Objective To investigate the prognostic value of ERBB2 Exon20ins (Exon20ins) in advanced non-small cell lung cancer (NSCLC) patients receiving first-line chemotherapy combined with immunotherapy. Methods A retrospective analysis was conducted on clinical data from ERBB2-mutant stage IV NSCLC patients who received first-line chemotherapy combined with immunotherapy at West China Hospital of Sichuan University between 2020 and 2024. ERBB2 wild-type patients were matched using propensity score matching. Clinical pathological characteristics, distant metastatic sites, and treatment outcomes were compared among patients with different mutation statuses. The primary endpoint was progression-free survival (PFS), and Kaplan-Meier method was used to plot survival curves. Cox regression analysis was performed to adjust for confounding factors. Results This study included 41 ERBB2-mutant stage IV NSCLC patients, of whom 22 had Exon20ins mutations, and 19 had other ERBB2 mutations. Forty-one ERBB2 wild-type patients were matched for comparison. The mean age of all patients was 60.0±9.3 years, with 61 males (74.4%). A total of 67 patients (81.7%) received chemotherapy combined with immunotherapy, and 15 patients (18.3%) received chemotherapy combined with immunotherapy and anti-angiogenesis therapy. The Exon20ins group showed a higher incidence of lymph node metastasis compared with the ERBB2 other mutation group and the wild-type group (36.4% vs. 15.8% vs. 9.8%, P=0.045). The median PFS in the Exon20ins group was significantly shorter than in the other mutation group (5.8 months vs. 10.3 months, P=0.025) and the wild-type group (5.8 months vs. 8.3 months, P=0.023). Univariate Cox regression analysis indicated that the ERBB2 Exon20ins mutation was an adverse prognostic factor (Exon20ins vs. other ERBB2 mutations, HR=2.9, 95%CI 1.18 - 7.1, P=0.014; Exon20ins vs. wild-type, HR=2.6, 95%CI 1.25 - 5.6, P=0.014). The combination with anti-angiogenesis therapy did not significantly affect the prognosis of PFS (HR=0.66, 95%CI 0.28 - 1.6, P=0.363). Multivariate Cox regression analysis revealed that the ERBB2 Exon20ins mutation was an independent adverse prognostic factor for PFS (Exon20ins vs. other ERBB2 mutations, HR=3.3, 95%CI 1.27 - 8.3, P=0.015; Exon20ins vs. wild-type, HR=2.7, 95%CI 1.2 - 5.88, P=0.014). For the 67 patients receiving chemotherapy combined with immunotherapy, Cox regression analysis showed that the ERBB2 Exon20ins mutation was still associated with poor prognosis in advanced NSCLC (Exon20ins vs. other ERBB2 mutations, HR=3.2, 95%CI 1.12 - 9.1, P=0.030; Exon20ins vs. wild-type, HR=2.5, 95%CI 1 - 5.88, P=0.040). Conclusions Advanced NSCLC patients with ERBB2 Exon20ins mutation have a worse prognosis compared with those with other ERBB2 mutation subtypes or ERBB2 wild-type when treated with first-line chemotherapy combined with immunotherapy. This suggests that ERBB2 Exon20ins mutation, as a particularly refractory mutation, requires the exploration of new combination strategies based on molecular subtyping to improve survival outcomes.
ObjectiveTo detect level of circulating tumor cells (CTCs) in peripheral venous blood of fasting patients with gastric cancer (GC) and to analyze relationships between CTCs and clinicopathologic features and prognosis of patients with GC.MethodsOne hundred patients with GC were selected (GC group), who underwent the surgery and confirmed by the histopathology in the 940 Hospital of Joint Service of PLA, from August 2015 to December 2016. Thirty-eight patients with gastric benign lesions who were treated in this hospital at the same time were selected as the control group. The 7 mL peripheral venous blood of the elbow in the morning was taken from the fasting patients and the CTCs were detected by the immunomagnetic microparticle negative enrichment combined with immunofluorescence in situ hybridization within 24 h. The positive rate of CTCs was calculated and its relationships with the clinicopathologic features (tumor location, tumor invasion depth, degree of differentiation, TNM stage, lymph node metastasis, and vascular tumor thrombus) and the progression-free survival of the patients with GC were analyzed.ResultsThe positive rate of peripheral venous blood CTCs in the GC group was 89.0% (89/100), which was higher than that in the control group (10.5%, 4/38), and the difference was statistically significant (P<0.001). The levels of CTCs in the patients with GC were significantly correlated with the tumor invasion depth (P=0.017), lymph node metastasis (P=0.038), and TNM stage (P=0.016), which were not associated with the age, gender, tumor location, degree of differentiation, and vascular tumor thrombus (P>0.050). The predictive value of CTCs for the diagnosis of GC was significantly superior to that of the tumor markers CEA, CA19-9, or CA125. The progression-free survival of patients with low CTCs expression was significantly longer than that in the patients with high CTCs expression (χ2=5.172, P=0.023).ConclusionsDetecting CTCs of patients with GC by immunomagnetic particle negative enrichment combined with immunofluorescence in situ hybridization has a high sensitivity. And it can improve early diagnosis of patients with GC. Preoperative CTCs detection has a certain value in guiding staging of GC and predicting prognosis of patients with GC.