Neoadjuvant Strategy Improves Survival in Pancreatic Cancer Resection

Pancreatic cancer is all too pervasive; it afflicts approximately 55,000 Americans annually, and prognostic indicators show that number is increasing. Although a diagnosis of pancreatic cancer is devastating, one study demonstrated that in some instances patients may live up to 5 times longer than the commonly predicted survival times of 12 to 18 months. The determining factor appears to depend on a presurgery strategy, according to surgeons at the Mayo Clinic in Rochester, Minnesota.

Mark Truty, MD, is a surgeon at the Mayo Clinic who often treats patients with pancreatic cancer. He is also the lead author on a paper that discusses how surgeons at Mayo extended survival time for some patients with pancreatic cancer.¹

Approximately one-third of patients with pancreatic cancer have the type of disease that has not metastasized to other organs but has grown outside the pancreas, wrapping itself around veins and arteries. These cases are termed borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). Surgery was always thought to be the only treatment that would enable long-term survival, but these patients are poor operative risks because most develop metastatic disease following surgery. However, medicine is constantly evolving and response to combination chemotherapy regimens, such as FOLFIRINOX and gemcitabine plus nab-paclitaxel (GA), have been improving right along. Furthermore, doctors now increasingly follow a strategy referred to as total neoadjuvant therapy (TNT), which is systemic induction chemotherapy followed by chemoradiation prior to surgery for BR or LA PDAC. The strategy also reduces the potential for positive margins in those patients who undergo resection.

Factors to Success

In this study, the Mayo Clinic team sought to identify predictive factors associated with morbidity, mortality, and survival outcomes in patients with BR or LA PDAC who undergo TNT prior to surgical resection. They followed 194 patients over 7 years of treatment. Their experience identified 3 factors that contribute to improved morbidity/mortality and survival outcomes.

Factor 1 All patients received individualized chemotherapy. FOLFIRINOX cycles were 2 weeks each, and GA cycles were 4 weeks each, per standard dosing. The more cycles patients underwent, the longer their survival. The researchers noted that finding the right chemotherapy was crucial. If the chemotherapy regimen had to be changed, data indicated the total number of all regimen cycles administered. Chemotherapy was continued until the CA 19-9 tumor marker was at normal levels. PET scans were used to confirm response to induction chemotherapy.

Factor 2 Following chemotherapy and confirmed tumor death and suppression of its growth, patients underwent long-course chemoradiotherapy (CRT) consisting of photon/proton external beam radiotherapy 50 to 50.4 Gy in 25 to 28 fractions over 5 weeks with 3D-conformal or intensity-modulated techniques.

Factor 3 Surgery was performed only after the chemotherapy and chemoradiation were completed. Surgery was a complex procedure that involved removing and restoring the veins and arteries that had been tangled up in the pancreatic cancer tumor.

Patients underwent pancreatoduodenectomy, subtotal pancreatectomy, or total pancreatectomy with associated lymphadenectomies. Vascular structures were resected with or without formal revascularization, as determined by anatomical necessity. Reconstruction of portal vein (PV), superior mesenteric vein (SMV), or PV/SMV confluence involved patch venoplasty, end-to-end primary anastomoses, or interposition grafts via autologous or synthetic grafts. En bloc arterial resections included the hepatic artery, celiac axis, superior mesenteric artery, or multiple arterial resections.