Mediastinal Lymph Node Stations Research Articles

Video-assisted mediastinoscopic lymphadenectomy combined with transcervical thoracoscopy.

Surgical techniques remain the gold standard to diagnose and staging lung and pleural tumours. Non-invasive techniques have become more accurate but actually they are not enough to plan and evaluating prognosis of lung and pleural tumours. In some cases, we need to explore the pleural cavity and the mediastinal lymph node status to confirm or rule out tumour dissemination. The combination of video-assisted mediastinoscopic lymphadenectomy (VAMLA) and thoracoscopy through a single transcervical incision allows the surgeon to widen the range of the exploration and to improve the staging for lung and pleural cancers. VAMLA allows to perform a complete lymphadenectomy of the subcarinal space, the right and pretracheal areas. We consider sampling more safety on the left side to avoid left recurrent nerve injuries. Once this mediastinal tissue is removed, the right mediastinal pleura can be identified and incised. Once mediastinal pleura is opened, a 5 mm 30º thoracoscope is inserted through the video- mediastinoscope into the pleural cavity. It allows to obtain samples of parietal or visceral pleural, pleural fluid or lung nodules if present. In case of left-sided thoracoscopy the access to the left pleural cavity is anterior to the aortic arch as for extended cervical mediastinoscopy. The combination of VAMLA and thoracoscopy is useful to explore the mediastinum and the pleural space from a single incision and in the same surgical setting through the transcervical approach.

Re-irradiation in locally recurrent lung cancer patients.

Lung cancer remains one of the tumour diagnoses with high lethality, although innovative treatment approaches have yielded improvements in local control and survival rates. There is still no consensus on how to treat local relapse in patients after first-line treatments. Radiotherapy may be considered in this situation; however, data supporting its effectiveness are rare. The purpose of this retrospective analysis was to evaluate outcomes of patients re-irradiated for thoracic tumours in terms of overall survival (OS), local progression-free survival (LPFS), toxicity and dose-volume parameters. Sixty-two patients with locally recurrent previously irradiated lung cancer were analysed retrospectively (NSCLC n = 52, SCLC n = 10). Target volumes both in lung and mediastinum were re-irradiated with conventional three-dimensional or intensity-modulated radiotherapy techniques. Median overall dose of re-irradiation was 38.5 Gy (range 20-60 Gy) with amedian single dose per fraction of 2 Gy (1.8-3.0 Gy). Clinical documents and treatment plans were evaluated. Median follow-up was 8.2months (range 0-27months). OS following re-irradiation was 9.3months (range: 0-27months) and LPFS was 6.5months (range: 0-24months). OS and LPFS were not affected by histology, total dose or patient age and gender. OS was improved in patients whose re-irradiation volumes included less than two mediastinal lymph node stations (p = 0.016). Twelve patients suffered from pneumonitis ≥gradeII (19%) and two from pneumonitis gradeIII. One patient presumably died from pneumonitis gradeV. Aslight decline in forced expiratory volume (FEV1) was detected in post-re-irradiation lung function testing. Re-irradiation is an option for patients with tumour recurrence to control local progression and lower the symptom burden. Oncological outcome appears to be affected by size, location of mediastinal target volumes and lung function. Prospective clinical trials are warranted to substantiate the role of re-irradiation in recurrent lung cancer.

Displaced Cartilage Within Lymph Node Parenchyma Is a Novel Biopsy Site Change in Resected Mediastinal Lymph Nodes Following EBUS-TBNA.

Biopsy site changes in mediastinal lymph nodes (LNs) attributable to prior endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have not been studied in a systematic manner. Twenty-four contributors from 14 institutions in 5 countries collaborated via social media (Twitter) to retrospectively review consecutive cases of resected mediastinal LNs from patients with prior EBUS-TBNA. Resected LNs were reexamined by submitting pathologists for changes attributable to EBUS-TBNA. Patients who received neoadjuvant therapy were excluded. Cases with suspected biopsy site changes underwent central review by 5 pathologists. A total of 297 mediastinal LN resection specimens from 297 patients (183 male/114 female, mean age: 65 y, range: 23 to 87) were reviewed. Biopsy site changes were most common in station 7 (10 cases) followed by 11R, 4R, and 10R, and were found in 34/297 (11.4%) cases, including displacement of tiny cartilage fragments into LN parenchyma in 26, intranodal or perinodal scars in 7, and hemosiderin in 1. Cartilage fragments ranged from 0.26 to 1.03 mm in length and 0.18 to 0.62 mm in width. The mean interval between EBUS-TBNA and LN resection was 38 days (range: 10 to 112) in cases with biopsy site changes. A control group of 40 cases without prior EBUS-TBNA, including 193 mediastinal LN stations, showed no evidence of biopsy site changes. Biopsy site changes are identified in a subset of resected mediastinal LNs previously sampled by EBUS-TBNA. The location of the abnormalities, temporal association with prior EBUS-TBNA, and the absence of such findings in cases without prior EBUS-TBNA support the contention that they are caused by EBUS-TBNA.

Prediction of EGFR mutations by conventional CT-features in advanced pulmonary adenocarcinoma

ObjectiveThis study assessed the ability of conventional computed tomography (CT) features (including primary tumors, metastatic lesions, lymph nodes, and emphysema) to predict epidermal growth factor receptor (EGFR) mutations in advanced pulmonary adenocarcinoma. MethodsPatients who were diagnosed with advanced pulmonary adenocarcinoma between January 2017 and August 2017 and had undergone a chest CT and EGFR mutation testing were enrolled in this retrospective study. Qualitative and quantitative CT-features and clinical characteristics evaluated in this study included: primary tumor location, size, and morphology (including degree of lobulation, density, calcification, cavitation, vacuole sign, and air bronchogram), size and distribution of lung and pleural metastatic nodules, size and status of hilar and mediastinal lymph nodes, emphysema, organs with distant metastasis, and patient age, sex, and smoking history. ResultsOf 201 patients, 107 (53.23%) were EGFR-mutation positive. The multivariate logistic regression indicated that EGFR mutations were significantly associated with smaller lymph nodes, a lower percentage of deep lobulation of the primary tumor and partial fusion of lymph nodes, and absence of emphysema. The area under the curve of logistic regression model for predicting EGFR mutations was 0.898. ConclusionsConventional CT-features, including emphysema, degree of primary tumor lobulation, and lymph node size and status, help to predict the presence or absence of EGFR mutations in advanced pulmonary adenocarcinoma. Additionally, these same CT-features demonstrated that the CT manifestations of the EGFR mutant group were of relatively lower malignancy and less invasive as compared to the wild-type EGFR group.

Diagnostic yield and safety of EUS-FNA biopsy in sub-aortic and para-aortic lymph node stations with the trans-aortic approach: a case series and literature review

ABSTRACTBackground: Sub-aortic (station 5) and para-aortic (station 6) lymph nodes are not easily accessible due to the interposition of the aorta and the left pulmonary artery. Taking a biopsy from those stations could be of value when there are no other mediastinal lymph node stations or when biopsy in other sites failed to reach a diagnosis. Surgery is the gold standard technique in the evaluation of those stations; endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been proposed as a minimally invasive technique through the trans-aortic approach, with an acceptable diagnostic yield and safety profile.Objective: To evaluate diagnostic accuracy and safety of the trans-aortic EUS-FNA in lymph node stations 5 and 6.Methods: We reviewed all patients who underwent trans-aortic EUS-FNA from 2010 to 2017, for mediastinal lymph node enlargement or positron emission tomography/computed tomography (PET/CT) positivity (integrated 2-deoxy-2-fluoro-d-glucose). Demographic characteristics, lesion site and size, needle, final diagnosis, and complications were collected.Results: A total of 11 patients were included, 5 males, mean age 59 years. Samples were inadequate in two cases, a diagnosis of lung cancer was reached in four patients (two adenocarcinoma and two squamous cell carcinoma) and five cases were negative for malignancy (one confirmed by surgery, two were found to be cancer at percutaneous lung biopsy and transbronchial biopsy, one patient received a diagnosis of Langerhans cell histiocytosis by transbronchial lung cryobiopsy, and one patient was lost at follow-up). The sensitivity for malignancy was 57%, and the overall diagnostic accuracy was 45%. No complications occurred.Conclusions: Trans-aortic EUS-FNA could be proposed as a valuable and safe approach for taking biopsy from mediastinal lymph node stations 5 and 6.

A prospective analysis of touch preparation cytology for intraoperative detection of mediastinal lymph node metastases

Patients diagnosed with lung cancer may require immediate evaluation of mediastinal lymph nodes to determine treatment plan. Typically, frozen section (FS) analysis has been used, but this analysis can be time-consuming and uses more tissue than touch preparation (TP) cytologic analysis. TP accuracy has been studied in other organs, but no prospective studies comparing TP to FS have been performed on mediastinal lymph nodes in lung cancer. Our goal was to compare the accuracy of TP to FS in these cases. After obtaining institutional review board approval, all patients undergoing mediastinal lymph node evaluation for a diagnosis of lung cancer were asked to participate. If consent was given, TP and FS analyses were performed on all mediastinal lymph node stations in all patients and compared to permanent hematoxylin and eosin analysis. Data were collected prospectively. Twenty patients were enrolled. Mean age was 67.7 years. Fifty-five percent (11 of 20) of patients were men. The mean number of lymph node stations sampled in each patient was 3.4. In predicting the stage of the patient, TP had a sensitivity and specificity of 95% and 100%, respectively. FS had a lower sensitivity, 85%, and a specificity of 100%. On permanent analysis, metastatic foci ranged in size from 0.15 mm to 1.5 mm. TP was more sensitive than FS in detecting mediastinal lymph node metastases. The technical difficulty of obtaining full-thickness sections without creating significant artifact may contribute to the lower sensitivity of FS in detecting micrometastases.

Postoperative survival analysis of patients with stage Ⅲ-pN2 non-small cell lung cancer

Objective: To investigate the effect of mediastinal lymph node resection, metastasis status and treatment on the prognosis of patients with stage Ⅲ-pN2 non-small cell lung cancer (NSCLC). Methods: Clinical data of 206 patients who were pathologically diagnosed as stage Ⅲ-pN2 NSCLC in Tongji Hospital from July 2006 to Dec 2009 were retrospectively analyzed and followed up. Log rank test and Cox proportional hazards regression model were used to analyze the prognostic significance of mediastinal lymph node excision, metastasis state and treatment. Results: The median overall survival (OS) time of the whole group was 29.6 months, and the median disease-free survival (DFS) time was 27.2 months. Univariate analysis showed that the less number of mediastinal lymph node stations with metastasis (single station), the less number of mediastinal lymph nodes involved (less than 2), and postoperative chemotherapy were associated with longer postoperative OS and DFS time (P<0.05 for all). The patients with skip metastasis, negative metastasis of subcarinal lymph node, the lower mediastinal lymph node metastasis rate (MLNR<33%) and postoperative radiotherapy had longer OS and DFS time than those without these factors (P<0.05 for all). Multivariate analysis showed that metastasis of subcarinal lymph node, MLNR and postoperative chemotherapy were the independent prognostic factors for patients with stage Ⅲ-pN2 NSCLC (P<0.05 for all). Conclusion: Metastasis of subcarinal lymph nodes and the higher MLNR might shorten the postoperative survival time of NSCLC patients with stage Ⅲ-pN2, whereas postoperative chemotherapy prolongs the survival time.

Lung Carcinoids: Long-Term Surgical Results and the Lack of Prognostic Value of Somatostatin Receptors and Other Novel Immunohistochemical Markers

Background/Aims: Lung carcinoids (LCs) are often diagnosed at an early stage and surgical intervention becomes the next phase of treatment. To date, there is lack of long-term follow-up data after surgery and prognostication based on WHO classification criteria and evolving prognostic markers, particularly the expression of somatostatin receptors (SSR). Methods: We included 102 consecutive patients (72 women; age at baseline 51 ± 16 years [mean ± SD]) with LCs, who underwent thoracic surgery (n = 99) and/or laser treatment (n = 8). Hospital charts were reviewed for clinico-pathological parameters. Immunohistochemical (IHC) expression of SSR1–5 and other novel markers were studied with regard to their prognostic value. Results: Five- and 10-year overall survival (OS) was 96 and 83% respectively; relative survival (RS) was 101 and 93% respectively; and event-free survival (EFS) was 80 and 67% respectively. Independent prognostic factors for OS, RS and/or EFS were age at diagnosis, histopathological type and the presence of ipsilateral mediastinal subcarinal lymph node metastases. Macro-radicality of resective surgery and its extent were associated with increased OS and EFS. The IHC expression of SSR1–5 and other novel markers was not associated with OS or EFS. Conclusion: The long-term outcome of surgically treated patients with LCs is favourable. Age, histopathological type and ipsilateral mediastinal subcarinal lymph node status at baseline were independent prognostic factors for survival and disease recurrence or progression. The extent of surgery and operative macro-radicality also had an impact on prognosis. None of the IHC markers tested appeared to be associated with disease prognosis.

Ultrasonography of the Mediastinum: Techniques, Current Practice, and Future Directions.

In the everyday practice of respiratory physicians, ultrasound techniques play a key role by enabling several diagnostic and interventional procedures. The application of ultrasound to endoscopic procedures allows both a visualization and a guided sampling of mediastinal and hilar lymph nodes. Endobronchial ultrasound can be combined with transbronchial needle aspiration, and, similarly, endoscopic ultrasound can be combined with fine-needle aspiration to sample virtually all mediastinal nodal stations from the airways and the esophagus. Endobronchial ultrasound-transbronchial needle aspiration and endoscopic ultrasound-fine needle aspiration showed a complementary diagnostic yield, and, recently, endoscopic ultrasound with bronchoscope was introduced in clinical practice to perform a transesophageal needle aspiration by using an ultrasound bronchoscope. This technique allows a single operator to perform both transbronchial and transesophageal needle sampling with the same instrument during a single bronchoscopic procedure. Mediastinal staging impacts the management of patients affected by lung cancer, and the most recent guidelines clearly state that endobronchial ultrasound and endoscopic ultrasound should be the initial tissue sampling procedure over surgical staging. In addition, endoscopic ultrasound techniques demonstrated an excellent yield in diagnosing lymphoma and benign diseases, for example, sarcoidosis. The aim of this review was to discuss the current role and future perspectives of endosonography techniques available for the evaluation of the mediastinum. Special emphasis was placed on equipment and technical aspects, the diagnostic role, and future directions of development.

Endobronchial Ultrasound for Nodal Staging of Patients with Non-Small-Cell Lung Cancer with Radiologically Normal Mediastinum. A Meta-Analysis.

An accurate assessment of the mediastinal lymph node status is essential in the staging and treatment planning of potentially resectable non-small-cell lung cancer. We performed this meta-analysis to evaluate the role of endobronchial ultrasound-guided transbronchial needle aspiration in detecting occult mediastinal disease in non-small-cell lung cancer with no radiologic mediastinal involvement. The PubMed, Embase, and Cochrane libraries were searched for studies describing the role of endobronchial ultrasound-guided transbronchial needle aspiration in patients with lung cancer with radiologically negative mediastinum. The individual and pooled sensitivity, prevalence, negative predictive value, and diagnostic odds ratio were calculated using the random effects model. Meta-regression analysis, heterogeneity, and publication bias were also assessed. A total of 13 studies that met the inclusion criteria were included in the meta-analysis. The pooled effect sizes of the different diagnostic parameters were estimated as follows: prevalence, 12.8% (95% confidence interval, 10.4-15.7%); sensitivity, 49.5% (95% confidence interval, 36.4-62.6%); negative predictive value, 93.0% (95% confidence interval, 90.3-95.0%); and log diagnostic odds ratio, 5.069 (95% confidence interval, 4.212-5.925). Significant heterogeneity was noticeable for the sensitivity, disease prevalence, and negative predictive value, but not observed for log diagnostic odds ratio. Publication bias was detected for sensitivity, negative predictive value, and log diagnostic odds ratio but not for prevalence. Bivariate meta-regression analysis showed no significant association between the pooled calculated parameters and the type of anesthesia, imaging used to define negative mediastinum, rapid on-site test usage, and presence of bias by Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Interestingly, we observed a greater sensitivity, negative predictive value, and log diagnostic odds ratio for studies published before 2010 and for prospective multicenter studies. Among patients with non-small-cell lung cancer with a radiologically normal mediastinum, the prevalence of mediastinal disease is 12.8% and the sensitivity of endobronchial ultrasound-guided transbronchial needle aspiration is 49.5%. Despite the low sensitivity, the resulting negative predictive value of 93.0% for endobronchial ultrasound-guided transbronchial needle aspiration suggests that mediastinal metastasis is uncommon in such patients.

EGFR and ERBB2 to determine the metastatic status of mediastinal lymph nodes in lung adenocarcinomas harbouring EGFR mutation.

e21215Background: Primary bronchogenic carcinomais the leading cause of cancer-related deaths worldwide and a serious threat to human health.Radiotherapy is one of the fundamental treatments for lu...

The role of plasma D-dimer levels for predicting lymph node and mediastinal lymph node involvement in non-small cell lung cancer.

Elevated plasma D-dimer levels have been suggested as a predictor of poor prognosis in NSCLC. But rare study showed the relationship between D-dimer levels and lymph node involvement. To evaluate the role of plasma D-dimer levels in predicting lymph node and mediastinal lymph node involvement in NSCLC. Preoperative plasma D-dimer levels were quantified in 253 NSCLC patients that underwent radical lung resection with systemic lymph node dissection. Patients were classified as lymph node negative (N0) versus lymph node positive (N1 + N2) and mediastinal lymph node negative (N0 + N1) versus mediastinal lymph node positive (N2). Median plasma D-dimer level was significantly lower in Group N0 (94.0 μg/L) compared to Group N1 + N2 (177.0 μg/L) and in Group N0 + N1 (122.0 μg/L) compared to Group N2 (198.0 μg/L). Similar results were found in patients stratified by age, sex, smoking status and histological type, expect in patients with squamous carcinoma. The Receiver Operating Characteristic (ROC) curve for plasma D-dimer levels of N0 versus N1 + N2 showed an area under the curve (AUC) of 0.757 and when a cutoff value was 124.0 μg/L DDU, the sensitivity and specificity was 0.80 and 0.68. The ROC curve for plasma D-dimer levels of N0 + N1 versus N2 showed an AUC of 0.720 and when a cutoff value was 147.0 μg/L DDU, the sensitivity and specificity was 0.75 and 0.67. Plasma D-dimer level has utility for predicting lymph node and mediastinal lymph node status in patients with operable NSCLC.

A dosimetric phantom study of thoracic radiotherapy based on three-dimensional modeling of mediastinal lymph nodes.

The aim of the present study was to investigate the optimal strategy and dosimetric measurement of thoracic radiotherapy based on three-dimensional (3D) modeling of mediastinal lymph nodes (MLNs). A 3D model of MLNs was constructed from a Chinese Visible Human female dataset. Image registration and fusion between reconstructed MLNs and original chest computed tomography (CT) images was conducted in the Eclipse™ treatment planning system (TPS). There were three plans, including 3D conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT), which were designed based on 10 cases of simulated lung lesions (SLLs) and MLNs. The quality of these plans was evaluated via examining indexes, including conformity index (CI), homogeneity index and clinical target volume (CTV) coverage. Dose-volume histogram analysis was performed on SLL, MLNs and organs at risk (OARs). A Chengdu Dosimetric Phantom (CDP) was then drilled at specific MLNs according to 20 patients with thoracic tumors and of a medium-build. These plans were repeated on fused MLNs and CDP CT images in the Eclipse™ TPS. Radiation doses at the SLLs and MLNs of the CDP were measured and compared with calculated doses. The established 3D MLN model demonstrated the spatial location of MLNs and adjacent structures. Precise image registration and fusion were conducted between reconstructed MLNs and the original chest CT or CDP CT images. IMRT demonstrated greater values in CI, CTV coverage and OAR (lungs and spinal cord) protection, compared with 3D-CRT and VMAT (P<0.05). The deviation between the measured and calculated doses was within ± 10% at SLL, and at the 2R and 7th MLN stations. In conclusion, the 3D MLN model can benefit plan optimization and dosimetric measurement of thoracic radiotherapy, and when combined with CDP, it may provide a tool for clinical dosimetric monitoring.

Tumor histology predicts mediastinal nodal status and may be used to guide limited lymphadenectomy in patients with clinical stage I non–small cell lung cancer

ObjectiveMethods to minimize surgical trauma from mediastinal lymphadenectomy in patients with early-stage lung cancer are still immature. This study aimed to identify predictors of negative pathologic N2, which may be used to select patients for limited mediastinal lymphadenectomy. MethodsClinicopathologic features of 1430 patients with resected clinical stage I non–small cell lung cancer and complete mediastinal lymphadenectomy were retrospectively analyzed for variables associated with negative N2 nodal metastasis (2008-2015). Overall and recurrence-free survival in patients after complete or limited mediastinal lymphadenectomy were assessed via Kaplan–Meier survival analysis and log-rank testing. The accuracy of frozen section diagnosis for predicting final pathology was retrospectively assessed in 126 randomly selected patients after the surgery. ResultsMultivariable analysis revealed that tumor size ≤2 cm, negative pN1, lymphovascular invasion, and lepidic adenocarcinoma were associated with negative mediastinal nodal metastasis. Notably, none of the patients with histology of adenocarcinoma in situ, minimally invasive adenocarcinoma, or lepidic pattern–predominant adenocarcinoma on final pathology had pN2 disease, and the 5-year overall and recurrence free-survival of these patients (99.3% and 99.3%, respectively) was not different from those after limited mediastinal lymphadenectomy (98.7% and 100%, P = .582 and .511, respectively). If these subtypes were classified together as the low-risk group, the concordance rate between frozen section and final pathology diagnosis was 88.9% in the retrospective test cohort. ConclusionsTumor histology may predict negative mediastinal metastasis in patients with early-stage lung cancer. Future prospective studies are merited to validate the feasibility of using frozen section to select patients for limited mediastinal lymphadenectomy.

Endosonographic Lymph Node Staging by Combined Endobronchial Ultrasound (EBUS) and Endoscopic Ultrasound: Technique and Technical Tricks

Surgical staging by mediastinoscopy has been considered the gold standard for staging of the mediastinum in non–small cell lung cancer for many years; however, more recently, minimally invasive endosonographic procedures using combined endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS) have replaced mediastinoscopy as the method of choice for mediastinal lymph node evaluation. A combination of EBUS and EUS performed in a single setting has been shown to have results comparable to surgical staging and increased yield in comparison with each procedure alone. It is actually superior to surgical mediastinal staging due to its ability to access lymph nodes out of the range of traditional surgical techniques. Correct identification of the mediastinal lymph node stations with endosonography requires knowledge of each lymph node station's ultrasonic anatomical positions and relationships. The aim of this paper is to describe to the reader how combined endosonographic techniques are performed, breaking up, and detailing each of the steps.

Prevalence of nodal metastases in lymph node stations 8 & 9 in a large UK lung cancer surgical centre without routine pre-operative EUS nodal staging

IntroductionEndoscopic ultrasound (EUS) allows access to the inferior mediastinal lymph node stations (8 and 9) which are beyond the reach of endobronchial ultrasound (EBUS). The addition of EUS to EBUS procedures requires cost and resource investment. This study sought to describe the prevalence of station 8/9 nodal metastases from intra-operative lymph node sampling in a UK region where routine pre-operative EUS is not available. MethodsA retrospective review of all lung cancer resections at the University Hospital South Manchester from 2011 to 2014. Surgical variables, pre-operative PET variables and survival outcomes were collected and analysed. Results1421 surgical resections were performed in the study period. Lymph node stations 8 and/or 9 were sampled in 52% (736/1421) of patients. Overall, there were 34 patients with lymph node metastases at station 8/9. This represents 2.4% of the study populations and 4.6% of patients in whom stations 8/9 were sampled intra-operatively. Of those patients with station 8/9 metastases, 65% (22/34) had multi-station N2 disease and the majority of the additional N2 disease was present in EBUS-accessible areas (lymph node stations 2, 4 and 7). Two percent (16/736) of patients in whom station 8/9 lymph nodes were sampled intra-operatively had N2 disease that was only accessible endoscopically with EUS. There was no significant difference in overall survival in patients with pathological N2 disease stratified according to whether stations 8/9 were involved or not. ConclusionsThe prevalence of lymph node metastases in stations 8/9 in this UK surgical centre where routine pre-operative EUS is not performed is low at approximately 5%. Given the identification of N2 disease in two-thirds of these patients can potentially be achieved through EBUS alone, this questions whether the resource implications of EUS are justified by the impact on patient management.

Stereotactic body radiation therapy for isolated hilar and mediastinal non-small cell lung cancers

ObjectivesThe seminal phase II trial for pulmonary stereotactic body radiation therapy (SBRT) suggested that SBRT to central lesions resulted in unacceptable toxicity. Alternative dose-fractionation schemes have been proposed which may improve safety without compromise of efficacy. We report our institutional outcomes of SBRT for hilar/mediastinal non-small cell lung cancer (NSCLC). Materials and methodsA retrospective review was conducted of patients with NSCLC in a hilar or mediastinal nodal station which was treated with SBRT. Patients presented with a lesion involving the hilum or mediastinum from primary or oligorecurrent NSCLC. Kaplan-Meier with log-rank testing and Cox analysis were utilized for outcomes analysis. ResultsFrom 2008–2015, 40 patients with median age of 70 were treated with SBRT for primary/oligorecurrent hilar/mediastinal NSCLC with median follow-up of 16.4 months. 85% presented with oligorecurrent disease at a median of 22.4 months following definitive therapy. The aortico-pulmonary window was the target in 40%, the hilum in 25%, lower paratracheal in 20%, subcarinal in 10%, and prevascular in 5%. The median dose was 48Gy in 4 fractions (range: 35–48Gy in 4–5 fractions).Median overall (OS) and progression-free (PFS) survivals were 22.7 and 13.1 months, respectively. Two-year local control was 87.7% and not significantly different between hilar and mediastinal targets. Median PFS was significantly improved in patients with hilar vs mediastinal nodal targets: 33.3 vs 8.4 months, respectively (p=0.031). OS was not statistically different between hilar and mediastinal targets (p=0.359). On multivariable analysis, hilar vs mediastinal target predicted for PFS (HR 3.045 95%CI [1.044–8.833], p=0.042), as did shorter time to presentation in patients with oligorecurrence (HR 0.983 [95%CI 0.967–1.000], p=0.049). Acute grade 3+ morbidity was seen in 3 patients (hemoptysis, pericardial/pleural effusion, heart failure) and late grade 3+ morbidity (hemoptysis) in 1 patient. ConclusionHilar/mediastinal SBRT appears to be a safe technique for the local control of isolated nodal disease with limited toxicity from the fractionation schemes utilized.

MTE 08.02 Clinical Aspects of EUS(B)-FNA

Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has been used for lung cancer staging and diagnosis since ‘90s. However, the usefulness of EUS-FNA has not been addressed in the lung cancer field due to the limited accessibility to mediastinal lymph nodes and the low availability of the technique by thoracic physicians. The development of endobronchial ultrasound guided-transbronchial needle aspiration (EBUS-TBNA) changed the staging process of lung cancer markedly. EBUS-TBNA, which can target mediastinal nodal stations accessible by cervical mediastinoscopy, has replaced standard cervical mediastinoscopy.

A Comparison of Trimodality Therapy Versus Definitive Concurrent Chemoradiation in Patients With Stage IIIA Non–small Cell Lung Cancer

The optimal treatment paradigm for pts with stage IIIA NSCLC with mediastinal (N2) involvement at diagnosis (dx) has not been established. Two common approaches include TM with preoperative chemotherapy, surgical resection and post-operative radiation vs. CRT. At our institution, the preferred approach for resectable pts is TM. Pts who are not surgical candidates undergo CRT. We retrospectively analyzed 267 pts treated with TM (N=135) or CRT (N=132) from 01/2004-07/2016. Extensive mediastinal involvement (EMI) was defined as > 2 mediastinal or hilar nodal stations involved at dx. Estimates for the endpoints of overall survival (OS), progression-free survival (PFS), distant metastasis free survival (DMFS) and local-regional control (LRC) were generated from the time of dx using the Kaplan-Meier method and compared using the log-rank test. LRC was assessed independently of distant control. Cox proportional hazards models were used for univariate (UVA) and multivariable analyses (MVA). The median follow-up time was 23.9 months for all pts and 46.2 months for survivors. Age (median 65 years), race (83% white), sex (43% male), and KPS (median 80) were similar between the 2 groups. More pts treated with CRT were current smokers (32% vs. 8%, p<0.01) with larger tumors (4.5 cm vs. 3.7 cm, p<0.01), higher T-stage (34% with T3 or T4 vs. 18%, p <0.01), squamous cell carcinoma histology (37.1% vs. 12.7%, p<0.01), subcarinal nodal involvement (52% vs. 33%, p<0.01) and EMI (31% vs. 14%, p<0.01). Pts in the TM group had R0 (79%), R1/2 (21%) resections. The median radiation dose was 54 Gy (range: 50-70 Gy) in the TM group and 64.8 Gy (range: 54-74 Gy) in the CRT group. Pts treated with TM had superior OS (2 yr: 69% vs. 46%, p<0.01), PFS (2 yr: 44% vs. 29%, p=0.04), and LRC (2 yr: 76% vs. 56%, p<0.01), but similar DMFS (2 yr: 46% vs. 41%, p=0.55). In patients with subcarinal involvement, TM no longer resulted in superior OS (64% vs. 56%, p=0.70), PFS (38% vs. 34%, =0.72), or LRC (75% vs. 58%, p=0.15). Similarly, in pts with EMI involvement, TM no longer resulted in superior OS (p=0.85), PFS (p=0.75) or LRC (p=0.92). On UVA, age, adenocarcinoma histology (AH) and TM were predictive of LRC. On MVA, age (1.03; 1.01-1.05) and AH (0.48; 0.30-0.80) were predictive of LRC. On MVA (HR; 95%CI), age (1.02; 1.01-1.04), AH (0.62; 0.42-0.91) and TM (0.64; 0.45-0.91) were predictive of OS. There were no predictive factors on MVA for DMFS or PFS. Sex, race, KPS, T-stage, tumor size, smoking status, nodal location, EMI and subcarinal involvement were not predictive. The superior OS and PFS in the TM pts may be attributable to a more fit patient population with less extensive disease and without progression after induction chemotherapy. TM and CRT resulted in similar rates of DMFS. CRT can be considered in pts with subcarinal disease or EMI to spare the morbidity of surgery. Prospective trials to control for pt and disease related confounders are needed to determine the best approach for pts with N2 Stage IIIA NSCLC.

Association of Pathologic Nodal Staging Quality With Survival Among Patients With Non–Small Cell Lung Cancer After Resection With Curative Intent

Pathologic nodal stage is the most significant prognostic factor in resectable non-small cell lung cancer (NSCLC). The International Association for the Study of Lung Cancer NSCLC staging project revealed intercontinental differences in N category-stratified survival. These differences may indicate differences not only in cancer biology but also in the thoroughness of the nodal examination. To determine whether survival was affected by sequentially more stringent definitions of pN staging quality in a cohort of patients with NSCLC after resection with curative intent. This observational study used the Mid-South Quality of Surgical Resection cohort, a population-based database of lung cancer resections with curative intent. A total of 2047 consecutive patients who underwent surgical resection at 11 hospitals with at least 5 annual lung cancer resections in 4 contiguous US Dartmouth hospital referral regions in northern Mississippi, eastern Arkansas, and western Tennessee (>90% of the eligible population) were included. Resections were performed from January 1, 2009, through January 25, 2016. Survival was evaluated with the Kaplan-Meier method and Cox proportional hazards models. Eight sequentially more stringent pN staging quality strata included the following: all patients (group 1); those with complete resections only (group 2); those with examination of at least 1 mediastinal lymph node (group 3); those with examination of at least 10 lymph nodes (group 4); those with examination of at least 3 hilar or intrapulmonary and at least 3 mediastinal lymph nodes (group 5); those with examination of at least 10 lymph nodes, including at least 1 mediastinal lymph node (group 6); those with examination of at least 1 hilar or intrapulmonary and at least 3 mediastinal nodal stations (group 7); and those with examination of at least 1 hilar or intrapulmonary lymph node, at least 10 total lymph nodes, and at least 3 mediastinal nodal stations (group 8). N category-stratified overall survival. Of the total 2047 patients (1046 men [51.1%] and 1001 women [48.9%]; mean [SD] age, 67.0 [9.6] years) included in the analysis, the eligible analysis population ranged from 541 to 2047, depending on stringency. Sequential improvement in the N category-stratified 5-year survival of pN0 and pN1 tumors was found from the least stringent group (0.63 [95% CI, 0.59-0.66] for pN0 vs 0.46 [95% CI, 0.38-0.54] for pN1) to the most stringent group (0.71 [95% CI, 0.60-0.79] for pN0 vs 0.60 [95% CI, 0.43-0.73] for pN1). The pN1 cohorts with 3 or more mediastinal nodal stations examined had the most striking survival improvements. More stringently defined mediastinal nodal examination was associated with better separation in survival curves between patients with pN1 and pN2 tumors. The prognostic value of pN stratification depends on the thoroughness of examination. Differences in thoroughness of nodal staging may explain a large proportion of intercontinental survival differences. More thorough nodal examination practice must be disseminated to improve the prognostic value of the TNM staging system. Future updates of the TNM staging system should incorporate more quality restraints.