Risk Factors for Occult Mediastinal Metastases in Clinical Stage I Non-Small Cell Lung Cancer

doi:10.1016/j.athoracsur.2007.03.081

The Annals of Thoracic Surgery

Volume 84, Issue 1, July 2007, Pages 177-181

Presented at the Poster Session of the Forty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 29–31, 2007.

https://doi.org/10.1016/j.athoracsur.2007.03.081 Get rights and content

Background

In patients deemed to have clinical stage I for non-small cell lung cancer (NSCLC) after computerized tomography (CT) and positron emission tomography (PET) scans, the utility of mediastinoscopy to detect occult mediastinal metastases is unclear. The goal of this study was to analyze the risk factors for occult mediastinal metastases in this subset of patients.

Methods

We conducted a retrospective review during a 7-year period to identify patients with potentially operable clinical stage I NSCLC screened by CT and PET scans. Medical records were reviewed, and the prevalence of pathologic N2 disease was analyzed according to clinical tumor location, size, histology, and PET uptake of the primary tumor.

Results

Of 224 patients identified with clinical stage I NSCLC with a CT-negative and PET-negative mediastinum, 16 patients had pathologic N2 disease proven by mediastinoscopy (n = 11) or after resection (n = 5). The overall prevalence of histologically confirmed N2 disease was 6.5% in clinical T1 patients and 8.7% in clinical T2 patients. Central tumors had a higher prevalence of N2 disease compared with peripheral tumors, 21.6% versus 2.9% (p < 0.001). Larger clinical T size predicted a higher prevalence of occult N2 disease (p < 0.001). All 16 patients with occult N2 metastases had adenocarcinoma as the primary tumor cell type. When the PET maximum standardized uptake value (SUV_max) of the primary tumors was analyzed, patients with occult N2 metastases had a higher median SUV_max of the primary tumor compared with patients without N2 metastases, 6.0 g/mL versus 3.6 g/mL (p = 0.017).

Conclusions

For patients deemed at clinical stage I NSCLC by CT and PET, the prevalence of missed N2 metastases increased significantly with larger tumor size and central location. Adenocarcinoma cell type and a high PET SUV_max of the primary tumor were other risk factors. Mediastinoscopy may have improved yield in the select subset of patients with one or more risk factor.

Section snippets

Material and Methods

We conducted a retrospective review of an institutional review board–approved prospective database to identify patients with potentially operable clinical stage I NSCLC with a CT-negative and PET-negative mediastinum from January 2000 to November 2006. This study was approved by the institutional review board of the Weill Medical College of Cornell University, and patient consent was waived. Patients were excluded if both PET and chest CT had not been performed. A total of 224 patients were

Clinical Findings

During the study period from January 2000 to November 2006, 224 patients (87 men, 137 women) were identified. Their median age was 69.5 years (range, 45 to 90 years). All patients were deemed to have clinical stage I NSCLC after radiologic assessments by CT of the chest and upper abdomen (including the adrenals), PET scanning, and any other appropriate imaging modalities including CT or magnetic resonance imaging of the brain. Cervical mediastinoscopies were done in 76 patients (34%), and 11

Comment

The diagnosis of bronchogenic carcinoma carries a dismal prognosis for most patients. The stage of carcinoma at diagnosis remains one of the most important determinants of survival in NSCLC, with earlier stage patients having a better chance of long-term survival [10]. For patients with resectable stage I disease, 5-year survival can be as high as 80% [11]. Patients with metastatic involvement of mediastinal lymph nodes have poor survival, however, and should not be offered surgical resection

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Cited by (197)

Tumor distance from the mediastinum predicts N2 upstaging in clinical stage I lower-lobe non–small cell lung cancer
2024, Journal of Thoracic and Cardiovascular Surgery
Pulmonary lymphatic drainage of the lower lobe into the mediastinal lymph nodes includes not only the pathway via the hilar lymph nodes but also the pathway directly into the mediastinum via the pulmonary ligament. This study aimed to determine the association between the distance from the mediastinum to the tumor and the frequency of occult mediastinal nodal metastasis (OMNM) in patients with clinical stage I lower-lobe non–small cell lung cancer (NSCLC).
Between April 2007 and March 2022, data of patients who underwent anatomical pulmonary resection and mediastinal lymph node dissection for clinical stage I radiological pure-solid lower-lobe NSCLC were retrospectively reviewed. In computed tomography axial sections, the ratio of the distance from the inner edge of the lung to the inner margin of the tumor within the lung width of the affected lung was defined as the inner margin ratio. Patients were divided into 2 groups based on whether the inner margin ratio was ≤0.50 (inner-type) or >0.50 (outer-type), and the association between inner margin ratio status and clinicopathological findings was assessed.
In total, 200 patients were enrolled in the study. OMNM frequency was 8.5%. More inner-type than outer-type patients had OMNM (13.2% vs 3.2%; P = .012) and skip N2 metastasis (7.5% vs 1.1%; P = .038). Multivariable analysis revealed that the inner margin ratio was the only independent preoperative predictor of OMNM (odds ratio, 4.72; 95% CI, 1.31-17.07; P = .018).
Tumor distance from the mediastinum was the most important preoperative predictor of OMNM in patients with lower-lobe NSCLC.
Oncological feasibility of segmentectomy for inner-located lung cancer
2024, JTCVS Open
Oncological feasibility of segmentectomy for internal non–small cell lung cancer (NSCLC) has not been assessed adequately. We assessed the oncological feasibility of segmentectomy for inner-located NSCLC by investigating surgical margins and patient prognosis after undergoing the procedure.
Of the 3555 patients who underwent resection for lung cancer between 2013 and 2019 at our institution, 659 patients who underwent segmentectomy for clinical stage 0 to stage1A NSCLC were included in this study. Patients were separated into 2 groups according to whether the tumor was in the inner or outer third of the lung area. Clinical characteristics and prognoses were retrospectively compared between the groups.
Of the included 659 cases, 183 (27.8%) were inner-located, and 476 (72.2%) had outer-located NSCLC. The surgical margin was significantly shorter in the inner-located group than in the outer group (median, 16 vs 25 mm; P < .001). The 5-year recurrence-free survival and overall survival probabilities were 91.1%/91.8% (P = .530) and 94.1%/95.6% (P = .345) for inner/outer-located groups, respectively. Multivariate analysis showed that clinical stage IA2 or 3 (P = .043), lymphovascular invasion (P < .001), and surgical margins <20 mm (P = .017) were independent prognostic factors for recurrence-free survival. The location of the inner or outer tumors was not related to the prognosis.
For clinical stage 0 to stage1A NSCLC, tumor location in the inner two-thirds of the lung was not associated with prognosis after segmentectomy. Because one of the independent prognostic factors is margin distance, segmentectomy for inner-located NSCLC would be oncologically acceptable when an adequate surgical margin is secured.
Prediction Models for Mediastinal Metastasis and Its Detection by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Potentially Operable Non-Small Cell Lung Cancer: A Prospective Study
2023, Chest
Prediction models for mediastinal metastasis and its detection by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have not been developed using a prospective cohort of potentially operable patients with non-small cell lung cancer (NSCLC).
Can mediastinal metastasis and its detection by EBUS-TBNA be predicted with prediction models in NSCLC?
For the prospective development cohort, 589 potentially operable patients with NSCLC were evaluated (July 2016-June 2019) from five Korean teaching hospitals. Mediastinal staging was performed using EBUS-TBNA (with or without the transesophageal approach). Surgery was performed for patients without clinical N (cN) 2-3 disease by endoscopic staging. The prediction model for lung cancer staging-mediastinal metastasis (PLUS-M) and a model for mediastinal metastasis detection by EBUS-TBNA (PLUS-E) were developed using multivariable logistic regression analyses. Validation was performed using a retrospective cohort (n = 309) from a different period (June 2019-August 2021).
The prevalence of mediastinal metastasis diagnosed by EBUS-TBNA or surgery and the sensitivity of EBUS-TBNA in the development cohort were 35.3% and 87.0%, respectively. In PLUS-M, younger age (< 60 years and 60-70 years compared with ≥ 70 years), nonsquamous histology (adenocarcinoma and others), central tumor location, tumor size (> 3-5 cm), cN1 or cN2-3 stage by CT, and cN1 or cN2-3 stage by PET-CT were significant risk factors for N2-3 disease. Areas under the receiver operating characteristic curve (AUCs) for PLUS-M and PLUS-E were 0.876 (95% CI, 0.845-0.906) and 0.889 (95% CI, 0.859-0.918), respectively. Model fit was good (PLUS-M: Hosmer-Lemeshow P = .658, Brier score = 0.129; PLUS-E: Hosmer-Lemeshow P = .569, Brier score = 0.118). In the validation cohort, PLUS-M (AUC, 0.859 [95% CI, 0.817-0.902], Hosmer-Lemeshow P = .609, Brier score = 0.144) and PLUS-E (AUC, 0.900 [95% CI, 0.865-0.936], Hosmer-Lemeshow P = .361, Brier score = 0.112) showed good discrimination ability and calibration.
PLUS-M and PLUS-E can be used effectively for decision-making for invasive mediastinal staging in NSCLC.
ClinicalTrials.gov; No.: NCT02991924; URL: www.clinicaltrials.gov
Results in mediastinal lymph node staging of surgical lung cancer: Data from the prospective cohort of the Spanish Video-Assisted Thoracic Surgery Group
2023, Cirugia Espanola
El objetivo del estudio es valorar el rendimiento diagnóstico de la tomografía computarizada (TC) y la tomografía por emisión de positrones (PET) en la estadificación clínica mediastínica del cáncer pulmonar quirúrgico según los datos de la cohorte prospectiva del Grupo Español de Cirugía Torácica Videoasistida (GEVATS).
Se han analizado 2.782 pacientes intervenidos por carcinoma pulmonar primario. Se ha estudiado el acierto diagnóstico en la estadificación mediastínica (cN2). Se ha realizado un análisis bivariante y multivariante de los factores que influyen en el acierto. Se ha estudiado el riesgo de pN2 inesperado en los factores con los que se recomienda una prueba invasiva de estadificación: cN1, tumor central o tamaño mayor de 3 cm.
El acierto global de la TC y PET en conjunto es del 82,9% con VPP y VPN de 0,21 y 0,93. En tumores mayores de 3 cm y a mayor SUVmax del mediastino, el acierto es menor, OR de 0,59 (0,44 – 0,79) y 0,71 (0,66 – 0,75), respectivamente. En el abordaje VATS el acierto es mayor, OR de 2,04 (1,52 – 2,73). El riesgo de pN2 inesperado aumenta con el número de los factores cN1, tumor central o tamaño mayor de 3 cm: entre el 4,5% (0 factores) y 18,8% (3 factores), pero no hay diferencias significativas con la realización de prueba invasiva.
La TC y PET en conjunto tienen un elevado valor predictivo negativo. Su acierto global es menor en tumores mayores de 3 cm y SUVmax del mediastino elevado, y mayor en el abordaje VATS. El riesgo de pN2 inesperado es mayor si cN1, tumor central o mayor de 3 cm y no varía significativamente con prueba invasiva.
The objective of this study was to assess the diagnostic performance of combined computerised tomography (CT) and positron emission tomography (PET) in mediastinal staging of surgical lung cancer based on data obtained from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS).
A total of 2782 patients underwent surgery for primary lung carcinoma. We analysed diagnostic success in mediastinal lymph node staging (cN2) using CT and PET. Bivariate and multivariate analyses were performed of the factors involved in this success. The risk of unexpected pN2 disease was analysed for cases in which an invasive testing is recommended: cN1, the tumour centrally located or the tumour diameter >3 cm.
The overall success of CT together with PET was 82.9% with a positive predictive value of 0.21 and negative predictive value of 0.93. If the tumour was larger than 3 cm and for each unit increase in mediastinal SUVmax, the probability of success was lower with OR 0.59 (0.44–0.79) and 0.71 (0.66–0.75), respectively. In the video-assisted thoracic surgery (VATS) approach, the probability of success was higher with OR 2.04 (1.52–2.73). The risk of unexpected pN2 increased with the risk factors cN1, the tumour centrally located or the tumour diameter >3 cm: from 4.5% (0 factors) to 18.8% (3 factors) but did not differ significantly as a function of whether invasive testing was performed.
CT and PET together have a high negative predictive value. The overall success of the staging is lower in the case of tumours >3 cm and high mediastinal SUVmax, and it is higher when VATS is performed. The risk of unexpected pN2 is higher if the disease is cN1, the tumour centrally located or the tumour diameter >3 cm but does not vary significantly as a function of whether patients have undergone invasive testing.
Integral mediastinal staging in patients with NON-SMALL cell lung cancer and risk factors for occult N2 disease
2023, Respiratory Medicine
In patients with non-small cell lung cancer (NSCLC), the presence of abnormal hiliar lymph nodes (clinical N1; cN1), central tumor location and/or tumor size (diameter >3 cm) increases the risk of occult mediastinal metastasis (OMM). This study investigates prospectively the diagnostic value of an integral mediastinal staging (IMS) strategy that combines EndoBronchial Ultrasound-TransBronchial Needle Aspiration (EBUS-TBNA) and Video-Assisted Mediastinoscopy (VAM) in patients with NSCLC at risk of OMM.
Patients with NSCLC and radiologically normal mediastinum assessed non-invasively by positron emission tomography and computed tomography of the chest (PET-CT), and OMM risk factors (cN1, central tumor and/or >3 cm) underwent EBUS-TBNA followed by VAM if the former was negative. Those with negative IMS underwent resection surgery of the tumor.
EBUS-TBNA identified OMM in 2 out of the 49 patients evaluated (4%) and VAM in 1 of the 47 patients with negative EBUS (2%). Two patients with a negative IMS had OMM at surgery. Overall, the prevalence of OMM was 10%. EBUS-TBNA has a sensitivity of 40%, a negative predictive value (NPV) of 93.6%, and negative likelihood ratio of 0.60 (95%CI:0.30–1.16). The risk of not diagnosing OMM after EBUS was 6% and after IMS was 4.4%.
Integral mediastinal staging in patients with NSCLC and clinical risk factors for OMM, does not seem to provide added diagnostic value to that of EBUS-TBNA, except perhaps in patients with cN1 disease who deserve further research.
Definitions of Central Tumors in Radiologically Node-Negative, Early-Stage Lung Cancer for Preoperative Mediastinal Lymph Node Staging: A Dual-Institution, Multireader Study
2022, Chest
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 vs 0.66; 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.

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Original articleGeneral thoracicRisk Factors for Occult Mediastinal Metastases in Clinical Stage I Non-Small Cell Lung Cancer

Background

Methods

Results

Conclusions

Section snippets

Material and Methods

Clinical Findings

Comment

Chest

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Chest

Ann Thorac Surg

Chest

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Cancer statistics, 2005

CA Cancer J Clin

Original article
General thoracic
Risk Factors for Occult Mediastinal Metastases in Clinical Stage I Non-Small Cell Lung Cancer