Locally Advanced Pancreatic Cancer Case Report: ATM mutation in the setting of FOLFIRINOX and MRI guided SBRT leads to near complete pathological response

Purpose: Pancreatic cancer (PC) carries one of the worse five-year survival rates (12.5%) with a median survival rate of less than 12 months (1,2). Current guidelines mandate genetic testing for all PC patients to determine mutations such as those in the Ataxia-Telangiectasia (ATM) gene which is involved in several DNA damage repair pathways. The ATM deficiency may increase sensitivity to radiation and oxaliplatin (2). This case report evaluates the treatment response of a patient with locally advanced PC (LAPC) and an ATM mutation in the setting of neoadjuvant FOLFIRINOX and MRI-guided SBRT.

Methodology: The treatment records of a patient with an ATM mutation were reviewed in accordance with an IRB-approved retrospective protocol. The clinical notes, radiation treatment plan and treatment summary, as well as all imaging, were reviewed and form the basis of this report.

Results: The patient is a 63-year-old female with a history of intraductal papillary mucinous neoplasm (IPMN) who was undergoing surveillance imaging until she was found to have a 3x2.1 cm mass in the pancreatic tail, biopsy positive for adenocarcinoma, with distant enlarged nodes suspicious for metastatic disease. Initial CA 19-9 was 4790 (normal: 0-37 U/mL). PET/CT scan showed no evidence of metastatic disease with uptake only in the pancreatic tail. Genetic testing revealed an ATM gene mutation. Her case was discussed at the institutional tumor board where she was staged as having inoperable LAPC. She received 7 cycles of FOLFIRINOX with mild toxicities and considerable biochemical response with normalization of her CA 19-9 (25.8). After subsequent MRI-guided SBRT to 40 Gy in 5 fractions, her case was reviewed with imaging showing a tumor size of 2.2 cm and vessel improvement warranting surgical exploration. A month later, she underwent a successful distal pancreatectomy and splenectomy with no complications during the procedure or postoperatively. Surgical pathological evaluation showed R0 resection, no lymphovascular invasion, tumor response grade (TRG) of 1 (near complete response) and stage pT1bN0. It has been four years since her initial diagnosis, and she continues to be disease-free on imaging and by tumor marker.

Conclusions: Most patients with LAPC are never eligible for surgical resection following neoadjuvant therapy. This case highlights an exceptional pathologic response in a patient with an ATM mutation, highlighting the importance of individualized genetic testing to guide neoadjuvant decision-making.

References: (1) - Cancer of the Pancreas - Cancer Stat Facts. SEER. Accessed October 29, 2023. https://seer.cancer.gov/statfacts/html/pancreas.html
(2) - Armstrong SA, Shultz CW, Azimi-Sadjadi A, Brody JR, Pishvaian MJ. ATM Dysfunction in Pancreatic Adenocarcinoma and Associated Therapeutic Implications. Mol Cancer Ther. 2019;18(11):1899-1908. doi:10.1158/1535-7163.MCT-19-0208
=