Malignant mesothelioma is a highly malignant disease that most often occurs in the pleural cavity, followed by the peritoneum and pericardium. Malignant peritoneal mesothelioma (MPM) accounts for 10%-15% of all mesothelioma. The most important risk factor for MPM is exposure to asbestos. MPM has no specific clinical symptoms, imaging and histopathology are critical for the diagnosis. There are currently no generally accepted guidelines for curative treatment of MPM. The patient mainly presented with abdominal pain, abdominal distension and discomfort. Due to extensive omentum metastasis, no further surgical treatment was performed. Pemetrexed combined with cisplatin chemotherapy was given for 2 cycles, and the patient is still alive.
Humans ; Mesothelioma, Malignant/drug therapy* ; Mesothelioma/diagnosis* ; Pemetrexed/therapeutic use* ; Cisplatin/therapeutic use* ; Peritoneal Neoplasms/diagnosis* ; Pleural Neoplasms ; Lung Neoplasms/drug therapy*

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*

BACKGROUND: In advanced non-small cell lung cancer (NSCLC), leptomeningeal metastases (LM) is a common consequence with rapid progression and a poor prognosis. LM affects roughly 3% to 5% of NSCLC patients, and it affects as many as 9.4% of individuals with epidermal growth factor receptor (EGFR) mutations. Cerebrospinal fluid cytology is the gold standard for diagnosing LM, while conventional cytopathology has a positive detection rate of less than 50%, resulting in a delay in diagnosis and treatment of LM. The fixation treatment of cerebrospinal fluid samples has a significant impact on the positive cytology detection rate, and how to improve the positive cytopathology detection rate of cerebrospinal fluid is a hot topic in clinical research. METHODS: From June 2019 to November 2021, 105 cases diagnosed with LM based on clinical symptoms and positive imaging were collected and retrospectively evaluated in the second ward of the Department of Oncology of The Second Affiliated Hospital of Harbin Medical University. The effect of different fixation methods on the positive rate of cerebrospinal fluid cytopathology was investigated, and specimens of cerebrospinal fluid were collected and sent for examination using different delivery methods, including the application of the TIB cell preservation solution kit (experimental group) and the routine application of sterile plastic tubes in lumbar puncture bags (control group). Biochemical assays (glucose and total protein) were performed on the cerebrospinal fluid fluid, and Logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the supplementary diagnostic value for LM patients with lung cancer. The relevance of chemical indexes in the assessment of therapeutic efficacy was examined, and biochemical (glucose, total protein) indices and cytological changes in cerebrospinal fluid fluid after pemetrexed intrathecal injection therapy were dynamically monitored. RESULTS: In the control group, 24 (45.28%) patients were positive for the first time, while 42 (80.77%) patients were positive for the first time and 10 (19.23%) patients were negative for the first time in the experimental group. Significant differences existed between the two groups (P<0.001). The results of Logistic regression analysis of patients with the first cerebrospinal fluid biochemical test showed that the risk of positive cerebrospinal fluid biochemical pathology with less than 2.5 mmol/L was 2.456 times greater than 2.5 mmol/L of cerebrospinal fluid glucose (OR=2.456, P<0.05), and total cerebrospinal fluid biochemical protein greater than 430 mg/L was 2.647 times less than 430 mg/L (OR=2.647, P>0.05). The ROC curve showed glucose sensitivity of 76.9% in cerebrospinal fluid, the specificity of 54.5%, Youden index of 0.315 and area under the curve (AUC) of 0.620, total protein sensitivity in cerebrospinal fluid of 44.4%, 90.6%, Youden index of 0.350 and AUC of 0.671. After 2 cycles of pemetrexed intrathecal treatment with complete cerebrospinal fluid cytology and cerebrospinal fluid biochemical (glucose, total protein) tests in 73 and 50 patients, respectively, the rate of cerebrospinal fluid cytology turning negative was gradually increased. Cerebrospinal fluid glucose levels increased after 2 cycles of treatment compared with the first time, with a statistically significant difference (P<0.001). CONCLUSIONS The use of a cell preservation solution kit to immediately fix cerebrospinal fluid samples following isolation in patients with clinical symptoms and positive imaging greatly enhances the rate of positive cerebrospinal fluid cytology detection. The effect of treatment can be assessed and predicted by continuous dynamic monitoring of cerebrospinal fluid biochemistry and cytology.
Humans ; Lung Neoplasms/pathology* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Pemetrexed/therapeutic use* ; Retrospective Studies ; Meningeal Carcinomatosis/secondary* ; Glucose/therapeutic use*

Bevacizumab, an anti-VEGF monoclonal antibody, has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC (ns-NSCLC). However, the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation. Thus, 59 patients were included in the present retrospective study, 22 patients in the bevacizumab plus pemetrexed and platinum (B + PP) group, and 37 patients in the pemetrexed and platinum (PP) group. For the entire cohort of patients, the median OS was 33.3 months, and the 1-year and 2-year overall survival rates were 88.5% and 67.8%, respectively. The median OS and 1-year and 2-year OS rates were 20.5 months, 70.3% and 0%, respectively, in the B + PP group and 33.4 months, 97.0% and 89.4%, respectively, in the PP group (P < 0.001). The incidence of grade ⩾ 3 adverse events was higher in the B + PP group than in the PP group (27.3% vs. 10.8%, respectively; P = 0.204). Univariate and multivariate analyses suggested that the receipt of ⩾ 5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS, whereas the addition of bevacizumab was an unfavorable prognostic factor. With increased toxicities, the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.
Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Bevacizumab/adverse effects* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/drug therapy* ; Pemetrexed/adverse effects* ; Platinum/therapeutic use* ; Retrospective Studies ; Treatment Outcome

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive disease arising from pleural mesothelial cells. Advanced pleural mesothelioma has a poor prognosis, with a median survival of no more than 15 months. First line standard chemotherapy regimen recommended is Pemetrexed based chemotherapy regimen, with or without bevacizumab. There is no consensus on whether patients who have received first-line standard chemotherapy can benefit from pemetrexed maintenance chemotherapy. The study aimed to investigate the efficacy and safety of pemetrexed maintenance therapy (PMT) after treatment with a pemetrexed and platinum regimen for patients with MPM. METHODS: A total of 40 MPM patients were collected from Cancer Hospital Chinese Academy of Medical Sciences from January 2013 to January 2018, eligible patients were unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum, including pemetrexed maintenance therapy group (22 cases) and observation group (18 cases). The last follow-up was conducted in January 2020. The primary endpoint were progression free survival (PFS), and the secondary end points were overall survival (OS), the efficacy, adverse reactions of PMT. RESULTS: The median PFS in the PMT arm was longer than that in the observation arm (8.5 mon vs 3 mon, P=0.008), but there was no significant difference in median OS (26.4 mon vs 15.7 mon, P=0.177). Objective response rate (ORR) of two group were 22.7% and 0%, respectively. The grade 3-4 toxicity in PMT group included grade 4 neutropenia in 1 patient (4.5%), grade 3 neutropenia in 1 patient (4.5%), grade 4 anemia in 1 patient (4.5%) and grade 3 nausea and anorexia in 1 patient (4.5%). CONCLUSIONS Pemetrexed maintenance therapy following initial pemetrexed and platinum chemotherapy improve PFS in patients with MPM, and is well tolerated.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Cisplatin/therapeutic use* ; Humans ; Lung Neoplasms/drug therapy* ; Mesothelioma/drug therapy* ; Mesothelioma, Malignant ; Neutropenia ; Pemetrexed/therapeutic use* ; Platinum/therapeutic use* ; Pleural Neoplasms/drug therapy*

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/drug therapy* ; Meningeal Carcinomatosis/drug therapy* ; Pemetrexed ; Treatment Outcome

OBJECTIVE: To evaluate the efficacy of iRoot BP Plus, a novel bioceramic material, and mineral trioxide aggregate (MTA) by comparing the clinical and radiographic results of pulpotomy in human primary molars, and to find out the influence factor. METHODS: Children who had at least one primary molar diagnosed as pulpitis, and received pulpotomy in the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology from January, 2017 to December, 2018 were searched by the selection criteria in the Electronic Medical Record Database of Peking University School and Hospital of Stomatology. The molars with the pulp capping agents were iRoot BP Plus or MTA were included, and the molars with other pulp capping agents were excluded. Molars using iRoot BP Plus were selected into the experimental group (iRoot BP Plus group). Molars using MTA were selected into the control group (MTA group) using propensity score matching model (1 ∶ 1), considering the gender, age, tooth position, the title of clinician, pulp status, restoration and length of follow-up as the potential influence factor. Basic information, the relevant medical records including symptoms, clinical and radiographic examination before and after operation, intraoperative information and follow up examination records were collected. The success rates were compared and the influence factors were analyzed respectively. RESULTS: The study included 132 children, 178 molars (89 molars from each group) and the mean follow-up time was (462±99) days by December, 2019. In the iRoot BP Plus group, 9 molars failed whilst 6 molars failed in MTA group. The success rate was 89.9% and 93.3%, respectively, showing no significant difference between the two groups. Through Cox proportional risk model analysis, the success rate of iRoot BP Plus was significantly lower when the pulp status was poor, while other factors including age, tooth position, title of clinician and restoration were not found to be associated with the clinical outcome. CONCLUSION Pulpotomy of human primary molars with iRoot BP Plus has the same effectiveness with MTA. The pulp status is the main factor that influences the outcome of iRoot BP Plus. Further studies with larger sample sizes and longer follow-up terms are needed.
Child ; Humans ; Pulpotomy/methods* ; Pulp Capping and Pulpectomy Agents ; Pemetrexed ; Silicates/therapeutic use* ; Aluminum Compounds/therapeutic use* ; Calcium Compounds ; Oxides ; Molar/surgery* ; Drug Combinations ; Treatment Outcome ; Tooth, Deciduous

OBJECTIVES: This study aimed to compare the shear bond strength (SBS) of a self-adhering flowable composite (Dyad Flow) and a bulk-fill flowable composite (Smart Dentin Replacement [SDR]) to several pulp-capping materials, including MTA Plus, Dycal, Biodentine, and TheraCal.MATERIALS AND METHODS: Eighty acrylic blocks with 2-mm-deep central holes that were 4 mm in diameter were prepared and divided into 2 groups (n = 40 each) according to the composite used (Dyad Flow or SDR). They were further divided into 4 sub-groups (n = 10 each) according to the pulp-capping agent used. SBS was tested using a universal testing machine at a crosshead speed of 1 mm/min. Data were analyzed using 2-way analysis of variance. A p value of < 0.05 was considered to indicate statistical significance.RESULTS: A statistically significant difference (p = 0.040) was found between Dyad Flow and SDR in terms of bond strength to MTA Plus, Dycal, Biodentine, and TheraCal.CONCLUSIONS: Among the 8 sub-groups, the combination of TheraCal and SDR exhibited the highest SBS.
Dentin ; In Vitro Techniques ; Pemetrexed

OBJECTIVES: The obturation quality of MTA, Biodentine, Total Fill BC root canal sealer (RCS), and warm gutta-percha (WGP) in teeth with simulated internal root resorption (IRR) was evaluated by using micro-computed tomography.MATERIALS AND METHODS: Standardized IRR cavities were created using 40 extracted maxillary central incisor teeth and randomly assigned into 4 groups (n = 10). IRR cavities were filled with MTA, Biodentine, Total Fill BC RCS (bulk-fill form) and WGP + Total Fill BC RCS. Percentage of voids between resorptive cavity walls and obturation material (external void), and inside the filling materials (internal voids) were measured.RESULTS: Total Fill BC sealer in the bulk-fill form presented significantly highest values of external and internal void percentages (p < 0.05). Biodentine showed a significantly lowest external void percentage (p < 0.05). WGP + Total Fill BC RCS presented significantly lower values of internal void percentages than all groups (p < 0.05), except Biodentine (p > 0.05).CONCLUSION: None of the filling materials were created void-free obturation in resorption cavities. Biodentine may favor its application in teeth with IRR over Angelus MTA and bulk-fill form of Total Fill BC.
Calcium ; Dental Pulp Cavity ; Gutta-Percha ; Incisor ; Pemetrexed ; Root Resorption ; Tooth

OBJECTIVES: This study investigated the indirect effect of calcium-enriched mixture (CEM) cement and mineral trioxide aggregate (MTA), as 2 calcium silicate-based hydraulic cements, on human dental pulp stem cells (hDPSCs) through different dentin thicknesses.MATERIALS AND METHODS: Two-chamber setups were designed to simulate indirect pulp capping (IPC). Human molars were sectioned to obtain 0.1-, 0.3-, and 0.5-mm-thick dentin discs, which were placed between the 2 chambers to simulate an IPC procedure. Then, MTA and CEM were applied on one side of the discs, while hDPSCs were cultured on the other side. After 2 weeks of incubation, the cells were removed, and cell proliferation, morphology, and attachment to the discs were evaluated under scanning electron microscopy (SEM). Energy-dispersive X-ray (EDXA) spectroscopy was performed for elemental analysis. Alkaline phosphatase (ALP) activity was assessed quantitatively. The data were analyzed using the Kruskal-Wallis and Mann-Whitney tests.RESULTS: SEM micrographs revealed elongated cells, collagen fibers, and calcified nucleations in all samples. EDXA verified that the calcified nucleations consisted of calcium phosphate. The largest calcifications were seen in the 0.1-mm-thick dentin subgroups. There was no significant difference in ALP activity across the CEM subgroups; however, ALP activity was significantly lower in the 0.1-mm-thick dentin subgroup than in the other MTA subgroups (p < 0.05).CONCLUSIONS: The employed capping biomaterials exerted biological activity on hDPSCs, as shown by cell proliferation, morphology, and attachment and calcific precipitations, through 0.1- to 0.5-mm-thick layers of dentin. In IPC, the bioactivity of these endodontic biomaterials is probably beneficial.
Alkaline Phosphatase ; Biocompatible Materials ; Calcium ; Cell Proliferation ; Collagen ; Dental Pulp Capping ; Dental Pulp ; Dentin ; Endodontics ; Humans ; Microscopy, Electron, Scanning ; Miners ; Molar ; Pemetrexed ; Spectrum Analysis ; Stem Cells