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. 2024 Jan 17:17:17562848231224943.
doi: 10.1177/17562848231224943. eCollection 2024.

Echoendoscopic ultrasound pancreatic adenocarcinoma diagnosis and theranostic approach: should KRAS mutation research be recommended in everyday practice?

Dominique Béchade  1 , Lola-Jade Palmieri  2 , Benjamin Bonhomme  3 , Simon Pernot  2   4 , Jeanne Léna  2 , Marianne Fonck  2 , Sophie Pesqué  2   5 , Gautier Boillet  2 , Antoine Italiano  2   4 , Gilles Roseau  6
Affiliations

Echoendoscopic ultrasound pancreatic adenocarcinoma diagnosis and theranostic approach: should KRAS mutation research be recommended in everyday practice?

Dominique Béchade et al. Therap Adv Gastroenterol. .

Abstract

Background: The impact of KRAS mutation testing on pancreatic ductal adenocarcinoma (PDAC) samples by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for reducing the need to repeat EUS-FNA has been demonstrated. Such testing however is not part of standard practice for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB).

Objectives: We aim to analyse the proportion of non-contributive samples by EUS-FNB and to evaluate the impact of KRAS mutation testing on the diagnosis, theranostics and survival.

Design: In this retrospective study, the impact on diagnosis and survival of KRAS testing for contributive and non-contributive samples by EUS-FNB was analysed.

Methods: The EUS-FNB samples, combined with KRAS testing using the Idylla® technique on liquid-based cytology from patients with PDAC between February 2019 and May 2023, were retrospectively reviewed. The cytology results were classified according to the guidelines of the World Health Organization System for Reporting Pancreaticobiliary Cytopathology (WHOSRPC).

Results: A total of 85 EUS-FNB specimens were reviewed. In all, 25 EUS-FNB samples did not lead to a formal diagnosis of PDAC according to the WHOSRPC (30.2%). Out of these 25, 11 (44%) could have been considered positive for a PDAC diagnosis thanks to the KRAS mutation test without carrying out further diagnosis procedures. The sensitivity of KRAS mutation testing using the Idylla technique was 98.6%. According to the available data, survival rates were not statistically different depending on the type of mutation.

Conclusion: KRAS mutation testing on liquid-based cytology using the Idylla or equivalent technique, combined with the PDAC EUS-FNB sample, should become a standard for diagnosis to avoid delaying treatment by doing another biopsy. Furthermore, knowledge of the KRAS status from treatment initiation could be used to isolate mutations requiring targeted treatments or inclusion in clinical research trials, especially for wild-type KRAS PDAC.

Keywords: EUS-FNB; Idylla® test; KRAS mutation; next-generation sequencing; pancreatic cancer diagnosis; pancreatic cancer treatment; pancreatic ductal adenocarcinoma; theranostic impact.

Plain language summary

Diagnostic and theranostic interest of searching for a KRAS mutation in echoendoscopic ultrasound biopsies of pancreatic adenocarcinomas The echoendoscopic ultrasound diagnostic of pancreatic adenocarcinomas sometimes remains difficult due to the nature of these tumors with a particular microenvironment. For more than 30 years, several authors have underlined the importance of searching for a KRAS mutation on samples taken by echoendoscopic ultrasound to improve diagnostic performance. However, this research is not common practice. Our retrospective study made it possible to review the files of 85 patients with pancreatic adenocarcinoma in whom an echoendoscopic ultrasound biopsy was performed with a search for the KRAS mutation (with second-generation fine needle biopsy). Forty-four percent could have been considered positive for the diagnosis of PDAC thanks to the search for the KRAS mutation without repeating new samples. Furthermore, knowledge of the KRAS mutation type from diagnosis would make it possible to isolate mutations justifying possible targeted treatments.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Flow chart of the study participants. EUS, endoscopic ultrasound; FNB, fine-needle biopsy; NGS, next-generation sequencing; WHOSRPC, World Health Organization System for Reporting Pancreaticobiliary Cytopathology.
Figure 2.
Figure 2.
Category 7: Well-differentiated adenocarcinomatous proliferation with pancreato-biliary morphology. Some fragments of a fibrous stroma are visible, containing tumour-like glands, indicating the infiltrating nature.
Figure 3.
Figure 3.
Category 1: Haemorrhagic suffusions with fibrous fragments and gastrointestinal contaminants.
Figure 4.
Figure 4.
Category 3: Epithelial atypia within subacute inflammatory changes for which it is difficult to tell the difference between dystrophy and dysplasia.
Figure 5.
Figure 5.
Category 5: Cribriform and adenomatoid structures with mucin-secreting cells or eosinophils with nucleolated atypical nuclei with loss of nuclear polarity.
Figure 6.
Figure 6.
Category 6: Hematic material with a fragment of fibro-hyalin tissue comprising some isolated atypical cells.
See this image and copyright information in PMC

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