Si-Yu Wang

In the primary report of the CORIN trial (NCT02264210), a 1‑year adjuvant icotinib regimen increased the 3-year disease-free survival (DFS) rate with acceptable toxicity in patients with resected epidermal growth factor receptor (EGFR)-mutated stage IB non-small cell lung cancer (NSCLC). This study reports its 5-year outcomes and exploratory circulating tumor DNA (ctDNA) monitoring plus primary tumor spatial transcriptomics to identify factors associated with recurrence. A total of 128 eligible patients were randomized 1:1 to 1‑year icotinib (63 patients) or observation (65 patients), with a median follow-up of 65.0 months. Survival outcomes showed icotinib resulted in significantly better DFS (HR=0.38, 95% CI 0.18–0.83, P=0.012) and marginally superior 5-year overall survival (OS, 98.3% vs 90.6%; HR=0.16, 95% CI 0.02–1.30, P=0.048) versus observation. Serial ctDNA detection on 62 patients revealed single-time ctDNA positivity rarely developed recurrence in the icotinib arm, while multiple ctDNA positivity linked to higher relapse risks in the observation group. Spatial transcriptomics uncovered five spatially distinct cancer-associated fibroblast (CAF) subtypes, among which CAF_S1 (within stroma) strongly correlated with recurrence. This updated 5-year CORIN data validates sustained efficacy of 1-year adjuvant icotinib for EGFR-mutated IB NSCLC; ctDNA dynamics and CAF_S1 serve as promising biomarkers to predict postoperative recurrence.

The efficacy, safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for patients with resected EGFR-mutated non-small-cell lung cancer (NSCLC) were not known until 2014, when this study was initiated. In this phase 3 ICTAN trial (GASTO1002, NCT01996098), patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after adjuvant chemotherapy were assigned in a 1:1:1 ratio to receive icotinib (125 mg, three times daily) for 12 months, to receive icotinib for 6 months, or to undergo observation. The primary endpoint was disease-free survival (DFS). This trial was terminated early. A total of 251 patients were randomized. Adjuvant icotinib for 12 months significantly improved DFS (hazard ratio [HR]: 0.40, 95% confidence interval [CI], 0.27–0.61; P < 0.001) and overall survival (OS; HR: 0.55, 95% CI, 0.32–0.96; P = 0.032) compared with observation. Adjuvant icotinib of 6 months also significantly improved DFS (HR: 0.41, 95% CI, 0.27–0.62; P < 0.001) and OS (HR: 0.56, 95% CI, 0.32–0.98; P = 0.038) compared with observation. Adjuvant icotinib for 12 months did not improve DFS (HR: 0.97; P = 0.89) or OS (HR: 1.00; P = 0.99) compared with 6 months of this drug. Rates of adverse events of grade 3 or higher were 8.3%, 6.0% and 2.4% for the 12-month icotinib, 6-month icotinib, and observation groups, respectively. Adjuvant icotinib for 12 months or 6 months following adjuvant chemotherapy improved DFS and OS compared with observation in patients with resected EGFR-mutated stage II-IIIA NSCLC with a manageable safety profile, supporting it as a potential treatment option.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor. Lung cancer patients with ALK and EML4 fusions respond significantly to ALK inhibitors. The EML4-ALK fusion gene mutation is the result of an inversion of chromosome 2, which juxtaposes the 5 end of the EML4 gene with the 3 end of the ALK gene. In SCLC, the frequency of fusion genes is very low, and to the best of our knowledge, only four cases of ALK fusion gene mutations in SCLC have been reported. In this report, we describe the treatment of a 74-year-old female patient with SCLC who developed recurrence of hilar lymph node metastasis three years after surgical resection. Postoperative NGS showed that this patient is a SCLC patient harboring a rare EML4-ALK fusion mutation, and a satisfactory 43-month overall survival (OS) was achieved after treatment with ensartinib targeting the EML4-ALK fusion gene mutation. The ALK-TKI may be a new treatment option for these patients. This article provides a therapeutic reference.

Background: Evidence regarding Chinese herbal medicine for facial rash related to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is limited. Therefore, this study aimed to investigate whether ex ternal application of a Xiaozhen zhiyang (XZZY) decoction is effective for EGFR-TKI-related facial rash in Chinese patients. Methods: In this prospective cohort study, 123 participants with EGFR-TKI-related facial rash were recruited from July 18, 2019 to May 20, 2021. The intervention was external application of the XZZY decoction twice daily for 2 weeks using a facial mask. Treatment efficacy, change in the WoMo score, and quality of life were evaluated as endpoints. Results: The average age of the 123 enrolled participants was 54.83 ± 12.45 years, and 48.78% were female. The total efficiency of treatment was 93.5%, including 12 (10%) cases were cured, 20 (16.26%) cases were markedly improved and 83 (67.48%) cases were improved. The generalized estimating equations showed decreased WoMo scores, itching, and pain, as well as an improved quality of life after the treatment. Only 1 participant reported skin allergies, and no other adverse effects were reported. Conclusion: This study showed the effectiveness and safety of a XZZY decoction for EGFR-TKI-related rash.

Background: Alectinib has demonstrated promising disease-free survival (DFS) benefit for early-stage non-small cell lung cancer (NSCLC) patients with ALK rearrangement positive in phase 3 ALINA trial. However, real-world evidence for the efficacy and safety of alectinib in early-stage ALK-positive NSCLC is limited.Materials and methods: We retrospectively reviewed 68 patients with stage IB-IIIB ALK-positive NSCLC who underwent complete pulmonary resections from April 2010 to July 2023 at a single institution. 38 (55.9%) enrolled patients had N2 lymph node metastasis, and 17 (24.9%) patients had multi-station N2 metastasis. Patients were stratified into two groups according to the adjuvant treatment regimen, with 19 patients in the alectinib group and 49 patients in the chemotherapy group. There were no significant differences in clinicopathological characteristics between the two groups. After curative resection surgery, patients in alectinib group received oral alectinib at a dose of 600 mg twice daily and patients in chemotherapy group received platinum-based doublet chemotherapy regimen every 3 weeks for 4 cycles. The primary endpoint was 3-year DFS. The Kaplan-Meier method was used to estimate DFS and overall survival (OS). Safety analyses were conducted by comparing the incidence of adverse events between the two groups.Results: At the last follow-up date (January 22th, 2024), A total of 1 (5.3%) and 28 (57.1%) DFS events were observed in alectinib group and chemotherapy group respectively. The 3-year DFS showed significant improvement in the alectinib group compared with chemotherapy group (91.7% vs 60.7%, P=0.051). In the IIIAN2 subgroup, the 3-year DFS rate in the alectinib group reached a satisfactory 87.5%. In both groups, the majority of AEs were graded as level 1 or 2, No grade 3-4 AEs were observed in alectinib group.Conclusion: Alectinib, as adjuvant therapy, demonstrated favorable efficacy and manageable safety in patients with completely resected ALK-positive stage I B-IIIB non-small cell lung cancer. A limitation of this study is the small sample size, and a larger-scale real-world sample study is needed to further evaluate the efficacy and safety of alectinib as adjuvant therapy.

The efficacy, safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for patients with completely resected EGFR-mutated non-small cell lung cancer (NSCLC) after adjuvant chemotherapy were not known until 2014, when this study was initiated. In this phase 3 ICTAN trial, patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after platinum-based adjuvant chemotherapy were assigned in a 1:1:1 ratio to receive icotinib (125 mg, three times daily) for 12 months, to receive icotinib for 6 months or to undergo observation. The primary endpoint was DFS according to investigator assessment. This trial was terminated early. A total of 251 patients were randomized. Baseline characteristics were balanced among the groups. After a median follow-up of 61.4 months, 6 months of icotinib significantly improved DFS (hazard ratio (HR): 0.41, 95% confidence interval (CI), 0.27–0.62; P < 0.001) and overall survival (OS, HR: 0.56, 95% CI, 0.32–0.98; P = 0.041) compared with observation. Adjuvant icotinib of 12 months also significantly improved DFS (HR: 0.40, 95% CI, 0.27–0.61; P < 0.001) and OS (HR: 0.55, 95% CI, 0.32–0.96; P = 0.035) compared with observation. Adjuvant icotinib for 12 months did not improve DFS (HR: 0.97; P = 0.89) or OS (HR: 1.00; P = 0.99) compared with 6 months of this drug. Rates of adverse events of grade 3 or higher were 8.3%, 5.9% and 2.4% for the 12-month icotinib, 6-month icotinib and observation groups, respectively. The safety profile remained similar to that reported previously for icotinib. Adjuvant icotinib for 12 months and 6 months following adjuvant chemotherapy provided a significant DFS and OS benefit compared with observation in patients with completely resected EGFR-mutated stage II-IIIA NSCLC with a manageable safety profile. Nevertheless, 12 months of icotinib had no additional benefit compared with 6 months.

The application of adjuvant treatment has significantly enhanced the survival of patients with resectable non-small cell lung cancer (NSCLC) carrying driver gene mutations. However, adjuvant-targeted therapy remains controversial for some NSCLC patients carrying rare gene mutations such as RET, as there is currently a lack of confirmed randomized controlled trials demonstrating efficacy. In this report, we describe the case of a 58-year-old man with stage IIIA NSCLC who underwent complete lobectomy with selective lymph node dissection. Postoperative next-generation sequencing revealed that the patient harbored a rare KIF13A-RET fusion. The patient elected to receive adjuvant treatment with pralsetinib monotherapy and underwent serial circulating tumor DNA (ctDNA) monitoring after surgery. During follow-up, despite experiencing dose reduction and irregular medication adherence, the patient still achieved a satisfactory disease-free survival (DFS) of 27 months. Furthermore, ctDNA predicted tumor recurrence 4 months earlier than imaging techniques. The addition of bevacizumab to the original regimen upon recurrence continued to be beneficial. Pralsetinib demonstrated promising efficacy as adjuvant therapy, while ctDNA analysis offered a valuable tool for early detection of tumor recurrence. By leveraging targeted therapies and innovative monitoring techniques, we aim to improve outcomes and quality of life for NSCLC patients in the future.

Background: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. Methods: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. Results: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). Conclusions: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.

Facing an anarchy world who tries to reach a consensus of peaceful and legalized governance, it’s unavoidable to discuss the actual effectiveness of international law, yet such discussion shall be continuous, taking long-term efforts in order to get closer to its goal before a cooperative world come into being. Starting from the vital case of Corfu Channel that shaped its sphere of application, this article aims to discuss the innocent passage principle in the international law system, emphasizing its characteristics, flaws and the reasons behind. The article mainly used the methods of regulatory research and case study. The analysis stressed that the flaws of innocent passage regulations was on account of its nature of being a part of soft laws, but similar principles performed well in some other areas, such as the arctic and the outer space. Eventually, the article suggested that the soft laws like the innocent passage can be commendably applied in areas that was unexploited and without obvious military threats.