Management Of Pancreatic Cancer Research Articles

Redefining pancreatic cancer management with tumor-agnostic precision medicine

Redefining pancreatic cancer management with tumor-agnostic precision medicine

A comparative analysis of robotic versus laparoscopic total pancreatectomy: insights from the National Cancer Database.

Total pancreatectomy is a complex procedure used in the management of pancreatic cancer. While minimally invasive techniques have been increasingly adopted, limited data exist comparing robotic total pancreatectomy (RTP) and laparoscopic total pancreatectomy (LTP). This study evaluates the utilization, short- and long-term outcomes of RTP and LTP using the National Cancer Database. Patients with stages I-III pancreatic adenocarcinoma who underwent RTP or LTP between 2010 and 2019 were identified. Patient demographics, treatment characteristics, pathologic outcomes, postoperative outcomes, and overall survival were compared. Multivariable logistic regression and Cox proportional-hazards models were used to assess the association of surgical approach with outcomes. Of the 995 patients included, 188 (19%) underwent RTP and 807 (81%) underwent LTP. The utilization of minimally invasive techniques increased over time, with RTP accounting for 24% of cases in 2019. RTP had lower conversion rates than LTP (16% vs. 24%, p = 0.031), but this difference was not significant after adjusting for confounders. Postoperative outcomes, including length of stay, 30-day readmission, and 30- and 90-day mortality, were similar between RTP and LTP. The median overall survival was 22.3months for RTP and 23.6months for LTP (p = 0.647). RTP and LTP demonstrate comparable perioperative, pathological, and oncological outcomes for the management of pancreatic adenocarcinoma. Despite the increasing adoption of minimally invasive total pancreatectomy, it remains a rare operation and should be performed in experienced centers to optimize outcomes.

Evaluating the Impact of Enhanced Recovery After Surgery (ERAS) on Postoperative Outcomes in Pancreatic Cancer Patients: A Historical Control Study

Objective: This study evaluates the impact of the Enhanced Recovery After Surgery (ERAS) program on postoperative outcomes in patients undergoing pancreatic cancer surgery. It compares traditional perioperative care with ERAS-based interventions, focusing on key rehabilitation indicators such as postoperative intestinal function recovery, length of hospital stays, medical costs, and the incidence of complications. Methods: A total of 74 patients were studied, with 37 receiving traditional perioperative care and 37 managed under the ERAS protocol. Data collection included intraoperative indicators such as operation time, fluid input, blood loss, and postoperative recovery measures like first ambulation, pain scores, and complications. Results: The ERAS group demonstrated significantly faster recovery of gastrointestinal function, earlier mobilization, and reduced postoperative pain within the first 12 hours compared to the control group (p<0.05). The incidence of postoperative complications was lower in the ERAS group (13.51% vs. 37.84%, p=0.0166). Furthermore, the ERAS protocol led to a shorter length of hospital stay and lower total medical costs (p<0.0001). Conclusion: The implementation of the ERAS protocol for pancreatic cancer surgery significantly improves recovery outcomes, reduces complications, and lowers healthcare costs. These findings support the broader adoption of ERAS protocols in pancreatic cancer management to optimize clinical and economic outcomes.

Sharing Mono-Institutional Experience of Treating Pancreatic Cancer with Stereotactic Body Radiation Therapy (SBRT).

Stereotactic body radiotherapy (SBRT) is an evolving treatment for the local management of pancreatic cancer (PC). The main purpose of this study is to report our initial experience in terms of local control (LC) and toxicity for PC patients treated with SBRT. We conducted a retrospective review of patients treated with SBRT using abdominal compression (AC) or an end-expiratory breath-holding (EEBH) technique. The median prescribed dose was 35 Gy, delivered in five fractions. Toxicities were recorded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and survival was estimated using the Kaplan-Meier method. From 2017 to 2023, 17 PC patients were offered SBRT. Their median age was 69 years. The median follow-up from the date of diagnosis was 22.37 months. The overall survival (OS) was 94% at 1 year and 60.9% at 2 years. The progression-free survival (PFS) was 63.1% at 6 months and 56.1% at 9 months. The median OS was 26.3 months, and the median PFS was 20.6 months. The 6-month and 1-year LC rates were 71% and 50.8%, respectively. We are successful in implementing the SBRT program at our centre. SBRT appears to be a promising treatment option for achieving LC with limited acute toxicities.

The Gut Microbiota Impacts Gastrointestinal Cancers through Obesity, Diabetes, and Chronic Inflammation

The gut microbiota’s pivotal role in human health is increasingly evident, particularly in chronic conditions like obesity, diabetes, and inflammatory diseases. This intricate symbiotic relationship influences metabolic balance and immune responses. Notably, gut microbial dysbiosis is linked to obesity’s metabolic disruption and chronic low-grade inflammation. Similarly, in diabetes, the microbiota’s impact on insulin resistance and glucose metabolism is becoming evident. Chronic inflammation, a common denominator in these conditions, is also a recognized precursor to carcinogenesis. This intersection prompts a compelling question: does the gut microbiota’s influence extend to gastrointestinal cancers like colorectal and pancreatic cancer? These malignancies are closely intertwined with inflammation and metabolic dysregulation. Exploring whether the microbial signatures associated with chronic conditions overlap with precancerous or cancerous states offers new perspectives. This article reviews emerging evidence on the interplay between the gut microbiota, chronic conditions, and gastrointestinal cancers. By elucidating these connections, we aim to uncover potential avenues for innovative diagnostic, preventative, and therapeutic strategies in colorectal and pancreatic cancer management.

Mesenchymal stem cell-delivered paclitaxel nanoparticles exhibit enhanced efficacy against a syngeneic orthotopic mouse model of pancreatic cancer

Pancreatic cancer is considered the deadliest among various solid tumors, with a five-year survival rate of 13 %. One of the major challenges in the management of advanced pancreatic cancer is the inefficient delivery of chemotherapeutics to the tumor site. Even though nanocarriers have been developed to improve tumoral delivery of chemotherapeutics, less than 1 % of the drugs reach tumors, rendering inadequate concentration for effective inhibition of tumors. As a potential alternative, mesenchymal stem cells (MSCs) can effectively deliver their cargo to tumor sites because of their resistance to chemotherapeutics and inherent tumor tropism. In this study, we used MSCs for the delivery of dibenzocyclooctyne (DBCO)-functionalized paclitaxel (PTX)-loaded poly(lactide-co-glycolide)-b-poly (ethylene glycol) (PLGA) nanoparticles. MSCs were modified to generate artificial azide groups on their surface, allowing nanoparticle loading via endocytosis and surface conjugation via click chemistry. This dual drug loading strategy significantly improves the PTX-loading capacity of azide-expressed MSCs (MSC-Az, 55.4 pg/cell) compared to unmodified MSCs (28.1 pg/cell). The in vitro studies revealed that PTX-loaded MSC-Az, nano-MSCs, exhibited cytotoxic effects against pancreatic cancer without altering their inherent phenotype, differentiation abilities, and tumor tropism. In an orthotopic pancreatic tumor model, nano-MSCs demonstrated significant inhibition of tumor growth (p < 0.05) and improved survival (p < 0.0001) compared to PTX solution, PTX nanocarriers, and Abraxane. Thus, nano-MSCs could be an effective delivery system for targeted pancreatic cancer chemotherapy and other solid tumors.

The Impact of Sugar Control on Pancreatic Cancer Progression for the Elderly

Pancreatic cancer is a type of cancer that originates in the pancreas, an organ that aids in digestion and blood sugar regulation. It is characterized as an aggressive type of cancer that presents with symptoms that often go undetected. In 2024, there were an estimated 66,440 new cases of pancreatic cancer and an estimated 51,170 deaths from pancreatic cancer, with a 5-year relative survival rate of 12.8% (SEER, 2023). While traditional medical interventions such as surgery and chemotherapy continue to be the cornerstone of treatment, there is an emerging focus on the potential impact of dietary and nutritional factors in both preventing and managing pancreatic cancer. This approach is particularly relevant for elderly patients due to the heightened risk associated with surgery at their age and their reduced tolerance to chemotherapy regimens. This paper presents a compelling case study of a pancreatic cancer patient who adopted a sugar-restricted diet, resulting in a notable decrease in the tumor marker CA 19-9, which is commonly associated with pancreatic cancer. Building on this individual case study, this paper provides a comprehensive review of current scientific literature to examine the potential relationship between sugar consumption and pancreatic cancer development and progression. By examining this intersection of nutrition and oncology, this study aims to expound upon possible alternative or complementary approaches to pancreatic cancer management, especially for vulnerable populations such as the elderly. This research could lead to new strategies for improving outcomes and quality of life in pancreatic cancer care.

Detection of liver metastases in patients with pancreatic adenocarcinoma: MRI versus CT

Introduction. Detection of liver metastases is important to guide therapeutic management of pancreatic cancer. Data suggest that magnetic resonance imaging (MRI) is more sensitive than computed tomography (CT) for the diagnosis of liver metastases from pancreatic cancer. However, MRI is currently not recommended in several guidelines. Purpose. To compare the performance of CT vs MRI in detection of liver metastases in patients with pancreatic adenocarcinoma. Methods. This was a retrospective single-center study over 24 months from January 2020 to December 2021 of patients suspected of having PDAC. All patients underwent contrast-enhanced triple phase CT and contrast-enhanced MRI/MRCP. The CT and MRI assessment of resectability and detection of metastases were performed according to NCCN version 1.2024 criteria by one observer based on clinical report. Composite reference standard based on decision of operability (based on multidisciplinary tumor board decision), surgical findings (delay of 2 to 3 weeks after imaging) and histopathologic findings. Results. 117 patients (M/F 52/65, mean age 62±11y) were included. The mean tumor size was 43.6±15.2mm (add range). 42/46 patients (34.2%/39.3%) were diagnosed with metastatic disease on CT/MRI, 40/36 patients (34.2%/30.8%) were resectable, 20/16 patients (17.1%/13.7%) were borderline resectable and 15/19 patients (12.8%/16.2%) were locally advanced. The detection of liver metastases on CT and MRI was compared with surgical findings in 45 patients (38.5%). The analysis showed that MRI had superior performance to CT, with sensitivity at 100% vs 60% and specificity at 97.1% vs 97.1%, PPV at 90.9% vs 85.7% and NPV 100% vs 89.5% (MRI/CT). Conclusion. MRI is more sensitive than CT in detection of liver metastases in patients with pancreatic adenocarcinoma.

Targeting RhoA expression with formononetin and salvianolic acid B to mitigate pancreatic cancer-associated endothelial cells changes

Ethnopharmacological relevanceAccording to the theory of Qi and blood in Traditional Chinese Medicine (TCM), the combination of Qi-reinforcing herbs and blood-activating herbs has a synergistic effect in improving blood stasis syndrome, especially in tumor treatment. The classic “Radix Astragali - Salvia miltiorrhiza” duo exemplifies this principle, renowned for invigorating Qi and activating blood flow, employed widely in tumor therapies. Our prior research underscores the potent inhibition of pancreatic tumor xenografts by the combination of Formononetin (from Radix Astragali) and Salvianolic acid B (from Salvia miltiorrhiza) in vitro. However, it remains unclear whether this combination can inhibit the abnormal vascularization of pancreatic tumors to achieve its anti-cancer effect. Aim of the studyAbnormal vasculature, known to facilitate tumor growth and metastasis. Strategies to normalize tumor-associated blood vessels provide a promising avenue for anti-tumor therapy. This study aimed to unravel the therapeutic potential of Formononetin combined with Salvianolic acid B (FcS) in modulating pancreatic cancer's impact on endothelial cells, illuminate the underlying mechanisms that govern this therapeutic interaction, thereby advancing strategies to normalize tumor vasculature and combat cancer progression. Materials and methodsA co-culture system involving Human Umbilical Vein Endothelial Cells (HUVECs) and PANC-1 cells was established to investigate the potential of targeting abnormal vasculature as a novel anti-tumor therapeutic strategy. We systematically compared HUVEC proliferation, migration, invasion, and lumenogenesis in both mono- and co-culture conditions with PANC-1 (H-P). Subsequently, FcS treatment of the H-P system was evaluated for its anti-angiogenic properties. Molecular docking was utilized to predict the interactions between Formononetin and Salvianolic acid B with RhoA, and the post-treatment expression of RhoA in HUVECs was assessed. Furthermore, we utilized shRhoA lentivirus to elucidate the role of RhoA in FcS-mediated effects on HUVECs. In vivo, a zebrafish xenograft tumor model was employed to assess FcS's anti-tumor potential, focusing on cancer cell proliferation, migration, apoptosis, and vascular development. ResultsFcS treatment demonstrated a significant, dose-dependent inhibition of PANC-1-induced alterations in HUVECs, including proliferation, migration, invasion, and tube formation capabilities. Molecular docking analyses indicated potential interactions between FcS and RhoA. Further, FcS treatment was found to downregulate RhoA expression and modulated the PI3K/AKT signaling pathway in PANC-1-induced HUVECs. Notably, the phenotypic inhibitory effects of FcS on HUVECs were attenuated by RhoA knockdown. In vivo zebrafish studies validated FcS's anti-tumor activity, inhibiting cancer cell proliferation, metastasis, and vascular sprouting, while promoting tumor cell apoptosis. ConclusionsThis study underscores the promising potential of FcS in countering pancreatic cancer-induced endothelial alterations. FcS exhibits pronounced anti-abnormal vasculature effects, potentially achieved through downregulation of RhoA and inhibition of the PI3K/Akt signaling pathway, thereby presenting a novel therapeutic avenue for pancreatic cancer management.

Surgical management of pancreatic cancer in Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: a 5 years retrospective descriptive study

IntroductionThe incidence of Pancreatic cancer is different in different parts of the world. It is a cancer with the worst prognosis of all malignancies. Pancreatic cancer is predominantly a disease of an older population. There are different environmental (modifiable) and non-modifiable risk factors associated with the development of pancreatic cancer. At present, surgical resection is the only potential cure for pancreatic cancer. However, as only 10–20% of the patients have resectable disease at the time of diagnosis. The morbidities associated with surgeries for pancreatic cancers remain high though the post-operative mortality has shown significant reduction in the past few decades. So far, no study has been conducted to investigate pancreatic cancer in Ethiopia.ObjectivesTo assess the clinico-pathologic profile, associated factors, surgical management and short-term outcome of patients with pancreatic cancer in Tikur Anbessa Specialized hospital.MethodsA 5 years retrospective hospital-based cross-sectional study was conducted on 52 patients operated with the diagnosis of pancreatic cancer with either curative or palliative intents. The study period was from April 2016 to July 2021. The data collected includes demographic profile, associated risk factors and comorbidities, clinical presentations, biochemical parameters, pathologic features of the tumors as well as type of treatment offered and short term treatment outcome. The data was analyzed using SPSS version 25.ResultThe mean and median age of patients was 54.1 and 54.5% respectively. Males constitute about 52% the patients. 21% of the patients have potential risk factors; whereas only 10 (19.2%) of the patients had medical comorbidities. Median duration of symptoms at diagnosis was 12 weeks. Abdominal pain (88.5%) was the most common presenting symptom followed by anorexia (80.8%) and significant weight loss (78.8%), while 71.2% of the patients have jaundice. On clinical evaluation, 69.2% were jaundiced, while 34.6% had a palpable gallbladder. More than two third of patients presented with advanced disease. 76.9% of the tumors are located in the head of pancreas. More than three quarters (77%) of the surgeries performed were palliative. Postoperative morbidity and mortality were 19.2% and 3.8% respectively.ConclusionAge at first diagnosis of pancreatic cancer is relatively earlier in our setup. Most patients present with advanced condition, only amenable for palliative measures. The post-operative morbidity and mortality are more or less comparable with similar studies. The need for adjuvant therapy in pancreatic cancer should be emphasized.

Advancements and Challenges in Artificial Intelligence-Driven Diagnosis and Management of Pancreatic Cancer

Advancements and Challenges in Artificial Intelligence-Driven Diagnosis and Management of Pancreatic Cancer

Potential Use of Human Mesenchymal Stem Cells (hMSCs) in Pancreatic Damage/Cancer

Pancreatic damage and pancreatic cancer pose significant challenges due to their complex pathogenesis, limited treatment options, and poor prognosis. In recent years, the potential use of human Mesenchymal Stem Cells (hMSCs) has been explored to address these complex pancreatic conditions and develop novel therapeutics. hMSCs, known for their regenerative and immunomodulatory properties, offer a novel therapeutic avenue for repairing damaged tissues and possibly inhibiting cancer progression. This communication discusses current research findings on the application of hMSCs in pancreatic damage and cancer treatment while evaluating hMSC-mediated gene therapy in pancreatic disorders. Moreover, the challenges and considerations associated with hMSC-based therapies and the potential best therapeutic approaches are discussed. Furthermore, the current scientific evidence regarding hMSCs in revolutionizing the management of pancreatic damage and cancer, offering future perspectives for improved therapeutic strategies for patients facing these daunting conditions, is critically discussed.

Identification and model construction of survival-associated proteins for pancreatic cancer based on deep learning

Pancreatic cancer (PC) is a malignancy typified by its insidious onset, rapid progression, limited resectability, poor treatment response, and exceedingly dismal prognosis. The transition from precursor lesions to infiltrating malignant tumors in pancreatic cancer is concomitant with the accrual of genetic mutations. The elucidation of proteins linked to the prognosis of pancreatic cancer holds paramount importance in the realm of pancreatic cancer management. Herein, we introduce DeepPCSA, a model tailored for the screening of target proteins and the prediction of survival time, employing both conventional methodologies and deep learning techniques for patient survival analysis. This framework leverages the LASSOCOX regression approach on differentially expressed genes (DEGs) to discern pivotal genes, succeeded by the development of a prognostic model employing convolutional and fully connected layers to prognosticate patient survival duration. Furthermore, we account for covariates such as age, gender, and other pertinent factors for independent prognostic scrutiny, affirming the autonomy of our model as a prognostic determinant. Employing unsupervised clustering methodologies, we delineated two molecular subtypes delineated by disparate biological processes. Ultimately, via drug sensitivity analysis, we delineated the interrelation between survival duration and pharmaceuticals, substantiating the necessity for tailored drug interventions catering to patients of varying risk strata.

Role of molecular biology in the management of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in patient management due to a dismal prognosis, increasing incidence, and limited treatment options. In this regard, precision medicine, which personalizes treatments based on tumour molecular characteristics, has gained great interest. However, its widespread implementation is not fully endorsed in current recommendations. This review explores key molecular alterations in PDAC, while emphasizing differences between KRAS-mutated and KRAS-wild-type tumours. It assesses the practical application of precision medicine in clinical settings and outlines potential future directions with respect to PDAC. Actionable molecular targets are examined with the aim of enhancing our understanding of PDAC molecular biology. Insights from this analysis may contribute to a more refined and personalized approach to pancreatic cancer treatment, ultimately improving patient outcomes.

Guidelines for holistic integrative management of pancreatic cancer

BackgroundPancreatic cancer ranks 10th in the incidence rate of malignant tumors in male, and 12th in female. Pancreatic cancer is the sixth leading cause of tumor-related deaths in China. It is a devastating malignancy with poor prognosis.MethodsDriven by the concept of "integrated medicine", the China Anti-Cancer Association Committee of Pancreatic Cancer organized relevant experts to complete this guideline.ResultsThis guideline aims to guide the integrated treatment and rehabilitation management of pancreatic cancer in an all-round way based on "Preventing, Screening, Diagnosing, Treating, and Rehabilitating".ConclusionsWe hope that this guideline will provide effective references for clinicians, so as to achieve the best treatment effects for pancreatic cancer patients in China.

The preclinical gap in pancreatic cancer and radiotherapy.

Pancreatic ductal adenocarcinoma is an aggressive malignancy with limited treatment options. Chemotherapy offers little benefit and, although there is some evidence that radiotherapy may improve response, its use in the clinical management of pancreatic cancer remains controversial due to conflicting reports on its survival benefit. There has also been a lack of clinical trials that directly investigate the efficacy of radiotherapy in pancreatic cancer. The limited progress in the development of radiotherapeutic strategies in pancreatic cancer can be attributed, at least in part, to a dearth of preclinical research and our limited understanding of the effects of radiation on the pancreatic tumour microenvironment. In this Perspective, we discuss how insight into the immunosuppressive tumour microenvironment and the complex signalling between tumour and stromal cells following radiation is needed to develop effective radiosensitising strategies for pancreatic cancer. We also highlight that to have the best chance for successful clinical translation, more preclinical research is required in appropriately complex models.

New Frontiers in Pancreatic Cancer Management: Current Treatment Options and the Emerging Role of Neoadjuvant Therapy.

Pancreatic ductal adenocarcinoma (PDAC) ranks among the 15 most prevalent cancers globally, characterized by aggressive growth and late-stage diagnosis. Advances in imaging and surgical techniques have redefined the classification of pancreatic PDAC into resectable, borderline resectable, and locally advanced pancreatic cancer. While surgery remains the most effective treatment, only 20% of patients are eligible at diagnosis, necessitating innovative strategies to improve outcomes. Therefore, traditional treatment paradigms, primarily surgical resection for eligible patients, are increasingly supplemented by neoadjuvant therapies (NAT), which include chemotherapy, radiotherapy, or a combination of both. By administering systemic therapy prior to surgery, NAT aims to reduce tumor size and increase the feasibility of complete surgical resection, thus enhancing overall survival rates and potentially allowing more patients to undergo curative surgeries. Recent advances in treatment protocols, such as FOLFIRINOX and gemcitabine-nab-paclitaxel, now integral to NAT strategies, have shown promising results in increasing the proportion of patients eligible for surgery by effectively reducing tumor size and addressing micrometastatic disease. Additionally, they offer improved response rates and survival benefits compared to traditional regimes. Despite these advancements, the role of NAT continues to evolve, necessitating ongoing research to optimize treatment regimens, minimize adverse effects, and identify patient populations that would benefit most from these approaches. Through a detailed analysis of current literature and recent clinical trials, this review highlights the transformative potential of NAT in managing PDAC, especially in patients with borderline resectable or locally advanced stages, promising a shift towards more personalized and effective management strategies for PDAC.

Extracellular Vesicular miRNA in Pancreatic Cancer: From Lab to Therapy.

Pancreatic cancer is a prevalent lethal gastrointestinal cancer that generally does not show any symptoms until it reaches advanced stages, resulting in a high mortality rate. People at high risk, such as those with a family history or chronic pancreatitis, do not have a universally accepted screening protocol. Chemotherapy and radiotherapy demonstrate limited effectiveness in the management of pancreatic cancer, emphasizing the urgent need for innovative therapeutic strategies. Recent studies indicated that the complex interaction among pancreatic cancer cells within the dynamic microenvironment, comprising the extracellular matrix, cancer-associated cells, and diverse immune cells, intricately regulates the biological characteristics of the disease. Additionally, mounting evidence suggests that EVs play a crucial role as mediators in intercellular communication by the transportation of different biomolecules, such as miRNA, proteins, DNA, mRNA, and lipids, between heterogeneous cell subpopulations. This communication mediated by EVs significantly impacts multiple aspects of pancreatic cancer pathogenesis, including proliferation, angiogenesis, metastasis, and resistance to therapy. In this review, we delve into the pivotal role of EV-associated miRNAs in the progression, metastasis, and development of drug resistance in pancreatic cancer as well as their therapeutic potential as biomarkers and drug-delivery mechanisms for the management of pancreatic cancer.

335P Management, outcome and prognostic factors of metastatic pancreatic cancer

335P Management, outcome and prognostic factors of metastatic pancreatic cancer

Phase I/II study of TROP2 CAR engineered IL15-transduced cord blood-derived NK cells delivered intraperitoneally for the management of platinum resistant ovarian cancer, mesonephric-like adenocarcinoma, and pancreatic cancer.

TPS5626 Background: Novel treatments are needed for patients with ovarian, pancreatic, and mesonephric-like adenocarcinoma (MLA) that has recurred or progressed after initial treatment, as current standard of care therapies in these settings result in low response rates. Chimeric antigen receptor-transduced natural killer (CAR-NK) cells have emerged as a therapeutic alternative to CAR-T cells, with decreased toxicity and enhanced feasibility as an “off-the-shelf” therapy. TROP2, or trophoblast cell-surface antigen 2, is a transmembrane calcium-signal transducer that is overexpressed in many cancer types and associated with poor clinical outcomes. Recent studies have demonstrated TROP2 as a promising target for adoptive cell therapy in breast and gastric cancers. An intraperitoneal route of adoptive cell therapy delivery may provide superior disease control and decreased toxicity in these target cancers with predisposition for intra-abdominal/peritoneal involvement. Pre-clinical studies have established the efficacy and safety of TROP2 CAR NK cells in ovarian and pancreatic cancers. Methods: This is a phase I/II study of the intraperitoneal delivery of TROP2-CAR/IL-15 transduced cord blood (CB)-NK cells for recurrent/progressive ovarian cancer, pancreatic cancer, and MLA (NCT05922930). Subjects must have disease present in the peritoneal cavity or retroperitoneal lymph nodes and tumors must demonstrate at least 1+ TROP2 expression by immunohistochemistry. The primary endpoints are toxicity rates and defining the recommended phase II dose (RP2D). Key secondary endpoints include treatment efficacy, circulating tumor DNA levels, serial characterization of the immune microenvironment, and patient-reported outcomes. There are four possible dose levels ranging from 8.0x106 to 4.0x109 cells. We will enroll patients from the three disease cohorts using the Bayesian optimal interval (BOIN) design to find the maximum tolerated dose and RP2D, with a maximum sample size of 21. Once the R2PD is chosen, we will enroll up to 10 patients within each disease cohort to further evaluate safety and efficacy. Subjects enrolled will be admitted to the hospital, receive lymphodepleting chemotherapy (fludarabine 30 mg/m2 and cyclophosphamide 300mg/m2) on days -5 to -3, and will receive a single dose of cryopreserved and thawed intraperitoneal TROP2-CAR/IL15-transduced CB-NK cells on day 0. The dose-limiting toxicity window will be from day 0 until day 28. Severity of adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5. The first patient on this trial was treated in January 2024. Clinical trial information: NCT0592293 .