Pathologic Mediastinal Lymph Node Research Articles

Investigation of mediastinal lymph node dissection in clinical stage IA pure-solid non-small cell lung cancer patients

ObjectiveTo explore the independent predictors of pathological mediastinal lymph node (pN2) metastasis in clinical stage IA (cIA) pure-solid non-small cell lung cancer (NSCLC) patients, and to find an appropriate method of mediastinal lymph node dissection.MethodsThis study retrospectively evaluated 533 cIA pure-solid NSCLC patients who underwent radical resection of lung cancer (lobectomy combined with systematic lymph node dissection) from January 2014 to December 2016. The relationship between clinicopathological characteristics and pN2 metastasis was analyzed, and the independent predictors of pN2 metastasis were determined by univariate and multivariate logistic regression analysis. We defined the new factor Y as composed of preoperative cT, CEA, and NSE.ResultsThere were 72 cases (13.5%) of pN2 metastasis in cIA pure-solid NSCLC patients. Preoperative clinical tumor diameter (cT), serum CEA level, serum NSE level, and pathological status of station 10 lymph nodes were independent predictors of pN2 metastasis. Patients with cT ≤ 21.5 mm, CEA ≤ 3.85 ng/mL, NSE ≤ 13.40 ng/mL and negative station 10 lymph node group showed lower rates of pN2 metastasis. The new factor Y was an independent predictor of pN2 metastasis. Only 3 (2.1%) of 143 patients in the Y low-risk group showed pN2 metastasis.ConclusionFor patients with low risk of pN2 metastasis, it might be feasible to take lobe-specific lymph node sampling or systematic lymph node sampling. As for those with high risk of pN2 metastasis, systematic lymph node dissection would be recommended.

Pathologic Nodal Staging Before SBRT for Early-stage NSCLC Does Not Impact Overall Survival: A Propensity Score-matched NCDB Analysis.

Stereotactic body radiation therapy (SBRT) for early-stage non-small cell carcinoma of the lung (NSCLC) is increasingly utilized. We sought to assess overall survival (OS) for early-stage NSCLC patients receiving SBRT depending on staging method. Early-stage NSCLC patients treated with definitive SBRT were identified in the National Cancer Database (NCDB), and OS was determined based on method of staging. Patient, disease, and treatment characteristics were also analyzed. A total of 12,106 patients were included; 865 (7%) received invasive staging (nodal sampling, NS) and 11,241 (93%) had no nodal sampling (NNS). From this larger dataset, a propensity score matching (1:1 without replacement) was performed, which yielded 839 patients for each group (NNS and NS). With a median follow-up time of 3.12 years, median survival for all patients included in the matched dataset was 2.75 years (95% CI: 2.55-2.93y), with 2- and 5-year OS estimated at 63.9% and 25.7%, respectively. In a multivariable analysis on matched data, there was no difference in mortality risk between the NNS and NS groups (hazard ratio=1.08, 95% CI: 0.94-1.24, P =0.25). Negative prognostic factors identified in the multivariable analysis of the matched data included: age more than 65, male sex, Charlson-Deyo Score ≥1, and tumor size ≥3cm. SBRT use in early-stage NSCLC steadily increased over the study period. Most patients proceeded to SBRT without nodal staging, conflicting with National Comprehensive Cancer Network (NCCN) guidelines which recommend pathologic mediastinal lymph node evaluation for all early-stage NSCLC cases, except stage IA. Our findings suggest similar OS in patients with early-stage NSCLC treated with SBRT irrespective of nodal staging. Furthermore, we highlight patient-related, disease-related, and treatment-related prognostic factors to consider when planning therapy for these patients.

An [18F]FDG-PET/CT deep learning method for fully automated detection of pathological mediastinal lymph nodes in lung cancer patients

PurposeThe identification of pathological mediastinal lymph nodes is an important step in the staging of lung cancer, with the presence of metastases significantly affecting survival rates. Nodes are currently identified by a physician, but this process is time-consuming and prone to errors. In this paper, we investigate the use of artificial intelligence–based methods to increase the accuracy and consistency of this process.MethodsWhole-body 18F-labelled fluoro-2-deoxyglucose ([18F]FDG) positron emission tomography/computed tomography ([18F]FDG-PET/CT) scans (Philips Gemini TF) from 134 patients were retrospectively analysed. The thorax was automatically located, and then slices were fed into a U-Net to identify candidate regions. These regions were split into overlapping 3D cubes, which were individually predicted as positive or negative using a 3D CNN. From these predictions, pathological mediastinal nodes could be identified. A second cohort of 71 patients was then acquired from a different, newer scanner (GE Discovery MI), and the performance of the model on this dataset was tested with and without transfer learning.ResultsOn the test set from the first scanner, our model achieved a sensitivity of 0.87 (95% confidence intervals [0.74, 0.94]) with 0.41 [0.22, 0.71] false positives/patient. This was comparable to the performance of an expert. Without transfer learning, on the test set from the second scanner, the corresponding results were 0.53 [0.35, 0.70] and 0.24 [0.10, 0.49], respectively. With transfer learning, these metrics were 0.88 [0.73, 0.97] and 0.69 [0.43, 1.04], respectively.ConclusionModel performance was comparable to that of an expert on data from the same scanner. With transfer learning, the model can be applied to data from a different scanner. To our knowledge it is the first study of its kind to go directly from whole-body [18F]FDG-PET/CT scans to pathological mediastinal lymph node localisation.

Pre-Operative Prediction of Mediastinal Node Metastasis Using Radiomics Model Based on 18F-FDG PET/CT of the Primary Tumor in Non-Small Cell Lung Cancer Patients.

Purpose: We investigated whether a fluorine-18-fluorodeoxy glucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based radiomics model (RM) could predict the pathological mediastinal lymph node staging (pN staging) in patients with non-small cell lung cancer (NSCLC) undergoing surgery.Methods: A total of 716 patients with a clinicopathological diagnosis of NSCLC were included in this retrospective study. The prediction model was developed in a training cohort that consisted of 501 patients. Radiomics features were extracted from the 18F-FDG PET/CT of the primary tumor. Support vector machine and extremely randomized trees were used to build the RM. Internal validation was assessed. An independent testing cohort contained the remaining 215 patients. The performances of the RM and clinical node staging (cN staging) in predicting pN staging (pN0 vs. pN1 and N2) were compared for each cohort. The area under the curve (AUC) of the receiver operating characteristic curve was applied to assess the model's performance.Results: The AUC of the RM [0.81 (95% CI, 0.771–0.848); sensitivity: 0.794; specificity: 0.704] for the predictive performance of pN1 and N2 was significantly better than that of cN in the training cohort [0.685 (95% CI, 0.644–0.728); sensitivity: 0.804; specificity: 0.568], (P-value = 8.29e-07, as assessed by the Delong test). In the testing cohort, the AUC of the RM [0.766 (95% CI, 0.702–0.830); sensitivity: 0.688; specificity: 0.704] was also significantly higher than that of cN [0.685 (95% CI, 0.619–0.747); sensitivity: 0.799; specificity: 0.568], (P = 0.0371, Delong test).Conclusions: The RM based on 18F-FDG PET/CT has a potential for the pN staging in patients with NSCLC, suggesting that therapeutic planning could be tailored according to the predictions.

Care of patients with non-small-cell lung cancer stage III - the Central European real-world experience.

BackgroundManagement of non-small-cell lung cancer (NSCLC) is affected by regional specificities. The present study aimed at determining diagnostic and therapeutic procedures including outcome of patients with NSCLC stage III in the real-world setting in Central European countries to define areas for improvements.Patients and methodsThis multicentre, prospective and non-interventional study collected data of patients with NSCLC stage III in a web-based registry and analysed them centrally.ResultsBetween March 2014 and March 2017, patients (n=583) with the following characteristics were entered: 32% females, 7% never-smokers; ECOG performance status (PS) 0, 1, 2 and 3 in 25%, 58%, 12% and 5%, respectively; 21% prior weight loss; 53% squamous carcinoma, 38% adenocarcinoma; 10% EGFR mutations. Staging procedures included chest X-ray (97% of patients), chest CT (96%), PET-CT (27%), brain imaging (20%), bronchoscopy (89%), endobronchial ultrasound (EBUS) (13%) and CT-guided biopsy (9%). Stages IIIA/IIIB were diagnosed in 55%/45% of patients, respectively. N2/N3 nodes were diagnosed in 60%/23% and pathologically confirmed in 29% of patients. Most patients (56%) were treated by combined modalities. Surgery plus chemotherapy was administered to 20%, definitive chemoradiotherapy to 34%, chemotherapy only to 26%, radiotherapy only to 12% and best supportive care (BSC) to 5% of patients. Median survival and progression-free survival times were 16.8 (15.3;18.5) and 11.2 (10.2;12.2) months, respectively. Stage IIIA, female gender, no weight loss, pathological mediastinal lymph node verification, surgery and combined modality therapy were associated with longer survival.ConclusionsThe real-world study demonstrated a broad heterogeneity in the management o f stage III NSCLC in Central European countries and suggested to increase the rates of PET-CT imaging, brain imaging and invasive mediastinal staging.

Metabolic tumor heterogeneity analysis by F-18 FDG PET/CT predicts mediastinal lymph node metastasis in non-small cell lung cancer patients with clinically suspected N2

ObjectivesAccurate prediction of pathological N2 metastasis is crucial for choosing the best therapeutic strategy for non-small cell lung cancer (NSCLC) patients. The aim of this study is to evaluate the usefulness of metabolic heterogeneity assessed by the positron emission tomography combined with computed tomography (PET/CT) using F-18 fluorodeoxyglucose (FDG) in primary NSCLC with clinically suspected N2 metastasis in predicting pathological mediastinal lymph node metastasis. Materials and methodsFifty patients with newly diagnosed NSCLC and clinically suspected N2 on preoperative CT and F-18 FDG PET/CT were included. Pathological results were confirmed by surgical specimens and the coefficient of variation (COV) was used to evaluate the metabolic heterogeneity of primary tumor mass by using F-18 FDG PET/CT. ResultsAmong the 50 patients with clinically suspected N2, 23 patients were pathologically confirmed as positive mediastinal lymph node metastasis and 27 patients were negative. Pathologically confirmed positive mediastinal lymph node metastasis group presented higher COV than the negative metastasis group (p < 0.001). An optimal cut-off value of 41.9 was proposed for discriminating metastasis from non-metastasis group. The sensitivity and specificity were 65.2% and 88.9%, respectively (AUC: 0.84; p < 0.0001). In addition, compared with other metabolic parameters, metabolic heterogeneity defined as COV showed the superior predictability of the mediastinal metastasis. (p = 0.001) ConclusionMetabolic heterogeneity which was defined as COV of primary tumor could predict pathological mediastinal lymph node metastasis in NSCLC patients with clinically suspected N2. Therefore, COV of primary tumor may play a complementary role to conventional imaging in providing nodal information before taking biopsy.

Reassessment of Right Middle Lobe Lung Cancer: Comparison of Segments 4 and 5 Tumors

The purpose of this study was to elucidate the clinical behavior of right middle lobe lung cancer, with focus on the tumor location. We reviewed retrospectively 711 patients who underwent lobectomy or bilobectomy for clinical stage I non-small cell lung cancer (upper lobe, 346; middle lobe, 82; lower lobe, 283). Factors affecting survival were assessed by log rank tests and Cox regression analyses. The prognosis of patients with segment 5 tumors (n= 39) was significantly worse than that of patients with segment 4 tumors (n= 43; 5-year overall survival rates, 69.8% versus 87.6%, p= 0.040; and 5-year recurrence-free survival rates, 58.4% versus 73.0%, p= 0.029). Segment 5 tumors were an independent factor for poor prognosis in multivariable Cox regression analysis, and tended to cause more pathologic mediastinal lymph node metastases than segment 4 tumors (12.8% versus 2.3%, p= 0.097). Compared with tumors in the other lobes, patients with segment 4 tumors demonstrated no significant difference in prognosis; however, patients with segment 5 tumors demonstrated a significantly and outstandingly worse prognosis than patients with other lobe tumors (5-year overall survival rates, 69.8% versus 82.2%, p= 0.020; and 5-year recurrence-free survival rates, 58.4% versus 71.4%, p= 0.0071). Patients with segment 5 tumors had a worse prognosis than patients with segment 4 and other lobe tumors. We speculate that is because segment 5 tumors cause more metastases to the mediastinal lymph nodes. Tumor location was an important prognostic factor for patients with right middle lobe lung cancer.

Clinical Prognosis of Superior Versus Basal Segment Stage I Non-Small Cell Lung Cancer

Despite its extensive size, variations in the clinicopathologic features of tumors in the lower lobe have been little studied. The present study investigated the prognostic differences in tumors originating from the superior and basal segments of the lower lobe in patients with non-small cell lung cancer. Data of 134 patients who underwent lobectomy or segmentectomy with systematic nodal dissection for clinical stage I, radiologically solid-dominant, non-small cell lung cancer in the superior segment (n= 60) or basal segment (n= 74) between April 2007 and December 2015 were retrospectively reviewed. Factors affecting survival were assessed by the Kaplan-Meier method and Cox regression analyses. Prognosis in the superior segment group was worse than that in the basal segment group (5-year overall survival rates 62.6% versus 89.9%, p= 0.0072; and 5-year recurrence-free survival rates 54.4% versus 75.7%, p= 0.032). In multivariable Cox regression analysis, a superior segment tumor was an independent factor for poor overall survival (hazard ratio 3.33, 95% confidence interval: 1.22 to 13.5, p= 0.010) and recurrence-free survival (hazard ratio 2.90, 95% confidence interval: 1.20 to 7.00, p= 0.008). The superior segment group tended to have more pathologic mediastinal lymph node metastases than the basal segment group (15.0% versus 5.4%, p= 0.080). Tumor location was a prognostic factor for clinical stage I non-small cell lung cancer in the lower lobe. Patients with superior segment tumors had worse prognosis than patients with basal segment tumors, with more metastases in mediastinal lymph nodes.

Rare Clinical Sign of Hodgkin's Lymphoma: Ocular Involvement.

Bilateral non-granulomatous anterior uveitis with left vitritis and macular edema were detected in a 19-year-old woman presenting with blurred vision in her left eye. Light microscopic study of the pathologic mediastinal lymph node that was detected via contrast computed tomography imaging during etiologic study revealed nodular sclerosing and mixed cellularity Hodgkin’s lymphoma (HL). Ocular findings completely resolved with adriablastin, bleomycin, vinblastine, dacarbazine chemotherapy treatment. Herein, it is emphasized that HL should be remembered as one of the differential diagnoses in patients with ocular inflammatory pathologies such as uveitis and vasculitis. The ocular findings of HL are discussed.

Induction chemoradiotherapy is superior to induction chemotherapy for the survival of non-small-cell lung cancer patients with pathological mediastinal lymph node metastasis

The purpose of this study was to compare the clinical outcomes of induction chemoradiotherapy and chemotherapy and to identify the prognostic factors for non-small-cell lung cancer patients with mediastinal lymph node metastasis who were treated with induction therapy. Between August 1995 and December 2010, 50 non-small-cell lung cancer patients with pathological mediastinal lymph node metastasis were scheduled to receive induction therapy followed by surgery. Irinotecan plus cisplatin was used for induction chemotherapy from June 1995 to April 1999, and docetaxel plus cisplatin with concurrent radiation at a dose of 40-46 Gy has been used for induction chemoradiotherapy since May 1999. Thirty-five patients were treated with induction chemoradiotherapy and 15 were treated with induction chemotherapy. For the entire population, the 3-year and 5-year overall survival rates were 64.1 and 53.9%, respectively, and the 1-year and 2-year disease-free survival rates were 70.0 and 53.1%, respectively. Among the clinicopathological factors, the chemoradiotherapy group exhibited longer overall survival and disease-free survival than the chemotherapy group (overall survival, P = 0.0020; disease-free survival, P = 0.015). Pathological downstaging was also significantly associated with favorable overall survival (P = 0.0042) and disease-free survival (P = 0.021). A multivariate analysis showed that chemoradiotherapy (P = 0.0099) and pathological downstaging (P = 0.039) were independent prognostic factors. Our results indicated that induction chemoradiotherapy was superior to induction chemotherapy with regard to the outcome of non-small-cell lung cancer patients with mediastinal lymph node metastasis.

Increased F-18 FDG Uptake in the Right Auricle of a Displaced Heart: Potential Cause of a False-Positive Pathologic Mediastinal Node

A positron emission tomography (PET) imaging study was performed in a patient with a history of lung cancer. The scan demonstrated increased fluorine-18 fluorodeoxyglucose uptake in the right auricle of a displaced heart.This same finding was also present on a prior PET study performed at an outside facility at which time it was erroneously interpreted to represent a pathologic mediastinal lymph node. This normal variant, particularly in patients with distorted anatomy, should be kept in mind to avoid a false-positive interpretation and to prevent unnecessary additional diagnostic workup or intervention.

FDG-PET in staging lung cancer: How does it change the algorithm?

Background: In patients with lung cancer, positron emission tomography (PET) using fluor-18-fluorodesoxyglucose (FDG) may be used both to detect extrathoracic metastases (ETM) and for mediastinal lymph node staging (MLS), potentially reducing the need for mediastinoscopy. We assessed the added value of FDG-PET in detecting ETM and focused on the reliability of FDG-PET and mediastinoscopy for MLS. Patients and methods: In 72 consecutive patients with non-small cell lung cancer, the impact of adding FDG-PET to full conventional clinical staging was prospectively analyzed. The predictive value of FDG-PET findings and tumor location for pathologic mediastinal lymph node status were assessed in a logistic regression analysis. Results: Unexpected extrathoracic metastases were detected by FDG-PET in 15% of patients. In MLS overall negative and positive predictive values were 71 and 83% for FDG-PET, and 92 and 100% for mediastinoscopy. However, the negative predictive value of FDG-PET was only 17% in case of FDG-PET positive N1 nodes and/or a centrally located primary tumor, whereas it was 96% in case of FDG-PET negative N1 nodes and a non-centrally located primary tumor. Conclusion: By incorporating FDG-PET in clinical staging, 15% of patients with lung cancer are upstaged due to unexpected extrathoracic metastases. In case of a negative mediastinal FDG-PET, mediastinoscopy can only be omitted in the presence of a non-centrally located primary tumor and without FDG-PET positive N1 nodes.

Prognostic significance of bcl-2 expression in resected pN2 non-small cell lung cancer

Aims: The prognosis of non-small cell lung cancer with pathologic mediastinal lymph node involvement (pN2) is poor, we wished to study the expression of p53, bcl-2 by immunohistochemistry in a series of such patients. Methods: Clinicopathologic factors were investigated in relation to prognosis in 60 patients with resected pN2 non-small cell lung cancer. Results: The 5-year survival rate was 21.7%. Positive staining for p53, and bcl-2 was found in 29/60 and 12/60, respectively. Patients with bcl-2 positive tumor had a more favorable survival than those with bcl-2 negative tumor ( P=0.0054). The expression of p53 was not related to patients' survival. Multivariate analysis showed that Bcl-2 expression and single N2 station were independent prognostic factors. Conclusions: Patients with bcl-2 positive tumors may comprise a favorable prognostic subgroup in pN2 non-small cell lung cancer.

Prognostic significance of metastases to mediastinal lymph node levels in resected non-small cell lung carcinoma.

The prognosis of patients who have non-small cell lung carcinoma (NSCLC) with mediastinal lymph node metastases remains a controversial issue. This study was performed to evaluate survival by level of mediastinal lymph node metastasis and the number of mediastinal levels involved. The authors retrospectively reviewed the cases of 113 patients with NSCLC and pathologic mediastinal lymph node involvement who underwent a complete tumor resection and ipsilateral mediastinal lymphadenectomy. Most patients presented with involvement of only one mediastinal lymph node level (68.2%). The overall survival rate was 17% at 3 years. No differences in survival were observed in relation to which lymph node level was involved (P = 0.667). Differences in survival based on the number of lymph node levels involved were statistically significant (P = 0.001). Although there were no differences in survival when only one of any of the three defined levels was involved, metastasis to more than one level was associated with significantly poorer survival.