CTNNB1 mutation-driven hybrid tumor: desmoid fibromatosis with an unusual associated epithelioid component arising in association with a neuromuscular choristoma.

CTNNB1 mutations play important roles in the development of soft tissue tumors, such as desmoid fibromatosis (DF), sinonasal tract angiofibroma, sinonasal glomangiopericytoma, intranodal palisaded myofibroblastoma, neuromuscular choristoma (NMC), and the recently reported pseudoendocrine sarcoma. Here, we report a unique hybrid soft tissue tumor with classic DF, unusual epithelioid component, and NMC in a 23-year-old female. The classic DF and NMC and the unusual epithelioid component and NMC were locally intermixed and closely related to each other. Immunohistochemically, the DF, unusual epithelioid component, and NMC exhibited nuclear positivity for ß-catenin to varying degrees. More critically, all of the above components harbored identical CTNNB1 p.Ser45Pro missense mutations. To the best of our knowledge, this is the only reported CTNNB1 mutation-driven hybrid tumor with DF, unusual epithelioid component, and NMC. The present case further confirmed that CTNNB1-mutational soft tissue tumors are highly heterogeneous, but the morphological spectrum is wide and consecutive.

Progress in research on the role of clinical nutrition in treating traumatic brain injury affecting the neurovascular unit.

The neurovascular unit (NVU) is composed of neurons, glial cells, and blood vessels. NVU dysfunction involves the processes of neuroinflammation, and microcirculatory disturbances, as well as neuronal injury after traumatic brain injury (TBI). Traditional anti-inflammatory drugs have limited efficacy in improving the prognosis of TBI. Thus, treatments that target NVU dysfunction may provide a breakthrough. A large number of clinical studies have shown that the nutritional status of patients with TBI was closely related to their conditions and prognoses. Nutrient complexes and complementary therapies for the treatment of TBI are therefore being implemented in many preclinical studies. Importantly, the mechanism of action for this treatment may be related to repair of NVU dysfunction by ensuring adequate omega-3 fatty acids, curcumin, resveratrol, apigenin, vitamins, and minerals. These nutritional supplements hold promise for translation to clinical therapy. In addition, dietary habits also play an important role in the rehabilitation of TBI. Poor dietary habits may worsen the pathology and prognosis of TBI. Adjusting dietary habits, especially with a ketogenic diet, may improve outcomes in patients with TBI. This article discusses the impact of clinical nutrition on NVU dysfunction after TBI, focusing on nutritional complexes and dietary habits.

Driver genes as predictive indicators of brain metastasis in patients with advanced NSCLC: EGFR, ALK, and RET gene mutations.

BACKGROUND: A retrospective analysis verified the role of gene mutations in brain metastasis in patients with non-small cell lung cancer (NSCLC). METHODS: Data from 552 patients with advanced NSCLC treated from January 2015 to June 2017 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. Next-generation sequencing was used to detect mutations in eight reported driver genes and various risk factors were evaluated. RESULTS: Of the 552 patients with advanced NSCLC, 153 (27.7%) had brain metastases. The univariate analysis showed that age (P = .008), gender (P = .016), smoking history (P = .010), lymph node metastasis (P = .003), and three driver genes, positive epidermal growth factor receptor (EGFR) mutation (P = .001), positive anaplastic lymphoma kinase (ALK) gene fusion (P = .021), and positive rearranged during transfection (RET) gene fusion (P = .003), were the factors influencing the incidence of brain metastasis. Logistic multivariate regression analysis revealed that positive EGFR mutation (P = .012), positive ALK gene fusion (P = .015), positive RET gene fusion (P = .003), pathological type (P = .009), lymph node N2-3 metastasis (P < .001), and a younger age (P < .001) were independent risk factors for brain metastasis. In addition, a receiver operating characteristic (ROC) curve was plotted with the above factors with an area under the curve = 0.705 (P < .001). CONCLUSIONS: An EGFR mutation, ALK gene fusion, and RET gene fusion in advanced NSCLC patients play roles in brain metastasis as positive driver genes. IMPACT: An EGFR mutation, and ALK and RET gene fusions are risk factors for brain metastasis in advanced NSCLC patients.

Efficacy and long-term survival of advanced lung adenocarcinoma patients with uncommon EGFR mutations treated with 1st generation EGFR-TKIs compared with chemotherapy as first-line therapy.

PURPOSE: This study aims to understand the effects and long-term survival of 1st generation epithelial growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)or platinum-based chemotherapy as first-line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations. PATIENTS AND METHODS: Specimens from 4276 advanced (IIIB/IV) patients were diagnosed with lung adenocarcinoma and underwent EGFR gene detection at the Affiliated Cancer Hospital of Zhengzhou University. The clinic characteristics, survival outcomes data, treatment outcomes and data of subsequent therapies after first-line treatment were collected of patients with uncommon EGFR mutations. The results were compared with common EGFR mutations. RESULTS: For patients with uncommon EGFR mutations, EGFR-TKIs or platinum-based chemotherapy as first-line therapy, showed no difference in objective response rate (ORR 33% vs 27.1% P = 0.499) and disease control rate (DCR 76.5% vs 87.5%, P = 0.194). EGFR-TKIs showed a superior progression-free survival than chemotherapy (median PFS, 7.2 vs 4.9 mt, HR = 0.604; P = 0.0088). Interestingly, compared with chemotherapy, we found that overall survival (median OS, 14.3 vs 20.7 mts, HR = 1.759; P = 0.0336) was significantly worse in patients with EGFR-TKIs. Multivariate analysis showed that extra metastases (HR = 2.240, P = 0.001) and smoking history (HR = 2.048, P = 0.013) were independent prognostic factors for OS in lung adenocarcinoma patients with EGFR uncommon mutations. CONCLUSIONS: Compared with chemotherapy, use of the 1st generation of EGFR-TKIs as first-line therapy can improve the short-term efficacy of patients with EGFR uncommon mutations advanced lung adenocarcinoma, but platinum-based chemotherapy showed a longer overall survival.

Mutation tracking of a patient with EGFR-mutant lung cancer harboring de novo MET amplification: Successful treatment with gefitinib and crizotinib.

OBJECTIVE: De novo mesenchymal-epithelial transition (MET) amplification is believed to promote primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in the non-squamous non-small cell lung cancer (NSCLC). We sought to seek the treatment of a patient with EGFR-mutant NSCLC harboring de novo MET amplification. MATERIALS AND METHODS: After clinical diagnosis, tissue and plasma samples were obtained from the patient and subjected to next-generation sequencing to identify and dynamic monitor the mutations. RESULTS: The patient was treated with gefitinib monotherapy in the beginning and experienced primary resistance to gefitinib but achieved a good response to the combination therapy of gefitinib and crizotinib. He achieved a 16.8-month progress free survival with the combination therapy. NGS of plasma circulating cell-free tumor DNA shown that L858R mutation was no longer detectable and the copy number of MET dropped when the patient got remission. CONCLUSIONS: The combination of EGFR- and MET- tyrosine kinase inhibitors may be an effective treatment for the rare mutations.

Efficacy of first-line treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) alone or in combination with chemotherapy for advanced non-small cell lung cancer (NSCLC) with low-abundance mutation.

OBJECTIVE: The objective of this study was to investigate whether first-line treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy improves the prognosis of patients with advanced non-small cell lung cancer (NSCLC) who harbour low-abundance EGFR mutations. PATIENTS AND METHODS: We retrospectively analysed the clinical data of 76 patients with advanced NSCLC who harboured low-abundance EGFR mutations. The patients were divided into the combination group and the monotherapy group. The combination group received EGFR-TKI combined with a platinum-based regimen. After the end of chemotherapy, EGFR-TKI was administered daily. The monotherapy group was administered EGFR-TKI therapy daily. RESULTS: No significant difference was observed in response rate between the different groups. The median PFS and OS were significantly longer in the combination group than in the monotherapy group (PFS: 7.9 months [95% CI,5.73-10.07] vs 5.9 months [95% CI, 4.99-6.81], p = 0.015; OS: 25.8 months[95% CI,16.27-35.33] vs 19.8 months [95% CI, 18.60-21.00], p = 0.047). Subgroup analysis showed that, for patients with the exon 21 L858R mutation, the PFS and OS were significantly longer in the combination group than in the monotherapy group (PFS: 7.2 months vs 5.8 months, p = 0.013; OS: 22.0 months vs 18.7 months, p = 0.024). The incidence of adverse events was significantly higher in the combination group. CONCLUSION: For patients with advanced NSCLC and low-abundance EGFR mutations, first-line treatment with EGFR-TKI plus chemotherapy significantly improved PFS and OS. The combination therapy increased the incidence of adverse reactions, but all adverse reactions were expected and tolerated.

Apatinib as maintenance therapy in extensive-stage small-cell lung cancer: results from a single-center retrospective study.

PURPOSE: To evaluate the efficacy of maintenance apatinib after chemotherapy for extensive-stage (ED) small-cell lung cancer (SCLC). PATIENTS AND METHODS: This was a retrospective analysis of 23 cases of extensive-stage SCLC admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2015 to December 2017. The patients without progression after induction chemotherapy received apatinib 250 mg per day until disease progression or unacceptable toxicity occurred. We analyzed the median progression-free survival (PFS), median overall survival (OS) and safety. RESULTS: Of 23 enrolled patients, 1 was lost to follow-up. The median PFS from the time of maintenance therapy was 4.1 months (95% CI 3.63-4.57 months). The median PFS from the time of induction chemotherapy was 8.3 months (95% CI 7.20-9.40 months). The median OS from the time of maintenance therapy was 12.5 months (95% CI 5.51-19.49 months). The median OS from the time of induction chemotherapy was 17.0 months (95% CI 9.86-24.14 months). The most frequent treatment-related adverse events were hand-foot syndrome (43.5%, 10/23) and secondary hypertension (30.4%, 7/23), followed by fatigue, proteinuria, nausea, and oral mucositis (17.4%, 13.0%, 13.0%, and 8.7%, respectively). Hematologic toxicity included thrombocytopenia (30.4%), leucopenia (26.1%), and anemia (17.4%). The main grade 3 or 4 toxicities were hand-foot syndrome (8.7%, 2/23) and hypertension (4.3%, 1/23). CONCLUSION: Maintenance apatinib was safe and achieved encouraging PFS and OS in extensive-stage SCLC.

[Efficacy and Safety of Bevacizumab Combined with Chemotherapy as Second-line or Later-line Treatment in Advanced Nonsquamous Non-small Cell Lung Cancer].

BACKGROUND: Bevacizumab combined with platinum-based chemotherapy has been recommended as the first-line agent in advanced nonsquamous non-small cell lung cancer (NSCLC) without driven gene, but this regimen is not common in the second-line or later-line treatment of non-squamous NSCLC. The aim of this study is to investigate the efficacy and safety of bevacizumab combined with chemotherapy as second-line or later-line treatment in advanced non-squamous NSCLC. METHODS: We retrospectively reviewed the clinical data of advanced nonsquamous NSCLC patients who were treated with bevacizumab after first-line treatment failure and they were hospitalized in the Affiliated Cancer Hospital of Zhengzhou University from January 2014 to June 2017, and Kaplan-Meier method, Log-rank test and Cox model were used for analysis. RESULTS: A total of 62 patients were included in the analysis. The total objective response rate (ORR) was 32.2%, and the disease control rate (DCR) was 96.8%. The median progression-free survival (PFS) was 6.4 months (95%CI: 6.05-6.83), and the median overall survival (OS) was 20.4 months (95%CI: 12.98-27.76). In the subgroup analysis, there was no significant difference in median PFS between patients with brain metastases and those without brain metastases (6.2 months vs 6.4 months, P=0.052). Cycles of bevacizumab (>6 or ≤6 cycles) was an independent influencing factor of PFS (P=0.004). The most common adverse events were leukopenia, fatigue, nausea, thrombocytopenia and hypertension. CONCLUSIONS: In the second-line or later-line treatment, bevacizumab combined with chemotherapy is an effective and safe regimen for advanced non-squamous NSCLC.

[Effects of plant growth regulators on cutting propagation of Rosa laevigata].

OBJECTIVE: To explore the optimal plant growth regulator and its suitable concentration for the cutting propagation of Rosa laevigata. METHODS: The cuttings were dealt with 6 kinds of plant growth regulators (IAA,IBA, NAA, PP333, 2, 4-D and ABT) at different concentrations (100, 200 and 500 mg/L) for 50 seconds. After 30 days growth, by analysis of variance and multiple comparisons,the most suitable cutting propagation method for Rosa laevigata was found. RESULTS: Under the same condition, different concentration of different kinds of plant growth regulators had different effects on cutting propagation of Rosa laevigata. Generally speaking,cuttings soaked with 200 mg/L PP333 for 50 seconds was the best,with the high multiple effectiveness index and average root number (12.42); Cuttings soaked with 200 mg/L IBA for 50 seconds also had significant effects, with the second high multiple effectiveness index and the highest survival rate (96.67%). CONCLUSION: 200 mg/L PP333 can promote cutting propagation of Rosa laevigata best.