Improving the Treatment of Locally Advanced Pancreatic Cancer - Episode 1

Approaching a Case of Locally Advanced Pancreatic Cancer

John Marshall, MD:Our case is not an unusual one, a 64-year-old woman who presents with a 2.8-cm pancreatic mass. Unfortunately, the mass is encased in some blood vessels, and that makes it locally advanced, so it’s not resectable. She was referred to a tertiary care center, where I think most of these folks should be taken care of. They underwent a laparoscopic look. They did a diagnostic lab test on the patient and found that there was no evidence of spread to any other parts of her abdominal cavity. Then they made a decision to go forward with intensive chemotherapy using FOLFIRINOX, with a nice response, followed by chemoradiation using capecitabine with radiation.

Reassessment showed that the cancer had indeed shrunk, and they did what I think is the right thing to do: go in with an operative approach, explore the patient, successfully remove the cancer with negative margins, sew her back up, and then send her back to us to decide what to do next. So, this is a case of locally advanced pancreatic cancer that’s technically unresectable at the beginning. Chemotherapy and chemoradiation got the patient to respond, and she subsequently had a surgery, which might be curative.

Regarding locally advanced pancreas cancer, we’re seeing more and more of it: not resectable but not metastatic. These are patients who really are a challenge for us because we want to try to cure them if we can. Typically, locally advanced pancreas cancer is fatal, unresectable and eventually metastatic. We try chemotherapy; we try local approaches. The fact that we have new medicines that can shrink the cancer and possibly convert them to resectable is a new area for us.

A patient who presents with locally advanced pancreas cancer should at least have very good imaging. We argue for something like an endoscopic ultrasound, if your center is very good at that, or MRI. I think it’s not standard to take a laparoscopic look at a patient like this, but it is not wrong to do that if in fact your overall goal is a surgical approach. You want to rule out peritoneal disease if you can before thinking about doing a surgical resection. You need all of that really good imaging to define where the cancer is and where it isn’t before embarking. Pancreas cancer is also a challenge in that we rarely get enough tissue to use broad molecular testing. When we are lucky enough to do that, I think every patient with pancreas cancer should be tested for microsatellite instability and forBRCAmutations because we have new data around PARP inhibitors in those folks who have homologous repair deficiency. If you have enough tissue, it’s probably worth doing broad molecular profiling.

The world of molecular profiling has really evolved over the past couple of years, frankly. It was considered research at the beginning of the story, so there was a lot of trouble getting those cases reimbursed. If you requested it, you weren’t getting reimbursed. What we’ve seen now is an evolution. We won the fight, in my opinion, to where broad molecular profiling is now increasingly being covered given new FDA approvals and acceptance that we need all that genetic testing to optimize our therapeutic recommendations. So, there are fewer barriers to approval and to payment when doing molecular profiling in all cancers.

Transcript edited for clarity.

May 2017

  • A 64-year-old female was diagnosed with locally advanced pancreatic adenocarcinoma and referred for consultation at a high-volume center
  • CT with contrast showed a 2.8-cm mass in the pancreatic body, invading the common hepatic, celiac, and splenic arteries, with abutment more than 180° to the superior mesenteric artery (SMA) but no encasement
  • Staging laparoscopy showed no distant metastasis; peritoneal washing cytology showed no malignant cells
  • She received FOLFIRINOX followed by capecitabine and concurrent RT

December 2017

  • Six months after the initial treatment, the tumor size had decreased to 1.2 cm, and abutment to the main artery was diminished but still detectable
  • She underwent distal pancreatectomy with celiac artery resection
  • Histopathology showed fibrous changes around the celiac artery; Evans grade IIb
  • No evidence of residual tumor at the periphery; R0