Prolonged Survival in Metastatic Pancreatic Acinar Cell Carcinoma Treated with Hepatic Arterial Infusion of Oxaliplatin: A Case Report with Longitudinal Molecular Profiling

Abstract

Introduction

Pancreatic acinar cell carcinoma (PACC) is a rare malignancy, representing 1–2% of pancreatic cancers. Although it generally has a better prognosis than ductal adenocarcinoma, optimal systemic management remains undefined. Hepatic arterial infusion (HAI) of chemotherapy has shown efficacy in colorectal liver metastases but is rarely reported in pancreatic cancer.

Case Presentation

We present a 36-year-old man diagnosed with metastatic PACC after developing abdominal pain and hepatomegaly. Imaging revealed a pancreatic tail mass and multiple liver metastases. After an initial partial response to FOLFIRINOX followed by several systemic regimens, the patient received a novel combination of intravenous 5-fluorouracil and HAIs of oxaliplatin. This strategy allowed a good hepatic response, and the patient had the administration of approximately 60 oxaliplatin-based cycles. The patient was included in a phase II trial thanks to serial molecular analyses that demonstrated progressive genomic evolution, with losses of RB1, PTEN, MTAP, CDKN2A/2B, and SMAD4.

Conclusion

This case illustrates a rare metastatic PACC achieving prolonged survival through local control at the hepatic level, thanks to 42 cycles of HAI of oxaliplatin. It suggests that HAI may represent a feasible and effective regional strategy for selected patients with predominant liver involvement. The longitudinal molecular profiling shows the importance of re-biopsy to detect emerging actionable alterations and guide inclusion in targeted clinical trials.

Introduction

Pancreatic acinar cell carcinomas (PACCs) are a rare entity, accounting for approximately 1% to 2% [1] of all pancreatic cancers. They have unique phenotypic and molecular characteristics and have a better prognosis than ductal pancreatic adenocarcinomas (PDACs), with median overall survival ranging from 13 to 47 months [2, 3].

PACCS are different from PDAC on several points. They rarely cause biliary obstruction and can be responsible for a paraneoplastic disease called “Schmid’s triad” with arthritis, eosinophilia, and subcutaneous fat necrosis [4]. On immunohistochemistry, there is trypsin and chymotrypsin reactivity in about 95% of cases [5]. Common molecular alterations include KRAS, SMAD4, CDKN2A, and TP53 [6, 7]. Some targetable genetic alterations have also been identified, such as BRCA1, BRCA2, PALB2, ATM, or MSH2 [8].

Treatment currently consists of surgery as soon as possible, with little evidence of the benefits of adjuvant chemotherapy, and 5-fluorouracil (5-FU)-based chemotherapy when surgery is not possible. These tumors appear to be less sensitive to gemcitabine than PDACs [9]. Targeted therapies could be a possible treatment for these patients, particularly since they frequently have mutations that can be targeted. Longitudinal monitoring of the molecular profile could be useful in order to offer appropriate treatments.

Hepatic arterial infusion (HAIs) are not currently used in pancreatic cancer but have demonstrated efficacy in prolonging survival in colorectal cancer with liver metastases; they represent an interesting therapeutic alternative when systemic toxicity is important. We report the case of a young man with metastatic PACC who achieved prolonged survival and who received innovative treatment with the use of HAI of oxaliplatin and with molecular profiling performed throughout the course of his treatment.

Case Presentation

A 36-year-old man with a past medical history of resected cerebral hamartoma at age 16 and residual epilepsy presented to the emergency department in February 2020 with abdominal pain and hepatomegaly. CT imaging revealed a multinodular liver and a 6-cm lesion in the pancreatic tail. Biopsy confirmed PACC expressing CK7 and BCL10, with no neuroendocrine differentiation and no BRCA mutations. All tumor markers at diagnosis, CA 19-9 CEA and alpha-fetoprotein, were normal. RECIST 1.1 criteria were used to assess responses.

As the patient was metastatic and therefore unresectable, systemic palliative treatment was initiated (Fig. 1). The patient initially received 18 cycles of FOLFIRINOX with good gastrointestinal and neurological tolerance, achieving partial response. Capecitabine maintenance was administered for 3 cycles prior to progression disease. Second-line therapy consisted of three cycles of gemcitabine-nab-paclitaxel, followed by third-line therapy with 12 cycles of 5-FU plus cisplatin.

Fig. 1.

Summary of the therapeutic timeline. HAI, Hepatic Arterial Infusion; IV, Intravenous.

Subsequent progression was confined to the liver, with progression of some lesions while others had partial response. The pancreatic lesion remained stable. After multidisciplinary tumor board, given to the isolated hepatic progression, an innovative palliative approach to control liver disease was initiated with intravenous (IV) leucovorin 200 mg/m² and 5-FU 2400 mg/m² combined with oxaliplatin 85 mg/m² administered via HAI every 2 weeks through a catheter placed in the common hepatic artery. This strategy allowed hepatic partial response without neurological or hematologic side effects (Fig. 2). Isolated pancreatic progression after seven cycles led to the introduction of IV irinotecan, resulting in a partial overall response for 11 additional cycles. The patient had grade 1 nausea for 3 days after each cycle and no neurological or hematologic toxicity. Due to fatigue and treatment burden, capecitabine was used as maintenance for 5 cycles.

Fig. 2.

Abdominal CT scan at the portal venous phase before the start of HAI of oxaliplatin (up) and after 6 cycles (down) showing partial response according to RECIST 1.1 criteria.

Further hepatic and pancreatic progression led to IV GEMOX therapy, later switched to gemcitabine IV combined with HAI oxaliplatin due to hematologic toxicity, for a total of 12 cycles. Isolated pancreatic progression with maintained hepatic stable disease was treated with chemoradiation to the pancreas (54 Gy in 27 fractions) with concurrent capecitabine, followed by four additional cycles of capecitabine.

Further progression with hepatic and bone involvement led to a FOLFIRINOX regimen with HAI oxaliplatin. Unfortunately, after 6 cycles, hepatic and bone progression occurred.

In 2021, molecular profiling of liver tissue revealed somatic loss of RB1 and PTEN (variant allele frequency 90%). Constitutional genetic testing ruled out a germline BRCA mutation and PTEN mutation, excluding Cowden syndrome.

In 2025, comprehensive genomic and transcriptomic analysis of a progressive hepatic lesion identified new homozygous deletions in MTAP, CDKN2A, CDKN2B, and SMAD4. Based on the MTAP deletion, the patient was eligible for and subsequently enrolled in a phase I clinical trial in September 2025, investigating a PRMT5 inhibitor.

At the first imaging evaluation in October 2025, the patient was classified as stable according to RECIST 1.1 criteria. However, the trial was discontinued due to a decline in the patient’s general condition, attributed to the onset of paraneoplastic Weber-Christian syndrome which is a rare condition characterized by subcutaneous nodules, inflammatory cells in the fat lobules, and systemic symptoms such as pain and fever. The patient received best supportive care from this moment. The patient died in January 2026, nearly 71 months after his diagnosis.

Over a period of 6 years, the patient received eight lines of systemic therapy which allowed a good control of his disease especially in the liver, with a combination of classic systemic treatments and HAI (Fig. 1). This case report has been prepared in accordance with the CARE (case report) guidelines. The completed CARE checklist is provided as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000552399).

Discussion

PACC represents 1–2% of exocrine pancreatic tumors, with distinct biology and prognosis compared with ductal adenocarcinomas, generally showing longer survival [10]. Chemosensitivity to oxaliplatin is often higher than in conventional PDAC, with rather the ineffectiveness of a gemcitabine-based regimen [11], as presented in our case report.

HAI exploits differential vascularization between normal liver and tumor tissue: hepatic metastases are perfused almost exclusively via the hepatic artery, whereas normal liver tissue is primarily perfused via the portal vein [12]. Some agents such as 5-FU or oxaliplatin can achieve high local hepatic concentrations while having limited systemic exposure and peak plasma levels. HAI can be delivered via a port-a-cath placed percutaneously by an interventional radiologist [13], with the catheter in the common hepatic artery or one of its branches [14].

Most clinical evidence for HAI comes from colorectal cancer. Multiple series and meta-analyses report high hepatic response rates (41–74%) [15–17] and suggest survival benefits in highly selected cohorts treated with HAI combined with systemic chemotherapy. The randomized phase II PACHA 01–12 trial, which evaluated HAI of oxaliplatin following resection of colorectal liver metastases, has recently demonstrated an improvement in liver PFS [18]. Further clinical trials are ongoing, including the French phase III PRODIGE 49-OSCAR trial, which is investigating HAI oxaliplatin in patients with colorectal liver metastases. Evidence in pancreatic cancer is limited to small series and case reports. They suggest hepatic responses and longer survivals, but it is low-level evidence [19–23].

HAI has a distinct toxicity profile. Common complications include cholecystitis, duodenal ulceration, and hepatic ischemia, and it is necessary to monitor liver enzymes. Systemic toxicity is generally lower though reductions in oxaliplatin-induced neuropathy or hematologic toxicity have not been clearly demonstrated [24, 25].

In our case, we report great outcomes following repeated HAI of oxaliplatin combined with systemic therapy to control liver metastases from a PACC. The patient had the administration of approximately 60 oxaliplatin-based cycles without significant neurological or hematological toxicity. This approach may be considered for selected patients with liver-dominant disease and preserved performance status, within specialized centers experienced in HAI. However, it remains difficult to attribute this observed tolerance only to HAI, given the sequential treatments and interindividual pharmacokinetic variability. PACC shares some genetic traits with colorectal adenocarcinoma (APC mutations, Wnt/β-catenin pathway activation, 18q loss, c-MYC amplification) [26], which may explain oxaliplatin sensitivity.

The molecular alterations observed in this case may explain both treatment sensitivity and resistance mechanisms. Loss of RB1 and PTEN could have contributed to increased cell cycle deregulation and genomic instability, potentially enhancing initial chemosensitivity. Some studies suggest that RB1 expressional loss is associated with higher sensitivity to conventional chemotherapies, including platine-based treatments [27].

The identification of MTAP deletion is interesting, as it creates a potential vulnerability through PRMT5 dependency, providing a biological rationale for enrollment in a PRMT5 inhibitor clinical trial. In MTAP-mutant cells, PRMT5 inhibitors work by exploiting the accumulation of methylthioadenosine, which partially suppresses PRMT5 activity and makes the cells dependent on it, so further inhibition selectively disrupts essential methylation processes and leads to cancer cell death [28]. It is valuable to do iterative molecular profiling, as the tumor evolves under therapeutic pressure and new alterations may emerge, potentially providing access to clinical trials.

This case should be interpreted with caution due to the likely presence of survivorship bias. This patient was young, with a preserved performance status at diagnosis, and the more favorable outcomes of PACC compared to PDAC may have contributed to this long survival.

Conclusion

This case demonstrates that a multimodal approach including HAI of oxaliplatin can contribute to sustained hepatic disease control and prolonged chemotherapy responsiveness, and possible durable survival in metastatic PACC. Longitudinal molecular profiling is important to guide personalized therapeutic strategies.

Acknowledgments

We would like to thank the patient for his courage and for giving us permission to describe his story, and his family for their support.

Statement of Ethics

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal. Ethical approval is not required for this study in accordance with national guidelines.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The authors declare that no funding was obtained for this study.

Author Contributions

J.D. and V.S. were major contributors in article writing and editing various drafts of the manuscript. M.K., A.B., L.B., and S.R. reviewed and edited various drafts of the manuscript. V.S. was the supervisor and is the corresponding author. All authors reviewed and approved the final manuscript.

Funding Statement

The authors declare that no funding was obtained for this study.

Data Availability Statement

The data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author upon reasonable request.