Mediastinal Lymph Node Staging Research Articles

Minimally Invasive with Maximal Yield: A Narrative Review of Current Practices in Mediastinal Lymph Node Staging in Non-Small Cell Lung Cancer.

Background: Lung cancer remains the leading cause of cancer deaths in the United States despite declining incidence and improved outcomes because of advancements in early detection and development of novel therapies. Accurate mediastinal lymph node staging is crucial for determining prognosis and guiding treatment decisions, particularly for non-small cell lung cancer (NSCLC). Materials and Methods: A systematic search of PubMed was conducted to identify English language articles published between January 2010 and January 2024 focusing on preoperative lymph node staging in adults with NSCLC. Case series, observational studies, randomized trials, guidelines, narrative reviews, systematic reviews, and meta-analyses were included. Results: Various imaging modalities, surgical and nonsurgical procedures for mediastinal lymph node staging were reviewed, including positron emission tomography with computed tomography, cervical mediastinoscopy, video-assisted cervical mediastinoscopy, anterior mediastinotomy, video-assisted thoracoscopy, endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA), transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), and computed tomography-guided percutaneous lymph node biopsy. EBUS-FNA emerged as the preferred initial staging procedure because of its high sensitivity and low complication rate. Combining it with other procedures or confirmatory testing may be helpful in determining appropriate treatment. Conclusions: Although cervical mediastinoscopy remains a valuable confirmatory procedure in select cases, its role as a first-line staging modality is diminishing with the widespread adoption of EBUS-FNA and EUS-FNA. The combination of EBUS-FNA and EUS-FNA allows access to nearly all mediastinal lymph node stations with high diagnostic accuracy. Future research may further refine the selection criteria for invasive mediastinal staging procedures, ultimately optimizing patient outcomes in the management of NSCLC.

A novel use of endobronchial ultrasound bronchoscope to biopsy supraclavicular lymph node

Background: Accurate staging for patients with lung cancer is essential for management and prognostication. Percutaneous ultrasound-guided fine needle aspiration (US FNA) of supraclavicular lymph nodes is not always performed clinically for variety of reasons. Our study explores the utility of supraclavicular lymph node biopsy using the endobronchial ultrasound (EBUS) bronchoscope at the time of a mediastinal staging procedure as a possible alternative to US FNA. Methods: This study included 22 patients who underwent supraclavicular lymph node biopsy using the EBUS bronchoscope during lung cancer staging procedure from 2019 to 2021 at the University of Pennsylvania. Feasibility and safety of the procedure were reported. Descriptive statistics were performed for baseline demographics, imaging features, pathology results, tumor cellularity and adequacy for oncological testing. Results: The procedures were safely performed in all patients with no safety events reported. All patients were diagnosed with malignancy and EBUS-guided supraclavicular lymph node FNA showed definitive diagnosis in 19. Of the 16 patients with the final diagnosis of non-small cell lung cancer (NSCLC), 14 had tumor seen in supraclavicular lymph node sampling and 9 were upgraded to Stage IIIB disease from lower mediastinal lymph node staging. Eleven supraclavicular lymph node samples had tumor cellularity >10%. Eight samples were sent for next generation sequencing (NGS). Three of them were the only source for NGS. Conclusions: Supraclavicular lymph node biopsy using the EBUS bronchoscope is a feasible and safe procedure to perform during lung cancer staging. Sampling has significant clinical value for accurate staging and oncologic testing.

Preoperative evaluation of mediastinal lymph nodes in non-small cell lung cancer using [68Ga]FAPI-46 PET/CT: a prospective pilot study.

Mediastinal nodal staging is crucial for surgical candidate selection in non-small cell lung cancer (NSCLC), but conventional imaging has limitations often necessitating invasive staging. We investigated the additive clinical value of fibroblast activation protein inhibitor (FAPI) PET/CT, an imaging technique targeting fibroblast activation protein, for mediastinal nodal staging of NSCLC. In this prospective pilot study, we enrolled patients scheduled for surgical resection of NSCLC based on specific criteria designed to align with indications for invasive staging procedures. Patients were included when meeting at least one of the following: (1) presence of FDG-positive N2 lymph nodes, (2) clinical N1 stage, (3) central tumor location or tumor diameter of ≥ 3 cm, and (4) adenocarcinoma exhibiting high FDG uptake. [68Ga]FAPI-46 PET/CT was performed before surgery after a staging workup including [18F]FDG PET/CT. The diagnostic accuracy of [68Ga]FAPI-46 PET/CT for "N2" nodes was assessed through per-patient visual assessment and per-station quantitative analysis using histopathologic results as reference standards. Twenty-three patients with 75 nodal stations were analyzed. Histopathologic examination confirmed that nine patients (39.1%) were N2-positive. In per-patient assessment, [68Ga]FAPI-46 PET/CT successfully identified metastasis in eight patients (sensitivity 0.89 (0.52-1.00)), upstaging three patients compared to [18F]FDG PET/CT. [18F]FDG PET/CT detected FDG-avid nodes in six (42.8%) of 14 N2-negative patients. Among them, five were considered non-metastatic based on calcification and distribution pattern, and one was considered metastatic. In contrast, [68Ga]FAPI-46 PET/CT correctly identified all non-metastatic patients solely based on tracer avidity. In per-station analysis, [68Ga]FAPI-46 PET/CT discriminated metastasis more effectively compared to [18F]FDG PET/CT-based (AUC of ROC curve 0.96 (0.88-0.99) vs. 0.68 (0.56-0.78), P < 0.001). [68Ga]FAPI-46 PET/CT holds promise as an imaging tool for preoperative mediastinal nodal staging in NSCLC, with improved sensitivity and the potential to reduce false-positive results, optimizing the need for invasive staging procedures.

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

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

Lung Cancer Staging—A Clinical Practice Review

Lung cancer is the leading cause of cancer-associated death globally. Staging provides classification of the anatomic extent of cancer that is used consistently worldwide. Lung cancer staging is necessary for prognostication, to inform treatment options, and to allow accurate representation in clinical trials. Staging also separates operable from inoperable disease. Since its introduction in the 1970s, the Tumor, Node and Metastasis (TNM) Staging System has undergone significant revisions, with the latest version, the eighth edition, being effective internationally since 2017. Advances in bronchoscopic and thoracoscopic technologies have expanded procedures to diagnose lung cancer and accurately define the anatomic stage. Understanding the advantages and disadvantages of available methods for staging lung cancer is critical to clinician decision making. In patients with lung cancer without distant metastases, the staging of mediastinal lymph nodes determines treatment options. To minimize the risk and cost, the most appropriate method of staging should identify the highest disease stage while carrying acceptable risk. Minimally invasive endoscopic needle techniques to stage the mediastinum are the first choice to assess for metastases in accessible lymph node stations. Surgical techniques are generally reserved for specific clinical situations, including following negative endoscopic needle techniques when suspicion for nodal involvement is high and to assess endoscopically inaccessible lymph nodes. This review provides a concise account of TNM staging of non-small cell lung cancer (NSCLC) and overview of procedures available for the staging of lung cancer.

Role of invasive mediastinal nodal staging in survival outcomes of patients with non-small cell lung cancer and without radiologic lymph node metastasis: a retrospective cohort study

Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%-77%) for IMNS and 71.7% (95% CI: 68.6%-74.9%; p=0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77-1.07), while 5-year RFS was 64.7% (95% CI: 61.5%-68.2%) and 67.5% (95% CI: 64.3%-70.9%; p=0.35 (HR 1.08, 95% CI: 0.92-1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. None.

Improved Accuracy and Sensitivity in Diagnosis and Staging of Lung Cancer with Systematic and Combined Endobronchial and Endoscopic Ultrasound (EBUS-EUS): Experience from a Tertiary Center.

Combined endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided tissue acquisition (EUS-TA) are accurate procedures for the diagnosis and staging of mediastinal lymph nodes (MLNs) in lung cancer. However, the respective contribution of separate and combined procedures in diagnosis and staging has not been fully studied. The aim of this study was to assess their respective performances. Patients with suspected malignant MLNs in lung cancer or recurrence identified by PET-CT who underwent combined EBUS-TBNA and EUS-TA were retrospectively reviewed. A total of 141 patients underwent both procedures. Correct diagnosis was obtained in 82% with EBUS-TBNA, 91% with EUS-TA, and 94% with the combined procedure. The overall sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of EBUS-TBNA, EUS-TA, and the combined procedure for diagnosing malignancy were [75%, 100%, 100%, 58%], [87%, 100%, 100%, 75%], and [93%, 100%, 100%, 80%], respectively, with a significantly better sensitivity of the combined procedure (p < 0.0001). Staging (82/141 patients) was correctly assessed in 74% with EBUS-TBNA, 68% with EUS-TA, and 85% with the combined procedure. The overall sensitivity, specificity, PPV, and NPV of EBUS-TBNA, EUS-TA, and the combined procedure for lung cancer staging were [62%, 100%, 100%, 55%], [54%, 100%, 100%, 50%], and [79%, 100%, 100%, 68%], respectively, significantly better in terms of sensitivity for the combined procedure (p < 0.001). The combined EBUS-EUS approach in lung cancer patients showed better accuracy and sensitivity in diagnosis and staging when compared with EBUS-TBNA and EUS-TA alone.

Endobronchial ultrasound (EBUS)-guided transbronchial miniforceps biopsy an urban center experience.

The role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in staging mediastinal and hilar lymph nodes in non-small cell lung cancer (NSCLC) is well established. However, evidence of its diagnostic utility in other pathologies-such as lymphoma-remains inadequate. This retrospective observational study aims to determine the diagnostic yield of EBUS-guided miniforceps biopsy (EBUS-MFB) compared to EBUS-TBNA in both malignant and nonmalignant conditions. We conducted a retrospective cross-sectional chart review of all adult patients referred for EBUS at our institution between January 2019 and December 2022. All patients who underwent both EBUS-TBNA and EBUS-MFB were included, with some patients also undergoing transbronchial cryobiopsy. Patients without pathology reports available were excluded. The combination of EBUS-MFB and EBUS-TBNA had the highest percentage of diagnostic results both in the overall cohort (34.4%) and in patients who did not undergo transbronchial cryobiopsy (46.2%). EBUS-MFB alone yielded more diagnostic results compared to EBUS-TBNA. Transbronchial cryobiopsy was the sampling method with the highest percentage of diagnostic results in the cryobiopsy group (64.5%). Statistical analysis revealed a significant difference in diagnostic yield between EBUS-MFB and EBUS-TBNA (P<0.001), with EBUS-MFB showing a higher diagnostic yield overall. EBUS-MFB had a significantly higher diagnostic yield than EBUS-TBNA in benign cases, in patients diagnosed with sarcoidosis, but not in malignant disease. Our study suggests that combining EBUS-MFB with EBUS-TBNA can improve the diagnostic yield, particularly in benign cases and sarcoidosis. These findings support the potential superiority of adding EBUS-MFB over EBUS-TBNA alone and highlight the need for further randomized control trials to validate these results. The retrospective nature of this study and certain limitations, such as the lack of adequate longer-term follow-up, selection and operator biases, and the absence of rapid on-site evaluation (ROSE) in some cases, should be considered when interpreting the results. Nonetheless, this study contributes to the growing evidence for the utility of EBUS-MFB in improving the diagnostic yield of EBUS procedures in specific clinical scenarios.

Dosimetric Impact of Systematic Mediastinal Staging via Endobronchial Ultrasound for Patients with Locally Advanced Lung Cancer: The SEISMIC Trial

The SEISMIC trial aims to find the best method for mediastinal staging in patients with lung cancer receiving chemoradiotherapy. Currently, CT or PET-CT scans are standard in clinical practice, but histological evaluation of the mediastinum is performed on a case-by-case basis. The study will examine the effect of systematic histological evaluation using Endobronchial Ultrasound (EBUS) on radiotherapy target volumes. The hypothesis of this study is that differences in staging between the diagnostic PET-CT and EBUS would result in reduced tumor coverage and/or increased doses to organs at risk (OAR). SEISMIC is a prospective multicenter international cohort study. Patients were enrolled from Australia, the Netherlands, USA and Canada after regional IRB approvals. Patients were treated with 4DCT simulation. Two iGTV and PTV target volumes were delineated for each patient with discordant staging according to both PET-CT and EBUS, as were OARs. Two VMAT plans were generated for each patient based on either PET-CT or EBUS target volumes using knowledge-based planning methodology. Plans aimed to achieve institutional guidelines for target coverage and OAR dose constraints, with a prescribed dose of 60 Gy in 30 fractions. Target coverage and OAR doses for the PET- and EBUS-defined volumes were compared. In 156 patients, EBUS showed a larger extent of disease than PET in 18 (11.5%) and a smaller extent of lymph node (LN) involvement than PET in 49 (31.4%). Out of 67 patients with PET-EBUS discordant results, 25 underwent upfront radiotherapy and were included in the study. EBUS revealed PET-occult LN involvement in 11/25 patients (44%). In these patients, 10/11 patients received <95% of the prescribed dose to PET-occult LN iGTVs; the median [range] minimum dose to the EBUS iGTV was 9.2 Gy [0.1 - 57.9 Gy]. When planning based on EBUS LN involvement, all patients received ≥95% of the prescribed dose to the iGTV (the median [range] minimum dose to the EBUS iGTV was 58.9 Gy [58.1 - 60.5 Gy]). This resulted in increased median [range] doses to OARs; mean lung dose increased by 1.1 Gy [0.3 - 8.4 Gy], esophagus mean dose increased by 3.6 Gy [0.2 - 24.8 Gy], and mean heart dose increased by 0.5 Gy [-0.6 - 8.5 Gy]. Systematic endoscopic evaluation of the mediastinum had a significant effect on tumor coverage in a clinically meaningful proportion of cases and consequent plan adaptation impacted on organ-at-risk (OAR) doses. Results suggest systematic mediastinal LN staging should be considered in all patients prior to curative-intent radiotherapy. ACTRN12617000333314.

Diagnostic potential of [18F]FDG PET/MRI in non-small cell lung cancer lymph node metastasis: a meta-analysis.

This meta-analysis evaluated the diagnostic accuracy and diagnostic value of [18F]FDG PET/MRI for mediastinal lymph node staging of NSCLC. Relevant articles in PubMed, Embase, Web of Science, and the Cochrane Library were searched until January 2023. Research evaluating [18F]FDG PET/MRI for mediastinal lymph node staging of NSCLC was included. Pooled estimates of sensitivity, specificity, PLR, and NLR were calculated by the "Stata" software. Nine researches were included, containing 618 patients. The pooled sensitivity of [18F]FDG PET/MRI for detecting mediastinal lymph node staging of NSCLC was 0.82 (0.70-0.90), and the pooled specificity was 0.88 (0.82-0.93). PLR and NLR were 7.38 (4.73-11.52) and 0.20 (0.11-0.36), respectively. The AUC value of this imaging modality was 0.92 (0.90-0.94). The post-test probability for [18F]FDG PET/MRI might rise to 88% when the pre-test probability was set at 50%. We considered [18F]FDG PET/MRI as an effective imaging tool with relatively high specificity and sensitivity. It has great potential to be used in the clinical management of patients in NSCLC who are amenable to early surgery. More studies with large sample sizes in the same direction are needed in future to obtain more reliable evidence-based support.

Endobronchial Ultrasound/Transbronchial Needle Aspiration-Biopsy for Systematic Mediastinal lymph Node Staging of Non-Small Cell Lung Cancer in Patients Eligible for Surgery: A Prospective Multicenter Study.

The treatment of lung cancer depends on histological and/or cytological evaluation of the mediastinal lymph nodes. Endobronchial ultrasound/transbronchial needle aspiration-biopsy (EBUS/TBNA-TBNB) is the only minimally invasive technique for a diagnostic exploration of the mediastinum. The aim of this study is to analyze the reliability of EBUS in the preoperative staging of non-small cell lung cancer (NSCLC). A prospective study was conducted from December 2019 to December 2022 on 217 NSCLC patients, who underwent preoperative mediastinal staging using EBUS/TBNA-TBNB according to the ACCP and ESTS guidelines. The following variables were analyzed in order to define the performance of the endoscopic technique-comparing the final staging of lung cancer after pulmonary resection with the operative histological findings: clinical characteristics, lymph nodes examined, number of samples, and likelihood ratio for positive and negative outcomes. No morbidity or mortality was noted. All patients were discharged from hospital on day one. In 201 patients (92.6%), the preoperative staging using EBUS and the definitive staging deriving from the evaluation of the operative specimen after lung resection were the same; the same number of patients were detected in downstaging and upstaging (8 and 8, 7.4%). The sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were 90%, 90%, 82%, 94%, and 90%, respectively. The likelihood ratio for positive and negative results was 9 and 0.9, respectively, confirming cancer when present and excluding it when absent. EBUS is the only low-invasive and easy procedure for mediastinal staging. The possibility to check the method in each of its phases-through direct visualization of the vessels regardless of their location in relation to the lymph nodes-makes it safe both for the endoscopist and for the patient. Certainly, the cytologist/histologist and/or operator must have adequate expertise in order not to negatively affect the outcome of the method, although three procedures appear to reduce the impact of the individual professional involved on performance.

Accuracy of nodal staging by 18F-FDG-PET/CT in limited disease small-cell lung cancer.

Small-cell lung cancer (SCLC) is highly aggressive with a nearly incurable disease in most cases. The most important prognostic factor is the status of the mediastinal lymph nodes. Only a small proportion of patients can be diagnosed at early stages and directed to curative multimodal treatment. Therefore, accuracy of nodal staging by (18F)-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) computed tomography (18F-FDG-PET/CT) in (very) limited disease SCLC, although not well investigated, is highly important. Treatment naive, non-bulky patients treated or diagnosed with SCLC between June 2012 and April 2020 with complete data including FDG-PET/CT and invasive mediastinal staging were retrospectively analyzed (n = 19). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy of mediastinal lymph node staging of 18F-FDG-PET/CT was calculated. The FDG-PET/CT showed a sensitivity of 91%, and the specificity was calculated as 87.5%. In this cohort, the disease prevalence in lymph nodes was 58% (n = 11). Positive predictive value was 91%, NPV 88% and accuracy calculated at 89%. One patient was upstaged from single-level N2 to multilevel N2. In one patient, upstaging in invasive staging was performed from N2 to N3, and one patient was downstaged from N1 to N0. FDG-PET/CT is a valuable tool for the detection of distant metastases, but in mediastinal staging of SCLC some limitations might remain. Invasive methods remain the gold standard. Therefore, the mediastinal lymph nodal status of patients with SCLC screened for multimodal treatment should be further evaluated by additional invasive techniques to verify the exact N-staging and to optimize treatment stratification.

Diagnostic Performance of Endosonography to Detect Mediastinal Lymph Node Metastasis in Patients with Radiological N1 Non-Small Cell Lung Cancer.

Guidelines recommend that non-small cell lung cancer (NSCLC) patients with suspected hilar lymph node (LN) metastases should undergo invasive mediastinal LN staging prior to surgical treatment via endosonography. We evaluated the diagnostic performance of endosonography for detecting occult mediastinal metastases (OMM) and determined the factors associated with OMM in NSCLC patients with radiological N1. Patients with confirmed primary NSCLC with radiological N1 who underwent endosonography for nodal staging assessment from January 2013 to December 2019 were retrospectively analyzed. The prevalence of OMM was found to be 83/279 (29.7%) and only 38.6% (32/83) were diagnosed via endosonography. However, five of them were confirmed as N3 by endosonography. The overall diagnostic sensitivity, negative predictive value, accuracy, and area under the curve of endosonography were 38.6%, 79.4%, 81.7%, and 0.69, respectively. In multivariable analysis, central tumor (adjusted odds ratio [aOR], 2.05; 95% confidence interval [CI], 1.15-3.68; p=0.016), solid tumor (aOR, 10.24; 95% CI, 1.32-79.49; p=0.026), and adenocarcinoma (aOR, 3.01; 95% CI, 1.63-5.55; p<0.001) were related to OMM in radiological N1 NSCLC patients. Although the sensitivity of endosonography for detecting OMM was only 40%, the prevalence of OMM was not low (30%) and some cases even turned out to be N3 diseases. Clinicians should be aware that OMM may be more likely in patients with central, solid, and adenocarcinomatous tumor when performing nodal staging in radiological N1 NSCLC via endosonography.

A machine learning tool to improve prediction of mediastinal lymph node metastases in non-small cell lung cancer using routinely obtainable [18F]FDG-PET/CT parameters

BackgroundIn patients with non-small cell lung cancer (NSCLC), accuracy of [18F]FDG-PET/CT for pretherapeutic lymph node (LN) staging is limited by false positive findings. Our aim was to evaluate machine learning with routinely obtainable variables to improve accuracy over standard visual image assessment.MethodsMonocentric retrospective analysis of pretherapeutic [18F]FDG-PET/CT in 491 consecutive patients with NSCLC using an analog PET/CT scanner (training + test cohort, n = 385) or digital scanner (validation, n = 106). Forty clinical variables, tumor characteristics, and image variables (e.g., primary tumor and LN SUVmax and size) were collected. Different combinations of machine learning methods for feature selection and classification of N0/1 vs. N2/3 disease were compared. Ten-fold nested cross-validation was used to derive the mean area under the ROC curve of the ten test folds (“test AUC”) and AUC in the validation cohort. Reference standard was the final N stage from interdisciplinary consensus (histological results for N2/3 LNs in 96%).ResultsN2/3 disease was present in 190 patients (39%; training + test, 37%; validation, 46%; p = 0.09). A gradient boosting classifier (GBM) with 10 features was selected as the final model based on test AUC of 0.91 (95% confidence interval, 0.87–0.94). Validation AUC was 0.94 (0.89–0.98). At a target sensitivity of approx. 90%, test/validation accuracy of the GBM was 0.78/0.87. This was significantly higher than the accuracy based on “mediastinal LN uptake > mediastinum” (0.7/0.75; each p < 0.05) or combined PET/CT criteria (PET positive and/or LN short axis diameter > 10 mm; 0.68/0.75; each p < 0.001). Harmonization of PET images between the two scanners affected SUVmax and visual assessment of the LNs but did not diminish the AUC of the GBM.ConclusionsA machine learning model based on routinely available variables from [18F]FDG-PET/CT improved accuracy in mediastinal LN staging compared to established visual assessment criteria. A web application implementing this model was made available.

Preoperative Hilar and Mediastinal Lymph Node Staging in Patients with Suspected or Diagnosed Lung Cancer: Accuracy of 18F-FDG-PET/CT:A Retrospective Cohort Study of 138 Patients.

The aim of this study was to evaluate the diagnostic accuracy of integrated 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG-PET/CT) in hilar and mediastinal lymph node (HMLN) staging of suspected or proven lung cancer, and to investigate potential risk factors for false negative and false positive HMLN metastases. We retrospectively analyzed 162 consecutive patients with suspected or pathologically proven non-small cell lung cancer (NSCLC). The receiver operating characteristic (ROC) curve was generated to determine the diagnostic efficacy of 18F-FDG-PET/CT. Univariate and multivariate analyses were conducted to detect risk factors of false positives and false negatives. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of integrated 18F-FDG-PET/CT in detecting HMLN metastases were 59.1% (26/44), 69.1% (65/94), 47.3% (26/55), 78.3% (65/83), and 65.9% (91/138), respectively. The ROC curve showed an area under the curve (AUC) of 0.625 (95%-CI 0.468-0.782). The incidence of false negative and false positive HMLN metastases was 21.7% (18/83) and 52.7% (29/55), respectively. Our data shows that integrated 18F-FDG-PET/CT staging provides lower specificity and sensitivity. This confirms the ESTS guideline on lymph node staging for PET-positive HMLN. Yet it advocates more invasive staging even for PET-negative HMLN.

Positron emission tomography - Computed tomography for staging of mediastinal lymph nodes in patients with non-small cell lung cancer.

The tumor involvement of lymph nodes (LN) in N2 station is a very important factor for the further therapy decision and the prognosis of lung cancer patients. Today, integrated positron emission tomography-computed tomography (PET-CT) is considered to be the new standard in the staging of bronchial carcinoma. The aim of this study is to investigate the correctness of the clinical staging of the mediastinal LNs in operated patients and to investigate the sensitivity and specificity of the PET-CT examination for mediastinal LNs. In the years 2010-2014, 359 patients underwent surgery for bronchial carcinoma. The histological examination of all mediastinal and hilar LNs was used as a reference to the data from the PET-CT examinations. The correctness of the PET staging, overestimation, and underestimation for the N stage was analyzed. In addition, the "sensitivity," "specificity," and "overall accuracy" of the PET-CT examination with regard to the N2 LNs were calculated. It was found that in 8.9% the staging of the mediastinal N2/N3 LN stations was rated too high by the PET and in 11.2% too low. The study showed a sensitivity of 47.37%, a specificity of 90.07%, and an accuracy of 81.01% for the mediastinal LNs. Our study confirms the limited ability of integrated PET-CT in staging the mediastinal LNs. We, therefore, recommend a histological examination of the LNs in patients with PET-positive N2 LNs to avoid false-positive results and to initiate correct therapy.

Performance of Telecytology in Endobronchial Ultrasound-Guided Fine Needle Aspiration on Mediastinal Lymph Node Staging: An Institutional Review

Performance of Telecytology in Endobronchial Ultrasound-Guided Fine Needle Aspiration on Mediastinal Lymph Node Staging: An Institutional Review

Value of 18F FDG-PET/CT parameters on long term follow-up for patients with non-small cell lung cancer.

ObjectivesThe purpose of this study was to investigate the value of PET/CT in the preoperative staging of non-small cell lung cancer in predicting long-term survival and diagnostic performance, validated by histopathology following surgical resection.MethodsBetween 02/2009 and 08/2011, 255 patients with non-small cell lung cancer were included in this single-center prospective study. All underwent 18F FDG-PET/CT for pre-operative staging, and in 243 patients complete surgical resection was possible. Regarding lymph node involvement and extrathoracic metastases, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the histopathological staging as reference. Median follow-up for censored patients was 9.1 years.ResultsOverall 5-year survival rate of all patients was 55.6%, and of patients who had complete surgical resection it was 58.2%. In multivariate analysis of all surgically resected patients lymph node involvement (p=0.029) and age >61 years (p=<0.001) were significant independent prognostic factors. SUVmax and SUVmean cut-offs between SUV 2 and 11, however, were not associated with better or ;worse survival. The PET-CT sensitivity, specificity, positive predictive value and negative predictive value for predicting lymph node involvement were 57, 95, 88, and 76%, respectively. Furthermore, sensitivity, specificity, positive predictive value, and negative predictive value for detecting extrathoracic metastases were 100, 58, 98, and 100%, respectively.ConclusionsIn this study, tumor 18F FDG-uptake values did not provide additional prognostic information. Age>61 years and lymph node metastasis were associated with worse long-term survival in surgically resected patients. 18F FDG-PET/CT scans allow for improved patient selection. However, in staging mediastinal lymph nodes, there is a high rate of false positives and false negatives, suggesting that tissue biopsy is still indicated in many cases.

Development and validation of a deep learning signature for predicting lymph node metastasis in lung adenocarcinoma: comparison with radiomics signature and clinical-semantic model.

To develop and validate a deep learning (DL) signature for predicting lymph node (LN) metastasis in patients with lung adenocarcinoma. A total of 612 patients with pathologically-confirmed lung adenocarcinoma were retrospectively enrolled and were randomly divided into training cohort (n = 489) and internal validation cohort (n = 123). Besides, 108 patients were enrolled and constituted an independent test cohort (n = 108). Patients' clinical characteristics and CT semantic features were collected. The radiomics features were derived from contrast-enhanced CT images. The clinical-semantic model and radiomics signature were built to predict LN metastasis. Furthermore, Swin Transformer was adopted to develop a DL signature predictive of LN metastasis. Model performance was evaluated by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, calibration curve, and decision curve analysis. The comparisons of AUC were conducted by the DeLong test. The proposed DL signature yielded an AUC of 0.948-0.961 across all three cohorts, significantly superior to both clinical-semantic model and radiomics signature (all p < 0.05). The calibration curves show that DL signature predicted probabilities fit well the actual observed probabilities of LN metastasis. DL signature gained a higher net benefit than both clinical-semantic model and radiomics signature. The incorporation of radiomics signature or clinical-semantic risk predictors failed to reveal an incremental value over the DL signature. The proposed DL signature based on Swin Transformer achieved a promising performance in predicting LN metastasis and could confer important information in noninvasive mediastinal LN staging and individualized therapeutic options. • Accurate prediction for lymph node metastasis is crucial to formulate individualized therapeutic options for patients with lung adenocarcinoma. • The deep learning signature yielded an AUC of 0.948-0.961 across all three cohorts in predicting lymph node metastasis, superior to both radiomics signature and clinical-semantic model. • The incorporation of radiomics signature or clinical-semantic risk predictors into deep learning signature failed to reveal an incremental value over deep learning signature.

Systematic endoscopic staging of mediastinum to determine impact on radiotherapy for locally advanced lung cancer (SEISMIC): protocol for a prospective single arm multicentre interventional study

BackgroundEndobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as the preferred method of mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). Selective (targeted) LN sampling is most commonly performed however studies in early stage NSCLC and locally advanced NSCLC confirm systematic EBUS-TBNA evaluation improves accuracy of mediastinal staging. This study aims to establish the rate of detection of positron emission tomography (PET)-occult LN metastases following systematic LN staging by EBUS-TBNA, and to determine the utility of systematic mediastinal staging for accurate delineation of radiation treatment fields in patients with locally advanced NSCLC.MethodsConsecutive patients undergoing EBUS-TBNA for diagnosis/staging of locally advanced NSCLC will be enrolled in this international multi-centre single arm study. Systematic mediastinal LN evaluation will be performed, with all LN exceeding 6 mm to be sampled by TBNA. Where feasible, endoscopic ultrasound staging (EUS-B) may also be performed. Results of minimally invasive staging will be compared to FDG-PET. The primary end-point is proportion of patients in whom systematic LN staging identified PET-occult NSCLC metastases. Secondary outcome measures include (i) rate of nodal upstaging, (ii) false positive rate of PET for mediastinal LN assessment, (iii) analysis of clinicoradiologic risk factors for presence of PET-occult LN metastases, (iv) impact of systematic LN staging in patients with discrepant findings on PET and EBUS-TBNA on target coverage and dose to organs at risk (OAR) in patients undergoing radiotherapy.DiscussionWith specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the exact extent of mediastinal LN involvement in NSCLC in patient with Stage III NSCLC is rarely established. Studies examining systematic LN staging in early stage NSCLC report a significant discordance between PET and EBUS-TBNA. In patients with locally advanced disease this has significant implications for radiation field planning, with risk of geographic miss in the event of PET-occult mediastinal LN metastases. The SEISMIC study will examine both diagnostic outcomes following systematic LN staging with EBUS-TBNA, and impact on radiation treatment planning.Trial registrationACTRN12617000333314, ANZCTR, Registered on 3 March 2017.