Role of skip N2 lymph node metastasis for patients with the stage III-N2 lung adenocarcinoma: a propensity score matching analysis.

PURPOSE: Recent studies have indicated some differences in the prognosis of patients with stage III-N2 lung adenocarcinoma, and the prognosis of patients with skip N2 lymph node metastasis (SKN2) is good. This study grouped patients with stage III-N2 lung adenocarcinoma by propensity score matching (PSM) to evaluate the impact of SKN2 on the prognosis of these patients. METHODS: The clinical data for patients who underwent radical lobectomy and had a postoperative pathological diagnosis of stage III-N2 lung adenocarcinoma at our centre from 2016 to 2018 were collected, and PSM was performed at a ratio of 1:1. RESULTS: A total of 456 patients were enrolled in this study. After PSM, 112 patients were included in the SKN2 group, and 112 patients were included in the non-SKN2 group. When comparing the SKN2 group with the non-SKN2 group, the 3-year OS rate was (71.4% vs. 12.5%, p < 0.001), and the 3-year DFS rate was (35.7% vs. 5.4%, p < 0.001). It is further divided into four groups:single-station SKN2 (N2a1),Multi-station SKN2 (N2a2),single-station non-SKN2 (N2b1) and Multi-station non-SKN2 (N2b2).The 3-year OS and DFS rates of skip lymph node metastasis were better than those of non-skip lymph node metastasis(OS:N2a1 vs. N2b1 68.4% vs. 23.5%,p < 0.001;N2a2 vs. N2b2 73.0% vs. 7.7%,p < 0.001)(DFS:N2a1 vs. N2b1 68.4% vs. 5.9%,p < 0.001;N2a2 vs. N2b2 62.2% vs. 5.1%,p < 0.001), regardless of the number of N2 station(OS:N2a1 vs. N2a2 68.4% vs. 73.0%,p = 0.584;N2b1 vs. N2b2 23.5% vs. 7.7%,p = 0.051). On multivariate analysis, sex (p = 0.008) ,Vascular tumour thrombus(p = 0.047),size(p = 0.002)and SKN2 (p < 0.001) were independent predictors of OS. CONCLUSION: For patients with stage III-N2 lung adenocarcinoma, the prognosis of SKN2 patients is better than non-SKN2 patients', and SKN2 may be used as an important factor in the N2 subgroup classification in future TNM staging.

Postoperative survival of pulmonary invasive mucinous adenocarcinoma versus non-mucinous invasive adenocarcinoma.

PURPOSE: In 2015, the World Health Organization renamed mucinous bronchioloalveolar adenocarcinoma as pulmonary invasive mucinous adenocarcinoma (IMA). Due to its low incidence and unclear prognosis with surgical treatment, previous studies have presented opposing survival outcomes. We aimed to investigate the differences in surgical prognosis and prognosis-related risk factors by comparing IMA with non-mucinous invasive adenocarcinoma (NMA). METHODS: A total of 20,914 patients diagnosed with IMA or NMA from 2000 to 2014 were screened from the Surveillance, Epidemiology, and End Results database. The screened patients were subjected to propensity score matching (PSM) in a 1:4 ratio to explore the survival differences between patients with IMA and NMA and the factors influencing prognosis. RESULTS: For all patients, IMA was prevalent in the lower lobes of the lungs (p < 0.0001), well-differentiated histologically (p < 0.0001), less likely to have lymph node metastases (94.4% vs. 72.0%, p < 0.0001) and at an earlier pathological stage (p = 0.0001). After PSM, the IMA cohort consisted of 303 patients, and the NMA cohort consisted of 1212 patients. Kaplan‒Meier survival analysis showed no difference in overall survival (OS) between patients in the IMA cohort and those in the NMA cohort (p = 0.7). Cox proportional hazards analysis showed that differences in tumor pathological type did not influence OS between the two cohorts (p = 0.65). Age (HR: 1.98, 95% CI 1.7-2.31, p < 0.0001), gender (HR: 0.64, 95% CI 0.55-0.75, p < 0.0001), and radiation treatment (HR: 2.49, 95% CI 1.84-3.37, p < 0.0001) were independent predictors of patient OS. CONCLUSION: There was no significant difference in OS between patients with IMA and those with NMA after surgical treatment. Age, sex, and radiation treatment can independently predict OS.

Case report: Different mechanisms of drug resistance in a synchronous multiple primary lung cancer patient after EGFR-TKI treatment.

Non-small-cell lung cancer (NSCLC) is the most common cancer in the world. In recent years, the incidence of synchronous multiple primary lung cancer (SMPLC) has gradually increased. Surgery is the preferred method to treat these patients. The management of SMPLC patients who cannot tolerate surgical treatment is controversial. We report a rare case in which a 70-year-old Chinese woman with no history of smoking had three primary lung adenocarcinoma lesions. Two lesions had epidermal growth factor receptor (EGFR) exon 19 deletion mutations, and one lesion had the L858R mutation. After first-generation EGFR-tyrosine kinase inhibitor (TKI) treatment, the three lesions all showed a good response until disease progression. After the corresponding drug treatments were given based on the different drug resistance mechanisms, good responsiveness was shown in each lessions. This case suggests that in the treatment of SMPLC, it is necessary to learn the molecular-biological information of each lesion due to the differences thereof, and a targeted treatment regimen should be developed on this basis.

Adjuvant chemotherapy can benefit the survival of stage I lung adenocarcinoma patients with tumour spread through air spaces after resection: Propensity-score matched analysis.

Background: It is still unclear whether stage I lung adenocarcinoma patients with tumour spread through air spaces (STAS) can benefit from postoperative adjuvant chemotherapy (ACT) after lobectomy. This study investigated the effect of ACT on the postoperative survival of patients with stage I (STAS+) lung adenocarcinoma. Methods: We retrospectively analysed the clinical data of stage I (STAS+) invasive lung adenocarcinoma patients who underwent lobectomy in the Department of Thoracic Surgery of our hospital from January 1, 2013 to January 1, 2016. Propensity score matching (PSM) was performed to group patients to investigate whether ACT could lead to better prognosis of patients. Results: A total of 593 patients with stage I (STAS+) lung adenocarcinoma were enrolled. The study after PSM included 406 patients. Kaplan-Meier survival analysis showed the experimental group had a better 3-year recurrence-free survival (RFS) rate (p = 0.037) and the 5-year RFS rate (p = 0.022) than the control group. It also had higher 5-year overall survival (p = 0.017). The multivariate analysis by Cox proportional hazard regression model showed that stage I STAS+ lung adenocarcinoma patients with lymphatic vessel invasion (HR: 1.711, 95% CI: 1.052-2.784; p = 0.045), vascular invasion (HR: 5.014, 95% CI: 3.154-7.969; p < 0.001), and visceral pleural invasion (HR: 2.086, 95% CI: 1.162-3.743; p = 0.014), and without ACT (HR: 1.675, 95% CI: 1.043-2.689; p = 0.033) had a significant survival disadvantage. Conclusion: ACT can boost the postoperative survival of patients with stage I (STAS+) lung adenocarcinoma.

Cystathionine ß-synthase expression correlates with tumor development and poor prognosis in lung squamous cell carcinoma patients.

The purpose of this study was to investigate the correlation between the expression of cystathionine ß-synthase (CBS) in lung squamous cell carcinoma (LUSC) and the microvascular density (MVD) and clinicopathological features. Firstly, the expression status of CBS in diffuse carcinoma and LUSC was searched through the public bioinformatics database. Subsequently, immunohistochemical staining and scoring were performed on tumor tissues and matched normal tissues from 108 LUSC patients to assess CBS expression; the MVD of tumor tissues was also detected. The results showed that CBS was overexpressed in some tumor tissues, including LUSC. Immunohistochemical results showed that the positive expression rate of CBS in tumor tissues (63.0%) was higher than that in normal tissues (17.6%). The expression of CBS was correlated with T (p=0.01), N (p=0.004), TNM (p=0.011) stages, and tumor differentiation degrees (p<0.001), with the increase of T, N, and TNM stages or the decrease of differentiation, the expression level of CBS also increased. In addition, the expression level of CBS was positively correlated with MVD (r=0.6997, p<0.0001). Survival analysis showed that the survival rate of the CBS negative expression group was better than that of the positive expression group (p=0.004). Cox multivariate analysis showed that CBS expression status (p<0.001), T stages (p=0.020), and TNM stages (p=0.021) were independent factors affecting the prognosis of LUSC. In conclusion, the high expression of CBS affects tumor development and is associated with the poor prognosis of LUCS, which may be used as a biomarker to evaluate prognosis and find a new direction for the treatment of LUSC.

Application Value of PET/CT and MRI in the Diagnosis and Treatment of Patients With Synchronous Multiple Pulmonary Ground-Glass Nodules.

Background: Synchronous multiple ground-glass nodules (SMGGNs) in synchronous multiple lung cancers are associated with specific imaging findings. It is difficult to distinguish whether multiple nodules are primary tumors or metastatic lesions in the lungs. The need for PET/CT and contrast-enhanced brain MRI for these patients remains unclear. This study investigated the necessity of these two imaging examinations for SMGGN patients by means of retrospective analysis. Methods: SMGGN patients who were diagnosed and treated in our hospital from October 2017 to May 2020 and underwent whole-body PET/CT(Cranial excepted) and/or contrast-enhanced brain MRI+DWI were enrolled in this study. We analyzed the imaging and clinical characteristics of these patients to evaluate SMGGN patients' need to undergo whole-body PET/CT and brain MRI examination. Results: A total of 87 SMGGN patients were enrolled. 51 patients underwent whole-body PET/CT examinations and did not show signs of primary tumors in other organs, metastatic foci in other organs, or metastasis to surrounding lymph nodes. 87 patients underwent whole-brain MRI, which did not reveal brain metastases but did detect an old cerebral infarction in 23 patients and a new cerebral infarction in one patient. 87 patients underwent surgical treatment in which 219 nodules were removed. All nodules were diagnosed as adenocarcinoma or atypical adenomatous hyperplasia. No lymph node metastasis was noted. Conclusion: For SMGGN patients, PET/CT and enhanced cranial MRI are unnecessary for SMGGNs patients, but from the perspective of perioperative patient safety, preoperative MRI+DWI examination is recommended for SMGGNs patients.

Clinical characteristics and prognostic value of EGFR mutation in stage I lung adenocarcinoma with spread through air spaces after surgical resection.

The clinical data of stage I invasive lung adenocarcinoma patients with spread through air spaces (STAS) who underwent lobectomy from January 1, 2013 to January 1, 2016 at the Department of Thoracic Surgery of Hebei Medical University were analyzed retrospectively, and statistical analysis was carried out to explore their clinical features and prognostic value of EGFR mutation. A total of 280 patients were included in the study cohort, and EGFR mutations were detected in 154 patients. EGFR mutations were more common in non-smokers (p=0.045), females (p<0.001), without vascular tumor thrombus (p=0.037), and histological subtype LPA/APA/PPA (p=0.001). Multivariate analysis of the Cox risk regression model showed that EGFR gene mutation (p=0.807) was not an independent influencing factor of recurrence-free survival (RFS), but EGFR mutation was an independent influencing factor of overall survival (OS) (p=0.012), and OS of patients with EGFR mutation was better. The EGFR mutation also significantly increased the progression-free survival (PFS) of relapsed patients (p<0.001), but the PFS of relapsed EGFR mutation patients who received adjuvant chemotherapy after the operation was worse than that of patients who did not receive adjuvant chemotherapy (p=0.029). EGFR gene mutation is not a risk factor for postoperative recurrence in patients with stage I lung adenocarcinoma with STAS but the 5-year survival rate of patients with EGFR gene mutation is better than that of wild-type. Postoperative adjuvant chemotherapy for patients with EGFR mutation should be carefully considered.

The Influence of KDR Genetic Variation on the Efficacy and Safety of Patients With Advanced NSCLC Receiving First-Line Bevacizumab Plus Chemotherapy Regimen.

OBJECTIVE: Angiogenesis plays an important role in the growth and metastasis of non-small cell lung cancer (NSCLC). Bevacizumab is a humanized monoclonal antibody that mainly acts on vascular endothelial growth factor A (VEGFA). Kinase insert domain receptor (KDR) is the most important target of VEGFA. The aim of present study was to investigate the influence of KDR genetic variation on the efficacy and safety of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimen. METHODS: A total of 169 patients with advanced NSCLC who received bevacizumab combined with chemotherapy were recruited in this study. Clinical outcome of the regimens was evaluated in the hospital. Peripheral blood and biopsy tissue specimens of patients were collected for the genotyping of KDR genetic variation and KDR mRNA expression, respectively. The association between KDR genotype status and other variables were analyzed. Univariate analysis of genotype status and prognosis was implemented using the Kaplan-Meier survival analysis method. Multivariate Cox regression analysis was performed to adjust the confounding factors. RESULTS: Of the polymorphisms analyzed, only V297 L was of clinical significance. The prevalence of V297 L among the study population were as follows: CC genotype 123 cases (72.8%), CT genotype 41 cases (24.3%), TT genotype 5 cases (2.9%). The minimum allele frequency is 0.15. The distribution frequencies of the 3 genotypes corresponded with Hardy-Weinberg equilibrium (P = 0.489). Patients with TT and CT genotypes were merged in the subsequent comparison of clinical outcomes. The analysis of efficacy exhibited that the objective response rates (ORR) of patients with CC genotype and CT/TT genotypes were 52.8% and 47.8% (P = 0.561), respectively. Prognosis indicated that the median progression free survival (PFS) of patients with CC genotype and CT/TT genotype were 8.9 and 5.5 months, respectively (P = 0.006). The median OS of the 2 genotypes were 20.0 and 14.9 months, respectively (P = 0.021). Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS [hazard ratio (HR) = 1.59, P = 0.011). Safety profile according to genotype status of V297 L failed to find significant difference. Interestingly, the expression of KDR mRNA of patients with CT/TT genotype was significantly higher than that of patients with CC genotype in the 58 cancer tissue specimens (P < 0.001). CONCLUSION: The clinical comes of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimens might be impacted by polymorphism V297 L through mediating the mRNA expression of KDR.

Tumor-associated eosinophilia in a patient with EGFR-positive, MET-amplified lung adenocarcinoma refractory to targeted therapy: a case report and review of literature.

Paraneoplastic eosinophilia is a rare complication observed in 1% solid tumor cases and appears to have tumor type-dependent prognostic impact, in which the increased eosinophil count was generally associated with unfavorable prognosis. In the English literature, more than 20 patients have been reported of eosinophilia associated with primary non-small cell lung cancer (NSCLC) at diagnosis, all of whom underwent either surgery, chemotherapy, or symptomatic therapy. Herein, we describe clinical course a stage IV NSCLC patient with paraneoplastic eosinophilia and leukocytosis and receiving targeted therapy. A 64-year-old male former smoker was diagnosed with lung adenocarcinoma harboring EGFR L858R mutation and MET amplification. Blood eosinophilia was manifested at diagnosis and confirmed to be paraneoplastic by eliminating other potential causes. The disease progressed rapidly within a month on EGFR inhibitor icotinib and then within three months on icotinib plus crizotinib after rapid response within the first month. A multi-target kinase inhibitor anlotinib was added, and the disease progressed one month later despite initial self-reported asymptomatic high-performance status. The patient was lost to subsequent follow-ups. Radiographic evaluation of disease control or progression coincided with respective distinct alleviation or worsening of eosinophilia. Consistent with previous reports of poor clinical outcome associated with blood eosinophilia, our results suggested a negative prognostic impact in EGFR-/MET-altered NSCLC. This case is, to the best of our knowledge, the first to provide evidence for blood eosinophilia paralleling disease progression in an EGFR- and MET-altered lung adenocarcinoma under targeted therapy, which suggested negative prognostic impact of blood eosinophilia in driver-positive NSCLC.

A case of different gene mutations in primary and metastatic lesions after EGFR-TKI treatment of lung cancer.

BACKGROUND: It remains controversial whether patients with EGFR-mutant lung adenocarcinoma should stop using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) after progression during treatment. CASE REPORT: We report a 35-year-old man with poorly differentiated adenocarcinoma of the left upper lobe and an exon 19 deletion (Ex19Del) mutation found by large-panel next-generation sequencing. The patient underwent video-assisted thoracoscopic surgery 12 months after oral administration of icotinib 125 mg tid, and the left upper lobe and surrounding lymph nodes were removed. Postoperative pathology supported a diagnosis of left upper lobe adenocarcinoma and subcarinal (1/2), main pulmonary artery window (1/2), and left hilar (1/2) lymph node metastases. The EGFR mutations in the residual lesions had disappeared, and Ex19Del mutations were still visible in the mediastinal lymph node metastasis. CONCLUSION: Spatial heterogeneity of the resistance mechanism may explain why patients who continue to receive EGFR-TKIs in combination with local therapies (e.g., radiotherapy) for progressing lesions may benefit even after progression during EGFR-TKI therapy. The loss of the EGFR mutation allele as a putative resistance mechanism requires additional preclinical and clinical confirmation.