Prediction of Surgical Resectability After FOLFIRINOX Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: the Role of Diffusion Weighted Magnetic Resonance Imaging, Radiomics and Liquid Biopsy (PeRFormanCe Trial)

NCT05298722 | Recruiting

• 1 other identifier: ONZ-2022-0088 - PeRFormanCe
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 8

Brief Summary

In this prospective study, new diagnostic tools will be explored for patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma (BR or LAPDA) who undergo neoadjuvant chemotherapy with FOLFIRINOX. The diagnostic work-up and therapy for the study population will not differ from the gold standard during the study; only additional diagnostic tools will be implemented, and their value will be analyzed post hoc. The 5-year survival rate of pancreatic cancer is 9%, but this can be drastically improved if surgery is possible. With its increasing incidence and poor prognosis, pancreatic cancer is becoming a global oncologic challenge where major breakthroughs are still required to improve patient outcomes. Patients with BR or LAPDA typically undergo neoadjuvant treatment with FOLFIRINOX chemotherapy, followed by referral for surgery if a response is observed. In these cases, surgical resectability is difficult to predict based on CT imaging due to the tumor's desmoplastic reaction, which obscures tumor-vessel contact without clear morphological changes. Consequently, patients without tumor progression on CT and with a decreased tumor marker (CA 19-9) are considered for surgical exploration to ensure that no potentially curative treatment is denied. However, the non-specific nature of CA 19-9 and the unreliable spatial changes on CT do not allow for accurate patient stratification. Therefore, alternative diagnostic strategies are needed to better predict resectability, minimizing unnecessary laparotomies while ensuring that potentially curative approaches are not overlooked. In this project, the investigator will apply diffusion-weighted magnetic resonance imaging (DW-MRI), as it has been shown to be useful in assessing tumor response beyond morphological parameters. DW-MRI enables the detection of functional tumor changes, variations in vascularization, and fibrosis without modifications in shape. The statistical evaluation of visual information using radiomics optimizes data analysis, allowing comparisons over time (before and after chemotherapy) and correlation with operative findings (resectable or unresectable tumor). The investigator will focus on patients with BR and LAPDA and assess whether a combination of clinical and genetic factors can predict successful surgical resection. To this end, DW-MRI imaging will be complemented by multi-omics profiling in liquid biopsies. Furthermore, the investigator aims to validate, in a prospective patient cohort, the predictive value of recently published single nucleotide polymorphisms (SNPs) in genes that regulate cancer progression, invasion, and metastasis. Some alleles of these SNPs have been associated with an increased risk of tumor-related mortality compared to protective genotypes.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (3)

• Prediction of surgical resectability

  Create an algorithm to predict surgical resectability of BR and LA PDAC after neoadjuvant FOLFIRINOX with radiomics analysis of CT and DW-MRI to determine the tumoral vascular invasion in combination with the evolution of CA19-9 and genetic profilling of liquid biopsies (phenotyping and quantification of the CTCs, longitudinal analysis of driver mutations and epigenetic changes in cfDNA).

  2 years

• R1 resection rate

  2 years

• Histopathological response

  2 years

Secondary Outcomes (6)

• Prediction of R0 resection

  2 years

• Perioperative complications

  2 years

• Generic measurement of health status

  4 years

• Overall survival

  4 years

• Disease free survival

  4 years

Study Arms (1)

Study arm

OTHER

Imaging with CT-scan and MRI-DWI and peripheral blood samples for liquid biopsy

Diagnostic Test: Imaging analysis of CT-scan and MRI with radiomics and genetic analysis of peripheral blood samples and questionnaires.

Interventions

Imaging analysis of CT-scan and MRI with radiomics and genetic analysis of peripheral blood samples and questionnaires. DIAGNOSTIC_TEST

* The images from CT scans and MRI with DWI will be processed using specialized software to determine the direction of diffusion tensors. This will indicate the diffusion direction using color coding (red, green, and blue for the x, y, and z components of the vector) and the intensity using anisotropy (brightness of voxels). Further analysis will be performed using fiber tracking, which provides a clear representation of the functional connectivity of adjacent tissues. * Genetic profiling of liquid biopsies: Multi-omics profiling of liquid biopsies (blood samples) will be conducted, followed by cell phenotyping, longitudinal analysis of driver mutations and epigenetic changes in cfDNA, and genotyping of germline variations. * Questionnaires for patient-reported outcomes and health economic analysis: EQ-5D-5L PAN 26 HADS

Also known as: Analysis of imaging with radiomics and genetic analysis of peripheral blood samples (liquid biopsy)

Study arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, aged 18 years and above
• Diagnosis of BR or LA PDAC according to NCCN guidelines (version 1.2020)
• Histologic diagnosis of PDAC
• No medical or anesthetic contra-indication for surgery
• Able to understand nature of the study procedures
• Willing to participate and give written informed consent

You may not qualify if:

• Age \< 18 years
• Distant metastases
• Histologic diagnosis of cholangiocarcinoma, duodenal carcinoma or neuroendocrine tumor
• Known hypersensitivity for MRI contrast
• Pacemaker or prosthesis with incompatibility for MRI
• Claustrophobia
• Pregnancy or breastfeeding
• Not able to understand nature of the study procedure
• Performance status ECOG score: \>2

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (8)

Ghent University Hospital

Ghent, East Flanders, 9000, Belgium

RECRUITING

AZ Sint Blasius Dendermonde

Dendermonde, 9200, Belgium

RECRUITING

AZ Alma Eeklo

Eeklo, 9900, Belgium

RECRUITING

AZ Jan Palfijn Ghent

Ghent, 9000, Belgium

RECRUITING

AZ Sint Lucs Ghent

Ghent, 9000, Belgium

RECRUITING

AZ Oudenaarde

Oudenaarde, 9700, Belgium

RECRUITING

AZ Vitaz Sint Niklaas - Lokeren

Sint-Niklaas, 9100, Belgium

RECRUITING

ZorgSaam ZH DeHonte Terneuzen

Terneuzen, Zeeland, 4535 PA, Netherlands

RECRUITING

Related Publications (14)

• Isaji S, Mizuno S, Windsor JA, Bassi C, Fernandez-Del Castillo C, Hackert T, Hayasaki A, Katz MHG, Kim SW, Kishiwada M, Kitagawa H, Michalski CW, Wolfgang CL. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology. 2018 Jan;18(1):2-11. doi: 10.1016/j.pan.2017.11.011. Epub 2017 Nov 22.

  PMID: 29191513 BACKGROUND

• Marchegiani G, Todaro V, Boninsegna E, Negrelli R, Sureka B, Bonamini D, Salvia R, Manfredi R, Pozzi Mucelli R, Bassi C. Surgery after FOLFIRINOX treatment for locally advanced and borderline resectable pancreatic cancer: increase in tumour attenuation on CT correlates with R0 resection. Eur Radiol. 2018 Oct;28(10):4265-4273. doi: 10.1007/s00330-018-5410-6. Epub 2018 Apr 20.

  PMID: 29679211 BACKGROUND

• Gemenetzis G, Groot VP, Yu J, Ding D, Teinor JA, Javed AA, Wood LD, Burkhart RA, Cameron JL, Makary MA, Weiss MJ, He J, Wolfgang CL. Circulating Tumor Cells Dynamics in Pancreatic Adenocarcinoma Correlate With Disease Status: Results of the Prospective CLUSTER Study. Ann Surg. 2018 Sep;268(3):408-420. doi: 10.1097/SLA.0000000000002925.

  PMID: 30080739 BACKGROUND

• Tang L, Zhou XJ. Diffusion MRI of cancer: From low to high b-values. J Magn Reson Imaging. 2019 Jan;49(1):23-40. doi: 10.1002/jmri.26293. Epub 2018 Oct 12.

  PMID: 30311988 BACKGROUND

• Rebelo et al. Circulating tumor cells in pancreatic cancer: a review. Journal of pancreatology (2019) 2:2.

  BACKGROUND

• Dimitrakopoulos C, Vrugt B, Flury R, Schraml P, Knippschild U, Wild P, Hoerstrup S, Henne-Bruns D, Wuerl P, Graf R, Breitenstein S, Bond G, Beerenwinkel N, Grochola LF. Identification and Validation of a Biomarker Signature in Patients With Resectable Pancreatic Cancer via Genome-Wide Screening for Functional Genetic Variants. JAMA Surg. 2019 Jun 1;154(6):e190484. doi: 10.1001/jamasurg.2019.0484. Epub 2019 Jun 19.

  PMID: 30942874 BACKGROUND

• Okubo K, Uenosono Y, Arigami T, Mataki Y, Matsushita D, Yanagita S, Kurahara H, Sakoda M, Kijima Y, Maemura K, Natsugoe S. Clinical impact of circulating tumor cells and therapy response in pancreatic cancer. Eur J Surg Oncol. 2017 Jun;43(6):1050-1055. doi: 10.1016/j.ejso.2017.01.241. Epub 2017 Feb 12.

  PMID: 28233633 BACKGROUND

• Poruk KE, Valero V 3rd, Saunders T, Blackford AL, Griffin JF, Poling J, Hruban RH, Anders RA, Herman J, Zheng L, Rasheed ZA, Laheru DA, Ahuja N, Weiss MJ, Cameron JL, Goggins M, Iacobuzio-Donahue CA, Wood LD, Wolfgang CL. Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma. Ann Surg. 2016 Dec;264(6):1073-1081. doi: 10.1097/SLA.0000000000001600.

  PMID: 26756760 BACKGROUND

• Poruk KE, Blackford AL, Weiss MJ, Cameron JL, He J, Goggins M, Rasheed ZA, Wolfgang CL, Wood LD. Circulating Tumor Cells Expressing Markers of Tumor-Initiating Cells Predict Poor Survival and Cancer Recurrence in Patients with Pancreatic Ductal Adenocarcinoma. Clin Cancer Res. 2017 Jun 1;23(11):2681-2690. doi: 10.1158/1078-0432.CCR-16-1467. Epub 2016 Oct 27.

  PMID: 27789528 BACKGROUND

• Harouaka RA, Nisic M, Zheng SY. Circulating tumor cell enrichment based on physical properties. J Lab Autom. 2013 Dec;18(6):455-68. doi: 10.1177/2211068213494391. Epub 2013 Jul 5.

  PMID: 23832928 BACKGROUND

• Sollier E, Go DE, Che J, Gossett DR, O'Byrne S, Weaver WM, Kummer N, Rettig M, Goldman J, Nickols N, McCloskey S, Kulkarni RP, Di Carlo D. Size-selective collection of circulating tumor cells using Vortex technology. Lab Chip. 2014 Jan 7;14(1):63-77. doi: 10.1039/c3lc50689d. Epub 2013 Sep 23.

  PMID: 24061411 BACKGROUND

• Kolostova K, Rzechonek A, Schutzner J, Grill R, Lischke R, Hladik P, Simonek J, Bobek V. Circulating Tumor Cells as an Auxiliary Diagnostic Tool in Surgery. In Vivo. 2017 Nov-Dec;31(6):1197-1202. doi: 10.21873/invivo.11190.

  PMID: 29102946 BACKGROUND

• Bobek V, Gurlich R, Eliasova P, Kolostova K. Circulating tumor cells in pancreatic cancer patients: enrichment and cultivation. World J Gastroenterol. 2014 Dec 7;20(45):17163-70. doi: 10.3748/wjg.v20.i45.17163.

  PMID: 25493031 BACKGROUND

• Abreu de Carvalho LF, Gryspeerdt F, Ceelen W, Geboes K, Ribeiro S, Hoorens A, Vandenbussche N, Claes KBM, Lecluyse C, Anisau A, Van Ongeval J, Lybaert W, Triest L, Vervaecke A, Sas S, Claerhout B, Beyls C, Sie M, Berrevoet F. Prediction of surgical resectability after FOLFIRINOX chemotherapy for borderline resectable and locally advanced pancreatic cancer (PeRFormanCe): a multicenter prospective trial - trial protocol. BMC Surg. 2025 May 13;25(1):204. doi: 10.1186/s12893-025-02938-1.

  PMID: 40361171 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Magnetic Resonance Imaging; Radiomics; Liquid Biopsy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: March 28, 2022
• Study Start: December 12, 2022
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 2, 2025

Record last verified: 2024-09

Locations

BE (7); NL (1)