Invasive Mediastinal Staging Research Articles

Persistent N2 After Induction Is Not a Contraindication to Surgery for Lung Cancer

BackgroundSurgical management for potentially resectable stage IIIA-N2 non-small cell lung cancer (NSCLC) is controversial. For some, persistent N2 disease after induction therapy is a contraindication to resection. We examined outcomes of a well-selected surgical cohort of postinduction IIIA-N2 NSCLC patients with persistent N2 disease. MethodsWe retrospectively reviewed all resected clinical IIIA-N2 NSCLC patients from 2001 to 2018. Thorough preoperative staging, including invasive mediastinal staging, was performed. Those with nonbulky N2 disease, appropriate restaging, and potential for a margin-negative resection were included. After resection, patients were classified as having persistent N2 disease or mediastinal downstaging (N2 to >N0/N1). Persistent N2 patients were further classified as uncertain resection (R[un]) or complete resection (R0) according to the International Association for the Study of Lung Cancer definition. Kaplan-Meier survival analysis was used. ResultsFifty-four patients met inclusion criteria. After induction, 31 patients (57%) demonstrated persistent N2 disease, and 23 patients (43%) had mediastinal downstaging. Preinduction invasive mediastinal staging was performed in 98.1%. Most had clinical single-station N2 disease (75.9%). Margin-negative resections were performed in 100%. Eight patients were reclassified as R(un) due to positive highest sampled mediastinal station. The median overall survival for persistent N2 was 26 months for R(un) and 69 months for R0. Overall survival for the downstaged group was 67 months (P = .31). ConclusionsOverall survival for patients with non-R(un) or persistent N2 (true R0) was similar to those with mediastinal downstaging. Well-selected patients with persistent N2 disease experience reasonable survival after resection and should have surgery considered as part of their multimodality treatment. This study underscores the importance of classifying the extent of mediastinal involvement for persistent N2 patients, supporting the proposed International Association for the Study of Lung Cancer R(un) classification.

How Much Delay Matters? How Time to Treatment Impacts Overall Survival in Early Stage Lung Cancer.

The aim of this study was to identify drivers of time from diagnosis to treatment (TTT) of surgically resected early stage non-small cell lung cancer (NSCLC) and determine the effect of TTT on post-resection survival. Large database studies that lack relevant comorbidity data have identified longer TTT asa driver of worse overall survival. From January 1, 2014 to April 1, 2018, 599 patients underwent lung resection for clinical stage I and II NSCLC. Random forest classification, regression, and survival were used to estimate likelihood of TTT = 0 (tissue diagnosis obtained at surgery), >0 (diagnosis obtained pre-resection), and effect of TTT on all-cause mortality. Patients with TTT > 0 (n = 413) had median TTT of 42 days (25-75 th percentile: 27-59 days). Patients with TTT = 0 (n = 186) had smaller tumors and higher percent predicted forced expiratory volume in 1 second (FEV 1 %). Patients with history of stroke, oncology consultation, invasive mediastinal staging, low and high extremes of FEV 1 % had longer TTT. Higher clinical stage, lack of preoperative stress test, anemia, older age, lower FEV1% and diffusion lung capacity, larger tumor size, and longer TTT were the most important predictors of all-cause mortality. One- and 5-year overall survival decreased when TTT was >50 days. Preoperative physiologic workup and multidisciplinary evaluation were the predominant drivers of longer TTT. Patients with TTT = 0have more favorable presentation and should be considered in TTT analyses for early stage lung cancer populations. The time needed to clinically stage and optimize patients for resection is not deleterious to overall survival until resection is performed after 50 days from diagnosis.

Definitions of Central Tumors in Radiologically Node-Negative, Early-Stage Lung Cancer for Preoperative Mediastinal Lymph Node Staging: A Dual-Institution, Multireader Study

Definitions for central lung cancer (CLC) have been ambiguous in guidelines, causing difficulty in selecting candidates for invasive mediastinal staging among patients with radiologically node-negative, early-stage lung cancer. What is the optimal definition for CLC that is robust to interreader and institutional variation to select candidates for invasive mediastinal staging among those with clinical T1N0M0 lung cancer? Two retrospective cohorts were evaluated for the associations of central lung cancer according to 13 definitions based on chest CT scan with occult nodal metastasis. Univariate and multivariate ordinal logistic regression analyses were performed with the pathologic N category as an ordinal outcome. Robust definitions, which retained statistical significance across multireader, dual-institutional datasets, were identified. For these definitions, binary diagnostic performance and interreader agreement were investigated. In the two cohorts, 807 patients (median age, 63 years; interquartile range [IQR], 56-71 years; 410 women; 33 pN1, 48 pN2, and 1 pN3) and 510 patients (median age, 65 years; IQR, 58-71 years; 267 women; 33 pN1, 20 pN2, and no pN3) were included, respectively. Three definitions robust to interreader variation and dataset heterogeneity were identified: definition 7 (concentric lines arising from the midline, inner one-third, medial margin; adjusted OR, 2.01; 95%CI, 1.13-3.51; P= .02), definition 10 (location index-based inner one-third, center; adjusted OR, 3.60; 95%CI, 1.49-8.25; P= .003), and definition 12 (location index-based inner one-third, medial margin; adjusted OR, 3.57; 95%CI, 1.91-6.52; P< .001). Definition 12 showed higher interreader agreement than definition 7 (Cohen κ, 0.80 vs0.66; P= .005). Nevertheless, the sensitivity and positive predictive value of the three definitions were< 50%. Three definitions exhibited robust associations with occult nodal metastasis. However, selecting candidates for invasive mediastinal staging solely based on a central tumor location would be suboptimal.

Patients' Preferences Regarding Invasive Mediastinal Nodal Staging of Resectable Lung Cancer.

BackgroundVariability in practice and ongoing debate on optimal invasive mediastinal staging of patients with resectable non-small cell lung cancer (NSCLC) are widely described in the literature. Patients’ preferences on this topic have, however, been underexposed so far.MethodsAn internet-based questionnaire was distributed among MEDIASTrial participants (NTR6528, randomization of patients to mediastinoscopy or not in the case of negative endosonography). Literature, expert opinion and patient interviews resulted in five attributes: the risk of a futile lung resection (oncologically futile in case of unforeseen N2 disease), the length of the staging period, resection of the primary tumor, complications of staging procedures and the mediastinoscopy scar. The relative importance (RI) of each attribute was assessed by using adaptive conjoint analysis and hierarchical Bayes estimation. A treatment trade-off was used to examine the acceptable proportion of avoided futile lung resections to cover the burden of confirmatory mediastinoscopy.ResultsNinety-seven patients completed the questionnaire (57%). The length of the staging period was significantly the most important attribute (RI 26.24; 95% CI: 25.05–27.43), followed by the risk of a futile surgical lung resection (RI 23.44; 95% CI: 22.28–24.60) and resection of the primary tumor (RI 22.21; 95% CI: 21.09–23.33). Avoidance of 7% (IQR 1– >14%) futile lung resections would cover the burden of confirmatory mediastinoscopy, with a dichotomy among patients always (39%) or never (38%) willing to undergo confirmatory mediastinoscopy after N2 and N3-negative endosonography.ConclusionAlthough a strong dichotomy among patients always or never willing to undergo confirmatory mediastinoscopy was found, the length of the staging period was the most important attribute in invasive mediastinal staging according to patients with resectable NSCLC.Trial RegistrationNot applicable.

N-staging in large cell neuroendocrine carcinoma of the lung: diagnostic value of [18F]FDG PET/CT compared to the histopathology reference standard

BackgroundLarge cell neuroendocrine carcinoma of the lung (LCNEC) is a rare entity occurring in less than 4% of all lung cancers. Due to its low differentiation and high glucose transporter 1 (GLUT1) expression, LCNEC demonstrates an increased glucose turnover. Thus, PET/CT with 2-[18F]-fluoro-deoxyglucose ([18F]FDG) is suitable for LCNEC staging. Surgery with curative intent is the treatment of choice in early stage LCNEC. Prerequisite for this is correct lymph node staging. This study aimed at evaluating the diagnostic performance of [18F]FDG PET/CT validated by histopathology following surgical resection or mediastinoscopy. N-staging interrater-reliability was assessed to test for robustness of the [18F]FDG PET/CT findings.MethodsBetween 03/2014 and 12/2020, 46 patients with LCNEC were included in this single center retrospective analysis. All underwent [18F]FDG PET/CT for pre-operative staging and subsequently either surgery (n = 38) or mediastinoscopy (n = 8). Regarding the lymph node involvement, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for [18F]FDG PET/CT using the final histopathological N-staging (pN0 to pN3) as reference.ResultsPer patient 14 ± 7 (range 4–32) lymph nodes were resected and histologically processed. 31/46 patients had no LCNEC spread into the lymph nodes. In 8/46 patients, the final stage was pN1, in 5/46 pN2 and in 2/46 pN3. [18F]FDG PET/CT diagnosed lymph node metastasis of LCNEC with a sensitivity of 93%, a specificity of 87%, an accuracy of 89%, a PPV of 78% and a NPV of 96%. In the four false positive cases, the [18F]FDG uptake of the lymph nodes was 33 to 67% less in comparison with that of the respective LCNEC primary. Interrater-reliability was high with a strong level of agreement (κ = 0.82).ConclusionsIn LCNEC N-staging with [18F]FDG PET/CT demonstrates both high sensitivity and specificity, an excellent NPV but a slightly reduced PPV. Accordingly, preoperative invasive mediastinal staging may be omitted in cases with cN0 disease by [18F]FDG PET/CT. In [18F]FDG PET/CT cN1-cN3 stages histological confirmation is warranted, particularly in case of only moderate [18F]FDG uptake as compared to the LCNEC primary.

Utility of PET-CT in non-small cell lung cancer clinical stage IB-IIA according to AJCC 8th edition staging system: an alternative to invasive mediastinal staging?

ObjectiveMediastinal nodal staging in lung cancer is essential to determine treatment strategy and prognosis. There are controversies as to whether a mediastinal negative result in PET-CT may spare the invasive staging of the mediastinum. The main endpoint is to evaluate the negative predictive value (NPV) of PET-CT in non-small cell lung cancer (NSCLC) clinical stage IB-IIA without clinical nodal involvement. The secondary endpoint is to evaluate the prevalence of mediastinal and hilar nodal affection in this population.MethodsWe performed an observational descriptive study from January 2010 to January 2020, including 76 patients with clinical stage IB-IIA, who underwent pulmonary resection with systematic nodal sampling (pre-determined lymph node stations based on tumour location) for primary NSCLC. Clinically, nodal involvement was defined as any lymph node greater than 1 cm in the short axis on a CT or with metabolic uptake greater than 2.5 SUV on PET-CT. The prevalence of nodal metastases was recorded.ResultsFifty six patients had clinical stage IB and 20 had clinical stage IIA. Mean tumour size was 3.74 ± 0.5 cm. Lobectomy was the resection procedure most frequently performed. Of the 76 patients with clinical N0 by PET-CT who underwent surgical resection, 10 (13.1%) were upstaged to pN1 and none were upstaged to pN2. NPV of PET-CT for overall nodal metastasis was 87% (95% CI: 0.79–0.94). NPV of PET-CT for N2 metastasis was 100%.ConclusionPET-CT might be an alternative to invasive mediastinal staging in patients with NSCLC clinical stage IB-IIA who are surgical candidates. Further prospective multi-institutional studies are necessary to verify the external validity of our study.

A Prediction Model to Optimize Invasive Mediastinal Staging Procedures for Non-small Cell Lung Cancer in Patients With a Radiologically Normal Mediastinum: The Quebec Prediction Model

Current guideline-recommended criteria for invasive mediastinal staging in patients with a radiologically normal mediastinum fail to identify a significant proportion of patients with occult mediastinal disease (OMD), despite it leading to a large number of invasive staging procedures. Which variables available before surgery predict the probability of OMD in patients with a radiologically normal mediastinum? We identified all cTxN0/N1M0 non-small cell lung cancer tumors staged by CT imaging and PET with CT imaging in our institution between 2014 and 2018 who underwent gold standard surgical lymph node dissection or were demonstrated to have OMD before surgery by invasive mediastinal staging techniques and divided them into a derivation and an independent validation cohort to create the Quebec Prediction Model (QPM), which allows calculation of the probability of OMD. Eight hundred three patients were identified (development set, n= 502; validation set, n= 301) with a prevalence of OMD of 9.1%. The developed prediction model included largest mediastinal lymph node size (P< .001), tumor centrality (P= .23), presence of cN1 disease (P= .29), and lesion standardized uptake value (P= .09). Using a calculated probability of more than 10%as a threshold to identify OMD, this model had a sensitivity, specificity, positive predictive value, and negative predictive value in the derivation cohort of 73.9%(95%CI, 58.9%-85.7%), 81.1%(95%CI, 77.2%-84.6%), 28.3%(95%CI, 23.4%-33.8%), and 96.8%(95%CI, 95.0%-98.1%), respectively. It performed similarly in the validation cohort (P = .77, Hosmer-Lemeshow test; P= .5163, Pearson χ2 and unweighted sum-of-squares statistics; and P= .0750, Stukel score test) and outperformed current guideline-recommended criteria in identifying patients with OMD (area under the receiver operating characteristic curve [AUC] for American College of Chest Physicians guidelines criteria, 0.65 [95%CI, 0.59-0.71]; AUC for European Society of Thoracic Surgeons guidelines criteria, 0.60 [95%CI, 0.54-0.67]; and AUC for the QPM, 0.85 [95%CI, 0.80-0.90]). The QPM allows the clinician to integrate available information from CT and PET imaging to minimize invasive staging procedures that will not modify management, while also minimizing the risk of unforeseen mediastinal disease found at surgery.

Validation of National Comprehensive Cancer Network Guidelines (NCCN) at a single institution.

e20556 Background: Invasive mediastinal staging is necessary to identify locally advanced non-small cell lung cancer (NSCLC). We sought to validate NCCN guidelines for invasive mediastinal staging. Methods: We retrospectively reviewed all patients who had curative lung resection for pathologically confirmed NSCLC from October 2018 to December 2019. We excluded patients who had induction therapy without undergoing invasive mediastinal staging first. We evaluated methods of mediastinal staging, staging results, and final pathology. Indications for staging were one or more of the following; mediastinal lymph nodes &gt; 1.0cm in short axis, Standardized Uptake Value of &gt; 3.0 on Positron Emission Tomography, &gt; 50% of tumor on medial side of mid-clavicular line (central vs peripheral), or peripheral lesion &gt; 3.0cm in diameter. Staging methods were mediastinoscopy, endobronchial ultrasound (EBUS), and video-assisted thoracoscopic surgery (VATS) ipsilateral mediastinal staging before resection of main tumor. Results: In total, 457 lung resections were performed. Staging was done in 144/275 indicated cases (52.4%). Mediastinoscopy was completed in 49 patients, with 20.4% (n = 10) N2-positive. The false negative rate of mediastinoscopy was 4.1% (n = 2 at station 7). EBUS was performed in 64 patients and 21.9% (n = 14) were N2 positive. The false negative rate for EBUS was 3.1% (n = 2 at station 7). Two mediastinoscopy and 9 EBUS patients had 0 N2 stations sampled. None of the patients were ultimately N2 positive. Staging of three mediastinal stations (4L, 4R, and 7) was done in 26/49 mediastinoscopies and 15/64 EBUS. Of 20 patients who had VATS ipsilateral mediastinal staging, none were N2 positive and there were 0 false negatives. This left 131 patients who did not received indicated staging. The most common indication in this group was central location, 83.2% (n = 109). Four of these unstaged patients were N2 positive at resection (3.1%). The sole indication for these 4 patients was a centrally located tumor. Clinical tumor sizes were 1.2 cm, 1.3 cm, 1.5 cm, and 1.9 cm. Overall, the N2-positive rate of the staged group was 24/144 (16.7%) vs 4/131 (3.1%) N2 positive in the unstaged group, p &lt; 0.001. Conclusions: The current NCCN staging guidelines accurately reflect the risk of N2 disease for NSCLC. The indication of central location for tumors may benefit from being reevaluated in a larger cohort, particularly given efficacy of adjuvant therapy.

Health Resource and Cost Savings Achieved in a Multidisciplinary Lung Cancer Clinic.

Background: Lung cancer (LC) care is resource and cost intensive. We launched a Multidisciplinary LC Clinic (MDC), where patients with a new LC diagnosis received concurrent oncology consultation, resulting in improved time to LC assessment and treatment. Here, we evaluate the impact of MDC on health resource utilization, patient and caregiver costs, and secondary patient benefits. Methods: We retrospectively analyzed patients in a rapid assessment clinic with a new LC diagnosis pre-MDC (September 2016–February 2017) and post-MDC implementation (February 2017–December 2018). Data are reported as means; unpaired t-tests and ANOVA were used to assess for significance. We also conducted a cost analysis. Resource utilization, out-of-pocket costs, procedure-related costs, and indirect costs were evaluated from the societal perspective and presented in 2019 Canadian dollars (CAD); multi-way worst/best case and threshold sensitivity analyses were conducted. Results: We reviewed 428 patients (78 traditional model, 350 MDC). Patients in the MDC model required significantly fewer oncology visits from LC diagnosis to first LC treatment (1.62 vs. 2.68, p < 0.001), which was significant for patients with stage 1, 3, and 4 disease. Compared with the traditional model, there was no change in mean biopsies/patient (1.32 traditional vs. 1.17 MDC, p = 0.18) or staging investigations/patient (2.24 traditional vs. 2.02 MDC, p = 0.20). Post-MDC, there was an increase in invasive mediastinal staging for patients with stage 2/3 LC (15.0% vs. 60.0%, p < 0.001). Over 22 months, MDC resulted in savings of CAD 48,389 including CAD 24,167 CAD in direct patient out-of-pocket expenses. For the threshold analyses, MDC was estimated to cost CAD 25,708 per quality-adjusted life year (QALY), considered to be below current willingness to pay thresholds (at CAD 80,000 per QALY). MDC also facilitated oncology assessment for 29 non-LC patients. Conclusions: An MDC led to a reduction in patient visits and direct patient and caregiver costs.

Changing trends of invasive mediastinal evaluation in India

Background:The utilization of mediastinoscopy for mediastinal staging or evaluation has been on the wane, because of the increasing use of methods such as endoscopic ultrasound (EUS)/endobronchial ultrasound (EBUS). The choice of one modality over the other is based on individual preferences, expertise, cost, and the disease in question.Objectives:This study was aimed at assessing the changing trends in the practice of mediastinoscopy and endoscopic techniques across India.Materials and Methods:This online, questionnaire-based survey was conducted at the Malabar Cancer Center, Kerala, India, between September 2019 and January 2020. Surgical oncologists, thoracic surgeons, and pulmonologists treating patients with lung cancer in the National Cancer Grid, India-affiliated institutions were enrolled. A total of 20 questions directed at determining the experience of the healthcare professionals, type of institutions where they practiced, the volume of patients with lung cancers being treated by them, and the temporal changes in the utility of mediastinoscopy and EBUS/EUS over the past 2 years were included in the questionnaire. The survey was conducted using Google Forms. Descriptive and inferential statistics were used for data analysis. AP&lt; 0.05 was considered statistically significant.Results:A total of 347 clinicians were invited to participate in the survey, of which 70 responded. A total of 62 (88.6%) respondents recommended invasive mediastinal staging in patients with lung cancer with positive mediastinal nodes on positron emission tomography (PET). In addition, 39 (55.7%) respondents believed that invasive staging is required even in those with a negative mediastinum on PET; 58 (82.9%) respondents were of the opinion that EBUS is the investigation of choice for suspicious mediastinal nodes, while 8 (11.4%) preferred mediastinoscopy.Conclusion:Endoscopic techniques have superseded mediastinoscopy for invasive mediastinal evaluation across the country.

Role of endobronchial ultrasound-guided transbronchial needle aspiration in staging of lung cancer: a thoracic surgeon's perspective.

In potentially resectable non-small cell lung cancer (NSCLC) accurate mediastinal staging is crucial not only to offer the optimal management but also to avoid unnecessary surgery. Mediastinal staging is generally performed by the use of imaging techniques (computed tomography and positron emission tomography). However, the accuracy of radiological imaging in mediastinal staging is suboptimal. Therefore, additional invasive mediastinal staging is frequently required to select patients who can benefit from a neoadjuvant treatment. In recent years, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has progressively replaced mediastinoscopy as a test for invasive mediastinal staging. The considerable potential of EBUS-TBNA as minimally invasive staging method has been understood by pulmonologists since the early 2000s but only recently by thoracic surgeons. The clinical impact of this diagnostic technology has been broadly highlighted in the literature and EBUS-TBNA is currently considered the test of first choice in preoperative nodal staging of NSCLC. We analyze the actual role of EBUS-TBNA in invasive mediastinal staging of NSCLC patients from the thoracic surgeon point of view, with particular emphasis on the performance characteristics of this endoscopic diagnostic method as well as its clinical use within the published guidelines.

MA09.10 Location of Lymph Nodes Missed after Invasive Mediastinal Staging in a Well-Staged Non-Small Cell Lung Cancer Cohort

Nodal stage is prognostic and predictive of adjuvant therapy benefit in potentially curable non-small cell lung cancer (NSCLC). Using a cohort of patients who met National Comprehensive Cancer Network (NCCN) pathologic nodal staging quality (examination of ≥1 N1 and ≥3 mediastinal nodal stations) as reference, we evaluated the thoroughness of invasive nodal staging to determine the frequency of non-examination of specific hilar/mediastinal nodes and missed node metastasis. We also compared survival between NCCN-quality and non-NCCN quality-attaining resections on the basis of missed nodal metastasis on invasive staging.

The impact of pathologic staging of the hilar/mediastinal nodes on outcomes in patients with early-stage NSCLC receiving stereotactic body radiotherapy.

BackgroundThe importance of invasive mediastinal nodal staging in early-stage non-small cell lung cancer (NSCLC) in the PET/CT era is dependent on tumor factors that increase risk of nodal metastasis. At our institution, patients undergo biopsy via either CT-guidance (without nodal staging) or navigational bronchoscopy with endobronchial ultrasound transbronchial needle aspiration for nodal staging. This study aims to compare outcomes after stereotactic body radiotherapy (SBRT) stratified by receipt of invasive mediastinal nodal staging.MethodsIn this retrospective study, records of all consecutive patients undergoing SBRT for early-stage NSCLC between 2010 and 2017 were analyzed. The association between time-to event outcomes (recurrence and survival) were evaluated with covariates of interest including tumor size, location, histology, smoking history, prior lung cancer history, radiation dose and receipt of nodal staging. Both univariable and multivariable analyses were used to examine these comparisons.ResultsOverall, 158 patients were treated with SBRT. One hundred forty-nine out of one hundred fifty-eight patients (94%) underwent PET/CT staging, and all patients underwent tumor-directed biopsy. Seventy-nine patients underwent navigational bronchoscopy with nodal staging and 79 patients underwent CT-guided biopsy without nodal staging. Receipt of nodal staging was not associated with tumor size (P=0.35), yet was associated with central tumor location (P<0.001). There was no statistically significant association between receipt of nodal staging and time-to-event recurrence or survival outcomes; for example 3-year overall survival (OS) was 65% vs. 67% (P=0.65) and 3-year freedom from nodal failure was 84% vs. 69% (P=0.1) for those with and without nodal staging, respectively.ConclusionsSimilar recurrence and survival outcomes were observed after SBRT regardless of receipt of invasive mediastinal nodal staging. Further prospective evaluation can help identify which patients might derive greatest benefit from invasive staging of the mediastinum in the PET/CT era.

Bridging the gap between guidelines and practice for invasive mediastinal staging in non-small-cell lung cancers

Bridging the gap between guidelines and practice for invasive mediastinal staging in non-small-cell lung cancers

Prediction of Unexpected N2 Disease Associated With Clinical T1-2N0-1M0 Non–Small-Cell Lung Cancer

BackgroundDespite the recent development of radiologic mediastinal staging modality, unexpected mediastinal lymph node metastasis still occurs. Preoperative accurate nodal staging is important to determine the optimal treatment. Therefore, this study aimed to identify predictors of unexpected N2 disease in non–small-cell lung cancer (NSCLC). Patients and MethodsData from a multicenter database of 2802 patients with clinical T1-2N0-1M0 NSCLC who underwent anatomical segmentectomy or lobectomy were retrospectively analyzed. Unexpected N2 disease was defined as pathologic N2 disease with clinical N0 or N1. The predictive criteria of unexpected N2 disease were established on the basis of the multivariable analysis results of a derivation cohort of 2019 patients, and the criteria were further tested in a validation cohort of 783 patients. ResultsIn multivariable analyses, maximum standardized uptake value (SUVmax) of the primary tumor on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (odds ratio, 1.072; 95% confidence interval, 1.018−1.129; P = .008) and clinical N1 (vs. clinical N0) disease (odds ratio, 5.40; 95% confidence interval, 1.829−15.94; P = .002) were independent predictors of unexpected N2 disease. The predictive criteria of unexpected N2 disease was defined as tumors with SUVmax of ≥ 3.1, determined by receiver operating characteristic curves, and clinical N1 disease. This criterion showed diagnostic accuracy of 90.6% (sensitivity 32.0%, specificity 94.5%) in the derivation cohort and 91.3% (sensitivity 32.6%, specificity 94.7%) in the validation cohort. ConclusionThe predictive criteria of unexpected N2 disease (tumors with SUVmax of ≥ 3.1 and clinical N1) can be used to select candidates for preoperative invasive mediastinal staging in patients with clinical T1-2N0-1M0 NSCLC.

Central location and risk of imaging occult mediastinal lymph node involvement in cN0T2-4 non-small cell lung cancer.

BackgroundAppropriate pre-operative staging is a cornerstone in the treatment of non-small cell lung cancer (NSCLC). Central location and size greater than 3 cm are amongst indications for pre-operative invasive mediastinal staging but the quality of the evidence behind this recommendation is low.MethodsWe retrospectively reviewed all cases of cT2-4N0M0 NSCLCL after CT and TEP-CT which underwent surgical resection with lymph node dissection or had a positive invasive pre-operative mediastinal staging in our institution from 2014 to 2018.ResultsThree hundred and ten patients met inclusion criteria, 79 (25.5%) central and 231 (74.5%) peripheral tumors. Central tumor location was associated with a higher prevalence of pN2-3 disease (17.7% vs. 6.1%, P<0.001). In a multivariate analysis, central tumor location remained the only factor statistically associated with imaging occult mediastinal disease (OR 3.23, 95% CI: 1.45–7.18). NPV of PET-CT for occult mediastinal disease was 0.83 (95% CI: 0.72–0.90) in central and 0.94 (95% CI: 0.90–0.97) in peripheral tumor. Central location was also associated with a higher prevalence of occult N1 to N3 disease (43.0% vs. 15.2%, P<0.001).ConclusionsThis study suggests that invasive mediastinal staging is required in central cT2-4N0 NSCLC but can be questioned in peripheral one, especially in cT2N2 subgroup if the patient is a candidate for lobar resection.

Community Size and Lung Cancer Resection Outcomes: Studying The Society of Thoracic Surgeons Database

Socioeconomic factors play key roles in surgical outcomes. Socioeconomic data within The Society of Thoracic Surgeons (STS) General Thoracic Surgery Database (GTSD) are limited. Therefore, we utilized community size as a surrogate to understand socioeconomic differences in lung cancer resection outcomes. We retrospectively reviewed all lung cancer resections from January 2012 to January 2017 in the STS GTSD. This captured 68,722 patients from 286 centers nationwide. We then linked patient zip codes with 2013 Rural-Urban Continuum Codes to understand the association between community size and postoperative outcomes. Demographic and clinical variables were evaluated for relationships with 30-day mortality, major morbidity, and readmission. Zip codes were included in 47.2% of patients. Zip-coded patients were older, were more comorbid, had less advanced disease, and were more commonly treated with minimally invasive approaches than were those without zip code classification. For geocoded patients, multivariable analyses demonstrated that sex, insurance payor, and hospital region were associated with all 3 major endpoints. Community size, based on Rural-Urban Continuum Codes coding, was not associated with any primary endpoint. Invasive mediastinal staging was related to morbidity, greater pathological stage predicted mortality, and worsened clinical stage was associated with readmission. More invasive surgery and greater extent of lung resection were associated with all primary endpoints. Incomplete data capture can promote selection bias within the STS GTSD and skew outcomes reporting. Moreover, community size is an insufficient surrogate, compared with sex, insurance payor, hospital region, for understanding socioeconomic differences in lung cancer resection outcomes.

Trends in mediastinal nodal staging and its impact on unforeseen N2 and survival in lung cancer

Guidelines for invasive mediastinal nodal staging in resectable nonsmall cell lung cancer (NSCLC) have changed over the years. The aims of this study were to describe trends in invasive staging and unforeseen N2 (uN2) and to assess a potential effect on overall survival. A nationwide Dutch cohort study included all clinical stage IA-IIIB NSCLC patients primarily treated by surgical resection between 2005 and 2017 (n=22 555). We assessed trends in invasive nodal staging (mediastinoscopy 2005-2017; endosonography 2011-2017), uN2 and overall survival and compared outcomes in the entire group and in clinical nodal stage (cN)1-3 patients with or without invasive staging. An overall increase in invasive nodal staging from 26% in 2005 to 40% in 2017 was found (p<0.01). Endosonography increased from 19% in 2011 to 32% in 2017 (p<0.01), while mediastinoscopy decreased from 24% in 2011 to 21% in 2017 (p=0.08). Despite these changes, uN2 was stable over the years at 8.7%. 5-year overall survival rate was 41% for pN1 compared to 37% in single node uN2 (p=0.18) and 26% with more than one node uN2 (p<0.01). 5-year overall survival rate of patients with cN1-3 with invasive staging was 44% versus 39% in patients without invasive staging (p=0.12). A significant increase in invasive mediastinal nodal staging in patients with resectable NSCLC was found between 2011 and 2017 in the Netherlands. Increasing use of less invasive endosonography prior to (or as a substitute for) surgical staging did not lead to more cases of uN2. Performance of invasive staging indicated a possible overall survival benefit in patients with cN1-3 disease.

Concordance of Clinical and Pathologic Nodal Staging in Resectable Lung Cancer

Clinical staging of lung cancer may not reliably predict nodal disease, and its accuracy in The Society of Thoracic Surgeons General Thoracic Surgery Database is not described. Among anatomic pulmonary resections for stages I to III lung cancer with complete clinical and pathologic staging (2012-2017), the accuracy of invasive mediastinal staging (IMS) was compared with noninvasive mediastinal staging only. Accuracy, defined as concordance between clinical and pathologic nodal status, was examined using logistic regression to determine factors associated with clinical nodal (cN) accuracy. Variation in accuracy across centers was recorded and categorized. We included 39,516 patients with stages I to III pulmonary cancer (adenocarcinoma, 66%; squamous, 23%; neuroendocrine, 5%; mixed, 3.3%; other, 2.4%), of whom 90.4% had cN0 disease. IMS was performed in 32.4%. The IMS group had more central tumors (14.8% vs 6.0%, P < .001) and cN1-2 (15.7% vs 6.8%, P < .001). Nodal accuracy was 79.8%. Although IMS had a lower nodal accuracy for cN0-2 disease (74.6% vs 82.6%, P<.001), IMS had higher accuracy when comparing patients with cN1-2 disease (53.9% vs 46.9%, P < .001). In multivariable analysis central tumors (odds ratio, 0.47; 95% confidence interval, 0.43-0.51) and >cN0 disease (odds ratio, 0.25; 95% confidence interval, 0.22-0.29) were associated with lower accuracy. Accuracy of IMS in the top 20 centers was 94.4% and in the bottom 20, 70.9%. Staging accuracy in lung cancers selected for initial resection declines with >cN0 and central tumors. Noninvasive staging in tumors without cN involvement misses nearly 20% of cN1-2. Center-specific accuracy is a target for quality improvement.

Geometrical Measurement of Central Tumor Location in cT1N0M0 NSCLC Predicts N1 but Not N2 Upstaging

In patients with non-small cell lung cancer (NSCLC) and normal mediastinum, the central tumor location predicts occult nodal disease (both N1 and N2). We evaluated a novel definition of central location based on a geometrical measurement of the tumor location within the lung that could predict N2, N1, or both. This retrospective study included patients with confirmed NSCLC, radiologically and metabolically staged T1 N0 M0, who underwent invasive mediastinal staging and/or lung resection. The central tumor location was measured considering 2 ratios. The inner margin ratio (IMR) and outer margin ratio (OMR) were both calculated as the distance from the inner margin of the lung to both margins of the tumor (inner [IMR], outer [OMR]) divided by the lung width. Optimal cutoffs for IMR and OMR were calculated. Tumors with values lower than the cutoffs were considered central. Prevalences of N1 and N2 upstaging were estimated and bivariate logistic regression analysis was performed to predict the odds of N1 and N2 upstaging using IMR and OMR cutoffs. A total of 209 patients were included. The prevalence of N1 and N2 upstaging was 11% and 5.3%, respectively. Cutoffs of 0.5 for IMR and 0.64 for OMR were estimated. Both ratios predicted N1 upstaging (adjusted odds ratio [95% confidence interval]: 4.2 [1.5-12]; P < .007; area under the curve, 0.65) but did not predict N2 upstaging. Central tumor location can be assessed by means of IMR and OMR and predicts N1 upstaging in patients with radiologically and metabolically T1 N0 M0 tumors. This is important for the selection of patients for therapies that require N0 tumors.