Angiogenesis inhibitors are of considerable interest for treating metastatic colorectal cancer (mcRc). This trial evaluated the efficacy and safety of apatinib in chemotherapy-refractory mCRC. Apatinib 500 mg was administered daily to patients who had progressed after two or more lines of standard fluorouracil-based chemotherapy. Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Overall, 48 patients were enrolled. ORR and DCR were 8.3% (4/48) and 68.8% (33/48), respectively. Median PFS and OS were 4.8 (95% confidence interval [CI], 3.653-5.887) and 9.1 months (95% CI, 5.155-13.045), respectively, and did not differ between subgroups stratified by previous anti-angiogenic therapies. The most prevalent grade 3-4 adverse events were hypertension (12.5%), hand-foot syndrome (HFS, 10.4%), thrombocytopenia (10.4%), and proteinuria (8.3%). Low baseline neutrophil/lymphocyte ratio (NLR, hazard ratios [HR], 0.619; P = 0.027), early carbohydrate antigen 19-9 (CA19-9) decrease (HR, 1.654; P = 0.016), and HFS (HR, 2.087; P = 0.007) were associated with improved PFS. In conclusion, apatinib monotherapy demonstrated encouraging efficacy with manageable toxicities in chemotherapy-refractory mcRc. previous anti-angiogenic therapies did not influence outcomes. Baseline NLR, early CA19-9 decrease, and HFS could predict the efficacy of apatinib. Colorectal cancer (CRC) remains the third leading cancer globally 1 , and approximately 40-50% patients present with advanced disease at diagnosis 2. Until recently, the standard of care for patients in this setting has been regorafenib or trifluridine/tipiracil (TAS102) after the progression of fluoropyrimidine-based chemotherapy with
Steel surface defect detection is an important issue when producing high-quality steel materials. Traditional defect detection methods are time-consuming and uneconomical and require manually designed prior information or extra supervisors. Surface defects have different representations and features at different scales, which make it challenging to automatically detect the locations and defect types. This paper proposes a real-time steel surface defect detection technology based on the YOLO-v5 detection network. In order to effectively explore the multi-scale information of the surface defect, a multi-scale explore block is especially developed in the detection network to improve the detection performance. Furthermore, the spatial attention mechanism is also developed to focus more on the defect information. Experimental results show that the proposed network can accurately detect steel surface defects with approximately 72% mAP and satisfies the real-time speed requirement.
3527 Background: Apatinib is an oral highly-selective tyrosine kinase inhibitor (TKI) that blocks vascular endothelial growth factor receptor 2 (VEGFR-2). This exploratory study evaluated the efficacy and safety of apatinib monotherapy in patients with chemotherapy-refractory metastatic colorectal cancer. Methods: In this multicenter, single-arm, prospective study, 48 patients with metastatic colorectal cancer who had failed at least two lines standard chemotherapies including fluorouracil, oxaliplatin and irinotecan were recruited from 14 centers in Guangdong, China. Apatinib at a 500mg dose was administered daily continuously. Each cycle was 4 weeks (28 days). The primary endpoint was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and toxicity. Results: A total of 48 patients was enrolled in the study from September 3, 2015 to June9, 2017. Four patients achieved a partial response, and 22 achieved stable disease, representing a response rate of 8.3% and a disease control rate of 60.4%. Median follow-up time was 10.3 months. Median progression-free survival (PFS) and overall survival (OS) of evaluable patients (n=41) were 4.7 months (95% confidence interval [CI] 3.7-5.9) and 9.7 months (95% CI 5.9-13.6). The most common grade 3 or 4 adverse events (AE) were hypertension (12.5%), hand-foot syndrome (10.4%), thrombocytopenia (10.4%), proteinuria (8.3%) and mucositis oral (6.3%). Conclusions: Apatinib monotherapy shows promising efficacy and manageable toxicities in patients with chemotherapy-refractory metastatic colorectal cancer. Further phase 3 trial is warranted. Clinical trial information: ChiCTR1900020503.
Homologous recombination deficiency (HRD) commonly occurs in breast cancer, which is the second cause of cancer death in women with a high rate of relapse and poor outcomes. Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Thus, we aim to develop a prognostic signature based on HRD expecting to help improve outcomes in TNBC. The Cancer Genome Atlas (TCGA)–TNBC cohort was divided into the training set and the testing set randomly. Sixteen genes were filtered from the prognostic HRD-associated genes to establish a prognostic model in the training set. Patients were divided into high-risk and low-risk groups based on the median value of the risk score. Prognosis analysis showed that the high-risk group was associated with a worse prognosis in the training set, the testing set, the entire TCGA–TNBC cohort, and the METABRIC–TNBC cohort. The time-dependent receiver operating characteristic curve showed that our model had very good accuracy in the prediction of 1–5-year overall survival in the TCGA–TNBC cohort. Besides, a comparison of the area under curve value and C-index between our model and four published models showed that our model had the best predictive efficiency compared to other models. Subsequently, a nomogram was established. Finally, our finding also indicated that our model was associated with immunoregulation in TNBC and had the potential to be the target for TNBC treatment. Therefore, our findings not only provided a new strategy in the personalized prognosis management of TNBC but also offered new insight into precision treatment in TNBC.
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