Study Aim The aim of this study is to assess whether the combination of radiomics,
diffusion-weighted magnetic resonance imaging (DW-MRI), and multi-omics profiling in
liquid biopsies-both before and after neoadjuvant chemotherapy-can predict the
probability of achieving successful surgical excision in patients with borderline
resectable (BR) and locally advanced pancreatic ductal adenocarcinoma (LAPDA).
Additionally, a subgroup analysis will be performed, taking into account risk alleles of
single nucleotide polymorphisms (SNPs) that have recently been associated with worse
survival outcomes.
The primary endpoint of this study is to improve the prediction of surgical resectability
following neoadjuvant chemotherapy with FOLFIRINOX in patients with BR and LAPDA. The
focus is on increasing diagnostic specificity to better identify patients with
unresectable tumors, thereby avoiding unnecessary exploratory laparotomies that may delay
further chemotherapy.
Secondary endpoints include the evaluation of postoperative complications, cost
minimization, and disease-free and overall survival.
Background & Rationale All factors evaluated in this study-DW-MRI, radiomics, genetic
markers (SNPs), and multi-omics profiling in liquid biopsies-have individually shown
promise for early diagnosis, prognosis assessment, and correlation with tumor response to
chemotherapy in pancreatic cancer. However, these modalities have never been combined in
an innovative study such as this, where they are integrated to enhance clinical
decision-making.
This project aims to apply existing knowledge to have an immediate impact on therapeutic
decision-making, reducing unnecessary surgical explorations and ultimately improving
patient quality of life while optimizing treatment efficiency.
Patients with BR or LAPDA typically undergo neoadjuvant treatment with FOLFIRINOX,
followed by referral for surgery if they respond to chemotherapy. However, surgical
resectability is challenging to predict using CT imaging alone, as the tumor's
desmoplastic reaction can obscure tumor-vessel contact without clear morphological
changes. As a result, patients with stable disease on CT and a decreased CA 19-9 level
are considered for surgical exploration to ensure that no potentially curative treatment
is withheld.
Since CA 19-9 is non-specific and CT lacks reliable spatial resolution for detecting
subtle tumor changes, alternative strategies are needed to improve resectability
predictions and avoid negative laparotomies. DW-MRI has demonstrated its value in
evaluating tumor response beyond morphological parameters, while radiomics can enhance
data analysis. Additionally, multi-omics profiling using liquid biopsies has shown a
correlation with tumor response to chemotherapy in pancreatic cancer, though its utility
in the neoadjuvant setting remains unclear.
Objective This multicenter prospective study aims to assess the utility of DW-MRI,
radiomics, and liquid biopsy in predicting tumor resectability after neoadjuvant
treatment with FOLFIRINOX in patients with BR and LAPDA.
When chemotherapy results in a reduction of CA 19-9 but no significant morphological
change on CT, some tumors may still be eligible for an R0 resection. The investigator
hypothesizes that these cases can be preoperatively identified by detecting a reduction
in multi-omics markers in liquid biopsies, along with decreased vascularity and
cellularity in the tumor-vessel interface on DW-MRI.
Study Design A prospective interventional study with a single study arm.
Study Population Patients with BR or LAPDA scheduled for neoadjuvant chemotherapy with
FOLFIRINOX and without contraindications for pancreatic surgery.
A minimum sample size of 45 patients undergoing surgical exploration has been calculated
(80% power, α = 0.05, two-tailed).
Intervention Patients with BR and LAPDA will be discussed in a multidisciplinary
oncologic meeting and will receive standard-of-care treatment. In addition to routine
clinical evaluation, CT imaging, and CA 19-9 assessment before and after chemotherapy,
participants will undergo DW-MRI and provide a peripheral blood sample for multi-omics
profiling in liquid biopsies.
If no tumor progression is observed on imaging and CA 19-9 levels decrease
post-chemotherapy, patients will be considered for surgical exploration. During surgery,
a blood sample will be collected from the supra-pancreatic portal vein to measure
circulating tumor cells (CTCs) before and after tumor resection-if an R0 resection is
feasible.
Additionally, a peripheral blood sample will be taken at the first postoperative
consultation to analyze multi-omics profiling in liquid biopsies and CA 19-9 levels.
Burden, Risks, and Benefits of Participation Compared to standard care, participants in
this study will undergo two additional DW-MRI scans and provide extra peripheral blood
samples.
DW-MRI is a widely used, safe imaging modality, and blood samples are routinely collected
as part of oncologic treatment. The study aims to refine surgical decision-making,
minimizing unnecessary procedures and ultimately improving patient outcomes.