Single-Pass vs 2-Pass Endoscopic Ultrasound-Guided Fine-Needle Biopsy Sample Collection for Creation of Pancreatic Adenocarcinoma Organoids

LaComb, Joseph F.; Plenker, Dennis; Tiriac, Hervé; Bucobo, Juan Carlos; DʼSouza, Lionel S.; Khokhar, Asim; Patel, Hardik J.; Channer, Breana; Joseph, Dimitri; Wu, Maoxin; Tuveson, David A.; Li, Ellen; Buscaglia, Jonathan M.

doi:10.1016/j.cgh.2020.02.045

Cited by 18 publications

(22 citation statements)

References 5 publications

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“…Several studies have previously shown that PDOs can be isolated from resection or biopsy specimen derived from the primary tumor or metastases at the time of the primary diagnosis [ 18 , 20 , 34 , 35 , 36 , 37 ]. However, a direct comparison of PDO generation efficacies across studies remains complicated as different definitions of a successful PDO culture establishment exist.…”

Section: Discussionmentioning

confidence: 99%

“…However, a direct comparison of PDO generation efficacies across studies remains complicated as different definitions of a successful PDO culture establishment exist. The latter refers to either the emergence of organoid structures within the first three passages [ 18 ] or the successful propagation beyond passage five [ 34 ], whereas a variable proportion of PDOs fails to expand and provide enough biomaterial for further characterization or drug testing. From a clinical perspective, drug response prediction is the paramount goal of developing such an in vitro tool.…”

Section: Discussionmentioning

confidence: 99%

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A Prospective Feasibility Trial to Challenge Patient–Derived Pancreatic Cancer Organoids in Predicting Treatment Response

Beutel

Schütte

Scheible

et al. 2021

Cancers

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Real-time isolation, propagation, and pharmacotyping of patient-derived pancreatic cancer organoids (PDOs) may enable treatment response prediction and personalization of pancreatic cancer (PC) therapy. In our methodology, PDOs are isolated from 54 patients with suspected or confirmed PC in the framework of a prospective feasibility trial. The drug response of single agents is determined by a viability assay. Areas under the curves (AUC) are clustered for each drug, and a prediction score is developed for combined regimens. Pharmacotyping profiles are obtained from 28 PDOs (efficacy 63.6%) after a median of 53 days (range 21–126 days). PDOs exhibit heterogeneous responses to the standard-of-care drugs, and are classified into high, intermediate, or low responder categories. Our developed prediction model allows a successful response prediction in treatment-naïve patients with an accuracy of 91.1% for first-line and 80.0% for second-line regimens, respectively. The power of prediction declines in pretreated patients (accuracy 40.0%), particularly with more than one prior line of chemotherapy. Progression-free survival (PFS) is significantly longer in previously treatment-naïve patients receiving a predicted tumor sensitive compared to a predicted tumor resistant regimen (mPFS 141 vs. 46 days; p = 0.0048). In conclusion, generation and pharmacotyping of PDOs is feasible in clinical routine and may provide substantial benefit.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Prospective Feasibility Trial to Challenge Patient–Derived Pancreatic Cancer Organoids in Predicting Treatment Response

Beutel

Schütte

Scheible

et al. 2021

Cancers

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“…Aspiration of core tissue with preserved architecture is also beneficial for diagnosis and obtaining a sufficient amount of sample for the organoid establishment and molecular genetic studies. The success rate of PDO establishment from tissues obtained through EUS-guided sampling is reported to be about 60% to 82% [ 61 , 62 , 70 , 71 , 72 , 73 , 74 ], which is the same success rate as with surgically resected tissues. Furthermore, there is no significant difference in the establishment efficiency between single-pass and double-pass punctures, therefore single-pass punctures with a 22-gauge FNB needle are recommended [ 74 ].…”

Section: Personalized Cancer Treatment Using Pharmacological Profimentioning

confidence: 99%

“…The success rate of PDO establishment from tissues obtained through EUS-guided sampling is reported to be about 60% to 82% [ 61 , 62 , 70 , 71 , 72 , 73 , 74 ], which is the same success rate as with surgically resected tissues. Furthermore, there is no significant difference in the establishment efficiency between single-pass and double-pass punctures, therefore single-pass punctures with a 22-gauge FNB needle are recommended [ 74 ]. However, there are still only a few reports regarding the method of EUS-guided sampling for PDO establishment; therefore, further research is needed.…”

Section: Personalized Cancer Treatment Using Pharmacological Profimentioning

confidence: 99%

Endoscopic Ultrasound-Guided Sampling for Personalized Pancreatic Cancer Treatment

et al. 2021

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Pancreatic cancer is the most lethal solid malignancy, and the number of patients with pancreatic cancer is increasing. Systemic chemotherapies are often ineffective for such patients, and there is an urgent need for personalized medicine. Unlike other types of cancer, personalized treatments for pancreatic cancer are still in development. Consequently, pancreatic cancer is less sensitive to anticancer drugs and is often refractory to common treatments. Therefore, advances in personalized medicine for pancreatic cancer are necessary. This review examined advances in personalized medicine for pancreatic cancer, including the use of endoscopic ultrasound (EUS)-guided sampling. EUS-guided sampling is widely used for diagnosing pancreatic tumors and is expected to be applied to sampled tissues. Additionally, there has been an increase in clinical research using EUS-guided sampling. The combination of precision medicine using genomic testing and pharmacological profiles based on high-throughput drug sensitivity testing using patient-derived organoids is expected to revolutionize pancreatic cancer treatment.

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“…Therefore, direct assessment of prediction of chemotherapy response, using tumour models such as organoids or xenograft models, can be an additional way of tailoring therapy for each pa-tient [36]. Lacomb et al [37] have recently shown that successful organoid creation was feasible in 84% of EUS-FNB samples from pancreatic cancer patients. Recently, Tiriac et al [36] performed drug sensitivity profiling of pancreatic cancer in organoid models and elucidated novel functional subtypes that predict chemotherapy sensitivity.…”

Section: Introductionmentioning

confidence: 99%

The Role of Endoscopic Ultrasound in Pancreatic Cancer Staging in the Era of Neoadjuvant Therapy and Personalised Medicine

Bispo

Marques

Rio-Tinto

et al. 2020

GE Port J Gastroenterol

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Precise staging of pancreatic cancer is crucial for treatment choice. In clinical practice, this includes the TNM staging and determination of tumour resectability, based on a multimodality imaging workup. International guidelines recommend multi-detector computed tomography (CT), with a dedicated pancreatic protocol, as the first-line tool for TNM staging and evaluation of tumour-vessel relationships. In non-metastatic disease upon initial CT assessment, both magnetic resonance imaging and endoscopic ultrasound (EUS) may add relevant information, potentially changing treatment sequence. EUS may have distinct advantages in pancreatic cancer diagnosis and staging when compared with other modalities, being particularly valuable in the determination of portal venous confluence involvement (particularly in small and ill-defined/isoattenuating tumours on CT), in locoregional nodal staging and in the detection of ascites. As we step forward to a more frequent use of neoadjuvant chemotherapy and to personalised medicine, the importance of EUS-guided fine-needle biopsy (EUS-FNB) also increases. The recent availability of third-generation biopsy needles significantly increased the diagnostic yield of EUS-guided tissue acquisition, providing diagnostic cell blocks in approximately 95% of cases with only two dedicated passes and allowing ancillary testing, such as immunohistochemistry and molecular profiling of the tumour. In this article, the authors present an updated perspective of the place of EUS and EUS-FNB in the staging algorithm of pancreatic cancer. Data supporting the increasing role of neoadjuvant therapy and the importance of a patient-tailored treatment selection, based on tumoural subtyping and molecular profiling, are also discussed.

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Single-Pass vs 2-Pass Endoscopic Ultrasound-Guided Fine-Needle Biopsy Sample Collection for Creation of Pancreatic Adenocarcinoma Organoids

Cited by 18 publications

References 5 publications

A Prospective Feasibility Trial to Challenge Patient–Derived Pancreatic Cancer Organoids in Predicting Treatment Response

A Prospective Feasibility Trial to Challenge Patient–Derived Pancreatic Cancer Organoids in Predicting Treatment Response

Endoscopic Ultrasound-Guided Sampling for Personalized Pancreatic Cancer Treatment

The Role of Endoscopic Ultrasound in Pancreatic Cancer Staging in the Era of Neoadjuvant Therapy and Personalised Medicine

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