Tumors In China Research Articles

Diagnosis and outcomes of pediatric central nervous system tumors in China: a single-center retrospective analysis from 2015 to 2020

Background: A primary central nervous system (CNS) tumor is the most common solid tumor among children, but few systematic and comprehensive studies on childhood CNS tumors in China. We aim to review the characteristics, treatments, and prognosis of childhood CNS tumors in a single-center and disclose the present issues on these tumors.

CD13 downregulation mediated by ubenimex inhibits autophagy to overcome 5-FU resistance by disturbing the EMP3/FAK/NF-κB pathway in gastric cancer cells.

BackgroundGastric cancer (GC) is one of the most common malignant tumours in China, but the efficacy of chemotherapy on GC is significantly reduced due to the occurrence of drug resistance. Some studies have shown that the expression level of CD13 is associated with tumour resistance, but whether ubenimex, as a CD13 inhibitor, reverses GC drug resistance and the underlying mechanism remain unclear.MethodsHerein, resistance to 5-fluorouracil (5-FU) was reversed in GC by ubenimex, and the underlying mechanism was determined using Cell Counting Kit-8 (CCK-8) assays, gene chip analysis, high content screening (HCS), transmission electron microscopy, flow cytometry, immunofluorescence and western blot assays.ResultsFlow cytometry, transmission electron microscopy and immunofluorescence analyses indicated that ubenimex, an inhibitor of CD13, regulated the autophagy and apoptosis of SGC7901/5-FU cells by downregulating CD13 expression. In addition, Gene chip analysis and HCS demonstrated that epithelial membrane protein 3 (EMP3)/focal adhesion kinase (FAK) was a putative signalling pathway downstream of CD13. Furthermore, western blot analyses showed that ubenimex not only inhibited EMP3, FAK and nuclear factor-κB (NF-κB) expression but also suppressed GC autophagy and activated apoptosis by targeting CD13. These findings indicated a potential mechanism via the CD13/EMP3/FAK/NF-κB pathway and that the activity of which was restrained.ConclusionsUbenimex affects autophagy and apoptosis to reverse GC cell resistance by targeting the CD13/EMP3/FAK/NF-κB pathway. These results showed that ubenimex is a promising agent that may inhibit GC autophagy to improve chemotherapeutic drug sensitivity and thereby reverse drug resistance.

Is there a relationship between two different anesthetic methods and postoperative length of stay during radical resection of malignant esophageal tumors in China?: a retrospective cohort study

BackgroundData providing a relationship between the anesthetic method and postoperative length of stay (PLOS) is limited. We aimed to investigate whether general anesthesia alone or combined with epidural anesthesia might affect perioperative risk factors and PLOS for patients undergoing radical resection of malignant esophageal tumors.MethodsThe study retrospectively analyzed the clinical data of 680 patients who underwent a radical esophageal malignant tumor resection in a Chinese hospital from January 01, 2010, to December 31, 2020. The primary outcome measure was PLOS, and the secondary outcome was perioperative risk-related parameters that affect PLOS. The independent variable was the type of anesthesia: general anesthesia (GA) or combined epidural-general anesthesia (E-GA). The dependent variable was PLOS. We conducted univariate and multivariate logistic regression and propensity score matching to compare the relationships of GA and E-GA with PLOS and identify the perioperative risk factors for PLOS. In this cohort study, the confounders included sociodemographic data, preoperative chemotherapy, coexisting diseases, laboratory parameters, intraoperative variables, and postoperative complications.ResultsIn all patients, the average PLOS was 19.85 ± 12.60 days. There was no significant difference in PLOS between the GA group and the E-GA group either before or after propensity score matching (20.01 days ± 14.90 days vs. 19.79 days ± 11.57 days, P = 0.094, 18.09 ± 9.71 days vs. 19.39 ± 10.75 days, P = 0.145). The significant risk factors for increased PLOS were lung infection (β = 3.35, 95% confidence interval (CI): 1.54–5.52), anastomotic leakage (β = 25.73, 95% CI: 22.11–29.34), and surgical site infection (β = 9.39, 95% CI: 4.10-14.68) by multivariate regression analysis. Subgroup analysis revealed a stronger association between PLOS and vasoactive drug use, blood transfusions, and open esophagectomy. The results remained essentially the same (stable and reliable) after subgroup analysis.ConclusionsAlthough there is no significant association between the type of anesthesia(GA or E-GA) and PLOS for patients undergoing radical esophageal malignant tumor resection, an association between PLOS and lung infection, anastomotic leakage, and surgical site infection was determined by multivariate regression analysis. A larger sample future study design may verify our results.

Thinking and suggestions on pathway management of perioperative enhanced recovery after surgery in gastrointestinal tumors in China

Enhanced recovery after surgery (ERAS) is a multimodal perioperative care program to decrease the risk of delayed hospitalization, medical complications, readmission and to improve patient short- and long-term outcomes with minimized level of surgical stress responses through multidisciplinary cooperation. Despite its huge success, the program has challenges for further optimization with a primary focus on modification according to the specific pathophysiology and perioperative management characteristics of patients with gastrointestinal tumors to improve the compliance and implementation rate of items. Patient education, prehabilitation, multimodal analgesia, precision surgery, early mobilization, early oral feeding and oral nutrition supplement (ONS) should be regarded as core terms suitable for all the patients. During the application of ERAS pathway management, it is necessary to fully understand the perioperative changes of organ function and pathophysiology, and to strictly implement the ERAS program and items based on evidence-based medicine. Moreover, the close collaboration of multidisciplinary teams is needed to improve the compliance and increase the adherence rate of ERAS protocol for patients, which emphasizes the dynamic, gap-free and whole course management that covers pre-hospital, pre-operative, intra-operative, post-operative and post-hospital periods. Concurrently, we encourage our patients and their families to participate in the whole healthcare activities. Even more concerning, it is indispensable to adjust ERAS program for special time and special patients. At present, several consensus and guidelines on the ERAS management of gastrointestinal tumor surgery have come out for clinical practice in China, which, however, still lacks a high-level evidence from more high-quality clinical trials conducted by Chinese researchers. It is urgent to carry out a series of large-scale randomized controlled studies in accordance with international standards to obtain high-level evidence-based medical evidence for clinical practice, which is problem-oriented and integrated with features of metabolism and perioperative management of gastrointestinal tumor surgery.

Treatment Benefits and Side Effects of Transarterial Chemoembolization with Drug-Eluting Bead Microspheres (DEB-TACE) in Hepatocellular Carcinoma Patients with Conventional TACE Resistance: A Retrospective Study

Background: Hepatocellular carcinoma (HCC) is currently the fourth most common malignant tumor and the second most fatal tumor in China, posing serious threats to the health and life of individuals. Objectives: This retrospective study aimed to investigate the treatment benefits and side effects of transarterial chemoembolization with drug-eluting bead microspheres (DEB-TACE) for HCC patients with conventional TACE (cTACE) resistance. Patients and Methods: A total of 17 HCC patients with cTACE resistance, treated by DEB-TACE, were retrospectively analyzed from July 2017 to December 2019. According to the modified response evaluation criteria in solid tumors (mRECIST), the efficacy of treatment was classified into complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD), and the objective remission rate (ORR) and the disease control rate (DCR) were also measured at 6 and 12 weeks post-DEB-TACE treatment. Changes in liver enzymes, routine blood tests, and alpha-fetoprotein (AFP) levels were also documented. Besides, the patients’ adverse reactions were observed within one week after surgery to assess the safety of DEB-TACE therapy. Results: In patients with cTACE resistance, the CR, PR, SD, PD, ORR, and DCR were 0, 35.29%, 47.06%, 17.65%, 35.29%, and 82.35% at six weeks after DEB-TACE and 5.88%, 47.06%, 29.41%, 17.65%, 52.94%, and 82.35% after 12 weeks, respectively. In the first week after DEB-TACE, the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, and white blood cells elevated temporarily (P < 0.05), and side effects, such as slight pain, fever, nausea, and vomiting, occurred after surgery. Following liver protection and symptomatic treatment, the patients recovered well. Conclusion: Based on the results of this study, DEB-TACE has treatment benefits and few side effects for HCC patients with cTACE resistance.

Pelvic limb-salvage surgery for malignant tumors: 30 years of progress in China

This article reviews the development and progress in the field of limb salvage treatment, surgical techniques, and function reconstruction of pelvic malignant tumors in China in the past 30 years. Based on the surgical classification of pelvic tumor resection in different parts, the development of surgical techniques and bone defect repair and reconstruction methods were described in detail. In recent years, in view of the worldwide problem of biological reconstruction after pelvic tumor resection, Chinese researchers have systematically proposed the repair and reconstruction methods and prosthesis design for bone defects after resection of different parts for the first time in the world. In addition, a systematic surgical classification (Beijing classification) was first proposed for the difficult situation of pelvic tumors involving the sacrum, as well as the corresponding surgical plan and repair and reconstruction methods. Through unremitting efforts, the limb salvage rate of pelvic malignant tumors in China has reached more than 80%, which has preserved limbs and restored walking function for the majority of patients, greatly reduced surgical complications, and achieved internationally remarkable results.

Role of circular RNAs in the diagnosis, regulation of drug resistance and prognosis of lung cancer.

Lung cancer is one of the most common malignant tumors in China and is the highest cause of mortality among male and female patients, both in urban and rural areas. A subset of patients with lung cancer only display chest tightness without any other obvious symptoms. This is because most symptoms do not manifest during the early stages of disease development. Consequently, most patients with lung cancer are diagnosed when the disease is in the advanced stages, when they are already unfit for surgical treatment. Furthermore, the prognosis of patients with lung cancer is poor. The 5-year survival rate of patients with stage IA lung cancer is 85%, compared with 6% in those with stage IV. This requires the development of strategies for early diagnosis, treatment and prognosis to improve the management of lung cancer. Circular RNAs (circRNAs) belong to a class of closed circular non-coding RNAs formed by reverse splicing of a precursor mRNA. These RNAs are highly stable, ubiquitously expressed, conserved, and show high specificity. CircRNAs regulate biological processes, such as the proliferation, differentiation and invasion of lung cancer cells. Therefore, they can be used as biomarkers for the early diagnosis and prognosis prediction of lung cancer, as well as novel targets for therapy design. In the present review, the biological characteristics and functions of circRNAs, as well as their application in the diagnosis, control of drug resistance and effect on the prognosis of patients with lung cancer, will be discussed.

FOCAD/miR-491-5p, downregulated by EGR1, function as tumor suppressor by inhibiting the proliferation and migration of gastric cancer cells

Gastric cancer is a common malignant tumor in China; however, its carcinogenesis remains unknown. Focadhesin (FOCAD) is a tumor suppressor gene in gliomas, its expression, role, and mechanism in gastric cancer have not been defined. The aim of the present study was to explore the expression pattern of FOCAD in human normal tissues and cancer tissues and elucidate the role and regulatory mechanism of Early Growth Response 1 (EGR1) in FOCAD and its intron, miR-491-5p, in gastric cancer. Immuno histochemical staining revealed that FOCAD is widely and highly expressed in normal gastric mucosa, but is absent in gastric cancer tissue. Based on an association analysis FOCAD expression was found to be negatively associated with lymph node metastasis (P = 0.004); higher FOCAD levels were associated with longer survival in patients with gastric cancer (P = 0.001). MTT, colony, Transwell chamber, and flow cytometry assays revealed that siFOCAD promoted cell proliferation, growth, and migration, and inhibited apoptosis. Furthermore, bioinformatic analysis, Fluorescence reporter gene and chromatin immunoprecipitation analyses confirmed that EGR1 binds to the promoter and negatively regulates FOCAD and miR-491-5p at the transcriptional level. The overexpression of EGR1 was also found to promote cell proliferation, growth, and migration, and inhibit apoptosis. Overall, FOCAD is specifically overexpressed in the gastric mucosa and is significantly downregulated in gastric cancer. To our knowledge, this is the first study to demonstrate that FOCAD is a tumor suppressor, higher FOCAD levels might be a better prognostic marker of gastric cancer, and FOCAD/miR-491-5p may be negatively regulated by EGR1.

Factors Influencing Men's Attitudes toward HPV Vaccination in Males Included in the Chinese National Immunization Program.

Background: Human papillomavirus (HPV) infection is the most common sexually transmitted disease, and it is associated with anogenital warts and oropharyngeal and anogenital cancers. Among female malignant tumors in China, the incidence of cervical cancer ranks second, with only breast cancer being more prevalent. HPV infection and related diseases affects both women and men. HPV vaccination is an optimal prevention strategy in preventing HPV infection and related diseases. The inclusion of the HPV vaccine in the national immunization program is an effective way to increase immunization coverage, reduce the burden of HPV related diseases, and increase national life expectancy. Objective: This study aimed to explore the factors influencing the attitudes of Chinese men toward the inclusion of the HPV vaccine in males included in the national immunization program, thus providing reference for launching the national immunization program policy. Methods: We invited men aged 20 to 45 to participate in an online survey. The participants were requested to complete a questionnaire, including sociodemographic characteristics, sexual behavior characteristics, knowledge of HPV and the HPV vaccine, and attitudes toward the HPV vaccine. A logistic regression model was constructed to analyze the influencing factors of attitudes. Results: A total of 660 males in China participated in this survey, and 80.45% supported the inclusion of HPV vaccines in national immunization programs. Participants earning CNY 100,000–200,000 (dds ratio (OR): 0.63, 95% confidence interval (CI): 0.39–1.00) or ≥200,000 (OR: 0.34, 95% CI: 0.17–0.68) were more likely to disapprove this strategy. Compared with people without a history of HPV infection, those with a history of HPV infection (OR: 1.84, 95% CI: 1.17–2.90) were more likely to approve. Men who had better knowledge of HPV were more likely to approve than men with less knowledge about HPV (OR: 1.44, 95% CI: 1.17–1.79). Compared with participants who did not know when the HPV vaccine should be given, those who knew that the ideal time of vaccination is before an individual becomes sexually active (OR: 1.75, 95% CI: 1.04–2.95) were more likely to approve. Conclusion: One in five men did not support the inclusion of HPV vaccines in national immunization programs, and they are likely to be from higher socioeconomic background and have poor knowledge of HPV. In order to implement comprehensive immunity, targeted actions need to be taken at national and public levels. In addition, when implementing measures, more attention needs to be paid to lower income men, men without a history of HPV infection and with poor knowledge of HPV, as well as young men.

Abstract CT513: Phase I study of IBI322 (anti-CD47/PD-L1 bispecific antibody) monotherapy therapy in patients with advanced solid tumors in China

Abstract Background: IBI322 is an anti-CD47/PD-L1 bispecific antibody that blocks both the PD-1/PD-L1 and CD47/SIRP-α pathways. By an “imbalanced” design with a lower binding affinity to CD47 and a higher binding affinity to PD-L1, preclinical models showed IBI322 blocks CD47 on CD47+/PD-L1+ tumors more selectively than a regular CD47 monoclonal antibody does, with minimal impact on RBCs. We conducted first-in-human, phase I study of IBI322 monotherapy in patients with advanced solid tumors. Here, we report the results from early dose escalation/expansion part of the study. Methods: Eligible patients (18-75 years of age, ECOG PS 0-1) had locally advanced, recurrent, or metastatic solid tumors without available therapies to confer clinical benefit. The dose escalation (0.01 to 45 mg/kg, QW/Q2W/Q3W, IV) followed an accelerated titration and a standard 3+3 design. Dose expansion part was conducted at 10-30mg/kg Q2-3W groups. The primary objectives of this study were to evaluate the safety, tolerability and preliminary anti-tumor activity (per RECIST v1.1) of IBI322. Results: As the data cut-off date on October 12, 2021, 58 patients were enrolled (age: 53±11.7 years, 37 [63.8%] males, ECOG PS 1: n=38 [65.5%], previously ICI treated: n=15 [25.9%]). Only one DLT of grade 4 reversible thrombocytopenia was observed at 20mg/kg Q2W group. Treatment-related adverse events (TRAEs) of any grade occurred in 43 (74.1%) patients. The most frequent TRAEs including anemia (31.0%), thrombocytopenia (22.4%), and pyrexia (15.5%). Grade ≥3 TRAEs occurred in 13 (22.4%) patients, the most frequent Grade ≥3 TRAE was thrombocytopenia (12.1%). All thrombocytopenia was asymptomatic, transient, and reversible within 10 days. No thrombocytopenia led to any hemorrhage. Investigator-determined immune-related adverse events occurred in 10 (17.2%) patients. Two (3.4%) patients experienced infusion reaction. Among 20 patients treated at active doses (≥10 mg/kg) and with at least one tumor assessment, 4 (20%) achieved PR, and 7 (35%) achieved SD. Among 9 patients with NSCLC (including 4 patients failed on prior ICI treatment) who were treated at active doses (≥10 mg/kg), 3 (33.3%) achieved PR, and 5 (55.6%) achieved SD. As of data cut-off date, all these 4 patients achieved PR mentioned above still remained on IBI322 monotherapy. Conclusion: IBI322 monotherapy showed a manageable safety profile with a promising anti-tumor activity in heavily treated patients with advanced malignancies. Study is ongoing to further evaluate IBI322 monotherapy and in combination with other regimen in various types of solid tumor. Clinical trial information: NCT04328831, NCT04912466 Citation Format: Jie Wang, Yuping Sun, Qian Chu, Jianchun Duan, Rui Wan, Zhijie Wang, Jun Zhao, Haoyuan Li, Yingmei Guo, Yuling Chen, Yan Wang. Phase I study of IBI322 (anti-CD47/PD-L1 bispecific antibody) monotherapy therapy in patients with advanced solid tumors in China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT513.

The advanced development of molecular targeted therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), one of the most common malignant tumors in China, severely threatens the life and health of patients. In recent years, precision medicine, clinical diagnoses, treatments, and innovative research have led to important breakthroughs in HCC care. The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC. Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment. Multiomics technologies, such as genomics, transcriptomics, and metabolomics, have enabled deeper understanding of the occurrence and development mechanisms, heterogeneity, and genetic mutation characteristics of HCC. The continued promotion and accurate typing of HCC, accurate guidance of treatment, and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC. Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.

Abstract 5249: Efficacy and safety of apatinib in treatment of unresectablehepatocellular carcinoma: A real-world study

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Apatinib is a small molecule TKI inhibitor. Its efficacy and safety for unresectable HCC patients have been demonstrated in randomized controlled clinical studies. However, the efficacy and safety of apatinib in real world is lacking. We are aiming to evaluate the efficacy and safety of apatinib in real world.MethodsPatients of older than 18 years with unresectable HCC confirmed by IHC (Immunohistochemistry) or CT and MR Imaging were enrolled in the study. All patients received apatinib monotherapy or combined with other treatments including TACE and chemotherapy. The enrolled patients were treated until disease progression, death, or severe intolerable toxicity, etc. The primary endpoint was overall response rate (ORR), and secondary endpoints were disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The adverse events (AEs) were also recorded.ResultsFrom February, 2019 to May, 2020, a total of 233 patients were enrolled. Among them, 66 (28.33%) patients received apatinib monotherapy and 167 (71.67%) patients received combination therapy. Patients with a history of hepatitis accounted for 70%. 8 patients achieved complete response (CR), 64 patients achieved partial response (PR), 120 patients achieved stable disease (SD), and 41 patients had progressive disease (PD), illustrating an ORR of 30.90% and a DCR of 82.40%. Median PFS and OS were 6.93 months (95% CI, 6.19-7.68 months) and 11.36 months (95% CI, 9.96-12.77 months), respectively. The safety profile indicated that the most common drug-related adverse events were hypertension (37.90%), hand-foot-skin reaction (27.39%), fatigue (19.11%), thrombocytopenia (16.02%). Grade 3/4 treatment related AEs included thrombocytopenia (4.30%), hypertension (3.82%), neutropenia (2.73%). After symptomatic treatment, all the adverse events were treated properly, and no unexpected adverse events were observed. Conclusions In current study, apatininb showed good tolerance with acceptable toxicity and high tumor response rate that translated into promising PFS and OS in unresectable HCC patients. ChiCTR1900021822 Citation Format: Jun Liu, Guangbing Li, Qiang He, Shijun Sun, Chuanlin Zhao, Chuandong Sun, Bo Zhang, Yi Cui, Yongqiang Ye, Xuting Zhi, Shiping Li, Shiping Li, Guozheng Pan, Changlin Ma, Jinhua Hu, Jun Li, Suling Wang, Yuangang Qiao, Wanhua Ren, Qi Meng. Efficacy and safety of apatinib in treatment of unresectablehepatocellular carcinoma: A real-world study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5249.

Single-cell sequencing analysis reveals gastric cancer microenvironment cells respond vastly different to oxidative stress

Gastric cancer is a common type of gastrointestinal malignant tumor in China. The mechanism of the development and progression of gastric cancer remains the continuing research focus. The tumor microenvironment plays an important role in the development and progression of tumors. The present study used single-cell sequencing data to characterize the microenvironment of gastric cancer, investigate the effects of oxidative stress on gastric cancer microenvironmental cells through the comparison between cancer tissue and normal tissue, and identify the key genes associated with gastric cancer patients’ survival. The results showed that compared with normal gastric tissue, gastric cancer tissue had a decreased oxidative stress response, weaker oxidative detoxification ability, and increased oxidative stress-induced cell death. In the different types of single cells of gastric cancer microenvironment, the oxidative stress response of T cell was increased, the ability of oxidative detoxification was enhanced, and the oxidative stress-induced cell death was exacerbate. Mucous cell showed the same trend as gastric cancer cells: decreased oxidative stress response, weak oxidative detoxification ability, and weakened oxidative stress-induced cell death. Moreover, TRIM62, MET, and HBA1, which were significantly associated with oxidative stress, may be biomarkers for the prognosis of gastric cancer. High expression of TRIM62 indicated a good prognosis, while MET and HBA1 indicated a poor prognosis, which will be confirmed by further clinical studies.

Comprehensive genomic profiling of MET rare tumors in China.

e15058 Background: The mesenchymal epithelial transition factor receptor (MET) is a potential therapeutic target in a number of cancers, commonly activated by amplification, mutation and fusion. Methods: Rare tumor was defined as solid tumors with an incidence lower than 2.5/100,000 per year. We retrospectively analyzed the next-generation sequencing and clinicopathological data of 3453 Chinese rare tumors patients in the Geneplus database, including 1021 genes, MSI loci, tumor mutational burden (TMB), and programmed cell death ligand-1 (PD-L1) expression analysis information. Results: MET-positive was identified in 115 patients (3.3%), including 109 cases of amplification (3.2%), 8 cases of exon 14 skipping (0.2%) and 1 cases of fusion. The prevalence of MET-positive varied widely across tumors systems and subtypes. Urinary, neural, skin and respiratory systems were the top 4 systems with 8.3% (1/12), 7.9% (58/732), 4.2% (1/24) and 2.9% (6/207) MET-positive rate, respectively. Considering the tumor subtypes, glioblastoma, sarcomatoid carcinoma, neuroendocrine tumor and glioma were higher, reaching 15.7% (16/102), 13.2% (7/53), 9.8% (4/41), and 7.4% (36/487) respectively (Table). Totally, 73.0% of patients had at least one common targetable gene mutation, including ATM，BRAF，BRCA，CDKN2A，EGFR substitution, ERBB2, FGFR1,2,3, KIT, NF1, PIK3CA, PTEN and RET. The proportions of TMB-H (≥9 mut/Mb) and MSI-H were very low, with only 8.9% and 2.2%, while PD-L1 positive rate reached to 60.9%. Conclusions: The treatment options for rare tumors are still limited. The approval of MET receptor tyrosine kinase has brought hope to patients with Non-Small Cell Lung Cancer. The MET-positive rate in rare tumors is higher than 2.7% in lung adenocarcinoma, so MET receptor tyrosine kinase have great application potential in rare tumors. However, since most patients co-occurred with other targetable driver mutations or PD-L1 positive, how to choose the best treatment strategy should be solved. The deployment of the best treatment strategy is a problem that should be solved in the follow-up study.[Table: see text]

Clinical performance of a liquid biopsy test based on the detection of multiple DNA methylation biomarkers for early detection of gastrointestinal cancers.

e16096 Background: Gastrointestinal cancers (colorectal cancer, gastric cancer and esophageal cancer) are the most prevalent malignant tumors in China, resulting in 975,537 new cases and 958,675 deaths in 2020. Currently, the gold standard for the early detection of these cancers remains to be gastrointestinal endoscopy. However, the invasiveness, low throughput and high cost of these procedures have prevented its wide acceptance by Chinese population. The objective of this study was to develop a liquid biopsy test based on the detection of multiple DNA methylation biomarkers (SpecGastro test) and evaluate its clinical performance for early detection of gastrointestinal cancers. Methods: Two hundred and eighty-two gastrointestinal cancer patients (98 colorectal cancers, 136 gastric cancers and 48 esophageal cancers) and 195 control subjects were included. Ten milliliters of peripheral blood was drawn and 3.5 mL plasma was separated for cell-free DNA extraction and bisulfite conversion. The converted DNA was subsequently examined by SpecGastro test, a multiplex qPCR assay that detected six methylation biomarkers and one internal control. Results: Overall sensitivity for SpecGastro test was 76.6% (95% CI: 71.1-81.3%) with a specificity of 89.2% (95% CI: 83.8-93.1%). Sensitivities for colorectal cancer, gastric cancer and esophageal cancer were 87.8% (95% CI: 79.2-93.2%), 69.9% (95% CI: 61.3-77.3%) and 72.9% (95% CI: 57.9-84.3%), respectively. A high AUC of 0.903 (95% CI: 0.873-0.928) indicated that SpecGastro test distinguished gastrointestinal cancer patients from control subjects with high accuracy. Conclusions: Our analysis demonstrated the utility of SpecGastro test to detect three types of gastrointestinal cancers with high sensitivity and specificity. These results supported the feasibility of this blood-based SpecGastro test as a complementary tool to the existing single-cancer early detection tests.

Frontline therapy of anlotinib combined with carboplatin/paclitaxel and maintenance anlotinib in patients with newly diagnosed advanced ovarian cancer: A phase II, single-arm, multicenter study.

TPS5607 Background: It has been reported that antiangiogenic drug combined with chemotherapy as first-line treatment, and subsequent antiangiogenic drug as maintenance therapy for ovarian cancer can achieve better clinical benefits. Anlotinib is a highly effective VEGFRs, FGFRs, PDGFRs and c-kit multi-target tyrosine kinase inhibitor which has been approved for the treatment of several solid tumors in China. This single arm, multicentric, phase II study is expected to investigate the efficacy and safety of anlotinib combined with carboplatin/paclitaxel as front-line treatment in patients with advanced ovarian cancer. Methods: Eligible patients with FIGO stage III–IV primary epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and ECOG PS 0-1 undergo primary debulking surgery or interval debulking surgery, will receive 6-8 cycles of chemotherapy (paclitaxel 175 mg/m2 + carboplatin area under the curve [AUC] 5 q3w) and anlotinib (12 mg po qd, days 1-14, 21 days per cycle, anlotinib will be omitted from the first treatment cycle to prevent delayed wound healing). Anlotinib as maintenance monotherapy will be continue until disease progression, unacceptable toxicity, or death. Patients with prior anti-angiogenic therapy and major surgical procedure within 28 days before the first date of anlotinib therapy will be excluded. This study will recruit approximately 56 patients. The primary endpoint is progression free survival. Key secondary endpoints include overall response rate, disease control rate per RECIST1.1, overall survival, safety. The study began enrolling patients in August 2021 and is ongoing. Clinical trial information: NCT04807166.

A phase I/II study of first-in-human trial of JAB-21822 (KRAS G12C inhibitor) in advanced solid tumors.

3089 Background: KRAS G12C mutation occurs in approximately 4% of non-small cell lung cancer (NSCLC), 1-2% of colorectal cancer (CRC) and other solid tumors in China. JAB-21822 (Jacobio, Beijing, PRC) is a highly selective, covalent oral inhibitor of KRAS G12C. Methods: NCT05009329 is an ongoing first-in-human, open label phase I/II study of JAB-21822 in patients with advanced solid tumors. The primary objective is to evaluate the safety and tolerability of JAB-21822. Other objectives include preliminary efficacy, pharmacokinetics, and biomarkers. Here we report the results from the dose escalation phase of the trial. Results: As of January 28th, 2022, 53 patients with a median age of 62 years (39-79) were enrolled in 5 different dose levels: 200mg QD, 400mg QD, 800mg QD, 400mg BID and 400mg TID. Most patients (55%) had ≥ 2 prior lines of therapy. No dosing-limiting toxicities were observed. Two treatment-related adverse events (TRAEs) were G4 neutropenia (1 in 400mg BID and 1 in 400mg TID). The most common TRAEs (≥ 10%) included anemia (24.5%), total bilirubin increase (20.8%), direct bilirubin increase (15.1%), proteinuria (13.2%) and indirect bilirubin increase (11.3%). Only Grade 1 and 2 TRAEs were observed in the QD cohorts. A total of 33 patients (22 NSCLC, 9 CRC and 2 pancreatic cancer) had at least 1 post-baseline tumor assessment; in the 800mg QD cohort, overall response rate (ORR) and disease control rate (DCR) were 50% (5/10) and 100% (10/10), respectively, including 4 non-confirmed partial response (PR); in the 400mg QD cohort had an ORR and DCR of 80% (4/5) and 100% (5/5) respectively, including 2 non-confirmed PR. Patients with NSCLC (400mg QD and 800mg QD), the ORR and DCR were 70% (7/10) and 100% (10/10), respectively, including 5 non-confirmed PR. With respect to the pharmacokinetics analysis, JAB-21822 was rapidly absorbed with an average Tmax of 2 hr and reached higher plasma exposures (Cmax and AUC0-24h) after a single dose and multiple doses at C1D8. Conclusions: JAB-21822 was well tolerated with impressive preliminary efficacy in patients with heavily treated solid tumors harboring KRAS G12C mutation. The study is enrolling patients in the expansion phase. Multiple JAB-21822-based combination trials are also ongoing. Clinical trial information: NCT05009329.

Diosbulbin B: An important component responsible for hepatotoxicity and protein covalent binding induced by Dioscorea bulbifera L.

BackgroundDioscorea bulbifera L. (DBL) is an herbal medicine used for the treatment of thyroid diseases and tumors in China. However, the hepatotoxicity of DBL limits its wide safe use. Diosbulbin B (DSB) is the most abundant diterpene lactone occurring in DBL. Numbers of studies showed that this furanoterpenoid plays an important role in DBL-induced liver injury and that DSB is metabolized to a cis-enedial intermediate which reacts with protein to form protein covalent binding and induces hepatotoxicity. PurposeThe present study aimed to define the association of DSB content in DBL with the severity of DBL hepatotoxicity to ensure the safe use of the herbal medicine in clinical practice and to determine the role of DSB in DBL-induced liver injury. MethodsChemical chromatographic fingerprints of DBL were established by UPLC-MS/MS. Their hepatotoxicity potencies were evaluated in vitro and in vivo. Metabolic activation of DSB was evaluated by liver microsomal incubation. Protein modification was assessed by mass spectrometry and immunostaining. ResultsThe contents of DSB in DBL herbs collected from 11 locations in China varied dramatically with as much as 47-fold difference. The hepatotoxicity potencies of DBL herbs were found to be proportional to the contents of DSB. Intensified protein adduction derived from the reactive metabolite of DSB was observed in mice administered DBL with high contents of DSB. ConclusionThe findings not only demonstrated that contents of DSB can be quite different depending on harvest location and special attention needs to pay for quality control of DBL but also suggest DSB is a key contributor for DBL-induced hepatotoxicity.

HMGB1-mediated autophagy promotes gefitinib resistance in human non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) ranks the first in incidence and mortality among malignant tumors in China. Molecular targeted therapies such as gefitinib, an oral inhibitor of the epidermal growth factor receptor tyrosine kinase, have shown significant benefits in patients with advanced NSCLC. However, most patients have unsatisfactory outcomes due to the development of drug resistance, and there is an urgent need to better understand the pathways involved in the resistance mechanisms. In this study, we found that HMGB1 is highly expressed in drug-resistant cells and confers to gefitinib resistance in NSCLC cells via activating autophagy process. Gefitinib upregulates HMGB1 expression in time-dependent and dose-dependent manners in human NSCLC cells. RNA interference-mediated knockdown of HMGB1 reduces PC9GR cell viability, induces apoptosis, and partially restores gefitinib sensitivity. Mechanistic analyses indicate that elevated HMGB1 expression contributes to gefitinib resistance by inducing autophagy. Thus, our results suggest that HMGB1 is an autophagy regulator and plays a key role in gefitinib resistance of NSCLC.

An investigation into the reproductive concerns of young women with breast cancer

ObjectiveBreast cancer has the highest incidence rate among malignant tumors in China, with a trend of affecting younger women. The survival rate of young patients with breast cancer has improved significantly, but the treatment to which they are subjected has short- and long-term adverse effects such as damage to the ovaries, which may result in infertility. Such consequences, in turn, increase patients’ concerns over future reproduction and childrearing. At present, patients lack easy access to the informative consultations and accurate patient education. Nor do medical staff continuously assess their overall wellbeing, engage in mental health interventions, or ensure that they have the knowledge necessary to manage their reproductive concerns. This study sought to investigate the reproductive concerns of young female patients with breast cancer, identify the factors that influence those concerns, and provide a theoretical and practical scientific basis for the future fertility management of this specific population. MethodsOur study is based on a cross-sectional survey of 112 young patients with breast cancer recruited by a convenience sampling method in the Shanghai Cancer Center, Fudan University, from October 2020 to January 2021. A self-designed questionnaire and the Chinese version of the Reproductive Concerns After Cancer were used for data collection. Multivariable linear regression was performed to analyze the data. ResultsThe total score for reproductive concerns was 59.96 ​± ​9.91, indicating that young women with breast cancer have relatively high levels of concern about reproduction. Multivariable linear regression analyses suggested that age, education level, and the desire for parenthood were the factors that influenced these concerns. The younger the patient, the higher the level of concern. Patients with a higher level of education and a greater desire for parenthood indicated greater levels of concern about reproductive issues. ConclusionsThe levels of concern about reproduction expressed by these young patients with breast cancer were high. The factors that influenced their concern were their age, education level, and desire to have children. We suggest that medical staff focus on young patients during treatment and develop effective intervention measures based on their desire for parenthood, disease condition, and psychological status to promote the patients’ physical and mental health.