Seddighzadeh, Bobak

PURPOSE Pancreatic acinar cell carcinoma (PACC) is a rare and aggressive form of pancreatic cancer that originates in the acinar cells of the exocrine pancreas. In this study, we aimed to investigate the clinical and molecular characteristics of patients with PACC at our institution. METHODS This was a retrospective study of patients with PACC seen at Mayo Clinic between 2002 and 2023. Baseline patient characteristics, tumor pathology, treatment strategies used, and survival outcomes were analyzed. Kaplan-Meier curves were estimated using newsurv macros in SAS. RESULTS The study included a total of 65 patients with PACC. The median age at diagnosis was 66 years. Almost half of the patients (48%) presented with resectable/borderline-resectable disease (n = 28). Five-year overall survival (OS) for resectable/borderline-resectable, locally advanced/unresectable, and metastatic disease were 72.0%, 21.6%, and 20.9%, respectively. Somatic and germline next-generation sequencing identified numerous potentially actionable targets including homologous recombination (43% somatic, 33% germline), RAF alterations (29% somatic), and mismatch repair (14% somatic). CONCLUSION Our findings underscore the heterogeneity and aggressive nature of PACC. Despite the improved prognosis for patients with resectable/borderline-resectable disease, OS remains poor, particularly for those with locally advanced or metastatic disease. The identification of actionable molecular targets in a significant proportion of patients highlights the potential for personalized therapeutic approaches. Future research should focus on tailored treatment strategies to exploit these molecular vulnerabilities, which may offer new options for improving outcomes in this rare malignancy.

Abstract Coccidioidomycosis is a common cause of community-acquired pneumonia in endemic regions. Approximately 20 000 cases of coccidioidomycosis occur annually; however, this statistic is limited by a widespread lack of testing. Here, we analyze emergency medicine provider attitudes toward coccidioidal testing and assess the effect of an intervention to improve testing rates.

688 Background: PACC is a rare malignancy originating from the exocrine pancreas, accounting for less than 1% of all pancreatic cancers. Due to the rarity of the disease entity, there is a paucity of data to guide treatment decisions. This retrospective study aims to provide additional clinical characteristics and outcomes to aid in future treatment decisions. Methods: Pathology records from Mayo Clinic (AZ, FL, MN) patients (pts) denoting acinar or mixed-acinar cell carcinoma were searched between 2002 to 2023 and selected for retrospective review. Pt demographics, treatment courses, and next generation sequencing (NGS) were collected. Results: A total of 62 pts (74% male, n = 46) were identified with median age 64 years old. Histologic subtypes were 67% pure acinar cell carcinoma (42/62), 24% mixed acinar-neuroendocrine (15/62), and 8% mixed acinar-adenocarcinoma (5/62). AJCC stages at diagnosis were 34% stage I/II (21/62), 16% stage III (10/62), and 50% stage IV (31/62). Early-stage disease was treated with upfront surgical resection (81%, 17/21). Locally advanced disease received neoadjuvant therapy (NAT) followed by surgical resection (80%, 8/10). FOLFIRINOX was most often chosen as NAT (65%, 11/17), while others received gemcitabine-based NAT. The R0 resection rate was 86%. The 3 and 5-year survival estimates for stage III were 90.9% (95% CI: 75.4 – 100%) and 67.3% (95% CI: 42.3 – 100%), respectively. The 3 and 5-year survival estimates for stage IV were 36.6% (95% CI: 18.6 – 71.9%) and 29.3% (95% CI: 13.1 – 65.5%), respectively. Median survival time for stage IV was 3 years. Somatic NGS testing was done in 24 pts with alterations found in: homologous recombination (HR) in 42% (10/24); RAF alterations in 25% (6/24); mismatch repair (MMR) in 13% (3/24; none of them with MMR germline mutations), 1 ETV6-NTRK3 fusion, and 1 FGFR mutation. Germline NGS testing was done in 21 pts and alterations in HR were seen in 33% (7/21) of pts. This led to additional therapeutic options in 46% (11/24) of pts. Conclusions: Unlike PDAC, PACC is a genomically diverse disease, with potentially targetable alterations in RAF, HRD, and MMR genes, offering additional therapeutic options for significant number of pts. In addition, more than one-third of the pts harbored germline mutations in HR genes. Therefore, somatic and germline testing should be considered for any pt diagnosed with PACC.