Sequential FDG-PET and miRNA as Biomarkers of Preoperative Treatment Strategy in LA Oesophago-Gastric Cancer

Sequential FDG-PET and Plasma/Tissue miRNA as a Biomarkers of Preoperative Treatment Strategy in Locally Advanced Oesophago-Gastric Cancer

GastroPET is a prospective, multicenter, non-randomized interventional study evaluating sequential FDG-PET as an early biomarker to guide preoperative treatment in patients with locally advanced resectable oesophago-gastric adenocarcinoma. All patients receive an initial cycle of standard preoperative chemotherapy followed by a second FDG-PET scan. Based on the change in tumor FDG uptake, patients are classified as metabolic responders or non-responders. Metabolic responders continue preoperative chemotherapy, whereas metabolic non-responders switch to preoperative chemoradiotherapy. The study evaluates surgical and long-term outcomes of this response-adapted treatment strategy. Exploratory objectives include the evaluation of tissue and circulating miRNA and immune biomarkers in relation to metabolic response and treatment outcomes.

The primary objective of the study is to evaluate sequential FDG-PET as an early biomarker for response-adapted preoperative treatment in locally advanced resectable oesophago-gastric adenocarcinoma. FDG-PET is performed before initiation of preoperative chemotherapy and after the first cycle of chemotherapy. The change in tumor standardized uptake value (SUV) is used to classify patients as metabolic responders (Arm A) or metabolic non-responders (Arm B).

Metabolic responders continue preoperative FLOT or FOLFOX chemotherapy, whereas metabolic non-responders switch to preoperative chemoradiotherapy with paclitaxel and carboplatin. The primary efficacy outcome is the R0 resection rate in Arm B. Secondary clinical outcomes include disease-free survival and overall survival in both metabolic response groups.

Additional exploratory objectives include the evaluation of tissue and plasma miRNA profiles as biomarkers of metabolic and pathological response, assessment of circulating immune cells and antibody profiles in relation to metabolic response and treatment outcomes, and a pharmacokinetic substudy evaluating interpatient variability in fluoropyrimidine exposure and its association with adverse drug reactions.

Inclusion Criteria:

1. Age of 18 years or more
2. Not currently participating in another study
3. Able and willing to sign informed consent and to comply with study procedures
4. Biopsy-proven locally advanced resectable oesophago-gastric adenocarcinoma (Siewert I - III) with T3N0, T4N0, T2 - T4N+, stage Ib - IIIc I. Adenocarcinoma of distal part of the oesophagus II. Adenocarcinoma of the real cardia III. Adenocarcinoma of the subcardial stomach
5. Staging procedures include endoscopy, endoscopic ultrasound and FDG-PET
6. Eligible patients have to be fit for platinum-containing chemotherapy
7. Tumours must be potentially R0 resectable tumours during consecutive operation.

Exclusion Criteria:

1. Participation in another clinical trial of a therapeutic drug during the past 14 days
2. Addiction to alcohol or drugs
3. Women of child-bearing potential who are not using a commonly accepted effective means of contraception; women of child-bearing potential will have negative blood pregnancy test before enrollment
4. Pregnant women and nursing mothers are not allowed to enroll on this study
5. Eastern Cooperative Oncology Group score >2
6. Previous or secondary malignancy in past 5 years (Excluding skin cancer and early cervical carcinoma)
7. Life expectancy of less than 3 months
8. Uncontrolled bleeding from the tumour
9. Uncontrolled diabetes
10. Patients are also ineligible if they have undergone previous chemotherapy, radiotherapy, or endoscopic laser therapy for EGJ