Objective To investigate the efficacy of Zorifertinib in first-line treatment of patients with untreated epidermal growth factor receptor(EGFR)mutation in non-small-cell lung cancer(NSCLC)with central nervous system(CNS)metastases.Methods Two patients received Zorifertinib as first-line treatment.The response of tumor treatment was evaluated by response evaluation criteria in solid tumors version 1.1(RECEST v1.1)and RANO criteria for brain metastases(RANO-BM).Results Case 1 had EGFR exon 19del mutation and multiple brain metastases at baseline.After 51.4 months of treatment with Zorifertinib,case 1 still maintained partial response(PR)in lung lesions and complete response(CR)in intracranial lesions.Case 2 had EGFR exon 19del mutation and a single brain metastasis at baseline.Case 2 achieved PR in lung lesions and CR in intracranial lesions during the treatment with Zorifertinib.After 13.7 months,lung disease progression(PD)and new single brain metastases occurred.The comprehensive evaluation was PD.Case 1 had three-grade treatment-related adverse events(TRAEs),including dry skin,and other TRAEs were rash,abnormal liver function and diarrhea.The TRAEs were generally controllable.Conclusion Zorifertinib has a good effect on controlling intracranial and extracranial lesions in patients with EGFR-mutated NSCLC with CNS metastases.The efficacy of Zorifertinib is consistent with the EVEREST study.Zorifertinib can be one of the first-line initial treatment options.

Background and objective Malnutrition is commonly associated with poor prognosis in patients with malignant tumors.The neutrophil-to-lymphocyte ratio(NLR)is an indicator of inflammation in the body and predicts the risk of malnutrition in a variety of diseases;however,its association with malnutrition in lung cancer patients is unclear.The aim of this study is to clarify the association between NLR and nutritional status in stage Ⅳ primary lung cancer and to further deter-mine the optimal NLR cut-off that best predicts the risk of malnutrition.Methods A retrospective analysis of 209 patients ad-mitted to the Department of Medical Oncology,Tianjin Medical University General Hospital with a primary diagnosis of stageⅣ lung cancer from May 2019 to February 2021 was performed,and the nutritional risk screening 2002(NRS 2002)was used to examine their nutritional status.Patient demographic information,pathology,Karnofsky performance status(KPS)score,body mass index(BMI),comorbidities and clinical biochemical indicators were also included.The correlation between NLR and NRS 2002 was investigated.Receiver operating characteristic(ROC)curve was used to determine the best NLR cut-off predi cting malnutrition risk.Multivariable Logistic regression was used to assess the association between NLR and malnutrition risk.Results The rate of patients with stage Ⅳ primary lung cancer at nutritional risk was 36.36％(76/209).A significant positive correlation was observed between NLR values and NRS 2002 risk score(r=0.765,P＜0.001).The ROC curve analysis indicated that an NLR of 3.94 was the optimal cut-off for predicting malnutrition risk(area under the curve=0.747,95％CI:0.678-0.815,P＜0.001),which showed a sensitivity of 55％,a specificity of 86％,a positive predictive value of 68％,and a negative predictive value of 77％.Patients in the NLR＞3.94 group had a significantly higher risk of malnutrition compared to those in the NLR≤3.94 group(69.49％vs 23.33％,P＜0.00 1).Furthermore,NLR was identified as a risk factor for malnutrition in stage Ⅳ primary lung cancer patients.Conclusion NLR is associated with the risk of malnutrition in stage Ⅳ primary lung cancer,and NLR can be used as one of the indicators for screening nutritional risk in patients with stage Ⅳ primary lung cancer

Objective:To determine the value of colonoscopy in the diagnosis and treatment of patients with immune checkpoint inhibitor-induced colitis.Methods:Patients who developed colitis and underwent colonoscopy after receiving immune checkpoint inhibitors(ICIs)therapy at Tianjin Medical University General Hospital between December 2020 and December 2023 were reviewed,according to the guidelines of the Chinese Society of Clinical Oncology for the management of ICI-related toxicity.The effect of the treatment and the rela-tionship between prognosis and the pathological features of colonoscopy were analyzed.Results:Patients with ICI-associated colitis who un-derwent colonoscopy had a more than 3 degrees diarrhea,and diffused inflammatory features such as mucosal erythema,exudate,erosion,loss of vascular markings,and edema were observed under the microscope,and the presence of ulcers greater than 1 cm in diameter and/or more than 2 mm deep indicate a poor prognosis for enteritis.Histopathological studies showed changes in glandular structures,such as cryptitis and crypt abscess.The pathological colonoscopic manifestations of patients with microscopic enteritis were inconsistent,and more deep samples should have been taken.Conclusions:The toxicity grading of ICI-associated colitis is not limited to clinical manifestations,but refers to the multi-dimensional analysis of colonoscopic features and histopathological characteristics.Soft colonoscopy can be used as an important follow-up method for patients with colitis,owing to its ease of operation and good tolerance.

Humans ; East Asian People ; Nausea/drug therapy* ; Vomiting/drug therapy* ; Antineoplastic Agents/adverse effects* ; Neoplasms/drug therapy*

Klotho gene was originally discovered as an anti-aging gene, Klotho protein encoded by Klotho gene is expressed in multiple human tissues, and its most prominent function is the regulation of phosphate homeostasis. Klotho protein possesses various activities, including inhibition of multiple signaling pathways, reducing oxidative stress and suppressing inflammation, and these activities are associated with cancer. Klotho protein is discovered as a universal tumor suppressor, and its expression is associated with tumorigenesis and prognosis of patients. Lung cancer is the most common malignancy tumor, and it is the leading cause of cancer deaths worldwide because of its high incidence and mortality. This article summarizes the research progress of the role of Klotho on pathogenesis, therapeutic effect and prognosis in lung cancer, in order to provide new biomarker and target for diagnosis, treatment and prognosis of lung cancer.
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Humans ; Lung Neoplasms ; Carcinogenesis ; Inflammation

With the development of sequencing technology, the detection rate of non-small cell lung cancer (NSCLC) with primary epidermal growth factor receptor (EGFR) T790M mutation is increasing. However, the first-line treatment for primary EGFR T790M-mutated NSCLC still lacks standard recommendations. Here, we reported three advanced NSCLC cases with EGFR-activating mutation and primary T790M mutation. The patients were initially treated with Aumolertinib combination with Bevacizumab; among which, one case was discontinued Bevacizumab due to bleeding risk after treatment for three months. Treatment was switched to Osimertinib after ten months of treatment. Another case switched to Osimertinib and discontinued Bevacizumab after thirteen months of treatment. The best effect response in all three cases was partial response (PR) after initial treatment. Two cases progressed after first-line treatment and progression-free survival (PFS) was eleven months and seven months respectively. The other one patient had persistent response after treatment, and the treatment duration has reached nineteen months. Two cases had multiple brain metastases before administration and the best response to intracranial lesions was PR. The intracranial PFS was fourteen months and not reached (16+ months), respectively. There were no new adverse events (AEs), and no AEs of grade three or above were reported. In addition, we summarized the research progress of Osimertinib in the treatment of NSCLC with primary EGFR T790M mutation. In conclusion, Aumolertinib combined with Bevacizumab in the treatment of advanced NSCLC with primary EGFR T790M mutation has a high objective response rate (ORR) and control ability of intracranial lesions, which can be used as one of the initial options for first-line advanced NSCLC with primary EGFR T790M mutation.
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Humans ; Bevacizumab ; Carcinoma, Non-Small-Cell Lung ; ErbB Receptors ; Lung Neoplasms ; Mutation ; Protein Kinase Inhibitors

In advanced non-small cell lung cancer (NSCLC), V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation is highly malignant and has poor prognosis, and currently Dabrafenib in combination with Trametinib is approved for first-line treatment of patients with BRAF V600 mutation. In addition to mutations, BRAF fusion can also occur. With the development of gene detection, the detection of BRAF fusion is gradually increasing, but there is a lack of effective therapeutic strategies for BRAF fusion. In this paper, we review the clinical characteristics, mechanism of action, and clinical treatment of BRAF fusion to provide a basis for the treatment of BRAF fusion in NSCLC patients.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Mutation ; Proto-Oncogene Proteins B-raf/genetics*

DNA damage repair (DDR) system plays an important role in maintaining of genomic stability. Accumulation of DNA lesions or deficiency of DDR system could drive tumorigenesis as well as promote tumor progression; meanwhile, they could also provide therapeutic opportunities and targets. Of all the antineoplastic agents of lung cancers, many of them targeted or were associated with DNA damage and repair pathways, such as chemotherapies and antibody-drug conjugates which were designed directly causing DNA damages, targeted drugs inhibiting DNA repair pathways, and immune-checkpoint inhibitors. In this review, we described the role of DNA damage and repair pathways in antitumor activity of the above agents, as well as summarized the application and clinical investigations of these antineoplastic agents in lung cancers, in order to provide more information for exploring precision and effective strategies for the treatment of lung cancer based on the mechanism of DNA damage and repair.
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Antineoplastic Agents/therapeutic use* ; DNA Damage ; DNA Repair ; Humans ; Lung Neoplasms/genetics* ; Neoplasms/drug therapy*

Immune checkpoint inhibitors (ICIs) are widely used in clinic, and the incidence of rare adverse events are increasing. The aim of this paper is to better define the rare adverse effect of diabetes mellitus associated with ICIs. We report 2 cases of diabetes mellitus associated with ICIs. Literature review was conducted and we discussed the clinical presentation, potential mechanisms and suggestions for optimal management. Two patients were both elderly women, case 1 had increased blood glucose after 7 months of using Durvalumab, and cases 2 had diabetic ketoacidosis after 6 weeks of using Pembrolizumab. Both patients were administered exogenous insulin to control blood glucose. Case 1 has been treated with Durvalumab until now and case 2 discontinued using of Pembrolizumab. HLA genotypes and other factors may explain the risk factors of diabetes associated with ICIs in some individuals. Diabetes mellitus associated with ICIs is an uncommon but potentially life-threatening endocrine system adverse event, which requires doctors to be vigilant. The patients who use ICIs need to monitor blood glucose. If they have hyperglycemia, endocrinologists should be asked to assist in diagnosis and treatment.
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Aged ; Blood Glucose ; Diabetes Mellitus/drug therapy* ; Female ; Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Lung Neoplasms/drug therapy*

Immune checkpoint inhibitors (ICIs) have become an important means of cancer treatment, and their application in the clinic is becoming more and more widespread. The adverse reactions caused by ICIs are gradually recognized. Among them, immunotherapy-related diabetes is a rare adverse reaction and type 1 diabetes mellitusis common. With the wide application of ICIs combined with chemotherapy in lung cancer patients, patients with type 2 diabetes mellitus have gradually been discovered during the treatment. However, the effect of continued use of ICIs maintenance therapy on blood glucose and ICIs treatment process in these patients is still unclear. This article reports two cases of type 2 diabetes mellitus induced by immune checkpoint inhibitor combined with chemotherapy, one of whom converted to type 1 diabetes mellitus, in order to increase the understanding of immunotherapy-related diabetes.
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Diabetes Mellitus, Type 2/drug therapy* ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy/adverse effects* ; Lung Neoplasms/therapy* ; Molecular Targeted Therapy