Incidence and risk of severe adverse events associated with trastuzumab emtansine (T-DM1) in the treatment of breast cancer: an up-to-date systematic review and meta-analysis of randomized controlled clinical trials.

OBJECTIVES: We performed an up-to-date meta-analysis to quantify the overall incidence and risk of severe adverse events (AEs) associated with T-DM1 in patients with breast cancer. METHODS: Pubmed, Embase, and oncology conference proceedings were searched for relevant studies. Data were extracted to calculate the summary incidence rate and relative risk (RR) of grade ≥3 AEs. RESULTS: A total of 5,045 patients from 7 RCTs were included in the meta-analysis. The use of T-DM1 was associated with an increased risk of severe thrombocytopenia (RR 10.66, 95% CI 3.23-35.18, P < 0.001), anemia (RR 1.68, 95% CI 1.15-2.44, P = 0.007), elevated ALT (RR 2.67, 95% CI 1.60-4.47, P < 0.001), and AST (RR 3.76, 95% CI 1.45-9.78, P = 0.007). In addition, the use of T-DM1 can increase the risk of severe hypertension (RR 1.59, 95% CI 1.03-2.45, P = 0.037) and peripheral sensory neuropathy (RR 8.13, 95% CI 1.89-35.03, P = 0.005). CONCLUSIONS: Treatment with T-DM1 increases the risk of severe hematologic toxicities, hepatotoxicity, hypertension, and peripheral sensory neuropathy in patients with breast cancer, while the overall incidence of these AEs is low.

Association of Adjuvant Radiation Therapy With Long-Term Overall and Recurrence-Free Survival After Hepatectomy for Hepatocellular Carcinoma: A Multicenter Propensity-Matched Study.

PURPOSE: R0 resection with a wide surgical margin is the gold standard for hepatocellular carcinoma (HCC), yet R0 resection with narrow margins and even R1 resection is not uncommon in real-world clinical practice. We sought to use a propensity-matched analysis to characterize the efficacy of adjuvant radiation therapy on long-term oncological survival after hepatectomy for HCC with narrow or positive margins. METHODS AND MATERIALS: Using a multi-institutional database, patients with HCC who underwent hepatectomy with negative margins of 0.1 to 1.0 cm or pathologically positive margins were analyzed. Using propensity score matching (PSM) and multivariate Cox-regression analysis, the effect of adjuvant radiation therapy on long-term overall survival (OS) and recurrence-free survival (RFS) was evaluated. RESULTS: Among 683 patients who met inclusion criteria, 82 patients received adjuvant radiation therapy within 10 weeks after surgery. Radiation therapy-related major toxic effects were minimal among patients receiving adjuvant radiation therapy. PSM analysis created 78 matched pairs of patients. In the PSM cohort, median OS and RFS among patients treated with adjuvant radiation therapy were more favorable than individuals who were not treated (72.5 and 37.3 months versus 52.5 and 24.0 months, both P < .05). After adjustment for other confounding factors on multivariate analyses, adjuvant radiation therapy remained independently associated with favorable OS and RFS after hepatectomy with close/positive surgical margins for HCC (hazard ratios, 0.821 and 0.827, respectively). CONCLUSIONS: Despite the lack of consensus on the role of adjuvant radiation therapy after HCC resection, this PSM analysis suggested improved OS and RFS with adjuvant radiation therapy after hepatectomy with close/positive surgical margins for HCC. Future randomized controlled trials are needed to further define the survival benefit of adjuvant radiation therapy for patients with HCC.

[Exploration of professor ZHANG Shan-chen's academic thoughts].

Professor ZHANG Shan-chen's clinical experience and academic thoughts in the field of acupuncture are summarized. Professor ZHANG stresses on theoretical exploration and has written Zhenjiu Jiayijing Shuxue Chongji, published a series of articles on textual research and expounded the nomenclature of acupoints. He believes that clinical practice should be guided by theory and the comprehensive syndrome differentiation be emphasized. Hence, a holistic idea should be cultivated, in which, the human body is considered as an organic whole and should be adaptive to the nature. Based on the theory above, the diagnosis can be determined and the effective treatment be received. He suggests selecting few acupoints, identifying the deficiency from the excess so as to determine the reinforcing or replenishing method and exerting appropriate needling manipulation. Additionally, the response should be enhanced on the identification of deqi after needle insertion. Moreover, a great consideration is laid on the clinical trial and application of moxibustion, which is complemented with acupuncture technique each other and mutually conductive to the clinical effect.

Everolimus inhibits PI3K/Akt/mTOR and NF-kB/IL-6 signaling and protects seizure-induced brain injury in rats.

BACKGROUND: Epilepsy is a common chronic neurological disease caused by the over-synchronization of neurons leading to brain dysfunction. Recurrent seizures can lead to cognitive and behavioral deficits, and irreversible brain damage. While the PI3K/Akt/mTOR pathway regulates various physiological processes of neurons and glia, it may also lead to abnormal neuronal signal transduction under pathological conditions, including that of epilepsy. Everolimus (Eve), an mTOR inhibitor, may modulate neuronal excitability and therefore exert protection against epilepsy. Therefore, this study aimed to investigate the neuroprotective effect of Everolimus on seizure-induced brain injury and its regulation of the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway. Kainic acid (KA) 15 mg/kg was used to induce seizures and Everolimus (1, 2, 5 mg/kg) was administered as a pretreatment. Hippocampal tissue was extracted 24 h post-seizure. RESULTS: The protein and mRNA expression levels of PI3K、p-AKt、p-mTOR、NF-kB and IL-6 as well as neuronal apoptosis and microglia activation, significantly increased after KA-induced seizures, however, these effects were inhibited by Everolimus treatment. Furthermore, pretreatment with Everolimus decreased seizure scores and increased seizure latency. CONCLUSIONS: Everolimus can decrease the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway, reduce neuronal apoptosis and microglia activation, and attenuate seizure susceptibility and intensity, thus having a protective effect on seizure-induced brain damage.

Nomogram for predicting the survival of patients with small cell carcinoma of the esophagus: A population study based on the surveillance, epidemiology, and end results database.

ABSTRACT: This study aims to establish an effective prognostic nomogram for small cell carcinoma of the esophagus (SCCE).A total of 552 patients with SCCE from 1975 to 2016 were extracted from the surveillance, epidemiology, and end results (SEER) database. A Cox proportional hazard regression model was used to analyze the prognostic factors of patients, and a nomogram was constructed. The nomogram was then validated internally by using a consistency index (C-index) and a correction curve to evaluate its predictive value.The Cox proportional hazard regression model showed that age, stage, surgery, primary site, radiotherapy, and chemotherapy were the prognostic factors of SCCE (P < .1), and they were used to construct the nomogram. The C-index of the nomogram for predicting survival was 0.749 (95% confidence interval [CI] = 0.722-0.776). The data were randomly divided into a modeling group and a validation group based on 7:3 for internal validation. The C-indices of the modeling and validation groups were 0.753 and 0.725, respectively, and they were close to 0.749. The calibration curves exhibited good consistency between the predicted and actual survival rates.The nomogram of the survival and prognosis of patients with SCCE in this study had a good predictive value and could provide clinicians with accurate and practical predictive tools. It could also be used to facilitate a rapid and accurate assessment of patients' survival and prognosis on an individual basis.

Conventionally fractionated stereotactic radiotherapy (CFRT) in combination with dose-dense temozolomide (TMZ) in relapsed malignant glioma: A case report.

RATIONALE: At present, there is no uniform consensus on the treatment of recurrent glioblastoma, especially the re-irradiation dose and temozolomide (TMZ) dose. The literature on the treatment of recurrent glioblastoma (GBM) by conventionally fractionated stereotactic radiotherapy (CFRT) is even rarer. PATIENT CONCERNS: A 44-year-old woman was admitted to our hospital for residual tumor after reoperation. DIAGNOSES: Postoperative pathological diagnosis was GBM, WHO grade IV. The brain magnetic resonance imaging re-examination showed abnormal enhancement around the local operative region after resection of the left frontal lobe tumor, and there was presence of residual tumor. INTERVENTIONS: The patient was treated with reoperation followed by re-irradiation plus dose-dense TMZ to achieve complete remission. OUTCOMES: Complete remission was observed at the end of radiotherapy and at the 1 month follow-up after radiotherapy. LESSONS: This study suggests that CFRT plus dose-dense TMZ might be a feasible option for the treatment in relapsed malignant glioma patients with good general condition.

S-1 plus cisplatin with concurrent radiotherapy for stage III non-small cell lung cancer: A meta-analysis (PRISMA) of randomized control trials.

INTRODUCTION: The present study aims to assess the efficacy and safety of S-1 plus cisplatin as concurrent chemoradiation (experimental group [EG]) compared with standard concurrent chemoradiation regimens (control group[CG]) in patients with local advanced non-small cell lung cancer. METHODS: The Cochrane library, pubmed, and Ovid (elsevier) were retrieved. The included randomized controlled trials (RCT) were evaluated, and the statistical analysis was performed using RevMan 5.3 software. Cochrane handbook was applied to evaluate the methodological quality. Statistical significance was considered as P <.05. RESULTS: There were 5 randomized control trials identified eligible for the meta-analysis. Meta-analysis of the pooled date suggested that overall survival (OS) (HR, 0.81; 95% CI, 0.58-1.13; P = .21, heterogeneity P = 1.00, I = 0%), progressives free survival (PFS) (HR, 0.82; 95% CI, 0.62-1.09; P = .18, heterogeneity P = .83, I = 0%) and 1,2,3-year OS (1-year OS: RR 1.03; 95% CI: 0.92-1.15, p = 0.59), (2-year OS: RR 1.14; 95% CI: 0.98-1.34, P = .09), (3 -year OS: RR 1.14; 95% CI: 0.90-1.44, P = .29) were not significantly different. The combination of S-1 and cisplatin had lower grade 3 or 4 leukocytopenia, neutropenia, (RR = 0.54, 95% CI: 0.38-0.75, P = .0003; RR = 0.23,95% CI: 0.14-0.36, P <.00001;, respectively). The rates of nausea, diarrhea, thrombocytopenia, pneumonitis, anorexia, anemia, febrile neutropenia were much the same in the 2 groups (RR = 1.35, 95% CI: 0.68-2.68, P = .38; RR = 1.85, 95% CI: 0.61-5.60, P = .28; RR = 1.67, 95% CI: 0.88-3.17, P = .12; RR = 1.19, 95% CI: 0.44-3.21, P = .73; RR = 1.35, 95% CI: 0.68-2.68, P = .38; RR = 0.86, 95% CI:0.55-1.34, P = .50; RR = 0.63, 95% CI:0.35-1.14, P = .13;, respectively). CONCLUSIONS: This meta-analysis of 5 randomized control trails demonstrates that EG results similar OS, PFS, and 1,2,3-year OS, compared with CG, with lower risk of leukocytopenia, neutropenia.

The efficacy and safety of olaparib in the treatment of cancers: a meta-analysis of randomized controlled trials.

PURPOSE: PARP inhibition is an exciting new anticancer strategy. As the first PARP inhibitor approved for the treatment of advanced BRCA-mutated ovarian cancer, olaparib has proven to be effective in the treatment of several solid tumors. We performed a meta-analysis of published randomized controlled trials to evaluate the efficacy and safety of olaparib in cancer patients. METHODS: PubMed, Embase, and oncology-conference proceedings were searched for relevant studies. End points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3/4 adverse events. Pooled hazard ratio (HR)/risk ratio (RR) and 95% CI were calculated using random or fixed-effect models. RESULTS: Eight trials involving 1,957 patients were ultimately identified. The pooled analysis demonstrated that olaparib treatment significantly improved PFS (HR 0.62, 95% CI 0.47-0.82; P=0.001), OS (HR 0.82, 95% CI 0.73-0.93; P=0.001), and ORR (RR 1.38, 95% CI 1.16-1.65; P<0.001) when compared with therapy not containing olaparib. This association was further confirmed by sensitivity analysis. Additionally, olaparib treatment offered a significant survival benefit for patients with BRCA mutation. Moreover, treatment with olaparib was associated with a significant increase in risk of severe anemia. CONCLUSION: Olaparib treatment has better treatment response compared with therapy not containing olaparib, whereas olaparib can increase the risk of severe anemia.

Stereotactic radiosurgery (SRS) alone versus whole brain radiotherapy plus SRS in patients with 1 to 4 brain metastases from non-small cell lung cancer stratified by the graded prognostic assessment: A meta-analysis (PRISMA) of randomized control trials.

BACKGROUND: The present study aims to assess the therapeutic effect of whole brain radiotherapy (WBRT) for brain metastases from non-small cell lung cancer stratified by graded prognostic assessment (GPA) through meta-analysis. METHODS: The Cochrane Library, PubMed, Ovid (Elsevier) were retrieved. The included randomized controlled trials (RCT) were evaluated, and the statistical analysis was performed using RevMan 5.3 software. Cochrane handbook was applied to evaluate the methodological quality. Statistical significance was considered as P < .05. RESULTS: There were 2 randomized control trials identified eligible for the meta-analysis. Stereotactic radiosurgery (SRS)+WBRT did not significantly improved overall survival (OS) in 2 subgroups. (GPA <2: HR, 0.93; 95% confidence interval [CI], 0.61-1.40; P = .71), (GPA ≥2: HR, 1.28; 95% CI, 0.58-2.80; P = .54). The use of SRS+WBRT significantly extended brain tumor recurrence (BTR) free time in both subgroups (GPA <2: HR, 5.46; 95% CI: 2.09-14.22; P = .0005), (GPA ≥2: HR, 4.24; 95% CI: 2.24-8.04; P < .00001). The meta-analysis showed salvage therapy was more frequent among the SRS-alone in 2 subgroups (GPA <2: RR, 5.83; 95% CI: 1.47-23.06; P = .01), (GPA ≥2: RR, 2.53; 95% CI: 1.30-4.93; P = .006). The rate of grade 3 or 4 late radiation toxic effects was similar in 2 subgroups between SRS and SRS+WBRT CONCLUSIONS:: Because there are few studies to meet inclusion criteria, we cannot include more researches. The results of this analysis must be carefully interpreted in view of the unclear risk of bias in inclusion in the study. This meta-analysis of 2 randomized trails indicated that the combined treatment group did not show a survival benefit over SRS alone. However, SRS+WBRT improved BTR free time in the subgroup both GPA <2 and GPA ≥2 with the similar grade 3 or 4 late radiation toxicities.

Extramedullary plasmacytoma of the trachea: A case report and review of the literature.

RATIONALE: Extramedullary plasmacytomas (EMPs) are rare solitary soft tissue tumors characterized by monoclonal proliferation of plasma cells. Most lesions occur in the head and neck, but primary tracheal lesions are very rare. PATIENT CONCERNS: In this report, we describe a case of tracheal EMP discovered in a 48-year-old man who presented with a history of progressive dyspnea. DIAGNOSES: Computed tomography (CT) revealed a well-defined nodular mass in the posterior wall of trachea without signs of invasion of the tracheal walls. Then, a reddish mass occluding approximately 90% of the trachea was evidenced by bronchoscopic examination. INTERVENTIONS: The patient was treated with surgery followed by adjuvant radiotherapy to achieve better local control. OUTCOMES: After the surgery, there was immediate symptomatic relief. There was no recurrence or metastasis during a 6-month follow-up. LESSONS: This study presents a rare case of tracheal EMP occluding approximately 90% of the lumen that was successfully managed by surgery followed by radiotherapy.

Pathological characteristics of esophageal cancer.

The pathological characteristics of esophageal squamous cell carcinoma, which include regularly occurring multiple carcinogenic lesions (MLs), severe dysplasia (SD) and direct intramural infiltration (DI), were investigated using large pathological sections. A total of 52 esophageal cancer patients underwent surgical resection and were diagnosed with esophageal squamous cell carcinoma. Large sections of the surgical resection specimens were then made for pathological examination. The actual length of the carcinoma was calculated during surgery from the length determined microscopically. ML, SD and DI were identified during pathological examination of the large sections by microscope and were statistically analyzed. The lesion lengths obtained by the various inspection methods differed from each other. ML, SD and DI were identified in 15, 28 and 41 patients, respectively. Furthermore, a higher incidence of DI was observed in patients with lymphatic infiltration or those with a later stage of disease. ML, SD and DI were identified as characteristics of esophageal squamous cell carcinoma, and ML and DI were found to correlate with lymphatic infiltration.

Radiosensitization of esophageal cancer cells ECA109 by knockdown of H2AX.

BACKGROUND: Genetic studies on mice have demonstrated that the key regulator of DNA damage in mammalian cells is the histone H2A variant, H2AX. We hypothesize that knockdown of H2AX will cause DNA damage pathway defects and may be able to increase the sensitivity to radiotherapy. METHODS: The formation of foci and the interaction of several important proteins in esophageal cancer ECA109, triggered by irradiation, were detected by immunofluorescence staining and Co-immunoprecipitation (Co-IP) assay before and after H2AX silencing. Clone formation assay was employed to detect cell radiosensitivity and cloning formation ability also before and after H2AX silencing. Cell cycle distribution and apoptosis were detected by flow cytometry. We constructed a nude mice esophageal cancer model and detected the above contents in vivo. RESULTS: H2AX and several proteins could form foci in nuclear triggered by irradiation and establish a relationship in vitro. The foci reduced after H2AX silencing. H2AX silencing could lead to radiosensitization via a colony-forming test. The apoptosis rate increased and the cell cycle was blocked in G2-M stage after H2AX silencing in vivo. The tumor volume was decreased in the H2AX silenced group after irradiation, while the tumor only slowed down the growth rate in the control groups. CONCLUSIONS: Knockdown of H2AX induced radiosensitization of esophageal cancer ECA109 cells both in vitro and in vivo. The mechanisms include defective cell cycle checkpoints and abolishment of foci formation for several important mediator and effector proteins in the DNA damage response to irradiation (IR).

Study on the thermal decomposition kinetics of nano-sized calcium carbonate.

This study of the thermal decomposition kinetics of various average diameter nano-particles of calcium carbonate by means of TG-DTA ( thermogravimetry and differential thermal analysis) showed that the thermal decomposition kinetic mechanisms of the same crystal type of calcium carbonate samples do not vary with decreasing of their average diameters; their pseudo-active energy (a); and that the top-temperature of decomposition T(p) decreases gently in the scope of micron-sized diameter, but decreases sharply when the average diameter decreases from micron region to nanometer region. The extraordinary properties of nano-particles were explored by comparing the varying regularity of the mechanisms and kinetic parameters of the solid-phase reactions as well as their structural characterization with the variation of average diameters of particles. These show that the aggregation, surface effect as well as internal aberrance and stress of the nano-particles are the main reason causing both E(a) and T(p) to decline sharply with the decrease of the average diameter of nano-particles.