Objective: Colorectal cancer (CRC) patients with high microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR) had heterogeneous pathology and distinct prognoses. This study aimed to examine the difference in the gene expression profile of dMMR/MSI-H CRC patients with different disease stages and explore the different molecular mechanisms of disease progression. Methods: A total of 47 patients with dMMR/MSI-H CRC were enrolled and retrospectively studied, including 27 stage II and 20 stage IV patients. Each patient had paired tumor tissue and white blood cell samples, which were analyzed by next-generation sequencing (NGS) of 416 cancer-relevant genes. Pathway enrichment analysis was then performed to analyze the disease stage-specific signaling pathways. Results: A total of 2878 mutation sites, spanning 378 mutated genes, were detected from the 47 dMMR/MSI-H CRC patients. The mutation frequencies of SMARCA4, EPHA3, MTHFR, RAD50, and PDGFRB were significantly higher in stage II patients than in stage IV patients (p < 0.05), whereas the stage II patients had significantly lower mutation frequencies of TSC2, FGFR1, PTPN13, SMAD3, and STK11 than stage IV patients (p < 0.05). Sixty-three mutated genes were unique to stage II tumors, while 36 mutated genes were exclusively present in stage IV tumors. Pathway analyses demonstrated the PI3K-AKT pathway was shared by both stage II and stage IV tumors, whereas multiple other signaling pathways showed disease stage-specific enrichment. Conclusion: There were profound differences in mutational profile and molecular mechanisms between stage II and stage IV dMMR/MSI-H CRC.

Background: While immune-chemotherapy represents the first-line standard for advanced esophageal squamous cell carcinoma (ESCC), fluorouracil-platinum (FP) and taxane-platinum (TP) regimens remain the fundamental cytotoxic backbones. Despite their widespread clinical application, robust comparative data on their relative efficacy and safety in real-world populations are lacking, creating an evidence gap that hampers optimal backbone selection. Objectives: This study aimed to compare the effectiveness and safety of first-line FP versus TP chemotherapy in patients with advanced ESCC using large-scale, multicenter real-world data. Design: This was a large-scale, multicenter, retrospective cohort study employing a propensity score-matched design to compare two treatment cohorts: patients receiving FP chemotherapy versus those receiving TP chemotherapy for unresectable advanced ESCC. Data spanned from January 2013 to December 2023, ensuring a contemporary and representative treatment population. Methods: Data were extracted from a national cancer database. Patients with unresectable ESCC receiving first-line FP or TP chemotherapy were included. Propensity score matching (PSM) in a 1:1 ratio was used to balance the baseline characteristics. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety. Results: After PSM, 3440 matched pairs were generated ( N = 6880 total). The median follow-up was 6.3 years. The TP regimen demonstrated superior short-term efficacy compared to FP: median PFS was 5.2 versus 4.4 months (hazard ratio (HR), 0.91; 95% confidence interval (CI), 0.86–0.96; p = 0.0004); ORR was 22.2% versus 19.5% ( p = 0.026); and among responders, median DOR was 10.8 versus 4.4 months (HR, 0.77; 95% CI, 0.64–0.94; p = 0.009). However, no significant difference was observed in OS (median OS: 15.9 vs 16.1 months; HR, 1.00; 95% CI, 0.94–1.06; p = 0.901). Toxicity profiles were distinctly regimen-specific, with FP associated with higher rates of hand-foot syndrome and gastrointestinal events, whereas TP was linked to higher incidences of neuropathy and alopecia. Conclusion: In this large-scale real-world analysis, first-line TP chemotherapy provided significantly better disease control and response durability compared to FP in advanced ESCC, albeit without an OS benefit. The distinct toxicity profiles of each regimen offer additional considerations for individualized treatment selection. These findings offer critical evidence to guide backbone selection in contemporary treatment algorithms.

Neuroendocrine neoplasms(NENs)are relatively rare tum-ors that arise from peptidergic neurons and neuroendocrine cells.NENs are highly heterogeneous and can occur in any part of the body,with a particular prevalence in the diges-tive system.NENs consist of a range of tumor types and the biological behaviors exhibit significant differences.NENs are classified into well-differentiated neuroendocrine tum-ors(NETs)and poorly differentiated neuroendocrine car-cinomas(NECs).

This study aims to assess the therapeutic efficacy and safety of nivolumab combined with chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, specifically comparing the outcomes of oxaliplatin-based versus albumin-bound paclitaxel (nab-paclitaxel)-based therapies. We retrospectively analyzed 93 patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma treated at the First Medical Center of Chinese PLA General Hospital from September 2017 to November 2022. Patients were categorized into the nivolumab + oxaliplatin (N-OX group) or nivolumab + nab-paclitaxel (N-AP group) based on the chemotherapy regimen. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated as endpoints. At the end of the follow-up period on September 31, 2023, we reported an ORR of 65.6

e16344 Background: Treatment options for patients (pts) with advanced neuroendocrine carcinoma (NEC) are very limited, of which etoposide and cisplatin (EP) is the first-line standard treatment. Combination of immune checkpoint inhibitors with chemotherapy is a potential therapeutic strategy in NEC. This study is designed to evaluate ZG005 (a recombinant humanized anti-PD-1/TIGIT bispecific antibody with dual-targeted blocking effects on PD-1 and TIGIT) plus EP as the first-line therapy in pts with NEC. Methods: This phase 1/2, multiple-centers, dose escalation (Part 1) and expansion (Part 2) study was conducted to evaluate the safety and efficacy of ZG005 in combination with EP as a first-line treatment in the pts with NEC (excluding small cell lung cancer [SCLC]). In Part 1, pts received escalating doses of ZG005 (10 mg/kg or 20 mg/kg) with a fixed dose of EP every three weeks (Q3W). In Part 2, pts were administered ZG005 10 mg/kg + EP, ZG005 20 mg/kg + EP, and placebo + EP, respectively. The primary objective of Part 1 was to evaluate the safety and determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ZG005 + EP. The primary efficacy endpoint of Part 2 was investigator-assessed ORR by RECIST V1.1, while key secondary endpoints included PFS, DOR, DCR, etc. Results: As of Jan 10, 2025, a total of 21 pts were enrolled. The median age was 61 (range 48-70), with 81% male, 100% Ki-67 ≥ 55%, and 66.7% liver metastasis. The most common primary site of the tumor was gastrointestinal (38.1%), and median treatment cycles were 4 (range 2-4). No dose-limiting toxicities (DLT) were observed in Part 1. The most common treatment-related adverse events (TRAEs) were anaemia (23.8%), white blood cell count decreased (14.3%), neutrophil count decreased (14.3%), and alanine aminotransferase increased (14.3%). Three (14.3%) pts experienced Grade ≥3 TRAEs. Serious adverse events (SAEs) occurred in 4 (19.0%) pts, with only immune-mediated enterocolitis (immune-related) being related to the ZG005. Of the 12 efficacy-evaluable pts, 6 (2 on ZG005 10 mg/kg + EP and 4 on ZG005 20 mg/kg + EP) achieved partial responses (PR, 4 confirmed PRs) and 5 pts were stable disease (SDs), with an ORR of 50% and DCR of 91.7%; DOR and mPFS were not reached yet. Conclusions: Combination of ZG005 with chemotherapy was well tolerated and showed encouraging ORR in patients with NEC. This clinical trial is still going on, and updated safety and efficacy will be presented in the future. Clinical trial information: NCT06372626 . Research Sponsor: Suzhou Zelgen Biopharmaceuticals Co., Ltd.

The patterns of postoperative recurrence vary among hepatocellular carcinoma (HCC) patients and infiltration of immune cells is correlated with patients prognosis. The present study aimed to develop and assess novel nomogram models for postsurgical recurrence and survival in HCC patients by combination of immune cell scores and clinicopathological features. A total of 233 patients with curative hepatic resection and complete clinicopathologic information were enrolled. The infiltration of CD8 + T lymphocytes, CD15 + neutrophils and CD68 + macrophages in the tumor microenvironment was assessed by immunohistochemistry in tissue microarray. Two prognostic nomogram models for disease-free survival (DFS) and overall survival (OS) were developed and multi-dimensionally evaluated to predict postsurgical HCC outcomes. The DFS nomogram was developed using AFP, GGT, tumor differentiation, Ki-67, and the densities of intratumoral CD15 + neutrophils and CD68 + macrophages. The OS nomogram was established based on gender, AFP, tumor differentiation, number of tumor nodules, microvascular vascular tumor thrombus (MVTT), Ki-67, microvessel density (MVD), the densities of intratumoral CD15 + neutrophils and CD68 + macrophages. The C-indexes for the DFS and OS nomogram were 0.708 (95

Background: Colorectal cancer (CRC) is the leading cause of cancer deaths, and treatment, especially in the metastatic stage, is challenging. Immune checkpoint inhibitors (ICIs) have revolutionized CRC treatment, but response varies, emphasizing the need for effective biomarkers. This study explores SPEN mutations as potential biomarkers. Methods: Using data from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA)—Colorectal Cancer, this research applied bioinformatics tools and statistical analysis to SPEN (Split Ends) mutant and wild-type CRC patients treated with ICIs. Focus areas included mutation rates, immune cell infiltration, and DNA damage response pathways. Results: The SPEN mutation rate was found to be 13.8% (15/109 patients) in the MSKCC cohort and 6.65% (35/526 patients) in the TCGA cohort. Our findings indicate that CRC patients with SPEN mutations had a longer median overall survival (OS) than the wild-type group. These patients also had higher tumor mutational burden (TMB), microsatellite instability (MSI) scores, and programmed death-ligand 1 (PD-L1) expression. SPEN mutants also exhibited increased DNA damage response (DDR) pathway mutations and a greater presence of activated immune cells, like M1 macrophages and CD8+ T cells, while wild-type patients had more resting/suppressive immune cells. Furthermore, distinct mutation patterns, notably with TP53, indicated a unique molecular subtype in SPEN-mutated CRC. Conclusions: We conclude that SPEN mutations might improve ICI efficacy in CRC due to increased immunogenicity and an inflammatory tumor microenvironment. SPEN mutations could be predictive biomarkers for ICI responsiveness, underscoring their value in personalized therapy and highlighting the importance of genomic data in clinical decisions. This research lays the groundwork for future precision oncology studies.

背景 目前免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)已成为晚期胃癌的一线及三线的标准治疗药物,但在二线治疗中仅被推荐用于伴有微卫星高度不稳定(MSI-H)或错配修复基因缺陷的患者,因此ICIs在晚期胃癌二线中的治疗模式需要更多的探索.目的 分析ICIs联合化疗、抗血管生成药物二线治疗晚期胃癌及胃食管结合部腺癌患者的疗效.方法 收集 2018年 6月-2022年 1月在解放军总医院第一医学中心二线行ICIs联合化疗、抗血管生成药物治疗的晚期胃癌或胃食管结合部腺癌患者的临床资料,分析入组患者的中位无进展生存期(median progression-free survival,mPFS)、客观缓解率(objective response rate,ORR)及疾病控制率(disease control rate,DCR).采用Kaplan-Meier法绘制生存曲线,并使用Cox回归分析影响mPFS的预后因素.结果 本研究共纳入 49例患者,其中男性 34例,女性 15例,中位年龄 54岁.在二线治疗中,ICIs为纳武利尤单抗或信迪利单抗,27例患者应用纳武利尤单抗,22例应用信迪利单抗.28例患者联合以紫杉醇(白蛋白结合型)为主的方案,21例联合阿帕替尼,6例联合以铂类为主的方案,5例联合以伊立替康为主的方案.69.4%患者选择了免疫药物联合两种及以上抗肿瘤药物的治疗方案.全组患者的ORR为 28.5%,DCR为 89.8%,mPFS为4.7(95%CI:3.830～5.570)个月.多因素Cox分析示,无腹膜转移患者mPFS显著优于有腹膜转移患者(HR=0.410,95%CI:0.197～0.854,P=0.017),一线未应用免疫治疗患者的mPFS显著优于一线应用免疫治疗的患者(HR=0.518,95%CI:0.272～0.987,P=0.045),二线联合≥2种治疗药物患者的mPFS显著优于联合 1种治疗药物的患者(HR=0.454,95%CI:0.231～0.890,P=0.021).结论 晚期胃癌及胃食管结合部腺癌患者二线应用ICIs联合化疗、抗血管生成药物可能提高患者治疗的有效率,延长无进展生存时间.

目的 回顾性分析信迪利单抗联合化疗一线治疗晚期胃癌或胃食管结合部腺癌的疗效.方法 收集2019-01至2022-10解放军总医院第一医学中心收治的信迪利单抗联合化疗一线治疗晚期胃癌或胃食管结合部腺癌患者临床资料,分析入组患者中位无进展生存期(mPFS)、客观缓解率(ORR)及疾病控制率(DCR).结果 共纳入71例患者,中位年龄60岁,男53例,女18例,其中45例给予信迪利联合以奥沙利铂为基础方案的治疗,26例给予信迪利联合以紫杉醇(白蛋白结合型)为基础方案的治疗.全组患者的ORR为67.6%,DCR为97.2%,mPFS为11.2个月(95%CI9.7～12.8).联合奥沙利铂为基础方案组的ORR为73.3%,DCR为97.8%,mPFS为11.3个月(95%CI5.5～17.2).联合紫杉醇(白蛋白结合型)为基础方案组的ORR为57.7%,DCR为96.2%,mPFS为10.9个月(95%CI 9.0～12.9),两组ORR及mPFS差异无统计学意义.结论 在晚期胃癌或胃食管结合部腺癌中,一线应用信迪利单抗联合化疗,患者无进展生存期明显获益.信迪利单抗联合以紫杉醇(白蛋白结合型)为基础的治疗组疗效与联合以奥沙利铂为基础治疗组相当.

背景 免疫检查点抑制剂目前已在多种实体肿瘤治疗中取得了初步成果,但其联合靶向及局部介入治疗对中晚期肝癌患者的疗效有待进一步研究.目的 探讨肝动脉化疗栓塞(transarterialchemoembolization,TACE)联合靶向药物及免疫检查点抑制剂对中晚期肝癌患者的治疗疗效及安全性.方法 收集2016年1月-2021年1月就诊于解放军总医院第一医学中心经病理学或临床诊断为中晚期肝细胞肝癌患者的临床资料,根据不同治疗方案分为两组,观察组患者采用TACE+靶向药物+免疫检查点抑制剂治疗,对照组患者应用TACE联合靶向药物治疗,分析两组的客观缓解率(objective response rate,ORR)、疾病控制率(diseasecontrolrate,DCR)、总生存期(overallsurvival,OS)及不良反应.结果 观察组98例,男性83例,女性15例,平均年龄为55.5岁;对照组52例,男性43例,女性9例,平均年龄为53.7岁.两组年龄和性别差异无统计学意义(P>0.05).观察组和对照组患者的ORR分别为56.1％和38.5％,DCR分别为81.6％和69.2％,中位总生存期分别为23.1个月和16.27个月,以上差异均有统计学意义(P均<0.05).观察组最常见的不良反应为高血压(22.4％),其次为腹泻(21.4％)、手足反应(20.4％),而对照组最常见的不良反应为手足反应(32.7％),其次为腹泻(19.2％)、高血压(15.4％),两组各不良反应发生率差异无统计学意义(P>0.05).结论 TACE联合靶向药物及免疫检查点抑制剂为延长中晚期肝癌患者的生存时间带来了希望,有望推动局部介入与药物联合治疗的新局面.

To investigate the association between tumor protein 53 polymorphism and esophageal cancer cases using systematic review and meta-analysis, this provides a basis for future researches. All studies on tumor protein 53 mutations in patients with esophageal cancer and its influencing factors, which published before May 2021, were collected by searching Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure and Wanfang data. Meta-analysis was performed using RevMan 5.3. Ten eligible studies (Chinese n=7, English n=3) involving 1379 cases were included in this analysis. Meta-analysis showed that the odds ratio value (95 % confidence interval) of tumor protein 53 mutations in Caucasian patients with esophageal cancer was 70.51 (9.77, 508.88), z=4.22, p<0.0001; the odds ratio value (95 % confidence interval) of tumor protein 53 mutations in Chinese Han patients with esophageal cancer was 1.06 (0.63, 1.79), z=0.22, p=0.83; the odds ratio value (95 % confidence interval) of tumor protein 53 mutations in Chinese Uyghur patients with esophageal cancer was 18.48 (4.44, 76.90), z=4.01, p<0.0001. The odds ratio value (95 % confidence interval) of tumor protein 53 mutations in patients with esophageal cancer was 1.01 (0.60, 1.72), z=0.05, p=0.96; the odds ratio value (95 % confidence interval) of tumor protein 53 deletions in patients with esophageal cancer was 23.02 (9.04, 58.63), z=6.57, p=0.00001. There was no significant difference in tumor protein 53 mutations between patients with esophageal cancer and the control group. There is a certain correlation between tumor protein 53 polymorphism and the incidence of esophageal cancer and the change of tumor protein 53 gene will affect the risk and prognosis of esophageal cancer.

目的 初步探索晚期胆管癌患者一线应用化疗联合PD-1单抗的疗效及安全性.方法 回顾性分析2016年1月至2021年5月就诊于解放军总医院第一医学中心一线单用化疗及化疗联合PD-1单抗的晚期胆管癌患者.化疗组共52例,一线化疗方案多以白蛋白结合型紫杉醇或吉西他滨为基础;联合组共68例,在化疗的基础上联合PD-1单抗治疗.结果 至随访截止时间,化疗联合PD-1单抗组和单用化疗组均无获完全缓解(CR)的患者,两组客观缓解率(ORR)分别为33.8％和17.3％(P=0.043),疾病控制率(DCR)分别为85.3％和55.8％(P<0.01).化疗联合PD-1单抗组和单用化疗组的中位无疾病进展生存期(PFS)分别为6.1个月(95％CI:5.39～6.81个月)和4.0个月(95％CI:2.49～5.51个月),差异有统计学意义(P=0.03);中位生存期(OS)分别为12.8个月(95％CI:11.45～14.15个月)和12.4个月(95％CI:11.40～13.40个月),差异无统计学意义(P>0.05).在药物的安全性方面,两组最常见的不良反应为恶心、呕吐,其次为血液学毒性、肝功能损害、皮疹等,均为1～2级,少数患者出现3～4级血液学毒性.结论 晚期胆管癌患者一线应用化疗联合PD-1单抗在一定程度上可延缓疾病的进展并具有良好的安全性,但在OS方面未见明显的优势.

306 Background: Combined therapy of an immune checkpoint inhibitor with a targeted antiangiogenic agent had been proved to be effective for the treatment of uHCC. Penpulimab was engineered to eliminate FcγR binding and ADCC/ADCP completely, where ADCC/ADCP effects could induce T-cell apoptosis and clearance and then compromise anti-tumor activity. Penpulimab demonstrated a slower PD-1 antigen binding off-rate, which resulted in better cellular activity and higher receptor occupancy. Penpulimab also showed numerous contacts with N58 glycosylation on the BC loop of PD-1 which could be an advantage to facilitate interaction of PD-1 antibody and might contribute to slower binding off-rate. These structural differentiations offer more robust biological effect and enhance anti-tumor activity of penpulimab. Anlotinib is a multi-targeted tyrosine kinase inhibitor selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit. Methods: In this open-label, multicenter phase Ib/II study, patients (pts) without prior systemic treatment, and classified as BCLC stage B (not amenable for locoregional therapy) or C, Child-Pugh ≤7, and ECOG PS ≤ 1 received Penpulimab (200mg IV Q3W) and Anotinib (8 mg PO 2weeks on/1 week off). Primary endpoint was ORR (RECIST v1.1); secondary endpoints were safety, DCR, DoR, TTP, PFS and OS. Results: 31 pts (median age 56 years [23–74], ECOG 0/1 [64%/36%], BCLC B/C [23%/77%], HBV/HCV [61%/7%]) received combined therapy. As of August 31, 2020, median follow-up time was 11.9 mons (range 3.7-17.7). Median PFS was 7.6 mons with 6-mons PFS rate was 57.6% while median TTP was 8.5 mons with 6-mons TTP rate was 62.7%. Median overall survival had not been met and 6-mons OS rate was 93.2%. The ORR was 31.0% (9/29) and DCR was 82.8% (24/29). At data cutoff, 77.8% of responders remained ongoing and still on treatment. Treatment-related adverse events (TRAEs) occurred in 90.3% of pts (≥G3 in 16.1% [5/31], no G5, treatment discontinuation in 9.7% [3/31]). Most common TRAEs (≥15%) were increased AST (38.7%) and ALT (35.5%), increased blood bilirubin (22.6%),asthenia (22.6%),decreased platelet count (19.4%) and rash (16.1%). Conclusions: Penpulimab plus Anlotinib showed favorable antitumor efficacy and an acceptable safety profile in pts with uHCC. The further randomized, phase 3 study of Penpulimab in combination with Anlotinib at a higher dose (10 mg PO 2 weeks on/1 week off) in this setting is ongoing (NCT04344158).

背景 尼妥珠单抗是以表皮生长因子受体(epidermal growth factor receptor,EGFR)为靶点的靶向药物,在国外的临床研究中取得良好的效果,但国内大规模的临床试验数据相对较少.目的 探讨尼妥珠单抗联合吉西他滨(gemcitabine,GEM)一线治疗晚期胰腺癌的疗效和安全性.方法 通过解放军总医院大数据平台,检索2012年1月-2019年6月在解放军总医院第一医学中心治疗的晚期胰腺癌患者的临床资料,根据不同治疗方案,通过倾向性匹配,共纳入122例晚期胰腺癌患者,联合组61例采用尼妥珠单抗+GEM,单药组61例采用GEM单药化疗.比较两组患者的一般资料、不良反应发生率、无进展生存期(progression free survival,PFS)和总生存期(overall survival,OS).结果 联合组PFS优于单药组(4.5个月vs 3.1个月,P<0.001);联合组OS也高于单药组(7.4个月vs 6.4个月,P<0.001).多因素分析显示,GEM联合尼妥珠单抗一线治疗晚期胰腺癌可延长晚期胰腺癌患者的生存期(P<0.001).两组间与治疗相关的不良事件发生率无统计学差异(P>0.05).结论 与GEM单药相比,尼妥珠单抗联合GEM一线治疗晚期胰腺癌可增加患者的生存获益,且未增加不良反应,对于晚期胰腺癌患者来说是一个可供选择的一线治疗方案.

1 病例资料 患者,女,73岁,因右半结肠切除术后5年余,肝转移复发综合治疗3年余,发现新发肝占位性病变10余天,于2019年10月就诊于解放军总医院第一医学中心. 患者于2014年3月初无明显诱因出现排便习惯改变,于当地医院行肠镜检查,提示"结肠占位".2014年4月30日至北京协和医院行经腹腔镜右半结肠切除术,术后病理诊断示:结肠中分化腺癌,部分为黏液腺癌,浸透肌层达周围脂肪组织,肠周脂肪组织中可见癌结节形成.淋巴结未见转移癌(结肠中动脉根部0/1、回结肠动脉根0/7、肠系膜上静脉周围0/4、结肠周围0/19).

Objective This study aims to assess the efficacy and safety of penpulimab (a humanized anti-PD-1 IgG1 antibody) with anlotinib in the first-line treatment of Chinese patients with uHCC. Methods In this open-label multicenter phase Ib/II trial, patients with histologically or cytologically confirmed uHCC, without previous systemic treatment, aged 18–75 years old, classified as BCLC stage B (not amenable for locoregional therapy) or C, with Child–Pugh score ≤7 and ECOG performance status ≤1 were enrolled. Patients received penpulimab [200 mg intravenous (i.v.) Q3W] and oral anlotinib (8 mg/day, 2 weeks on/1 week off). The primary endpoint was objective response rate (ORR). Secondary endpoints included safety, disease control rate (DCR), progression-free survival (PFS), time to progression (TTP), duration of response (DoR), and overall survival (OS). This trial is registered with ClinicalTrials.gov (NCT04172571). Results At the data cutoff (December 30, 2020), 31 eligible patients had been enrolled and treated with a median follow-up of 14.7 months (range, 1.4–22.1). The ORR was 31.0% (95% CI, 15.3–50.8%), and the DCR was 82.8% (95% CI, 64.2–94.2%). The median PFS and TTP for 31 patients were 8.8 months (95% CI, 4.0–12.3) and 8.8 months (95% CI, 4.0–12.9) respectively. The median OS was not reached; the 12-month OS rate was 69.0% (95% CI, 48.9–82.5%). Only 19.4% (6/31) of patients had grade 3/4 treatment-related adverse events (TRAEs). Conclusion Penpulimab plus anlotinib showed promising anti-tumor activity and a favorable safety profile as first-line treatment of patients with uHCC.

Dimethyl fumarate (DMF) is an approved drug used in the treatment of multiple sclerosis (MS) and psoriasis therapy. Multiple studies have demonstrated other pharmacological activities of DMF such as an anti-cancer agent. In particular, studies have shown that DMF can modulate the NRF2/HO1/NQO1 antioxidant signal pathway and inactivate NF-κB to suppress the growth of colon and breast cancer cells, and induce cell death. In this study, we aimed to evaluate the anti-tumor activities of DMF in pancreatic cancer (PC) focusing on cell death as the predominant mechanism of response. We showed that both mitochondrial respiration and aerobic glycolysis were severely depressed following treatment with DMF and the effects could be abrogated by treatment with L-cysteine and N-acetyl-L-cysteine (NAC). Importantly, we verified that DMF induced metabolic crisis and that cell death was not related to alterations in ROS. Our data implied that MTHFD1 could be a potential downstream target of DMF identified by molecular docking analysis. Finally, we confirmed that MTHFD1 is up-regulated in PC and overexpression of MTHFD1 was negatively related to outcomes of PC patients. Our data indicate that DMF induces metabolic crisie to suppress cell growth and could be a potential novel therapy in the treatment of PC.

We aim to evaluate the tumor metabolic suppressive activity of Oridonin (extract of Rabdosia rubescens) in glioma and elucidate its potential mechanism. Effects of Oridonin on U251/U87 cells were determined by CCK8, RTCA, colony formation, flow cytometry, wound healing, and Transwell assay. Xenograft tumor model to evaluate the effect of Oridonin on glioma cells in vivo. Cellular bioenergetics were measured by Seahorse. RNA-seq was performed to screen potential biological pathways in Oridonin treated cells. Bioinformatics analysis of PCK2 in glioma was performed based on TCGA/CGGA. Endogenous PCK2 was knocked-down by lentivirus packaged shRNA. We found Oridonin significantly inhibited cell growth in U251/U87 in vitro and in vivo. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were decreased in Oridonin-treated U251/U87 cells. Oridonin treatment led to PCK2 down-regulation. Additionally, PCK2 was up-regulated in higher grade glioma and correlated with poor outcomes. Furthermore, PCK2 depletion significantly inhibited cell growth and decreased OCR/ECAR in U251/U87 which coincided with the effects of Oridonin. Therefore, we evaluated the potent anti-tumor property of Oridonin in glioma. Importantly, we demonstrated that PCK2 might be a novel target of Oridonin on glioma by inducing energy crisis and increasing oxidative stress.

The occurrence and acuteness of liver cirrhosis were strongly associated with the hepatocarcinogenesis and the prognosis of hepatocellular carcinoma (HCC). This study compared the prognostic significance of non-invasive fibrosis panel containing 15 indices in hepatitis-B-associated HCC patients’ post-curative resection. Four hundred and five consecutive hepatitis-B-related HCC patients who went through curative hepatectomy were investigated retrospectively. The multivariate Cox proportional hazard model was used to evaluate independent prognostic factors for overall survival (OS). The accuracy in diagnosis of each non-invasive fibrosis index in cirrhosis detection was determined by the area under receiver operating characteristic (AUC) curve. Preoperative AST to platelet ratio index (APRI), Goteburg University Cirrhosis Index (GUCI), and King Score all exhibited a superior performance in diagnosis of cirrhosis detection with AUC > 0.7. APRI and Fibro-α Score were the risk factors that behaved independently in predicting the OS of HCC patients, with an hazard ratio (HR) value of 1.550 (P = 0.012) and 1.420 (P = 0.033), respectively. Preoperative APRI was a relatively accurate predictor of cirrhotic status and prognosis in HCC due to hepatitis-B among the 15 non-invasive fibrosis indices. Impact statement Non-invasive fibrosis indices, according to regular laboratory and clinical data, could be useful in assessing liver fibrosis in chronic hepatitis patients. However, the role of these biomarkers remains unclear in predicting the outcome of HBV-associated HCC in patients. This study was carried out retrospectively and included a relatively large sample size (n = 405) with a heterogeneous population of HBV infected patients and longer duration of prospective follow-up. Our study suggested that APRI and Fibro-α Scores are inversely correlated with overall survival in HBV-associated HCC patients. Meanwhile, GUCI, King Score, and APRI were highly correlated with cirrhosis status. Also, in subgroups of cirrhosis or non-cirrhosis, Fibro-α Scores could differentiate patients with good prognosis from those with poor outcome. This result would aid clinicians in acquiring preventive and therapeutic methods in patients with high risk.

目的 观察安罗替尼联合PD-1单抗(AK105)治疗晚期转移性肝细胞癌的疗效和不良反应.方法 选取2019年1-8月在我科使用安罗替尼联合PD-1单抗治疗的13例晚期原发性肝癌患者的临床资料,观察疗效及不良反应.随访时间截至2019年9月27日,结果安罗替尼联合PD-1单抗(AK105)治疗晚期转移性肝癌主要不良反应为手足综合征、皮肤反应及高血压等,未出现3～4级不良反应.13例患者中,3例达到了部分缓解,6例获得了疾病稳定,客观缓解率为23.1％,疾病控制率为69.2％.结论 我们的初步研究显示安罗替尼联合PD-1单抗治疗晚期转移性肝癌不良反应可控,具有较好的疗效.