Background: Polymeric micellar paclitaxel (pm-Pac) is a novel Cremophor EL-free, nanoparticle micellar formulation of paclitaxel. We aimed to compare the efficacy and safety between pm-Pac plus cisplatin and solvent-based paclitaxel (sb-Pac) plus cisplatin in advanced non-small-cell lung cancer (NSCLC). Patients and methods: A total of 448 stage IIIB to IV NSCLC patients were randomly assigned (2:1) to receive six 3-week cycles of either pm-Pac (230 mg/m 2 ) plus cisplatin (70 mg/m 2 ; n ¼ 300), followed by dose escalation of pm-Pac to 300 mg/m 2 from the second 3-week cycle if prespecified toxic effects were not observed after the first cycle, or sb-Pac (175 mg/m 2 ) plus cisplatin (70 mg/m 2 ; n ¼ 148). The primary end point was objective response rate (ORR) assessed by independent review committees (IRCs). The secondary end points included IRC-assessed progression-free survival (PFS), overall survival (OS), and safety. Results: Patients in the pm-Pac-plus-cisplatin group showed significant improvements in IRC-assessed ORR compared with those in the sb-Pac-plus-cisplatin group (50% versus 26%; rate ratio 1.91; P < 0.0001). Additionally, subgroup analysis showed that a higher ORR was consistently observed in both squamous and nonsquamous histological types. IRC-assessed median PFS was significantly higher in the pm-Pac-plus-cisplatin group than in the sb-Pac-pluscisplatin group (6.4-month versus 5.3-month; hazard ratio 0.63; P ¼ 0.0001). Median OS was not significantly

Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. Its alterations, including mutation, amplification and overexpression, could result in oncogenic potential and have been detected in many cancers such as non-small-cell lung cancer (NSCLC). Such alterations are, in general, considered markers of poor prognosis. Anti-HER2 antibody-drug conjugates, e.g. trastuzumab deruxtecan (T-DXd, DS-8201) and disitamab vedotin (RC48), were recently approved for HER2-positive breast and gastric cancers. Meanwhile, several HER2-targeted drugs, such as T-DXd, neratinib, afatinib, poziotinib and pyrotinib, have been evaluated in patients with advanced NSCLC, with several of them demonstrating clinical benefit. Therefore, identifying HER2 alterations is pivotal for NSCLC patients to benefit from these targeted therapies. Recent guidelines on HER2 testing were developed for breast and gastric cancer, however, and have not been fully established for NSCLC. The expert group here reached a consensus on HER2 alteration testing in NSCLC with the focus on clinicopathologic characteristics, therapies, detection methods and diagnostic criteria for HER2-altered NSCLC patients. We hope this consensus could improve the clinical management of NSCLC patients with HER2 alterations.

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Our results suggest that using a tourniquet from the beginning of osteotomy to the completion of arthroplasty could significantly reduce TBL in TKA, and decrease the incidence of complications; thereby facilitating early post-operative functional recovery.

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Background: The advent of genotype-directed therapy in personalized medicine requires the identification of driver-mutations that are often under-diagnosed due to limitations in tissue biopsy and high false negative rates associated with genomic tests. Studies have demonstrated that the mutation status of cancer cells correlates with changes in cellular morphology. The automated Cell-CT ® platform produces isometric, high-resolution 3D images of cells in liquid biopsies, such as sputum, where published studies have demonstrated 92% sensitivity to biopsy confirmed lung cancer with 95% specificity. This study reports the development of cell classifiers for lung cancer cell lines that harbor known mutations, helping pave the way to driver-mutation targeted therapy. Method: Noninvasive sputum specimens from patients without lung cancer ("normal cells") and the following cell lines were analyzed using the Cell-CT ® platform: Small Cell Lung Cancer cell line NCI-H69 Adenocarcinoma cell lines A549 (EGFR wild-type,-c.1_471del471, KRASp.G12S) NCI-H1650 (EGFR-p.E746_A750del, CDKN2Ac.1_471del471, TP53-c.673-2A>G) NCI-H1975 (EGFR-T790M, CDKN2A-p.E69*, PIK3CA-p.G118D, TP53-p.R273H) NCI-H2228 (EML4-ALK+, CDKN2A-c.1_471del471, RB1-p.E204fs*10, TP53p.Q331* high PD-L1). Result: 15,000 normal cells from sputum and 500 malignant cells from each of the five cancer cell lines were analyzed using Cell-CT ® platform, measuring 704 structural biomarkers to sub-classify the cancer cells by mutation status. Cell classifiers were operated to drive the highest specificity (avoidance of false positives) while maintaining sensitivity above 50%. The area under ROC (aROC), sensitivity and specificity for each classifier were (see Table). Conclusion: This study demonstrates the feasibility of processing non-invasive sputum specimens by the Cell-CT ® platform to accurately identify driver mutations in cancer cells to promote mutation-directed targeted therapy for the treatment of lung cancer.

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