Beneficial implications of adjuvant chemotherapy for stage IB lung adenocarcinoma exhibiting elevated SUVmax in FDG-PET/CT: a retrospective study from a single center.

Background: Controversy surrounds the efficacy of adjuvant chemotherapy (ACT) in the treatment of stage I lung adenocarcinoma (LUAD). The objective of this study was to examine the impact of the maximum standardized uptake value (SUVmax) as measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on the efficacy of ACT in patients diagnosed with stage I LUAD. Methods: We scrutinized the medical records of 928 consecutive patients who underwent complete surgical resection for pathological stage I LUAD at our institution. The ideal cut-off value for primary tumor SUVmax in terms of disease-free survival (DFS) and overall survival (OS) was determined using the X-tile software. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: Based on the SUVmax algorithm, the ideal cutoff values were determined to be 4.9 for DFS and 5.0 for OS. We selected 5.0 as the threshold because OS is the more widely accepted predictive endpoint. In a multivariate Cox regression analysis, SUVmax ≥ 5.0, problematic IB stage, and sublobectomy were identified as independent risk factors for poor DFS and OS. It is noteworthy that patients who were administered ACT had significantly longer DFS and OS than what was observed in the subgroup of patients with pathological stage IB LUAD and SUVmax ≥ 5.0 (p < 0.035 and p ≤ 0.046, respectively). However, there was no observed survival advantage for patients in stages IA or IB who had an SUVmax < 5.0. Conclusion: The preoperative SUVmax of tumors served as an indicator of the impact of ACT in the context of completely resected pathological stage I LUAD. Notably, patients within the Stage IB category exhibiting elevated SUVmax levels emerged as a subgroup experiencing substantial benefits from postoperative ACT.

Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial.

OBJECTIVES: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been approved for EGFR-mutant non-small-cell lung cancer (NSCLC). We aimed to evaluate the efficacy and safety of neoadjuvant osimertinib in patients with EGFR-mutant resectable locally advanced NSCLC. MATERIALS AND METHODS: This single-arm, phase 2b trial (ChiCTR1800016948) was conducted at six centers in mainland China. Patients with a measurable stage IIA-IIIB (T3-4 N2) lung adenocarcinoma and EGFR exon 19 and/or 21 mutations were enrolled. The patients were treated with osimertinib 80 mg orally once per day for six weeks, followed by surgical resection. The primary endpoint was the objective response rate (ORR) assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. RESULTS: Between October 17, 2018, and June 08, 2021, 88 patients were screened for eligibility. Forty patients were enrolled and treated with neoadjuvant osimertinib therapy. The ORR was 71.1 % (27/38) (95 % confidence interval: 55.2-83.0) in 38 patients who completed the 6-week osimertinib treatment. Thirty-two patients underwent surgery, and 30 (93.8 %) underwent successful R0 resection. Thirty (75.0 %) of 40 patients had treatment-related adverse events during neoadjuvant treatment, and three (7.5 %) had treatment-related adverse events of grade 3. The most common treatment-related adverse events were rash (n = 20 [50 %]), diarrhea (n = 12 [30 %]), and oral ulceration (n = 12 [30 %]). CONCLUSIONS: The third-generation EGFR TKI osimertinib, with satisfying efficacy and acceptable safety profile, could be a promising neoadjuvant therapy in patients with resectable EGFR-mutant NSCLC.

Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma.

BACKGROUND: Early diagnosis of lung adenocarcinoma (LUAD), one of the most common types of lung cancer, is very important to improve the prognosis of patients. The current methods can't meet the requirements of early diagnosis. There is a pressing need to identify novel diagnostic biomarkers. Secretory proteins are the richest source for biomarker research. This study aimed to identify candidate secretory protein biomarkers for early diagnosis of LUAD by integrated bioinformatics analysis and clinical validation. METHODS: Differentially expressed genes (DEGs) of GSE31210, gene expression data of early stage of LUAD, were analyzed by GEO2R. Upregulated DEGs predicted to encode secreted proteins were obtained by taking the intersection of the DEGs list with the list of genes encoding secreted proteins predicted by the majority decision-based method (MDSEC). The expressions of the identified secreted proteins in the lung tissues of early-stage LUAD patients were further compared with the healthy control group in mRNA and protein levels by using the UALCAN database (TCGA and CPTAC). The selected proteins expressed in plasma were further validated by using Luminex technology. The diagnostic value of the screened proteins was evaluated by receiver operating characteristic (ROC) analysis. Cell counting kit-8 assay was carried out to investigate the proliferative effects of these screened proteins. RESULTS: A total of 2183 DEGs, including 1240 downregulated genes and 943 upregulated genes, were identified in the GSE31210. Of the upregulated genes, 199 genes were predicted to encode secreted proteins. After analysis using the UALCAN database, 16 molecules were selected for further clinical validation. Plasma concentrations of three proteins, Midkine (MDK), WAP four-disulfide core domain 2 (WFDC2), and C-X-C motif chemokine ligand 14 (CXCL14), were significantly higher in LUAD patients than in healthy donors. The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them. Overexpression of the three proteins enhanced the proliferation activity of A549 cells. CONCLUSIONS: MDK, WFDC2, and CXCL14 were identified as candidate diagnostic biomarkers for early-stage LUAD and might also play vital roles in tumorigenesis.

Neoadjuvant PD-1 inhibitor combines with chemotherapy versus neoadjuvant chemotherapy in resectable squamous cell carcinoma of the lung.

BACKGROUND: A single-agent of anti programmed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) therapy has been explored for resectable lung cancer before surgery. However, the effectiveness and safety of neoadjuvant programmed cell death 1 (PD-1) blockade combined with chemotherapy have not been published. METHODS: Twenty-one consecutive patients with potentially resectable squamous cell carcinoma of the lung who received neoadjuvant therapy followed by surgery in Beijing Cancer Hospital were included in this study. Eight patients received two cycles of neoadjuvant platinum-based doublet chemotherapy combined with anti-programmed cell death 1 (anti-PD-1) therapy, while 13 patients received two cycles of neoadjuvant platinum-based doublet chemotherapy only. Chest computed tomography was repeated before neoadjuvant treatment and surgery. Adverse events were monitored. The major pathological response (MPR) rate was determined after surgery. Selected specimens were sent for immunohistochemical and multiplex immunofluorescence analyses, and T-cell receptor DNA sequencing. RESULTS: Compared with neoadjuvant chemotherapy alone, the combination of PD-1 blockade and chemotherapy increased the pathological complete response rate (37.5% vs. 7.69%) and MPR rate (50% vs. 38.46%). The pathological and radiological evaluations are not consistent. No unknown adverse effects were reported for all the patients. More tumor infiltrating lymphocytes were observed in patients who received PD-1 blockade. No unknown pathological features associated with PD-1 blockade were found. Immune suppression in the peritumoral spaces around the residual tumor cells was observed. The amino acid sequences of the T-cell receptors are not significantly shared among the patients. CONCLUSIONS: The combination of neoadjuvant chemotherapy and PD-1 blockade is safe and feasible, and might indicate an increased MPR and pathological complete response rate. More investigations are needed for the best combination of the neoadjuvant therapy.

Aneuploid Circulating Tumor Cells as a Predictor of Response to Neoadjuvant Chemotherapy in Non-Small Cell Lung Cancer.

PURPOSE: This study aimed to explore the potential application of circulating tumor cells (CTCs) in predicting the therapeutic effect of neoadjuvant chemotherapy (NAC) in non-small-cell lung cancer (NSCLC). METHODS: Using integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization, the serial CTCs of patients with NSCLC were detected in 7.5 mL of blood at baseline and after two cycles of cisplatin-based NAC, and all aneuploidies of chromosome 8 were examined in the enriched CTCs. Tumor responses were evaluated radiologically with serial chest computed tomography (CT) using the response evaluation criteria in solid tumors and microscopically using the tumor cell necrosis rate (TCNR) of the resected specimen after NAC. RESULTS: After two cycles of cisplatin-based NAC, 89% (8/9) of the patients with radiological partial response to NAC had reduced CTC numbers, while 73% (8/11) of the patients with stable disease exhibited increased CTC numbers (P = 0.0098). On pathological examination, 90% (9/10) of patients with a TCNR lower than 30% had >1 CTC post-NAC, while 80% (4/5) of patients with a TCNR higher than 30% had ≤1 CTC post-NAC (P = 0.017). In aneuploidy analysis, the positive rate (CTC > 0) of triploid CTCs was found to have increased after NAC, in contrast with the tetraploid and multiploid CTCs. Furthermore, tetraploid and multiploid CTCs were found to be significantly downregulated in the patients with partial response to NAC. CONCLUSION: The correlations of aneuploid CTCs with both radiological and pathological responses in patients with NSCLC who received NAC were summarized, and the findings indicate that enumerating and karyotyping aneuploid CTCs can serve as a surrogate marker for disease monitoring in NSCLC.

[Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer].

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS: Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

[Occlusion with Bronchial Covered Stent in the Management of Bronchial Stump Fistula after Right Middle and Lower Lobectomy: A Case Report and Literature Review].

BACKGROUND: Bronchopleural fistula (BPF) is one of the most serious and rare postoperative complications, especially the bronchial stump fistula after lobectomy/pneumonectomy. Common treatment options include conservative medical treatment combined with surgery. However, due to the delayed healing of the fistula, the chest cavity continues to communicate with the outside world, and the patient is prone to complicated with severe thoracic infection and respiratory failure, so that the physical condition can hardly tolerate the second surgical procedure. Endoscopic treatment provides a new option for the treatment of this complication. METHODS: A case of right pulmonary squamous cell carcinoma was admitted to the Department of Thoracic Surgery II, Peking University Cancer Hospital in June 2016. The diagnosis and treatment was retrospectively analyzed, and the literature was reviewed. RESULTS: A 65 year old male patient was admitted to hospital because of "cough with blood in sputum for 3 months". Chest computed tomography (CT) showed soft tissue density mass shadow in the right lower lobe. A tumor could be seen in the opening of the right middle lobe and basal segment of lower lobe. Biopsy confirmed squamous cell carcinoma. Diagnosis consideration: squamous cell carcinoma of the middle and lower lobe of the right lung (cT2aN2, IIIa). Patients received gemcitabine plus cisplatin neoadjuvant chemotherapy for 2 cycles, and the effect of chemotherapy showed stable disease (SD). Four weeks after chemotherapy, the patient underwent video-assisted thoracic surgery (VATS) assisted right middle and lower lobectomy and mediastinal lymph node dissection. On the 5th day after operation, the patient developed acute respiratory distress syndrome (ARDS) and was transferred to intensive care unit (ICU) again after endotracheal intubation. On the 7th day after operation, the patient developed a right intermediate trunk bronchial stump fistula, but due to ARDS, the patient's physical condition could not tolerate the second operation. Under the support of extracorporeal membrane oxygenation (ECMO), a membrane covered, expandable, hinged stent was inserted into the intermediate trunk bronchial stump through rigid bronchoscope, and was successfully blocked. Due to no improvement in ARDS and irreversible pulmonary interstitial fibrosis, the patient received double lung transplantation successfully after systemic anti-infection treatment. CONCLUSIONS: Endoscopic implantation of covered stent is a simple, safe and effective method for closure of bronchial stump fistula. When the patient's clinical situation is not suitable for immediate surgery, endoscopic stent implantation can be used as a preferred treatment method to create opportunities for follow-up treatment.

Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

Validation of the 8th Edition Nodal Staging and Proposal of New Nodal Categories for Future Editions of the TNM Classification of Non-Small Cell Lung Cancer.

BACKGROUND: The International Association for the Study of Lung Cancer (IASLC) N classifications, which depend on the location and involvement of the lymph nodes, provide accurate prognoses. This study validated the efficiency of classifications using a single-institution dataset and proposed a modified system based on 5-level N1 node dissection. METHODS: From January 2005 to December 2014, 1851 patients with completely resected non-small cell lung cancer were reviewed. According to the IASLC recommendations, N1 is further subdivided into N1a (single) and N1b (multiple), N2 is divided into N2a1 (single station without N1), N2a2 (single station with N1), and N2b (multiple station). Additionally, we evaluated dividing N0 into N0a (with level 13/14 examination) and N0b (without level 13/14 examination), and N1 into N1a* (only level 13/14 positive) and N1b* (level 10-12 positive). Overall survival was also compared. RESULTS: Multivariate analysis showed that the N classifications recommended by the IASLC and those proposed and evaluated by this study could both significantly predict the prognoses of patients (p < 0.001, respectively). There was no significant difference in survival between N1b and N1a (hazard ratio [HR] 1.049, p = 0.83) and N2a1 and N1b (HR 1.314, p = 0.261); however, there were significant differences between N0a and N0b (HR 1.778, p < 0.001) and N1a* and N1b* (HR 2.014, p = 0.019). The survival curve of N1a* overlapped N0b (HR 0.997, p = 0.991), and N2a1 overlapped N1b* (HR 0.842, p = 0.444). CONCLUSION: More detailed nodal information is required to facilitate future revisions of N staging.

Does neoadjuvant targeted therapy provide an opportunity for resectable EGFR-mutant lung cancer: a real-world retrospective study.

BACKGROUND: Although neoadjuvant chemotherapy could improve survival outcome in resectable non-small cell lung cancer (NSCLC), the efficacy of neoadjuvant targeted therapy is still unclear. METHODS: We retrospectively reviewed clinical records of stage I-IIIA lung adenocarcinoma patients treated with neoadjuvant targeted therapy or chemotherapy prior to surgery. The collected data were compared between the two groups. Tumor samples were collected and analyzed by sequencing to explore the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance mechanisms. RESULTS: A total of 134 patients were enrolled; of these, 119 (88.8%) had clinical stage II-IIIA disease. Radiographic response rate was significantly higher with neoadjuvant targeted therapy than with chemotherapy among patients harboring EGFR mutation [objective response rate (ORR): 55.8% vs. 32.6%; P=0.030]. EGFR exon 19 deletion achieved better tumor response than those with exon 21 L858R mutation (ORR: 70.0% vs. 40.0%; P=0.057). Postoperative complications, operation time, drainage volume, and postoperative hospital length of stay were comparable between two groups. There was no difference on disease free survival (DFS) between patients receiving neoadjuvant targeted therapy and chemotherapy (P=0.871), but those who continued long-term adjuvant targeted therapy had significantly longer DFS than those only treated with adjuvant chemotherapy postoperatively (P=0.011). A series of potential molecular mechanisms of EGFR-TKI primary resistance were detected; these included BIM deletion polymorphisms, EGFR T790M mutation, and PTEN, TSC1, PIK3CA, or STAT3 mutations. Patients who presented stable disease (SD) response after TKI therapy had significantly lower EGFR mutation abundance than PR response (P=0.032). CONCLUSIONS: Neoadjuvant EGFR-TKI appears to be more effective than conventional chemotherapy for EGFR-mutant NSCLC patients. This study provides evidence that needs to be investigated further in randomized controlled trials (RCT).

[Correlation between Lymph Node Ratio and Clinicopathological Features and Prognosis of IIIa-N2 Non-small Cell Lung Cancer].

BACKGROUND: IIIa-N2 non-small cell lung cancer was significant different in survival, although N stage of lung cancer based on anatomic location of metastasis lymph node. Lymph node ratio considered of prognostic factor might be the evaluation index for IIIa-N2 non-small cell lung cancer prognosis. Therefore, the aim of the study was to evaluate the correlation between lymph node ratio and clinicopathological features and prognosis of IIIa-N2 non-small cell lung cancer prognosis. METHODS: A total of 288 cases of pathological IIIa-N2 non-small cell lung cancer were enrolled who received radical resection at the Department of Thoracic Surgery II, Peking University Cancer Hospital from January 2006 to December 2016. The univariate analysis between clinicopathological variables and lymph node ratio used Pearson's chi-squared test. Cox regression was conducted to identify the independent prognosis factors for IIIa-N2 non-small cell lung cancer. RESULTS: There were 139 cases in the lower lymph node ratio group, another 149 cases in the higher lymph node ratio group. Adenocarcinoma (χ²=5.924, P=0.015), highest mediastinal lymph node metastasis (χ²=46.136, P<0.001), multiple-number N2 metastasis (χ²=59.347, P<0.001), multiple-station N2 metastasis (χ²=77.387, P<0.001) and skip N2 lymph node metastasis (χ²=61.524, P<0.001) significantly impacted lymph node ratio. The total number of lymph node dissection was not correlated with the lymph node ratio (χ²=0.537, P=0.464). Cox regression analysis confirmed that adenocarcinoma (P=0.008), multiple-number N2 metastasis (P=0.025) and lymph node ratio (P=0.001) were the independent prognosis factors of disease free survival. The 5-year disease free survival was 18.1% in the higher lymph node ratio group, and 44.1% in the lower. Lymph node ratio was the independent prognosis factor of overall survival (P<0.001). The 5-year overall survival was 36.7% in the higher lymph node ratio group, and 64.1% in the lower. CONCLUSIONS: Lymph node ratio was correlative with the pathology, highest mediastinal lymph node metastasis, multiple-number N2 metastasis, multiple-station N2 metastasis and skip N2 lymph node metastasis. Lymph node ratio was the independent prognosis factor for IIIa-N2 non-small cell lung cancer.

Long-term survival of patients with locally advanced esophageal squamous cell carcinoma receiving esophagectomy following neoadjuvant chemotherapy: a cohort study.

PURPOSE: The role of neoadjuvant chemotherapy and subsequent adjuvant therapy in the treatment of patients with locally advanced esophageal squamous cell carcinomas (ESCC) is not well established. PATIENTS AND METHODS: We retrospectively reviewed 228 patients with locally advanced ESCC receiving esophagectomy following neoadjuvant chemotherapy from January 2007 through December 2016. The probabilities of disease-free survival (DFS) and overall survival (OS) were estimated by means of the Kaplan-Meier method and were compared with the use of the log-rank test. Univariate and multivariate analyses of predictors of DFS and OS were performed using a Cox proportional-hazards model. Propensity score matching analysis was performed for further analysis regarding the benefit of adjuvant therapy. RESULTS: The pathological complete response of neoadjuvant chemotherapy was achieved in 13 of 228 patients (5.7%). With a median follow-up of 59.6 months, the median DFS and OS were 35.4 and 45.4 months, respectively. The multivariate Cox model determined chemotherapy regimens (P=0.003) and ypT category (P=0.006) were significant independent predictors of DFS; and chemotherapy regimens (P=0.001), ypT category (P<0.001), and ypN category (P=0.013) were significant independent predictors of OS. Furthermore, patients who received adjuvant therapy seemed to be associated with poorer survival (both DFS and OS) compared with those who did not in full cohort (P=0.001 and P=0.184, respectively) and matched cohort (P=0.251 and P=0.374, respectively). CONCLUSION: Surgery following neoadjuvant chemotherapy was applicable. Chemotherapy regimens and ypT category were significant independent predictors of both DFS and OS and ypN category was also a significant independent predictor of OS. However, these patients did not seem to benefit from subsequent adjuvant therapy. The necessity of adjuvant therapy requires further investigation.

Does postoperative treatment bring survival benefits to patients with locally advanced esophageal squamous cell carcinoma who have received neoadjuvant chemotherapy with TP regimen? / 中国胸心血管外科临床杂志

@#To investigate whether postoperative therapy can bring survival benefits to patients with locally advanced esophageal squamous cell carcinoma who have received neoadjuvant chemotherapy with TP regimen. Methods     We retrospectively reviewed clinical data of 115 patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant chemotherapy with TP regimen and underwent esophagectomy in our hospital from January 2007 through December 2016. Patients were divided into two groups including a non-receiving treatment group (54 patients with 47 males and 7 females) and a receiving treatment group (61 patients with 52 males and 9 females). There were 31 patients with postoperative chemotherapy, 14 with postoperative radiotherapy, and 16 with postoperative chemotherapy and radiotherapy in the receiving treatment group. Results     In the non-receiving treatment group, the 5-year median disease free survival (DFS) rate was 54.7%, and the 5-year overall survival (OS) rate was 55.3%. In the receiving treatment group, the median DFS was 46.0 months (95% CI 22.9–69.1), the 5-year DFS rate was 42.3%; and the   median OS was 68.0 months (95% CI 33.0–103.0), the 5-year OS rate was 51.3%. Furthermore, there was no statistical difference between the two groups with regards to DFS (P=0.641) or OS (P=0.757) using Kaplan-Meier method. Besides, in each subgroup, the results of Cox proportional hazard model analysis showed postoperative treatment did not improve survival (P>0.05, respectively). Conclusion     Postoperative treatment does not bring survival benefits to patients with esophageal squamous cell carcinoma who have received neoadjuvant chemotherapy with TP regimen.

Prognostic analysis of node status of 1 851 non-small cell lung cancer patients on the basis of the eighth TNM staging system: A cohort study / 中国胸心血管外科临床杂志

@#Objective    To evaluate the prognosis of different node status on the basis of the eighth TNM classification for lung cancer. Methods    We retrospectively reviewed the clinical data of 1 851 non-small cell lung cancer (NSCLC) patients who underwent radical resection between January 2005 and December 2014. There were 1 078 males and 773 females at age of 16–86 (59.7±9.7) years. Survival probability was estimated by the Kaplan-Meier method and significance was assessed by the log-rank test. Results    This cohort study was consisted of 1 209 patients with N0, 305 with N1 and 337 with N2. N0 patients were divided into a N0a group and a N0b group according to whether the 13 and 14 level of lymph nodes were examined. The survival rate of the N0a group was significantly higher than that of the N0b group, and the 5-year survival rate was 88.9% and 81.3% (P<0.001), respectively. According to the number of lymph node metastasis stations, N1 was divided into a N1a (single) group and a N1b (multiple) group. And no significant difference was observed between the two groups in survival rate (P=0.562). Based on the presence of lymph nodes of 10–12 level, N1 was divided into a negative group and a positive group. And the negative group was found with significantly higher survival rate than the positive group (5-year survival rate of 78.4% vs. 64.3%, P=0.007). The N2 patients were divided into a single station metastasis group (a N2a1 group), a single station with N1 positive group (a N2a2 group) and a multiple station group (a N2b group), and the percentage was accounted for 22.0% (74/337), 37.7% (127/337) and 40.3% (136/337), respectively. There was a statistical difference in 5-year survival rate (62.2% vs. 56.5% vs. 37.3%) among the three groups (P=0.001). Conclusion    Subgroup analysis of N staging in NSCLC patients shows significant survival differences which may be more consistent with multidisciplinary therapy under precise staging patterns.

Impact of maximum standardized uptake value of non-small cell lung cancer on detecting lymph node involvement in potential stereotactic body radiotherapy candidates.

BACKGROUND: The retrospective study investigated the association between the maximum standardized uptake value (SUVmax) of primary tumor and lymph node involvement in potential stereotactic body radiotherapy (SBRT) candidates. METHODS: A total of 185 patients with clinical stage I NSCLC were enrolled in the current study. All patients underwent lobectomy with systematic lymph node dissection following preoperative FDG-PET/CT scanning. The association between clinicopathological variables and lymph node involvement was analyzed by univariate and multivariate analysis. Spearman's correlation test was used to evaluate the correlation between them. Receiver operating characteristic (ROC) analysis was performed to calculate the area under the curve. RESULTS: Among these patients, 22.1% had occult lymph node involvement, 15.1% were N1 and 7.0% were N2. Greater tumor size (P=0.007), elevated CEA (P=0.006), central location (P=0.002), higher SUVmax (P<0.001), solid nodule type (P=0.002), visceral pleural invasion (P=0.001) and presence of micropapillary and solid patterns (P=0.002) were significantly associated with lymph node involvement. In multivariate analysis, lymph node involvement was associated with central location (OR 5.784, 95% CI: 1.584-21.114, P=0.008), SUVmax (increase of 1 unite, OR 1.147, 95% CI: 1.035-1.272, P=0.009) and visceral pleural invasion (OR 3.044, 95% CI: 1.369-6.769, P=0.006). ROC area under the curve of SUVmax for lymph node involvement was 0.770 (95% CI: 0.698-0.841), the sensitivity and specificity were 85.4% and 63.2%, respectively. Spearman's correlation test showed that SUVmax of tumor mostly depended on tumor size and nodule type. CONCLUSIONS: SUVmax of primary tumor was a predictor of lymph node involvement for potential SBRT candidates. Centrally located tumor and visceral pleural invasion were related to higher rate of nodal metastasis. Lobectomy and systemic lymph node dissection should be performed in these patients, instead of SBRT.

Blockade of Notch3 inhibits the stem-like property and is associated with ALDH1A1 and CD44 via autophagy in non-small lung cancer.

Acquired resistance to standard chemotherapy causes treatment failure in patients with local advanced and advanced non-small lung cancer (NSCLC). Cancer stem cells (CSCs) are a small subpopulation within cancer that is thought to be resistant to conventional chemotherapy. The Notch pathway is one of the most intensively studied for putative therapeutic targets of CSCs in solid tumors. In our study, suppression of Notch3 decreased colony and sphere formation of stem-like property in lung cancer cells. In addition, Notch3 expression was demonstrated to be upregulated in the patients with chemoresistance and related to poor prognosis of NSCLC patients. Our results also showed that CSC markers ALDH1A1 and CD44 were highly expressed in NSCLC patients with chemoresistance and these two markers were positively correlated with Notch3 expression in lung cancer specimens from TCGA database. Furthermore, the lung cancer cells with drug resistance were shown to be associated with activation of autophagy. All the data support a crucial role of Notch3 in the increase of stem-like property in NSCLC cells that might be associated with upregulation of ALDH1A1 and CD44 and activation of autophagy.

Identification of lung adenocarcinoma mutation status based on histologic subtype: Retrospective analysis of 269 patients.

BACKGROUND: To evaluate differences in the clinical characteristics and molecular pathology of lung adenocarcinoma subtypes as defined by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international histological classification. METHODS: We retrospectively reviewed 269 patients with initial primary lung adenocarcinoma who had undergone complete resection at our department from August 2013 to December 2014, focusing on the new histologic subtype classification, clinical characteristics, and molecular pathology. RESULTS: All specimens were invasive adenocarcinoma, and were lepidic (13.0%), papillary (19.7%), acinar (51.7%), solid (8.6%), micropapillary (1.1%) or mucinous predominant (5.9%). Epidermal growth factor receptor (EGFR) mutations were detected in 132 cases (60.3%). Female patients and non-smokers had higher EGFR mutation rates (P = 0.022 and 0.026, respectively). The lepidic, papillary, acinar, solid, micropapillary, and mucinous predominant patterns had EGFR mutation rates of 70.6%, 64.8%, 72.5%, 33.3%, 100%, and 5.9%, respectively. The exon mutation distribution differed according to serum carcinoembryonic antigen (CEA) levels (P = 0.018). v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were detected in 20 cases (9.2%), and were frequently found in the mucinous and solid predominant subtypes. The serum CEA levels differed among the subtypes. CONCLUSIONS: In China, there are significant differences between lung adenocarcinoma histologic subtypes. The presence of well-differentiated components in lung adenocarcinoma indicates higher EGFR mutation rates; the presence of solid or mucinous components indicates higher KRAS mutation rates. Serum CEA levels are associated with histologic subtype and EGFR exon mutations.