The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. @*Materials and Methods@#From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. @*Results@#A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). @*Conclusion@#Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.

The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)–mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR–tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status. RESULTS: A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). CONCLUSION: PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746-A750 mutation are associated with the frequency of T790M mutation.

use of -magnetic resonance spectroscopy in studying radiation-induced injury of the brain in elderly and young patients with nasopharyngeal carcinoma

Background: This study aims to investigate the metabolic characteristics of radiotherapy-induced temporal lobe injury in elderly patients with nasopharyngeal carcinoma using

Materials and Methods: Data were collected from 21 elderly patients and 33 young patients before and during therapy with different radiation dosages [20, 40, and 60 Gy] The Student's t-test was used to compare the 1H -MRS-based N-acetyl aspartate /Creatine [NAA/Cr], Choline/Creatine [Cho/ Cr], and NAA/Cho ratios in the temporal lobes

Results: Statistically significant differences in the NAA/Cr and NAA/Cho ratios was found between the two groups [P < 0.05] at 20, 40, and 60 Gy. The Cho/Cr ratios [20/40/60 Gy] were 1.82 +/- 0.16/1.61 +/- 0.29/1.37 +/- 0.13 and 1.77 +/- 0.19/1.48 +/- 0.17/1.06 +/- 0.14 in the elderly and young patients, respectively. We found significant differences between the two groups at the dosages of 40 and 60 Gy [P<0.05]. The decrease in the NAA/Cr and NAA/Cho ratios in the elderly group was significantly higher than that in the young patients with dosages of 20, 40, and 60 Gy. The decrease in the Cho/Cr ratio in the elderly group [2.15%/11.29%/12.90%] was significantly lower than that in the young patients [3.30%/15.93%/17.58%]

Conclusion: Under the same radiotherapy pattern and radiation dosage, the injury to the neurons in the temporal lobes was significantly greater in elderly patients than that in young patients. The intervention conducted in elderly patients at a dosage of 20 Gy might help minimize the injury to the neurons?

Integrated biomarker responses of Carassius auratus exposed to BDE-47, BDE-99 and their mixtures

Polybrominated diphenyl ethers [PBDEs] have been widely used in many products as flame retardants, which resulted in their release into the environment. Little is known about the impact of coexisting PBDEs on organisms. In this study, the in vivo effects of BDE-47 and BDE-99 on a suite of biomarkers, acetyl cholinesterase [AChE], ethoxyresorufin-O-deethylase [EROD], glutathione-S-transferase [GST], superoxide dismutase [SOD] and catalase [CAT], in goldfish [Carassius auratus] were investigated. The enzyme activities were significantly altered by the two PBDEs [alone and in combination] after 2, 4, and 7 days of exposure, and obvious dose-response and time-response relationships were observed at most cases. The results suggest that these biomarkers could be used to assess ecological risks of PBDEs on fish. An integrated biomarker response [IBR] was calculated by combining multiple biomarkers to single value and used to quantitatively evaluate the toxicological effects of different chemicals. In general, BDE-99 showed more adverse biological effects than BDE-47. The joint action of mixtures seemed to be synergism at low dosage and antagonism at high dosage with regard to IBR variation

Thrombotic thrombocytopenic purpura in pediatric patients / 中国当代儿科杂志

Although thrombotic thrombocytopenic purpura (TTP) is rarely seen in pediatric patients, failure to recognize this condition often leads to severe consequences and poor outcomes. Classic features of TTP include thrombocytopenia, microangiopathic hemolytic anemia, acute kidney injury, fever, and central nervous system involvement. However, patients suffering from this condition may not present with all of the symptoms simultaneously. Therefore, it is of utmost importance for healthcare providers to have a high index of suspicion. Laboratory investigations may reveal the presence of schistocytes on peripheral blood smear, negative Coombs test, high lactate dehydrogenase levels and severely low platelet counts. The etiology of TTP is mainly due to insufficient cleavage of the large multimers of von Willebrand factor (vWF) secondary to decreased activity of ADAMTS13 (a disintegrin and metalloprotease with Thrombospondin type 1 repeats, member 13). TTP can be broadly classified into familial TTP (Upshaw Schulman syndrome) and non-familial TTP. Familial TTP is due to a congenital deficiency of ADAMTS13. Its mainstay of therapy is initiation of plasmapheresis during the acute phase, followed by regular fresh frozen plasma (FFP) infusions. Alternatively, non-familial TTP is due to a decrease in ADAMTS13 activity secondary to the presence of anti-ADAMTS13 antibodies. Once again, the primary treatment is plasmapheresis; however, recent anecdotal data also supports the use of rituximab in select cases.

Information policy and management framework for environmental protection organization with ecosystem conception

Rapid development of information technology has changed people's attitudes towards information usage. To tender to the public's expectation, information system must feature facilities to increase the efficiency of information usage using modern information technology. Facing this challenge, it is necessary to establish a sustainable information environment, including information policy, data quality regulations and information management framework to deal with the rapidly increasing environmental data and changing behavior related to data/information usage except upgrading the hardware and software devices. Taking the uniqueness and complexity of environmental data into account, this study proposes a systematic framework based on the principle of life cycle assessment to outline the elements and its associated guidance required for a sustainable information environment. Simultaneously, the concept of information ecology is also embedded into such a planning for the purpose of establishing a self-evolutional information environment. Finally, the environmental protection administration of Taiwan is used as a case study to explain the practice of proposed framework

Individual virtual phantom reconstruction for organ dosimetry based on standard available phantoms

In nuclear medicine application often it is required to use computational methods for evaluation of organ absorbed dose. Monte Carlo simulation and phantoms have been used in many works before. The shape, size and volume in organs are varied, and this variation will produce error in dose calculation if no correction is applied. A computational framework for constructing individual phantom for dosimetry was performed on five liver CT scan data sets of Japanese normal individuals. The Zubal phantom was used as an original phantom to be adjusted by each individual data set. This registration was done by Spherical Harmonics [SH] and Thin-Plate Spline methods. Hausdorff distance was calculated for each case. Result of Hausdorff distance for five individual phantoms showed that before registration ranged from 140.9 to 192.1, and after registration it changed to 52.5 to 76.7. This was caused by index similarity ranged from%56.4 to%70.3. A new and automatic three-dimensional [3D] phantom construction approach was suggested for individual internal dosimetry simulation via Spherical Harmonics [SH] and Thin-Plate Spline methods. The results showed that the individual comparable phantom can be calculated with acceptable accuracy using geometric registration. This method could be used for race-specific statistical phantom modeling with major application in nuclear medicine for absorbed dose calculation