cN1 Non-small Cell Lung Cancer Research Articles

Systematic endoscopic staging of mediastinum to guide radiotherapy planning in patients with locally advanced non-small-cell lung cancer (SEISMIC): an international, multicentre, single-arm, clinical trial

Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning. This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314. From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29-44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7-17]) participants, including 16 (13% [7-19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2-12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1-52·3). No serious adverse events following endoscopic staging were reported. Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC. None.

Role of fluorodeoxyglucose-positron emission tomography in predicting the pathological response and prognosis after neoadjuvant chemoradiotherapy for locally advanced non-small-cell lung cancer.

OBJECTIVESThe present study compared the utility of fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) for predicting the pathological response and prognosis following neoadjuvant therapy for locally advanced non-small-cell lung cancer (NSCLC).METHODSThis retrospective analysis included 72 patients in whom adjacent structures showed involvement and/or cN2 NSCLC who received induction chemoradiotherapy (ICRT) and subsequent surgery at our hospital from 2008 to 2019. FDG-PET and CT were performed in all patients before and after ICRT using the same scanner with similar techniques. We calculated the reduction in the maximum standardized uptake value in FDG-PET (ΔSUVmax) and tumour size on CT (ΔCT-size) before and after ICRT and investigated the relationship between the pathological response and prognosis.RESULTSThe disease response was classified as a major pathological response in 43 patients, and a minor response in 29 patients. ΔSUVmax 60% and ΔCT-size 30% were identified as the optimal cut-off values for predicting a major pathological response. ΔSUVmax was superior to ΔCT-size in terms of sensitivity, specificity, positive predictive value and negative predictive value. Furthermore, ΔSUVmax was superior to ΔCT-size for predicting the prognosis.CONCLUSIONSBased on the results of the present study, FDG-PET appeared to have greater utility than CT in predicting the pathological response following ICRT and the postoperative prognosis in patients with locally advanced NSCLC.

Diagnostic utility of metabolic parameters on FDG PET/CT for lymph node metastasis in patients with cN2 non-small cell lung cancer

BackgroundThe aim of this study was to assess the diagnostic utility of metabolic parameters on fluorine-18-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) for predicting lymph node (LN) metastasis in patients with cN2 non-small cell lung cancer (NSCLC).MethodsWe retrospectively reviewed patients who underwent surgery for cN2 NSCLC between 2007 and 2020. Those who had clinically diagnosed positive hilar and mediastinal LNs by routine CT and PET/CT imaging were investigated. To measure the metabolic parameters of LNs, the data according to maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN-to-primary tumor ratio of SUVmax (LPR) were examined. The diagnosis of each retrieved LN was confirmed based on histopathological examination of surgical tissue specimens. Receiver operating characteristics (ROC) curves with area under the curve (AUC) calculations and multivariate analysis by logistic regression were performed.ResultsForty-five patients with 84 clinically diagnosed positive hilar or mediastinal LNs were enrolled in the present study. Of the 84 LNs, 63 LNs were pathologically proven as positive (75%). The SUVmax, MTV, TLG, and LPR of LN metastasis were significantly higher than those of benign nodes. In the ROC analysis, the AUC value of LPR [AUC, 0.776; 95% confidence interval (CI), 0.640–0.913] was higher than that of LN SUVmax (AUC, 0.753; 95% CI, 0.626–0.880) or LN TLG3.5 (AUC, 0.746; 95% CI, 0.607–0.885). Using the optimal LPR cutoff value of 0.47, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.1, 66.7, 88.3, 58.3, and 79.8%, respectively. Multivariate analysis by logistic regression showed that LPR was an independent predictor for LN metastasis (odds ratio, 6.45; 95% CI, 1.785–23.301; P = 0.004). In the subgroup analysis of adenocarcinoma patients (n = 18; 32 LNs), TLG3.5 was a better predictor (AUC, 0.816; 95% CI, 0.639–0.985) than LPR (AUC, 0.792; 95% CI, 0.599–0.986) or LN SUVmax (AUC, 0.792; 95% CI, 0.625–0.959).ConclusionsOur findings suggest that LPR on FDG-PET is a useful predictor for LN metastasis in patients with cN2 NSCLC. TLG can be a good predictor for LN metastasis in patients with adenocarcinoma.

P07.01 Less Accuracy of CT and PET in the Evaluation of N1 Node may Result in Overlooking Skip Metastasis of Single Station cN2 Non-Small Cell Lung Cancer

P07.01 Less Accuracy of CT and PET in the Evaluation of N1 Node may Result in Overlooking Skip Metastasis of Single Station cN2 Non-Small Cell Lung Cancer

Preoperative identification of clinicopathological prognostic factors for relapse-free survival in clinical N1 non-small cell lung cancer: a retrospective single center-based study

BackgroundGiven the difficulty in preoperatively diagnosing lymph node metastasis, patients with Stage I–III non-small cell lung cancer (NSCLC) are likely to be included in the clinical N1 (cN1) group. However, better treatment options might be selected through further stratification. This study aimed to identify preoperative clinicopathological prognostic and stratification factors for patients with cN1 NSCLC.MethodsThis retrospective study evaluated 60 patients who were diagnosed with NSCLC during 2004–2014. Clinical nodal status had been evaluated using routine chest computed tomography (CT) and/or positron emission tomography (PET). To avoid biasing the fluorodeoxyglucose uptake values based on inter-institution or inter-model differences, we used only two PET systems (one PET system and one PET/CT system). Relapse-free survival (RFS) and overall survival (OS) were the primary study outcomes. The maximum standardized uptake value (SUVmax) was calculated for each tumor and categorized as low or high based on the median value. Patient sex, age, histology, tumor size, and tumor markers were also assessed.ResultsPoor OS was associated with older age (P = 0.0159) and high SUVmax values (P = 0.0142). Poor RFS was associated with positive carcinoembryonic antigen (CEA) expression (P = 0.0035) and high SUVmax values (P = 0.015). Multivariate analyses confirmed that poor OS was independently predicted by older age (hazard ratio [HR] = 2.751, confidence interval [CI]: 1.300–5.822; P = 0.0081) and high SUVmax values (HR = 5.121, 95% CI: 1.759–14.910; P = 0.0027). Furthermore, poor RFS was independently predicted by positive CEA expression (HR = 2.376, 95% CI: 1.056–5.348; P = 0.0366) and high SUVmax values (HR = 2.789, 95% CI: 1.042–7.458; P = 0.0410). The primary tumor’s SUVmax value was also an independent prognostic factor for both OS and RFS.ConclusionsFor patients with cN1 NSCLC, preoperative prognosis and stratification might be performed based on CEA expression, age, and the primary tumor’s SUVmax value. To enhance the prognostic value of the primary tumor’s SUVmax value, minimizing bias between facilities and models could lead to a more accurate prognostication.

Optimal adjuvant therapy in clinically N2 non-small cell lung cancer patients undergoing neoadjuvant chemotherapy and surgery: The importance of pathological response and lymph node ratio

ObjectivesOptimal adjuvant therapy in patients with clinically N2 (cN2) non-small cell lung cancer (NSCLC) who undergo neoadjuvant chemotherapy followed by surgery is controversial. We evaluated the impact of adjuvant chemotherapy (CT) and/or radiation (RT) in this patient population. Materials and methodsPatients with non-metastatic, cN2 NSCLC diagnosed from 2004 to 2015 were identified from the National Cancer Database, which captures 70% of cancer cases diagnosed in the United States. Patients underwent neoadjuvant CT and surgical resection. Patients couldn’t receive RT before surgery. Survival was compared using log-rank and Cox proportional hazards modeling. Subset analyses were performed based on post-chemotherapy surgical nodal staging (ypN0-2) and lymph node ratio (LNR), including 0%, 1–15%, or >15% involvement. LNR was defined as number of nodes involved by tumor divided by number of nodes examined. Results and conclusionsWe identified 1541 patients. The percentage of patients who received adjuvant CT and RT was 18.9% and 35.7% respectively. ypN status and LNR were predictive of survival on univariate analysis, but only LNR maintained significance on multivariate analysis. There was no benefit observed for adjuvant CT or RT in the entire cohort. On subset analyses, a survival benefit was observed in ypN2 patients with receipt of CT or RT (HRs 0.77 and 0.81, respectively, p < 0.05). In patients with LNR > 15%, there was a significant benefit of RT (HR 0.76, p = 0.007) and borderline benefit of CT (HR 0.78, p = 0.058). Patients with cN2 disease with subsequent ypN0-1 and/or LNR < 15% following induction chemotherapy do not benefit from adjuvant therapy. Patients with persistent N2 disease and LNR > 15% who receive adjuvant CT and RT have improved survival. Aggressive consolidative therapy appears to improve survival in patients with persistent or high nodal burden disease.

Practice patterns and impact of post-operative radiation therapy on overall survival after neoadjuvant chemotherapy for cN2 non-small cell lung cancer

Practice patterns and impact of post-operative radiation therapy on overall survival after neoadjuvant chemotherapy for cN2 non-small cell lung cancer

EP-1378 Brain imaging pre/post treatment in cN2 non-small cell lung cancer treated with chemo-radiation

EP-1378 Brain imaging pre/post treatment in cN2 non-small cell lung cancer treated with chemo-radiation

Review on Treatment Modalities for Resectable IIIa/N2 Non-small Cell Lung Cancer

临床可切除Ⅲa/N2期非小细胞肺癌（non-small cell lung cancer, NSCLC）的治疗模式一直存在争议，化疗、放疗、手术等治疗手段都有可改善其生存的报道，靶向治疗和免疫治疗的研究也有较多新进展，联合治疗的选择更是很多临床试验研究的重点。联合治疗包括化疗联合手术或放疗，以及化疗、放疗和手术三种治疗的联合。对于NSCLC最佳治疗模式目前尚无定论。本文通过对多项Ⅱ期、Ⅲ期临床试验及meta分析、个案报道的综述回顾，比较不同治疗方式对临床可切除Ⅲa/N2期NSCLC的生存影响，结果显示多学科治疗中手术对于延长患者生存是必要的选择，而新辅助化疗后联合手术并不优于联合放疗。依据肿瘤大小、淋巴结累及情况等进行个体化治疗是未来值得进一步探索的方向。

Pathologic nodal clearance and complete response following neoadjuvant chemoradiation for clinical N2 non-small cell lung cancer: Predictors and long-term outcomes

PurposeFrom prospective studies, pathologic nodal clearance (PNC, ypN0) and pathologic complete response (pCR, ypT0N0) correlate with overall survival (OS) following neoadjuvant chemoradiation for cN2 non-small cell lung cancer (NSCLC). Contemporary cooperative group trials attempt to increase radiation doses to achieve nodal clearance and/or pCR. However, long-term comparative outcomes of dose-escalated neoadjuvant chemoradiation are lacking. The goal of this study was to evaluate rates of PNC and pCR in a large population of cN2 NSCLC, predictors thereof, and long-term outcomes thereafter. MethodsThe National Cancer Database was queried (2004–2015) for histologically-confirmed cT1-4N2M0 NSCLC undergoing neoadjuvant chemoradiation followed by lobectomy. Statistics included multivariable logistic regression, Kaplan-Meier OS analysis before and following propensity matching, Cox proportional hazards modeling, and sensitivity analysis when varying neoadjuvant radiation dose. ResultsOf 1750 patients, the pCR and PNC rates were 17% and 37%, respectively. Radiation dose >54 Gy independently predicted for pCR. Patients achieving pCR experienced significantly higher OS than non-pCR cases (p < 0.001) and ypT + ypN0 cases (p < 0.001). In the subset of non-PNC patients, there was a trend towards higher OS in patients in whom ypT0 was achieved (p = 0.059). On sensitivity analysis, when separating the cohort into doses of 45.0–50.4 Gy, 50.5–54.0 Gy, 54.1–59.4 Gy, and >59.4 Gy, 30-day mortality rates in the respective groups were 2.9%, 1.8%, 1.2%, and 3.4%. ConclusionsAlthough neoadjuvant dose-escalation increases pCR rates, there is no OS benefit with dose-escalation, and high dose-escalation (i.e., >59.4 Gy) was associated with numerically higher mortality rates, indicating the importance of careful multidisciplinary discussion.

P2.16-42 Standard Mediastinoscopy Versus Video-Assisted Mediastinoscopic Lymphadectomy in Clinical N1 Non-Small Cell Lung Cancer

A considerable number of patients with clinical N1 (cN1) non-small cell lung cancer (NSCLC) based on positron emission tomography–computed tomography (PET-CT) imaging have occult mediastinal nodal involvement (N2 disease). We aimed to compare the role of video-assisted mediastinoscopy lymphadenectomy(VAMLA) and standard mediastinoscopy in pre-resectional mediastinal staging in patients with cN1 disease. A total of 821 patients with potentially resectable NSCLC seen between January 2004 and November 2016 were included in the study. The preoperative mediastinal staging was accomplished by standard cervical mediastinoscopy or VAMLA in all patients except those with peripheral cT1N0 tumors. Resection via thoracotomy or video-assisted thoracoscopic surgery was performed in patients with no mediastinal lymph node metastasis. A systematic lymph node sampling or systematic lymph node dissection was performed during resectional surgery. Surgical-pathological results were compared with the pathological findings. Primary aim was to compare the sensitivities and accuracies to detect N2 by two methods. Out of 85 patients with cN1 on PET-CT, a mediastinal metastasis was disclosed in 29 patients (34.1%). Of 56 patients who underwent VAMLA 24(42.9%) were found to have N2/3 disease, whereas standard mediastinoscopy revealed N2/N3 disease in 7 patients(24.1%)(p=0.029) VAMLA and standard mediastinoscopy had both sensitivities of 85.7% to detect N2 disease(p=1). The NPVs were 87.5% and 85.7% by VAMLA and standard mediastinoscopy respectively(p=0.821). VAMLA is more accurate to detect mediastinal nodal disease in operable cN1 lung cancer, and could be used in patients with cN1 NSCLC patients since it discloses N2 disease in an important fraction of patients.

P1.17-17 The Impact of Induction Chemoradiotherapy Followed by Surgery for N1 Involved Non-Small Cell Lung Cancer

Induction chemoradiotherapy (iCRT) followed by surgery is usually selected for locally advanced non-small cell lung cancer (NSCLC) patients with mediastinal lymph node (LN) metastasis or invasion to adjacent organs, whereas it is occasionally performed for clinical N1 (cN1) NSCLC patients harboring such as a centrally located primary tumor or a bulky LN to improve local control rate and secure a cancer-free surgical margin. However, the survival benefit of iCRT followed by surgery for NSCLC patients with N1 LN involvement remains controversial. Furthermore, the accuracy of the radiological examination for N1 metastasis is unsatisfactory. In this study, we investigated the clinical outcomes of surgery with or without iCRT based on the estimation of the pretreatment LN metastatic status from fibrotic or necrotic changes of resected LNs in the cN1 NSCLC patients. cN1 NSCLC patients who underwent complete resection with or without iCRT at our institution between January 1999 and December 2016 were subjected. We divided the enrolled patients into two groups as the primary surgery (PS) group and the iCRT followed by surgery (IC) group. As for IC group, we determined the pretreatment LN metastatic status based on the pathological features of resected LNs. We compared the clinical outcomes of pretreatment N1 involved patients with or without iCRT. Among 127 cN1 NSCLC patients, 40 patients were considered as pretreatment N1 involvement, consisting of 26 and 14 patients in the PS and IC groups, respectively. The central type tumor and the continuous type of LN, which frequently required the extended surgical procedures, were significantly more frequent in the IC group than in the PS group (P < 0.01). Although there was no significant difference in the recurrence pattern between the two groups, none of patients developed local recurrence in the IC group. Regarding the patients with a centrally located tumor or a bulky LN (> 2.0cm), the 5-year recurrence-free survival was significantly better in the IC group than in the PS group (74.1% vs, 36.4%; P =0.03). Our study demonstrated that iCRT followed by surgery could suppress the disease recurrence in the N1-involved NSCLC patients especially for the patients harboring a centrally located tumor or bulky LNs at N1 level, suggesting that these patients may be good candidates for iCRT followed by surgery to avoid extended resections and to suppress the local recurrence.

P2.01-71 Clinical Outcome of Induction Chemoradiotherapy Followed by Surgery for the Patients with cN2 Non-Small Cell Lung Cancer

P2.01-71 Clinical Outcome of Induction Chemoradiotherapy Followed by Surgery for the Patients with cN2 Non-Small Cell Lung Cancer

Neoadjuvant and adjuvant therapy for Stage III non-small cell lung cancer.

The treatments for advanced non-small cell lung cancer (NSCLC) should control both local and microscopic systemic disease, because the 5-year survival of patients with Stage III NSCLC who underwent surgical resection alone has been dismal. One way to improve surgical outcome is the administration of chemotherapy before or after the surgical procedure. During the last two decades, many clinical studies have focused on developing optimal adjuvant or neoadjuvant chemotherapy regimens that can be combined with surgical treatment and/or radiotherapy. Based on the results of those clinical studies, multimodality therapy is considered to be an appropriate treatment approach for Stage IIIA NSCLC patients; although, optimal treatment strategies are still evolving. When N2 nodal involvement is discovered postoperatively, adjuvant cisplatin-based chemotherapy confers an overall survival benefit. The addition of postoperative radiotherapy might be considered for patients with nodal metastases. Although definitive chemoradiation remains a standard of care for cN2 NSCLC, alternative approaches such as induction chemotherapy or chemoradiotherapy and surgery can be considered for a selective group of patients. When surgical resection can be performed after induction therapy with low risk and a good chance of complete resection, the outcome may be optimal. The decision to proceed with resection after induction therapy must include a detailed preoperative pulmonary function evaluation as well as a critical intraoperative assessment of the feasibility of complete resection.

Predictors for hilar/intrapulmonary lymph node metastasis in discrete type of clinical N1 non-small cell lung cancer.

Accurate preoperative evaluation of lymph nodes can provide optimal treatment for patients. However, in patients with clinical N1 disease (cN1) non-small cell lung cancer (NSCLC), no suitable predictor has been identified for hilar/intrapulmonary lymph node metastasis (pathological N1 disease; pN1). The purpose of this study was to identify pN1 in cN1 NSCLC patients. We retrospectively reviewed the clinicoradiological features of 109 patients with a discrete type of cN1 NSCLC who had undergone complete resection at our institution from 2004 to 2015. The association between clinicoradiological variables and nodal status was analyzed to identify predictors for pN1. The cohort consisted of 77 males and 32 females, ranging in age from 39 to 84years. The breakdown by pathological N category was 40 (37%) pN0, 41 (38%) pN1, and 28 (25%) pN2 patients. Maximum lymph node diameter was identified as a significant predictor for pN1, with an odds ratio of 1.25 (P=0.010). When limited to 63 patients who underwent positron emission tomography (FDG-PET) at our institution, the maximum standardized uptake value (SUVmax) of the lymph node was an independent predictor, with an odds ratio of 1.91 with logistic regression analysis (P=0.004). The size of lymph node and the SUVmax were significant factors for pN1, with optimal cut-off values of 13mm and 4.28, respectively. Among the patients with cN1, maximum lymph node size and SUVmax of the FDG-PET were significant predictors for pN1.

Histological type predicts mediastinal metastasis and surgical outcome in resected cN1 non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) patients at cN1 have unfavorable outcomes. It has been reported that a substantial proportion of cN1 patients have occult mediastinal disease, and treatment guidelines suggest invasive preoperative mediastinal evaluation. However, the population that would most benefit from invasive staging has not been defined. The aims of this study are to identify factors predicting mediastinal metastasis and outcomes in cN1 NSCLC patients to select appropriate candidates for invasive mediastinal evaluation. We retrospectively studied 164 patients with radiologically diagnosed cN1 NSCLC. Clinicopathological factors including radiological nodal findings were reviewed. Factors predicting the pN2 status, disease-free survival (DFS), and overall survival (OS) were investigated. Among 164 patients with cN1 disease, pN2 was diagnosed in 43 (26.4%). This pN2 subgroup included a higher proportion of cases with adenocarcinoma (AD) histology than the pN0/1 subgroup (60.5 vs. 38.8%, p=0.012). Logistic regression analyses revealed AD as an independent predictor of the pN2 status, while radiological nodal findings were unrelated. Cox regression analyses identified lower preoperative serum CEA, non-AD, and pN0/1 status as favorable factors of DFS and adjuvant therapy to be associated with OS. Five-year DFS was much lower in the pN2 subgroup than the pN0/1 subgroup of AD patients (p<0.001), while DFS was independent of pN status in non-AD patients. Adenocarcinoma is predictive of pN2 and poor prognosis in radiologically diagnosed cN1 NSCLC. Accurate mediastinal staging may be more beneficial for prognoses and optimal treatment planning in NSCLC patients with AD histology.

P1.03-073 Predictors for Pathological N1 and N2 Disease in Clinical N1 Non-Small-Cell Lung Cancer

Patients with clinical N1 (cN1) non-small-cell lung cancer (NSCLC) is usually considered to be candidates for curative resection. However, they sometimes have unexpected mediastinal nodal involvement (pN2). To avoid futile pulmonary resection, accurate preoperative evaluation of nodal status would be necessary. The purpose of this study was to identify predictors for lymph node metastasis in cN1 NSCLC patients. We retrospectively reviewed data on the clinicopathological and radiological features of 170 patients with cN1 NSCLC who had undergone complete resection at Nagoya University Hospital between 2004 and 2015. Hilar and/or intrapulmonary lymph nodes with ≥ 1.0 cm in the short axis on computed tomography or with high accumulation of [18F] Fluorodeoxyglucose (FDG) in positron emission tomography compared with that of the adjacent mediastinal tissue were considered as cN1 in our institution. The association between clinicoradiological variables and nodal status was analyzed to identify predictors for lymph node metastasis. The cohort consisted of 125 males and 45 females, ranging in age 39 to 84 years. There were 62 (36%) adenocarcinomas, 82 (48%) squamous-cell carcinomas, 10 (6%) large-cell carcinomas, and 16 (10%) other types of cancers. The breakdown by pathological N category was 61 (36%) pN0, 72 (42%) pN1, and 37 (22%) pN2 patients. Among pN2 patients, only three showed negative N1 lymph nodes (skip pN2 metastasis). Female gender, adenocarcinoma histology, middle or lower lobe origin and positive N1 lymph node (pN1) were significantly associated with pN2 by univariate analysis. Logistic regression analysis showed that the female and pN1 were significant predictor for pN2 with the odds ratio of 3.0 and 13.1, respectively (P = 0.02 and 0.0001, respectively). In addition, using the 63 patients extracted from our cohort of this study, we sought the predictor of pN1. The maximum size of the lymph node and standardized uptake value of the FDG were significant factor for pN1 with the cut-off value of 1.3 cm and 4.28, respectively. Female gender and pN1 was significantly associated with pN2 in cN1 NSCLC patients of our cohort. The large size and a high accumulation of FDG of hilar or intrapulmonary lymph node might predict the pN1.

PUB032 Surgical Management of cN1 Non-Small Cell Lung Cancer: Histological Impact on Nodal Status and Survival Outcomes

Surgical resection is employed as a standard treatment for cN1 non-small cell lung cancer (NSCLC). In the resected cases, not a small population of unfavorable prognosis including pN2 cases is observed. Invasive mediastinal evaluations using endobronchial ultrasonography and/or mediastinoscopy are suggested for patients with radiological cN1 NSCLC in the several guidelines. However, practical benefits of those modalities remain unclear due to its heterogeneous population. We retrospectively reviewed clinicopathological factors of 161 patients who underwent surgical resection for radiologically diagnosed cN1 NSCLC treated from 2001 to 2013 in our institute. The patients without preoperative invasive mediastinal evaluation and induction treatment were enrolled. To identify the population who can benefit from invasive mediastinal staging, we analyzed predictive factors of pN2 status. Furthermore, disease free survival (DFS), overall survival (OS) and factors affecting them were also investigated. One hundred nineteen patients (73.9%) with pN0-1 and 42 patients (26.1%) of pN2 were identified. More patients of female sex, high serum CEA and adenocarcinoma (AD) histology were included in the pN2 group (p=0.044, 0.028 and 0.024, respectively). The univariate analyses showed that higher age and AD histology were potential predictor for pN2 status (p=0.048 and 0.01, respectively) and the multivariate analysis demonstrated AD histology was a significant predictor for pN2 status (HR: 2.445, p=0.015). Five-year OS rate of the pN0-1 and pN2 AD patients were 56.8% and 34.0%, respectively (p=0.46), those of non-AD patients were 70.2% and 64.9%, respectively (p=0.94). In AD patients, five-year DFS rate of the pN0-1 was 50.2%, which was significantly better than that of pN2 patients, 5.8% (p<0.001), while those of non-AD patients were not different, demonstrating 55.4% and 73.9%, respectively (p=0.48). Out of 26 AD patients with pN2 disease, 24 patients (92.6%) experienced recurrence. Twenty-one patients (80.8%) of them were accompanied with non-local disease. AD histology was the independent predictor for pN2 status in resected cN1 NSCLC. Surgical outcomes of cN1/pN2 AD patients were poor and the efficacies of surgery is considered to be limited for them. While those of non-AD patients was favorable being identical with pN1-0 patients. Mediastinal evaluation of invasive modalities may be more beneficial for AD patients in terms of prognostic distinction and decision of treatment strategies.

Perioperative outcomes and lymph node assessment after induction therapy in patients with clinical N1 or N2 non-small cell lung cancer.

Induction therapy has been shown to benefit patients with resectable stage-2 or stage-3 non-small cell lung cancer (NSCLC). We aimed to determine if induction chemotherapy (CTx) with or without radiation therapy (± RT) for NSCLC with clinical lymph node (LN) involvement (cN1 or cN2) affects LN dissection or perioperative outcomes during robotic-assisted video thoracoscopic (RAVTS) lobectomy. We retrospectively analyzed patients who underwent RAVTS lobectomy for NSCLC over 45 months. We assessed clinical LN status by CT scan, PET scan, endobronchial ultrasound, and/or mediastinoscopy. We grouped patients with cN1 or cN2 as: "no induction therapy", "induction CTx alone" (ICTx), or "induction CTx + RT" (ICTx + RT). Intraoperative estimated blood loss (EBL), operative times, tumor size, LN status, and restaging were noted. Of 256 NSCLC patients who had lobectomy, there were 52 cN1 or cN2 patients, of whom 39 patients had "no induction", 7 had ICTx, and 6 had ICTx + RT. Higher rates of recurrent laryngeal nerve (RLN) injury, tracheal/bronchial injury, and pulmonary embolism were observed with ICTx ± RT (P=0.02, 0.04, and 0.02, respectively). Total number of complications was not significantly different, nor were perioperative outcomes, such as EBL, operative time, and in-hospital mortality. Fewer N2 LN stations were assessed after ICTx ± RT (3.7±0.2 vs. 4.2±0.2 stations; P=0.04), but total number of LNs reported were not significantly different (13.0±2.3 vs. 16.2±1.0 LNs, P=0.22). Of "no induction" patients, 15.4% were upstaged pathologically; no patients were upstaged after induction therapy. While 30.8% of ICTx ± RT patients were downstaged, 38.5% of "no induction" patients were also downstaged on final pathology. Induction CTx ± RT for cN1 or cN2 NSCLC patients did not affect EBL, operative times, or in-house mortality after RAVTS lobectomy. Patients undergoing RAVTS lobectomy after ICTx+ RT may be at greater risk for RLN injury, tracheal/bronchial injury, and pulmonary embolism. Fewer N2 LN stations, but not numbers of LNs, are assessed after ICTx ± RT. Induction therapy does not lead to increased downstaging.

Induction Chemotherapy is Not Superior to a Surgery-First Strategy for Clinical N1 Non-Small Cell Lung Cancer

Guidelines recommend primary surgical resection for non-small cell lung cancer (NSCLC) patients with clinical N1 disease and adjuvant chemotherapy if nodal disease is confirmed after resection. We tested the hypothesis that induction chemotherapy for clinical N1 (cN1) disease improves survival. Patients treated with lobectomy or pneumonectomy for cT1-3 N1 M0 NSCLC from 2006 to 2011 in the National Cancer Data Base were stratified by treatment strategy: surgery first vs induction chemotherapy. Propensity scores were developed and matched with a 2:1 nearest neighbor algorithm. Survival analyses using Kaplan-Meier methods were performed on the unadjusted and propensity-matched cohorts. A total of 5,364 cN1 patients were identified for inclusion, of which 565 (10.5%) were treated with induction chemotherapy. Clinical nodal staging was accurate in 68.6% (n= 3,292) of patients treated with surgical resection first, whereas 16.3% (n= 780) were pN0 and 10.7% (n= 514) were pN2-3. Adjuvant chemotherapy was given to 60.9% of the surgery-first patients who were pN1-3 after resection. Before adjustment, patients treated with induction chemotherapy were younger, with lower comorbidity burden, were more likely to be treated at an academic center and to have private insurance (all p < 0.001), but were significantly more likely to have T3 tumors (28.7% vs 9.9%, p < 0.001) and to require pneumonectomy (23.5% vs 18.5%, p=0.005). The unadjusted and propensity-matched analyses found no differences in short-term outcomes or survival between groups. Induction chemotherapy for cN1 NSCLC is not associated with improved survival. This finding supports the currently recommended treatment paradigm of surgery first for cN1 NSCLC.