Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis.

PURPOSE:This meta-analysis aimed to assess the efficacy and safety of cyclin-dependent kinase (CDK) 4/6 inhibitors plus endocrine therapy (ET) in hormonal receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). METHODS:We searched PubMed, Embase, Cochrane, ClinicalTrials.gov., ASCO, ESMO and AACR databases from inception to October 10, 2019 for randomized controlled trials (RCTs) that compared CDK 4/6 inhibitors plus ET to single-agent ET with no treatment-line restriction. The main outcomes analyzed were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and adverse events (AEs). RESULTS:Of 938 identified studies, 9 RCTs with 5043 women were eligible and included. Compared with ET alone, CDK 4/6 inhibitors and ET combination improved in PFS (hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.50-0.59, p< 0.00001) and OS (HR 0.77, 95% CI 0.69-0.85, p< 0.00001), regardless of ET strategies (HR 0.54, 95% CI 0.50-0.59 in PFS; HR 0.77, 95% CI 0.69-0.85 in OS), treatment line of advanced disease (HR 0.52, 95% CI 0.46-0.59 in PFS; HR 0.75, 95% CI 0.66-0.85 in OS) and menopausal status (HR 0.54, 95% CI 0.50-0.58 in PFS; HR 0.76, 95% CI 0.68-0.84 in OS). Higher risk of grade 3/4 AEs (RR 2.66, 95% CI 2.44-2.90, p < 0.00001) were observed in the combination group than in the ET group. CONCLUSIONS:Combination therapy with CDK 4/6 inhibitors and ET prolongs survival in HR+/ HER2- ABC. This combination is a better therapeutic strategy than endocrine monotherapy in HR+/HER2- ABC, regardless of treatment line, menopausal status and other individual characteristics

Global Standard Stratotype-Section and Point (GSSP) for the Base of the Jiangshanian Stage (Cambrian: Furongian) at Duibian, Jiangshan, Zhejiang, Southeast China

The International Commission on Stratigraphy and the IUGS Executive Committee have recently approved a Global Standard Stratotype-section and Point (GSSP) defining the base of the second stage of the Furongian Series, Cambrian System. This stage is named the Jiangshanian Stage, after Jiangshan City, western Zhejiang Province, China, where the GSSP is located. The GSSP is exposed in a natural outcrop near Duibian Village. It is defined at the base of a limestone (wackestone) layer 108.12 m above the base of the Huayansi Formation in the Duibian B section, coinciding with the first appearance of the cosmopolitan agnostoid trilobite Agnostotes orientalis (base of the A. orientalis Zone). The GSSP is at a position of 28 degrees 48.977'N latitude and 118 degrees 36.887 'E longitude. Secondary global markers at or near the base of the stage include the first appearance of the cosmopolitan polymerid trilobite Irvingella angustilimbata, which coincides with the FAD of the primary marker in the stratotype section, and near the end of a large positive carbon isotopic excursion (SPICE excursion). Faunal turnovers close to the base of the Jiangshanian Stage have been recognized as being at the base of the Iverian Stage in Australia, the Gonggrian Stage in Korea, and the Agnostotes orientalis Irvingella perfecta Zone in Siberia, and near the base of the Aksayan Stage in Kazakhstan, the Sunwaptan Stage in Laurentia, and the Parabolina brevispina Zone in Baltica

Expert consensus on the diagnosis and treatment of RET gene fusion non‐small cell lung cancer in China

Abstract The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy

Chinese expert consensus on the diagnosis and treatment of malignant pleural mesothelioma

Abstract Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high‐risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow‐up

Carbon-Isotope Excursions Recorded in the Cambrian System, South China: Implications for Mass Extinctions and Sea-Level Fluctuations

Cambrian carbonates with abundant fossils of agnostoid trilobites deposited on the southern slope (Jiangnan slope belt) of the Yangtze Platform and in the Jiangnan deepwater basin are well exposed in the Wangcun Section of western Hunan, South China, and in the Duibian A Section of western Zhejiang, southeastern China, respectively. To better understand the response of carbon-isotope excursions to depositional environment changes, mass extinctions and eustatic events, we collected 530 carbonate samples in fresh roadcut exposures of the two measured sections for analysis of carbon and oxygen isotopic compositions. Data of δ13C from the Wangcun Section, western Hunan, South China, demonstrate that the Cambrian carbon-isotope profile includes three remarkable positive excursions CPEwc-1, 2, 3 in the Upper Series 2, in the Lower and in the Middle Furongian Series. Three distinctive negative excursions CNEwc-1, 2, 3 were separately tested in the Lower Terreneuvian Series, Lower Series 3 and in the Upper Furongian Series. Similarly, in the corresponding horizons in the Duibian A Section, Zhejiang Province, southeastern China, three positive excursions CPEdb-1, 2, 3 and three negative excursions CNEdb-1, 2, 3 also have been discovered. We interpret these significant carbon-isotope excursions as being associated with enhanced biogenic productivity, mass extinctions and eustatic events