Pathological Response to Perioperative FLOT in Gastric Adenocarcinoma

Background: Gastric cancer is the fifth most frequent cancer and the fourth leading cause of cancer death worldwide. In resectable disease, perioperative FLOT (four preoperative and four postoperative cycles) improved pathological regression and overall survival compared with epirubicin-based regimens in the FLOT4-AIO trial. Real-world series such as RealFLOT reported a lower pathological complete response rate (7.3%) than the pivotal trial, and a Colombian series reported 8.4%. There is no systematic institutional characterization of tolerance, pathological response, adherence and completion of perioperative FLOT in Colombia.

Design: Single-center, observational, descriptive, retrospective cohort (case series) study. All patients received the same regimen and there is no comparator group; the study has no hypothesis-testing purpose.

Population and identification: Adults older than 18 years with histologically confirmed stage I, II or III gastric or gastroesophageal junction adenocarcinoma who started perioperative FLOT at Fundación Santa Fe de Bogotá between January 1, 2021 and December 31, 2025. Patients will be identified through institutional oncology, chemotherapy pharmacy and surgical pathology databases, and all eligible patients will be included (census sampling; approximately 90 patients). Data collection will start only after notification of the study to INVIMA (Colombian regulatory agency) as a phase IV observational study.

Data collection and outcome ascertainment: Data will be recorded in an institutional REDCap database with pseudonymized study codes and validation rules. Outcomes will be identified through a systematic multi-source search (surgical pathology reports, oncology records, chemotherapy pharmacy records, imaging reports, emergency, inpatient and consultation notes). Key events (pathological response, toxicity, progression and recurrence) will be independently adjudicated by two investigators, with disagreements resolved by consensus, and a random 10% sample of records will be double-checked for data-entry quality. Follow-up runs from FLOT initiation (index date) until recurrence, death, end of follow-up or loss to follow-up.

Outcomes: The primary outcome is pathological response in the institutional surgical specimen, reported as the Mandard tumor regression grade (TRG) and the pathological complete response rate. Secondary outcomes include grade 3-4 adverse events according to CTCAE version 5.0, dose modifications (reduction, delay or discontinuation) and their reasons, adherence and completion of the planned perioperative regimen, cumulative incidence of recurrence and overall survival.

Statistical analysis: The analysis will be exclusively descriptive, without significance testing or causal inference, using available cases with explicit denominators and no imputation. Categorical variables will be summarized as frequencies and proportions with Wilson 95% confidence intervals, and continuous variables as means and standard deviations or medians and interquartile ranges. Results will be stratified by prespecified categories (stage, Lauren subtype, TRG). Overall survival will be estimated with the Kaplan-Meier method from FLOT initiation, with probabilities at 12, 24 and 36 months. Recurrence will be described from the date of R0 resection with the cumulative incidence function (Aalen-Johansen estimator), treating death without recurrence as a competing event. Analyses will be performed in R.

Ethics: The study is classified as research without risk under Colombian Resolution 8430 of 1993, with a waiver of informed consent for retrospective record review. The protocol (version 3.0, July 29, 2026) was approved by the Comité Corporativo de Ética en Investigación of Fundación Santa Fe de Bogotá (CCEI-20373-2026). Data will be handled in accordance with the Declaration of Helsinki (2024 revision) and Colombian Law 1581 of 2012.

• FLOT Chemotherapy (Drug), also known as 5-Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel, FLOT: Perioperative chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT), planned as four preoperative and four postoperative cycles or modified according to routine clinical practice, combined with gastrectomy. The study does not assign or modify treatment; exposure data are abstracted retrospectively from medical records.

Primary outcomes

• Pathological Complete Response Rate [At surgical resection, after completion of preoperative FLOT (approximately 8 to 12 weeks after FLOT initiation)]

Secondary outcomes

• Tumor Regression Grade (Mandard) [At surgical resection, after completion of preoperative FLOT (approximately 8 to 12 weeks after FLOT initiation)]
• Incidence of Grade 3-4 Adverse Events [From FLOT initiation until 30 days after the last FLOT dose, up to approximately 8 months]
• Proportion of Patients With FLOT Dose Modifications [From FLOT initiation until the last FLOT dose, up to approximately 8 months]
• Completion of Planned Perioperative FLOT [From FLOT initiation until the last FLOT dose, up to approximately 8 months]
• Cumulative Incidence of Recurrence [From R0 resection until recurrence, death or last follow-up, assessed at 12, 24 and 36 months (up to approximately 6 years)]
• Overall Survival [From FLOT initiation until death or last follow-up, assessed at 12, 24 and 36 months (up to approximately 6 years)]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients older than 18 years with histologically confirmed stage I, II or III adenocarcinoma of the stomach or gastroesophageal junction.
* Initiation of perioperative FLOT chemotherapy at Fundación Santa Fe de Bogotá between January 1, 2021 and December 31, 2025.
* Sufficient clinical and treatment information to classify the patient and evaluate at least one study outcome (pathological response, toxicity, treatment adherence and completion, recurrence or vital status).

Exclusion Criteria:

* Metastatic (stage IV) disease documented at initial diagnosis, before starting perioperative FLOT.
* Gastric or gastroesophageal junction tumors of non-adenocarcinoma histology (for example, lymphoma, gastrointestinal stromal tumor or neuroendocrine carcinoma).
* Lack of the minimum information required for classification (no record of the FLOT regimen received, of clinical or pathological stage, or of at least one assessment of the primary outcome).
* Oncology follow-up performed exclusively outside the institution, without adequate traceability of postoperative and long-term outcomes.

• Henry Alexander Vargas Díaz, MD, Principal investigator, Fundación Santa Fe de Bogotá