Successful management of camrelizumab-induced immune-checkpoint-inhibitors-related myocarditis.

INTRODUCTION: Immune checkpoint inhibitors can cause immune-related toxicity in various systems, with myocarditis being the most severe and life-threatening manifestation. This report presents a case in which myocarditis developed following administration of programmed cell death protein-1 (PD-1) inhibitors therapy. We describe the diagnosis and treatment of this patient in detail. CASE REPORT: We present the case of a 59-year-old female diagnosed with post-operative esophageal cancer and hepatic metastases. The patient underwent second-line treatment with domestically-made PD-1 inhibitor, camrelizumab, in combination with paclitaxel (albumin-bound) and carboplatin for two cycles. During the course of treatment, an electrocardiogram (ECG) revealed ST segment elevation in leads II, III, aVF, V2, V3, and V4, along with T wave changes in leads I and aVL. Laboratory examinations showed abnormal levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT). Despite the absence of clinical symptoms, the patient was routinely hospitalized three weeks later. Based on the findings from the ECG, cardiac biomarkers, echocardiography, echocardiogram, cardiac magnetic resonance, and angiography, she was diagnosed with immune-checkpoint-inhibitors-related myocarditis. MANAGEMENT AND OUTCOME: The patient received immunoglobulin (0.5 g/kg/day) and was initially given methylprednisolone (1000 mg/day). Methylprednisolone was gradually reduced to 40 mg/day in 2 weeks. During this time, the levels of biomarkers indicative of myocardial injury also exhibited a simultaneous decline. DISCUSSION: This case highlights the importance of early detection and prompt intervention, including initiating appropriate steroid therapy and discontinuing of immune checkpoint inhibitors. Such measures can effectively prevent morbidity and mortality, ultimately leading to an improved prognosis.

High expression of FGFR3 predicts a better prognosis for patients with non-small cell lung cancer in a Chinese population.

Background: This study sought to examine the expression and mutation status of fibroblast growth factor receptor 3 (FGFR3) in non-small cell lung cancer (NSCLC) tissues and explore the prognostic potential of FGFR3 in NSCLC. Methods: Immunohistochemistry (IHC) was used to evaluate the FGFR3 protein expression of 116 NSCLC tissues. Sanger sequencing was used to examine the mutation status of exons 7, 10, and 15 in FGFR3. A Kaplan­Meier survival analysis was conducted to evaluate the association between the expression level of FGFR3 and the overall survival (OS) and disease-free survival (DFS) of NSCLC patients. Univariate and multivariate Cox analyses were conducted to examine the association between the risk score and clinical features. Results: FGFR3 was immunoreactive in 26 of the 86 NSCLC cases. Further, FGFR3 was positively expressed in 84.6% of the lung adenocarcinoma (AC) cases and 15.4% of the lung squamous cell carcinoma (SCC) cases. FGFR3 mutations were detected in 2 NSCLC patients (2/72, 2.8%), who both harbored the T450M mutation, a novel mutation in exon 10 of FGFR3. In NSCLC, a high expression of FGFR3 was positively correlated with gender, smoking, histology type, T stage, and the epidermal growth factor receptor (EGFR) mutation (P<0.05). FGFR3 expression was also correlated with better OS and DFS. The multivariate analysis revealed that FGFR3 served as an independent prognostic factor (P=0.024) for the OS of NSCLC patients. Conclusions: This study showed that FGFR3 was highly expressed in NSCLC tissues, and the frequency rate for the FGFR3 mutation at T450 M in NSCLC tissues was low. The survival analysis suggested that FGFR3 may be a useful prognostic biomarker in NSCLC.

Risk of Congestive Heart Failure in Early Breast Cancer Patients Undergoing Adjuvant Treatment With Trastuzumab: A Meta-Analysis.

BACKGROUND: The use of trastuzumab has proven to be a successful strategy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, it is associated with an increased risk of cardiac dysfunction. We performed an up-to-date, comprehensive meta-analysis to clarify the risk of congestive heart failure (CHF) in patients with early breast cancer receiving different durations of adjuvant trastuzumab with the longest-term follow-up. METHODS: Eligible studies included randomized control trials of HER2-positive early breast cancer patients with or without trastuzumab in adjuvant chemotherapy. Adequate reporting of CHF data were required for inclusion. Statistical analyses were conducted to calculate the overall incidence, relative risk (RR), and 95% confidence interval (CI) by use of a fixed-effects model. RESULTS: Six randomized control trials including 18,111 patients were identified. The overall incidence of high-grade CHF in patients treated with trastuzumab versus placebo was 1.44% (95% CI, 0.79%-2.64%) and the RR was 3.19 (95% CI, 2.03-5.02; p < .00001). In subgroup analysis, the difference in CHF incidence failed to achieve significance. The RR for 8 mg/kg trastuzumab (high dose) was greater than that for 4 mg/kg (low dose) (RR, 6.79, 95% CI, 2.03-22.72, p = .0001; versus RR, 2.64; 95% CI, 1.61-4.32; p = .002). Additionally, higher RRs were observed for patients receiving trastuzumab for 1 year (RR, 3.29; 95% CI, 2.07-5.25) and 2 years (RR, 9.54; 95%CI, 2.19-41.43), but not 9 weeks (RR, 0.50; 95% CI, 0.05-5.49) compared with control groups. No evidence of publication bias was observed. CONCLUSION: Adjuvant trastuzumab therapy was strongly associated with an increased risk of significant CHF in patients with early breast cancer, particularly in 2-year use. IMPLICATIONS FOR PRACTICE: This comprehensive meta-analysis evaluated the risk of congestive heart failure with a usage profile of adjuvant trastuzumab in patients with early breast cancer. Before initiating treatment with trastuzumab, a risk-benefit analysis for individual patients should be critically evaluated, considering that the prognosis is closely related to drug dose and duration of use. Cardiac function should be monitored throughout the treatment period and also during follow-up. Thus, early identification of trastuzumab-related cardiac dysfunction can allow effective medical intervention, elimination of symptoms, recovery of function, and continuation of trastuzumab therapy.

[Manual immunohistochemistry for detecting ALK gene fusion antibody in 519 cases of non-small lung cancer].

OBJECTIVE: To investigate the expression of anaplastic lymphoma kinase (ALK) gene fusion antibody in non-small cell lung cancer (NSCLC) and explore the clinicopathological significance. METHODS: Using manual immunohistochemistry (IHC) with D5F3 rabbit monoclonal antibody, we detected the expression of ALK gene fusion protein in 519 cases of NSCLC. The relations of ALK fusion protein with the clinical characteristics of the patients and the histological classification of the tumors were analyzed. The expressions of ALK fusion protein were compared between surgical specimens and biopsy samples, and the consistency of manual IHC results was evaluated with the results of a fully automated IHC instrument and fluorescence in situ hybridization (FISH). RESULTS: The positivity rate of ALK fusion protein was 11.37% (59/519) among the cases detected by manual IHC. The patients tended to have a young age of onset (P=0.048) and most of the tumors were adenocarcinoma. In the surgical specimens, ALK fusion protein was expressed mostly in invasive mucinous adenocarcinoma (P<0.01), and it was a high risk factor of lymph node metastasis [OR=2.188(95%C.I:1.161-4.122)]. No statistical difference was found in the test results of manual IHC between surgical specimens and biopsy samples. The results by manual IHC suggesting a strong expression were consistent with the results by automated IHC and FISH. CONCLUSION: Manual IHC can be reliable for screening ALK fusion arrangement in patients with NSCLC.

Expression of paired basic amino acid-cleaving enzyme 4 (PACE4) correlated with prognosis in non-small cell lung cancer (NSCLC) patients.

BACKGROUND: Paired basic amino acid-cleaving enzyme 4 (PACE4) was shown to enhance tumor cells proliferation and invasive. This study provides the first investigation of PACE4 expression in non-small cell lung cancer (NSCLC) and the correlation with clinicopathologic features, prognostic indicators of 172 cases. METHODS: Quantitative real-time PCR (RT-PCR) and immunofluorescence (IF) were applied to detect PACE4 expression in NSCLC and 16HBE cell lines, then 172 consecutive NSCLC and 15 normal lung tissues were studied through immunohistochemistry (IHC). The association between PACE4 expression and clinicopathological parameters was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of PACE4 expression on survival. RESULTS: PACE4 expression in NSCLC were significantly higher than normal lung cell and tissues (P<0.05). PACE4 had cytoplasmic expression and was observed in 111 of the 172 (64.5%) NSCLC patients. Clinicopathologically, PACE4 expression was significantly associated with lymph node metastasis (N stage) (P=0.007), and clinical stage (P=0.024). Multivariable analysis confirmed that PACE4 expression increased the hazard of death after adjusting for other clinicopathological factors [hazards ratio (HR): 1.584; 95% confidence interval (CI): 1.167-2.151; P<0.001]. Overall survival (OS) was significantly prolonged in PACE4 negative group when compared with PACE4 positive group (5-year survival rates, 23.1% vs. 54.5%, log-rank test, χ(2)=17.717, P<0.001), as was disease-free survival (DFS) (5-year survival rates, 23.4% vs. 55.4%, log-rank test, χ(2)=20.486, P<0.001). CONCLUSIONS: Our results suggest that positive expression of PACE4 is an independent factor for NSCLC patients and it might serve as a potential prognostic biomarker for patients with NSCLC.