Struggle to Find a Role for Radiotherapy in Pancreatic Cancer

M. Alexander Otto, PA, MMS

July 20, 2022

Radiotherapy continues to be the odd man out in pancreatic cancer, according to Daniel Ahn, DO, and Tanios Bekaii-Saab, MD, medical oncologists at the Mayo Clinic in Phoenix, Arizona.

"While perioperative chemotherapy has been shown to be an effective strategy and is integral in managing localized pancreas cancer, the clinical benefit from adding radiotherapy" remains "unproven," they say.

Studies may one day "define a role in a select subgroup of patients," but for now, "there is very little evidence to support the use of radiotherapy in nonmetastatic adenocarcinoma of the pancreas," they write in an editorial published on July 14 in JAMA Oncology.

The editorial accompanies an article that reports negative results from a trial that actually found that adding radiotherapy to neoadjuvant chemotherapy was potentially detrimental for patients with borderline resectable tumors.

"Notable" Findings With Stand-Alone mFOLFIRINOX

This was the A021501 phase 2 randomized clinical trial (NCT02839343), from investigators led by Matthew Katz, MD, a surgical oncologist at the MD Anderson Cancer Center in Houston, Texas.

In this trial, 70 patients were randomly assigned to receive eight cycles of neoadjuvant mFOLFIRINOX (oxaliplatin, irinotecan, leucovorin, and infusional fluorouracil), and 56 patients were assigned to receive seven cycles of neoadjuvant mFOLFIRINOX followed by stereotactic body radiotherapy (33–40 Gy in five fractions) or hypofractionated image-guided radiotherapy (25 Gy in five fractions) before pancreatectomy.

For both groups, surgery was followed by additional chemotherapy.

Among the first 30 evaluable patients enrolled in each arm, 17 in the chemotherapy-alone group (57%) went on to undergo R0 resection, vs 10 (33%) who received add-on radiotherapy, which led to early closure of the radiotherapy arm.

Overall survival at 18 months among evaluable patients was 66.7% in the chemotherapy arm but just 47.3% in the chemotherapy-plus-radiotherapy group.

Median overall survival was 29.8 months with stand-alone mFOLFIRINOX ― which the investigators called "notable," given historical outcomes ― vs just 17.1 months with the addition of radiotherapy.

These findings establish mFOLFIRINOX as "a reference neoadjuvant treatment regimen for borderline resectable pancreatic cancer," the investigators comment.

However, "we could not conclude" that adding radiotherapy "was effective," they say.

Previous studies have yielded findings that are similar when radiotherapy comes after surgery.

"While advances in adjuvant systemic chemotherapy have translated into a gradual improvement in overall survival of patients with resected pancreas cancer, there has been no measurable clinical benefit from the addition of radiation," Ahn and Bekaii-Saab say.

However, the struggle to find patients who might benefit from radiotherapy continues, the editorialists comment.

There are studies, for instance, that have found higher R0 resection rates for patients with locally advanced pancreatic ductal adenocarcinoma with modern radiotherapy techniques, but "unfortunately," they were "limited to single-institution retrospective studies at high-volume centers, thus limiting their general interpretability and applicability," the editorialists note.

A subgroup analysis of the PREOPANC trial also suggested a potential benefit from more conventional add-on radiotherapy for patients with borderline resectable disease, but in that study, neoadjuvant gemcitabine monotherapy was used instead of the current standard of gemcitabine/capecitabine or FOLFIRINOX.

"Ongoing clinical trials will hopefully provide further insight on the role" of chemoradiotherapy "in these settings," they say.

The trial was sponsored by the National Cancer Institute. Katz has disclosed no relevant financial relationships. Other investigators and the editorialists, have a variety of ties to many companies, including AstraZeneca, Boehringer Ingelheim, and Celgene.

JAMA Oncol. Published online July 14, 2022. Abstract, Editorial

M. Alexander Otto is a physician assistant with a master's degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape and is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.

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