LBA8507 Background: PD-1/PD-L1 inhibitors plus chemotherapy remain standard first-line therapy for EGFR/ALK/ROS1-wild type advanced non-squamous non-small cell lung cancer (nsq-NSCLC). Pre-clinical data suggest angiogenesis inhibitors may potentiate immune checkpoint inhibitors (ICIs). This phase 3 trial evaluated sequential benmelstobart (anti-PD-L1 mAb) plus chemo followed by benmelstobart plus anlotinib versus standard therapy for PFS improvement in this patient population. Methods: TQB2450-III-11 (NCT05346952) is a randomized, open-label, parallel-controlled phase 3 trial. Eligible patients were diagnosed with locally advanced (stage IIIB/C, unfit for surgery or curative-intent chemoradiotherapy) or metastatic nsq-NSCLC. Previous systemic treatment for advanced disease was not allowed. Other key inclusion criteria included ECOG PS of 0-1, aged 18-75 and no EGFR mutations, no ALK or ROS1 rearrangements. Patients were stratified by PD-L1 TPS level (＜1%/1-49%/≥50%) and randomized 1:1 to receive benmelstobart or tislelizumab plus platinum and pemetrexed for 4 cycles, then followed by maintenance with benmelstobart plus anlotinib and pemetrexed or tislelizumab plus pemetrexed until disease progression or unacceptable toxicities. Anlotinib dosing was 10 mg, while benmelstobart or tislelizumab was given at a dose of 1200 mg or 200 mg Q3W. The primary endpoint was PFS by independent review committee according to the RECIST version 1.1. Results: From January 24, 2022 to May 8, 2023, 596 eligible patients were randomized 1:1 to benmelstobart group and tislelizumab group. Baseline characteristics were well balanced between two groups. Median PFS was significantly improved in benmelstobart group (14.42 months, 95% CI, 12.35–NE) versus tislelizumab group (8.34 months, 95% CI, 6.97–12.39), HR 0.67 (95% CI, 0.52–0.86; P = 0.0017). The subgroup analysis showed that PFS benefit favored benmelstobart group in almost all subgroups, particularly in patients with ECOG PS 0 (HR 0.36, 0.20-0.65) and PD-L1 TPS ＜1% (HR 0.61, 0.43-0.86). OS was immature. Safety profiles were similar in two groups. Treatment-emergent adverse events of any grade was 92.28% (benmelstobart group) and 90.94% (tislelizumab group) respectively. ≥Grade 3 treatment-related adverse events was 56.38% (benmelstobart group) and 48.66% (tislelizumab group). Immune-related adverse events was 19.13% (benmelstobart group) and 18.46% (tislelizumab group). Conclusions: Benmelstobart in combination with chemotherapy followed by sequential combination with anlotinib significantly improved PFS compared to tislelizumab in combination with chemotherapy followed by sequential tislelizumab, with a manageable safety profile. It might be a new first-line treatment for nsq-NSCLC. Clinical trial information: NCT05346952 .

107 Background: Nectin-4 is a cell adhesion molecule that is highly expressed in a wide variety of cancers and is associated with poor prognosis. SHR-A2102 is a novel ADC consisting of a fully humanized Nectin-4–directed monoclonal antibody, bound to topoisomerase I inhibitor payload via a cleavable linker. We conducted a multi-center, phase 1 trial to evaluate SHR-A2102 in advanced solid tumors. Methods: Patients (pts) with Nectin-4 positive, locally advanced unresectable or metastatic solid tumors were enrolled. The study included dose-escalation (D-ESC), dose-expansion (D-EXP) and efficacy-expansion (E-EXP) phases. SHR-A2102 was given IV at 2–10 mg/kg, Q3W during D-ESC, and at 6 mg/kg and 8 mg/kg Q3W during D-EXP and E-EXP. The primary objectives were to assess safety and tolerability. Results: As of Dec. 20, 2024,369 pts were enrolled and treated (median age, 59 y; ECOG PS 1, 85.6%; ≥2 lines of prior therapy, 64.0%). During D-ESC, DLT occurred in 1 pt (10 mg/kg; grade 4 decreased platelet count). Overall, grade ≥3 TRAEs occurred in 167 (45.3%) pts, with the most common (≥3%) being decreased neutrophil count (25.5%), decreased white blood cell count (16.3%), anaemia (11.7%), decreased lymphocyte count (8.7%), decreased platelet count (4.9%), asthenia (3.5%) and nausea (3.3%). 2 (0.5%) pts discontinued treatment due to TRAE. ILD occurred in 1 (0.3%; grade 3) pt. In 304 evaluable pts for response, ORR was 35.2% (95% CI 29.8-40.9) and DCR was 84.2% (95% CI 79.6-88.1). As of data cutoff, 146 (39.6%) pts had disease progression or died; median PFS was 4.7 mo (95% CI 4.3-5.6). Efficacy in selected tumor types is shown in Table. Conclusions: SHR-A2102 demonstrated a manageable safety profile and promising activity across a variety of pretreated advanced solid tumors. Multiple trials are ongoing to further assess SHR-A2102 both as monotherapy and in combination therapy for solid tumors. Clinical trial information: NCT05701709 . Efficacy in selected tumor types (efficacy evaluable set). EGFR -mut Nsq NSCLC (N=69) EGFR -wt Nsq NSCLC (N=44) Sq NSCLC (N=44) HR+/HER2-BC (N=20) TNBC (N=32) HNSCC (N=12) All patients † (N=304) Best overall response, n (%) CR * 0 1 (2.3) 0 0 0 0 1 (0.3) PR * 30 (43.5) 10 (22.7) 11 (25.0) 13 (65.0) 18 (56.3) 6 (50.0) 106 (34.9) SD 28 (40.6) 21 (47.7) 33 (75.0) 4 (20.0) 9 (28.1) 5 (41.7) 149 (49.0) PD 11 (15.9) 11 (25.0) 0 3 (15.0) 5 (15.6) 1 (8.3) 47 (15.5) Not evaluable 0 1 (2.3) 0 0 0 0 1 (0.3) ORR * , % (95% CI) 43.5 (31.6-56.0) 25.0 (13.2-40.3) 25.0 (13.2-40.3) 65.0 (40.8-84.6) 56.3 (37.7-73.6) 50.0 (21.1-78.9) 35.2 (29.8-40.9) DCR, % (95% CI) 84.1 (73.3-91.8) 72.7 (57.2- 85.0) 100.0 (92.0-100.0) 85.0 (62.1-96.8) 84.4 (67.2-94.7) 91.7 (61.5-99.8) 84.2 (79.6-88.1) PFS ‡ , mo (95% CI) 5.7 (5.1-NR) 4.3 (2.0-7.3) 4.5 (4.1-6.8) 5.6 (4.3-NR) 5.6 (4.3-7.1) 6.8 (2.4-6.8) 4.7 (4.3-5.6) * Include responses to be confirmed. † Other tumor types include ESCC, PAAD, CRC, CC and UC. ‡ Evaluated in full analysis set (n=369).

SHR-A1811 is a novel ADC consisting of a humanized HER2-directed monoclonal antibody, cleavable tetrapeptide-based linker, and DNA topoisomerase I inhibitor. We conducted a multicenter, open-label, phase 1/2 study to evaluate SHR-A1811 in HER2-altered NSCLC. In the registrational phase 2 portion in patients (pts) with HER2-mutant NSCLC, the primary endpoint of IRC-assessed ORR was met (DCO, Jun. 14, 2024). Here, we presented an updated analysis after an additional 6-mo follow-up, focusing on survival outcomes. Pts with advanced NSCLC and centrally confirmed HER2 mutation, previously treated with (or intolerance to) platinum-based chemo and anti-PD-1/PD-L1 therapy, were enrolled. SHR-A1811 was administered at 4.8 mg/kg IV Q3W. 94 pts were enrolled and treated. Median prior lines of therapy was 2 (range 1-9); all received platinum-based chemo and anti-PD-1/PD-L1 therapy and 23.4% received anti-HER2 TKI. 25.5% had BM at baseline. The most common HER2 mutation was exon 20 insertions (overall, 94.7%; A775_G776insYVMA, 72.3%). As of DCO (Dec. 14, 2024), median follow-up was 14.2 mo (range 4.7-18.2). Per IRC, ORR was 74.5% (95% CI 64.4-82.9); median DoR was 9.8 mo (95% CI 8.3-13.9). Median PFS was 11.5 mo (95% CI 9.7-15.2), with consistent benefits observed across baseline subgroups (Table 1). Efficacy per INV is shown in Table 1. Median OS was not reached; 12-mo OS rate was 88.2% (95% CI 79.8-93.3). Grade ≥3 TRAEs occurred in 63 (67.0%) pts; all with incidence ≥5% were haematological toxicities. ILD occurred in 8 (8.5%; grade 1-2, n=7; grade 3, n=1) pts. TRAEs led to dose discontinuation in 2 (2.1%) pts. There was no treatment-related death. At the updated analysis, SHR-A1811 continued to show clinically meaningful efficacy with a manageable safety profile in pts with previously treated HER2-mutant NSCLC, supporting it as a potential new treatment option for this population. Shun Lu, Ziming Li, Yan Wang, Yuping Sun, Linlin Wang, Xingya Li, Longhua Sun, Zhiyi He, Haiyan Yang, Yongsheng Wang, Qiming Wang, Zhengbo Song, Wei Hong, Yong Wang, Guohao Xia, Yan Yu, Min Peng, Yong Song, Donglin Wang, Rui Meng, Jian Fang, Yongzhong Luo, Wenhua Liang, Sheng Hu, Zhihui Wang, Haichuan Su, Zhiyong He, Liuning Li, Wei Guo, Zhentian Liu, Qitao Yu, Yun Zhao, Runxiang Yang, Peng Chen, Yiru Wang, You Li, Lulu Yang, Wei Shi. SHR-A1811, a HER2-directed antibody-drug conjugate (ADC), in advanced HER2-mutant non-small cell lung cancer (NSCLC): Updated phase 2 results from HORIZON-Lung [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT009.

Background:Lung cancer is the most common cancer in the world, and non-small cell lung cancer (NSCLC) constitutes about 80-85%. In this phase III trial, we evaluate the efficacy and safety of anti-programmed cell death-1 (PD-1) monoclonal antibody (SCT-I10A) plus docetaxel compared to docetaxel in patients with previously treated advanced squamous cell NSCLC (sqNSCLC). Methods:Patients were randomized 2:1 to finotonlimab plus docetaxel group (finotonlimab plus docetaxel) and docetaxel group (placebo plus docetaxel) for up to 6 cycles, followed by maintenance monotherapy with finotonlimab/placebo. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) as well as assessments of safety and immunogenicity. Results:There were 188 eligible patients enrolled (finotonlimab plus docetaxel group: n=126; docetaxel group: n=62). Median OS (mOS) was 17.1 months [95% confidence interval (CI): 11.2, 20.0] in the finotonlimab plus docetaxel group and 10.4 months (95% CI: 5.9, 14.0) in the control group. Hazard ratio (HR) was 0.66 (95% CI: 0.45, 0.96; P=0.03). Median PFS (mPFS) was 4.2 months (95% CI: 3.3, 6.9) and 2.9 months (95% CI: 1.5, 3.8) respectively in the finotonlimab plus docetaxel group and control group. Patients in the finotonlimab plus docetaxel group achieved an ORR of 27.0% (95% CI: 19.5%, 35.6%), which was significantly higher than the 3.2% (95% CI: 0.4%, 11.2%) in the control group. The DCR was 68.3% (95% CI: 59.4%, 76.3%) in the finotonlimab plus docetaxel group and 56.5% (95% CI: 43.3%, 69.0%) in the control group. Treatment-related adverse events (TRAEs) occurred in 91.3% (115/126) patients of finotonlimab plus docetaxel group and 87.1% (54/62) patients of control group. Conclusions:SCT-I10A combined with docetaxel significantly prolonged OS and improved clinical outcomes in patients with treated advanced sqNSCLC compared to docetaxel, without increasing safety risk. Trial Registration:NCT04171284, ClinicalTrials.gov.

BACKGROUND:Although cancer stem cells (CSCs) contribute to tumorigenesis, progression, and drug resistance, stemness-based classification and prognostic signatures of lung squamous cell carcinoma (LUSC) remain unclarified. This study attempted to identify stemness-based subtypes and develop a prognostic risk model for LUSC.METHODS:Based on RNA-seq data from The Cancer Genome Atlas (TCGA), Gene-Expression Omnibus (GEO) and Progenitor Cell Biology Consortium (PCBC), mRNA expression-based stemness index (mRNAsi) was calculated by one-class logistic regression (OCLR) algorithm. A weighted gene coexpression network (WGCNA) was employed to identify stemness subtypes. Differences in mutation, clinical characteristics, immune cell infiltration, and antitumor therapy responses were determined. We constructed a prognostic risk model, followed by validations in GEO cohort, pan-cancer and immunotherapy datasets.RESULTS:LUSC patients with subtype C2 had a better prognosis, manifested by higher mRNAsi, higher tumor protein 53 (TP53) and Titin (TTN) mutation frequencies, lower immune scores and decreased immune checkpoints. Patients with subtype C2 were more sensitive to Imatinib, Pyrimethamine, and Paclitaxel therapy, whereas those with subtype C1 were more sensitive to Sunitinib, Saracatinib, and Dasatinib. Moreover, we constructed stemness-based signatures using seven genes (BMI1, CCDC51, CTNS, EIF1AX, FAM43A, THBD, and TRIM68) and found high-risk patients had a poorer prognosis in the TCGA cohort. Similar results were found in the GEO cohort. We verified the good performance of risk scores in prognosis prediction and therapy responses.CONCLUSION:The stemness-based subtypes shed novel insights into the potential roles of LUSC-stemness in tumor heterogeneity, and our prognostic signatures offer a promising tool for prognosis prediction and guide therapeutic decisions in LUSC.

Surgery is the optimal choice for early invasive mucinous lung adenocarcinoma (IMA). A systematic review and meta-analysis were conducted to explore the prognostic factors for resected IMA. We systematically reviewed the prognostic role of clinicopathological and genomic factors in resected IMA patients. Eligible studies on the treatment of IMA following the systematic search of PubMed, Embase and the Cochrane Library from January 2015 to January 2024 were identified. Outcomes of interest were overall survival (OS) and disease-free survival/recurrence-free survival (DFS/RFS). The hazard ratio (HR) and 95

IntroductionComprehensive information about the genome analysis and its prognostic values of NSCLC patients in Chinese population are still needed.PatientsA total of 117 Chinese patients with NSCLC were enrolled in this study. Tumor tissues or blood were collected and sequenced by targeted next-generation sequencing of 556 cancer related genes. The associations between clinical outcomes and clinical characteristics, TMB, mutated genes, treatment therapies were analyzed using Kaplan-Meier methods and further evaluated using multivariable Cox proportional hazards regression model.ResultsA total of 899 mutations were identified by targeted NGS. The most frequently mutations included EGFR (47%), TP53 (46%), KRAS (18%), LRP1B (12%) and SPTA1 (10%). Patients with mutant TP53, PREX2, ARID1A, PTPRT and PIK3CG had lower median overall survival (OS) than those patients with wild-type (P = 0.0056, P < 0.001, P < 0.0001, P < 0.0001 and P = 0.036, respectively). Using a multivariate Cox regression model, PREX2 (P < 0.001), ARID1A (P < 0.001) and PIK3CG (P = 0.04) were independent prognostic factors in NSCLC. In the patients received chemotherapy, squamous patients had a significantly longer median OS than adenocarcinoma patients (P = 0.011). In the patients received targeted therapy, adenocarcinoma patients had a significantly longer survival period than squamous patients (P = 0.01).ConclusionsOur study provided comprehensive genomic alterations in a cohort of Chinese NSCLC. We also identified new prognostic biomarkers, which could provide potential clues for targeted therapies.

This article reviews studies on the knowledge transfer theory (KTT) in sport psychology using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) method to identify any existing research gaps. This review utilizes a systematic process that involves searching for studies aimed at clarifying the relationship between KTT and crossover selection, promoting crossover development of winter sports, and cultivating outstanding athletes across six different databases. This work provides the foundation for future research on KTT in the field of selection of athletes for professional sports and those intending to showcase KTT's success in the selection of winter sports athletes. This review found that crossover selection of qualified athletes helps solve the issue of the shortage of professional athletes in specific sports.

Background: Brain metastasis, with an incidence of more than 30%, is a common complication of non-small cell lung cancer (NSCLC). Therefore, there is an urgent need for an assessment method that can effectively predict brain metastases in NSCLC and help understand its mechanism.Materials and methods: GSE30219, GSE31210, GSE37745, and GSE50081 datasets were downloaded from the GEO database and integrated into a dataset (GSE). The integrated dataset was divided into the training and test datasets. TCGA-NSCLC dataset was regarded as an independent verification dataset. Here, the limma R package was used to identify the differentially expression genes (DEGs). Importantly, the RiskScore model was constructed using univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis. Moreover, we explored in detail the tumor mutational signature, immune signature, and sensitivity to treatment of brain metastases in NSCLC. Finally, a nomogram was built using the rms package.Results: First, 472 DEGs associated with brain metastases in NSCLC were obtained, which were closely associated with cancer-associated pathways. Interestingly, a RiskScore model was constructed using 11 genes from 472 DEGs, and the robustness was confirmed in GSE test, entire GSE, and TCGA datasets. Samples in the low RiskScore group had a higher gene mutation score and lower immunoinfiltration status. Moreover, we found that the patients in the low RiskScore group were more sensitive to the four chemotherapy drugs. In addition, the predictive nomogram model was able to effectively predict the outcome of patients through appropriate RiskScore stratification.Conclusion: The prognostic RiskScore model we established has high prediction accuracy and survival prediction ability for brain metastases in NSCLC.

Abstract Background Multidrug-resistant organisms (MDRO) infection is a major public health threat in the world. We aim to predict risk of MDRO infections in Intensive Care Unit (ICU) patients by developing and validating a machine learning (ML) model.Methods This study included patients in the ICU from January 1, 2020 to December 31, 2022, and retrospectively analyzed the clinical characteristics of the patients. Lasso regression was used for feature selection. We use 6 machine learning methods to analyze clinical features and build prediction models. Furthermore, we illustrate the effects of the features attributed to the model and interpret the prediction process based on the SHapley Additive exPlanation(SHAP).Results A total of 888 cases were collected, 63 cases were excluded based on inclusion and exclusion criteria, and 825 final cases were included in the analysis, of which 375 were MDRO-infected patients. A total of 45 clinical variables were collected, and after selection, 31 variables were associated with outcomes and were used to develop machine learning models. We have build six ML models to predict MDRO infections, among which, the Random Forest (RF) model performs the best with an AUC of 0.83 and an accuracy of 0.767.Conclusions We built and validated an ML model for predicting patients who will develop MDRO infections, and the SHAP improves the interpretability of machine learning models and helps clinicians better understand the mechanisms behind the results. The model can provide guidance to ICU healthcare professionals in the prevention and control of patients at high risk of infection.

EGFR exon 20 insertion (20ins)-positive non-small-cell lung cancer (NSCLC) is an uncommon disease with limited therapeutic options and dismal prognosis. Here we report the activity, tolerability, potential mechanisms of response and resistance for dual targeting EGFR 20ins with JMT101 (anti-EGFR monoclonal antibody) plus osimertinib from preclinical models and an open label, multi-center phase 1b trial (NCT04448379). Primary endpoint of the trial is tolerability. Secondary endpoints include objective response rate, duration of response, disease control rate, progression free survival, overall survival, the pharmacokinetic profile of JMT101, occurrence of anti-drug antibodies and correlation between biomarkers and clinical outcomes. A total of 121 patients are enrolled to receive JMT101 plus osimertinib 160 mg. The most common adverse events are rash (76.9%) and diarrhea (63.6%). The confirmed objective response rate is 36.4%. Median progression-free survival is 8.2 months. Median duration of response is unreached. Subgroup analyses were performed by clinicopathological features and prior treatments. In patients with platinum-refractory diseases ( n = 53), confirmed objective response rate is 34.0%, median progression-free survival is 9.2 months and median duration of response is 13.3 months. Responses are observed in distinct 20ins variants and intracranial lesions. Intracranial disease control rate is 87.5%. Confirmed intracranial objective response rate is 25%.

Background: Resistance training has been widely used in various sports and improves competition performance, especially in swimming. Swimming performance is highly dependent on muscle strength, especially short distances. For adolescent athletes, the existing literature has bound to prove that resistance training is undoubtedly bound to improve swimmers' performance.Objectives: This study adopts a systematic literature review to (1) examine the effects of resistance training on the performance of adolescent swimmers, and (2) summarize their training methods and intensity.Methods: The literature search was undertaken in five international databases: the SCOUPS, PubMed, EBSCOhost (SPORTDiscus), CNKL, Web of Science. The searches covered documents in English and Chinese published until 30th December 2020. Electronic databases using various keywords related to "strength training " and "adolescent swimmers " were searched. Sixteen studies met the inclusion and exclusion criteria where the data was then systematically reviewed using the PRISMA guideline. Furthermore, the physical therapy evidence database (PEDro) scale was used to measure each study's scientific rigor.Results: This review found that to improve the swimming performance of adolescents, two types of resistance training were used, specifically in water and on land, where both types of training can improve swimming performance. In addition, training with two types of resistance machines were better in the water than with one equipment. Resistance training can improve the swimming performance of adolescent swimmers at 50 m, 100 m, 200 m and 400 m distances. However, most studies only focused on the swimming performance at 50 m and 100 m lengths. A low-intensity, high-speed resistance training programme is recommended for adolescent swimmers to obtain the best training results.Conclusion: Water or land resistance training can improve the swimming performance. Given that both types of exercises have their strengths and weaknesses, combining these methods may enhance the swimmers' performance. In addition, despite the starting and turning phases consuming up to one-third of the total swimming time for short distances, literature in this area is limited.Systematic Review Registration:https://www/crd.york.ac.uk/prospero, identifier: CRD42021231510.

Objective The purpose of this review was to collate evidence on the prognostic ability of the geriatric nutritional risk index (GNRI) for predicting overall survival (OS) and disease-free survival (DFS) in non-small cell lung cancer (NSCLC). Methods The datasets of PubMed, Scopus, Embase, CENTRAL, and Google Scholar were searched up to 24 May 2022 for English-language studies reporting the association between GNRI and OS or DFS in NSCLC patients. Results Eleven studies with 2865 patients were included. We noted that low GNRI was a significant predictor of poor OS (HR: 1.96 95% CI 1.66, 2.30 I-2 = 0% p < 0.00001) and poor DFS (HR: 1.74 95% CI: 1.36, 2.23 I-2 = 34% p < 0.0001) in NSCLC patients. The results did not change on sensitivity analysis. There was no evidence of publication bias. Most results were significant on subgroup analysis based on study location, tumor stage, therapy type, sample size, and GNRI cut-off. Conclusion Data indicate that GNRI has good prognostic ability in patients with NSCLC. Individuals with low GNRI are at an increased risk of poor OS and DFS. GNRI could be incorporated as a simple, easy-to-use tool for the initial stratification of patients thereby allowing focused treatment plans.

9087 Background: Genomic profiling of cerebrospinal fluid (CSF) could be used to detect actionable mutations to guide the clinical treatment of NSCLC patients with central nervous system (CNS) metastases. Examining the performance of CSF samples in a real-world setting can further confirms the potential of CSF in genotyping for guiding therapy in clinical practice. Methods: A total of 1097 samples were collected from 773 treated NSCLC patients with CNS metastases in a real-world setting, including 117(10.67%) CSF samples, 287(26.16%) tissue samples and 693(63.17%) plasma samples. All samples were subjected to the targeted next-generation sequencing of 1021 cancer-relevant genes. Results: Of these 1097 treated samples, somatic alterations were identified in 112 (95.72%) of the CSF samples, comparing with 287 (100%) of tumor tissue samples and 592 (85.43%) of plasma. Among the tumor tissue samples, 242 were non-intracranial tissues, which could not reveal the unique genetic profiles of intracranial metastases. The median of maximal somatic allele frequency of CSF samples (72.35%) was significantly higher than those of plasma (1.30%) and tumor tissues (37.30%) (all p<0.001). In the thirty-two pairs CSF and plasma samples tested simultaneously, 442 alterations were detected, of which 377 were detected in CSFs and 92 in plasma. 27 alterations could be detected in both plasma and CSF, 65 were not detected in CSFs and 350 were not in plasma, the same alterations were 10.91% (27/442). For SNV or InDel, 220 mutations were detected, of which 155 were detected in CSFs and 89 in plasma, the same mutations were 10.91% (24/220). For CNVs, 216 CNV alterations were detected, of which 216 were detected in CSFs and only one in plasma. We compared actionable mutation of these 1097 treated samples to further analyze the detection capability of actionable mutations of CSF samples in this real-world setting (Table). Compared with plasma, the detection rates of all actionable mutation and actionable EGFR in CSF were significantly higher than those in plasma samples (93.16% vs. 53.97% for all actionable mutation, 83.76% vs. 39.54% for EGFR, all p<0.001).Conclusions: This real-world large cohort study verified that CSF had higher sensitivity than plasma for identifying actionable mutations. In the process of multiple comparison, it can be seen that CSF is better than plasma in detecting alterations, especially in detecting CNV alteration. CSF can be used as a substitute in genomic profiling for NSCLC patients with CNS metastases when there is no intracranial tumor tissue.[Table: see text]

Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, People’s Republic of China Aim: Apatinib, a specific tyrosine kinase inhibitor (TKI) that targets mainly vascular endothelial growth factor receptor-2 (VEGFR-2) as well as Ret, c-Kit and c-Src, has been assessed in patients with advanced osteosarcoma (phase II), the primary report of which has been published in PMID 30559126. This sub-study explored the potential signs of Adverse Events (AEs) for apatinib-treated osteosarcoma. Methods: Participants with advanced osteosarcoma progressing upon chemotherapy received apatinib until disease progression or unacceptable toxicity. Toxicities, progressionfree survival (PFS), and clinical benefit rate (CBR) following treatment were evaluated. Results: Of the 41 patients recruited to the study, 37 received treatment and constituted the safety population. At data cut-off (December 30, 2017), median follow-up for safety was 7.37 (IQR, 6.33–11.07) months. The most common grade 3–4 AEs were pneumothorax (16.22%), wound dehiscence (10.81%), proteinuria (8.11%), diarrhea (8.11%), and skin reaction (8.11%). Only hypertension was an independent predictive factor for both PFS (hazard ratio [HR], 0.44; P = 0.07) and CBR (P = 0.07). Anorexia was also significantly related to a longer PFS in a Cox regression model (HR, 0.35; P =0.01). For CBR, pneumothorax and hypothyroidism showed more clinical benefit (P = 0.07 and 0.00, respectively). Conclusion: The results of this study suggest that anorexia, hypertension, pneumothorax, and hypothyroidism might be markers for a favorable clinical outcome following apatinibtreated refractory osteosarcoma.

Non-small cell lung cancer (NSCLC) is a profoundly devastating disease that is the leading cause of cancer-related death worldwide. With the rapid development of next-generation sequencing (NGS), which has supplied the ability to decode tumors at the DNA level, so that targeted therapy plays a crucial role in improving NSCLC survival. We first reported a 32-year-old Chinese female patient received the ninth-line treatment, who was initially diagnosed with advanced NSCLC with EGFR 19 deletion. The patient had a satisfactory clinical response to initial gefitinib treatment. Subsequently, an EGFR T790M mutation was detected from plasma-derived circulating tumor DNA (ctDNA) by ddPCR after disease progression, while NGS did not. Osimertinib was still tried but had no therapeutic effect. Then the disease even progressed on the administration of chemotherapy and gefitinib in succession. Rebiopsy for NGS detection was performed, and gefitinib plus anlotinib/vemurafenib were tried. And then, gefitinib plus crizotinib were administrated for MET amplification after the third biopsy. Furthermore, chemotherapy combined with immunotherapy was performed due to the PD-L1 positive expression. Up to now, osimertinib treatment was undertaken to base on an EGFR exon 20 T790M mutation using NGS-based genotyping in cerebrospinal fluid (CSF) ctDNA. Tumor genome dynamic monitoring can identify tumor driving genes and drug resistance mechanisms to guide tumor treatment. This study found that the total survival time of advanced NSCLC patients was more than four years after chemoradiotherapy and targeted therapy, indicating the significance of dynamic monitoring of gene alterations for cancer treatment.

Background The aim was to compare the laboratory data of patients with suspected and confirmed new coronavirus pneumonia (COVID-19) and look for diagnostic predictive and early warning indicators, which will help to better manage the disease. Methods A total of 36 confirmed COVID-19 patients were divided into the general (n = 17) and critical group (n = 19). The suspected group enrolled 23 suspected COVID-19 patients with the negative nucleic acid test result. We collected all patients' clinical characteristics and some laboratory indicators at the time of admission and conducted Logistic regression analysis after comparing the differences between groups. Results There were no significant differences in age, gender, disease duration, fever history, and comorbidities between the suspected and general group (P > 0.05); however, fibrinogen was statistically different (P < 0.05). Compared with the general group, the oxygenation index and lymphocytes were significantly reduced and the Neutrophil-to-lymphocyte Ratio (NLR) and total bilirubin were increased in the critical group (P < 0.05). The fibrinogen OR value was 2.52 (95% CI 1.18-5.36, P = 0.017) and the NLR OR value was 2.91 (95% CI 1.36-6.21, P = 0.006). Conclusions Fibrinogen is a valuable diagnostic predictor for patients with suspected COVID-19. For confirmed COVID-19 patients, the NLR is a valuable early warning indicator.

Background: Sacral tumors and tumor-like lesions are a rare group of lesions that can affect children and adults of all ages. Little is known about clinical characteristics of age, gender, histologic type and anatomic site in China.Methods: 1385 patients with sacral tumors and tumor-like lesions, which had the clinical record at our bone tumor center from January 2000 to November 2018 were analyzed. The metastatic cancers were not included in the present study.Results: 51.7% (716 cases) were malignant and 48.3 % (669 cases) were benign tumors or tumor-like lesions. Of malignant tumors, chordoma was the most common malignant tumor (316 cases, 22.8% of all tumors), followed by chondrosarcoma, myeloma and other histologic types. The most common histological type of benign tumors was giant cell tumor accounting for 14.8% (205 cases) of all tumors, followed by neurofibroma, schwannoma and other types. The most common age group affected by malignant bone tumors was the 51- to 60-year-old group, followed by the 41- to 50-year-old group. The most commonly affected age group for benign tumors and tumor-like lesions was the 31- to 50-year-old group, followed by the 21- to 30-year old group. Furthermore, the following histologic types had the gender predilection. Chordoma, chondrosarcoma, myeloma and osteosarcoma affected more frequently males than females. Malignant peripheral nerve sheath tumor, lymphoma, giant cell tumor, neurofibroma, tuberculosis, teratoma and epidermoid cyst more frequently affected females than males.Conclusions: The large cohort of sacral tumors and tumor-like lesions in our database may reveal their clinical characteristics of age, gender, histologic type and anatomic site in China and features of sacral tumors and tumor-like lesions is fairly distinct from the mobile spine and extremities.

RATIONALE:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for hematological malignancies. Common complications are opportunistic infections and graft-versus-host disease (GVHD). Cytomegalovirus (CMV) is one of the most common causes of opportunistic infections. PATIENT CONCERNS:A 30-year-old male was diagnosed with T-cell lymphoma after persistent cough and lymphadenopathy. Fever, abdominal pain, diarrhea, rash, and dyspnea occurred after HSCT. DIAGNOSIS:The young man developed severe CMV infection with CMV detected in the bronchoalveolar lavage fluid and gastrointestinal tract. INTERVENTIONS:Intravenous ganciclovir and high-dose glucocorticoids were administered after the patient was diagnosed with CMV pneumonia and enteritis. OUTCOMES:After 3 weeks, the young man died from respiratory failure and infectious toxic shock caused by severe CMV infection. LESSONS:Patients after HSCT should be closely monitored CMV-DNA in blood and other specimen, and treated first if necessary, so as to avoid the occurrence of severe infections such as CMV gastroenteritis and pneumonia.

Lu Xie Jie Xu Sen Dong Jian Gao Xiaodong Tang Taiqiang Yan Rongli Yang Wei Guo 1Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Catheterization Room & Radiology Department, Peking University People’s Hospital, Beijing, People’s Republic of China Purpose: We intend to analyze the gain and loss from transcatheter intra-arterial (IA) limb infusion of cisplatin for extremity osteosarcoma in the past six years. Patients and methods: Between December 2009 and August 2014, a total of 99 patients were analyzed for efficiency and followed up for long-term survival. Based on the different administration methods of cisplatin, we divided them into the following two cohorts: IA infusion of cisplatin (n=48) and intravenous (IV) infusion of cisplatin (n=51). Except for cisplatin, all the other drugs were given intravenously. Cisplatin was given intra-arterially with an infusion time of 3 hrs or 6 hrs using a pump, whereas historical controls received IV infusion of cisplatin within 60 mins. Tumor neovascularity (TNV) was analyzed before infusion, and subsequent arteriograms were compared with the baseline to determine percent changes. Definitive surgery with intended wide resection and postoperative pathological evaluation were performed in all these patients. Results: No local or overall survival benefit was found in the patients preoperatively treated with IA infusion of cisplatin compared with IV infusion (P=0.336 and 0.173, respectively). Furthermore, serial arteriography was used to predict a good histologic response with an accuracy of 73.1% and a sensitivity of 100%. There were sporadic cases with the telangiectatic subtype, which did not respond very well to IV chemotherapy, but later, the tumor obviously shrank after IA infusion of cisplatin. Our study also showed that the rates of the complication of skin and muscle necrosis were not so low as reported. Conclusion: We did not observe any survival advantage of chemotherapy using IA infusion in osteosarcoma of the extremities. Arteriography for TNV can be used to predict the tumor histologic response. Malposition of the catheter might severely increase the complication of skin or muscle necrosis.