Pemetrexed-based chemotherapy for non-small-cell lung cancer patients with EGFR exon 20 insertion mutation: a multicenter study.

BACKGROUND: Chemotherapy is the major choice for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor exon 20 insertion (EGFR ex20ins). The efficacy of pemetrexed-based with other chemotherapy regimens and EGFR ex20ins subtypes in this population has not been well studied. METHODS: We screened patients with EGFR ex20ins by next-generation sequencing (NGS) from a large cohort. The clinicopathologic and medical information were collected in advanced NSCLC patients with EGFR ex20ins. We also compared the clinical outcomes among patients with different subtypes of EGFR ex20ins. RESULTS: We retrospectively collected 119 stage IIIB/IV NSCLC patients with EGFR ex20ins from 9142 NSCLC patients across China from June 2013 to December 2018. The subtypes of EGFR ex20ins included A767_V769dupASV (33/119, 27.73%), S768_D770dupSVD (19/119, 15.97%), N771_H773dupNPH (11/119, 9.24%), A763_Y764insFQEA (2/119, 1.68%) and others (54/119, 45.38%). A total of 64.7% (77/119) of patients received pemetrexed-based first-line chemotherapy and 13.45% (16/119) of patients received pemetrexed-based second-line chemotherapy. Pemetrexed-based chemo-treated patients had longer median progression-free survival (PFS) than patients without pemetrexed-based chemo-treated (5.5 vs. 3.0 months, P=0.0026). Survival data was available for 66 patients and the median overall survival (OS) was 24.7 months. Pemetrexed-based chemo-treated patients had longer OS tendency than patients without pemetrexed-based chemo-treated (25.0 vs. 19.6 months, P=0.0769). Patients harboring A767_V769dupASV had better OS than other subtypes of EGFR ex20ins but without statistical significance (P=0.0676). Multivariate analysis revealed that histological type of NSCLC and bone-metastasis before treatment were independent prognostic factors for OS in all patients after adjusting all characteristic and treatment factors (P<0.05). CONCLUSIONS: To the best of our knowledge, it is the largest cohort study of advanced NSCLC patients with EGFR ex20ins across China. Pemetrexed-based treatment could have better control of disease than non-pemetrexed-based chemotherapies in this population. Furthermore, more effective agents are expected for patients harboring EGFR ex20ins.

The role of segmental nodes in the pathological staging of non-small cell lung cancer.

BACKGROUND: Segmental nodes are not examined routinely in current clinical practice for lung cancer, the role of segmental nodes in pathological staging of non-small cell lung cancer after radical resection was investigated. METHODS: A total of 113 consecutive non-small cell lung cancer patients who underwent radical resection between June 2009 and December 2011 were retrospectively reviewed. All the operations were performed by the same group of surgeons. N2 nodes, hilar nodes, interlobar nodes and some lobar nodes were collected during surgery. The removed lung lobes were dissected routinely along lobar and segmental bronchi to collect lobar nodes and segmental nodes. The collected lymph nodes were separately labeled for histological examination. RESULTS: The detection rates of hilar nodes, interlobar nodes, lobar nodes and segmental nodes were 61.1%, 85.0%, 75.2% and 80.5%, respectively. The metastasis rates of hilar nodes, interlobar nodes, lobar nodes and segmental nodes were 5.3%, 10.5%, 16.8% and 14.2%, respectively. There were 68 cases of N0 disease, 16 cases of N1 disease and 29 cases of N2 disease. If an analysis of segmental lymph nodes had been omitted, six patients (37.5% of N1 disease) would have been down-staged to N0, and two cases of multiple-zone N1 disease would have been misdiagnosed as single-zone N1 disease, one patient would have been misdiagnosed as N2 disease with skip metastases. CONCLUSION: Segmental nodes play an important role in the accurate staging of non-small cell lung cancer, and routinely dissecting the segmental bronchi to collect the lymph nodes is feasible and may be necessary.

Complete mediastinal lymph node dissection in video-assisted thoracoscopic lobectomy versus lobectomy by thoracotomy.

BACKGROUND: Although video-assisted thoracic surgery (VATS) lobectomy has been used more and more frequently for the treatment of patients with early-stage lung cancer, controversies are mainly focused on whether the complete mediastinal lymph node dissection (MLND) can be achieved by VATS. This retrospective study aimed to compare the validity of MLND between VATS and open thoracotomy. METHODS: Patients with lung cancer were matched from a pool of pulmonary lobectomies performed by one surgeon. Patients undergoing VATS were matched with those undergoing thoracotomy in terms of gender, age, clinical tumor stage, tumor location, and surgical procedure. RESULTS: After matching, 31 patients in VATS group and 31 patients in open group were eligible for analysis. In the VATS and open groups, the mean total number of dissected lymph nodes was 28.2 ± 8.4 and 29.8 ± 11.6 (p = 0.517), respectively. In the VATS and open groups, the number of N1 nodes was 9.5 ± 4.1 and 8.4 ± 4.7 (p = 0.333), respectively. And the number of N2 nodes was also similar between the VATS and open group (18.6 ± 7.0 vs 21.4 ± 10.0, p = 0.211). No significant differences were observed between the two groups in the operating time, the blood loss, the length of chest tube drainage, the length of hospital stay, and the rate of specific complications. CONCLUSION: Our early experience suggests that, with regard to the number of the dissected lymph nodes, VATS lobectomy can achieve complete MLND, compared with the traditional approach. MLND by VATS is technically feasible and safe for early-stage lung cancer.

The accumulation and prognosis value of tumor infiltrating IL-17 producing cells in esophageal squamous cell carcinoma.

BACKGROUND: The role of IL-17 producing cells in tumors is controversial. In the present study, we investigated the prognostic value of measuring tumor-infiltrating IL-17 producing cell levels in human esophageal squamous cell carcinoma (ESCC). METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemical staining was performed to investigate the levels of IL-17+ tumor infiltrating lymphocytes (TILs), as well as CD8+ cytotoxic T lymphocytes (CTLs) and CD57+ natural killer (NK) cells from 181 ESCC patients. The prognostic value of measuring the densities of IL-17+TILs and the correlation with CTLs and NK was evaluated. IL-17 producing cells were detected in esophageal squamous cell carcinoma tissues. The IL-17 producing cells were major CD4 positive, but Foxp3 negative. The median level of IL-17+TILs was 3.90 cells/high power microscopic field (HPF). The density of IL-17 producing cells correlated negatively with T stage (P=0.042). The higher densities of tumor infiltrating IL-17+ lymphocytes were associated with better overall survival (P=0.031). Furthermore, we found that there were positive correlations between levels of IL-17 producing cells and the densities of CD8+cells, as well as CD57+cells (r=0.198, P=0.008 for CD8+ cells and r=0.261, P<0.001 for CD57+ cells, respectively). The prognosis analysis also showed that the higher levels of CD8+ CTLs and CD57+ NK cells correlated with better overall survival of ESCC patients. CONCLUSIONS: Our study suggests that tumor infiltrating IL-17 producing cells in ESCC patients may have protective roles in the tumor microenvironment and may be treated as a prognostic marker for ESCC patients.