BACKGROUND: The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses. METHODS: Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework. RESULTS: This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively. CONCLUSION Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Afatinib/therapeutic use* ; Lung Neoplasms/metabolism* ; Bevacizumab/therapeutic use* ; Bayes Theorem ; Network Meta-Analysis ; Protein Kinase Inhibitors/therapeutic use* ; Pemetrexed/therapeutic use* ; ErbB Receptors/genetics* ; Brain Neoplasms/genetics* ; Mutation/genetics*

Antibody drug conjugates (ADCs) are a novel class of anti-cancer drugs, which combined the specificity of monoclonal antibodies with the cytotoxic palyload via the linkers. Many ADCs have not only verified impressive activity in a variety of cancers, including breast cancer and hematological system tumors, but also in lung cancer. The aim of this study was to provide informations for practice by summarizing the mechanism of action, clinical application and problems and challenges of ADCs.
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Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Humans ; Immunoconjugates/therapeutic use* ; Lung Neoplasms/drug therapy* ; Neoplasms/drug therapy*

Advanced non-small cell lung cancer (NSCLC) patients are commonly with brain metastases, leading to poor survival and quality of life. Epidermal growth factor receptor (EGFR) is common sensitive mutation type in NSCLC. Compared with other molecular types, it has different molecular biological characteristics. For patients with brain metastases and EGFR-mutated advanced NSCLC, EGFR-tyrosine kinase inhibitors can prolong overall survival and improve intracranial and extracranial control rate. To understand the characteristics of brain metastases of patients with sensitively EGFR-mutated NSCLC, the incidence, onset time, site, number and size of lesions, symptoms, targeted treatment effect and disease outcomes were reviewed, which can provide reference for interventional timing and local treatment technology selection of local treatment for brain parenchymal metastases.

In addition to rare incidence of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 receptor kinase (ROS1) positive patients, patients with brain metastases of non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) sensitive mutation have no effective systemic therapy at present, and the overall prognosis is poor. Since the low blood-brain barrier permeability of chemotherapy drugs, the local treatment plays an important role in brain metastases. To understand the clinical characteristics and treatment of brain parenchymal metastases in patients with NSCLC and EGFR mutation negative, we reviewed the incidence, onset time, site, numbers, size, symptom, therapeutic effect and disease evolution in them, which can provide reference for interventional timing and local treatment technology selection of local treatment for brain parenchymal metastases.
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Objective To discuss the clinical characteristics for lateral cervical lymph node metastasis in stage cN0 papillary thyroid microcarcinoma and significance and feasibility of preventive dissection,and provide reference for clinical treatment.Methods Reviewd the clinical data of 191 patients with stage cN0 papillary thyroid microcarcinoma patients from Jul.2011 to Dec.2016 underwent surgery in the Department of General Surgery of Lianyungang Oriental Hospital.Assessed the need for preventive cervical lymph node dissection.Chisquare test and logistic regression were used to analyze the relationship between cervical lymph node metastasis and gender,age,tumor number,tumor size,capsule infiltration,single and bilateral tumors,Hashimoto's disease,and central lymph node metastasis.Results The positive rate of cervical lymph node metastasis in papillary thyroid microcarcinoma was 27.9％ (50/191).Univariate analysis showed that the metastasis of the cervical lymph nodes was associated with infiltration of the capsule,Hashimoto disease,and CLN metastasis (all P ＜ 0.05).Multivariate logistic regression analysis showed that the capsule infiltration (OR =7.563,P =0.000),Hashimoto's disease (OR =4.635,P =0.003),and central lymph node metastasis (OR =3.075,P ＜ 0.001) were able to be independent risk factors for cervical lymph node metastasis.When the positive number of lymph node metastasis in the central region was ≥ 2,the positive rate of cervical lymph nodes was significantly increased (P ＜ 0.001).Eleven patients (5.8％) had temporary recurrent laryngeal nerve palsy,29 patients (15.1％) had transient hypoparathyroidism,and no patients with permanent recurrent laryngeal nerve palsy and hypoparathyroidism.Conclusions The removal of the cervical lymph nodes helps to accurately classify the tumor and assess the risk.It is important to choose the postoperative treatment follow-up plan for patients.For patients with capsule infiltration,Hashimoto's disease,and central lymph node metastasis,cervical lymph node dissection should be routinely performed.

Standard treatment for resectable IIIa/N2 non-small-cell lung cancer (NSCLC) is still under debate. Optional treatments include chemotherapy, radiotherapy and surgery, other options include target therapy and immunotherapy. Multidisciplinary treatment has therefore been emphasized by various clinical trials, including bimodality strategy which has been defined as chemotherapy plus surgery or chemotherapy plus radiotherapy, and trimodality treatment which refers to chemotherapy plus surgery and radiotherapy. However, there is still no consensus on the optimal strategy on treating resectable IIIa/N2 NSCLC. Therefore, we reviewed a series of phase II and III clinical trials as well as some meta-analyses and case reports to compare the efficacy of different strategies on survival of cN2 NSCLC, and concluded that for resectable IIIa/N2 NSCLC surgery is recommended, and that strategy of chemotherapy plus surgery may not achieve better survival than that of chemotherapy plus radiotherapy. Size of tumor as well as lymph nodes should be taken into account when choosing optimal therapy, so that promising individualized strategy could be given to patients with resectable stage IIIa/N2 NSCLC.
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Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Lung Neoplasms ; drug therapy ; radiotherapy ; surgery ; therapy ; Meta-Analysis as Topic ; Neoplasm Staging ; Treatment Outcome

Objective To evaluate clinical outcome of uremic secondary hyperparathyroidism (sHPT) using total parathyroidectomy combined with autologous transplantation for treatment.Methods Clinical data of patients undergoing thyroid secondary parathyroidectomy combined with autologous transplantation in our hospital were retrospectively analyzed.The clinical symptoms and parathyroid hormone (iPTH),and changes of free calcium,serum phosphorus,alkaline phosphatase before and after parathyroidectomy were recorded and analyzed.Results The clinical symptoms such as bone pain and pruritus were completely disappeared in six months after surgery.Postoperative iPTH,serum calcium,phosphorus,and calcium-phosphorus products decreased significantly compared with preoperative values (P ＜ 0.05).There were 29 patients (87.9％) developed hypocalcemia.There was no significant change in alkaline phosphatase within one week after surgery compared with preoperation (P ＞ 0.05);iPTH,serum calcium,phosphorus,and calcium-phosphorus product fluctuated in normal levels at follow-up.Preoperative PTH level was positively correlated with preoperative ALP before surgery (r =0.984,P =0.000).Conclusion Total parathyroidectomy combined with auto-transplantation is considered to be a feasible,safe and effective surgical option for the treatment of sHPT.

Objective To evaluate clinical outcome of uremic secondary hyperparathyroidism (sHPT) using total parathyroidectomy combined with autologous transplantation for treatment.Methods Clinical data of patients undergoing thyroid secondary parathyroidectomy combined with autologous transplantation in our hospital were retrospectively analyzed.The clinical symptoms and parathyroid hormone (iPTH),and changes of free calcium,serum phosphorus,alkaline phosphatase before and after parathyroidectomy were recorded and analyzed.Results The clinical symptoms such as bone pain and pruritus were completely disappeared in six months after surgery.Postoperative iPTH,serum calcium,phosphorus,and calcium-phosphorus products decreased significantly compared with preoperative values (P ＜ 0.05).There were 29 patients (87.9％) developed hypocalcemia.There was no significant change in alkaline phosphatase within one week after surgery compared with preoperation (P ＞ 0.05);iPTH,serum calcium,phosphorus,and calcium-phosphorus product fluctuated in normal levels at follow-up.Preoperative PTH level was positively correlated with preoperative ALP before surgery (r =0.984,P =0.000).Conclusion Total parathyroidectomy combined with auto-transplantation is considered to be a feasible,safe and effective surgical option for the treatment of sHPT.

The aim of this study was to identify antigens for a vaccine or drug target to control rabbit coccidiosis. A combination of 2-dimensional electrophoresis, immunoblotting, and mass spectrometric analysis were used to identify novel antigens from the sporozoites of Eimeria stiedae. Protein spots were recognized by the sera of New Zealand rabbits infected artificially with E. stiedae. The proteins were characterized by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) analysis in combination with bioinformatics. Approximately 868 protein spots were detected by silver-staining, and a total of 41 immunoreactive protein spots were recognized by anti-E. stiedae sera. Finally, 23 protein spots were successfully identified. The proteins such as heat shock protein 70 and aspartyl protease may have potential as immunodiagnostic or vaccine antigens. The immunoreactive proteins were found to possess a wide range of biological functions. This study is the first to report the proteins recognized by sera of infected rabbits with E. stiedae, which might be helpful in identifying potential targets for vaccine development to control rabbit coccidiosis.
Coccidiosis* ; Computational Biology ; Eimeria ; Electrophoresis ; HSP70 Heat-Shock Proteins ; Immunoblotting ; Mass Spectrometry ; Rabbits ; Sporozoites