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

Masaryk Memorial Cancer Institute144 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Interventions

FDG-PETDIAGNOSTIC_TEST

FDG-PET scans will be performed before (baseline) and after 14 days of standard neoadjuvant treatment in specialized PET centers (MOÚ Brno, VFN Praha, FN Olomouc) according to the standard operation procedure and in accordance with the EANM guidelines. Data and records of the FDG-PET scans will be sent for central reading to PET Center MOÚ. Tracer uptake will be assessed semiquantitatively (standardized uptake values (SUV) using a circular region of interest (ROI) (diameter, 1.5 cm) with the TrueD software (Siemens Medical Solutions)). The percentage change in SUV will be calculated as ΔSUV = 100 × (SUVbaseline - SUVfollow-up)/SUVbaseline and used to classify patients as metabolic responders or non-responders and guide subsequent preoperative treatment.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

R0 resection rate in arm B (metabolic non-responders)

The proportion of patients in Arm B (metabolic non-responders) who achieve an R0 resection. Metabolic non-response is defined as a decrease in tumor standardized uptake value (SUV) of \<35% on FDG-PET performed after the first cycle of preoperative chemotherapy compared with baseline FDG-PET. R0 resection is defined as curative surgical resection with negative resection margins.

Time frame: At surgery, following completion of preoperative treatment

Secondary Outcomes

Overall survival in arm A and arm B

Overall survival (OS) is defined as the time from the second FDG-PET scan to death from any cause. OS will be evaluated in Arm A (metabolic responders) and Arm B (metabolic non-responders).

Time frame: From the second FDG-PET scan until death from any cause, assessed up to 5 years

Disease free survival in arm A and arm B

Disease-free survival (DFS) is defined as the time from curative-intent resection (R0/R1) to disease recurrence or death from any cause. DFS will be evaluated separately in Arm A (metabolic responders) and Arm B (metabolic non-responders).

Time frame: From curative-intent resection (R0/R1) until disease recurrence or death from any cause, assessed up to 5 years