Evaluation of MMR Status and PD-L1 Expression Using Specimens Obtained by EUS-FNB in Patients With Pancreatic Cancer

PD-L1 and MMR Status Provided by Endoscopic Ultrasound-Guided Fine-Needle Biopsies as a Predictor of PrognosiS in Patients With Pancreatic Ductal Adenocarcinoma

Sponsors

Lead Sponsor: Ponderas Academic Hospital

Collaborator: University of Medicine and Pharmacy Craiova

Source Ponderas Academic Hospital
Brief Summary

Pancreatic ductal adenocarcinoma (PDAC) has a suboptimal response to standard therapies that modestly impact survival due to its ability to evade host immune surveillance. Emerging evidence has shown that the co-inhibitory receptors, such as programmed death 1 (PD-1), play a critical role in cancer immune-editing. Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. The advent of immunotherapy, with checkpoint inhibitors, which block PD-L1 interaction between tumor cells and activated T cells, has significantly altered the treatment algorithm for several solid tumors. However, the clinicopathologic significance and prognostic value of PD-L1 in PDAC remains controversial. The main technical ground may be that PDAC PD-L1 expression quantification is limited to surgical resection specimens and dependent on specific immunohistochemistry (IHC) tests. In addition, PD-L1 expression has not been extensively assessed before surgery in treatment-naive PDAC patients, due to the current IHC test requirement for a histologic rather than a cytologic evaluation. However, a recent study showed that EUS-fine needle biopsy (FNB) can successfully determine primary pancreas malignancy PD-L1 status. One recently identified subtype within the genomic landscape of PDAC is the mismatch repair-deficient (dMMR) tumor. Evaluation of dMMR status is particularly important following the FDA approval of the PD-1 inhibitor, pembrolizumab, for the treatment of unresectable or metastatic, microsatellite instability-high (MSI-H) or dMMR PDAC that have progressed following prior treatment, and have no satisfactory alternative treatment options. The objectives of the project will include the assessment of tumor PD-L1/dMMR expression in patients with PDAC using EUS-FNB samples and the prospective correlation of MMR status and PD-L1 expression with overall survival and progression-free survival of PDAC patients.

Overall Status Not yet recruiting
Start Date 2019-02-01
Completion Date 2022-01-01
Primary Completion Date 2021-01-01
Study Type Observational
Primary Outcome
Measure Time Frame
Feasibility of PD-L1 expression analysis on EUS-FNB pancreatic specimens 1 year
Feasibility of MMR status analysis on EUS-FNB pancreatic specimens 1 year
Secondary Outcome
Measure Time Frame
Tumor response 3 months
Overall survival up to 12 months
Progression-free survival up to 12 months
Enrollment 30
Condition
Intervention

Intervention Type: Diagnostic Test

Intervention Name: EUS-FNB

Description: EUS WITH EUS-FNB will be performed for confirmation of diagnosis and analysis of MMR status and PD-L1 expression Protocol of EUS with EUS-FNB should include linear EUS instruments with complete examinations of the pancreas. Tumor characteristics (echogenicity, echostructure, size) will be described as well as presence/absence of power Doppler signals. EUS-FNB will be performed in all pancreatic masses with at least three passes in the absence of an onsite cytopathologist using a fanning technique with a 22-gauge needle (SharkCore FNB needle Medtronic Corp. or Acquire FNB needle Boston, MA).

Arm Group Label: PATIENTS WITH PANCREATIC CANCER

Intervention Type: Other

Intervention Name: Immunohistochemistry

Description: IHC will be performed on treatment-naïve formalin-fixed paraffin-embedded EUS-FNB pancreatic specimens. Briefly, 4-μm-thick tissue sections will be stained using the Ventana BenchMark XT automated slide-staining system using the following antibodies: Anti-PD-L1 (clone SP263, VENTANA, Tucson, AZ), MLH1 (clone G168-728, Cell Marque, Rocklin, California, United States), MSH2 (clone FE11, Biocare Medical, Concord, Massachusetts, United States), MSH6 (clone BC/44, Biocare Medical, Concord, Massachusetts, United States), and PMS2 (clone A16-4, Biocare Medical, Concord, M Massachusetts, United States). Antigen-antibody reactions will be visualized using UltraView detection with diaminobenzidine as the chromogen. The specimen will be considered to have PD-L1 expression if PD-L1 is expressed in ≥ 1 % of tumor cells and a high level of expression if ≥ 50 %. Tumors will be classified as dMMR if they exhibit absent nuclear staining of DNA mismatch repair proteins (MLH1, MSH2, MSH6, or PMS2).

Arm Group Label: PATIENTS WITH PANCREATIC CANCER

Eligibility

Sampling Method:

Probability Sample

Criteria:

Inclusion Criteria - Age 18 to 90 years old - men or women - signed informed consent for EUS and EUS -FNB - the diagnosis of adenocarcinoma histologically confirmed by FNB - resectable, Unresectable, locally advanced and/or metastatic disease Exclusion Criteria: -previous chemotherapy or radiotherapy

Gender:

All

Minimum Age:

18 Years

Maximum Age:

90 Years

Healthy Volunteers:

No

Overall Contact Contact information is only displayed when the study is recruiting subjects.
Verification Date

2019-01-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Ponderas Academic Hospital

Investigator Full Name: alina constantin

Investigator Title: principal investigator

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Label: PATIENTS WITH PANCREATIC CANCER

Description: All patients with a suspicion of pancreatic masses will undergo EUS (including EUS-FNB for confirmation of diagnosis). A positive cytological diagnosis will be taken as a final proof of malignancy of the pancreas mass. The diagnoses obtained by EUS-FNB will be further verified during a clinical follow-up of at least 6 months. Immunochemistry will be performed on the EUS-FNB specimens to determine PD-L1 expression and MMR status

Acronym SUCCESS
Patient Data No
Study Design Info

Observational Model: Cohort

Time Perspective: Prospective

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