Combined chemotherapy and endoscopic ultrasound-guided intratumoral 32P implantation for locally advanced pancreatic adenocarcinoma: a pilot study

Abstract

Background This study evaluated clinical outcomes of combined chemotherapy and endoscopic ultrasound (EUS)-guided intratumoral radioactive phosphorus-32 (³²P) implantation in locally advanced pancreatic adenocarcinoma (LAPC).

Methods Consecutive patients with newly diagnosed LAPC were recruited over 20 months. Baseline computed tomography and ¹⁸F-2-fluoro-2-deoxy-D-glucose (¹⁸FDG) positron emission tomography–computed tomography were performed and repeated after 12 weeks to assess treatment response. Following two cycles of conventional chemotherapy, patients underwent EUS-guided ³²P implantation followed by six chemotherapy cycles.

Results 12 patients with LAPC (median age 69 years [interquartile range 61.5–73.3]; 8 male) completed treatment. Technical success was 100 % with no procedural complications. At 12 weeks, median reduction in tumor volume was 8.2 cm³ (95 % confidence interval 4.95–10.85; P = 0.003), with minimal or no ¹⁸FDG uptake in nine patients (75 %). Tumor downstaging was achieved in six patients (50 %), leading to successful resection in five (42 %), including four R0 resections (80 %).

Conclusions EUS-guided ³²P implantation was feasible, well tolerated, and resulted in a 42 % surgical resection rate. Further evaluation in a larger randomized multicenter trial is warranted.

• References

• 1 Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol 2019; 10: 10-27
• 2 Neoptolemos JP, Kleeff J, Michl P. et al. Therapeutic developments in pancreatic cancer: current and future perspectives. Nat Rev Gastroenterol Hepatol 2018; 15: 333-348
• 3 Torgeson A, Lloyd S, Boothe D. et al. Multiagent induction chemotherapy followed by chemoradiation is associated with improved survival in locally advanced pancreatic cancer. Cancer 2017; 123: 3816-3824
• 4 Jin Z, Du Y, Li Z. et al. Endoscopic ultrasonography-guided interstitial implantation of iodine 125-seeds combined with chemotherapy in the treatment of unresectable pancreatic carcinoma: a prospective pilot study. Endoscopy 2008; 40: 314-320
• 5 Sun S, Xu H, Xin J. et al. Endoscopic ultrasound-guided interstitial brachytherapy of unresectable pancreatic cancer: results of a pilot trial. Endoscopy 2006; 38: 399-403
• 6 Gholami YH, Wilson N, James D. et al. Toward personalized dosimetry with 32P microparticle therapy for advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2017; 99: 1029-1038
• 7 Rosemurgy A, Luzardo G, Cooper J. et al. 32P as an adjunct to standard therapy for locally advanced unresectable pancreatic cancer: a randomized trial. J Gastrointest Surg 2008; 12: 682-688
• 8 Ross PJ, Croagh D, Aghmesheh M. et al. PanCO: an open-label, single-arm pilot study of phosphorus-32 (P-32; Oncosil) microparticles in patients with unresectable locally advanced pancreatic adenocarcinoma (LAPC) in combination with FOLFIRINOX or gemcitabine + nab-paclitaxel (GNP) chemotherapies. J Clin Oncol 2019; 37 (15) 4125-4125
• 9 Tempero MA, Malafa MP, Al-Hawary M. et al. Pancreatic adenocarcinoma, version 2. NCCN Clinical Practice Guidelines in Oncology. . J Natl Compr Canc Netw 2017; 15: 1028-1061
• 10 Søreide K, Aagnes B, Møller B. et al. Epidemiology of pancreatic cancer in Norway: trends in incidence, basis of diagnosis and survival 1965–2007. Scand J Gastroenterol 2010; 45: 82-92
• 11 Garcea G, Dennison AR, Pattenden CJ. et al. Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. . JOP 2008; 9: 99-132
• 12 Park HJ, Griffin RJ, Hui S. et al. Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS). Radiat Res 2012; 177: 311-327
• 13 Olive KP, Jacobetz MA, Davidson CJ. et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009; 324: 1457-1461
• 14 Ye J, Mills BN, Zhao T. et al. Assessing the magnitude of immunogenic cell death following chemotherapy and irradiation reveals a new strategy to treat pancreatic cancer. Cancer Immunol Res 2020; 8: 94-107