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Background: Unexpected N2 involvement occurs in approximately 10% to 20% of patients with non-small-cell lung cancer (NSCLC) and patients' prognostic factors remain unclear. The aim of this study was to evaluate prognostic factors in these patients., Methods: From January 2002 to December 2012, we retrospectively analyzed data of 550 patients with NSCLC with preoperative negative, but pathologic positive N2 involvement, who underwent anatomical lung resection and hilo-mediastinal lymphadenectomy, obtained from 6 institutions. An established prognostic factor panel and N2-type involvement were correlated to overall (OS), cancer-specific (CSS), and disease-free survival (DFS) using multivariate Cox Regression model. The following lymph node patterns were analyzed: number of resected nodes (#RNs), metastatic nodes (#MNs), ratio between #MNs and #RNs (NR), N2 subgroups proposed for the eighth TNM edition, and lobe-specific versus nonspecific metastasis., Results: Regarding our cohort, 419 patients were staged IIIA (T1-2N2), 131 IIIB (T3-4 N2), 113 pT1, 306 pT2, 94 pT3, and 37 pT4; 5-year OS, DFS, and CSS were 34.1%, 20.1%, and 64.6%, respectively. Independent prognostic factor for OS, in the multivariable analysis, were as follows: NR <17% (P = .009), proposed N2 classification subgroups (P = .014), age <66 (P < .001), and pT (P = .005); for DFS: NR <17% (P = .003), adjuvant treatment (P = .026), and pT (P = .026); and for CSS: NR <17% (P = .008), grading (P = .001), and adjuvant treatment (P < .001)., Conclusion: Our study confirms that adjuvant therapy is fundamental and NR, in patients with unexpected N2 involvement, has a strong prognostic factor. In particular, a NR cutoff value of 17% could predict OS, DFS, and CSS in patients with NSCLC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Lung carcinoids (LCs) are staged using the non-small-cell lung cancer tumour/node/metastasis staging system; the possibility of an LC-specific staging system is still being debated. The goal of our study was to construct a composite prognostic score for LC., Methods: From January 2002 to December 2014, data from 293 patients who underwent surgical treatment for LC in 7 research institutes were retrospectively analysed. A panel of established prognostic factors in addition to lymph node metastasis patterns (single/multiple N1-N2 station, skip metastasis, lobe specific), numbers of lymph nodes resected and the ratio between the numbers of metastatic lymph nodes and the numbers of lymph nodes resected (node ratio) were correlated to overall survival (OS) and disease-free survival (DFS). The log-hazard ratio (HR), obtained from the Cox model, was used to derive weighting factors for a continuous prognostic index, designed to identify differential outcome risks. The score was dichotomized according to maximally selected log-rank statistics., Results: Pathological analysis showed typical carcinoids in 223 (76.1%) and atypical carcinoids in 70 (23.9%) patients; the tumour/node/metastasis pattern was stage I in 72.4%, stage II in 18.1%, stage III in 9.5% and stage IV in 0.03% cases. The median numbers of lymph nodes resected was 12 (range 0-53); hilar and mediastinal node metastases were identified in 14% and 6.8% of cases, respectively. Overall, the 5-year OS and 5-year DFS rates were 90.6% and 76.7%, respectively. At multivariable analysis, sex, age, pathological T stage and node ratio were significantly related to a better OS; age, histological type, pathological T stage and node ratio were related to DFS. These factors were used to generate the prognostic score, which showed statistically significant differences between the high-risk and low-risk groups: 5-year OS = 96.6% if score <3.1 vs 63.5% if score ≥3.1 [P < 0.0001; HR 17.56, 95% confidence interval (CI) 5.45-56.53]; 5-year DFS 92.3% if score <1.5 vs 52.5% if score ≥ 1.5 (P < 0.0001; HR 7.95, 95% CI 3.48-18.16)., Conclusions: The proposed prognostic scores seem to be effective in predicting outcomes for patients with LCs., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background The incidence of synchronous multiple primary lung cancer (SMPLC) has progressively increased, due to recent advances in imaging. To date, no guidelines defining recommendations for patients' selection and no standard treatment of cases with SMPLC have been defined. The primary aim of this systematic review was to assess survival among patients treated with lobectomy or sublobar resection MPLC. Methods Comprehensive literature search of Medline, the Cochrane Library, reference lists, and ongoing studies was performed according to a prospectively registered design (PROSPERO: CRD42019115487). All studies published between 1998 and December 2020 that examined treatments with lobectomy compared to sublobar resection were included. Two double-blind investigators independently selected articles. Primary outcomes were to assess the 5-year overall survival (OS) rate among patients treated with lobectomy or sublobar resection and the impact of lymph node status on 5-year OS and 5-year disease-free survival in patients with MPLC. Results The search yielded 424 articles; 4 observational studies met the inclusion criteria and collectively evaluated 298 patients with a mean age ranging from 61.5 to 67 years. A total of 112 patients were treated for bilateral synchronous tumors and 186 patients for unilateral multiple synchronous tumors. All included studies showed that the type of resection, lobectomy or limited resection, had no significant impact on survival. Conclusion Limited resection is a valuable treatment option for MPLC. However, the clinical level of evidence of the studies found is low and randomized studies are needed to clarify the extent of resection in MPLC. [ABSTRACT FROM AUTHOR]

Results from analyzing this parameter in patients with persistent nodal involvement in our study (N1 + N2) showed that patients with more than six mediastinal lymph nodes presented a better survival rate compared to patients with less than six removed nodes, with the I p i -value close to the statistical significance ( I p i = 0.057). A difference was also observed between the number of resected lymph nodes and pathological N2 or N1 patients, even if it was not statistically significant: 5YOS of 56.1% in N1 vs. 29.7% in N2 ( I p i = 0.144) and 5YOS of 0% in patients with #RN < 6 vs. 56.6% in patients with #RN >= 6 ( I p i = 0.057) (Figure 4). 4. In this context, the lymph node ratio could also be used to identify patients who could benefit from adjuvant treatments, such as postoperative radiotherapy in patients who still have margin for treatment, or they could be selected to continue consolidation chemotherapies postoperatively. Clinical Stage III NSCLC Patients Treated with Neoadjuvant Therapy and Surgery: The Prognostic Role of Nodal Characteristics †. [Extracted from the article]

Simple Summary: Incidence of lung carcinoids is rapidly increasing, but the correct management of these patients is still debated. Although their clinical behaviour differs from Non-Small Cell Lung Cancer, the same staging system is used for these tumors, even if it presents limitations in prognosis prediction and overlapping curves especially regarding sub-stages. For these reasons, in recent years, ad hoc scores have been constructed aiming to better stratify prognosis and indicate appropriate treatment options. In particular, a score including the node ration as nodal factor was proposed, although external validation was not possible. The aim of this study is to validate this score, for the possibility of identifying a specific class of patients that may benefit from specific follow-up schedules or post-operative treatments. Background: A prognostic score including T-dimension, age, histology and lymph node ratio was previously proposed in absence of an external validation dataset. The aim of the current study was to validate the proposed prognostic score using an independent dataset. Methods: Data of patients with lung carcinoids, who underwent surgical resection and lymphadenectomy in five institutions from 1 January 2005 to 31 December 2019, were retrospectively analyzed. Two risk groups were created based on the following data: age, histology, node ratio and pT for disease-free survival (DFS); age, sex, node ratio and pT for overall survival (OS). The previously proposed score was validated, identifying two groups of patients: a high risk (HRG) and low risk (LRG) group. Results: The final analysis was conducted on 283 patients. Regarding DFS, 230 (81.3%) patients were assigned to the LRG and 53 (18.7%) to the HRG. Considering OS, 268 (94.7%) were allocated in the LRG and 15 (5.3%) in the HRG. The 5-year DFS was 92.7% in the LRG vs. 67% in the HRG (p < 0.001) while the 5-year OS was 93.6% in the LRG vs. 86.2% in the HRG (p = 0.29) with clear curve separation. Conclusion: Our analysis confirmed the validity of the composite score for DFS in lung carcinoids. Regarding OS, statistical significance was not reached because of a low number of deaths and patients in the HRG. [ABSTRACT FROM AUTHOR]

Aim of this study is to identify the factors that may influence the lymphadenectomy during VATS anatomical lung resection with particular interest on operator experience. Clinical and pathological data from the prospective VATS Italian nationwide registry were reviewed and analysed. Patients with incomplete data regarding tumor and surgical characteristics, GGO, or with distant metastases were excluded. Patients clinical data, tumor characteristics, operation information and surgeon experience were collected and compared to resected lymph nodes number (#RN), resected N2 nodes number (#N2RN) and resected N2 stations number. A multivariable model was built using logistic regression analysis. Surgeon experience was categorized considering the number of VATS major anatomical resection and years after residency. The final analysis was conducted on 3727 patients. The median #RN and #N2RN were 11 (1–51) and 5 (0–41). Regarding the analysed outcomes, #N2RN > 6 resulted in 1812 (48.8%)cases, #RN > 10 in 2124 (57.0%)cases and more than 3 N2 stations were harvested in 1447 (38.8%)patients. First operator experience with number of VATS lobectomies>50 (p < 0.001), operator seniority after residency5-10years (p < 0.001), cTNM II/III(p = 0.017), lobectomy/bilobectomy vs segmentectomy (p < 0.001), and upper/middle lobe tumor location (p < 0.005)resulted significantly associated to #N2RN > 6 at the multivariable analysis. First operator experience with number of VATS lobectomies>50 (p < 0.001), operator seniority after residency5-10years (p < 0.001) and lobectomy/bilobectomy (p < 0.001) resulted significantly associated to #RN > 10 at the multivariable analysis. Our study showed that lymphadenectomy during VATS lobectomy is influenced by tumor factors such as cTstage and tumor location but also by operator experience, with a higher number of resected lymph nodes in surgeons with a high number of VATS procedures and years after residency compared to surgeons with less experience. [ABSTRACT FROM AUTHOR]

OBJECTIVES Open in new tab Download slide Open in new tab Download slide Overlapping survival curves for N1b (multiple N1 stations), N2a2 (single N2 station + N1 involvement) and N2a1 (skip N2 metastasis) limit the current tumour–node–metastasis (TNM) node (N) subclassification for node involvement. We validated externally the proposed subclassification. METHODS Clinical records from a multicentric database comprising 1036 patients with pulmonary adenocarcinoma (ADC) or squamous cell carcinoma with N1/N2 involvement who underwent, from January 2002 to December 2014, complete lung resections were retrospectively reviewed. Patients were categorized according to the 8th TNM N subclassification proposal. Histological type, number of resected nodes (#RN) and adjuvant therapy (ADJ) were considered limiting factors. RESULTS No difference in the 5-year overall survival (-OS) was noted between N1b and N2a1 (49.6% vs 44.8%, P  = 0.72); instead, the 5-year-OS was significantly improved in patients with squamous cell carcinoma (63% in N1b vs 30.7% in N2a1, P  = 0.04). In patients with ADC, the 5-year-OS was better in those with N2a1 than with N1b (50.6% vs 37.5%, P  = 0.09). When we compared N1b with N2a2, the 5-year-OS was statistically significant (49.6% vs 32.8%, P  = 0.02); considering only patients with squamous cell carcinoma (63% vs 25.8%, P  = 0.003), #RN >10 (63.2% vs 35.3%, P  = 0.05) and without ADJ (56.4% vs 24.5%, P  = 0.02), the 5-year-OS was significantly different. Differences were not significant for ADC, #RN <10 and ADJ. Finally, the 5-year-OS was statistically significant when we compared N2a1 with N2a2 of the total cohort (44.8% vs 32.8%, P  = 0.04), in ADC (5-year-OS 50.6% vs 36.5%, P  = 0.04) and #RN >10 (5-year-OS 49.8% vs 32.1%, P  = 0.03) without ADJ. CONCLUSIONS Histological type, ADJ and #RN are relevant prognostic factors in N + non-small-cell lung cancer. Considering these results, we may better interpret the prognosis prediction limits of the proposed 8th TNM subclassification for the N descriptor. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung adenocarcinoma is the most common histology in non-small cell lung cancer that has a large variety of histological and also pathological presentations. However, mediastinal lymph node involvement remains one of the most important prognosticators in these patients, and treatment can vary from upfront surgery to induction therapy or definitive radio-chemotherapy. One of the most intriguing issues regards the identification of the most appropriate treatment for a patient and one of the parameters that may indicate upfront surgical resection is the presence of single mediastinal station involvement. Moreover, another interesting argument regards the adjuvant therapy indication for these patients. For these reasons, we investigated the survival outcome of patients who underwent surgical resection for lung adenocarcinoma and single mediastinal station involvement, with the aim to investigate the prognostic factors in this class of patients. Background: Prognostic factors in patients with single mediastinal station (sN2) involvement continues to be a debated issue. Methods: Data on 213 adenocarcinoma patients with sN2 involvement and who had undergone complete anatomical lung resection and lymphadenectomy, were retrospectively reviewed. Clinical and pathological characteristics together with adjuvant therapy (AD) and node (N) status classifications (number of resected nodes (#RN), number of metastatic nodes (#MN), and node ratio (#MN/#RN = NR) were analyzed. Results: Univariable analysis confirmed that age (0.009), #MN (0.009), NR (0.003), #N1 involved stations (p = 0.003), and skip metastases (p = 0.005) were related to overall survival (OS). Multivariable analysis confirmed, as independent prognostic factors, age <66 years and NR with a three-year OS (3YOS) of 78.7% in NR < 10% vs. 46.6% in NR > 10%. In skip metastases, NR (HR 2.734, 95% CI 1.417–5.277, p = 0.003) and pT stage (HR2.136, 95% CI 1.001–4.557, p = 0.050) were confirmed as independent prognostic factors. AD did not influence the OS of patients with singular positive lymph nodes (p = 0.41), while in patients with multiple lymph nodes and AD, a significantly better 3YOS was demonstrated, i.e., 49.1% vs. 30% (p = 0.004). In patients with N2 + N1 involvement, age (p = 0.002) and AD (p = 0.022) were favorable prognostic factors. Conclusions: Adenocarcinoma patients with single N2 station involvement had a favorable outcome in the case of skip metastases and low NR. Adjuvant therapy improves survival with multiple nodal involvement, while its role in single node involvement should be clarified. [ABSTRACT FROM AUTHOR]