Occult N2 Research Articles

P2.02-033 The Role of Surgery for Treating Occult N2 Non-Small Cell Lung Cancer

The presence of mediastinal nodal metastasis is one of the most important factors in the treatment of non-small cell lung cancer (NSCLC). The role of surgical intervention for treating N2 disease is controversial, and two randomized trials failed to show an overall survival benefit. Consequently, the purpose here is to elucidate the needs for surgical intervention of resectable N2 NSCLC. Between April 2010 and May 2016, 316 patients with NSCLC underwent pulmonary resection and mediastinal lymph node dissection. Patients with pathologic N2 were 26. Clinical outcomes and risk factors for pathologic N2 disease were retrospectively analyzed for this cohort. Surgical treatment was performed of 26 pathologic N2 disease patients; there were 18 men and 8 women with a mean age of 68.3 years old (range 55-84). Occult pathologic N2 disease was identified in 22 patients (84.6%). The most common type of resection was lobectomy (96.1%). Adjuvant chemotherapy was administered in 21 patients (80.8%). N2 involvement was single-station in 4 (15.4%) and multiple-station in 22 (84.6%). All patients recovered and were discharged home. There was no operative mortality, and no hospital deaths. The 5-year overall and disease-free survival rates were 58.6% and 33.4%, respectively. The 5-year survival rates of single-station and multiple-station N2 were 50% and 73.2%, respectively (p =0.92). Patients with clinical (expected) N2 disease exhibited better survival outcomes compared with those with occult N2 disease (100% vs 59.8%). The group receiving adjuvant chemotherapy had significantly higher the 5-year survival rates. The 5-year survival rate in patients who received 4 or more cycles of adjuvant chemotherapy was 78.1%, as compared with 0% in non-treated patients (p =0.0008). The 5-year overall and disease-free survival rates of N2 disease tend to improve in recent years. The reasons for improved survival are the increasingly successful treatment options for recurrent disease, including chemotherapy, radiotherapy, and/or molecular targeting drugs. It is common knowledge that therapy of N2 disease needs not only surgery but also chemotherapy. The multiple courses of adjuvant chemotherapy may further improve the outcome in N2 disease. However, patients treated with surgery and chemotherapy had significantly better the 5-year survival rates than patients treated with chemotherapy alone. Though surgery might be very important in that way, the role of surgery for treating N2 disease remains an open question. Because we acknowledge that as a single-institution and retrospective analysis, our sample size was limited. We consider that large-scale, multicenter clinical trials are needed.

MA10.06 Centrality Definition in Non-Small Cell Lung Cancer. Predictor For Occult Mediastinal Lymph Node Involvment

Central tumor location is considered as an independent risk factor for occult mediastinal metastases in patients with non-small cell lung cancer (NSCLC) after negative computerized tomography (CT) and integrated positron emission tomography/CT. However, the distinction between a central and a peripheral tumor has not been codified, some authors consider any tumor in the innerthird of the hemithorax to be central, and others in the inner twothirds. The objective of this study is to identify the best centrality tumor definition for detecting occult mediastinal metastasis. We retrospectively reviewed our thoracic surgery database for cases between January 2011 and December 2015. It was identified patients with potentially operable NSCLC screened by CT and PET/CT and they were classified according to tumor location in the inner third, middle third or outer third. The prevalence of occult mediastinal lymph node metastases was analyzed in relation to tumor location. Statistical analysis for best centrality definition was performed. Univariable analysis was performed using the Fisher exact test and multivariable analysis using logistic regression. A total of 359 patients with clinical operable NSCLC were included in our study. Seventy-five (20.9%) tumors were located in the inner third, 137 (38.2%) in the middle third and 147 (40.9%) in the outer third. It was detected 23 patients with N2 disease and negative TC and PET/CT, 8/38 (21.1%) in the inner third, 6/121 (5.0%) in the middle third and 9/122 (7.4%) in the outer third. Defining centrality as tumor located in the inner third of the hemithorax the incidence of occult N2 was 21.1% and 6.2% for central and peripheral tumor respectively. And defining centrality as tumor located in the inner two-thirds the incidence of occult N2 was 8.8% for central tumors and 7.4% for peripheral. Univariable analysis shows statistical differences in occult N2 involvement between central or peripheral defining central lesion as inner third (p=0.002), but not for central definition of internal two-thirds (p=0.651). In multivariable analysis considering centrality possible definition, histology, Clinical T factor and Clinical N1 affection, only inner third as centrality definition was statistical significance predictor factor for occult mediastinal lymph node involvement (p= 0.027). Considering the results of our study the best definition for central tumor location is limited to the inner third of the hemithorax. Given the low rate of occult N2 disease in the middle third location, the systematic evaluation of the mediastinum by ecobronchoscopy and/or mediastinoscopy in this group of patients is not justified.

P1.08-019 Risk Factors and Survival of Occult N2 Lymph Node Metastasis in NSCLC Patients with Clinical N0-1 Diagnosed by Preoperative PET-CT

Accurate staging of NSCLC for N2 lymph node metastasis is crucial for prognosis and optimal therapy. Suggestion of occult mediastinal lymph node metastasis could help physicians for decision making of staging and management. This study was aimed to know risk factors and survival for occult N2 lymph node metastasis in NSCLC patients with clinical N0 and N1 diagnosed by preoperative PET-CT. This study was evaluated NSCLC patients with clinical N0-1 who underwent R0 lung resection with complete lymphadenectomy. Clinicopathological factors such as tumor size, tumor location, tumor laterality, histology, and FDG uptake were analyzed to delineate risk factors. Overall survival was analyzed. Between November 2005 and December 2014, the incidence of N2 lymph node metastasis was 13.3% (22 patients of 166). The risk factors for pN2 were central located tumor (p<0.001), larger tumor size on CT (p=0.038), and high SUV on PET (p=0.001). Patients having risk factor of central tumor had shorter survival, significantly (p<0.001). The central located tumor, larger tumor size on CT, and high SUV of primary tumor were predictable factors for N2 lymph node metastasis in clinical N0-1 NSCLC. Therefore, these factors may help determined whether to enforce cN0-1 patients to do mediastinal staging selectively.

PUB004 Preoperative Therapy is Not Required for Clinically Occult N2 Non-Small Cell Lung Cancer

Patients with clinically evident N2 NSCLC are usually treated by definitive chemoradiation or by resection following neoadjuvant therapy. To date, No clinical-trials compared survival differences between induction and adjuvant therapy for occult N2-disease. We tested the hypothesis that patients with occult-N2 have equivalent survival after either neoadjuvant or adjuvant therapy. A retrospective review of a prospective database (2005-2014) was performed to identify patients with CT/PET negative mediastinal nodes, who were subsequently found to have positive N2 nodes either by mediastinoscopy or after resection. Demographic, clinical, and pathological data were reviewed. Disease free survival (DFS) was analyzed using Kaplan-Meier and differences compared using log-rank. Cox proportional hazards regression analysis was performed to determine the independent predictors of DFS. Univariate predictors (p<0.20) were selected for inclusion in a multivariate model. Among 1693 patients with cN0-cN1 by PET/CT, 116 (6.8%) had pathologically confirmed N2 disease, of whom 101 had surgical resection. Fifty two patients had mediastinoscopy, of whom 20 (38%) were positive and received induction chemotherapy followed by surgical resection. Surgical resection followed by adjuvant chemotherapy was done in the remaining 81 patients. There was no difference between the induction and no induction groups in clinical variables (Table1), the number of positive mediastinal nodal stations (median 1 in both groups, p=0.605), or in 5 years DFS (31% vs. 36%, p= 0.644) (Fig1). In the multivariate model of the whole cohort, timing of chemotherapy (preoperative or adjuvant) was not associated with worse DFS, while increased clinical tumor size was the strongest predictor of worse DFS (HR:1.47, CI: 1.16-1.85, p= 0.001). Patients with NSCLC and clinically occult N2 by PET/CT maybe treated by primary surgical resection followed by adjuvant chemotherapy. Invasive mediastinal staging in this setting has a low sensitivity and is not necessary.

PS01.43: Clinically Occult N2 Non–Small Cell Lung Cancer: Timing of Chemotherapy does not affect the Oncologic Outcomes.

PS01.43: Clinically Occult N2 Non–Small Cell Lung Cancer: Timing of Chemotherapy does not affect the Oncologic Outcomes.

Association of maximum standardized uptake value with occult mediastinal lymph node metastases in cN0 non-small cell lung cancer.

The management of non-small cell lung cancer (NSCLC) relies on the tumour-node-metastasis (TNM) stage, and the treatment regimen differs based on the N status. Positron emission tomography-computed tomography (PET-CT) has emerged as a powerful imaging tool for the detection of various cancers with a relatively low false-negative rate. We explored predictors to identify false-negative N2 disease in PET-CT. A total of 284 consecutive cN0 patients with peripheral NSCLC who underwent PET-CT scans followed by curative intent resections were enrolled as a training set to identify predictors of occult N2 metastases by multivariable analysis. The accuracy and cut-off values for the predictors were calculated using a receiver operating characteristic curve. Clinical and pathological data were analysed retrospectively. An additional 151 patients were collected as a test set to validate the results, including the occult N2 rate and accuracy. In total, 8.5% (24/284) PET-CT-diagnosed N0 NSCLC cases had pathologically diagnosed N2 metastases. The SUVmax of the primary tumour was a unique independent risk factor for occult N2 NSCLC [P = 0.003, 95% confidence interval = 0.81-0.96, odds ratio (OR) = 0.88]. Occult N2 metastases occurred more frequently in the subcarinal (16/24) and right lower paratracheal lymph nodes (12/24). Accordingly, we divided the patients into two groups by SUVmax: the occult N2 rates in the SUVmax of <2.6 and SUVmax of ≥2.6 groups were 1.0% (1/100) and 12.5% (23/184), respectively (P = 0.001). In the test set, the occult N2 incidence rate was 9.3% (14/151), with the highest rates occurring in the subcarinal (9/14) and right lower paratracheal lymph nodes (6/14). In the two groups defined by SUVmax, the occult N2 rates were 4% (2/50) and 11.9% (12/101), respectively. The SUVmax of the primary tumour was an independent risk factor for occult N2 metastases in NSCLC patients diagnosed as clinical N0 by PET-CT. SUVmax of ≥2.6 of the primary tumour may indicate the risk of N2 metastases, and invasive mediastinal staging techniques or comprehensive therapy should not be ignored in these patients.

Factors predicting occult lymph node metastasis in completely resected lung adenocarcinoma of 3 cm or smaller.

The aim of the study is to demonstrate the relationship between clinicopathological variables and occult lymph node metastasis in resected lung adenocarcinoma. The clinicopathological characteristics of 471 patients with clinical N2-negative status undergoing resection for lung adenocarcinoma of 3 cm or smaller at Taipei Veterans General Hospital between 2004 and 2012 were retrospectively reviewed. The association between clinicopathological variables and lymph node metastasis was analysed by univariate and multivariate logistic regression. Among the 471 patients, there were 386 (82.0%) patients with pathological N0 status, 35 (7.4%) with pathological N1 status and 50 (10.6%) with pathological N2 status. Greater tumour size (P = 0.002), presence of a micropapillary pattern (P < 0.001), presence of a solid pattern (P < 0.001) and predominant pattern group (micropapillary/solid predominant) (P = 0.001) were significantly associated with higher percentage of occult N2 lymph node metastasis. In multivariate analysis, greater tumour size (P = 0.008), presence of micropapillary pattern (P < 0.001) and presence of solid pattern (P = 0.001) were significant predictors of occult N2 lymph node metastasis in tumours of 3 cm or smaller. When histological pattern was entered as the predominant pattern in multivariate analysis, micropapillary/solid predominant pattern (P = 0.005) was also a significant predictor of occult N2 lymph node metastasis. The presence of micropapillary or solid pattern, as well as micropapillary/solid predominant pattern, is significantly associated with occult N2 lymph node metastasis in lung adenocarcinoma. Radical mediastinal lymph node dissection may help to identify occult lymph node metastasis in these patients.

434P Nomogram to predict occult N2 lymph nodes metastases in patients with squamous non-small cell lung cancer

434P Nomogram to predict occult N2 lymph nodes metastases in patients with squamous non-small cell lung cancer

Nomogram to Predict Occult N2 Lymph Nodes Metastases in Patients With Squamous Nonsmall Cell Lung Cancer

For nonsmall cell lung cancer (NSCLC) patients without distant metastases, occult involvement of N2 lymph nodes would be of the utmost importance in determining both treatment and survival. The key to optimal treatment strategies relied on accurate diagnosis, in particular accurate clinical tumor staging. Patients with clinical N0 or N1 staging preoperatively had a sizeable risk to have occult N2 lymph nodes metastases.From November 2004 to March 2007, the entire database in a tertiary hospital of all patients with a pathologic diagnosis of squamous NSCLC underwent anatomical pulmonary resection and systematic mediastinal lymph node dissection were retrospectively collected and reviewed. A nomogram was developed on the basis of a multivariable logistic regression model with a combination of all potential variables. In order to surmount the potential of overestimating predictive performance, both bootstrapping for internal validation and an independent external validation set were employed.A nomogram incorporating the significant risk factors was created to predict the probability of occult N2 lymph nodes metastases. The calibration plot for the probability of occult N2 lymph nodes metastases showed an optimal agreement between the predicted probabilities by nomogram and actual observed probabilities. An objective and accurate nomogram predictive model for occult N2 lymph nodes metastases was drawn up and validated internally and externally in patients with squamous NSCLC.The nomogram model, as a robust tool in predicting occult N2 lymph nodes involvement, could be involved in a cost-effective application of specific diagnostic and therapeutic strategies.

Invited Commentary

Is this article by Cho and colleagues [1] just another paper on unsuspected or occult N2? In fact, the authors found occult N2 in about 1 in 10 patients with clinical N0. Occult N2 disease found at thoracotomy has been a source for an everlasting dispute between surgeons looking at locally advanced disease from different perspectives. In fact, arguments have been raised supporting the need for systematic frozen section analysis of mediastinal nodes during thoracotomy. Some have suggested that, should a positive N2 node station be identified, the resection is aborted and the patient sent for chemotherapy or for chemoradiation and only in the presence of complete response retaken back to the operative room.

Modern Outcome and Risk Analysis of Surgically Resected Occult N2 Non-Small Cell Lung Cancer

This study was performed to assess the incidence, survival, and risk factors associated with unsuspected pathologic N2 disease in patients with resectable clinical N0-1 non-small cell lung cancer. Between January 2002 and December 2010, 1,821patients with clinical N0-1 non-small cell lung cancer underwent pulmonary resection and mediastinal lymph node dissection. Clinical outcomes and risk factors for pathologic N2 disease were retrospectively analyzed for this cohort. Unsuspected pathologic N2 disease was identified in 196 patients (10.8%). The most common type of resection was lobectomy (81.6%). Adjuvant therapy was administered in 177 patients (90.3%). The median follow-up time was 28 months (range, 1 to 101 months). N2 involvement was single-station in 121 (66.8%) and multiple-station in 65 (33.2%). The 5-year overall and disease-free survival rates were 56.1% and 35.0%, respectively. The 5-year survival rates of single-station and multiple-station N2 were 66.6% and 36.4%, respectively (p < 0.001). Adenocarcinoma, clinical N1, tumor size (>3 cm), and a right middle lobe tumor were identified as independent risk factors for unsuspected multiple-station N2 disease by multivariate analysis. Incidence of unsuspected multiple-station N2 disease in low-risk classes (aggregate score, 0 to ≤2) was only 5.5%. The incidence of unsuspected N2 disease in our cohort was similar to that of previous reports. Survival outcomes were favorable for unsuspected single-station N2 disease but were poor for unsuspected multiple-station N2 disease. Clinical N0-1 non-small cell lung cancer patients with risk class of low score for unsuspected multiple-station N2 disease can be exempted from aggressive mediastinal staging.

Prognostic Value of Primary Tumor FDG Uptake for Occult Mediastinal Lymph Node Involvement in Clinically N2/N3 Node-negative Non–Small Cell Lung Cancer

The objective of this study was to identify predictive factors of occult mediastinal nodal involvement on staging positron emission tomography with F-fluorodeoxyglucose in patients with non-small cell lung cancer. We performed a retrospective review of 665 patients with suspected non-small cell lung cancer who underwent staging positron emission tomography with F-fluorodeoxyglucose from January 1, 2000 through August 31, 2010 at the Hospital of the University of Pennsylvania with clinical stage I or II disease and no evidence of N2 or N3 involvement on staging positron emission tomography (PET). A total of 201 of these patients underwent invasive pathologic staging of the mediastinum at the Hospital of the University of Pennsylvania with pathology reports available at the time of review. A total of 63 of the 201 patients were found to have N2 disease at the time of pathologic staging. The mean standardized uptake value (SUV) of the primary tumor for patients with occult N2 metastases was significantly higher than the node-negative patients (SUV 9.31 vs. 7.24, P=0.04). Histology, tumor location (central vs. peripheral), sex, and age were not predictive for occult N2 disease. A multivariate analysis was performed and identified primary tumor SUV>6 was the only significant predictor (P=0.02). An analysis by quartile identified a primary tumor SUV>10 to have an odds ratio of 1.72 compared with an SUV<4 of occult N2 involvement. Increased primary tumor SUV predicted for increased risk of mediastinal nodal disease. Tumor location was not predictive of PET-occult mediastinal nodal involvement, in contrast to previous publications. Pathologic staging of the mediastinum should be strongly considered in these patients even with a negative mediastinum on PET.

Endobronchial Ultrasonography-Guided Transbronchial Needle Aspiration Biopsy for Preoperative Nodal Staging of Lung Cancer in a Veteran Population

Recently, preoperative lung cancer staging has evolved to include endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) biopsies of the hilar and mediastinal lymph nodes, but the feasibility and usefulness of the procedure have not been well studied in the veteran population. To determine the safety and effectiveness of EBUS-TBNA as a key component of a preoperative staging algorithm for lung cancer in veterans. Review of a prospectively maintained thoracic surgery database that includes patients who underwent lung resection for lung cancer between January 1, 2009, and December 31, 2012, at a single Veterans Affairs medical center among a consecutive cohort of 166 patients with clinically early-stage (I or II) lung cancer who underwent lobectomy with nodal dissection. Endobronchial ultrasonography-guided transbronchial needle aspiration mediastinal staging (EBUS group) in 62 patients (37.3%) was compared with noninvasive nodal staging plus integrated positron emission tomography-computed tomography only (PET/CT-only group) in 104 patients (62.7%). The accuracy of nodal staging was assessed by comparison with the final pathological staging after complete nodal dissection (the gold standard). Primary outcomes were feasibility, safety, accuracy, and negative predictive value of EBUS-TBNA for preoperative nodal staging. A secondary outcome was the rate of nontherapeutic lung resection for occult N2 disease, with comparison between the EBUS group and the PET/CT-only group. No significant complications were attributable to the EBUS-TBNA procedure. In the EBUS group, 258 lymph node stations were sampled. N1 hilar metastases were diagnosed in 8 patients (12.9%) before surgery, and the remainder were staged N0. Accuracy and negative predictive value of EBUS-TBNA were 93.5% (58 of 62) and 92.6% (50 of 54), respectively. The overall rate of nontherapeutic lung resection performed in patients with occult N2 disease was 10.8% (18 of 166) (8.1% in the EBUS group and 12.5% in the PET/CT-only group) (P = .37). A preoperative lung cancer staging strategy that includes EBUS-TBNA seems to be safe and effective in a veteran population, resulting in a low rate of nontherapeutic operations because of occult N2 nodal disease.

Development and Validation of a Clinical Prediction Model for N2 Lymph Node Metastasis in Non-Small Cell Lung Cancer

The true incidence of occult N2 lymph node metastasis in patients with clinical N0 non-small cell lung cancer (NSCLC) remains controversial. Estimation of the probability of N2 lymph node metastasis can assist physicians when making diagnosis and treatment decisions. We reviewed the medical records of 605 patients (group A) and 211 patients (group B) with computed tomography-defined N0 NSCLC that had an exact tumor-node-metastasis stage after surgery. Logistic regression analysis of group A's clinical characteristics was used to estimate the independent predictors of N2 lymph node metastasis. A prediction model was then built and internally validated by using cross validation and externally validated in group B. The model was also compared with 2 previously described models. We identified 4 independent predictors of N2 disease: a younger age; larger tumor size; central tumor location; and adenocarcinoma or adenosquamous carcinoma pathology. The model showed good calibration (Hosmer-Lemeshow test: p = 0.96) with an area under the receiver operating characteristic curve (AUC) of 0.756 (95% confidence interval, 0.699 to 0.813). The AUC of our model was better than those of the other models when validated with independent data. Our prediction model estimated the pretest probability of N2 disease in computed tomography-defined N0 NSCLC and was more accurate than the existing models. Use of our model can be of assistance when making clinical decisions about invasive or expensive mediastinal staging procedures.

Surgical Approach to Locally Advanced Non-Small Cell Lung Cancer

Treatment for locally advanced non-small cell lung cancer is complex. It may best be described as chemotherapy-based multimodality therapy, but there is little consensus on the optimal approach for local therapy. With the integration of the 7th edition of the staging system, the role for surgery in stage IIIB is limited to only biopsies and staging procedures. Surgery plays a more important role in stage IIIA disease, when the extent of mediastinal lymph node involvement is the principal factor dictating the benefit that can be derived from resection. In N2-negative, stage IIIA patients (T4N0, T3N1, T4N1), surgery is the primary therapy. These tend to be large and complex resections that include removal of neighboring involved structures. In the larger cohort of N2-positive, stage IIIA patients, surgery is reserved for those with occult or resectable N2 involvement and not used for bulky mediastinal disease. Significant controversy exists regarding which patients with potentially resectable N2 should receive surgery and how to best integrate a resection with chemotherapy and radiation.

Stage migration: results of lymph node dissection in the era of modern imaging and invasive staging for lung cancer†

Lung cancer staging has improved in recent years. Assuming that contemporary detailed preoperative staging may yield a lower rate of stage change after surgery, we were interested to determine the impact of our lymph node dissections performed at the time of surgical resection. We retrospectively analysed a database in our surgical unit that prospectively captured information on all patients assessed and treated for lung cancer. We reviewed the data on patients who underwent lung cancer surgery with curative intent between January 2006 and August 2010 so as to reflect contemporary practice. Prior to potentially curative treatment, patients systematically underwent staging computerized tomography (CT), integrated positron emission tomography (PET) with CT and brain imaging. Enlarged and/or PET-positive nodes were subject to invasive evaluation to establish the nodal status in line with the current guidelines. This was performed by needle aspiration or biopsy usually with ultrasound guidance, endobronchial or endo-oesophageal ultrasound with needle biopsy; mediastinoscopy; mediastinotomy; video-assisted or open surgery. Three hundred and twelve lung cancer resections were performed (a mean age of 68 years [range 42-86] and a male-to-female ratio of 1.14:1). Despite thorough preoperative evaluations, 25.3% of patients had a change in nodal status after lung resection and lymph node dissection; of which 20.8% of patients had a nodal status upstaging. Occult N2 disease was identified in 31 (9.9%) of 312 patients. Patients with cT1 tumours showed a nodal upstaging of 12.3% compared with 25.3% in cT2 tumours. There was no difference in the rate of N2 disease for different tumour histological types. Despite systematic preoperative staging, there continues to be a high rate of nodal status change following surgical resection and lymph node dissection. If considering non-surgical treatments for the early stage lung cancer, the impact of this discrepancy should be considered. If not, errors in prognosis and in determining correct adjuvant treatment may arise.

Comparison of Integrated Positron Emission Tomography/Computed Tomography and Mediastinoscopy in Mediastinal Staging of Non-Small Cell Lung Cancer: Analysis of 212 Patients

Background : Mediastinal staging is crucial to determine the prognosis and treatment options for patients with non-small cell lung cancer (NSCLC). In this study, we compared the results of integrated positron emission tomography-computerised tomography (PET/CT) with those of mediastinoscopy in mediastinal staging of NSCLC patients. Methods : PET/CT and mediastinoscopy was performed on 250 consecutive patients diagnosed with NSCLC between September 2005 and March 2008. Thirty-eight patients were excluded from the study. Standard cervical mediastinoscopy was performed in all patients, and simultaneous extended cervical mediastinoscopy was performed in 52 patients with left sided lesions. Patients with negative mediastinoscopy underwent resection. The pathological results were correlated with PET/CT findings.Results : A total of 212 patients (199 male, 13 female; mean age: 58.3 years) were evaluated. In PET/CT analysis 60 true-positive, 45 false-positive, 103 true-negative and 4 false-negative patients were found. The rate of PET/CT positivity of mediastinal lymph nodes was 49.5%. The sensitivity, specificity, positive and negative predictive values and accuracy for PET/CT were 93.8%, 69.6%, 57.1%, 96.3% and 76.9% respectively. The incidence of N2 disease in NSCLC patients with negative mediastinal lymph node uptake on PET/CT was 3.7% (4 of 107). In univariate analysis, right upper lobe tumours were significantly (p < 0.05) more associated with occult N2 disease.Conclusions : In patients with positive mediastinal lymph node uptake on PET/CT invasive mediastinal staging appears necessary for exact staging. Mediastinoscopy can be omitted in NSCLC patients with negative mediastinal uptake on PET/CT in regions where the rate of PET/CT positivity of mediastinal lymph nodes is high.

Standard uptake value of positron emission tomography in clinical stage I lung cancer: clinical application and pathological correlation

The aim of this study was to assess the standard uptake value in clinical stage I non-small cell lung cancer (NSCLC) and its correlation with pathological status and prognosis. We retrospectively reviewed 674 patients diagnosed with NSCLC between January 2002 and June 2005. Patients with clinical stage I diseases undergone a preoperative positron emission tomography-computed tomography scan followed by anatomic resection. We reviewed the clinical features of 152 patients with an average follow-up of 87 months. We analysed the clinical features of 108 patients with stage I NSCLC and 44 patients with non-stage I NSCLC. There were no statistical differences in age, histological type, location or tumour differentiation between the two groups. In the Stage I group, the patients had lower maximum standard uptake value (SUVmax; 3.80 ± 3.17 vs 5.73 ± 3.65, P = 0.001), lower carcinoembryonic antigen (CEA) levels (2.86 ± 4.80 vs 9.11 ± 17.21 ng/ml, P = 0.027) and smaller tumour size (2.39 ± 0.98 vs 3.73 ± 2.04 cm, P < 0.001). The patients with higher SUVmax had a more advanced pathological stage, poorer tumour differentiation and larger tumour size. A higher SUVmax was an independent factor predicting an advanced pathological stage (SUVmax ≥ 3.3, odds ratio 3.246). The median survival of patients with SUVmax ≥ 3.3 and SUVmax <3.3 were 64.32 and 53.08 months, respectively (P = 0.654). Higher preoperative 18-fluorodeoxyglucose uptake by a tumour was significantly associated with an advanced pathological stage but not correlated with a poorer prognosis. An aggressive preoperative work-up for occult N2 disease should be emphasized, avoiding inappropriate thoracotomy.

Number of Lymph Nodes Harvested From a Mediastinal Lymphadenectomy: Results of the Randomized, Prospective American College of Surgeons Oncology Group Z0030 Trial

Lymph node status is a major determinant of stage and survival in patients with lung cancer; however, little information is available about the expected yield of a mediastinal lymphadenectomy.The American College of Surgeons Oncology Group Z0030 prospective, randomized trial of mediastinal lymph node sampling vs complete mediastinal lymphadenectomy during pulmonary resection enrolled 1,111 patients from July 1999 to February 2004. Data from 524 patients who underwent complete mediastinal lymph node dissection were analyzed to determine the number of lymph nodes obtained.The median number of additional lymph nodes harvested from a mediastinal lymphadenectomy following systematic sampling was 18 with a range of one to 72 for right-sided tumors, and 18 with a range of four to 69 for left-sided tumors. The median number of N2 nodes harvested was 11 on the right and 12 on the left. A median of at least six nodes was harvested from at least three stations in 99% of patients, and 90% of patients had at least 10 nodes harvested from three stations. Overall, 21 patients (4%) were found to have occult N2 disease.Although high variability exists in the actual number of lymph nodes obtained from various nodal stations, complete mediastinal lymphadenectomy removes one or more lymph nodes from all mediastinal stations. Adequate mediastinal lymphadenectomy should include stations 2R, 4R, 7, 8, and 9 for right-sided cancers and stations 4L, 5, 6, 7, 8, and 9 for left-sided cancers. Six or more nodes were resected in 99% of patients in this study.ClinicalTrials.gov; No.: NCT00003831; URL: clinicaltrials.gov.

Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non–small cell carcinoma: Results of the American College of Surgery Oncology Group Z0030 Trial

To determine whether mediastinal lymph node dissection improves survival compared with mediastinal lymph node sampling in patients undergoing resection for N0 or nonhilar N1, T1, or T2 non-small cell lung cancer. Patients with non-small cell lung cancer underwent sampling of 2R, 4R, 7, and 10R for right-sided tumors and 5, 6, 7, and 10L for left-sided tumors. If all tumors were negative for malignancy, patients were randomized to no further lymph node sampling (mediastinal lymph node sampling) or complete mediastinal lymph node dissection. Of 1111 patients randomized, 1023 (mediastinal lymph node sampling in 498, mediastinal lymph node dissection in 525) were eligible and evaluable. There were no significant differences between the 2 groups in terms of demographics, Eastern Cooperative Oncology Group status, histology, cancer location, type or extent of resection, and pathologic stage. Occult N2 disease was found in 21 patients in the mediastinal lymph node dissection group. At a median follow-up of 6.5 years, 435 patients (43%) have died: mediastinal lymph node sampling in 217 (44%) and mediastinal lymph node dissection in 218 (42%). The median survival is 8.1 years for mediastinal lymph node sampling and 8.5 years for mediastinal lymph node dissection (P = .25). The 5-year disease-free survival was 69% (95% confidence interval, 64-74) in the mediastinal lymph node sampling group and 68% (95% confidence interval, 64-73) years in the mediastinal lymph node dissection group (P = .92). There was no difference in local (P = .52), regional (P = .10), or distant (P = .76) recurrence between the 2 groups. If systematic and thorough presection sampling of the mediastinal and hilar lymph nodes is negative, mediastinal lymph node dissection does not improve survival in patients with early stage non-small cell lung cancer, but these results are not generalizable to patients staged radiographically or those with higher stage tumors.