Efficacy and Safety of Radiotherapy Combined with Pyrotinib in the Treatment of HER2-Positive Breast Cancer with Brain Metastases.

Purpose: To explore the efficacy and safety of pyrotinib combined with different radiotherapy modes in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) patients with brain metastasis (BM). Patients and Methods: This study is a retrospective analysis of patients diagnosed with BM who underwent treatment with pyrotinib between November 2018 and April 2023. A total of 66 patients were administered radiotherapy in conjunction with pyrotinib (Group A), while 26 patients received pyrotinib as a standalone treatment (Group B). Within Group A, 18 patients underwent conventional fractionated radiotherapy (2Gy/F), while 48 patients received hyperfractionated radiotherapy (HFRT) (≥3Gy/F). The primary endpoints were intracranial progression-free survival (IC-PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR) and clinical benefit rate (CBR). Results: The ORR of Group A was 54.5% (36/66), while the ORR of Group B was 34.6% (9/26) (P= 0.047). The CBR of Group A was 89.4% (59/66) and that of Group B was 69.2% (18/26) (P= 0.041). The IC-PFS between Group A and Group B were 12 months and 8 months, respectively (P< 0.001), and the OS were 20 months and 16 months, respectively (P= 0.065). In Group A, the IC-PFS and OS between the conventional fractionation radiotherapy group and the HFRT group were 10 months and 12 months, respectively (P= 0.001) and 16 months and 24 months, respectively (P< 0.001). No serious adverse reactions were observed in Group A and Group B. Conclusion: For HER2-positive BC patients with BM, it is recommended to adopt the treatment mode of HFRT combined with pyrotinib, which can improve the local control and survival of patients.

Analysis of the prognostic factors of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) in 220 cases of locally advanced squamous esophageal cancer: a retrospective cohort study.

Background: Esophageal cancer is one of the most common malignant tumors in China. Patients with advanced esophageal cancer often cannot be treated by surgery; in these cases, radiation therapy is usually applied. However, there are currently few studies on the clinical efficacy of this treatment method. The present study aimed to investigate and observe the clinical efficacy and related prognostic factors of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) in esophageal squamous carcinoma, and to provide a reference for clinicians in radiotherapy (RT) departments. Methods: The clinical and follow-up data of 220 patients with esophageal squamous carcinoma admitted to the First Affiliated Hospital of Bengbu Medical College from January 2017 to December 2018 were retrospectively analyzed to assess the relevant prognostic factors and analyze their effects on 3-year overall survival (OS) and progression-free survival (PFS). The prognostic influencing factors were analyzed using the log-rank test and Cox multi-factor regression analysis. Results: The median follow-up time was 56.0 months (3.0 to 66.0 months). The 1-, 2-, and 3-year survival rates were 68.6%, 49.1%, and 36.3%, respectively, for the entire cohort, and the 1-, 2-, and 3-year PFS rates were 52.3%, 37.7%, and 25.5%, respectively. The median OS time was 24 months [95% confidence interval (CI): 19.16-28.84 months] and the median PFS time was 15 months (95% CI: 11.04-18.96 months). The multifactorial analysis results showed that gender, RT dose, treatment modality, absolute lymphocyte count (ALC), and gross tumor volume (GTV) were independent prognostic factors affecting 3-year OS (P<0.05); while gender, N-stage, RT dose, and GTV were independent prognostic factors affecting 3-year PFS (P<0.05). Conclusions: In the SIB-IMRT era, the survival of esophageal squamous cell carcinoma (ESCC) patients treated with radical (chemo)radiotherapy is relatively satisfactory. As a single-institution study on radiation therapy for esophageal cancer, this study yielded accurate results that help to provide references for subsequent related studies and clinicians' selection of treatment options.

Analysis of Immunotherapy Combined with Radiotherapy in Patients with Brain Metastasis of Driver Gene-Negative Non-Small-Cell Lung Cancer.

Purpose: To observe the remission rate and side effects of immunotherapy combined with radiotherapy in patients with brain metastasis of driver gene-negative non-small-cell lung cancer (NSCLC). Methods: 152 patients with NSCLC brain metastasis admitted to our hospital from January 2019 to December 2021 were selected as the research objects. Patients were divided into a single group (85 cases) and a combined group (67 cases) according to treatment methods. The therapeutic effects and side effects of the single group and combined group were compared. In addition, the patients who received immunotherapy combined with radiotherapy were divided into three subgroups: A, B, and C, and the therapeutic effects and side effects of different radiotherapy modes were compared among group A [whole brain radiotherapy (WBRT)], group B (WBRT combined with local radiotherapy) and group C (local radiotherapy). Results: The objective response rate (ORR) and disease control rate (DCR) in the combined group were higher than those in the single group (P < 0.05). The incidence of reactive capillary hyperplasia and immune-related pneumonia in the combined group were higher than that in the single group (P < 0.05). There was no significant difference in the incidence of other side effects between the two groups (P > 0.05). ORR and DCR in group B were higher than those in group A (P < 0.05). There was no significant difference in the incidence of side effects among the three groups (P > 0.05). Conclusion: Immunotherapy combined with radiotherapy is effective in patients with brain metastasis of driver gene-negative NSCLC, which can improve the disease control rate without increasing the side effects. In addition, WBRT combined with local push radiotherapy is effective and safe. Clinical Study Registration Number. The Clinical study registration number is K2019086.

Significance of intratreatment tumor volume change during chemoradiotherapy for potentially resectable thoracic esophageal squamous cell carcinoma.

OBJECTIVE: The purpose of this study was to investigate the clinical significance of tumor response assessment at a twentieth fraction of radiotherapy when predicting the survival of patients with potentially resectable esophageal squamous cell carcinoma (ESCC). METHODS: A total of 123 ESCC patients with clinical stages II to IVa were enrolled and analyzed. Gross tumor volume (GTV) of the esophagus (GTVe) and GTV of the metastatic lymph node (GTVnd) were manually contoured by at least 2 senior professional radiotherapists on the simulated computed tomography (CT) images in a process that followed the delineating rules for ESCC. RESULTS: The GTVe reduction ratio (RR) and GTVnd RR were calculated based on the evaluation of the tumor volume at a twentieth fraction of radiotherapy. Univariate analysis showed that GTVe and GTVnd before treatment, and GTVe RR and GTVnd RR at the twentieth fraction of radiotherapy were all significantly associated with complete clinical response (cCR) and overall survival (OS). The Kaplan-Meier method was used to estimate OS and locoregional recurrence-free survival (LRRFS). CONCLUSIONS: The GTVe RR ≥27.92% and GTVnd RR ≥21.49% at a twentieth fraction of radiotherapy are positive predictive factors of LRRFS, and according to multivariate analysis, only GTVe RR at the twentieth fraction of radiotherapy ≥27.92% is prognostic for a favorable OS.

Progress of clinical study on hypofractionated radiotherapy after breast-conserving surgery.

Whole-breast radiotherapy after breast-conserving surgery (BCS) can improve patient survival while reducing local tumor recurrence. Although standard breast radiotherapy can achieve good tumor control and cosmetic effects with low toxicity, the 5- to 7-week treatment time is relatively long for patients and can result in wasted medical resources. Therefore, there is a growing trend toward hypofractionated radiotherapy (HFRT), which accelerates partial-breast irradiation. Both short-course radiotherapy and conventional fractionated radiotherapy are safe and effective treatment modes, with similar survival and local tumor control effects as those of conventional radiotherapy (CRT), and adverse reactions can be tolerated. Compared with conventional fractionated radiotherapy, short-course radiotherapy saves medical resources and has a shorter total treatment time, reduced treatment costs, and an improved quality of life for patients.

Matrine induces apoptosis in acute myeloid leukemia cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

Matrine has been demonstrated to exert anticancer effects on acute myeloid leukemia (AML) cell lines. However, the mechanisms of matrine in AML remain largely unknown. The present study investigated the anticancer effects and underlying mechanisms of matrine on human AML cells in vitro. THP-1 cell lines were cultured and treated with different doses of matrine (0.4, 0.8, 1.2, 1.6 and 2.0 g/l). The effects of matrine on the cell proliferation were assessed by the Cell Counting Kit-8 assay. The apoptotic effects were evaluated by DAPI and annexin V/propidium iodide staining assays. The effects of the drug on phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ mechanistic target of rapamycin kinase (mTOR) protein expression were studied by western blot analysis. The results of the present study demonstrated that matrine suppressed the viability of THP-1 cells. The anticancer effects were identified to be dose-dependent and the IC50 value was 1.2 g/l in THP-1 cells. Matrine inhibited cell viability and induced cell apoptosis of AML cell lines in a dose- and time-dependent manner. In addition, it was observed that matrine decreased the expression of phosphorylated (p)-PI3K, p-Akt and p-mTOR in a concentration-dependent manner. However, the expression levels of PI3K, Akt and mTOR remained almost unaltered. These findings indicated that matrine may inhibit cell proliferation and induce apoptosis of AML cells and may be a novel effective chemotherapeutic agent against AML.

[Matrine inhibits proliferation and promotes autophagy and apoptosis in non-small cell lung cancer cells by deactivating PI3K/AKT/mTOR pathway].

OBJECTIVE: To investigate the inhibitory effect of matrine on the proliferation of human non-small cell lung cancer (NSCLC) and explore the possible molecular mechanism. METHODS: Cultured human NSCLC A549 cells were treated with 0.4, 0.8, 1.2, 1.6, and 2.0 g/L matrine for 24, 48 or 72 h. CCK-8 assay was used for measuring the changes in A549 cell viability. The morphological changes of the cells were observed under a fluorescence microscope, and flow cytometry was employed for analyzing the cell apoptosis. The effects of matrine and the PI3K specific inhibitor LY294002 (10 nmol/L) on AKT pathway and autophagy-related proteins in A549 cells were investigated using Western blotting. RESULTS: Matrine significantly inhibited the proliferation of A549 cells in a time- and dose-dependent manner (P < 0.05). At the concentration of 1.6 g/L or higher, matrine caused obvious cell shrinkage and fragmentation and significantly increased floating cells; autophagy vacuoles could be observed in the cells after acridine orange staining. Within the concentrations range of 0.8-1.6 g/L, matrine time- and dosedependently increased the cell apoptosis. Treatment of the cells with 1.6 g/L matrine and 10 nmol/L LY294002 resulted in significantly lowered expressions of p-AKT and p-mTOR proteins and increased the expression of light chain 3B (LC 3B), an autophagy-related protein, as compared with those in the control cells (P < 0.05). CONCLUSIONS: We demonstrate that matrine inhibits the proliferation and induces autophagy and apoptosis of A549 cells by deactivating AKT pathway, suggesting the potential of matrine as an anti-cancer agent for lung cancer.

Factors relevant to the prognosis of patients with esophageal cancer who received intensity-modulated radiotherapy.

BACKGROUND: The aim of this study was to evaluate the clinical factors relevant to the prognosis of patients with esophageal cancer who received intensity-modulated radiotherapy (IMRT). METHODS: The data of 60 patients admitted to our hospital from January 2014 to December 2015 with pathologically confirmed esophageal cancer were retrospectively reviewed. All patients received IMRT. Patients were divided into groups according to two-year survival: those who survived > 2 years after treatment, and those who died within 2 years of treatment. The potential clinical factors relevant to prognosis were evaluated by logistic regression analysis. RESULTS: Single factor analysis showed that lesion length (P < 0.05), tumor diameter (P < 0.05), T stage (P < 0.05), N stage (P < 0.05), and combined chemotherapy (P < 0.05) were associated with the prognosis of esophageal cancer patients who received IMRT. Logistic regression analysis demonstrated that T stage (odds ratio = 3.62; P < 0.05) and N stage (odds ratio = 2.98; P < 0.05) were independent factors relevant to prognosis. CONCLUSION: T stage and N stage influence the long-term curative effects of IMRT for esophageal cancer. The higher the stage, the lower the two-year survival rate.