MAESTRO Study: Metabolic Imaging to Improve Patient-Specific Therapy Outcomes

Primary objective

-In this study we will investigate whether biochemical imaging of change (Δ, figure 1) in the metabolic phospholipid ratios of PME and PDE between baseline and after 2 weeks of therapy are predictive for progression free survival (PFS) and/or overall survival (OS) in gastro-oesophageal cancer patients within 27 weeks of treatment.

Secondary objectives:

• In this study we will investigate whether biochemical imaging of change (Δ, figure 1) in the metabolic phospholipid ratios of PME and PDE between baseline and after 2 weeks of therapy are predictive for RECIST progression in gastro-oesophageal cancer patients after the first 9 week treatment period.
• Investigate whether biochemical imaging of the metabolic phospholipid ratios of PME and PDE at baseline of therapy are predictive for RECIST progression after the first 9-week treatment period, and for PFS and OS in gastro-oesophageal cancer patients.
• Investigate whether biochemical imaging of change (δ, figure 1) in the metabolic phospholipid ratios of PME and PDE after a 9-week treatment period are predictive for RECIST progression following that treatment period, and for PFS and OS in gastro-oesophageal cancer patients.
• Exploratory multi variable analysis for the development of a prediction model to predict resistance to treatment within 3 weeks after the start of chemotherapy with the use of all chemistry imaging data including all MR detectable nuclei and clinical parameters.

Study population: We aim to include a total of 70 patients with metastatic gastro-oesophageal cancer before start of palliative chemotherapy.

Intervention: Participants will undergo multiple 7T MR imaging sessions which include advanced 31P MRSI techniques, before start of palliative chemotherapy and during treatment until progression of disease or until week 9.

Main study parameters/endpoints: Study parameters include; metabolic ratios of the phospholipids PME and PDE from the area under the curve (AUC) of the corresponding spectral peaks, size measurements from CT and MRI scans, coded radiology reports, clinical patient data, e.g. chemotherapy details extracted from clinical notes which are coded before storage to preserve anonymity. Main endpoint is defined by progression or death after 27 weeks measured using the RECIST progression criteria for which chemical imaging its predictive value is investigated in the primary objective.

Nature and extent of the burden and risks associated with participation, benefit, and group relatedness: Patients will be asked for three extra hospital visits to undergo 7T MRI of approximately one hour per session (3x 1 hour). MRI is a safe non-invasive technique without use of ionizing radiation and so far, extensive research has not shown any side-effects of the high magnetic field used in 7T MRI, resulting in low inherent risks for the participants. This study will be started only after approval of the IGJ and the medical device investigation agency of the AMC. Patients' therapy is not delayed by participation in this study and patients with MRI contraindications are excluded from participation.

Inclusion criteria

• Patients with liver metastasis of gastrointestinal cancer, with histological or cytological proof of metastasis or a high suspicion on CT imaging.
• Tumour size ≥ 1cm.
• WHO-performance score 0-2.
• Scheduled for first- or second-line palliative chemotherapy containing capecitabine combined with oxaliplatin (CAPOX) or fluorouracil combined with oxaliplatin and folinic acid (FOLFOX).
• Written informed consent.

Exclusion criteria

• Any psychological, familial, sociological, or geographical condition potentially hampering adequate informed consent or compliance with the study protocol.
• Contra-indications for MR scanning, including patients with a pacemaker, cochlear implant or neurostimulator; patients with non-MR compatible metallic implants in their eye, spine, thorax or abdomen; or a non-MR compatible aneurysm clip in their brain; patients with claustrophobia.