Supplementary Material for: Continuous regression of metastatic pancreatic adenocarcinoma after suspending chemotherapy: a case report.

Background:
Regression of malignancy in the absence of cancer-directed therapy is an uncommon and poorly understood phenomenon. Its occurrence is particularly rare for pancreatic ductal adenocarcinoma (PDAC). The interaction between tumor and microenvironment may induce an immune response in which both innate and acquired immunity have been found to be implicated. An immunogenic tumor may promote antigen presentation and effector T cell activity, leading to cancer cell death and tumor inhibition.

Case:
We present the case of a 57-year-old man diagnosed three years ago with a borderline-resectable PDAC confirmed by biopsy. The patient received first-line 5-fluorouracil-based chemotherapy with progression of disease including new hepatic metastases. He then received twelve cycles of gemcitabine and nab-paclitaxel with successful reduction in the number and size of liver metastases. Upon patient request, a treatment holiday was initiated, during which his abdominal imaging showed continued tumor regression. After eleven months without any systemic therapy, there are no remaining metastases in the liver, and the primary pancreatic mass continues to recede. He currently remains on surveillance.

Conclusion:
Our patient’s rare clinical course raises questions including the optimal next steps in treatment, such as continued observation or local treatment such as surgical resection. The decision to continue observation results from our belief that minimal disruption of the tumor microenvironment (TME) may allow for continued control and cancer regression. More laboratory and clinical studies are imperative to understanding the physiological basis of sustained tumor regression after chemotherapy discontinuation and may impact real-world clinical decision-making. Additionally, the definition of spontaneous tumor regression may need revision to distinguish between prolonged therapeutic response and regression due to immunogenic features in the absence of prior therapy.