N2 Non-small Cell Lung Cancer Research Articles

Approach to Resectable N1 Non-Small Cell Lung Cancer: An Analysis of the National Cancer Database

BackgroundIn patients with clinical N1 disease, minimally invasive surgery (MIS) has potentially better perioperative outcome compared to open thoracotomy. Additionally, whether adjuvant or neoadjuvant chemotherapy produces the best long-term survival is still debatable. MethodsWe queried The National Cancer Database for patients with clinical N1 NSCLC who underwent surgical resection between 2010 and 2014. Comparison between patients receiving MIS and patients who underwent open thoracotomy was done using an intention-to-treat analysis. Comparison was also done among neoadjuvant, adjuvant chemotherapy, and only surgery. Proportional hazard models were used to evaluate the effects of surgical approach and timing of chemotherapy on overall survival. ResultsA total of 1440 and 3942 patients underwent MIS and open thoracotomy respectively. MIS achieved better surgical margins (90.0% versus 88.6%) and shorter length of stay (6.5 ± 6.5 versus 7.3 ± 6.4 d, P ≤ 0.01) compared to open thoracotomy. There were no differences in 30-day and 90-day mortality, nor readmission rates. Neoadjuvant and adjuvant chemotherapy were administered to 13.5% and 57.2% of patients respectively. There was no significant difference in the 5-year overall survival between MIS and open thoracotomy (46% versus 46% P = 0.08). There was significantly better 5-year overall survival in neoadjuvant and adjuvant chemotherapy versus only surgery, but no difference between neoadjuvant and adjuvant chemotherapy (48% versus 47% versus 44%, P < 0.01). ConclusionsIn clinical N1 NSCLC, MIS does not compromise oncological quality or overall survival when compared to open thoracotomy. Overall survival improved in patients treated with chemotherapy but there is no difference when given as neoadjuvant versus adjuvant chemotherapy.

Does the carinal involvement have the same surgical outcome as the main bronchus involvement in patients with non-small cell lung cancer?

Carinal and main bronchus involvement were compared in terms of the survival of patients with N0-1 non-small cell lung cancer (NSCLC). Sixty-six NSCLC patients who underwent complete surgical carinal resection/reconstruction (Carina group) and complete resection because of main bronchus involvement (Main Bronchus group) between 2006 and 2016 were retrospectively analyzed. The Carina group included 30 patients and the Main Bronchus group included 36. In the Carina group, conditions other than carinal involvement that rendered patients pathological (p) T4, and in the Main Bronchus group, conditions that would upstage the pT status from pT2 were excluded. Patients with mediastinal lymph node metastases were excluded. Thus, an isolated main bronchial invasion and isolated carinal invasion patient population was tried to be obtained. The overall 5-year survival rate was 49.4% (median 61.5 ± 19.9months). The 5-year survival rates of patients in the Carina group was 49.2% (median 63.3months), and that of patients in the Main Bronchus group was 46.4% (median 55.9months). The difference between survival rates was not statistically significant (p = 0.761). The survival rates of pN0 and pN1 patients also did not differ significantly (63.2% vs. 45.5%, p = 0.207). Recurrence was significantly more common in the Main Bronchus group than the Carina group (28.1% vs. 7.1%; p = 0.04). Isolated carinal invasion had a comparable outcome to isolated main bronchus invasion in pN0-1 patients with NSCLC who are undergoing anatomical surgical resection.

Long-term outcomes of video-assisted thoracoscopic lobectomy for clinical N1 non-small cell lung cancer: A propensity score-weighted comparison with open thoracotomy

ObjectivesAlthough the video-assisted thoracic surgery (VATS) approach has been accepted as a safe and effective alternative to lobectomy, its advantage remains unclear in advanced-stage lung cancer. This study is aimed to evaluate the feasibility and long-term outcomes of VATS in lung cancer with clinical N1 (cN1) disease. Materials and MethodsWe retrospectively reviewed the records of 1149 consecutive patients who underwent lobectomy for cN1 disease from 2006 to 2016. Perioperative outcomes and long-term survival rates were compared using a propensity score-based inverse probability of treatment weighting (IPTW) technique. ResultsWe performed VATS and open thoracotomy for 500 and 649 patients, respectively. All preoperative characteristics became similar between the two groups after IPTW adjustment. Compared to thoracotomy, VATS was associated with shorter hospitalization (7.7 days vs. 9.2 days, p < 0.001), earlier adjuvant chemotherapy (41.7 days vs. 46.6 days, p = 0.028), similar complete resection rates (95.2 % vs. 94.0 %, p = 0.583), and equivalent dissected lymph nodes (27.5 vs. 27.8, p = 0.704). On IPTW-adjusted analysis, overall survival (OS) (59.4 % vs. 60.3 %, p = 0.588) and recurrence-free survival (RFS) (59.2 % vs. 56.9 %, p = 0.651) at 5 years were also similar between the two groups. Multivariable Cox analysis revealed that VATS was not a significant prognostic factor for cN1 disease (p = 0.764 for OS and p = 0.879 for RFS). ConclusionsVATS lobectomy is feasible for patients with cN1 disease, providing comparable perioperative outcomes, oncologic efficacy, and long-term outcomes as open thoracotomy.

Postoperative Radiotherapy (PORT) Improves the Survival of Patients With N2 Non-Small Cell Lung Cancer (NSCLC) with Regional Nodes Examined (RNE) ≤16 - A Real World Study Using Surveillance, Epidemiology, and End Results (SEER) Database

PORT is widely used in patients with N2 NSCLC, but which subgroup population can benefit from PORT is still controversial. Our study is to evaluate the relationship between the RNE and the effect of PORT on survival of patients with N2 NSCLC from SEER database. Data from the SEER database were filtrated by the inclusion criteria of patients with NSCLC diagnosed at 2010-2016, with N2 disease (AJCC 7th) and treated with lobectomy or pneumonectomy. We excluded patients with unclear basic information (such as sex, histology or cause of death), multiple primary malignant tumors and M1 disease. All data were analyzed using the R version 3.6.2 software. And propensity-score matched (PSM) analysis was used to match the baseline characteristics between PORT group and non-PORT group. Kaplan-Meier method was used to estimate overall survival (OS) and cancer specific survival (CSS). Univariable and multivariable Cox proportional hazards models were adopted to estimate hazard ratios (HR) of predictors of survival. The HR of PORT for patients with different RNE was calculated to determine the best cut-off value of RNE. 2904 patients were included. The baseline characteristics were as follows: age≤70 (62.9%), white (80.5%), female (51.2%), grade 1-2 (53.0%), adenocarcinoma (67.1%), T2 (51.1%), lobectomy (89.9%), chemotherapy (74.9%), median number of positive regional nodes (3), median number of RNE (12). There were 1188 patients (40.9%) with PORT. RNE≤16 was chosen as the cut-off value and divided the patients into two cohorts. PSM was then conducted between the PORT group and the non-PORT group of each cohort. In RNE≤16 cohort (1398 patients), the median OS of the PORT and non-PORT groups were 48 months vs 40 months and 5-year OS rates were 42.93% vs 39.09%, respectively (P = 0.013). The median CSS were 59 months vs 44 months and 5-year CSS rates were 48.82% vs 43.15%, respectively (P = 0.008). Univariable analysis showed that PORT significantly improved OS (HR = 0.815, P = 0.013) and CSS (HR = 0.794, P = 0.008). Multivariable analysis confirmed that PORT was the significant predictor of OS (HR = 0.816, P = 0.014) and CSS (HR = 0.799, P = 0.011). In RNE>16 cohort (550 patients), The median OS of the PORT and non-PORT groups was 44 months vs 64 months and 5-year OS rates were 42.75% vs 50.69%, respectively (P = 0.210). The median CSS of the two groups were 47 months and not reached, the 5-year CSS rates were 46.17% vs 54.10%, respectively (P = 0.207). Neither univariable nor multivariable analysis showed that PORT was an individual predictive factor. For N2 NSCLC patients with RNE≤16, PORT can significantly improve the OS and CSS. However, for those with RNE>16, PORT may not improve survival, but even have the tendency of damage. These results need to be clarified by prospective randomized clinical trials.

The Efficacy of Local Radiotherapy after Failure of First-Line Treatment for Piiia-N2 Non-Small Cell Lung Cancer

A large portion of patients with pIIIA-N2 non-small cell lung cancer (NSCLC) experience local recurrence and distant metastasis after radical surgery despite postoperative adjuvant chemotherapy ± radiotherapy, and the best option for these relapses remains unclear. This study retrospectively analyzed the correlation between follow-up treatment and survival of these patients and explored the optimal therapy for these patients. From January 2003 to January 2015, patients with pIIIA–N2 NSCLC who experienced local recurrence or distant metastasis after radical first-line treatment in our hospital were retrospectively analyzed to find the correlation between the choice of follow-up treatment and survival of the patients. The Kaplan-Meier, Log Rank test, and Cox regression were used for survival analysis and identification of prognostic factors. A total of 739 patients were enrolled for this study, including 440 males and 299 females, aged 25∼80 years old with an average of 57 years. The first-line treatment was surgery alone for 170 (23.00%) of the patients, surgery + adjuvant chemotherapy for 389 (52.64%), surgery + adjuvant radiotherapy for 13 (1.76%), surgery + adjuvant chemoradiotherapy for 167 (22.60%). Recurrences included 141 case of local-regional recurrence (19.08%), 390 cases of distant metastasis (52.77%), and 208 cases of local recurrence + distant metastasis (28.15%). In the follow-up treatment, chemotherapy was performed for 289 patients (39.11%), local radiotherapy for 279 (37.75%), target therapy (TKI) for 195 (26.39%). As a whole, median survival time of the patients was 47.5 months, and the 2-year and 5-year survival rates were 76.4% and 41.8% respectively. Multivariate Cox regression revealed age, KPS, pathological differentiation, pathological T staging, use of radiotherapy after recurrence, use of targeted therapy after recurrence, and type of recurrence as independent prognostic factors affecting survival. Subgroup analysis showed that for patients who had EGFR- or ALK-positive recurrence and received targeted therapy (TKI) after failure of first-line treatment, local radiotherapy in the follow-up treatment brings no significant benefits to survival, and may even have adverse effects on median survival time (53.26 months for those had local radiotherapy vs. 163.88 months for those didn't); but for those who did not receive targeted therapy, local radiotherapy significantly improved OS (median survival time: 59.14 months vs. 34.43 months, p <0.001). For patients with pIIIA–N2 NSCLC who had relapses after first-line radial therapy, local radiotherapy for local recurrence or distant metastasis may improve OS of those who did not receive targeted therapy (TKI) after recurrence, but may have adverse effect on survival of patients who received targeted therapy and is not recommended as follow-up treatment for the latter.

Trends and Outcomes in Minimally Invasive Surgery for Locally Advanced Non–Small-Cell Lung Cancer With N2 Disease

Few studies examine outcomes by surgical approach in non-small-cell lung cancer (NSCLC) with N2 disease. We examined time trends in surgical approach and outcomes among patients undergoing minimally invasive (MIS, robotic and video-assisted thoracoscopic surgery [VATS]) vs open lobectomy in this patient population. We performed a retrospective analysis of patients from the National Cancer Database diagnosed with clinical Stage IIIA-N2 NSCLC from 2010 to 2016. We examined the yearly proportion of MIS vs open resections. Multivariable regression was used to assess the association of surgical approach with length of stay, unplanned readmissions, 30-day and 90-day mortality. Multivariable Cox proportional hazards modeling was used to assess the association of surgical approach with 5-year overall mortality. We identified 5741 patients who underwent lobectomy for Stage IIIA-N2 NSCLC (459 robotic, 1403 VATS, 3879 open). From 2010 to 2016, the proportion of minimally invasive procedures increased from 20% to 45%. MIS patients, on average, stayed 1 day less in the hospital (95% confidence interval [CI] 0.7, 1.5) and had lower odds of 90-day (odds ratio [OR] 0.74; 95% CI 0.54, 0.99) and 5-year mortality (OR 0.82; 95% CI 0.75, 0.91), compared to open resections. There was no difference in odds of readmission by surgical approach (OR 0.97; 95% CI 0.71, 1.33). Among MIS procedures, robotic resections had lower odds of 90-day mortality (OR 0.42; 95% CI 0.18, 0.97) than VATS. Among patients undergoing lobectomy for locally advanced N2 NSCLC robotic and VATS techniques appear safe and effective compared to open surgery and may offer short- and long-term advantages.

Video-assisted thoracoscopic lobectomy is feasible for selected patients with clinical N2 non-small cell lung cancer

Few studies have evaluated the usefulness of video-assisted thoracoscopic surgery (VATS) for advanced-stage lung cancer. We aimed to evaluate the feasibility of VATS for treating clinical N2 (cN2) lung cancer. A retrospective cohort analysis was performed with data from 268 patients who underwent lobectomy for cN2 disease from 2007 to 2016. Using propensity score-based inverse probability of treatment weighting (IPTW), perioperative and long-term survival outcomes were compared. We performed VATS and open thoracotomy on 121 and 147 patients, respectively. Overall, VATS was preferred for patients with peripherally located tumors (p < 0.001). After IPTW-adjustment, all preoperative information became similar between the groups. Compared to thoracotomy, VATS was associated with shorter hospitalization (7.7 days vs. 9.1 days, p = 0.028), despite equivalent complete resection rates (92.6% vs. 90.5%, p = 0.488) and dissected lymph nodes (mean, 31.9 vs. 29.4, p = 0.100). On IPTW-adjusted analysis, overall survival (50.5% vs. 48.4%, p = 0.127) and recurrence-free survival (60.5% vs 44.6%, p = 0.069) at 5 years were also similar between the groups. Among selected patients with resectable cN2 disease and peripherally located tumors, VATS is feasible, associated with shorter hospitalization and comparable perioperative and long-term survival outcomes, compared with open thoracotomy.

Clinical features and prognosis of clinical N0 non-small cell lung cancer exceeding 30mm.

This study aimed to determine the characteristics, ground glass opacity ratio and prognosis of patients with clinical N0 non-small cell lung cancer tumours exceeding 30mm in size. Patients with clinical N0 non-small cell lung cancer and total tumour size >30mm on preoperative computed tomography who underwent complete resection with lobectomy between January 2007 and December 2017 were included. The patients were divided into three groups: pure solid tumour, low ground glass opacity ratio (1-39%) tumour and high ground glass opacity ratio (≥40%) tumour. The cut-off line was determined based on the recurrence rate for every 10% ground glass opacity ratio. Among the 227 study patients, 129 (56.8%) had a pure solid tumour, 54 (23.8%) had a low ground glass opacity ratio tumour and 44 (19.4%) had a high ground glass opacity ratio tumour. Three-year recurrence-free survival was significantly shorter in patients with a pure solid tumour (57.4%) than in patients with a low ground glass opacity ratio (74.5%; P=0.009) or a high ground glass opacity ratio tumour (92.1%; P<0.001). Multivariable analysis showed that ground glass opacity ratio was a significant independent prognostic factor for recurrence-free survival (hazard ratio, 0.175; P=0.037). Pure solid tumours comprised a large proportion of non-small cell lung cancer tumours >30mm in size and their prognosis was poor. The presence of ground glass opacity and their relative proportion affect prognosis in patients with clinical N0 non-small cell lung cancer tumours >30mm in size, similar to those with small-sized tumours.

Preoperative identification of clinicopathological prognostic factors for relapse-free survival in clinical N1 non-small cell lung cancer: a retrospective single center-based study

BackgroundGiven the difficulty in preoperatively diagnosing lymph node metastasis, patients with Stage I–III non-small cell lung cancer (NSCLC) are likely to be included in the clinical N1 (cN1) group. However, better treatment options might be selected through further stratification. This study aimed to identify preoperative clinicopathological prognostic and stratification factors for patients with cN1 NSCLC.MethodsThis retrospective study evaluated 60 patients who were diagnosed with NSCLC during 2004–2014. Clinical nodal status had been evaluated using routine chest computed tomography (CT) and/or positron emission tomography (PET). To avoid biasing the fluorodeoxyglucose uptake values based on inter-institution or inter-model differences, we used only two PET systems (one PET system and one PET/CT system). Relapse-free survival (RFS) and overall survival (OS) were the primary study outcomes. The maximum standardized uptake value (SUVmax) was calculated for each tumor and categorized as low or high based on the median value. Patient sex, age, histology, tumor size, and tumor markers were also assessed.ResultsPoor OS was associated with older age (P = 0.0159) and high SUVmax values (P = 0.0142). Poor RFS was associated with positive carcinoembryonic antigen (CEA) expression (P = 0.0035) and high SUVmax values (P = 0.015). Multivariate analyses confirmed that poor OS was independently predicted by older age (hazard ratio [HR] = 2.751, confidence interval [CI]: 1.300–5.822; P = 0.0081) and high SUVmax values (HR = 5.121, 95% CI: 1.759–14.910; P = 0.0027). Furthermore, poor RFS was independently predicted by positive CEA expression (HR = 2.376, 95% CI: 1.056–5.348; P = 0.0366) and high SUVmax values (HR = 2.789, 95% CI: 1.042–7.458; P = 0.0410). The primary tumor’s SUVmax value was also an independent prognostic factor for both OS and RFS.ConclusionsFor patients with cN1 NSCLC, preoperative prognosis and stratification might be performed based on CEA expression, age, and the primary tumor’s SUVmax value. To enhance the prognostic value of the primary tumor’s SUVmax value, minimizing bias between facilities and models could lead to a more accurate prognostication.

The impact of order with radiation therapy in stage IIIA pathologic N2 NSCLC patients: a population-based study

BackgroundThe aim of this study was to investigate the optimal order of radiation therapy in patients affected by stage IIIA pathologic N2 (IIIA/N2) non-small-cell lung cancer (NSCLC) and to identify its potential risk factors.Methods17,654 (8786 men and 8868 women) diagnosed with NSCLC stage IIIA-N2 from 2004 to 2015 patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Among the relevant clinical parameters, we evaluated overall survival (OS), lung cancer-specific survival (LCSS) and other variables such as age, sex and tumor size in patients who were treated with different combinations of surgery and radiotherapy strategies.ResultsWe discovered that surgery benefit in younger IIIA/N2 NSCLC patients (age ≤ 75), and compared with surgery only, preoperative radiotherapy significantly improved the survival rate most (p < 0.001). When we performed the OS and LCSS analysis in the subgroup of patients’ age > 75 years old, who underwent postoperative radiotherapy (PORT) had the highest survival rate (p < 0.001). Multivariate analyses showed that the following parameters had a negative impact on survival: female sex, older age, no chemotherapy, large tumor size, high tumor grade, no surgery or radiotherapy.ConclusionsIn IIIA/N2 NSCLC patients, surgery, radiotherapy and chemotherapy were associated with improved OS and LCSS. Younger patients underwent surgical resection and chemotherapy, the main population we studied, benefited most from preoperative radiotherapy in all orders with radiation therapy (p < 0.001). In patients more than 75 years old, there was no clear benefit from only surgery, and PORT was recommended in case of having surgery.

How Effective Is Neoadjuvant Therapy Followed by Surgery for Pathologic Single-Station N2 Non–Small Cell Lung Cancer?

The optimal treatment strategy for pathologic single-station N2 (pN2a1) non-small cell lung cancer (NSCLC)-surgery first followed by adjuvant treatment (SF) or neoadjuvant therapy followed by surgery (NS)-remains unclear. We compared disease-free survival (DFS) and overall survival (OS) after NS versus SF for pN2a1 NSCLC. We retrospectively identified patients with pN2a1 NSCLC resected between 2000 and 2018. Patients in the SF group had cN0 disease and were treated with surgery before adjuvant chemotherapy; patients in the NS group had known preoperative nodal disease, cN2 disease, and were treated with neoadjuvant therapy before surgery. The matching-weights procedure was applied to generate a cohort with similar characteristics between groups. DFS and OS were calculated using the Kaplan-Meier approach and compared between groups using weighted log-rank test and Cox proportional hazards models. We identified 227 patients with pN2a1 disease: 121 treated with SF and 106 with NS. After the matching-weights procedure, 5- and 10-year DFS were 45% and 27% for SF versus 26% and 21% for NS (log-rank P = 0.056; hazard ratio [HR], 1.61; 95% confidence interval [CI], 0.98-2.65); 5- and 10-year OS were 49% and 30% for SF versus 43% and 20% for NS (log-rank P = 0.428; HR, 1.24; 95% CI, 0.67-2.28). SF and NS for pN2a1 NSCLC resulted in similar survival. A study comparing SF for known preresectional pN2a1 with occult pN2a1 disease could be a next step. Further investigation of SF for known N2a1 versus occult pN2a1 disease could power a clinical trial focused on N2a NSCLC.

Abstract 4304: Radio-chemotherapy efficacy is predicted by intra-tumor CD8+FoxP3+ double positive T cell density in locally advanced non-small cell lung carcinoma

Abstract Background: radiotherapy is a standard of care for locally advanced stage III (N2) non-small cell lung cancer (NSCLC) combined with surgery and/or chemotherapy. Radiotherapy is hypothesized to induce intra-tumoral immune infiltration via neoantigen release from dying tumor cells sometimes resulting in an abscopal effect. However, intra-tumoral immune cell characteristics that predict radiotherapy efficacy have not been identified. Patients and Methods: we retrospectively analyzed tumor samples and clinical data from 113 patients, 89 resected) and 24 non-resected stage III (N2) NSCLC treated within the same radiotherapy department (2002 to 2015). We performed multiplex staining (CD8, FoxP3, PD-L1, pan-keratin) in order to correlate immune environment (density and location) to overall survival (OS) and disease free survival (DFS). Results: high density of CD8+ T cells was associated with DFS (p=0.0036, HR=2.42 [1.31 - 4.47]) and OS (p=0.049, HR=1.93 [0.99 - 3.78]) in resected group only. High density of CD8+/FoxP3+ double positive T cells was associated with OS (p=0.017, HR= 1.97 [1.11 - 3.48]) in the global population; and in resected group for OS (p=0.05, HR=1.92 [0.98 - 3.74]) and PFS (p=0.03, HR=1.83 [1.03 - 3.23]), with a trend of significance for OS and PFS in the non-resected group (p=0.06, HR=2.84 [0.88 - 9.13] and p=0.05, HR=3.03 [0.91 - 10.10], respectively). Intermediate PD-L1 expression in tumor cells (TPS=1-49%) was associated with a higher survival in the resected group. Conclusions: we demonstrated that intra-tumoral CD8+ T cell and particularly the CD8+/FoxP3+ cell density predict radiotherapy efficacy and survival in stage III N2 NSCLC. Thus, it suggests that radiotherapy rather improves than promotes tumor immunogenicity. Citation Format: Yoan Velut, Geoffroy Boulle, Audrey Mansuet Lupo, Laure Gibault, Hélène Blons, Jean Tredaniel, Ludovic Fournel, Aurélie Boni, Isabelle Cremer, Marie Wislez, Veronique Duchatelle, Scott Hammond, Marco Alifano, Philippe Giraud, Diane Damotte. Radio-chemotherapy efficacy is predicted by intra-tumor CD8+FoxP3+ double positive T cell density in locally advanced non-small cell lung carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4304.

Spontaneous regression of ALK fusion protein-positive non-small cell lung carcinoma: a case report and review of the literature

BackgroundALK-rearrangement is observed in < 5% non-small cell lung cancer (NSCLC) cases and prior to the advent of oral tyrosine kinase inhibitors, the natural history of oncogenic NSCLC was typically poor. Literature relating to regression of treatment-naïve NSCLC is limited, and regression without treatment has not been noted in the ALK-rearranged sub-population.Case presentationA 76 year old ‘never smoker’ female with an ALK-rearranged left upper lobe T2 N0 NSCLC experienced a stroke following elective DC cardioversion for new atrial fibrillation. Following a good recovery, updated imaging demonstrated complete regression of the left upper lobe lesion and a reduction of the previously documented mediastinal lymph node. Remaining atelectasis was non-avid on repeat PET-CT imaging, 8 months from the baseline PET-CT. When the patient developed new symptoms 6 months later a further PET-CT demonstrated FDG-avid local recurrence. She completed 55 Gy in 20 fractions but at 18 months post-radiotherapy there was radiological progression in the lungs with new pulmonary metastases and effusion and new bone metastases. Owing to poor performance status, she was not considered fit for targeted therapy and died 5 months later.ConclusionAll reported cases of spontaneous regression in lung cancer have been collated within. Documented precipitants of spontaneous regression across tumour types include biopsy and immune reconstitution; stroke has not been reported previously. The favourable response achieved with radical radiotherapy alone in this unusual case of indolent oncogenic NSCLC reinforces the applicability of radiotherapy in locally advanced ALK-rearranged tumours, in cases not behaving aggressively. As a common embolic event affecting the neurological and pulmonary vasculature is less likely, an immune-mediated mechanism may underpin the phenomenon described in this patient, implying that hitherto unharnessed principles of immuno-oncology may have relevance in oncogenic NSCLC. Alternatively, high electrical voltage applied percutaneously adjacent to the tumour during cardioversion in this patient may have induced local tumour cell lethality.

Intentional Segmentectomy for Clinical T1 N0 Non-small Cell Lung Cancer: Survival Differs by Segment

Outcomes after segmentectomy compare favorably with those after lobectomy in patients with stage I non-small cell lung cancer (NSCLC). Whether long-term outcomes vary by segmentectomy location is unclear. We investigated whether disease-free survival (DFS) and overall survival (OS) differ by segmentectomy location after intentional segmentectomy for clinical T1 N0 M0 NSCLC. Patients who received intentional segmentectomy for cT1 N0 M0 NSCLC from 2000 to 2018 were reviewed. Patients with prior lung cancer, forced expiratory volume in 1 second of less than 50%, or R1/R2 resection were excluded. Segmentectomy groups were left (L) basilar, L segment 6, L lingula, L trisegment; right (R): basilar (R_Bas), segment 6 (R_S6), and R upper. The 5- and 10-year DFS and OS were estimated using Kaplan-Meier and compared between groups using the log-rank test. Factors associated with DFS and OS were determined using Cox proportional hazards models. In total, 416 patients met the inclusion criteria. Segmentectomy groups differed with regard to surgical approach, mediastinal lymphadenectomy, lymphovascular invasion, tumor histology, margin distance, and adjuvant therapy. Long-term outcomes were worst after R_S6 resection (5-year DFS, 57.6% [95% confidence interval {CI}, 45.7%-72.7%]; OS, 66.3% [95% CI, 54.7%-80.3%]) and best after R_Bas resection (5-year DFS, 77.1% [95% CI, 59.2%-100%]; OS, 79.5% [95% CI, 60.9%-100%]). On multivariable analysis, R_S6 resection was independently associated with DFS vs R_Bas (hazard ratio, 2.89; 95% CI, 1.18-7.08; P= .02) and OS vs R_Bas (hazard ratio, 4.35; 95% CI, 1.61-11.76; P= .004). Resection of R_S6 is independently associated with worse DFS and OS in patients receiving intentional segmentectomy for cT1 N0 M0 NSCLC and may warrant more extensive resection, complete lymph node dissection, and closer postoperative surveillance.

Fibrosis or Necrosis in Resected Lymph Node Indicate Metastasis Before Chemoradiotherapy in Lung Cancer Patients.

The histological features of lymph nodes (LNs) treated by chemoradiotherapy (CRT) in non-small cell lung cancer (NSCLC) have not been well studied. The purpose of this study was to evaluate the histological findings of LNs affected by CRT. Among 107 clinically N2 NSCLC patients who underwent induction CRT followed by surgery from 1999 to 2017, 24 patients who received pathological evaluation of mediastinal LN before CRT were enrolled in this study. Postoperatively, we histologically reviewed all resected LNs (n=117) of the station evaluated before CRT. Fibrosis and/or necrosis were observed in all investigated LN stations. Histological observation of fibrosis and/or necrosis in the resected LNs after CRT indicated the presence of LN metastasis before CRT. The metastatic LNs that responded to CRT showed specific histological features, which enabled us to know the accurate clinical stage of the patient even though cancer cells were not found in the post-treated LNs.

Surgical Results in Pathological N1 Nonsmall Cell Lung Cancer

This retrospective study investigated the prognosis of patients with pathological N1 (pN1) nonsmall cell lung cancer (NSCLC). We included patients with pN1 NSCLC who underwent lobectomy or pneumonectomy with mediastinal lymph node dissection and achieved complete resection (R0) between January 2000 and December 2012. Patients who received neoadjuvant therapy were excluded. A total of 249 patients were included. The mean age was 63.2 years, and 172 patients were males. Of the 249 patients, 200, 20, and 29 underwent lobectomy, bilobectomy, and pneumonectomy, respectively. The median observation period was 5.5 years. The 5-year overall survival (OS) rate was 64.6% (95% confidence interval: 58.3-70.4). Five-year OS rates were 79.8% for positive lymph nodes at station 13 or 14 (n = 57), 59.6% at station 12 (n = 72), 62.7% at station 11 (n = 69), and 56.9% at station 10 (n = 51) (log-rank test; p = 0.016); furthermore, the 5-year OS rate was 75.2% for patients with positive lymph nodes at a single station (n = 160) and 45.4% for patients with positive lymph nodes at multiple stations (n = 89) (log-rank test; p < 0.001). Five-year cumulative incidences of recurrence were equivalent between patients who received adjuvant chemotherapy and patients who did not (45.9 vs. 55.1%; Gray's test; p = 0.366). Distant recurrence was the most frequent mode of recurrence in both groups (70.8 and 67.3%). The locations and the number of stations of the positive lymph nodes were identified as prognostic factors in patients with pN1 NSCLC. The primary mode of recurrence was distant recurrence irrespective of postoperative adjuvant chemotherapy.

Propensity-Matched Analysis of Clinical Relevance of the Highest Mediastinal Lymph Node Metastasis

The clinical relevance of the highest mediastinal lymph node (HMLL) metastasis in patients with pathological N2 non-small cell lung cancer (NSCLC) is still controversial. Our study aimed to reassess the effect of HMLL metastasis on survival. Patients with stage pT1-4N2M0 NSCLC who underwent major lung resection and systemic lymphadenectomy at Peking University People's Hospital from 2004 to 2015 were identified. Patients in the HMLL-positive group were matched to patients in the HMLL-negative group using 1:1 propensity score matching analysis. Overall survival was estimated by Kaplan-Meier method and compared using log-rank test, and multivariable Cox proportional hazard regression was constructed to identify risk factors associated with overall survival. The cumulative incidence of cancer specific mortality was evaluated through a competing risk analysis. A total of 266 NSCLC patients with stage pT1-4N2M0 NSCLC were enrolled. Of those, 128 cases were HMLL positive and 138 cases were HMLL negative. A higher proportion of patients in the HMLL-positive group were female (P= .034) and had a higher rate of adenocarcinoma (P= .003). Compared with the HMLL-negative, the HMLL-positive group was not associated with worse survival in unmatched cohorts (adjusted hazard ratio= 1.21; 95% confidence interval, 0.87-1.68). After propensity score matching, 109 pairs were selected. No survival difference remained in matched cohorts (adjusted hazard ratio= 1.00; 95% confidence interval, 0.70-1.42). Highest mediastinal lymph node metastasis does not exhibit worse survival in patients with stage pT1-4N2M0 NSCLC. The clinical relevance of HMLL metastasis needs further examination.

Impact of the number of resected lymph nodes during multi-portal VATS lobectomy for clinical N0 non-small cell lung cancer

Background: The adequacy of lymphadenectomy based on the number of resected lymph nodes in video-assisted thoracoscopic surgery (VATS) for patients with non-small cell lung cancer (NSCLC) has been questioned. Therefore, this study aimed to identify the role of lymph node dissection during VATS lobectomy for NSCLC, and reveal the relationship between the number of lymph node retrieved and overall and recurrence-free survival.

Association of postoperative radiotherapy with survival in patients with completely resected pathologic N2 non-small cell lung cancer treated with chemotherapy.

e21008 Background: The current staging system for completely resected pathological N2 non-small-cell lung cancer (NSCLC) treated with chemotherapy is not suitable for predicting those patients most likely to benefit or not from post-operative radiotherapy (PORT). This study aimed to construct a survival prediction model that will enable individualized predictions of the net survival of PORT. Methods: A total of 3094 cases between 2002 and 2014 were extracted from the Surveillance, Epidemiology, and End Results databases. Patient characteristics were included as covariates, and their association for overall survival (OS) with and witout PORT was assessed. Externally validate data of 602 patients were included from China. Results: A total of 3696 patients were included for analysis. Age, gender, examined lymph node, positive lymph node, tumor size, extent of surgery, and visceral pleural invasion were significantly associated with OS, with P &lt; .05. The calibration curve for OS showed great agreement between prediction by survival prediction model and actual observation.In the training cohort, the C-index for OS was 0.619 (95% CI, 0.598-0.641) in the PORT group and 0.627 (95% CI, 0.605-0.648) in the non-PORT group. In the externally validation cohort, the C-index for OS was 0.599 (95% CI, 0.485- 0.713) in the PORT group and 0.595 (95% CI, 0.544-0.646) in non-PORT group. The two survival prediction models were developed based on clinical variables to estimate an individual's net survival gain or not attributable to PORT. We found that PORT could improve OS (HR, 0.861; P = 0.044) for patients with a positive PORT net survival benefit. Conclusions: We established a practical survival prediction model that can be used to make individualized predictions about the expected survival of PORT or without PORT in patients with completely resected pathological N2 NSCLC, treated with chemotherapy.

Results of video-assisted thoracic surgery versus thoracotomy in surgical resection of pN2 non-small cell lung cancer in a Chinese high-volume Center.

To investigate the short-term outcomes and long-term oncological efficacy of video-assisted thoracic surgery (VATS) for surgical treatment of pN2 non-small cell lung cancer (NSCLC) compared with open thoracotomy (OT). We retrospectively collected data from 1034 patients who underwent pulmonary resection and systemic lymph node dissection for pathological N2 NSCLC from September 2005 to December 2017 (536 patients in VATS group and 498 patients in OT group). Propensity score matching was applied to reduce the confounding effects. Factors affecting survival were assessed by Kaplan-Meier estimates and Cox regression analysis. The VATS procedure was associated with shorter operative time compared with the OT procedure (147.96 ± 58.91min vs. 165.34 ± 58.91min, P < 0.001). No significant difference was identified between the two groups in the number of dissected mediastinal lymph nodes (MLNs) and number of dissected MLNs stations. More patients after VATS procedure received postoperative adjuvant therapy (83.4% vs. 75.5%, P = 0.002). At a median follow-up of 36 (range 4-150) months, comparing VATS procedure and OT procedure, no significant differences were noted in 5-year DFS (20.7% vs. 22.5%, P = 0.89) and 5-year OS (30.7% vs. 34.5%, P = 0.821). The VATS procedure was not found to be an independent predictor of DFS (hazard ratio, 0.986; 95% CI, 0.809 to 1.202) or OS (hazard ratio, 0.977; 95% CI 0.802 to 1.191). In this large propensity-matched comparison, the VATS procedure offered comparable short-term outcomes and long-term oncological efficacy for patients with pN2 NSCLC when compared with OT procedure.