Characterization of Biophysical Stromal Properties in Human Cancer: Towards Personalized Computational Oncology

Characterization of Biophysical Stromal Properties in Human Cancer: Towards Personalized Computational Oncology

Drug delivery in solid tumors, whether administered systemically or locoregionally, is hindered by an elevated interstitial fluid pressure (IFP). Stromal targeting therapies are in active development, aiming to enhance drug transport after systemic or locoregional delivery. To date, no clinical methods are available to quantify tumor biophysical properties (including IFP). The investigators aim to use a combination of dynamic contrast enhanced MRI and computational fluid modeling (CFD) to measure stromal IFP in patients with pancreatic cancer and in patients with ovarian or colonic peritoneal carcinomatosis (PC). Computational data will be correlated with therapy response, platinum drug penetration, and invasively measured biophysical parameters after intravenous (pancreas) or intraperitoneal (ovarian/colonic PC) administration of a platinum compound. This would be the first in depth clinical study addressing this important topic, and could pave the way to developing personalized computational based treatment approaches aimed at targeting the biophysical environment of the tumor stroma in order to enhance cancer drug delivery.

Inclusion Criteria:

• Patients with non-cystic adenocarcinoma the pancreas requiring neoadjuvant chemotherapy (any) because of borderline resectability
• Patients with stage IIIC or IVA ovarian cancer planned for debulking and HIPEC.
• Patients with stage IIIC or IVA colorectal cancer planned for debulking and HIPEC

Exclusion Criteria:

• Age <18 years

• Pregnancy, or suspected inadequate contraception during study period

• Clinically detectable ascites

• Intestinal or urinary tract obstruction

• Hepatic and/or extra-abdominal metastatic disease

• Impaired renal function (serum creatinine > 1.5mg/dl or calculated GFR (CKD-EPI) < 60mL/min/1.73 m²)

• Impaired liver function (serum total bilirubin > 1.5 mg/dl, except for known Gilbert's disease)

• Platelet count < 100.000/µl

• Hemoglobin < 9g/dl

• Neutrophil granulocytes < 1.500/ml

• Irresectable or metastatic disease

• Contra-indication for contrast enhanced MRI

  • Known allergy or intolerance to Gadolinium based contrast agents
  • Severe claustrophobia
  • Patients with metallic foreign bodies (pacemaker, neurostimulator, pedicle screw, cerebral aneurysm clips…) that may dislodge in a strong magnetic field

• Frail and medically unfit patients (Karnofsky index < 60% and WHO Performance score 3 or 4)

• Estimated life expectancy < 12 months

• In case of ovarian/colon cancer: no visible peritoneal metastasis on CT scan

• Acute or chronic pancreatitis