Prognostic comparison between superior and basal segments in pure-solid non-small cell lung cancer.

Commentary:Segmentectomy as a standard surgery, a new era in small sized, peripheral, non-small cell lung cancer.

Objective: The aim of the study was to compare the prognoses between part-solid and pure-solid tumors for clinical stage IA non-small-cell lung cancer (NSCLC) patients in the eighth edition TNM classification.Methods: We searched the literature in PubMed and Web of Science for all eligible articles published before November 31, 2018. The pooled data included overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS). The hazard ratio (HR) of OS (pure-solid/part-solid) was used as the measure of differential effects. Pure-solid or part-solid tumors in all studies included were matched according to the solid component size or according to the eighth edition TNM classification. Results: Seven studies including 2,037 patients with c-stage IA NSCLC were pooled in the meta-analysis. Patients with pure-solid tumors had significantly poorer OS (HR 1.69, 95% CI 1.21‒2.35, P=0.002), DFS (HR 1.27, 95% CI 1.07‒1.51, P=0.006) and RFS (HR 1.74, 95% CI 1.08‒2.80, P=0.020). In subgroup analyses, when the meta-analysis was limited to T1a-1b (≤2 cm) lung cancer, the prognosis for pure-solid tumors was inferior to that for part-solid tumors regarding both OS and RFS. In adenocarcinoma subgroup, there was no difference between the two groups in terms of OS and RFS, but we detected a meaningful difference in DFS. Conclusion: Part-solid tumors may have a better prognosis than pure-solid tumors in clinical stage IA patients according to the eighth edition TNM classification, and similar results were found for the T1a-1b (≤2 cm) subgroup. There were no substantial differences in OS and RFS between two groups in lung adenocarcinoma. However, we detected a meaningful difference in DFS, which might also suggest a superior prognosis for part-solid tumors. We propose that the part-solid and pure-solid tumors in the same T component category be considered separately.

It is still debatable whether complete mediastinal lymph node dissection (MLND) is associated with better survival than mediastinal lymph node sampling (MLNS) in surgical treatment of nonsmall cell lung cancer (NSCLC). We aimed to assess the impact of lymph node dissection on long-term survival among stage I NSCLC patients.In this cohort study, 317 stage I NSCLC Chinese patients in Shanghai Chest Hospital were followed up for at least 10 years to evaluate the impact of different lymph node dissection modes on their survival. Among them, 161 patients were in the MLND group and 156 in the MLNS group. Overall survival and median survival times were calculated for the 2 groups. The association between lymph node dissection and the survival of NSCLC patients was assessed using Cox proportional-hazard models.Patients in the MLND group presented better survival (median survival time = 154.67 months) than those in the MLNS group (median survival time = 124.67 months). The MLNS had higher mortality than the MLND group, with the crude hazard ratio of the MLNS group relative to the MLND group as 1.32 (95% confidence interval [CI] 0.97, 1.78). After adjusting for age and sex, the association between lymph node dissection and mortality (hazard ratio 1.36, 95% CI 1.00, 1.84) was statistically significant (P = .047). Further adjusting for baseline clinical characteristics, the association (hazard ratio 1.40, 95% CI 1.02, 1.92) remained statistically significant (P = .036). The association between lymph node dissection mode and mortality was strong among patients with tumor size between 2.0 and 3.0 cm (hazard ratio 2.79, 95% CI 1.45, 5.37).We found that the MLND was associated with better survival for patients with early-stage NSCLC, compared with the MLNS. The effects of MLND on survival may depend on tumor size. Our findings have important implications in the treatment of early-stage NSCLC. Further prospective studies with a large sample size are needed to confirm our findings.

The therapeutic value of mediastinal lymph node dissection (LND) for early-stage non-small cell lung cancer (NSCLC) remains controversial. We conducted a retrospective study to investigate the impact of mediastinal LND on survival in patients with stage I NSCLC. Clinical data of patients with stage I NSCLC who were treated with surgical resection during a period of ten years were reviewed. The patients were categorized into lobectomy (or pneumonectomy) combined with mediastinal LND or lymph node sampling (LNS) according to the record of their operative procedures. The Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for multivariate analysis. Of the 319 patients who were included in the study, 139 patients received mediastinal LND, while 180 underwent LNS. There was a significant difference in overall survival (OS) between the group with LND and the group with LNS (5-year survival rate: 76.4 % vs. 65.9 %, P = 0.015 by log rank test). Multivariate analysis showed that lymph node dissection (RR = 0.548, 95 %CI: 0.350 - 0.858, P = 0.009), together with the stage, significantly influenced overall survival. Lobectomy combined with mediastinal LND can improve survival in patients with stage I NSCLC. It should be performed in all patients with clinical stage I NSCLC.

We investigated the long-term outcomes of lobe-specific nodal dissection (LSD) and systematic nodal dissection (SND) in patients with non-small-cell lung cancer (NSCLC). Patients with c-stage I and II NSCLC who underwent lobectomy with mediastinal nodal dissection were retrospectively analysed. After propensity score matching, we assessed the overall survival (OS), recurrence-free survival (RFS) and cumulative incidence of death (CID) from primary lung cancer and other diseases. The median follow-up period was 8.4 years. Among 438 propensity score-matched pairs, OS and RFS were similar between the LSD and SND groups [hazard ratio (HR), 0.979; 95% confidence interval (CI), 0.799-1.199; and HR, 0.912; 95% CI, 0.762-1.092, respectively], but the LSD group showed a better prognosis after 5 years postoperatively. CID from primary lung cancer was similar between the 2 groups (HR, 1.239; 95% CI, 0.940-1.633). However, the CID from other diseases was lower in the LSD group than in the SND group (HR, 0.702; 95% CI, 0.525-0.938). According to c-stage, the LSD group tended towards worse OS and RFS, with higher CID from primary lung cancer than the SND group, in patients with c-stage II. LSD provides acceptable long-term survival for patients with early-stage NSCLC. However, LSD may not be suitable for patients with c-stage II NSCLC due to the higher mortality risk from primary lung cancer.

The optimal extent of lymph node resection for early-stage non-small cell lung cancer (NSCLC) remains a topic of debate in the medical community. We aimed to assess the surgical and prognostic outcomes based on the extent of mediastinal lymph node dissection (MLND) for resectable clinical stage IA NSCLC. From 2016 to 2018, 1,166 patients with clinical stage IA NSCLC who underwent lobectomy or segmentectomy with complete mediastinal lymph node dissection (C-MLND) or selective mediastinal lymph node dissection (S-MLND) at five hospitals were enrolled. Propensity score matching (PSM) was used to reduce selection bias. Perioperative parameters, postoperative complications, survival and disease control were compared between the groups. S-MLND and C-MLND were performed on 197 and 969 patients, respectively. After PSM, each group comprised 126 patients and there was no significant difference in 5-year recurrence-free survival (RFS) (C-MLND vs. S-MLND, 87.5% vs. 82.9%; P=0.32) or overall survival (OS) (C-MLND vs. S-MLND, 92.0% vs. 95.9%; P=0.39) between the groups. Similar results were observed for perioperative parameters, pN2 detection (6.3% vs. 4.8%, P=0.11) and recurrence patterns (P=0.28). However, the incidence of postoperative complications was significantly lower in the S-MLND cohort than that in the C-MLND cohort (12.7% vs. 23.0%, P=0.03). S-MLND demonstrated outcomes that were comparable to those of C-MLND and a reduction in complications, indicating the potential of S-MLND as an alternative approach for selected patients with stage IA NSCLC. Prospective, randomized trials are recommended to confirm these findings and establish clear clinical guidelines.

BackgroundAmong the key factors influencing the prognosis of lung cancer, the primary tumor site has garnered significant attention in recent years, as it may affect the surgical difficulty and the risk of lymph node metastasis, thereby impacting overall prognosis. Numerous retrospective studies have produced conflicting conclusions, highlighting the necessity for a meta-analysis to consolidate these findings and ascertain the effects of primary tumor location in the basal versus superior segment of the lower lobe(S6) on survival outcomes.MethodsWe conducted a comprehensive literature search up to January 2025 and identified six relevant retrospective studies. We then used the random-effects model in Stata software to perform a meta-analysis to evaluate the impact of the primary tumor location on overall survival(OS) and event-free survival(EFS), EFS was defined as an aggregate of freedom from recurrence (FFR), disease-free survival (DFS), and progression-free survival (RFS).ResultThis study demonstrated that there were no statistically significant differences in OS (S6 vs. Basal segment HR = 1.40, 95% CI: 0.81,2.42 I²=71.8%) and EFS(S6 vs. Basal segment HR = 1.32, 95% CI: 0.69,2.54, I²=76.6%) between patients with the tumor in the S6 segment or basal segment. Begg’s test did not find publication bias (p > 0.05). Subgroup analysis indicated that the year of publication, clinical stage, sample size, and both univariate and multivariate analyses did not significantly influence the results.ConclusionThe direct impact of tumor location (S6 vs. Basal segment)on survival is not statistically significant.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12957-025-03945-5.

BackgroundExtent of lymph node involvement in patients with non-small cell lung cancer (NSCLC) is the cornerstone of staging and influences both multimodality treatment and final outcome. The aim of this study was to investigate accuracy and characteristics of intraoperative ultrasound guided systematic mediastinal nodal dissection in patients with resected NSCLC. MethodsFrom January 2008 to June 2013, 244 patients undergoing intraoperative surgical staging after radical surgery for NSCLC were included in prospective study. The patients were divided in two groups according to systematic mediastinal nodal dissection: 124 patients in intraoperative ultrasound nodal dissection guided group and 120 in standard nodal dissection group. The lymph nodes were mapped by their number and station and histopathologic evaluation was performed. ResultsOperating time was prolonged for 10 min in patients with ultrasound guided mediastinal nodal dissection, but number and stations of evaluated lymph nodes were significantly higher (p < 0.001) in the same group. Skip nodal metastases were found in 24% of patients without N1 nodal involvement. Twelve (10%) patients were upstaged using US guided mediastinal lymphadenectomy. In US guided group 5-year survival rate was 59% and in the group of standard systematic mediastinal lymphadenectomy 43% (p = 0.001) Standard staging system seemed to be improved in ultrasound guided mediastinal lymphadenectomy patients. Complication rate showed no difference between analyzed groups. ConclusionHigher number and location of analyzed mediastinal nodal stations in patients with resected NSCLC using ultrasound is suggested to be of great oncological significance. Our results indicate that intraoperative ultrasound may have important staging implications.

The Lung Cancer Staging Program of the International Association for the Study of Lung Cancer (IASLC) has proposed using solid component size, rather than overall tumor size, for T-staging. However, studies focusing on patients with ground-glass opacity (GGO) lesions with a diameter larger than 2 cm are limited. This study aims to validate the T stage classification strategy recommended by IASLC in this specific and less-studied patient group. Patients diagnosed with primary non-small cell lung cancer (NSCLC) who underwent lobectomy between December 2009 and December 2018 were included in this study. Clinical, pathological, and prognostic data were prospectively collected and retrospectively reviewed. Patients were eligible if they were confirmed to have NSCLC, underwent lobectomy, had complete follow-up data, and were not diagnosed with any other malignancies. The propensity score matching (PSM) method was employed to ensure baseline characteristic balance. Two groups of patients matched with the GGO group at baseline were stratified based on overall tumor size (group matched by overall size) and solid component size (group matched by solid component size), respectively. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using the Cox proportional model and Kaplan-Meier method. Follow-up was conducted regularly to assess these outcomes. The T-staging applied was based on the solid component size according to the 8th edition IASLC staging guidelines. A total of 4,472 NSCLC patients who underwent lobectomy were included in the study (including 4,083 cases of solid lesions and 389 cases of subsolid lesions). The median follow-up time was 75.4 months. Patients in the GGO group had significantly better OS and RFS than those in the solid group [OS: hazard ratio (HR) =0.55, 95% confidence interval (CI): 0.40-0.73, P<0.001; RFS: HR =0.53, 95% CI: 0.42-0.67, P<0.001]. Comparing patients' PSM by overall size, the GGO group still had better OS and RFS (OS: HR =0.60, 95% CI: 0.43-0.85, P=0.004; RFS: HR =0.59, 95% CI: 0.44-0.79, P<0.001). After PSM by solid component size, no significant difference was detected between the GGO group and the group matched by solid component size on OS and RFS (OS: HR =0.89, 95% CI: 0.61-1.28, P=0.52; RFS: HR =0.92, 95% CI: 0.67-1.26, P=0.61). In subgroup analysis, after PSM by solid component size, the results showed no difference in OS and RFS between the restaged patients (c-T1 and c-T2) and the corresponding patients in the solid group (for OS, HR =1.06, 95% CI: 0.61-1.83, P=0.83; HR =1.11, 95% CI: 0.60-2.07, P=0.73, respectively; and RFS, HR =1.17, 95% CI: 0.75-1.82, P=0.49; HR =0.80, 95% CI: 0.48-1.34, P=0.39, respectively). The T stage classification strategy proposed by ISALC remains applicable in patients with GGOs larger than 2 cm.

BackgroundPatients with completely resected non-small cell lung cancer (NSCLC) have an excellent outcome; however tumor recurs in 30%–77% of patients. This study retrospectively analyzed the clinicopathologic features of patients with any operable stage of NSCLC to identify the prognostic factors that influence tumor recurrence, including intratumoral blood vessel invasion (IVI), tumor size, tumor necrosis, and intratumoral lymphatic invasion.MethodsFrom January 2002 to December 2011, 227 consecutive patients were enrolled in this study. They were divided into two groups: the “no recurrence” group and the “recurrence” group. Recurrence-free survival was analyzed by multivariable Cox regression analysis, stratified by tumor staging, chemotherapy, and nodal involvement.ResultsIVI, tumor necrosis, tumor diameter more than 5 cm, and nodal involvement were identified as independent prognostic factors of tumor recurrence. The hazard ratio (HR) of patients with IVI was 2.1 times higher than that of patients without IVI (95% confident interval [CI]: 1.4–3.2) (P = 0.001).The HR of patients with tumor necrosis was 2.1 times higher than that of patients without tumor necrosis (95% CI: 1.3–3.4) (P = 0.001). Patients who had a maximum tumor diameter greater than 5 cm had significantly higher risk of recurrence than patients who had a maximum tumor diameter of less than 5 cm (HR 1.9, 95% CI: 1.0–3.5) (P = 0.033).ConclusionIVI, tumor diameter more than 5 cm, and tumor necrosis are prognostic factors of tumor recurrence in completely resected NSCLC. Therefore, NSCLC patients, with or without nodal involvement, who have one or more prognostic factors of tumor recurrence may benefit from adjuvant chemotherapy for prevention of tumor recurrence.

Lobectomy (LOB) remains the standard treatment for stage I non-small cell lung cancer (NSCLC), though sublobar resection (SLR) has emerged as a potential alternative with comparable outcomes. Spread through air spaces (STAS) has been confirmed as an independent risk factor after lung cancer surgery. The prognosis differences between LOB and SLR in patients with stage I NSCLC with STAS are controversial. After systematic retrieval across multiple databases, 25 eligible studies involving 14,126 patients were identified. We extracted hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival (OS) comparing lobectomy versus sublobar resection, along with reconstructed individual patient data (IPD) and adjuvant chemotherapy (ACT) records. These datasets were subsequently subjected to meta-analysis with complementary subgroup and sensitivity analyses. STAS was confirmed as an independent risk factor (RFS: HR 2.61, 95% CI 2.17-3.14; OS: HR 2.15, 95% CI 1.75-2.63). In subgroup analysis of SLR versus LOB in patients with STAS, the inferior RFS and comparable OS were observed in the SLR group (RFS: HR 1.70, 95% CI 1.16-2.49, n = 3488; OS: HR 1.10, 95% CI 0.83-1.46, n = 3581). Furthermore, ACT following SLR effectively reduced recurrence risk in STAS-positive patients compared with LOB (LOB: RFS: HR 1.03, 95% CI 0.48-2.22; SLR: RFS: HR 0.44, 95% CI 0.23-0.82). Surgical approach significantly impacts survival outcomes in stage I NSCLC patients with STAS. LOB remains the preferred option due to its lower recurrence rate and prolonged survival outcomes; for high-risk patients undergoing SLR, ACT is recommended in the case of postoperative STAS.

Meta-Analysis of EGFR Kinase Inhibitors: Not Always Greater Than the Sum of Its Parts

Objective To summarize the clinical experience of single-port thoracoscopic anatomic segmentectomy for early-stage non-small-cell lung cancer(NSCLC). Methods The clinical data of 27 patients undergoing single-port thoracoscopic anatomic segmentecomy for early-stage NSCLC in Department of Thoracic Surgery, Union Hospital affiliated to Fujian Medical University between May 2014 and March 2015 were retrospectively analyzed. A double lumen endotracheal tube was input, and the contralateral one-lung ventilated. A 4-5 cm incision was put on the anterior axillary line in the 4th or 5th intercostal space. Anatomic segementecomy was carried out firstly, and mediastinal lymph node dissection or sampling was executed when NSCLC was confirmed by intraoperative frozen pathology. The outcomes included perioperative parameters (operative time, volume of blood loss, duration of drainage, length of postoperative hospital stay, etc.), oncological results (total number of lymph node resection, total number of mediastinal lymph node resection, and number of stations of mediastinal lymph node resection), and pain score. Results All cases of single-port thoracoscopic surgery were completed, without adding auxiliary incision or converting to thoracotomy. There was no case of perioperative death, while there were 3 cases of complications (2 cases of pulmonary infection, and 1 case of arrhythmia), with the prevalence of complications of 11.1%. All cases of complications were cured. The mean operative time was (192.2 ± 56.1) min, the volume of blood loss was (83.8 ± 50.5) ml, the duration of drainage was (4.5±1.3) d, the length of postoperative hospital stay was (6.2±2.7) d, and the postoperative pain VAS score was (3.4 ± 0.9). The total number of lymph node dissection was (13.7±5.3), the total number of mediastinal lymph node dissection was (9.5 ± 4.3), and the number of stations of mediastinal lymph node dissection was (5.6±1.3). Conclusion In an center with extensive experience of thoracoscopic surgery, the single-port thoracoscopic anatomic segmentectomy for early-stage NSCLC is technically feasible and safe, and is a more minimally invasive surgical approach. Key words: Single-port; Thoracoscopic surgery; Segmentectomy; Non-small-cell lung cancer

Background: Copy number alterations (CNAs) arise during the evolution of tumors as a consequence of its genomic instability. It is reported that the increase of gene copy number of AKT1/2 correlated with clinicopathological profiles in lung cancer. On the other hand, tumor heterogeneity was also reported to associate with clinical outcomes of the patients in several cancers. However, the clinical significance of AKT1/2 CNAs in patients with non-small cell lung cancer (NSCLC) has been still unclear, especially its contribution to patients’ prognoses. We here explored the relationships between intertumoral heterogeneity of CNAs of AKT1/2 and clinicopathological features using the resected tissue pairs of primary sites and corresponding lymph node metastases (LNM). Method: AKT1/2 CNAs in 130 tissue pairs of NSCLC were assessed by fluorescent in situ hybridization (FISH), which were classified into three categories: amplification, polysomy, and disomy. The associations between CNAs and clinical features were retrospectively analyzed. In addition, we investigated the effect of the increased AKT1/2 copy number and intertumoral heterogeneity of AKT1/2 CNAs between the resected tissue pairs on the patient prognoses. Result: The median age of patients was 66.0 years old (33-84 years old) and 98 (75.4%) patients were male. 100 (76.9%) patients had smoking history and 69 (53.1%) patients had adenocarcinoma. AKT1 CNAs including amplification and polysomy were observed in 27.3% of primary sites (2.3% for amplification and 25% for polysomy), and in 43.8% of LNM (9.4% for amplification and 34.4% for polysomy). AKT2 CNAs were observed in 33.1% of primary sites (5.5% for amplification and 27.6% for polysomy), and in 36.3% of LNM (9.7% for amplification and 26.6% for polysomy). AKT1 CNAs were significantly associated with sex (p=0.004 for primary sites, p=0.034 for LNM) and smoking history (p=0.004 for primary sites, p=0.038 for LNM). EGFR mutations were more frequently observed in the patients with AKT1/2 CNAs in primary sites (p=0.009 for AKT1, and p=0.037 for AKT2). The mean copy number significantly increased in the LNM compared to the primary sites in AKT1 (2.1 for primary sites vs 3.4 for LNM, p&amp;lt;0.001), whereas there were no significant differences but an increasing tendency in AKT2 (2.9 for primary sites vs 3.5 for LNM, p=0.147). There were no significant differences for recurrence-free survival (RFS) according to AKT1/2 CNA categories. However, cases with the increased AKT1/2 copy number in the corresponding LNM showed significantly worse survivals for RFS (Log-rank, p=0.02 for AKT1, and p=0.04 for AKT2). Conclusion: AKT1/2 copy number increased in LNM compared to primary sited, and which also associated with worse prognosis. The intertumoral heterogeneity of AKT1/2 CNAs may possess distinct clinical significance in NSCLC. Citation Format: Kazuo Tsuchiya, Katsuhiro Yoshimura, Yusuke Inoue, Yuji Iwashita, Takashi Yamashita, Akikazu Kawase, Masayuki Tanahashi, Hiroshi Ogawa, Kazuhito Funai, Kazuya Shinmura, Hiroshi Niwa, Takafumi Suda, Haruhiko Sugimura. The impact of heterogeneity of AKT1/2 copy number alterations between primary tumors and lymph node metastases in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1563.

Survival of patients with left-sided stage I non-small cell lung cancer (NSCLC) is unsatisfactory, probably because of the high incidence of contralateral mediastinal node involvement. In this study, occult micrometastases to the right upper mediastinal nodes were retrospectively investigated in patients with left-sided stage I NSCLC. Nineteen patients with clinical stage I NSCLC underwent video-assisted thoracoscopic lobectomy and bilateral mediastinal node dissection (BMD). Clinical data and survival of patients with BMD were compared with those of 25 left-unilateral mediastinal node dissection (UMD) patients. Occult micrometastases were detected using the cytokeratin 19 mRNA reverse transcription-polymerase chain reaction method. Pathological N2 disease was found in 1 patient, and 18 had pN0 disease. The operative time, blood loss, duration of chest tube drainage and duration of postoperative hospital stay were not different between BMD and UMD patients. Nodal micrometastases were detected in 11/19 (57.8%) patients. Skip micrometastases to the level N3 nodes without N1 and N2 node involvement were observed in 8/11 (72.7%) patients. Patients with BMD are all alive and have had no recurrence during the median follow-up period of 21.4 months. Overall 3-year survival and disease-free 3-year survival were not significantly different between the two groups. In this preliminary study, occult micrometastases to the level N3 nodes occurred frequently in patients with left-sided clinical N0 stage I NSCLC. Postoperative survival of patients with occult micrometastases to the level N3 node does not appear to be poor. Further follow-up and work are needed.