Case Report: Long-term remission of metastatic pancreatic ductal adenocarcinoma after surgery and high-dose nicotinamide supplementation.

Pancreatic ductal adenocarcinoma carries a poor prognosis, with the worst outcomes observed in UICC stage IV disease characterized by hepatic-and less frequently pulmonary-metastases. Considerable genetic heterogeneity, including mutations in KRAS, BRCA1/2, and ERBB2, enables the development of individualized therapeutic strategies. We report here a patient with KRAS- and BRCA1/2-wild-type but mutant TP53 and ERBB2 disease who achieved apparent remission of hepatic metastases. A 78-year-old Caucasian male presented with newly detected dilation of the distal main pancreatic duct and prepapillary stenosis associated with a hypodiffused region. After 8 months of surveillance, rising CA19-9 levels prompted pylorus-preserving pancreaticoduodenectomy. Two small hepatic nodules were resected and confirmed as metastatic lesions. The primary tumor was identified as invasive micropapillary pancreatic ductal adenocarcinoma (PDAC). Surgery did not slow or halt the progressive rise of CA19-9 levels in serum. Adjuvant gemcitabine therapy was discontinued at the patient's request after four infusions, and high-dose nicotinamide treatment (3 x 500 mg per day) was initiated 11 weeks later. CA19-9 levels declined from 1376 U/ml to the normal range within 5 months. Initial magnetic resonance imaging revealed multiple small hepatic metastases, which regressed in parallel with CA19-9 levels and were no longer detectable one and two years later. Regression of CA19-9 levels and imaging-detectable hepatic metastases occurred concurrently after initiation of high-dose nicotinamide. This temporal relationship may be incidental, and the remission could represent a delayed effect of the preceding gemcitabine infusions. Nicotinamide supplementation may also have contributed anti-tumor activity. High-dose nicotinamide elevates systemic NAD+ levels, which may enhance immune function within the metastatic tumor microenvironment. In addition, partial inhibition of poly(ADP-ribose) polymerase by high-dose nicotinamide can impair DNA repair in tumor cells with underlying repair deficiencies, thereby promoting tumor cell death.