Successful creation of pancreatic cancer organoids by means of EUS-guided fine-needle biopsy sampling for personalized cancer treatment

Tiriac, Hervé; Bucobo, Juan Carlos; Tzimas, Demetrios; Grewel, Suman; LaComb, Joseph F.; Rowehl, Leahana; Nagula, Satish; Wu, Maoxin; Kim, Joseph; Sasson, Aaron R.; Vignesh, Shivakumar; Martello, Laura; Muñoz-Sagastibelza, María; Somma, Jonathan; Tuveson, David A.; Li, Ellen; Buscaglia, Jonathan M.

doi:10.1016/j.gie.2017.12.032

Cited by 129 publications

(134 citation statements)

References 29 publications

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“…A recent study concluded that EUS‐FNB specimens of PDAs were adequate for mismatch repair protein and programmed death ligand‐1 immunohistochemistry in 97.2% and 94.9% cases, respectively . Tiriac and colleagues have even shown that pancreatic cancer organoids can be successfully created from FNB samples at the time of initial tissue diagnosis for enhancing personalized treatment options …”

Section: Discussionmentioning

confidence: 99%

“…26 Tiriac and colleagues have even shown that pancreatic cancer organoids can be successfully created from FNB samples at the time of initial tissue diagnosis for enhancing personalized treatment options. 27 In the non-neoplastic group, autoimmune pancreatitis was given a descriptive diagnosis on FNA. On FNB, however; with intact histologic architecture and sufficient material for IgG and IgG4 IHC, the diagnosis of autoimmune pancreatitis could be made.…”

Section: Discussionmentioning

confidence: 99%

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Endoscopic ultrasound‐guided tissue acquisition of solid mass lesions of the pancreas: A retrospective comparison study of fine‐needle aspiration and fine‐needle biopsy

Sweeney

Soong

Goyal

2020

Diagnostic Cytopathology

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Background Although endoscopic ultrasound guided fine‐needle biopsy (EUS‐FNB) has emerged as an alternative to fine‐needle aspiration (FNA) for the sampling of solid pancreatic mass lesions, it remains unclear which method is more effective. We compared the diagnostic yields of FNA, FNB, and combined FNA/FNB at a tertiary care institution. Methods Specimens from EUS‐FNA (04/2014‐08/2017) and EUS‐FNB (10/2015‐08/2017) with SharkCore needle of pancreatic solid mass lesions were retrieved. Clinical, radiologic, and pathologic data was recorded. Pathology results of malignancy/neoplasms with uncertain malignant potential were considered as true positive. The “negative” cases included were with ≥6 months of follow‐up. Nondiagnostic cases showed unremarkable pancreatic tissue, nonpancreatic elements, atypia, or features suspicious for malignancy. Diagnostic yield was defined as percentage of lesions sampled in which a benign or malignant tissue diagnosis, as defined above, was obtained. Statistical comparisons were performed using Fisher's exact test and univariable and multivariable logistic regression analysis. Results The study cohort included 76 FNA only cases, 88 FNB only cases, and 40 combined FNA/FNB cases. Diagnostic yields were 70% (FNA), 70% (FNB), and 83% (FNA/FNB), which were not statistically different. Increase in lesion size and presence of ROSE were significantly associated with a diagnostic outcome on both univariable and multivariable analysis, unlike the number of passes. Conclusion Our results demonstrate that for solid pancreatic lesions, the diagnostic yields of FNA, FNB, and combined FNA and FNB are comparable. Presence of ROSE and increasing lesion size increased the diagnostic yield while the number of passes had no significant impact.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Endoscopic ultrasound‐guided tissue acquisition of solid mass lesions of the pancreas: A retrospective comparison study of fine‐needle aspiration and fine‐needle biopsy

Sweeney

Soong

Goyal

2020

Diagnostic Cytopathology

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“…Organoids also recapitulate biological features of a 3D environment, as demonstrated in pancreatic, colorectal, prostate and mammary cancers (12) (13) (14) (15). Importantly, PDAC organoids can be grown with a high rate of success from very small amounts of tissue collected from diagnostic fine-needle biopsies (16,17), core needle biopsies, and in excisional intraoperative biopsies and these tissues are more likely to be passaged over time when grown in 3D versus 2D cultures (18) (19) (16) (17). Some barriers to the use of organoids in personalized therapies include lack of in-depth assessment of the histopathology, genetic stability, and molecular profiling of organoid models.…”

Section: Introductionmentioning

confidence: 97%

Pancreatic adenocarcinoma human organoids share structural and genetic features with primary tumors

Calvo

Weber

Ray

et al. 2018

Preprint

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Patient-derived pancreatic ductal adenocarcinoma (PDAC) organoid systems show great promise for understanding the biological underpinnings of disease and advancing therapeutic precision medicine. Despite the increased use of organoids, the fidelity of molecular features, genetic heterogeneity, and drug response to the tumor of origin remain important unanswered questions limiting their utility. To address this gap in knowledge, we created primary tumor- and PDX-derived organoids, and 2D cultures for in-depth genomic and histopathological comparisons to the primary tumor. Histopathological features and PDAC representative protein markers showed strong concordance. DNA and RNA sequencing of single organoids revealed patient-specific genomic and transcriptomic consistency. Single-cell RNAseq demonstrated that organoids are primarily a clonal population. In drug response assays, organoids displayed patient-specific sensitivities. Additionally, we examined the in vivo PDX response to FOLFIRINOX and Gemcitabine/Abraxane treatments, which was recapitulated in vitro by organoids. The patient-specific molecular and histopathological fidelity of organoids indicate that they can be used to understand the etiology of the patient’s tumor and the differential response to therapies and suggests utility for predicting drug responses.

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“…PDACs demonstrate only 5 % to 20 % neoplastic cellularity and are characterized by a prominent desmoplastic reaction considered to be a hostile tumor microenvironment (TME) for subsequent therapy 11 12 . Cytology smears are thought to be superior for multiplex gene panel NGS evaluations, as their overall cellularity, tumor fraction, and sequencing metrics are considered to be superior to that of FNB, yet, successful preclinical disease models to include organoid development require that EUS-FNB deliver tumor cells and the corresponding TME 13 14 15 . …”

Section: Discussionmentioning

confidence: 99%

EUS fine-needle pancreatic core biopsy can determine eligibility for tumor-agnostic immunotherapy

et al. 2018

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Background and study aims The US FDA recently approved a cancer treatment with pembrolizumab based upon the tumor biomarker status of deficient mismatch repair (dMMR) rather than a specific disease-based approach. We sought to determine if endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) could determine dMMR and quantification of PD-L1 expression to potentially guide the delivery of tumor agnostic immunotherapy. Patients and methods Immunohistochemistry was performed on archived pancreas core biopsy specimens. Tumors with absent nuclear staining of DNA mismatch repair proteins represented dMMR. Tumors were considered to have any or high PD-L1 expression, if expressed in ≥ 1 % or ≥ 50 % of tumor cells. Results Histologic specimen adequacy for MMR status assessment was satisfactory in 97.2 % of tumors. dMMR and high PD-L1 expression was identified in 3 % and 8.1 % of the cohort. Conclusion In the setting of tumor type agnostic immunotherapy, it is projected that at least 3 % of malignant pancreas lesions will be sensitive to pembrolizumab and up to 8 % sensitive to the family of immune checkpoint inhibitors. This highlights the expanding role of EUS-FNB in the field of precision immuno-oncology.

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Successful creation of pancreatic cancer organoids by means of EUS-guided fine-needle biopsy sampling for personalized cancer treatment

Cited by 129 publications

References 29 publications

Endoscopic ultrasound‐guided tissue acquisition of solid mass lesions of the pancreas: A retrospective comparison study of fine‐needle aspiration and fine‐needle biopsy

Endoscopic ultrasound‐guided tissue acquisition of solid mass lesions of the pancreas: A retrospective comparison study of fine‐needle aspiration and fine‐needle biopsy

Pancreatic adenocarcinoma human organoids share structural and genetic features with primary tumors

EUS fine-needle pancreatic core biopsy can determine eligibility for tumor-agnostic immunotherapy

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