(1) Background: Afatinib has been approved for patients with non-small cell lung cancer (NSCLC) carrying major uncommon epidermal growth factor receptor gene (EGFR) mutations. Dacomitinib, another second-generation tyrosine kinase inhibitor, has also shown promising potential for uncommon EGFR mutations. However, no comparative study has been conducted. (2) Methods: Two cohorts were employed: the AFANDA cohort, an ambispective cohort including 121 patients with uncommon EGFR mutations admitted to two tertiary hospitals in China, and an external validation afatinib cohort (ex-AC), extracted from the Afatinib Uncommon EGFR Mutations Database (N = 1140). The AFANDA cohort was divided into an afatinib cohort (AC) and a dacomitinib cohort (DC) for internal exploration. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were assessed for comparison. Progression patterns and resistance mechanisms were explored. (3) Results: In total, 286 patients with advanced NSCLC carrying uncommon EGFR mutations treated with afatinib or dacomitinib were enrolled, including 79 in the AFANDA cohort (44 in the DC, 35 in the AC) and 207 in the ex-AC. In internal exploration, the ORR of the DC was significantly higher than that of the AC (60.5 vs. 26.7%, p = 0.008), but there was no significant difference in median PFS between the DC and the AC (12.0 months vs. 10.0 months, p = 0.305). Multivariate analysis confirmed an independent favorable effect of dacomitinib on PFS (hazard ratio (HR), 1.909; p = 0.047). In external validation, multivariate analysis confirmed the independent prognostic role of dacomitinib in PFS (HR, 1.953; p = 0.029). Propensity score matching analysis confirmed the superiority of dacomitinib over afatinib in terms of PFS in both univariate and multivariate analyses. Toxicity profiling analysis suggested more G1 (p = 0.006), but fewer G3 (p = 0.036) AEs in the DC than in the AC. Progression patterns revealed that the incidence of intracranial progression in the AC was significantly higher than that in the DC (50 vs. 21.1%, p = 0.002). Drug resistance analysis indicated no significant difference in the occurrence of T790M between the AC and the DC (11.8 vs. 15.4%, p = 0.772). (4) Conclusions: Compared with afatinib, dacomitinib demonstrated a more favorable activity with manageable toxicity and different progression patterns in patients with NSCLC carrying uncommon EGFR mutations.

Background: Evidence on the influence of programmed death‐ligand 1 (PD‐L1) expression on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in EGFR‐mutant non‐small cell lung cancer (NSCLC) patients is at variance.Methods: A single‐center retrospective study was conducted to evaluate the influence of PD‐L1 expression on the efficacy of EGFR‐TKIs for NSCLC patients with EGFR mutation. Clinical information was retrieved from electronic medical records. The patients were divided into three subgroups according to PD‐L1 expression level: PD‐L1 < 1% (negative), PD‐L1 1%–49% and PD‐L1 ≥ 50%. The clinicopathological features, overall response rate (ORR), progression‐free survival (PFS) and comutation information were collected and compared between the three subgroups.Results: A total of 117 patients were included. For PD‐L1 < 1%, PD‐L1 1%–49% and PD‐L1 ≥ 50% group, there were 39 (33.3%), 51 (43.5%) and 27 (23.0%) patients respectively, and the ORR was 43.2%, 64.0%, and 51.9%, respectively (p = 0.162), and the median progression‐free survival (mPFS) was 22.0 months (95% CI: 14.0–29.9 months), 15.4 months (95% CI: 8.9–21.8 months) and 13.0 months (95% CI: 10.6–15.3 months), respectively (log‐rank, p = 0.01). The mPFS was negatively correlated with PD‐L1 expression level (r = −0.264, p = 0.041) and PD‐L1 expression was an independent risk factor for worse PFS of EGFR‐TKIs in multivariate Cox regression. Patients with concurrent TP53 mutation had shorter PFS (p = 0.039) and the patients harboring both mutant TP53 and positive PD‐L1 had the shortest PFS (p = 0.006).Conclusions: The efficacy of EGFR‐TKIs was influenced by the baseline PD‐L1 expression. Higher PD‐L1 expression was associated with shorter PFS. The combined indicators of TP53 and PD‐L1 identified subgroups showing divergent benefits from EGFR‐TKIs.

Esophageal squamous cell carcinoma comprises the majority of esophageal carcinoma in the Eastern Asia. The need of early detection of precancerous neoplastic lesions and cancer has been necessitated due to the probability of progression to the advanced stage and its poor prognosis. In recent times, many endoscopic modalities have come into practice for early detection and treatment. Endoscopic radiofrequency ablation (RFA) has been recommended as an efficient therapy in treating the dysplastic mucosa in Barretts esophagus (BE). Its potential in reversing neoplastic lesions in squamous epithelium has been gradually explored. This article is aimed at reviewing the current evidence regarding the use of RFA on esophageal squamous cell neoplasia.

Background: Although some targeted therapies have been shown to be effective in treating HER2‐altered non‐small cell lung cancer (NSCLC), the survival demands have not yet been met due to the high cost and limited availability. This study aimed to assess the effectiveness and safety of pyrotinib plus antiangiogenic agents, including apatinib, anlotinib, and bevacizumab, in previously treated patients with HER2‐altered advanced NSCLC.Methods: In this retrospective real‐world study, patients with HER2‐altered NSCLC who received pyrotinib plus antiangiogenic agents as a second‐ or later‐line treatment between November 2015 and January 2022 were reviewed. The objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety profiles of patients were analyzed.Results: A total of 107 patients were included in the analysis, of which 59 patients (55.1%) had received at least two lines of prior chemotherapy or tyrosine kinase inhibitors. Most of them (87.9%) were identified as harboring HER2 exon 20 insertions. At the data cutoff date (May 13, 2022), the ORR, DCR, median PFS, and median OS were 19.6% (21/107), 94.4% (101/107), 7.13 months (95% confidence interval [CI]: 6.26–8.01), and 19.50 months (95% CI: 12.83–26.17), respectively. There was no difference in the PFS between patients receiving apatinib or anlotinib/bevacizumab (median PFS, 7.13 vs. 6.27 months, hazard ratio [HR] = 1.49, 95% CI: 0.87–2.54, p = 0.15). The most frequent grade 3 or higher treatment‐related adverse events was diarrhea (17.6%), followed by hypertension (11.0%) and nausea (3.3%). No treatment‐related death occurred.Conclusion: In this study, pyrotinib plus antiangiogenic agents demonstrated promising efficacy and were tolerable in HER2‐altered NSCLC patients.

PURPOSE: Circulating tumor DNA (ctDNA)–based minimal residual disease (MRD) detection has become a strong prognostic stratification factor in postoperation non–small cell lung cancer (NSCLC). Here, we sought to investigate the guiding potential of MRD in informing adjuvant therapy (AT) decisions. MATERIALS AND METHODS: Patients with stage IA to IIIB NSCLC who had undergone confirmed R0 resection were enrolled. Blood samples were collected 1 month after surgery before initiation of AT (landmark) and longitudinally every 3-6 months since surgery. Postoperative AT was conducted according to the guideline recommendations, and regular radiographical examinations were recommended for relapse surveillance. MRD detection was conducted using the MinerVa platform (Genecast Precision Diagnostic Co., Ltd. Wuhan, China) using a tumor-informed strategy based on a fixed next-generation sequencing panel spanning 769 cancer-related genes. RESULTS: One hundred sixty-five patients were included in this study, with 35 (21.2%) relapses. At landmark, positive MRD was associated with shorter disease-free survival (DFS) than negative MRD ( P < .001, hazard ratio, 12.0). MRD was an independent risk factor for shorter DFS, irrespective of the disease stage and high-risk factors. In the case of negative landmark MRD, there was no significant difference between the DFS of (1) those who received AT and those who did not in stage IB patients with high-risk factors ( P = .974), (2) epidermal growth factor receptor ( EGFR )–mutant patients with or without adjuvant chemotherapy before adjuvant targeted therapy ( P = .502), and (3) EGFR / ALK wild-type with or without adjuvant immunotherapy ( P = .534). Clearance of ctDNA during AT was associated with a better prognosis than persistently detected ctDNA ( P < .001). CONCLUSION: ctDNA-based MRD stratifies prognosis after curative resection in NSCLC, with MRD negativity indicating limited benefit from treatment in selected patients and ctDNA clearance reflecting improved outcomes. These findings support the clinical utility of MRD-guided adjuvant treatment strategies.

Objective: To conduct a systematic review and meta-analysis on the prediction of severity of gastric intestinal metaplasia (GIM) in localized and entire gastric mucosa using endoscopy. Methods: The...