Management of borderline and locally advanced pancreatic cancer: where do we stand?

Abstract

Many patients with pancreas cancer present with locally advanced pancreatic cancer (LAPC). The principle tools used for diagnosis and staging of LAPC include endoscopic ultrasound, axial imaging with computed tomography and magnetic resonance imaging, and diagnostic laparoscopy. The definition of resectability has historically been vague, as there is considerable debate and controversy as to the definition of LAPC. For the patient with LAPC, there is some level of involvement of the surrounding vascular structures, which include the superior mesenteric artery, celiac axis, hepatic artery, superior mesenteric vein, or portal vein. When feasible, most surgeons would recommend possible surgical resection for patients with borderline LAPC, with the goal of an R0 resection. For initially unresectable LAPC, neoadjuvant should be strongly considered. Specifically, these patients should be offered neoadjuvant therapy, and the tumor should be assessed for possible response and eventual resection. The efficacy of neoadjuvant therapy with this approach as a bridge to potential curative resection is broad, ranging from 3%-79%. The different modalities of neoadjuvant therapy include single or multi-agent chemotherapy combined with radiation, chemotherapy alone, and chemotherapy followed by chemotherapy with radiation. This review focuses on patients with LAPC and addresses recent advances and controversies in the field.

Keywords: Chemotherapy; Irreversible electroporation; Locally advanced; Pancreas; Pancreatic cancer; Radiation.

Figure 1

Computed tomography of locally advanced pancreatic cancer. Encasement is defined as greater than 180-degree involvement of the major vessels. A: Celiac axis is encased by locally advanced pancreatic cancer (arrow); B: Superior mesenteric artery and the replaced right hepatic artery are encased by pancreatic cancer (arrow); C: The portal vein and its confluence with splenic vein are encased by pancreatic cancer (arrow).

Figure 2

Magnetic resonance imaging of locally advanced pancreas cancer with vascular invasion and dilated pancreatic duct. LAPC: Locally advanced pancreatic cancer.

Figure 3

Depiction of stereotactic body radiation plan using computed tomography. Typically the tumor is expanded 2-3 mm to account for set up error microscopic extension and set-up error planning treatment volume. In the lower panel, (patient b) this represents a plan integrating intensity modulated radiation therapy (IMRT) where the tumor is expanded 1-3 cm to cover the tumor and peripancreatic lymph nodes. Stereotactic body radiation is often delivered over 1-5 d without chemotherapy. IMRT is delivered over 5-6 wk with concurrent chemotherapy.

Figure 4

An intraoperative image of in situ irreversible electroporation being used in a patient with locally advanced pancreatic cancer. Three probes are placed around the tumor which is encasing the superior mesenteric vein causing complete occlusion plus superior mesenteric artery involvement.

Figure 5

This is the representative base unit and generator for irreversible electroporation, manufactured by AngioDynamics, Latham, NY.