For patients receiving ablative radiotherapy for inoperable pancreatic ductal adenocarcinoma (PDAC), an expanded treatment area may improve local disease control, a retrospective cohort study found.

Among 121 consecutive patients, nearly all of whom received definitive MR-guided radiotherapy with a clinical target volume (CTV) design, only 14% experienced locoregional failure at a median follow-up of 14 months. And among 36 patients given radiotherapy to the widest treatment area — the “triangle volume” — none experienced locoregional failure.

“These are among the lowest, if not the lowest, locoregional failure rates that have been published to date,” said lead researcher Michael Chuong, MD, of Florida International University and Miami Cancer Institute, Miami.

Typically, about half of patients have locoregional failure within 2 years of treatment with pancreatic stereotactic body radiation therapy (SBRT). Expanding the radiotherapy treatment area allows for microscopic-disease targeting, and potentially better local control, Chuong noted in an interview with Medscape Medical News.

“As a field,” he said, “we should be thinking about not just treating the gross tumor but also electively covering other areas for microscopic disease control.”

A radiation oncologist who was not involved in the study called it “critically important.”

“This study further defines the best way to have a complete strategy to treat not only the local tumor, but the extensions of the local tumor along the vessels and the lymph nodes,” Christopher Crane, MD, of Memorial Sloan Kettering Cancer Center in New York City, told Medscape Medical News.

Chuong and his colleagues reported the findings in the International Journal of Radiation Oncology, Biology, Physics.

A Wider Treatment Target

Roughly one third of patients with pancreatic cancer have a locally advanced form without metastases and are not eligible for surgery. For many of those patients, Chuong said, it’s not the tumor size that precludes surgery but its relationship to major abdominal blood vessels.

SBRT is an increasingly used alternative, but the approach has traditionally been conservative in both radiation dose and target volume — with guidelines recommending treatment of the gross tumor alone, without elective coverage of areas at risk for microscopic disease.

Chuong said researchers at his center and others have been investigating more aggressive strategies.

“The tumors that I treat get probably 3-4 times higher than the highest radiation dose that most other radiation oncologists are giving,” he said. “We’re truly ablating these tumors.”

In a multicenter phase 2 study published in 2024, Chuong and colleagues reported on the use of their treatment strategy, dubbed stereotactic MR-guided adaptive radiation therapy (SMART). Over a median follow-up of 14.2 months post-radiotherapy, 2-year overall survival was 40.5% — “notably higher” than what’s been reported with nonablative SBRT, the researchers reported. 

For the new study, Chuong’s team conducted a retrospective analysis of patients with nonmetastatic PDAC who received definitive MR-guided ablative SBRT between 2018 and 2024. Most (87.6%) had received induction chemotherapy, and nearly all (93%) were treated with some elective CTV coverage.

The CTV strategy evolved over time, with patients initially receiving radiotherapy to a limited area (involved vessels at the same axial plane as the gross tumor volume), while those treated in more recent years receiving expanded approaches. That included 36 patients who received treatment to the triangle volume — between the celiac artery, superior mesenteric artery, common hepatic artery, and portal vein/superior mesenteric vein.

The median prescribed gross tumor volume and CTV doses were 50 Gy and 33 Gy in five fractions, respectively.

Locoregional Failure and Survival

At a median follow-up of 14 months, 17 of 121 patients had experienced locoregional failure, including 5 in the primary tumor, 4 in para-aortic lymph nodes, 4 in porta hepatis nodes, 3 at the superior mesenteric artery, and 1 at the celiac artery.

None of the locoregional failures occurred in patients treated to the triangle volume — and that strategy is now standard of care for preoperative and definitive pancreatic SBRT at Miami Cancer Institute, according to Chuong’s team.

The researchers also compared 21 patients who either had no CTV or the most limited variant against 100 patients who had an expanded CTV approach.

The 2-year locoregional failure rates for the two groups were 33% and 21.8%, respectively (P = .521). Two-year distant failure and progression-free survival rates were 83.3% vs 100% (P = .016) and 25% vs 13.6% (P = .063), respectively. Overall survival rate at 2 years was 35% vs 20.9% (P = .142).

An ongoing phase 3 trial, the researchers noted, is looking at whether escalated-dose radiotherapy “meaningfully improves” overall survival in patients with locally advanced PDAC.

As for safety, the SMART approach had a low rate of serious side effects in this study. Acute grade 3 adverse events, including nausea, diarrhea, and bowel obstruction, occurred in 4% of patients who received expanded radiotherapy and in none of those who received no or limited CTV. There were no acute grade 4 or 5 events.

Chuong said that he now prophylactically treats patients with anti-nausea medication before each treatment, which has reduced that side effect.

The researchers acknowledged several limitations of the study, including its retrospective nature and the small number of patients treated with limited or no elective coverage — precluding a robust comparison of outcomes with those in patients who received expanded radiotherapy.

“Our data,” they wrote, “are hypothesis-generating that elective coverage may reduce the incidence of [locoregional failure] and support future studies to more clearly define the long-term clinical impact of incorporating a CTV during ablative SBRT.”

In the meantime, Crane recommended that clinicians considering this approach refer patients to a high-volume center with experience in MR-guided adaptive radiotherapy.

“This treatment has a long learning curve,” he said.

The study had no funding. Chuong disclosed relationships with ViewRay, Novocure, StratPharma, and other sources. Additional disclosures are listed in the published paper. Crane disclosed having a relationship with Elekta.