The Role of Radiation Therapy in Treating Locally Advanced Pancreatic Cancer

At the 2023 World Congress on Gastrointestinal Cancers in Barcelona, Spain, Florence Huguet, MD, PhD, debated in favor of the role of radiation therapy in the treatment of locally advanced pancreatic cancer.  

Dr Huguet discussed the importance of getting patients to a resectable status, the advances for stereotactic body radiation therapy, and the need for a biomarker to select patients in this population for radiation therapy.

Transcript:

Hello. I'm Florence Huguet. I'm the head of radiation oncology department in Tenon Hospital at Sorbonne University in Paris. I had the chance to debate at the 2023 World Congress on Gastrointestinal Cancers about the role of radiation therapy in the treatment of locally advanced pancreatic cancer. The debate was quite hard, because my opponent was Professor Philip Philip, MD, [AC1] from [Wayne State University] Detroit, [Michigan] and he has some very good arguments, but I have mine to advocate for radiation therapy.

For locally advanced pancreatic cancer, there isn't a standard treatment. The patients with locally advanced pancreatic cancer have a high risk of metastasis, so they need chemotherapy, no discussion about that. But local control remains an important issue too because we know that almost 1/3 of the patients will die with a locally destructive only disease. For local control, the best treatment is radiation therapy. Chemotherapy and radiation therapy have been compared in different trials with very contradictory results.

In France 10 years ago, we started to think that combining an induction chemotherapy followed by chemoradiation for the non-progressive patients could be a good idea, rather than opposite chemotherapy and chemoradiation. That's why we did the LAP07 trial. Unfortunately, there was no benefit in overall survival in the patients who received chemoradiation after induction chemotherapy. These results were confirmed last year in ASCO by the CONKO-007 trial, a German trial with almost the same design that LAP07 trial.

But what was interesting in this trial, is that they looked to the resection rate. It was the same in the chemotherapy arm and in the chemoradiation arm, but in the chemoradiation arm there was a lot of R0 resection, it was significantly higher, and there was some pathological complete response and there was none in the chemotherapy arm. In this trial, the resected patients had a longer survival than the other group. I think it's a very important point. I think that for locally advanced pancreatic cancer, we should try to push the treatment to send these patients to the operative room, as it's their only chance to have a prolonged survival.

How can we intensify our treatments to make more patients resectable? One way could be to increase the dose of radiation therapy. It's now possible with the new radiation techniques as SBRT, stereotactic body radiation therapy. With this technique, we can deliver a higher dose to the tumor, while protecting the at-risk organs around. The first studies with SBRT were quite disappointing in terms of overall survival, even if the local control was very high. Now, we have a new way to deliver SBRT with LINAC [linear accelerator] combined with MRI. It's called SMART, and it is stereotactic MRI-guided radiation therapy. With this technique we can deliver even higher doses. We have already the results of a phase 2 study showing very promising results. In few days in July, we’ll start a phase 3 trial titled LAP-ABLATE will start and will compare chemotherapy, versus chemotherapy followed by SMART, a high dose SBRT at a dose of 50 Gy in 5 fractions.

Beside these evolutions, I strongly believe that some of our patients will benefit from radiation therapy, but we don't know how to identify them. We need to work to try to find some biomarkers to identify these patients better. We have a lot of work still to do for locally advanced pancreatic cancer patients.

Source:

Huguet, Florence. Radiotherapy in Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC). Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain.