Natural history study of patients with pancreatic acinar cell carcinoma: A 3-year prospective longitudinal analysis.
Authors: Patel Krishna , Skorupan Nebojsa , Aldape Kenneth D. , Raffeld Mark , Raygada Margarita , Reilly Karlyne , Widemann Brigitte C. , Wedekind Mary Frances Frances , Alewine Christine Campo 
Published: January 2025

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Background:
Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas that comprises 0.2-2% of all pancreatic malignancies. There are no prospective randomized studies in this disease and most data about PACC comes from retrospective database analyses and case reports.
Methods:
The Cancer Moonshot-funded My Pediatric and Adult Rare Tumor (MyPART) network’s Rare Solid Tumor Natural History study (NCT03739827) is a prospective, single-institution observational study that enrolls patients of all ages with rare solid tumors (<15 cases per 100,000 people per year), including PACC. Patients can participate remotely (field cohort) or visit the NIH for annual evaluations (in-person cohort). All participants complete medical and family histories, patient reported outcomes (PROs) measures, and provide saliva for DNA analysis. Relevant data such as clinical and family histories, surgical and molecular pathology, and imaging results are extracted from patient medical records and entered in the central study database. Archival tumor samples (when available) are analyzed using a 500+ gene panel (TruSight500, Illumina) and discussed in a molecular tumor board. Patients participating in the in-person cohort undergo additional evaluations including clinical examination, imaging studies, genetic counseling, and blood sample collection for clinical and research purposes (standard clinical labs, germline DNA/RNA, immune phenotypes, cytokines) as indicated.
Results:
From 09/2021 until 09/2024, 17 PACC patients (n=13 for the field cohort, n=4 for the in-person cohort) were accrued. The mean age of diagnosis is 64.7 (48-78) years, and the male to female ratio is 14:3. At the time of diagnosis, 6 patients had Stage I or II, 1 had Stage III, and 10 had Stage IV disease. The median follow-up time since accrual is 7.6 months, and 4 patients have died. No patients have been lost to follow-up. Of the 6 patients diagnosed with early-stage disease, 5 had surgery and all received adjuvant chemotherapy, while 1 patient is receiving neoadjuvant chemotherapy. Among the 9 patients diagnosed with advanced disease, 8 received platinum-based regimens as a first-line therapy. Tumor molecular profiling was available for 16 patients. The most common tumor mutations observed were in CDKN2A (29.4%), BRCA2 (29.4%), and SMAD4 (23.5%). Six patients received targeted therapies matched to their tumor molecular profile.
Conclusions:
The demographic profile of our cohort aligns with previous studies, with a mean age of diagnosis in the early-to-mid 60s and a high male to female ratio. Our cohort highlights a shift in first-line treatment to platinum-based therapies over the past decade. Many PACC tumors have targetable mutations found in molecular profiling, and the efficacy of matched therapy warrants further exploration.
Clinical trial information: NCT03739827
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