Celiac plexus radiosurgery for pain management in advanced cancer: a multicentre, single-arm, phase 2 trial.

Background: Refractory upper abdominal pain or lower back pain (retroperitoneal pain syndrome) related to celiac plexus involvement characterises pancreatic and other upper gastrointestinal malignancies and is an unmet need. We hypothesised that ablative radiation delivered to the celiac plexus would decrease pain.
Methods: This multicentre, single-arm, phase 2 study was done at eight hospitals in five countries (Israel, Poland, Canada, the USA, and Portugal). Eligible patients aged 18 years or older with an average pain level of 5-10 on the Brief Pain Inventory short form (BPI-SF), an Eastern Cooperative Oncology Group performance status score of 0-2, and either pancreatic cancer or other tumours involving the celiac axis, received a single fraction of 25 Gy of external-beam photons to the celiac plexus. The primary endpoint was complete or partial pain response based on a reduction of the BPI-SF average pain score of 2 points or more from baseline to 3 weeks after treatment. All evaluable patients with stable pain scores were included in response assessment. The trial is registered with ClinicalTrials.gov, NCT03323489, and is complete.
Findings: Between Jan 3, 2018, and Dec 28, 2021, 125 patients were treated, 90 of whom were evaluable. Patients were followed up until death. Median age was 65·5 years (IQR 58·3-71·8), 50 (56%) were female and 40 (44%) were male, 83 (92%) had pancreatic cancer, and 77 (86%) had metastatic disease. Median baseline BPI-SF average pain score was 6 (IQR 5-7). Of the 90 evaluable patients at 3 weeks, 48 (53%; 95% CI 42-64) had at least a partial pain response. The most common grade 3-4 adverse events, irrespective of attribution, were abdominal pain (35 [28%] of 125) and fatigue (23 [18%]). 11 serious adverse events of grade 3 or worse were recorded. Two grade 3 serious adverse events were probably attributed to treatment by the local investigators (abdominal pain [n=1] and nausea [n=1]), and nine were possibly attributed to treatment (seven were grade 3: blood bilirubin increased [n=1], duodenal haemorrhage [n=2], abdominal pain [n=2], and progressive disease [n=2]; and two were grade 5: gastrointestinal bleed from suspected varices 24 days after treatment [n=1] and progressive disease [advanced pancreatic cancer] 89 days after treatment [n=1]).
Interpretation: Celiac plexus radiosurgery could potentially be a non-invasive palliative option for patients with retroperitoneal pain syndrome. Further investigation by means of a randomised comparison with conventional celiac block or neurolysis is warranted.
Funding: Gateway for Cancer Research and the Israel Cancer Association.
Competing Interests: Declaration of interests YRL reports receiving grant funding for this study from Gateway for Cancer Research and the Israel Cancer Association; has received research funding for other studies from Karyopharm Therapeutics, Checkmate Pharmaceuticals (purchased by Regeneron Pharmaceuticals), and Bristol-Myers Squibb; and has received honoraria from Roche Genetech, and has stock ownership in Protean Biodiagnostics. LAD reported being past president and chair of the American Society for Radiation Oncology; had a licensing agreement with Raysearch during the accrual for the present study; and has accepted honoraria from AstraZeneca. LSF reported his institution receiving payment from Gateway for Cancer Research; has clarified that he was at first chairman of the data and safety monitoring board for this trial, and later switched to be the statistician of the data and safety monitoring board; no separate payments were made to him or to his institution for this work. ASB reported having received an honorarium from Eisai. DADP reported having received payment or honoraria from the American Society of Clinical Oncology and travel support from the American Society for Radiation Oncology. All other authors declare no competing interests.
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