Celiac plexus radiosurgery for pain management in advanced cancer: a multicentre, single-arm, phase 2 trial - 17/07/24

Doi : 10.1016/S1470-2045(24)00223-7

Yaacov R Lawrence, MBBS FASTRO ^a,^n,^o,⁎ , Marcin Miszczyk, MD PhD ^f,^h, Laura A Dawson, MD ^q, Dayssy Alexandra Diaz Pardo, MD ^p, Artur Aguiar, MD ^e, Dror Limon, MD ⁱ, Raphael M Pfeffer, MBBS ^d, Michael Buckstein, MD PhD ^j, Aisling S Barry, ProfMB BCh ^k,^l, Tikva Meron, PhD ^b, Adam P Dicker, ProfMD PhD ^o, Jerzy Wydmański, MD PhD ^g, Camilla Zimmermann, MD PhD ^r, Ofer Margalit, MD PhD ^b,ⁿ, David Hausner, MD ^c,ⁿ, Ofir Morag, MD ^b,ⁿ, Talia Golan, ProfMD ^b,ⁿ, Galia Jacobson, MD ⁱ, Sergey Dubinski, PhD ^a, Teo Stanescu, PhD ^q, Ronen Fluss, PhD ^m, Laurence S Freedman, ProfPhD ^m, Maoz Ben-Ayun, PhD ^a, Zvi Symon, ProfMD ^a,ⁿ

^a Department of Radiation Oncology, Sheba Medical Center, Ramat Gan, Israel

^b Department of Medical Oncology, Sheba Medical Center, Ramat Gan, Israel

^c Department of Palliative Care, Sheba Medical Center, Ramat Gan, Israel

^d Department of Radiation Oncology, Assuta Medical Center, Tel Aviv, Israel

^e Department of Radiation Oncology, Instituto Português de Oncologia, Porto, Portugal

^f III Department of Radiotherapy and Chemotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland

^g Department of Radiation Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland

^h Collegium Medicum, Faculty of Medicine, WSB University, Dąbrowa Górnicza, Poland

ⁱ Department of Radiation Oncology, Rabin Medical Center, Petah Tikvah, Israel

^j Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

^k Cancer Research @UCC, University College Cork, Cork, Ireland

^l Department of Radiation Oncology, Cork University Hospital, Cork, Ireland

^m The Biostatistics and Biomathematics Unit, The Gertner Institute for Health Policy and Epidemiology, Sheba Medical Center, Ramat Gan, Israel

ⁿ School of Medicine, Tel Aviv University, Tel Aviv, Israel

^o Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA

^p Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA

^q Department of Radiation Oncology, Princess Margaret Hospital Cancer Centre, University of Toronto, Toronto, ON, Canada

^r Department of Supportive Care, Princess Margaret Hospital Cancer Centre, University of Toronto, Toronto, ON, Canada

^* Correspondence to: Dr Yaacov R Lawrence, Department of Radiation Oncology, Sheba Medical Center, Ramat Gan 52621, Israel Department of Radiation Oncology Sheba Medical Center Ramat Gan 52621 Israel

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 17 July 2024
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Summary

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.