Occult N2 Research Articles

PET/CT based cross-modal deep learning signature to predict occult nodal metastasis in lung cancer

Occult nodal metastasis (ONM) plays a significant role in comprehensive treatments of non-small cell lung cancer (NSCLC). This study aims to develop a deep learning signature based on positron emission tomography/computed tomography to predict ONM of clinical stage N0 NSCLC. An internal cohort (n = 1911) is included to construct the deep learning nodal metastasis signature (DLNMS). Subsequently, an external cohort (n = 355) and a prospective cohort (n = 999) are utilized to fully validate the predictive performances of the DLNMS. Here, we show areas under the receiver operating characteristic curve of the DLNMS for occult N1 prediction are 0.958, 0.879 and 0.914 in the validation set, external cohort and prospective cohort, respectively, and for occult N2 prediction are 0.942, 0.875 and 0.919, respectively, which are significantly better than the single-modal deep learning models, clinical model and physicians. This study demonstrates that the DLNMS harbors the potential to predict ONM of clinical stage N0 NSCLC.

Occult lymph node metastasis is not a favorable factor for resected NSCLC patients

BackgroundThis study was to compare the clinical presentations and survivals between the non-small cell lung cancer (NSCLC) patients with occult lymph node metastasis (OLNM) and those with evident lymph node metastasis (ELNM). We also intended to analyze the predictive factors for OLNM.MethodsKaplan–Meier method with log-rank test was used to compare survivals between groups. Propensity score matching (PSM) was used to reduce bias. The least absolute shrinkage and selection operator (LASSO)-penalized Cox multivariable analysis was used to identify the prognostic factors. Random forest was used to determine the predictive factors for OLNM.ResultsA total of 2,067 eligible cases (N0: 1,497 cases; occult N1: 165 cases; evident N1: 54 cases; occult N2: 243 cases; evident N2: 108 cases) were included. The rate of OLNM was 21.4%. Patients with OLNM were tend to be female, non-smoker, adenocarcinoma and had smaller-sized tumors when compared with the patients with ELNM. Survival curves showed that the survivals of the patients with OLNM were similar to those of the patients with ELNM both before and after PSM. Multivariable Cox analysis suggested that positive lymph nodes (PLN) was the only prognostic factor for the patients with OLNM. Random forest showed that clinical tumor size was an important predictive factor for OLNM.ConclusionsOLNM was not rare. OLNM was not a favorable sign for resected NSCLC patients with lymph node metastasis. PLN determined the survivals of the patients with OLNM. Clinical tumor size was a strong predictive factor for OLNM.

Abstract 3387: ctDNA dynamics in early stage node negative lung cancers

Abstract Introduction: Patients with early-stage lung cancers have a high risk of relapse and death even after curative surgery. Detection of circulating tumour DNA (ctDNA) in plasma perioperatively is associated with shorter recurrence free survival (RFS). ctDNA-Lung-Detect is an investigator-initiated prospective study of ctDNA detection and association with RFS in patients with early stage non-small cell lung cancer (NSCLC). Methods: Patients with clinically staged T<4cm N0 NSCLC planned for surgical resection at the Princess Margaret/University Health Network underwent ctDNA assessment before and after surgery (~1 month and 1 year). ctDNA minimal residual disease (MRD) was detected using the highly sensitive and specific tumor-informed Residual Disease and Recurrence (RaDaR®, Inivata, Cambridge, UK) assay, which can track up to 48 tumor-specific variants in plasma. Results: Since August 2021, 64 eligible patients were enrolled (Table 1). One had isolated metastasis from a remote non-lung primary and subsequently excluded; another had their preoperative sample missed but was included. Preoperative ctDNA was detected in 15/62 (23.8%) patients and 1/63 (1.6%) post-operatively at the 1-month landmark timepoint (occult N2 disease found at surgery). All but one (93.3%) had ctDNA clearance with surgical resection. Two patients have recurred radiographically and in plasma at 1 year post-operatively, 1/15 with preoperative ctDNA detected (6.7%) and 1/47 without preoperative ctDNA detected (2.1%). Patients with higher T stage, tumor size, squamous histology, and without actionable driver alterations were more likely to have ctDNA detected at any timepoint. Conclusions: In patients with early stage NSCLC (small node negative tumors), 24% have detectable ctDNA pre-operatively. Surgical resection led to ctDNA clearance in 93% of cases. Our results support ongoing testing beyond the initial MRD landmark. Assessment of the impact on RFS post resection is ongoing. Citation Format: Jamie Feng, Tom Waddell, Kazuhiro Yasufuku, Andrew Pierre, Shaf Keshavjee, Jonathan Yeung, Marcelo Cypel, Laura Donahoe, Elliot Wakeam, Marc de Perrot, Jennifer Law, Alexandra Salvarrey, Lisa W. Le, Jennifer Lister, Michael Cabanero, Ming Tsao, Christodoulos Pipinikas, Karen Howarth, Natasha Leighl. ctDNA dynamics in early stage node negative lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3387.

Integral mediastinal staging in patients with NON-SMALL cell lung cancer and risk factors for occult N2 disease

BackgroundIn 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. MethodsPatients 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. ResultsEBUS-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%. ConclusionIntegral 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.

Lobar versus sublobar resection in clinical stage IA primary lung cancer with occult N2 disease.

Sublobar resection is increasingly being utilized for early-stage lung cancers, but optimal management when final pathology shows unsuspected mediastinal nodal disease is unclear. This study tested the hypothesis that lobectomy has improved survival compared to sublobar resection for clinical stage IA tumours with occult N2 disease. The use of sublobar resection and lobectomy for patients in the National Cancer Database who underwent primary surgical resection for clinical stage IA non-small-cell lung cancer with pathologic N2 disease between 2010 and 2017 was evaluated using logistic regression. Survival was assessed with Kaplan-Meier analysis, log-rank test and Cox proportional hazards model. A total of 2419 patients comprised the study cohort, including 320 sublobar resections (13.2%) and 2099 lobectomies (86.8%). Older age, female sex, smaller tumour size and treatment at an academic facility predicted the use of sublobar resection. Patients undergoing lobectomy had larger tumours (2.40 vs 2.05 cm, P < 0.001) and more lymph nodes examined (11 vs 5, P < 0.001). Adjuvant chemotherapy use was similar between the 2 groups (sublobar 79.4% vs lobectomy 77.4%, P = 0.434). Sublobar resection was not associated with worse survival compared to lobectomy in both univariate (5-year survival 46.6% vs 45.2%, P = 0.319) and multivariable Cox proportional hazards analysis (hazard ratio 0.97, P = 0.789). Clinical stage IA non-small-cell lung cancer patients with N2 disease on final pathology have similar long-term survival with either sublobar resection or lobectomy. Patients with occult N2 disease after sublobar resection may not require reoperation for completion lobectomy but should instead proceed to adjuvant chemotherapy.

Occult lymph node metastasis in radiologic stage I non-small cell lung cancer: The role of endobronchial ultrasound.

The use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is currently recommended for staging non-small cell lung cancer (NSCLC) in centrally located tumors, tumors >3cm, or with radiologic evidence of lymph node (LN) metastasis. Current guidelines do not recommend staging EBUS-TBNA in patients with stage I NSCLC who do not have any of the aforementioned conditions. We hypothesize that using EBUS-TBNA is useful for detecting occult metastasis in radiologic stage I NSCLC. In this single-center, retrospective study, charts of patients ≥18years old who underwent staging EBUS-TBNA from January 2005 to May 2019 were reviewed. Only patients with combined positron-emission tomography and computed tomography (PET/CT) scans consistent with radiologic stage I NSCLC were included. Identified variables included: age, gender, personal history of any cancer, smoking history, tumor location, tumor centrality, tumor size, tumor PET activity, histopathologic type of NSCLC, and LN biopsy results. Patients whose LN samples showed a diagnosis other than NSCLC were excluded. The association between LN positivity, and each of the variables was assessed using Pearson's correlation for categorical variables, and logistic regression analysis for continuous variables. From the 2,892 initially screened patients, 188 were included. Of those, 13 (6.9%; 95% CI, 4%-11%) had a malignancy-positive LN biopsy. The number needed to test (NNT) in order to detect one case of any occult metastasis was 15. Among the included variables, a significant association was found between LN positivity and tumor centrality, with central tumors found in 61.5% of patients with positive LN (n=8) (p<0.01). This association stayed significant after adjusting for age, gender, smoking history, tumor size, tumor location, and PET activity (p=0.015). Among patients with malignancy-positive LN biopsies, five (38.5%; 95% CI, 17.6%-64.6%) were upstaged to N1, and eight (61.5%; 95% CI, 35.4%-82.4%) were upstaged to N2, with NNT of 23 to detect one case of occult N2 metastasis. Subgroup analysis comparing LN-positive patients based on their N stage did not show statistically significant association with any of the variables. Based on our results and along with the existing evidence, EBUS-TBNA should be recommended as part of the routine staging in all patients with radiologic stage I NSCLC.

Occult lymph node metastases in clinical N0/N1 NSCLC; A single center in-depth analysis

ObjectivesLymph node staging in patients with non-small cell lung cancer is crucial for determining prognosis and treatment. Our objective was to evaluate the clinical- to pathological agreement of guideline-concordant nodal staging in patients with resectable NSCLC and assess occurrence and distribution of occult lymph node metastases (OLM). Materials and methodsIn a retrospective single center cohort study (n = 390), we analyzed all surgically treated NSCLC patients from January 2015 until April 2019. Patients were classified into sub-groups (1) mediastinal staging by PET-CT/CT-scan (IMAGE-group) or (2) invasive staging by endobronchial ultrasound and mediastinoscopy (INVAS-group). Agreement between final clinical (cN) and pathological nodal stage (pN) and the presence and location of OLM are analyzed. ResultsAgreement between cN- and pN-stage was 86.3 % in the IMAGE-group (n = 117) and 50.9 % in the INVAS-group (n = 167). Occult N1 disease was found in 33 patients (16.6 % in cN0) of which 52 % occurred in LN-regions 12−14. Occult N2 disease was found in 20 cases (6.5 % in cN0 and 12.7 % in cN1). Combined, 23.1 % of all pre-operatively cN0-staged patients (n = 46/199) had OLM (pN+), of which 12.1 % (24/199) had metastases in regions 5–6 and/or 12−14. Of all patients with OLM, 50.0 % (23/46) had primary tumors ≤30 mm. ConclusionOLM are frequently identified in clinically N0/N1 NSCLC, also in tumors <3 cm, and often in regions beyond reach of current staging techniques. These findings should be addressed when non-surgical treatment or sub-lobar resections are considered for early stage lung cancer.

P1.03 Survival Benefit of Surgically Resected Occult N2 (C-N0,1 and P-N2) Non-Small-Cell Lung Cancer

P1.03 Survival Benefit of Surgically Resected Occult N2 (C-N0,1 and P-N2) Non-Small-Cell Lung Cancer

Combined Endosonographic Mediastinal Lymph Node Staging in Positron Emission Tomography and Computed Tomography Node-Negative Non–Small-Cell Lung Cancer in High-Risk Patients

Positron emission tomography (PET) with computed tomography (CT) is routinely utilized to investigate lymph node (LN) metastases in non-small-cell lung cancer. However, it is less sensitive in normal-sized LNs. This study was performed in order to define the prevalence of mediastinal LN metastases discovered on combined endosonography by endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS) fine needle aspiration in patients with a radiologically normal mediastinum. This study consists of a retrospective, single-institution, tertiary care referral center review of a prospectively maintained database. Patients were identified from a cohort between January 2009 and December 2014. One hundred and sixty-one patients with biopsy-proven, non-small-cell lung cancer were identified in whom both the preendosonography CT and PET-CT were negative for mediastinal LN metastases. Combined endosonography (EBUS + EUS-FNA) was performed in all patients. Z test was used for statistical analysis. A P value of <0.05 was considered statistically significant. A total of 161 consecutive patients were included. Patients were staged if they had central tumor, tumor size >3 cm, N1 lymph node involvement on PET-CT/CT, or if there was low SUV (<2.5) in the primary tumor. A total of 416 lymph nodes were biopsied in the 161 patients using combined endosonography; 147 with EBUS and 269 with EUS. Mean and median number of lymph nodes biopsied per patient using combined EBUS/EUS was 2.5 and 3, respectively (mean and median EBUS: 0.91 and 2.5; mean and median EUS 1.6 and 3). Endosonographic staging upstaged 13% of patients with radiologically normal lymph nodes in the mediastinum, hilum, lobar, and sublobar regions (confidence interval 8.22-19.20). Twenty-one out of 161 patients (13%) with radiologically normal mediastinum were positive on combined EBUS/EUS staging. Out of 21 patients upstaged on endosonography, 15 (71%) had tumor size >3 cm. Six (28%) had occult N1 disease. Thirteen (61%) had occult N2 disease and 2 (9%) had adrenal involvement. None of the upstaged patients had N1 LN involvement on PET-CT or CT scan. Combined endosonographic lymph node staging should be considered in the pretreatment staging of high-risk patients with non-small-cell lung cancer in the presence of radiologically normal mediastinal lymph nodes due to the significant rate of radiologically occult lymph node metastases.

Which definition of a central tumour is more predictive of occult mediastinal metastasis in nonsmall cell lung cancer patients with radiological N0 disease?

BackgroundGuidelines recommend invasive mediastinal staging for centrally located tumours, even in radiological N0 nonsmall cell lung cancer (NSCLC). However, there is no uniform definition of a central tumour that is more predictive of occult mediastinal metastasis.MethodsA total of 1337 consecutive patients with radiological N0 disease underwent invasive mediastinal staging. Tumours were categorised into central and peripheral by seven different definitions.ResultsAbout 7% (93 out of 1337) of patients had occult N2 disease, and they had significantly larger tumour size and more solid tumours on computed tomography. After adjustment for patient- and tumour-related characteristics, only the central tumour definition of the inner one-third of the hemithorax adopted by drawing concentric lines arising from the midline significantly predicted occult N2 disease (adjusted OR 2.13, 95% CI 1.17–3.87; p=0.013). This association was maintained after excluding patients with pure ground-glass nodules (adjusted OR 2.54, 95% CI 1.37–4.71; p=0.003) or only including those with solid tumours (adjusted OR 2.30, 95% CI 1.08–4.88; p=0.030).ConclusionsWe suggest that a central tumour should be defined using the inner one-third of the hemithorax adopted by drawing concentric lines from the midline. This is particularly useful for predicting occult N2 disease in patients with NSCLC.

Pneumonectomy in Stage IIIA-N2 NSCLC: Should It Be Considered After Neoadjuvant Chemotherapy?

BackgroundOwing to the expected poor long-term outcomes and high postoperative morbidity and mortality, patients with stage IIIA-N2 tumors candidate to pneumonectomy (PN) are usually excluded from surgery. This study aims to analyze the outcome of patients who underwent PN to prove its safety and feasibility. Patients and MethodsWe retrospectively analyzed data from 233 patients who underwent PN for N2 non–small-cell lung cancer (NSCLC) between 1998 and 2015. Eighty-five patients were occult N2 disease (group 1), whereas 148 patients underwent induction therapy (IT) for stage IIIA-N2 (group 2). ResultsOverall morbidity, postoperative mortality, and 90-day mortality rates were 46.8%, 2.6%, and 8.6%, respectively. The 2 groups (group 1 vs. 2) had similar postoperative and 90-day mortality rates: 2.4% versus 2.7% (P = 1.00), and 9.4% versus 8.1% (P = .81), respectively. The incidence of major morbidity was higher and statistically significant in group 2 compared with group 1: 23% versus 12.9% (P = .1). Postoperative bronchopleural fistula occurred in 4.7% (4/85) of patients with occult N2 (group 1) and in 10.1% (15/148) of patients undergoing IT (group 2) (P = .10). Median overall survival (OS) was 2.2 years, with a 3 and 5-year OS of 43.4% and 31.6%, respectively. Disease-free survival (DFS) was 1.5 years, with 3 and 5-year DFS of 41.6% and 32%, respectively; no difference in OS and DFS between the 2 groups was found. ConclusionsConsidering the acceptable morbidity and mortality rate and the long-term survival, PN should not be excluded for selected patients with stage IIIA-N2 NSCLC as a matter of principle.

Relevance of Intraoperative Pleural Lavage Cytology and Histologic Subtype in Lung Adenocarcinoma

The association between pleural lavage cytology (PLC) and histologic subtype remains unknown. In this study, we evaluated the effect of a micropapillary pattern (MPP) in lung adenocarcinomas on results of PLC. We retrospectively reviewed 600 consecutive patients with surgically resected pulmonary adenocarcinomas and investigated the relationship between PLC status and clinicopathologic factors, including a histologically identified MPP component. PLC was positive in 25 patients (4.2%). Positive PLC was significantly associated with MPP (p=0.0001), lymph node metastasis (p= 0.01), and pleural invasion (p < 0.0001) according to multivariate analysis. Furthermore, the presence of MPP reinforced the effect of some established predictive factors, such as large tumor size, lymph node metastasis, pleural invasion, and lymphovascular invasion, on positive PLC. Two factors-MPP and positive PLC-were associated with a higher incidence of occult N2 lymph node metastases. The prognosis of adenocarcinomas in patients with MPP or positive PLC was significantly worse than that of patients without these features. Furthermore, the survival of MPP and positive PLC group (MPP+ PLC+) was significantly worse than that of MPP and negative PLC group (MPP+ PLC-, p= 0.03). The presence of MPP in lung adenocarcinoma can be an independent predictor of positive PLC. These two factors have complementary and synergistic roles as prognostic factors. Detailed preoperative or intraoperative examination of histologic subtype and PLC findings may provide important information for prediction of tumor progression and decisions regarding the surgical procedure.

Long term and disease-free survival following surgical resection of occult N2 lung cancer.

Despite systematic investigation with computed tomography (CT), positron emission tomography (PET)/CT, CT or magnetic resonance imaging (MRI) brain imaging and supplementary investigation using endobronchial ultrasound guided biopsy (EBUS), endo-oesophageal ultrasound guided biopsy (EUS), fine needle aspiration (FNA), mediastinoscopy or mediastinotomy, there is an approximately 10% rate of occult N2 disease identified at pathological staging. It has been hypothesised that such occult disease, too small or inactive to be identified during pre-operative multi-modality staging, may represent low volume disease that may have equivalent survival to patients with similar stage at clinical, pre-operative assessment. We compared the long-term survival and disease-free survival of patients with the same clinical TNM stage with and without occult N2 disease. We retrospectively analysed a database that prospectively captured information on all patients assessed and treated for lung cancer in our surgical unit. We reviewed data on patients who underwent lung cancer surgery with curative intent between January 2006 and August 2010. A total of 312 lung cancer resections were performed [mean age 68 (range, 42-86) years old and male:female ratio 1.14:1]. Occult N2 disease was identified in 28 (8.7%) of 312 patients. There was no difference in the rate of N2 disease for different tumour histological types. Five-year survival with occult N2 disease was 35.8% vs. 62.5% without. Median survival was 34 months with occult N2 disease vs. 84 months without. With contemporary staging techniques, so-called occult N2 disease, even with low volume and PET non-avid disease, does not have an indolent course and should still be considered a risk factor for poorer prognosis.

Clinical Misstagings and Risk Factors of Occult Nodal Disease in Non-Small Cell Lung Cancer

Our objective was to compare the clinical to the pathologic stage in patients with non-small cell lung cancer (NSCLC). A prospective database from 1 surgeon was reviewed. Patients had NSCLC, chest tomography (CT), and most had positron emission tomography (PET). Those with suggested N1, N2, central tumors, or tumors larger than 5 cm underwent mediastinoscopy or endobronchial ultrasound, or both, and if N2 negative, underwent resection with complete thoracic lymphadenectomy. Between January 2006 and December 2016, there were 1,444 consecutive patients. The sensitivity and specificity for CT was 76% and 79% for pathologic stage I, 48% and 89% for stage II, and 58% and 88% for stage III. The sensitivity and specificity for PET was 77% and 70% for pathologic stage I, 43% and 88% for stage II, and 46% and 93% for stage III. Pathologic N1 disease was proven in 7% of patients and missed in 4% by CT, 5% by PET, and 3% by both. Pathologic N2 disease was proven in 20% of patients and missed in 9% by CT, 10% by PET, and 8% by both. Occult N2 disease was present in 10% of clinically stage Ipatients and in 21% of clinically stage II patients. Independentpredictors of occult N1 disease included highmaximum standardized uptake value (p= 0.034) and predictors of N2 disease included African American race (p= 0.020) and large tumor size (p= 0.047). Despite advancements in CT, PET, and minimally invasive nodal biopsy, there remains significant NSCLC misstaging, especially for N2 disease. Improved, targeted N2 lymph node biopsy may improve preresection staging.

Robotic resection of Stage III lung cancer: an international retrospective study.

Minimally invasive surgery is accepted for early-stage lung cancer, but its role in locally advanced disease is controversial, especially using a robotic platform. The aim of this retrospective study was to assess the safety and effectiveness of robot-assisted resection in patients with Stage IIIA non-small-cell lung cancer (NSCLC) or carcinoid tumours in the series as a whole and in different subgroups according to adjuvant treatment. This was a retrospective multicentre study of consecutive patients with clinically evident or occult N2 disease (210 NSCLC and 13 carcinoid) who, in 2007-2016, underwent robot-assisted resection at 7 high-volume centres. Perioperative outcomes, recurrences and overall survival were assessed. N2 disease was diagnosed preoperatively in 72 (32%) patients and intraoperatively in 151 (68%) patients. Surgical margins were negative in 98.4% of cases with available data. Thirty-four (15.2%) patients received neoadjuvant treatment, 140 (63%) patients received postoperative treatment, and 49 (22%) patients underwent surgery only. There were 22 (9.9%) conversions to thoracotomy, 23 (10.3%) had serious (Grades III-IV) postoperative morbidity and the mean hospital stay was 5.3 days. Complications and outcomes did not differ significantly between treatment groups. Of the 34 patients who were given neoadjuvant chemotherapy, all had R0 resection, 5 (15%) patients required conversion but none required conversion because of bleeding and 4 (12%) patients had Grade III or IV postoperative complications. After a median of 18 (interquartile range 8-33) months, 3-year overall survival in NSCLC patients was 61.2% and 60.3% (P = 0.6) of patients in the subgroup were given induction treatment. However, overall survival was significantly better (P = 0.012) in NSCLC patients with ≤2 positive nodes (vs >2). Nineteen (8.5%) patients developed local recurrence. Robot-assisted lobectomy is safe and effective in patients with Stage III NSCLC or carcinoid tumours with low conversions and complications. Among patients with NSCLC, including those who were given induction chemotherapy, survival was similar to that reported for open surgery.

Is the prognosis of occult N2 disease similar to that of positive positron emission tomography-computed tomography (PET/CT) scan single-station N2 disease in patients with non-small cell lung cancer treated by surgical resection?

ObjectiveA retrospective study, using a prospective database, was conducted on patients treated with surgery in order to analyze the prognosis between two groups: NSCLC (non-small cell lung cancer) patients with occult N2 disease and patients with single station N2 disease observed on pre-operative integrated PET/CT scan. MethodsA total of 772 patients underwent surgical treatment for lung cancer from January 2007 to December 2014. All of them had an integrated PET/CT scan in the pre-operative work-up and a pulmonary resection plus mediastinal lymphadenectomy were performed in all cases. In the selected cases, no one received induction treatment. All patients from both groups had N2 disease after examination of the histopathology specimen. Clinical and pathological characteristics, disease free survival, and overall survival, were analyzed in both groups. ResultsA total of 34 cases presented occult N2 disease, whereas 11 cases showed single station N2 disease on pre-operative PET/CT scan. Mean disease free survival and mean overall survival for occult N2 disease compared to single-station N2 disease on PET/CT scan was 36.0 months (95% CI: 24.9–47.1) and 38.9 months (95% CI: 20.6–57.1), p=.586; and 52.3 months (95% CI: 38.9–65.7) and 38.2 months (95% CI: 21.9–54.5), p=.349, respectively. ConclusionThe prognosis of patients with single-station N2 disease on PET/CT scan treated by surgical resection and mediastinal lymphadenectomy as first line treatment was similar to those with occult N2 disease. More studies are needed to support our findings.

Should all candidates with operable non-small cell pulmonary malignancy undergo cervical mediastinoscopy preoperatively?

BackgroundMediastinoscopy is the procedure of choice for the assesment of mediastinal lymph node (MLN) metastatic disease. Cervical mediastinoscopy allows exploration of lymph nodes in the paratracheal and pretracheal regions, in the tracheobronchial angles, and in the anterior aspect of the subcarinal space. So we aimed to investigate the role of mediastinoscopy in the diagnosis of MLN involvement in patients with non small cell lung cancer. MethodsThis study is a cross-sectional, randomized study. Inclusion criteria included patients with potentially operable bronchogenic carcinoma who showed no evidence of MLN involvement using the CT scan. PET scan was added as an investigative tool as a routine in all patients with lung cancer.Exclusion criteria included patients who were preoperatively known to have small cell lung cancer, and patients with negative MLN affection (N0/N1) by the FDG- PET. Cervical mediastinoscopy was done to all included patients. Results34 patients were full filling our inclusion criteria for mediastinoscopy.31 Patients proved to have MLN metastasis by mediastinoscopy, and were referred back to the chest oncologist for neo-adjuvant chemo or radiotherapy.3 patients, were negative on mediastinoscopy underwent surgery for resection. Their post operative MLN sampling had shown that they had no MLN metastasis. Their pathology results had shown that, two of them had adenocarcinoma and one squamous cell carcinoma. ConclusionsPatients with operable NSCLC with negative mediastinal CT scan, should perform PET scan and mediastinoscopy if they are highly suspicious of having occult N2 disease to prevent an unnecessary thoracotomy.

Robotic assisted lobectomy for locally advanced lung cancer.

Some series report the use of video-assisted thoracic surgery (VATS) in patients with locally advanced non-small cell lung cancer (NSCLC) but, few studies describe the use of the robotic approach specifically for locally advanced disease. One potential advantage of the robotic approach over traditional VATS is the increased radicality. While the benefit of the robotic approach over open thoracotomy is directly related to reduced surgical trauma and the improved tolerability in fragile patients that have received induction treatment. In case of occult N2 disease, robotic assisted surgery can translate into a quicker recovery with improved compliance with adjuvant treatments following surgery. Technical details are reported and described. The robotic instrument technology allows sharp and controlled dissection compared to the typical blunt sweeping methods used in most VATS lobectomy techniques. The authors believe that robotic technology favors a more radical resection in the case of complex locally advanced tumors. Robotic technology has some limitations that have affected adoption such as significant capital and maintenance costs, reduced operating room efficiencies, and a steep learning curve.

Indications for invasive mediastinal staging in patients with early non-small cell lung cancer staged with PET-CT

Purpose/Objective(s)Appropriate use of invasive mediastinal staging in patients with clinically node-negative NSCLC staged by PET-CT is critical in selecting patients for curative-intent therapy such as surgery or SBRT, but little data exists to guide this decision-making. We examined a large population of patients with clinical stage I NSCLC referred for mediastinoscopy or EBUS to find risk factors for occult N2 lymph nodes and determine which patients benefit from invasive staging. Materials/MethodsWe identified consecutive clinical T1-2N0 NSCLC patients being evaluated for curative-intent therapy between 2011 and 2015. None had evidence of nodal disease by PET-CT; the endpoint was pathologic confirmation of occult N2 disease by EBUS or mediastinoscopy. Tumor size, location, histology, SUVmax, and radiographic appearance were evaluated as determinants of occult N2 disease. Two group comparisons of continuous variables were done with independent t-tests and categorical variables were compared with χ2 or Fisher’s exact test. ResultsIn 284 patients with PET-CT-staged clinical T1-2N0 disease, the prevalence of occult N2 metastases was 7.0%. The negative predictive value of PET-CT was 92.9% and the negative predictive value of mediastinoscopy/EBUS was 96.3%.T2 tumors were more likely to have occult N2 disease than T1 tumors (11.8% v 3.6% p=0.009). Pure solid tumors had greater involvement of N2 nodes than tumors with any ground glass component (12.6% v 3.1%, p<0.001). 17.5% of central tumor cases were found to have occult N2 metastases while 4.4% of patients with peripheral tumors (P<0.001). 33.3% of patients with solid central T2 tumors had occult N2 metastases whereas 2.0% of patients with peripheral T2 tumors with a ground glass component, 1.2% of patients with peripheral T1 tumors with a ground glass component and 3.6% of patients with peripheral T1 solid tumors had N2 metastases. ConclusionsInvasive mediastinal staging should be strongly encouraged in central tumors and solid T2 tumors because the risk of occult nodal involvement is greater than 10% in these cohorts. However, for patients with peripheral T1 tumors or peripheral T2 tumors with a significant ground glass component, the yield of invasive staging after a negative PET-CT is very low and invasive staging may not be warranted.

Incidence of occult pN2 disease following resection and mediastinal lymph node dissection in clinical stage I lung cancer patients.

Early clinical stage (T1 and T2) non-small cell lung cancer (NSCLC) is commonly treated with anatomic lung resection and lymph node sampling or dissection. The aims of this study were to evaluate the incidence and the distribution of occult N2 disease according to tumour location and the short- and long-term outcomes. We performed a retrospective review of patients with clinical stage I NSCLC who underwent anatomic lung resection and lymphadenectomy. Mediastinal lymphadenectomy (ML) was defined as resection of at least 2 mediastinal stations, always including station 7 lymph nodes. Patients who had a lobe-specific lymphadenectomy were excluded. One thousand six hundred and sixty-seven consecutive patients met inclusion criteria and were included. Overall, 9% (146/1667) of the patients had occult pN2 disease. At multivariable analysis, adenocarcinoma histology and vascular invasion were independently associated with greater risk of occult pN2 disease. In left and right upper lobe tumours, station 7 nodes were involved in 5 and 13% of pN2 positive cases, respectively. Station 5 and station 2/4 nodes were involved in 29 and 18% of left and right lower lobe pN2 tumours, respectively. There was no postoperative mortality, and postoperative morbidity was 28%. The median overall survival was 77.4 months. N0 patients had a median overall survival of 83.7 months vs 48.0 months and 37.9 months in N1 and N2 populations, respectively ( P < 0.001). Sixteen percent of pN2 patients had mediastinal lymph node metastasis beyond the lobe-specific lymphatic drainage. We recommend a complete lymphadenectomy be performed, even in clinical stage I NSCLC.