proportional hazards model was applied for investigation.ResultsOS and LCSS favored PORT for patients with stage IIIA (pN2) NSCLC. Multivariable analyses showed that PORT and the exact number of positive LNs (n ≤ 3) were independently associated with better OS and LCSS. Both better OS and LCSS emerged for positive LNs (n > 3) after the use of PORT in survival analyses, whereas the benefits of OS and LCSS were not observed anymore for positive LNs (n ≤ 3) group. More importantly, multivariable analyses showed that the use of PORT is an independent risk factor of survival for positive LNs (n > 3) but not for positive LNs (n ≤ 3).ConclusionsIn Stage IIIA (pN2) NSCLC, the use of PORT demonstrated better survival results than no PORT for patients with positive LNs (n > 3), but not for patients with positive LNs (n ≤ 3).

Impact of Omission of Intrapulmonary Lymph Node Retrieval on Outcome Evaluation of Lung Cancer Patients Without Lymph Node Metastasis: A Propensity Score Matching Analysis

IntroductionClinical practice of retrieval of segmental (station 13) and subsegmental (station 14) lymph nodes for pathologic examination varies during lung cancer surgery. This study aimed to evaluate whether omitting retrieval of nodes from stations 13 and 14 could affect outcome evaluation for patients with pN0 non–small-cell lung cancer (NSCLC). MethodsThis retrospective study analyzed 442 patients with NSCLC who were treated with both R0 resection and systematic mediastinal lymphadenectomy with pathologically confirmed stage pN0 NSCLC. The study group included patients in whom N1 nodes including stations 10 to 14 were investigated, and the control group included patients in whom stations 10 to 12 only were investigated. Clinical and pathologic parameters of the groups were balanced by propensity score matching, and oncologic outcomes were assessed by the log-rank test. ResultsA total of 435 cases were included in the final analysis (170 in the study group and 265 in the control group). In the study group, a mean ± SD of 5.0 ± 3.0 nodes per case were collected from nodes 13 and 14. After propensity score matching, 143 cases were included in each group. Overall and disease-free survival improved in the study group compared to the control group (P = .027 and P = .021, respectively). T staging and intrapulmonary node collection were prognostic factors for pN0 cases. ConclusionInferior oncologic outcomes of pN0 cases without intrapulmonary node retrieval suggest that the procedure of intrapulmonary lymph node retrieval may play a role in outcome evaluation for pN0 NSCLC patients.

Effect of visceral pleural invasion on the prognosis of patients with lymph node negative non-small cell lung cancer.

BackgroundVisceral pleural invasion (VPI) is an adverse prognostic factor in non‐small cell lung cancer (NSCLC); however, its effect in relation to tumor size remains under debate. To better understand the prognostic impact and potential consequences for staging, we examined correlations between VPI and clinicopathologic characteristics in patients with NSCLC, particularly those with lymph node negative NSCLC.MethodsWe retrospectively analyzed 813 cases of radically resected NSCLC treated in our institution between December 2005 and December 2011. Patients were divided into two groups according to VPI status to compare their clinicopathologic characteristics. Survival analysis was performed in 521 cases with pN0 NSCLC.Results VPI was diagnosed in 379 (46.6%) cases. It was more common in women, patients with non‐squamous cell carcinoma, elevated preoperative serum carcinoembryonic antigen levels, moderately or poorly differentiated tumors, and larger‐sized tumors. The incidence of mediastinal lymph node metastasis, particularly multi‐station metastasis, was higher in patients with VPI. Patients with pN0 NSCLC, 2–3 cm tumors, and VPI had a significantly poorer prognosis (VPI vs. non‐VPI: five‐year overall survival 78.3% vs. 84.5%, P = 0.039; five‐year disease‐free survival 69.2% vs. 80.0%, P = 0.046, respectively); however, no significant effect was observed for tumors ≤2, 3–5, and 5–7 cm. P‐N0 patients with VPI had a significantly higher incidence of postoperative local recurrence and distant metastasis than those without VPI (P = 0.01), especially ipsilateral pleural recurrence.Conclusion VPI was an adverse prognostic factor in radically resected pN0 NSCLC, especially for tumors 2–3 cm in size.

P2.02-038 Surgical Outcome of Stage III A-cN2/pN2 Non-Small Cell Lung Cancer

Treatment for patients with confirmed mediastinal lymph node involvement (cN2/IIIA) is still a controversial issue. In this study, we evaluated the effect of surgical outcome in patients with clinical(c-) stage IIIA-N2 non-small cell lung cancer (NSCLC) pathologically proven N2(cN2/pN2) before surgery. The subjects selected for analysis were 63 patients with Stage IIIA-cN2/pN2 NSCLC who underwent surgical complete pulmonary resection among 1340 cases receiving surgical resection for NSCLC at Nagasaki University between January 2000 and July 2013. Of these 63 cases, 32 patients pathologically proven N2-positive stage III NSCLC underwent induction therapy. As for the induction therapy, 21 cases had chemotherapy, and 11 cases had induction chemoradiotherapy (Cisplatin plus oral S-1 and concurrent 40 Gy radiation in 10 cases, Cisplatin, Vinorelbine, and Bevacizumab plus 60Gy radiation in 1 case). In all 63 cases, 5-year overall survival (OS) was 32.3%. On univariate analysis, patholocial T factor (pT1-2), upper lobe origin, single-station pathological N2, negative subcarinal node status, and extent of N2 metastasis (localized N2 metastasis) were favorable predictive factors in OS. On multivariate analysis, identified adjuvant chemotherapy was the only independent predictors of survival. In the cases of induction therapy, partial response (PR) was observed in 20 patients (63%). Pathological down staging of N2 disease (from pN2 to pN0-1) was confirmed in 12 cases (37%). OS in this cases was 33.5%. In 10 patients with cisplatin plus oral S-1 and concurrent radiation, there were 4 patients (40%) had a down staging of disease with complete lymph node response. In these patients 3 cases are alive without recurrence during 12-32 months follow up. Induction therapy containing cisplatin plus oral S-1 and concurrent radiation seems be feasible and had good response rate. At present, although no improvement in survival was shown for the statistical analysis with induction chemoradiotherapy followed by surgery in cN2/pN2 NSCLC because the number of cases was low, we come to expect improving outcomes in the future.