Endoscopic ultrasound as a reliable tool for assessment of pancreatic adenocarcinoma treatment: Example of in situ gene therapy

Abstract

Background and study aims In pancreatic cancer, the antitumor effect can only be assessed by means of a computed tomography (CT) scan using RECIST (Response Evaluation Criteria in Solid Tumours) criteria. The aim of this study was to assess the intra-observer and interobserver agreement of endoscopic ultrasound (EUS) imaging in assessing tumor volume in primary pancreatic cancer.

Patients and methods During a Phase 1 gene therapy trial, 21 patients had EUS before the first and second EUS-guided in situ gene therapy injections. All anonymized EUS files were then randomly distributed to three gastroenterologists/endosonographers and three radiologists (blind status). The largest tumor diameter was measured and the intraclass correlation coefficient (ICC) was determined.

Results Intra-observer and interobserver agreements were good to excellent, regardless of operator experience (junior versus senior member of staff) (ICC: 0.65 to 0.84). A comparison of pretreatment and post-treatment measurements by the investigators highlighted a significant antitumor effect (–11 %; P = 0.0098), similar to that obtained during the generic protocol (–10 %; P = 0.0045).

Conclusions Interobserver agreement regarding primary pancreatic adenocarcinoma measurements appears good to excellent, thus paving the way for the future inclusion of EUS assessments, particularly in trials assessing local therapies for pancreatic tumors.

Publication History

Received: 15 November 2021

Accepted after revision: 17 February 2022

Article published online:
10 June 2022

• References

• 1 Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med 2014; 371: 2140-2141
• 2 Rahib L, Smith BD, Aizenberg R. et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014; 74: 2913-2921
• 3 Burris 3rd HA, Moore MJ, Andersen J. et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15: 2403-2413
• 4 Conroy T, Desseigne F, Ychou M. et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364: 1817-1825
• 5 Von Hoff DD, Ervin T, Arena FP. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369: 1691-1703
• 6 Rouanet M, Lebrin M, Gross F. et al. Gene therapy for pancreatic cancer: specificity, issues and hopes. int J Mol Sci 2017; 18: E1231
• 7 Buscail L, Bournet B, Vernejoul F. et al. First-in-man phase 1 clinical trial of gene therapy for advanced pancreatic cancer: safety, biodistribution, and preliminary clinical findings. Mol Ther 2015; 23: 779-789
• 8 Krishna SG, Brugge WR, Dewitt JM. et al. Needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cystic lesions: an international external interobserver and intraobserver study (with videos). Gastrointest Endosc 2017; 86: 644-654.e2
• 9 Napoleon B, Lemaistre AI, Pujol B. et al. In vivo characterization of pancreatic cystic lesions by needle-based confocal laser endomicroscopy (nCLE): proposition of a comprehensive nCLE classification confirmed by an external retrospective evaluation. Surg Endosc 2016; 30: 2603-2612
• 10 Soares JB, Iglesias-Garcia J, Gonçalves B. et al. Interobserver agreement of contrast-enhanced harmonic endoscopic ultrasonography in the evaluation of solid pancreatic lesions. Endosc Int Open 2015; 3: E205-E209
• 11 Del Pozo D, Poves E, Tabernero S. et al. Conventional versus Rosemont endoscopic ultrasound criteria for chronic pancreatitis: interobserver agreement in same day back-to-back procedures. Pancreatology 2012; 12: 284-287
• 12 de Jong K, Verlaan T, Dijkgraaf MG. et al. Interobserver agreement for endosonography in the diagnosis of pancreatic cysts. Endoscopy 2011; 43: 579-584
• 13 Stevens T, Lopez R, Adler DG. et al. Multicenter comparison of the interobserver agreement of standard EUS scoring and Rosemont classification scoring for diagnosis of chronic pancreatitis. Gastrointest Endosc 2010; 71: 519-526
• 14 Fabbri C, Baron T, Gibiino G. et al. Endoscopic ultrasound features of pancreatic fluid collection and their impact on therapeutic decision: interobserver agreement study. Endoscopy 2021; DOI: 10.1055/a-1640-4365.
• 15 Rustagi T, Chhoda A. Endoscopic radiofrequency ablation of the pancreas. Dig Dis Sci 2017; 62: 843-850
• 16 Barthet M, Giovannini M, Gasmi M. et al. Long-term outcome after EUS-guided radiofrequency ablation: Prospective results in pancreatic neuroendocrine tumors and pancreatic cystic neoplasms. Endosc Int Open 2021; 9: E1178-E1185
• 17 Luo XM, Niu LZ, Chen JB. et al. Advances in cryoablation for pancreatic cancer. World J Gastroenterol 2016; 22: 790-800
• 18 Hajda J, Leuchs B, Angelova AL. et al. Phase 2 trial of oncolytic H-1 parvovirus therapy shows safety and signs of immune system activation in patients with metastatic pancreatic ductal adenocarcinoma. Clin Cancer Res 2021; 27: 5546-5556
• 19 Buscail L, Bournet B, Cordelier P. Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer. Nat Rev Gastroenterol Hepatol 2020; 17: 153-168