Various first-line gemcitabine-based or fluorouracil-based combination regimens were approved in patients with advanced pancreatic cancer. Recent randomized clinical trials (RCTs) have investigated chemotherapy backbones in combination with novel investigational drugs, including chemotherapy agents or targeted drugs. However, the comparative efficacy of these different combination therapies remains limited. This systematic review and network meta-analysis aimed to assess the efficacy of first-line combination therapies for advanced pancreatic cancer. The study included 46 RCTs with 10,499 patients and 47 distinct regimens, using data sources from MEDLINE, EMBASE, Cochrane Clinical Trials, and ClinicalTrials.gov from January 1, 2010 to April 23, 2024. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included overall response rate (ORR) and disease control rate (DCR). The analysis revealed that gemcitabine+nab-paclitaxel (GA), GA with platinum and fluorouracil (GA+Plat+FU), gemcitabine with fluorouracil (G+FU), G+Plt+FU, and FOLFIRINOX were associated with superior OS and PFS compared to gemcitabine monotherapy. Triplet or quadruplet polychemotherapy combinations, such as GA+Plat+FU, G+Plt+FU, and FOLFIRINOX, demonstrated better OS benefit with hazard ratios of 0.42 (95% CI, 0.26-0.68), 0.41 (95% CI, 0.24-0.71), and 0.58 (95% CI, 0.48-0.71), respectively, compared to doublet regimens like GA and G+FU, which had hazard ratios of 0.70 (95% CI, 0.59-0.82) and 0.82 (95% CI, 0.72-0.95), respectively. Notably, no targeted drugs, monoclonal antibodies, or other medications showed improved survival when added to chemotherapy backbones. These findings support the use of gemcitabine-based or fluorouracil-based triplet or quadruplet regimens for better survival outcomes in patients with advanced pancreatic cancer. Further research is warranted to explore the potential benefits of adding chemotherapy agents, such as fluorouracil, to the GA doublet regimen.

Immunotherapy, led by programmed cell death protein-1 (PD-1) inhibitors, has emerged as a prominent antitumor therapy, yet prognostic challenges persist in pancreatic cancer (PC). This retrospective, single-center study evaluated prognostic factors in advanced PC patients treated with PD-1 inhibitors at the PLA General Hospital\'s Oncology Department from 2015-2022. With ethics approval by the Ethics Committee of the General Hospital of the People\'s Liberation Army (S2021-228-03), we analyzed 126 patients using Kaplan-Meier and Cox models. p < .05 was considered a statistically significant difference. Median overall survival (mOS) and progression-free survival (mPFS) were 12.1 and 4.6 months, respectively. Significant mOS predictors were surgery history (44.2 months vs. 10 months, *p = .022), absence of liver metastases (44.2 months vs. 6.4 months, *p = .034), and baseline CA19-9 ≤ 216.15 U/ml (18.5 months vs. 9.2 months, *p = .049). For mPFS, histologic differentiation (5.5 months vs. 3.2 months, *p = .022) and first-line PD-1 inhibitor use (5.1 months vs. 1.5 months, ***p = .001) were key. Subgroup analyses highlighted early progression in low histologic differentiation and earlier death without surgery. History of surgery, absence of liver metastases, baseline CA19-9 level, and histologic intermediate/high differentiation may predict PD-1 inhibitor efficacy in advanced PC, pending validation in prospective trials.

OBJECTIVE: Exocrine pancreatic insufficiency (EPI) contributes to malnutrition, marked by muscle loss during chemotherapy for advanced pancreatic cancer (aPC). Pancreatic enzyme replacement therapy (PERT) is recommended for patients with EPI; however, it\'s efficacy for attenuating muscle loss has not been demonstrated. We aimed to delineate the impact of PERT dose on muscle loss using a 7-year population-based cohort with aPC who were provided PERT at the discretion of their oncologist or dietitian according to clinical indications of EPI.
METHODS: All patients treated with chemotherapy for aPC from 2013 to 2019 in Alberta, Canada (population ∼4.3 million) were included if they had computed tomography (CT) scans both prior to and 12 ± 4 weeks after chemotherapy initiation. Change in muscle area (cm2) was measured at 3rd lumbar level on repeated CT scans. Muscle loss was defined by measurement error (loss >2.3 cm2). Clinical and pharmaceutical data were retrieved from provincial registries. For patients who were dispensed PERT -8 to +6 weeks from chemo start (PERT users), estimated dose consumed per day was calculated as: (total dose dispensed) / (days, first to last dispensation). PERT users were categorized as high dose or low dose users according to the median estimated dose consumed. Non-users were classified as No PERT. Association between PERT use and muscle loss was analyzed with multivariable logistic regression.
RESULTS: Among 210 patients, 81 (39%) were PERT users. Median estimated dose consumed per day of 75 000 USP lipase units defined the cutoff between low dose and high dose uses. There were no significant differences in baseline characteristics between high dose and low dose groups. Muscle loss was more prevalent among low dose compared to both high dose and No PERT groups (88% vs. 58% and 67%, p < 0.05). In the multivariable model predicting muscle loss, low dose PERT was independently associated with greater odds of muscle loss (OR 5.4, p = 0.004) vs. high dose, independent of tumour response, disease stage, and chemotherapy regimen.
CONCLUSIONS: In patients with clinical indications of EPI during chemotherapy for aPC, low doses of PERT were insufficient to prevent muscle loss. Patients with EPI consuming higher doses of PERT had similar odds of muscle maintenance to patients without clinical indications of EPI. Provider education for optimal PERT dosing in patients with EPI should be prioritized, and resources must be allocated to support dose titration.

BACKGROUND: Nanoliposomal irinotecan (nal-IRI) is a novel regimen for pancreatic cancer, featuring a longer half-life and an increased area under the concentration-time curve. This study aims to assess the safety and efficacy of nal-IRI as a second-line treatment for advanced pancreatic cancer.
METHODS: A systemic literature search was conducted based on articles published before September 26th, 2023 in databases, including PubMed, Cochrane Library, EMBASE and Web of Science. The fixed effects model was used to calculate the pooled mean difference for overall survival (OS) and progression-free survival (PFS), as well as the pooled odds ratio for the overall response rate (ORR) and the risk of adverse events.
RESULTS: A total of 21 studies, including 3044 patients with locally advanced unresectable or metastatic pancreatic cancers, were considered eligible. The use of nal-IRI, combined with 5-fluorouracil and leucovorin, resulted in significantly improved PFS (pooled mean difference=1.01 months, 95 % confidence interval [CI]=0.97-1.05, p<0.01) and OS (pooled mean difference=0.29 months, 95 %CI=0.18-0.39, p<0.01), as well as significantly better ORR (pooled odds ratio=2.06, 95 %CI=1.30-3.27, p=0.002) compared to other second-line regimens. Nonetheless, an increased risk of grade 3 or greater neutropenia, anemia, hypokalemia, diarrhea, and vomiting was also noted.
CONCLUSIONS: Second-line treatments based on nal-IRI exhibited significantly improved PFS, OS, and ORR compared to other available treatments in advanced pancreatic cancer. Further research is necessary to corroborate these findings and define the role of nal-IRI in both first and later lines of therapy.

Advanced pancreatic cancer is one of the prominent contributors to cancer-related mortality globally. Chemotherapy, especially gemcitabine, is generally used for the treatment of advanced pancreatic cancer. Despite the treatment, the fatality rate for advanced pancreatic cancer is alarmingly high. Thus, the dire need for better treatment alternatives has drawn focus to cancer vaccinations. The Wilms tumor gene (WT1), typically associated with Wilms tumor, is found to be excessively expressed in some cancers, such as pancreatic cancer. This characteristic feature is harvested to develop cancer vaccines against WT1. This review aims to systematically summarize the clinical trials investigating the efficacy and safety of WT1 vaccines in patients with advanced pancreatic cancer. An extensive literature search was conducted on databases Medline, Web of Science, ScienceDirect, and Google Scholar using the keywords \"Advanced pancreatic cancer,\" \"Cancer vaccines,\" \"WT1 vaccines,\" and \"Pulsed DC vaccines,\" and the results were exclusively studied to construct this review. WT1 vaccines work by introducing peptides from the WT1 protein to trigger an immune response involving cytotoxic T lymphocytes via antigen-presenting cells. Upon activation, these lymphocytes induce apoptosis in cancer cells by specifically targeting those with increased WT1 levels. WT1 vaccinations, which are usually given in addition to chemotherapy, have demonstrated clinically positive results and minimal side effects. However, there are several challenges to their widespread use, such as the immunosuppressive nature of tumors and heterogeneity in expression. Despite these limitations, the risk-benefit profile of cancer vaccines is encouraging, especially for the WT1 vaccine in the treatment of advanced pancreatic cancer. Considering the fledgling status of their development, large multicentric, variables-matched, extensive analysis across diverse demographics is considered essential.

BACKGROUND: Advanced pancreatic cancer is resistant to chemotherapeutic drugs, resulting in limited treatment efficacy and poor prognosis. Combined administration of the chemotherapeutic gemcitabine and erlotinib is considered a potential first-line treatment for advanced pancreatic cancer. However, their comparative benefits and potential risks remain unclear.
OBJECTIVE: To assess the clinical efficacy and safety of erlotinib combined with other chemotherapy regimens for the treatment of advanced pancreatic cancer.
METHODS: Literature on the clinical efficacy and safety of erlotinib combined with chemotherapy for advanced pancreatic cancer was retrieved through an online search. The retrieved literature was subjected to a methodological qualitative assessment and was analyzed using the RevMan 5.3 software. Ten randomized controlled trials involving 2444 patients with advanced pancreatic cancer were included in the meta-analysis.
RESULTS: Compared with chemotherapeutic treatment, erlotinib combined with chemotherapy significantly prolonged the progression-free survival time of pancreatic cancer patients [hazard ratio (HR) = 0.78, 95%CI: 0.66-0.92, P = 0.003]. Meanwhile, the overall survival (HR= 0.99, 95%CI: 0.72-1.37, and P = 0.95) and disease control rate (OR = 0.93, 95%CI: 0.45-0.91, P = 0.84) were not significantly favorable. In terms of safety, the erlotinib and chemotherapy combination was associated with a significantly higher risk of diarrhea (OR = 3.59, 95%CI: 1.63-7.90, P < 0.05) and rash (OR = 3.63, 95%CI: 1.64-8.01, P < 0.05) compared with single-agent chemotherapy. Moreover, the risk of vomiting (OR = 1.27, 95%CI: 0.62-2.59, P = 0.51), regurgitation/anorexia (OR = 1.61, 95%CI: 0.25-10.31, P = 0.62), and infection (OR = 0.72, 95%CI: 0.28-1.87, P = 0.50) were not significant in either group.
CONCLUSIONS: Compared with a single chemotherapeutic modality, erlotinib combined with gemcitabine can prolong progression-free survival in pancreatic cancer, but does not improve survival benefit or disease control rate, and can increase the risk of diarrhea and rash.

OBJECTIVE: Neutrophil-to-lymphocyte ratio (NLR) is a prognostic indicator for several malignancies, including pancreatic cancer. We developed a novel combined NLR score (cNLRS) based on baseline NLR and change in NLR after chemotherapy (ΔNLR), and examined its prognostic value and role in chemotherapeutic response in patients with advanced pancreatic cancer.
METHODS: This study retrospectively assessed 210 advanced pancreatic cancer patients receiving chemotherapy between 2010 and 2021. The cNLRS was developed and its association with chemotherapeutic response and prognosis was investigated.
RESULTS: The cNLRS consisted of baseline NLR ≥2.5 and ΔNLR ≥0, both of which were remained as independent poor predictors of prognosis adjusting for other traditional clinicopathological features. A high cNLRS served as an independent prognostic factor of reduced overall survival. Of note, the cNLRS was significantly associated with disease control rate and treatment duration not only in 1st line treatment but also in 2nd line treatment.
CONCLUSIONS: The cNLRS established as a useful prognostic biomarker might be associated with chemotherapeutic response and could predict survival in advanced patients with pancreatic ductal adenocarcinoma treated with chemotherapy.

Pancreatic cancer (PC) is one of the most malignant tumors in digestive system due to its highly invasive and metastatic properties. At present, conventional treatment strategies for PC show the limited clinical efficacy. Therefore, novel effective therapeutic strategies are urgently needed. Here, we report a case of complete remission of advanced PC induced by claudin18.2-targeted CAR-T cell therapy. The patient was a 72-year-old man who was diagnosed with pancreatic ductal adenocarcinoma 2 years ago, and he experienced tumor recurrence and multiple metastases after pancreaticoduodenectomy and multi-line chemotherapies, including liver, peritoneum, and cervical lymph node metastases. Then, the patient was referred to our department for further treatment of metastatic PC, and he was enrolled in a clinical trial of claudin18.2-targeted CAR-T cell therapy. After lymphodepleting chemotherapy, the patient received claudin18.2-targeted CAR-T cell infusion at a dose of 1.2 × 106 cells/kg on November 21, 2022. During CAR-T cell therapy, the patient experienced grade 2 cytokine release syndrome (CRS) and gastric mucosa injury, which were controlled by tocilizumab and conventional symptomatic and supportive treatment. The patient achieved a complete response (CR) 1 month after claudin18.2-targeted CAR-T cell therapy, and remained in clinical remission for 8 months. Unfortunately, the patient experienced claudin18.2-negative relapse in July, 2023. Despite antigen-negative relapse after claudin18.2-targeted CAR-T cell infusion, the patient achieved sustained remission for 8 months, which indicates that claudin18.2-targeted CAR-T cell therapy is an extremely effective therapeutic strategy for the treatment of advanced PC.

Patients diagnosed with pancreatic cancer who have 5-year survival rates of ~5% are typically in the advanced stage. Pancreatic cancer has become the third leading cause of cancer-related death in the United States and there is still a lack of effective treatments to improve patient survival rate. Hence, the purpose of the present retrospective study was to assess the potential clinical impact of repeated high-intensity focused ultrasound (HIFU) combined with iodine-125 (125I) interstitial brachytherapy for the treatment of patients with advanced pancreatic cancer who were ineligible for or declined surgery and chemotherapy. A total of 52 patients diagnosed with advanced pancreatic cancer were included in the study. At least one course of HIFU therapy combined with percutaneous ultrasound-guided 125I seed implantation was administered to each patient. The clinical assessment included an evaluation of Karnofsky Performance Scale (KPS) score at baseline, and at 1 and 2 months after combined therapy. Pain intensity was additionally evaluated with the numerical rating score (NRS). Overall survival (OS) times and survival rates at 3, 6, 9 and 12 months after combined treatment were evaluated. Adverse events commonly associated with HIFU and 125I seed implantation were recorded, and the severity of adverse events was graded according to the Common Terminology Criteria for Adverse Events, version 4. All 52 patients received successful repeated HIFU treatment combined with 125I seed implantation and were included in the analysis of efficacy and safety. The median OS time of patients was estimated to be 13.1 months (95% CI, 11.3-14.8). The survival rates at 3, 6, 9 and 12 months were 100.0, 86.5, 61.5 and 53.8%, respectively. The mean KPS score was 62.7±6.3 at baseline, 73.7±7.9 at 1 month and 68.8±6.5 at 2 months after combined treatment. KPS score increased significantly after combined therapy. The mean NRS score was 6.7±1.6 at baseline, and 4.7±1.7 and 5.4±1.5 at 1 and 2 months after combined treatment, respectively. The number of patients with severe pain and the NRS score were both significantly lower at 1 and 2 months after 125I seed implantation compared with those at baseline. No serious complications were detected during the follow-up period. In conclusion, the present study demonstrated the survival benefit and improvement in quality of life of patients with advanced pancreatic cancer receiving repeated HIFU treatment combined with 125I interstitial brachytherapy, which may provide new ideas and methods for the treatment of pancreatic cancer.

UNASSIGNED: This study aimed to investigate the relationship between the incidence of VTE and the prognosis of patients with advanced pancreatic cancer, as there is currently a lack of systematic research on this topic, despite the prevalence of venous thromboembolism (VTE) in patients with pancreatic cancer.
UNASSIGNED: Databases including PubMed, Embase, Web of Science, and Cochrane Library were searched until April 9, 2023, to identify studies that explored the relationship between VTE and the prognosis of advanced pancreatic cancer. Duplicate publications, studies without full text or sufficient information for data extraction, animal experiments, reviews, and systematic reviews were excluded. The extracted data were analyzed using STATA 15.1.
UNASSIGNED: The pooled results indicated a significant association between the incidence of VTE and poorer overall survival (HR=1.38, 95% CI: 1.24 - 1.53, p < 0.001) and disease-free survival (HR=2.42, 95% CI: 1.94 - 3.04, p < 0.001) among patients with advanced pancreatic cancer. Additionally, early VTE showed a significant impact on overall survival (HR=2.03, 95% CI: 1.33 - 3.12, p = 0.001), whereas late VTE did not demonstrate a significant association with poor overall survival (HR=1.22, 95% CI: 0.96 - 1.54, p = 0.099).
UNASSIGNED: This study found that advanced pancreatic cancer patients with VTE had poorer overall and disease-free survival than those without. Meanwhile, the patients with early VTE had a significantly poorer prognosis, whereas late VTE did not. The findings highlight the importance of timely detection of VTE for patients with advanced pancreatic cancer patients and offer a partial theoretical basis for future clinical endeavors.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023427043, identifier CRD42023427043.