Stereotactic radiotherapy more than halved local recurrence in high-risk pancreatic cancer

Design

Open-label randomised phase 2 trial, closed early

Population

74 adults with high-risk localised pancreatic ductal adenocarcinoma

Primary outcome

12-month locoregional recurrence

Effect

20.2% vs 52.0%; subdistribution HR 0.44 (95% CI 0.22–0.88)

MASTERPLAN, an open-label phase 2 trial at 14 hospitals in Australia and New Zealand, randomised patients with high-risk localised pancreatic cancer — large, node-positive, borderline resectable or locally advanced — 2:1 to perioperative chemotherapy (mFOLFIRINOX or gemcitabine with nab-paclitaxel) with or without stereotactic body radiotherapy, 40 Gy in five fractions.

It closed early for slow accrual after 74 of 120 planned patients. At a median 3.2 years, 12-month locoregional recurrence was 20% with radiotherapy and 52% without (subdistribution HR 0.44). Severe adverse events were similar, and two serious events were attributed to radiotherapy.

Local recurrence is common in pancreatic cancer, and earlier conventional chemoradiotherapy trials were disappointing. Short-course stereotactic radiotherapy, delivered with real-time quality assurance, offers a more focused option.

The trial was small and stopped early, and locoregional control is not survival. It supports a phase 3 trial rather than routine use.

• Discuss high-risk localised pancreatic cancer at a multidisciplinary meeting that includes radiation oncology.
• Consider trial enrolment for stereotactic radiotherapy with perioperative chemotherapy where available.
• Keep multi-agent perioperative chemotherapy as the backbone of treatment.
• Do not offer stereotactic radiotherapy routinely on this phase 2 evidence alone.

Why it matters

It revives radiotherapy as a serious question in localised pancreatic cancer.

Don't overread it

A small, early-stopped phase 2 trial; it does not show longer survival.

The statistics, in plain English

A subdistribution hazard ratio of 0.44 accounts for patients dying before recurrence. The confidence interval (0.22 to 0.88) is wide because only 74 patients were randomised, and early closure makes the estimate less stable.

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