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A Phase II Clinical Trial of Molecular Profiled Neoadjuvant Therapy for Localized Pancreatic Ductal Adenocarcinoma. Ann Surg 2018 10;268(4):610-619

Date

08/07/2018

Pubmed ID

30080723

DOI

10.1097/SLA.0000000000002957

Scopus ID

2-s2.0-85067054610   17 Citations

Abstract

OBJECTIVES: One facet of precision medicine is the use of tumor molecular profiling to guide chemotherapeutic selection. We conducted the first prospective clinical trial of molecular profiling to guide neoadjuvant therapy in patients with operable pancreatic ductal adenocarcinoma (PDAC). We hypothesized that more effective systemic therapy would prevent disease progression during neoadjuvant therapy and, therefore, allow more patients to undergo surgery.

METHODS: In patients with resectable and borderline resectable (BLR) PDAC, molecular profiling consisted of immunocytochemical staining of pretreatment endoscopic ultrasound-guided fine needle aspiration tumor biopsies using 6 biomarkers. Neoadjuvant systemic therapy was selected based on the molecular profiling results. The primary endpoint was the completion of all intended neoadjuvant therapy and surgery.

RESULTS: The trial enrolled 130 patients; 61 (47%) resectable and 69 (53%) BLR. Molecular profiling was reported within a median of 5 business days (IQR: 3). Of the 130 patient samples, 95 (73%) had adequate cellularity for molecular profiling and 92 (71%) patients received molecular profile-directed therapy. Of the 92 patients who had predictive profiling, 74 (80%) received fluoropyrimidine-based therapy and 18 (20%) received gemcitabine-based therapies. Of the 130 patients, 107 (82%) completed all intended neoadjuvant therapy and surgery; 56 (92%) of the 61 with resectable PDAC and 51 (74%) of 69 with BLR PDAC.

CONCLUSIONS: We report the first prospective clinical trial that utilized molecular profiling to select neoadjuvant therapy in patients with operable PDAC. Such high resectability rates have not been observed in prior neoadjuvant trials, suggesting that molecular profiling may improve the efficacy of chemotherapy in these patients.

Author List

Tsai S, Christians KK, George B, Ritch PS, Dua K, Khan A, Mackinnon AC, Tolat P, Ahmad SA, Hall WA, Erickson BA, Evans DB

Authors

Kathleen K. Christians MD Professor in the Surgery department at Medical College of Wisconsin
Kulwinder S. Dua MD Professor in the Medicine department at Medical College of Wisconsin
Beth A. Erickson MD Professor in the Radiation Oncology department at Medical College of Wisconsin
Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin
Ben George MD Associate Professor in the Medicine department at Medical College of Wisconsin
Parag P. Tolat MD Chief, Associate Professor in the Radiology department at Medical College of Wisconsin
Susan Tsai MD Associate Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Aged
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Carcinoma, Pancreatic Ductal
Chemotherapy, Adjuvant
Disease Progression
Female
Humans
Image-Guided Biopsy
Male
Neoadjuvant Therapy
Ohio
Pancreatectomy
Pancreatic Neoplasms
Precision Medicine
Prospective Studies
Radiotherapy, Adjuvant
Treatment Outcome
Ultrasonography, Interventional
Wisconsin
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a