Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and limited first-line treatments. This phase Ib/II randomized trial (NCT05218889) investigated the efficacy and safety of surufatinib plus camrelizumab and nab-paclitaxel/S-1 (NASCA) versus nab-paclitaxel and gemcitabine in patients with locally advanced or metastatic PDAC. The primary endpoints were dose-limiting toxicities and the recommended phase II dose (RP2D) of surufatinib in phase Ib, and the objective response rate (ORR) in phase II. Phase Ib used a 3 + 3 dose-escalation design to determine the RP2D of surufatinib in six patients, which was established at 200 mg. In phase II, patients were randomized 1:1 to receive the NASCA (45 patients) or nab-paclitaxel and gemcitabine (45 patients). NASCA group showed an ORR of 51.1% (23/45) versus 24.4% (11/45) in the nab-paclitaxel and gemcitabine group (odds ratio 3.2, 95% CI 1.3–8.2, p = 0.01). The median progression-free survival (PFS) was 7.9 vs. 5.3 months (HR 0.63, 95% CI 0.40–0.99, p = 0.045). The median overall survival was 13.0 vs. 11.0 months (HR 0.77, 95% CI 0.47–1.28, p = 0.318). The most common Grade ≥3 treatment-related adverse event was decreased neutrophil count (33.3% vs. 35.6%). In the NASCA group, enrichment of CD8+ and CD8+PD-1+ cells, a high baseline M1/M2 macrophage ratio, and a reduction in CA19-9 levels at weeks 6 and 12 were associated with improved PFS compared to patients without these features. The NASCA regimen showed promising efficacy with tolerable safety relative to nab-paclitaxel and gemcitabine for locally advanced or metastatic PDAC.

e15541 Background: Bevacizumab plus FOLFIRI therapy is currently the standard second-line treatment for RAS-mutant metastatic colorectal cancer (mCRC); however, its efficacy is limited. To improve outcomes in this subgroup, we investigated the efficacy and safety of fruquintinib in combination with FOLFIRI as a second-line treatment for RAS-mutant mCRC. Methods: This prospective, single-center phase 2 study enrolled patients with RAS-mutant mCRC who had progressed on or were intolerant to first-line treatment. In a 2-week cycle, fruquintinib was administered orally at a daily dose of 3 mg. Irinotecan was administered intravenously at a dose of 180 mg/m² on day 1, leucovorin (LV) was administered intravenously at a dose of 180 mg/m² on day 1, and fluorouracil was administered as an intravenous bolus at 400 mg/m² followed by a continuous infusion of 2400 mg/m² over 46 hours. Tumor assessments were performed every three cycles according to RECIST version 1.1. The primary endpoint was overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response (DoR), and safety. Results: From August 31, 2022, to January 10, 2025, a total of 24 patients were enrolled, including 14 (58%) males with a median age of 59 years (range: 33-79 years), and 17 (71%) patients had an ECOG performance status (PS) of 1. The primary lesion was located in the rectum in 7 (29%) patients, the left-side colon in 11 (46%) patients, and the right-side colon in 6 (25%) patients. The most common metastatic site was liver (83%). For the primary endpoint, 21 patients underwent at least one efficacy assessment. The ORR was 14.3% (3/21), and the disease control rate (DCR) was 90.5% (19/21). With a median follow-up time of 5.1 months (95% CI: 1.6-8.6), the median PFS was 5.0 months (95% CI: 2.9-7.1). OS data were immature. The most common adverse events included leukopenia (67%), neutrophil count decrease (58%), and anemia (54%). The most common grade 3-4 adverse events were neutrophil count decrease (21%), leukopenia (17%), and thrombocytopenia (17%). Gastrointestinal disorders (grade 1-2) occurred in 58% of patients, including nausea, anorexia, and vomiting. Diarrhea occurred in 25% of patients, with 4% being grade 3. Conclusions: The study is ongoing. These preliminary results demonstrate that fruquintinib in combination with FOLFIRI has promising efficacy as a second-line treatment for RAS-mutant metastatic colorectal cancer, with moderate toxicity. Clinical trial information: NCT05522738 .

Background: The lung immune prognostic index (LIPI) has attracted considerable interest for its prognostic value in several malignancies. However, its prognostic value in pancreatic ductal adenocarcinoma (PDAC) has not yet been clarified. Objective: This study aimed to assess the role of LIPI with regard to overall survival (OS) in locally advanced or metastatic PDAC patients undergoing chemotherapy. Methods: Data from 256 patients with PDAC treated via chemotherapy at the Chinese PLA General Hospital between January 1, 2011 and July 1, 2018 were retrospectively reviewed. Their neutrophil-to-lymphocyte ratio (dNLR) with lactate dehydrogenase (LDH) values were used to calculate each one's LIPI. The Cox proportional hazard model was used to identify the association between LIPI and OS. Results: Of the included patients, 154 were in the good LIPI group and 102 were in the intermediate/poor LIPI group. The OS in the two groups were 9.0 months (95% CI: 7.351-10.649) and 6.0 months (95% CI: 4.812-7.188), respectively. Patients in the good LIPI group had better OS compared to those in the intermediate/poor LIPI group (HR, 0.720; 95% CI: 0.554-0.935; P = 0.014). Conclusion: This study revealed LIPI is significantly associated with OS in PDAC and could play a significant role in helping clinicians make appropriate decisions for PDAC patients undergoing chemotherapy.

4161 Background: PDAC is a highly aggressive cancer with limited treatment options. Previous reports of NCT05218889 showed promising efficacy of nab-Paclitaxel/S-1/Surufatinib/Camrelizumab (anti-PD-1 antibody) combination regimen (NASCA) in mPDAC (2023 ASCO abs# 4142; 2024 ASCO GI abs# 671). Here, we present the updated results. Methods: In phase Ib, a 3+3 dose escalation design was used to determine the RP2D of surufatinib. In phase II, patients were randomized 1:1 to receive the NASCA regimen or nab-paclitaxel plus gemcitabine (AG). The NASCA regimen was administered in 3-week cycles for up to 8 cycles. Patients without disease progression continued treatment with surufatinib, S-1, and camrelizumab, while the control group received AG regimen , q3w. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, or death. The primary endpoints were DLTs and the RP2D of surufatinib in phase Ib, and the ORR in phase II. Results: As of Dec 16, 2024, 96 patients were enrolled in the study (6 in phase Ib, 90 in Phase II). In phase Ib, the RP2D for surufatinib was determined to be 200 mg (1 DLT out of 6 patients). In phase II, 45 patients were assigned to each group. Baseline characteristics were balanced between the groups. Most patients had metastatic disease (82.2% in NASCA vs 77.8% in AG). The NASCA group showed a confirmed ORR of 51.1% (23/45) versus 24.4% (11/45) in the AG group (OR: 3.2, 95% CI 1.3-8.2; p = 0.01). The median PFS were 7.9 and 5.4 months (HR: 0.63, 95% CI 0.40-0.99, p = 0.046), with 12-month OS rates of 55.5% (95% CI 39.4-68.9) in NASCA group and 52.7% (95% CI 36.6-66.5) in AG group. In the subgroup analysis of PFS, the NASCA group showed longer PFS in male patients (HR: 0.56, 95% CI 0.31-1.01), those with metastatic disease (HR: 0.57, 95% CI 0.35-0.94), and patients without liver metastasis (HR: 0.45, 95% CI 0.23-0.90). Furthermore, multiplex immunohistochemistry was performed on baseline tissue samples of 26 NASCA patients. The ratio of M1/M2 macrophage percentages was significantly higher in patients with PR than those with SD and PD (p = 0.04). Using the median as a cutoff, patients with higher levels of M1/M2 cells (p = 0.039), CD8 + cells (p = 0.0024), and CD8 + PD-1 + cells (p = 0.0064) in the stroma had longer PFS than those with lower levels. For Grade 3 and 4 TEAEs, the most frequently observed events in the NASCA group were decreased white blood cell count (31.1%), decreased neutrophil count (33.3%), and decreased lymphocyte count (20.0%). Similarly, these events were common in the AG group (26.7%, 28.9%, 8.9%, respectively). Conclusions: The NASCA regimen demonstrated promising efficacy with a manageable safety profile, showing a significantly higher ORR and longer PFS compared to AG group in patients with locally advanced or metastatic PDAC. Further studies are warranted to confirm these findings. Clinical trial information: NCT05218889 .

Background Despite some therapeutic advances, improvement in survival rates of unresectable and/or metastatic pancreatic ductal adenocarcinoma (PDAC) has been minimal over recent decade. We aimed to evaluate the impact of different treatment sequences on clinical outcomes of advanced PDAC at our academic institution. Methods In this single institution retrospective analysis, we assessed characteristics and survival rates of unresectable and/or metastatic pancreatic PDAC patients who started a systemic treatment between 01/2015 and 12/2021. Survival analyses were performed by Kaplan-Meier and Cox proportional hazards model. Results The number of 285 patients received at least two lines of treatment, but only 137 patients were suitable for third-line treatment. Subgroup analysis showed that thirty-seven patients received A line (gemcitabine/nab-paclitaxel or nab-paclitaxel combined therapy to FOLFIRINOX) therapy, 37 patients received B line (nab-paclitaxel combined therapy to gemcitabine combined therapy to FOLFIRINOX) therapy, 21 patients received C line (nab-paclitaxel combined therapy to gemcitabine combined therapy to oxaliplatin or irinotecan combined therapy) therapy. Survival rates for different treatment lines were significantly different and median overall survival (OS) was 14.00, 18.00, and 14.00 months, respectively (p<0.05). Conclusion Our study provides real-world evidence for the effectiveness of different treatment sequences and underscores the treatment sequences on survival outcome when considering the entire management in advanced PDAC.

Background: In the second -line treatment of advanced pancreatic cancer (APC), there is only one approved regimen based on the phase III NAPOLI-1 trial. However, for patients progressing after Nabpaclitaxel and Gemcitabine (Nab-P/Gem) or Nab -P combinations, second -line treatment were very limited. Methods: This is a retrospective single -center analysis of patients. Our aim was to determine the effectiveness and tolerability of a novel regimen, gemcitabine plus Anlotinib and anti-PD1, in APC patients and to compare it with oxaliplatin, irinotecan, leucovorin, and fluorouracil (FOLFIRINOX) in the second -line setting who have failed on the first -line Nab -P combinations. Results: In total, twenty-three patients received Gemcitabine plus Anlotinib and anti-PD1 in the secondline, 28 patients were treated with FOLFORINOX. There was no significant difference in overall survival (OS) or progression free survival (PFS) for either of the two sequences (p > 0.05). Patients who received Gemcitabine plus Anlotinib and anti-PD1 had a median PFS of 4.0 months (95% CI: 1.1-6.9) versus 3.5 months (95% CI 1.8-5.2) in FOLFORINOX group (p = 0.953). The median OS of Gemcitabine plus Anlotinib and anti-PD1 was 9.0 months (95% CI: 4.0-13.7) and 8.0 months (95% CI: 5.5-10.5) in FOLFORINOX group (p = 0.373). Grade >= 3 treatment -emergent adverse events (AEs) occurred for 13% of patients with Gemcitabine plus Anlotinib and anti-PD1 and 40% for FOLFORINOX. Conclusion: Our data confirms the effectiveness of Gemcitabine plus Anlotinib and anti-PD1 as a welltolerated regimen in the second -line treatment of APC and extends available data on its use as a second -line treatment option when compared with FOLFIRINOX. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

671 Background: This prospective, randomized controlled phase 1b/2 clinical study was designed to explore the efficacy and safety of surufatinib combined with camrelizumab, nab-paclitaxel and S-1 as first-line treatment compared with nab-paclitaxel and gemcitabine (AG) in mPDAC. Preliminary data was reported (Guanghai Dai, 2023 ASCO, 4142). Here we presented the updated data as more patients (pts) were recruited. Methods: In phase 1b, pts with mPDAC received surufatinib (200mg to 300mg, qd po), camrelizumab (200mg, I.V., D1, Q3W), nab-paclitaxel (125mg/m2, I.V., D1, D8, Q3W), and S-1 (40mg bid, D1-14, Q3W). Phase 2 is a prospective, open-label, randomized (1:1) trial comparing NASCA with AG in the first-line setting. The primary objective was the RP2D and overall response rate (ORR) per RECIST v1.1. Tumor tissue samples were collected at diagnosis and were subjected to mIHC to evaluate tumor immune microenvironment. Results: From Aug 2021 to Jun 2023, 49 pts were enrolled. As previously reported, 6 pts were enrolled in phase 1b and RP2D was determined as surufatinib 200mg. Of the 49 pts, 48 were evaluable for efficacy (28 in NASCA and 20 in AG group). ORR was 53.6% (15/28) (95% CI: 35.8-70.5) in pts receiving NASCA (pts in phase 1b included) and 15.0% (3/20) (95% CI: 5.2-36.0) in AG group. In NASCA group, pts with liver metastases exhibited higher ORR than those without liver metastases (71.4% vs 35.7%, p=0.13). Median progression-free survival and overall survival was 9.17m (95% CI: 5.5-NA) and 15.57m (95% CI: 9.27-NA) in NASCA group, 6.3m (95% CI: 4.87-NA) and 8.63m (95% CI: 7.90-NA) in AG group at the median follow-up of 13.7m. The most frequent adverse events (AEs) of all-grade in NASCA were neutropenia (57.1%), hepatotoxicity (42.9%), and neuropathy (39.3%). Immune-related AEs were observed in 5 pts with grade 3 hepatotoxicity in 4 pts and grade 2 enteritis in 1 pt. Safety was comparable in two groups except for hepatotoxicity and diarrhea. Using mIHC, the tissue of 13 pts treated with NASCA were stained for multiple markers of immune cells. CD3+ T cells infiltrated the tumor core at the highest level, followed by CD68+CD163- (M1) macrophages, and FOXP3+ T cells. Majority of immune cells and ICI biomarkers were expressed at higher proportion in the stroma. Pts with liver metastases displayed elevated tumoral FOXP3+ T cells (p=0.031), PD-L1+CD68+ macrophages (p=0.014), and decreased infiltration of stromal CD8+ T cells (p=0.064) than pts without liver metastases. In pts with liver metastases, responders displayed a higher stromal PD-1+ cells than nonresponders (p=0.036). Conclusions: Updated results proved that NASCA regimen presented higher clinical activity than the standard AG treatment, especially in pts with liver metastases, with a manageable safety profile. This trial is ongoing and NASCA regimen deserves further exploration in mPDAC. Clinical trial information: NCT05218889 .

BackgroundLung immune prognostic index (LIPI), a combination of derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH), is currently attracting considerable interest as a potential prognostic indicator in many malignancies. Our study aimed to investigate the prognostic value of preoperative LIPI in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing radical resection.MethodsWe retrospectively reviewed PDAC patients treated with radical resection from February 2019 to April 2021 at Chinese People's Liberation Army (PLA) general hospital. Based on the cut-off value of dNLR and LDH identified by X-tile, patients were divided into LIPI good and LIPI intermediate/poor group. Kaplan-Meier curve and log-rank test were used to compare the recurrence-free survival (RFS) and overall survival (OS) of the two groups. Univariate and multivariate Cox regression was used to identify the independent prognostic value of LIPI. Subgroup analysis was performed to identify specific population benefited from radical resection.ResultsA total of 205 patients were included and the median RFS and OS was 10.8 and 24.3 months, respectively. Preoperative LIPI intermediate/poor was related to worse RFS and OS (p < 0.05). Preoperative LIPI intermediate/poor, vascular invasion and no adjuvant chemotherapy were indicators of poor OS. Patients with LIPI intermediate/poor had worse OS especially among females and those with adjuvant chemotherapy (p < 0.05). Adjuvant chemotherapy related to better RFS and OS in patients with LIPI good (p < 0.05).ConclusionsPreoperative LIPI intermediate/poor can be an indicator of poor prognosis in patients with PDAC undergoing radical resection. LIPI good could be an effective marker of benefit from adjuvant chemotherapy. Larger studies are warranted for further validation.

背景 患者的营养状况和全身炎症与肿瘤进展存在一定相关性,因此白蛋白和中性粒细胞联合预后分级(albuminand neutrophil combined prognostic grade,ANPG)可能对使用免疫检查点抑制剂(immune checkpoint inhibitor,ICI)的晚期胃癌(advanced gastric cancer,AGC)患者预后具有一定的评估作用.目的 探讨ANPG与使用免疫治疗后AGC患者的总体生存率(overall survival,OS)和无进展生存率(progression-free survival,PFS)的关联.方法 纳入解放军总医院第一医学中心2014年12月-2018年11月初次接受ICI治疗的Ⅲ～Ⅳ期胃癌(gastric cancer,GC)患者共123例.低水平人血白蛋白(<35 g/L)和高水平中性粒细胞绝对值(≥4.26 g/L)被认为是ANPG的两个危险因素.根据这两个危险因素,将患者分为两组,不含有危险因素为高ANPG评分组,含有一个危险因素或者两个危险因素的为中/低ANPG评分组,同时评估两组OS和PFS的差异.结果 AGC患者,中位年龄58岁,女性31例,男性92例.中/低ANPG评分组患者的OS(5.4个月vs 12.7个月,P<0.001)和PFS(3.3个月vs 4.6个月,P=0.009)均短于高ANPG评分组.Cox多因素回归分析显示,中/低ANPG评分组的死亡风险约是高ANPG评分组2.3倍(HR:2.302,95％CI:1.507～3.515,P<0.001).中/低ANPG评分组的疾病进展风险约是高ANPG评分组1.9倍(HR:1.885,95％CI:1.284～2.767,P=0.001).结论 本研究显示ANPG是影响接受免疫治疗的AGC患者生存的独立因素.ANPG评分高组患者使用免疫治疗后OS和PFS较中/差组延长.

背景 程序性死亡受体配体1(programmed?cell?death?1?ligand?1,PD-L1)和微卫星不稳性(microsatellite?instability,MSI)的表达被认为能够有效评估晚期胃癌(advanced?gastric?cancer,AGC)患者免疫治疗预后.但目前仍没有公认且有效的生物标志物可以识别AGC免疫治疗的受益人群.目的 探讨衍生中性粒细胞与淋巴细胞比率(derived?neutrophil-to-lymphocyte?ratio,dNLR)与AGC免疫治疗预后的关系.方法 纳入2014年12月-?2018年11月解放军总医院肿瘤中心学部接受免疫治疗的123例AGC患者.根据国外大型临床研究选取dNLR=3为临界值,分析不同dNLR水平组AGC患者免疫治疗后的中位总生存(overall?survival,OS)和中位无进展生存(progression-free?survival,PFS).采用Kaplan-Meier和Cox比例风险回归模型进行生存分析.结果 AGC患者中位年龄58岁,女性31例,男性92例.中位OS为9.4个月,中位PFS为3.8个月.dNLR高水平组中位PFS为4.6个月,dNLR低水平组为2.6个月(HR:1.952,95％?CI:1.248?～?3.053,P=0.008).dNLR高水平组OS为11.2个月,dNLR低水平组为4.8个月(HR:0.59,95％?CI:1.691?～?4.188,P<0.001).dNLR高、低水平组的客观缓解率(25.0％?vs?24.2％,P=0.932)、疾病控制率(46.4％vs?48.4％,P=0.853)差异无统计学意义.结论 治疗前dNLR水平是独立预测AGC患者免疫治疗后PFS和OS的生物标志物.基线dNLR低水平组患者或许可以从免疫治疗中获益.

Background The highly heterogeneous characteristics of GC may limit the accuracy of a single biomarker for screening populations benefiting from immunotherapy. However, the combination of multiple indicators can provide more directed information for the detection of potential immune benefit subgroups. At present, there are no recognized complex indexes to identify advanced GC (AGC) in patients who likely benefited from immunotherapy. The objective of this research is to explore whether the composite biomarker of derived neutrophil–lymphocyte ratio (dNLR) and platelet–lymphocyte ratio (PLR) can be used as a reliable prognostic factor for the survival of AGC patients receiving immunotherapy. Methods From December 2014 to May 2021, a total 238 AGC patients at a single Center were included in this retrospective cohort research study. The cutoff value of dNLR was obtained by the ROC curves to predict the disease progression rate at the 8th month and the cutoff value of PLR was estimated by the median value. The cutoff values of dNLR and PLR were 1.95 and 163.63, respectively. The high levels of dNLR (≥1.95) and PLR (≥163.63) were considered to be risk factors. Based on these two risk factors, patients were categorized into 3 groups: the risk factor number for the “good” group was 0, that for the “intermediate” group was 1, and that for the “poor” group was 2. The subjects were divided into two groups: dNLR/PLR-good and dNLR/PLR-intermediate/poor. Results Of the 238 patients, the median overall survival (mOS) and progression-free survival (mPFS) were 12.5 and 4.7 months, respectively. Multivariate analysis revealed that the good dNLR/PLR group was independently associated with better prognosis. The intermediate/poor dNLR/PLR group was independently correlated with an over 1.4 times greater risk of disease progression (4.1 months vs. 5.5 months; p = 0.016) and an over 1.54 times greater risk of death (11.1 months vs. 26.3 months; p = 0.033) than the good dNLR/PLR group. However, no clear differences in the disease control rate (DCR) and overall response rate (ORR) were observed between the intermediate/poor dNLR/PLR group and the good dNLR/PLR group (51.5% vs. 56.3%, 26.3% vs. 29.6%; p = 0.494, p = 0.609). Conclusion Our study firstly verifies that the composite biomarker of dNLR and PLR is an independent prognostic factor affecting survival of advanced AGC patients receiving immunotherapy. It may be difficult for patients with the intermediate/poor dNLR/PLR group to benefit from immunotherapy.

Background:The application of immunotherapy is gradually increasing in advanced bile tract carcinoma (BTC), but only some patients could benefit from it. Validated biomarkers can screen out the beneficiaries. Therefore, the objective of this research is aimed at exploring the predictive value of lung immune prognostic index (LIPI) in advanced BTC patients receiving immunotherapy.Methods:This study was conducted on 110 BTC patients. The cut-off value of the derived neutrophil-to-lymphocyte (dNLR) ratio was obtained by the ROC curves to predict the tumor progression rate at the 6th month. The high levels of dNLR (≥the cut-off value) and lactate dehydrogenase (≥the upper limit of normal) were considered to be two risk factors for LIPI. Based on these two risk factors, patients were categorized into 3 groups based on risk factors: 0 for the good group, 1 for the intermediate group, and 2 for the poor group. Due to the limited number of patients in the poor group, it was integrated into the intermediate group to be the intermediate/poor group. Finally, the subjects were divided into two groups: LIPI-good and LIPI-intermediate/poor.Results:The results shed light on the 110 BTC patients' LIPI in advanced BTC patients receiving immunotherapy, indicating that the cut-off value of dNLR was 1.74. According to the risk stratification, 38 (34.5%) patients had a good LIPI score, whereas the LIPI score was intermediate/poor in 72 (65.5%). In addition, patients with good LIPI were related to longer progression-free survival (PFS) and overall survival (OS), compared to those with intermediate/poor LIPI (12.17 months vs. 3.17 months; 20.2 months vs. 8.7 months). According to multivariate analysis, the intermediate/poor LIPI group was independently correlated with over 2.3 times greater risk of tumor progression (HR = 2.301; 95% CI, 1.395-3.796; P = 0.001) and over 1.8 times greater risk of death (HR = 1.877; 95% CI, 1.076-3.275; P = 0.027) than the good group. Moreover, the result also revealed that there were significant differences of DCR for patients of the good group and the intermediate/poor group (86.8% vs. 65.3%; P = 0.012).Conclusion:Finally, this study verifies, for the first time, that LIPI is an independent factor affecting the survival and clinical efficacy of advanced BTC patients receiving immunotherapy. It may be difficult for patients with intermediate/poor LIPI to benefit from immunotherapy.

Objective:To study the combined use of neoadjuvant chemotherapy and immunotherapy in patients with borderline resectable pancreatic cancer.Methods:The clinical data of patients with pancreatic cancer who were planned to undergo perioperative treatment before surgical treatment at the Fifth Medical Center of PLA General Hospital from January 2019 to June 2021 were retrospectively studied. Of 22 patients with pancreatic cancer, there were 10 males and 12 females, aged (56.0±10.2) years old. Preoperative treatment with chemotherapy (nab-paclitaxel and S-1, AS) and immunotherapy regimen before surgery were given. The baseline characteristics, treatment efficacy, surgical pathology and prognosis were analyzed.Results:Of 22 patients who were treated with neoadjuvant chemotherapy combined with programmed death-1 (PD-1) monoclonal antibody, 11 patients (50%) had tumors in the head, neck and uncinated process of pancreas. On radiographic assessment, one patient achieved CR (4.5%, 1/22), 9 patients PR (40.9%, 9/22), and 11 patients SD (50.0%, 11/22). All patients subsequently underwent R 0 resection. The postoperative pTNM staging showed 91% (20/22) of patients were in stage IA-IIB, 31.8% (7/22) of patients had pT2, 63.6% (14/22) had N0, and 1 patient had pCR. Thirteen patients (54.2%, 13/22) received postoperative adjuvant therapy. The median recurrence-free survival (RFS) was 6.4 months and the median time to progression (TTP) was 12.8 months. The median overall survival of patients was not reached. Postoperative pathology TNM staging IIA to III ( HR=3.63, 95% CI: 1.18-11.20, P=0.025) and postoperative pathology T2-3 stage ( HR=2.02, 95% CI: 1.01-5.05, P=0.049) were significantly associated with RFS. Postoperative pathology TNM stages IIA to III ( HR=2.39, 95% CI: 1.04-5.50, P=0.041) and postoperative pathology T2-3 stage ( HR=2.53, 95% CI: 1.26-5.09, P=0.009) were significantly associated with TTP. Conclusion:AS combined with PD-1 monoclonal antibody showed good efficacy as a neoadjuvant therapy for patients with borderline-resectable pancreatic cancer.

Purpose Pancreatic cancer is an aggressive solid tumor with a severe prognosis. Although tumor biomarkers are often used to identify advanced pancreatic cancer, this is not accurate, and the currently used biomarkers are not indicative of prognosis. The present study evaluated circulating tumor DNA (ctDNA) as a biomarker for prognosis prediction and disease monitoring in metastatic pancreatic adenocarcinoma (PAC). Methods From 2017 to 2018, 40 patients with metastatic PAC were enrolled, and tumor tissue and blood samples were collected from 40 and 35 patients, respectively. CtDNA was sequenced by next-generation sequencing (NGS) with a 425-gene capture panel. The association of clinical characteristics, laboratory indicators, and dynamic ctDNA with patient outcomes was analyzed. Results Mutations in KRAS (87.5%, N = 35) and TP53 (77.5%, N = 31) were most common in 40 tumor tissue. Patients’ ECOG score, CA19-9, CEA, neutrophil-lymphocyte ratio (NLR), platelet- lymphocyte ratio (PLR) levels and mutations in ≥ 3 driver genes were strongly correlated with patients’ overall survival (OS). Patients’ gender, ECOG score, CA19-9, and CEA levels were associated with progression-free survival (PFS) (P<0.05). In 35 blood samples, univariate analysis showed a significant association between ECOG score, CA19-9, KRAS or CDKN2A mutation in ctDNA and OS and between CA19-9, CDKN2A or SMAD4 mutation in ctDNA and PFS. Cox hazard proportion model showed that patients’ CDKN2A mutation in ctDNA (HR=16.1, 95% CI=4.4-59.1, P<0.001), ECOG score (HR=6.2, 95% CI=2.4-15.7, P<0.001) and tumor location (HR=0.4, 95% CI=0.1-0.9, P=0.027) were significantly associated with OS. Patients’ CDKN2A mutation in ctDNA (HR=6.8, 95% CI=2.3-19.9, P=0.001), SMAD4 mutation in ctDNA (HR=3.0, 95% CI=1.1-7.9, P=0.031) and metastatic organ (HR=0.4, 95% CI=0.2-1.0, P=0.046) were significantly associated with PFS. Longitudinal changes in gene mutation allelic frequency (MAF) value were evaluated in 24 patients. Detection of progression disease (PD) by ctDNA was 0.9 months earlier than by radiological imaging (mean PFS: 4.6m vs 5.5m, P=0.004, paired t-test). Conclusions The ctDNA has the potential as a specific survival predictive marker for metastatic PAC patients. Longitudinal ctDNA tracking could potentially help identify disease progression and be a valuable complement for routine clinical markers and imaging.

背景 免疫检查点抑制剂(immune checkpoint inhibitor,ICIs)在晚期胆道系统恶性肿瘤(bile tract carcinoma, BTC)患者中的应用逐渐增多,但仅有部分患者获益,且存在免疫相关不良反应等风险,寻找有效的免疫疗效相关预测指标可更早地筛选出获益人群.目的 探讨中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)与晚期胆道恶性肿瘤免疫治疗疗效及预后的关系.方法 纳入2015年9月- 2021年4月于解放军总医院第一医学中心和第五医学中心初次接受ICIs治疗的晚期BTC患者106例.通过基线NLR预测疾病控制状态的ROC曲线以获取NLR最佳Cut-off值,根据是否大于NLR最佳Cut-off值将患者分为NLR高水平组和NLR低水平组.采用Kaplan-Meier进行单因素分析,Cox回归进行多因素分析.结果 BTC患者,中位年龄59岁,女性44例,男性62例.NLR的最佳Cut-off值为2.54.与NLR低水平组比较,NLR高水平组有更高概率出现疾病进展(OR=4.365,95％ CI:1.849 ～ 10.302,P=0.001).NLR高水平组和NLR低水平组的中位总生存(overall survival,OS)率分别为33.9个月和8.7个月,中位无进展生存(progression-free survival,PFS)率分别为10.7个月和4.6个月,差异均有统计学意义(P均<0.05).多因素分析结果显示NLR是OS和PFS的有效预测指标.结论 基线NLR为晚期BTC免疫治疗预后的独立影响因素.基线NLR高水平患者可能较难从免疫治疗中获益.

Abstract Background:CA199, CEA and CA125 were the most widely used tumor markers in pancreatic cancer. However, the studies associated with the relationship between the three markers and pancreatic cancer were limited. This study aimed to explore the correlation between baseline serum CA199, CEA, CA125 levels and clinical characteristics in pancreatic cancer. Methods:278 patients with advanced pancreatic cancer received first-line chemotherapy treatments enrolled in this research. Correlated analysis between tumor markers and disease characteristics was performed by Pearson’s Chi-squared test or Fisher exact test. We used Pearson’s correlation test to investigate the relationship between tumor markers and peripheral blood parameters. Univariate analysis was estimated by Kaplan-Meier method and compared using the log-rank test. Multivariate analysis and HR calculation was determined by the Cox regression model. Results: Baseline CA199, CEA, and CA125 both positively associated with the primary tumor site (p=0.007; p=0.012; p=0.003, respectively);liver metastasis (p=0.001; p=0.001; p=0.028, respectively); number of organ metastasis (p=0.001; p=0.008;p=0.042, respectively); baseline WBC levels (p<0.001; p<0.001; p<0.001, respectively), LDH levels (p<0.001; p=0.004; p<0.001, respectively). And CA199 also correlated with years of smoking(p=0.024); diabetes and year of diabetes (p=0.012; p=0.012); baseline glycemic levels (p=0.004). CA199 and CA125 levels had the relationship with baseline neutrophil counts (p<0.001; p<0.001, respectively). Years of smoking, baseline neutrophil counts, LDH levels, CA199 levels and CA125 levels were independent prognostic factors. Conclusion: Combinations of the four factors were also correlated with survival. It’s concluded that CA199, CEA, CA125 correlated with multi-factors of clinical factors. And combinations of baseline neutrophil counts, LDH levels, CA199 levels and CA125 levels were also prognostic factor.

Purpose: In pancreatic cancer (PC), CA 19-9, CEA and CA 125 are the most widely used tumor markers. The aim of this study was to explore the prognostic significance of baseline levels of serum CA 19-9, CEA, and CA 125, and to evaluate the clinical significance of these markers in PC patients. Patients and Methods: A total of 278 patients with advanced PC that had received first-line chemotherapy treatments were examined. Correlation analysis between the tumor markers and clinical characteristics was performed using a Pearson's Chi-squared test or Fisher's exact test. A Pearson's correlation test was utilized to investigate the relationship between tumor markers and peripheral blood parameters. Univariate analysis was estimated using a Kaplan Meier analysis and compared using a Log rank test. Multivariate analysis was performed using a Cox proportional hazards regression model. Results: Both individually and collectively, the baseline CA 19-9, CEA and CA 125 levels were positively associated with the primary tumor site (p < 0.01), liver metastasis (p < 0.05), and number of organ metastases (p < 0.05). Furthermore, CA 19-9, CEA and CA 125 were correlated to baseline WBC (p < 0.001) and LDH (p < 0.01) levels. Additionally, CA 19-9 was correlated with years of smoking (p = 0.024); diabetes and years of diabetes (p = 0.012); baseline glycemic levels (p = 0.004); and neutrophil counts (p < 0.001). Moreover, CA 125 levels were associated with the baseline neutrophil counts (p < 0.001) and peritoneal metastasis (p = 0.008). When examining neutrophil, LDH, CA 19-9 and CA 125 levels were found to be associated with overall survival (OS) and shown to be independent prognostic factors. Conclusion: CA 19-9, CEA and CA 125 are correlated with multiple clinical factors. Baseline neutrophil, LDH, CA 19-9 and CA 125 levels are associated with OS and may potentially serve as prognostic factors.

BACKGROUND Pancreatic cancer (PC) is a common digestive system tumor. For patients with advanced pancreatic cancer (APC), chemotherapy is still the predominant treatment. However, no large-scale clinical studies have been done of it as first-line therapy for APC. The goal of the present study was to assess real-world outcomes with chemotherapy in that setting. MATERIAL AND METHODS We retrospectively analyzed data from 322 patients with APC who were treated with chemotherapy at 4 hospitals in different cities in China. The first-line regimens used were AS (nab-paclitaxel and S-1), AG (nab-paclitaxel and gemcitabine), and FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin). RESULTS Of the patients, 232 received AS, 79 received AG, and 11 received FOLFIRINOX. The median number of chemotherapy cycles was 5. The median overall survival (mOS) was 9 months and the median progression-free survival (mPFS) was 5 months. The AS, AG, and FOLFIRINOX regimens were associated with mOS rates of 9 months, 9 months, and 10 months, respectively. The mPFS rates for the AS, AG, and FOLFIRINOX regimens were 5, 4, and 5 months, respectively. The differences between the PFS rates for the regimens were statistically significant. The overall response rate (ORR) and overall disease control rate (DCR) for chemotherapy were 38% and 81.8%, respectively. The ORRs for the AS, AG, and FOLFIRINOX regimens were 46.9%, 18.7%, and 0%, respectively. The DCRs for the AS, AG and FOLFIRINOX regimens were 87.2%, 69.3%, and 63.6%, respectively. The differences between the ORRs and DCRs for the regimens were statistically significant. The incidences of grade 3/4 adverse events (AEs) associated with the AS, AG, and FOLFIRINOX regimens were 29.9%, 25%, and 36.4%, respectively. CONCLUSIONS The AS regimen was associated with a higher ORR and DCR than the other 2 regimens, with a lower rate of AEs.

目的研究化疗2周期后CA199下降水平与晚期胰腺癌预后的关系。方法本研究纳入了解放军总医院第一医学中心2010-2018年110例晚期胰腺癌患者,男性74例,女性36例,年龄范围在30～79岁;检测基线CA199值及2周期化疗后CA199值,按照不同下降水平（化疗2周期后的CA199值较基线水平下降vs未下降、下降≥20%vs下降＜20%、下降≥40%vs下降＜40%）以及不同的化疗方案进行分组,并进行亚组生存分析。结果化疗2周期后,较基线CA199水平下降者比CA199未下降者mOS更长（10.4个月vs5.8个月,P=0.009）,mPFS也更长（4.7个月vs3.1个月,P=0.002）。CA199下降≥20%者较下降＜20%者mOS（11.0个月vs 5.9个月,P=0.004）、mPFS更长（5.0个月vs 3.1个月,P=0.001）。CA199下降≥40%者较下降＜40%者的mOS（11.1个月vs 6.6个月,P=0.014）、mPFS（4.8个月vs3.5个月,P=0.042）更长。在不同化疗方案中,吉西他滨联合白蛋白紫杉醇及吉西他滨联合替吉奥疗效较其他方案效果更好。同时,在每种化疗方案中,CA199下降比例越大,预后越好。结论化疗2周期后CA199的下降水平可以作为化疗疗效的评估指标。