Heterogeneity and Clinical Effect of Epidermal Growth Factor Receptor in Primary Lung and Brain Metastases of Nonsmall Cell Lung Cancer.

INTRODUCTION: This study aimed to analyze the heterogeneity in epidermal growth factor receptor (EGFR) gene mutation and its impact on clinical outcomes in primary tumor and corresponding brain metastasis (BM) in nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Primary pulmonary tumors and paired BMs of 27 NSCLC patients were surgically removed. All brain lesions were histologically confirmed as metastatic NSCLC. EGFR gene mutation status was detected by using amplification refraction mutation system. McNemar test was performed to compare EGFR mutation status between lung primary tumors and metastatic brain tumors and Kappa test was performed to quantify the agreement between the two. RESULTS: Of the 27 patients, nine cases were found to have EGFR mutations in BMs and 10 had a positive EGFR mutation status in primary lung tumor tissue. The rate of consistency of the matched tumor was 24/27 (88.9%). Among the three cases presenting EGFR mutational heterogeneity, two patients harbored an EGFR mutation in the primary tumor but not in the BMs; meanwhile, the last patient demonstrated the opposite pattern. Compared to patients with consistent EGFR mutations, patients with inconsistent mutations showed better outcomes. Further analysis revealed that the two patients whose EGFR mutant-type primary tumor progressed to wild-type cerebral metastatic tumor had longer overall survival than the patient whose EGFR wild-type primary tumor progressed to mutant-type brain metastatic tumor. CONCLUSIONS: Heterogeneity of EGFR mutation status was observed between primary NSCLC and paired BM. Patients possessing a wild-type EGFR mutation in BM might have better outcomes, especially those with transition from mutant to wild-type.

A new method for accurately localizing and resecting pulmonary nodules.

With the use of low-dose CT for early screening of lung cancer, more and more early lung cancers are found. At the same time, patients with small lung nodules have also increased, it is a great challenge for surgeons to resect pulmonary nodules with small volume, deep position and no solid components under video-assisted thoracoscopic surgery. Many studies have reported preoperative and intraoperative methods for localizing lung nodules before minimally invasive resection. Methods for preoperative localization include CT-guided hook-wire positioning, coil positioning, or dye injection and radionuclide location Methods for intraoperative localization include intraoperative ultrasound localization and tactile pressure-sensing localization. After the localization of pulmonary nodules under the guidance of CT patients need to restrict their activities; otherwise, it is easy for the nodules to move, causing the operation to fail, and may also cause complications such as pneumothorax, puncture site pain, and pulmonary parenchymal bleeding. In the past, we injected melamine dye under the guidance of electromagnetic navigation bronchoscope to locate lung nodules. The purpose of this case is introducing a new method for accurately localizing and resecting pulmonary nodules by injecting indocyanine green (ICG) under the guidance of electromagnetic navigation bronchoscope and the resection of small pulmonary nodules under the fluoroscope.

Impact of Different Types of Lymphadenectomy Combined With Different Extents of Tumor Resection on Survival Outcomes of Stage I Non-small-cell Lung Cancer: A Large-Cohort Real-World Study.

Background: To investigate the prognostic impact of different types of lymphadenectomy with different extents of tumor resection on the outcomes of stage I non-small-cell lung cancer (NSCLC). Methods: Patients were classified into lobectomy and sublobectomy groups, and then each group was subdivided according to the types of lymphadenectomy. The end points of the study were overall survival (OS) and disease-free survival (DFS). Propensity score matched (PSM) comparative analysis and univariate and multivariate Cox regression analyses were performed. Result: A total of 1,336 patients were included in the current study. Lobectomy was associated with better OS and DFS. In the lobectomy group, lobectomy with bilateral mediastinal lymphadenectomy (BML) was associated with better OS than lobectomy with systematic nodal dissection (SND) or lobe-specific systematic node dissection (L-SND). Lobectomy with SND or L-SND was associated with better OS than lobectomy with systematic nodal sampling (SNS) or selected lymph node biopsy (SLNB). Additionally, lobectomy with BML or SND was associated with better DFS than lobectomy with L-SND or SNS or SLNB. After PSM, compared with lobectomy with SNS or SLNB, lobectomy with SND resulted in more favorable OS and DFS. There was no survival difference between different types of lymphadenectomy for patients who underwent sublobectomy. A multivariable analysis revealed independent associations of lobectomy with BML or SND with better OS and DFS compared with those of lobectomy with SNS or SLNB. Conclusion: This study reveals an association of lobectomy with more systematic and complete lymph node dissection, such as BML or SND, with better prognosis in stage I NSCLC patients.

Time distribution of recurrence risk of oesophageal squamous cell carcinoma with complete resection (R0) in a Chinese population.

OBJECTIVES: We aimed to clarify the correlation between clinic-pathological characteristics and the distribution of recurrence probability during follow-up of oesophageal squamous cell carcinoma (OSCC) patients with complete resection analysis by hazard function, and to try to provide evidence-based data for optimal timing for adjuvant therapy. METHODS: A single-institution, retrospective study was conducted on 553 Chinese patients with OSCC who underwent R0 resection between January 2005 and October 2007. Survival curves were generated using the Kaplan-Meier method, and hazard function was used to analyse the annual recurrence hazard. RESULTS: The median recurrence-free survival time of these patients was 3.4 years. In univariate analysis, the favourable prognostic factors were gender, smoking status, a tumour length of ≤4.0 cm, tumour invasion thickness, normal level of squamous cell carcinoma (SCC) antigen, pathological T category and pathological N category. In multivariate analysis, pathological T category and pathological N category were independent prognostic factors. Overall, the recurrence hazard curve for the entire cohort showed that the first major recurrence surge began to increase from the first year at 22.97% and peaked at 1.3 years at 27.4% during follow-up. The second recurrence surge peaked during the seventh year at 13.0%. A lower recurrence risk was observed in patients with the following clinic-pathological characteristics: gender, smoking status and N0. CONCLUSIONS: We identify the presence of two peaks for recurrence risk in Chinese patients with resectable OSCC, which might contribute to choosing the optimal timing for adjuvant therapy after an operation to decrease or delay the recurrence hazard for patients with resectable OSCC.

Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase rearrangement and epidermal growth factor receptor mutation coexisting in Chinese patients with lung adenocarcinoma.

BACKGROUND: The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement is almost in mutual exclusion to epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, with rare exceptions. This study aimed to search for the coexisting gene alterations in Chinese patients with lung adenocarcinoma (LAC). METHODS: We detected mutations in the EGFR, KRAS, and ALK gene rearrangements in samples from 131 Chinese patients with LAC. ALK rearrangements were identified by fluorescent in situ hybridization. Mutations in EGFR (exons 19 to 21) and KRAS (codons 12 and 13) were determined by real time polymerase chain reaction. RESULTS: All patients were classified into four distinct genotype groups: EGFR mutations (n = 63; 48.1%), ALK rearrangements (n = 9; 6.9%), KRAS mutations (n = 8; 6.1%), and the wild-type (unmutated) genotype of all three genes (WT/WT/WT) (n = 53; 40.5%). Interestingly, two never-smoking women (2/131, 1.5%) harbored coexisting ALK rearrangement and EGFR mutation. ALK rearrangement occurred more frequently in young patients (8/9) (P = 0.687), non-smokers (8/9) (P = 0.077), and those who had no family history of LAC (8/9) (P = 1.000); all KRAS mutations occurred in the EGFR wild type (P = 0.007). KRAS mutations were generally detected in young patients (6/8) (P = 0.658) and in those who had no family history (7/8) (P = 1.000); EGFR mutations correlated with gender (P = 0.001), and smoking status (P < 0.001). CONCLUSIONS: Two patients harboring both EGFR mutation and EML4-ALK rearrangement were detected in this study. Our data was apparently inconsistent with the traditional view that the EML4-ALK fusion gene in patients is resistant to EGFR-TKIs.

High plasma fibrinogen concentration and platelet count unfavorably impact survival in non-small cell lung cancer patients with brain metastases.

High expression of fibrinogen and platelets are often observed in non-small cell lung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P < 0.001), and platelet count (P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months; P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.