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Can EGFR-TKIs be used in first line treatment for advanced non-small cell lung cancer based on selection according to clinical factors ? -- A literature-based meta-analysis

<p>Abstract</p> <p>Background</p> <p>In the first line treatment of non-small cell lung cancer (NSCLC), several clinical trials have shown that not all NSCLC patients can benefit from treatment with tyrosine kinase inhibitors (TKIs) than receiving chemotherapy. Some trials treated patients with TKI according to their clinical characteristics. A few studies only chose patients with an epidermal grouth factor receptor (EGFR) mutation for TKI therapy. We aimed to determine whether patients could be treated with TKIs based on clinical factors in the first-line setting.</p> <p>Methods</p> <p>We performed a meta-analysis of randomized trials involving patients with advanced NSCLC treated with chemotherapy or TKIs by different selections. Efficacy outcomes of interest were the objective response rate (ORR), progression-free survival (PFS) and the overall survival (OS) of each treatment arm.</p> <p>Results</p> <p>Four trials enrolled unselected patients, and two trials selected East Asian patients using the clinical factors of gender and smoking history. Five trials chose patients with an EGFR mutation who were randomized for treatment with TKI or chemotherapy. For unselected patients, the risk ratio (RR) of the ORR was 3.52, the hazard ratio (HR) of the PFS was 1.29 and the HR of the OS was 1.35. For the clinically selected patients, the RR of the ORR was 0.64. The HRs of the PFS and OS were 0.83 and 0.92, respectively. The ORR and PFS were better for TKIs than for chemotherapy in patients with an EGFR mutation. The ORR was 0.47, and the HRs of the PFS and OS were 0.36 and 1.00, respectively.</p> <p>Conclusions</p> <p>Advanced NSCLC patients with an EGFR mutation benefit most from TKIs. EGFR-TKI treatment is justified for patients with unknown EGFR status,and those who cannot tolerate chemotherapy owing to age, poor performance status (PS) or other medical conditions, when selected according to clinical factors in the first-line setting.</p

Erlotinib in the Second/Third Line Treatment of Patients with Advanced Non-small Cell Lung Cancer

Background and objective Erlotinib is a targeted drug for non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the efficacy, influencing factors and toxicity of erlotinib in patients with NSCLC. Methods Patients with NSCLC who had been previously treated with at least one course of platinum based chemotherapyreceived 150 mg oral doses of erlotinib once daily until disease progression. Response rate, progression free survival, overall survival and toxicity profile were analyzed. Kaplan-Meier methods was used to analyze the survival rate. Cox regression was used to define the predictive factors. Results Forty-eight patients were enrolled into the study from Dec, 2005 to Sep, 2006. We followed up these patients until 08.Dec.2008. Median follow up time was 30 months. The compliance rate was 100%. The median symptom improving time was 7 days. Partial response 33.4% (16/48), stable disease 22.9% (11/48), and progressive disease 43.7% (21/48). Response rate was 33.4% (16/48). Disease control rate was 56.3% (27/48). One and two-year progression-free survival rates and overall survival rates were 25％(events 36), 8.3％ (events 40) and 43.8％ (death 27), 20.8％ (death 38); three-year overall survival 5.6％. The median progression-free survival time and median overall survival time was 5 months and 8 months, respectively. Performance status was the only predictor for overall survival in the Cox model (P <0.001). Skin toxicity(grade 1 to 3) was found in 93.7% patients. One patient discontinued erlotinib because of perianal abscess. Conclusion Erlotinib is another effective drug for patients with previously chemotherapy advanced NSCLC and accepted toxicity profile

Future climate change will severely reduce habitat suitability of the Critically Endangered Chinese giant salamander

1. Being the largest extant amphibian in the world, the IUCN Critically Endangered Chinese giant salamander Andrias davidianus is a charismatic species with great international public interest. While threats such as commercial overexploitation and habitat degradation have been extensively documented to affect natural populations of A. davidianus, still no information is available about the species sensitivity to climate change. 2. Here, we develop an ensemble of species distribution models (SDMs) for A. davidianus and projected its habitat suitability under present-day and future climate change scenarios. We based our SDMs on bioclimatic and topographic predictors, and recent (2012–2018) field-collected occurrence data across the whole distribution range of the species. 3. The ensemble SDMs exhibited good predictive capacity and suggested that slope, maximum temperature of warmest month, precipitation of driest month, and isothermality are the most influential predictors in determining distribution patterns in this species. The projections of our models point to a pronounced impact of climate changes over A. davidianus, with more than two-thirds of its suitable range expected to be lost in all scenarios of future climates tested. 4. In concert with the numerous other threats that are affecting this species, climate change poses a serious hindrance to the long-term survival of A. davidianus. We emphasise the urgent need of undertaking strict measures to manage this species and safeguard the few remaining available suitable habitats. We suggest that adaptive management strategies including designation of new reserves should be considered to mitigate the impacts of climate change on A. davidianus.info:eu-repo/semantics/publishedVersio

Two Hawks with One Arrow: A Review on Bifunctional Scaffolds for Photothermal Therapy and Bone Regeneration

Despite the significant improvement in the survival rate of cancer patients, the total cure of bone cancer is still a knotty clinical challenge. Traditional surgical resectionof bone tumors is less than satisfactory, which inevitably results in bone defects and the inevitable residual tumor cells. For the purpose of realizing minimal invasiveness and local curative effects, photothermal therapy (PTT) under the irradiation of near-infrared light has made extensive progress in ablating tumors, and various photothermal therapeutic agents (PTAs) for the treatment of bone tumors have thus been reported in the past few years, has and have tended to focus on osteogenic bio-scaffolds modified with PTAs in order to break through the limitation that PTT lacks, osteogenic capacity. These so-called bifunctional scaffolds simultaneously ablate bone tumors and generate new tissues at the bone defects. This review summarizes the recent application progress of various bifunctional scaffolds and puts forward some practical constraints and future perspectives on bifunctional scaffolds for tumor therapy and bone regeneration: two hawks with one arrow

Intratumoral heterogeneity of EGFR-activating mutations in advanced NSCLC patients at the single-cell level

Abstract Background Intratumoral epidermal growth factor receptor (EGFR) mutational heterogeneity is yet controversial in non-small cell lung cancer (NSCLC) patients. Single-cell analysis provides the genetic profile of single cancer cells and an in-depth understanding of the heterogeneity of a tumor. Methods Firstly, single H1975 cells harboring the EGFR L858R mutation were submitted to flow cytometry isolation, nested polymerase chain reaction (nested-PCR) amplification, and direct DNA sequencing to assess the feasibility of single-cell direct DNA sequencing. Then, the single cells of patients with lung adenocarcinoma receiving gefitinib were captured by laser capture microdissection and analyzed by the above methods to identify the intratumoral heterogeneity of the EGFR L858R mutant. Three patients with progression-free survival (PFS) > 14 months were categorized as the long PFS group, and 3 patients with PFS < 6 months as the short PFS group. The correlation between the abundance of EGFR L858R mutant and PFS was analyzed. Results 104 single H1975 cells were isolated. 100/104 were amplified by nested-PCR and confirmed by direct sequencing. We captured 135 tumor cells from the tissues of six patients. 120 single tumor cells were successfully amplified and sequenced. The rate of EGFR exon 21 mutation was only 77.5% (93/120). Furthermore, the rate of mutation in exon 21 of EGFR was significantly higher in the long PFS group than in the short PFS group (86.4 ± 4.9% vs. 68.9 ± 2.8%, P = 0.021). Conclusion Our study suggested the intratumoral heterogeneity of EGFR-activating mutations in lung adenocarcinoma confirmed on the single-cell level, which might be associated with EGFR-TKIs response in lung adenocarcinoma patients harboring the EGFR L858R mutation