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Histopathological tumor regression as a prognostic predictor in patients with gastric adenocarcinoma undergoing neoadjuvant chemotherapy with FLOT in cancer center
Neoadjuvant chemotherapy (NAT) has been successfully introduced as standard of care for locally advanced gastric adenocarcinoma. Recently, the FLOT4 trial has demonstrated superiority of the FLOT regimen (5-FU, leucovorin, oxaliplatin and docetaxel) compared with previous regimens. However, there are still no objective tools to characterize proper tumor regression. Histopathological regression tumor grading system has been proven to be an useful objective parameter to response to NAT and prognosis.
This study aimed to evaluate tumor pathological response (RPT) to FLOT as a possible prognostic predictor in patients with gastric cancer.
This is an observational prospective study who included patients undergoing NAT with FLOT for gastric adenocarcinoma in a cancer center. Surgical specimens after curative resection were characterized according to RPT to NAT, and its correlation with survival and clinical features were analyzed.
40 patients were included, of which 32.5% had complete or almost complete pathological response (group RPT 0/1), and 67.5% had minimum or none pathological response (group RPT 2/3). Pathological complete response (pCR) was 12.5%, smaller than the one found in the FLOT4 trial (p=NS). The RPT 0/1 group had improved disease-free survival compared with RPT 2/3 group (HR 0.16, 95% IC 0.042 to 0.63, log-rank p value= 0.0086). Microsatellite instability (MSI) was found in 15% of all patients, as well as in 22% of patients in RPT 2/3 group, and none in RPT 0/1 group, (p=NS). There was no statistically significant difference between the groups regarding overall survival, age, sex, tumor location, family history of cancer and clinical staging. The RPT 2/3 group had a bigger proportion of undifferentiated diffuse tumors with signet-ring cells, with no statistical significance. Resectability and perioperative morbidity were lower in this study compared with FLOT4, with similar R0 resectability. Chemotherapy compliance was similar, and grade III toxicity was higher in FLOT4 trial.
RPT is a good predictor for disease-free survival in patients undergoing NAT with FLOT for gastric cancer, with acceptable compliance and tolerance, and it may be a useful tool to guide therapy. MSI frequency was higher in RPT 2/3 group. Predictive markers of good pathological tumor response to FLOT were not identified.
pathological tumor response, FLOT, gastric cancer
Trato gastrointestinal alto*
CECÍLIA ARAÚJO CARNEIRO LIMA, DANIELE DE GODOY MAGALHÃES, GABRIEL LOTERO LIMA, SÉRGIO RICARDO SOARES DE MOURA, MÁRIO RINO MARTINS