In recent years, the incidence of primary liver cancer has been increasing, among which hepatocellular carcinoma (HCC) being the most common subtype. The treatment of early HCC is mainly surgery, but most patients are not diagnosed until the late stage of the disease. The treatment methods and effects are very limited and the prognosis is very poor. Although targeted therapy has prolonged the overall survival of patients with HCC, the overall efficacy is unsatisfactory. The emergence of immunotherapy has brought new therapeutic prospects for HCC. Immune checkpoint inhibitors, among which programmed death-1/programmed death ligand-1 and cytotoxic T-lymphocyte associated antigen-4 are the representative immunological checkpoints, have attracted more attention. This article will introduce the application of immune checkpoint inhibitors in the treatment of advanced HCC, in order to provide a theoretical basis for the use of immune checkpoint inhibitors in the treatment of advanced HCC.
In recent years, immune checkpoint inhibitors have begun to be used in targeted cancer therapy. Despite the favorable results in terms of oncological outcomes, these treatments have been associated with a variety of immune-related adverse events. Neuromuscular disease is more common among adverse events involving the nervous system. With the increasing use of immune checkpoint inhibitors, the early recognition and treatment of neuromuscular immune-related adverse events are very important. In this review, we are focused on the epidemiology, pathogenesis, clinical manifestations, evaluation, diagnosis, and treatment of neuromuscular diseases (including peripheral neuropathy, myasthenia gravis, and myositis) caused by immune checkpoint inhibitors, aiming to provide a theoretical basis for improving the diagnosis and treatment ability of users of immune checkpoint inhibitors for such neuromuscular diseases and reducing the disability rate and mortality rate caused by immune checkpoint inhibitors.
Brain metastases are the most common intracranial malignant tumors in adults. Radiotherapy isa common treatment for brain metastases. In particular, stereotactic radiosurgery can control tumors well, and can significantly reduce the impact on cognitive function compared with whole brain radiation therapy. Immune checkpoint inhibitors have less toxic side effects in the treatment of patients with advanced tumors, and show good survival advantages. This article introduces radiotherapy, immunotherapy, stereotactic radiosurgery combined with immune checkpoint inhibitors for brain metastases, discusses the mechanism of stereotactic radiosurgery combined with immune checkpoint inhibitors, and its therapeutic value and research progress in brain metastases, aiming to provide a theoretical basis for the better application of stereotactic radiosurgery combined with immune checkpoint inhibitors to brain metastases.
Objective To analyze the clinical features of immune checkpoint inhibitor-related pneumonia (CIP) in patients with lung cancer. Methods The case data of patients with CIP admitted to Zhongshan Hospital of Fudan University from January 2017 to December 2020 were retrospectively collected, and the basic data, clinical manifestations, imaging data, laboratory examination results, treatment and prognosis of the patients were analyzed. Results The ratio of male to female was 18:1, and the median age was 65 years (from 41 to 74 years). Fourteen patients received a programmed death protein-1 (PD-1) inhibitor and five patients received a programmed death protein-ligand-1 (PD-L1) inhibitor. The median time to CIP was 3.5 months. The respiratory symptoms of 15 patients were dyspnea in 11 cases, cough in 9 cases, chest tightness in 8 cases, fever in 4 cases, expectoration in 4 cases and hemoptysis in 2 cases. Chest CT findings mainly showed interstitial pneumonia, including 8 cases of implicit organizational pneumonia (COP), 7 cases of non-specific interstitial pneumonia (NSIP), 2 cases of acute interstitial pneumonia, and 2 cases of allergic pneumonia. C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase were higher in CIP than before, and the difference was statistically significant. Follow-up observation was performed in 3 patients alone, 14 patients were treated with glucocorticoid alone, 2 patients were treated with immunosuppressant therapy, 19 patients had stable or more absorption of pneumonia lesions, and 5 patients had restarted immunotherapy. There were no deaths from CIP. Conclusions CIP mainly occurs in men, with slow onset, lack of specificity in clinical manifestations, and increased inflammatory indicators. Imaging findings are mainly NSIP and COP changes. Early identification, diagnosis and rational application of glucocorticoid therapy have good effects.
ObjectiveTo explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. MethodsThe clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. ResultsAfter preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. ConclusionPembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.
Objective To systematically review the efficacy and safety of immune checkpoint inhibitors (ICIs) as first-line treatment for advanced non-small cell lung cancer (NSCLC). MethodsTo collect clinical randomized controlled trials of ICIs for the first-line treatment of patients with NSCLC, computer searches were conducted on PubMed, The Cochrane Library, and EMbase databases. The search time frame was inception to January 2023. A meta-analysis was performed using Revman 5.4 software. ResultsTwelve clinical studies were included, all of which were assessed as high-quality literature with a total of 7 121 patients. Meta-analysis showed that the first-line treatment of NSCLC patients with ICIs significantly improved median overall survival (OS) (HR=0.72, 95%CI 0.64 to 0.80, P < 0.000 01), prolonged median progression-free survival (PFS) (HR=0.65, 95%CI 0.53 to 0.78, P<0.000 01), and improved objective response rate (ORR) (RR=1.52, 95%CI 1.28 to 1.79, P<0.000 01), compared to chemotherapy. Subgroup analysis showed that the ICIs combination therapy group significantly improved OS, PFS, and ORR in NSCLC patients compared to the ICIs monotherapy group. In terms of safety, the ICIs group had a lower risk of treatment-related adverse events (TRAEs) of any grade and grade 3-5 TRAEs than the chemotherapy group. However, the ICIs group had a higher incidence of TRAEs leading to treatment cessation than the chemotherapy group. Subgroup analysis showed that the incidence of any grade TRAEs, grade 3-5 TRAEs, leading to treatment discontinuation TRAEs was higher in the immune combination therapy group than in the immune monotherapy group. ConclusionThe first-line treatment of NSCLC patients with ICIs inhibitors significantly improved OS, PFS, and ORR compared to chemotherapy. Immune-combination chemotherapy significantly improved the outcomes of NSCLC patients, compared to immune monotherapy, but patients were at a higher risk of TRAEs.
ObjectiveTo investigate the risk of myocarditis caused by immune checkpoint inhibitors (ICI). MethodsThe adverse reaction (ADR) reports on myocarditis caused by atelizumab, duvalizumab, pabolizumab, and navulizumab were downloaded from the FDA Adverse Event Reporting System (FAERS) from January 1, 2014 to September 30, 2022. The relevant analysis was conducted on the gender, age, medication dosage, and occurrence time of ICI related myocarditis patients. ResultsA total of 1 892 reports of myocarditis induced by ICI were included. The proportion of myocarditis caused by ICI was higher in males than in females (1.9∶1). The incidence of myocarditis in patients with basic diseases such as diabetes and heart disease, and in the age group 65-75 was relatively high. The incidence of myocarditis caused by navulizumab was high within 30 days with the use of conventional doses, and that of the other three drugs were high within 31 to 90 days. And the incidence of myocarditis is higher when used in combination than when used alone. ConclusionDifferent varieties of ICI can lead to the occurrence of myocarditis, and male, elderly, underlying diseases, and combination therapy may be risk factors for myocarditis caused by ICI.
Tumor immunotherapy includes immune checkpoint inhibitor (ICI), tumor vaccines, and adoptive cell therapy. Immunotherapy, as the main systemic treatment for advanced malignant tumors, kills tumor cells by activating the immune system and prolongs the survival of patients. However, excessive immune responses can cause immune-related adverse events (irAE), causing damage to systemic tissues. ICI are the main tumor immunotherapy drugs that cause optic nerve irAE. The most common optic nerve irAE are optic neuritis, only a few patients appeared arteritic anterior ischemic optic neuropathy. Sudden painless loss of bilateral vision is the most common clinical manifestation. In severe cases, the vision decrease to no light perception. Early diagnosis and early adequate glucocorticoid treatment can improve the symptoms. Therefore, neuro-ophthalmologists and oncologists should know the clinical characteristics of optic nerve irAE, in order to diagnose and treat early and improve the prognosis.
ObjectiveTo analyze the efficacy and safety of immunotherapy and bevacizumab combined with chemotherapy (BIC), bevacizumab combined with chemotherapy (BC), chemotherapy (CT), immunotherapy combined with chemotherapy (IC), bevacizumab combined with immunotherapy (BI), bevacizumab (B) in the first-line treatment of advanced wild-type non-squamous non-small cell lung cancer. MethodsThe PubMed, Embase, Cochrane Library and Web of Science databases were searched to collect phase Ⅱ/Ⅲ randomized controlled trials (RCTs) related to the objectives of the study from January 2010 to December 1, 2022. After two investigators independently screened the literatures, extracted the data and evaluated the risk of bias of the included studies, a reticular meta-analysis was performed using R 3.6.1 software. ResultsA total of 11 RCTs were finally included, including 5 329 patients and six treatment combinations. Meta-analysis results showed that BIC was superior to CT for progression-free survival (PFS) (HR=0.34, 95% CI 0.18 to 0.69), but BIC did not show a significant advantage over the other groups for overall survival (OS). Bayesian ranking results showed that the BIC group had the greatest probability in terms of OS, PFS, and ORR. Among all programmed death ligand 1 (PD-L1) expressing subgroups, there was no significant difference in OS between BIC, BC, IC, CT, BI, and B. Compared with CT, IC was significantly improved in OS (HR=0.68, 95%CI 0.52 to 0.92), PFS (HR=0.58, 95%CI 0.45 to 0.75), and ORR (HR=0.47, 95%CI 0.33 to 0.66). ConclusionIn the first-line treatment of wild-type advanced non-squamous NSCLC, immunotherapy and bevacizumab combined with chemotherapy may improve the efficacy in the short term, but do not change the long-term survival time. Immunotherapy combined with chemotherapy can significantly improve the survival time and prognosis of patients compared with chemotherapy alone. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.
Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology by regulating the interaction between immune cells and cancer cells and promoting the disinhibition of the immune system, thus targeting various types of malignant tumors. However, the regulation of the immune system can also trigger related adverse reactions. Currently, there are no specific clinical guidelines for the treatment of these adverse reactions. Treatment decisions largely depend on clinical judgment and experience.The pathogenesis of ICI-related ocular adverse events is not fully understood at present. Further research on the specific mechanisms of action can provide new insights into the early diagnosis and treatment of ICI-related ocular adverse events.