PATHOMORPHOLOGICAL TUMOR REGRESSION AS A CRITERION FOR THE EFFECTIVENESS OF TOTAL NEOADJUVANT CHEMOTHERAPY IN THE FLOT REGIMEN IN PATIENTS WITH LOCALLY ADVANCED GASTRIC AND GASTROESOPHAGEAL JUNCTION CANCER

A.Yu. Anokhin1,2, P.V. Kononets1, D.Yu. Kanner3, D.L. Stroyakovsky3, A.O. Shveykin3, A.E. Kalinin1, V.Yu. Kirsanov2, A.S. Tyulyandina1,2

1N.N. Blokhin National Medical Research Center of Oncology, Moscow

2N.V. Sklifosovsky Institute of Clinical Medicine of the Sechenov First Moscow State Medical University (Sechenov University), Moscow

3Moscow City Oncological Hospital №62, Moscow region, Krasnogorsk, Istra

Anokhin Aleksandr Yu. ― Oncologist of the department of antitumor drug therapy №4 of the N.N. Blokhin National Medical Research Center of Oncology

24 Kashirskoe highway, Moscow, 115522, Russian Federation, tel. (499) 324-98-64, e-mail: anokhinaleks@mail.ru, ORCID: 0000-0001-8981-5748

Abstract

Background. In recent years, there has been an observable trend in the treatment of various oncologic diseases, marked by an expanding range of indications for neoadjuvant drug therapy. The primary objectives of this approach include increasing the frequency of pathomorphological responses, reducing the prevalence of the disease process, and eliminating micrometastases. These objectives aim to enhance treatment outcomes for patients with locally advanced forms of the disease. We hypothesize that the intensification of preoperative treatment through the administration of 8 courses of neoadjuvant chemotherapy with FLOT regimen may contribute to the improved efficacy of combined treatment in individuals with locally advanced gastric cancer and gastroesophageal junction cancer.

The aim of the study is to assess the frequency of pathomorphological responses following total neoadjuvant chemotherapy with FLOT regimen among patients with locally advanced gastric cancer. Additionally, we seek to analyze the long-term outcomes based on the degree of tumor regression.

Material and methods. This study reports the outcomes of a retrospective analysis, involving patients diagnosed with histologically confirmed locally advanced gastric cancer and gastroesophageal junction cancer. The participants, treated between 2014 and 2020, received care at N.N. Blokhin National Medical Research Center of Oncology, and Moscow City Oncological Hospital №62, State Budgetary Institution of Healthcare, Department of Healthcare of Moscow. Inclusion criteria comprised clinical stage T2-4, N0-3, and the absence of distant metastases. During the study, the control group underwent 8 courses of perioperative chemotherapy (4 preoperatively and 4 postoperatively), while the experimental group received 8 courses of total neoadjuvant chemotherapy. In both cohorts, the administered drug therapy strictly followed the FLOT protocol, involving 5-fluorouracil 2600 mg/m2, intravenous drip, over 24 hours, leucovorin 200 mg/m2, intravenous drip, oxaliplatin 85 mg/m2, intravenous drip, and docetaxel 50 mg/m2, intravenous drip; all initiated on day 1, with a 14-day intercourse interval.

Results. A total of 187 patients participated in the study, with the cohort divided into two groups: 95 in the total neoadjuvant chemotherapy group and 92 in the perioperative chemotherapy group. The frequency of complete pathomorphological responses in the neoadjuvant chemotherapy group was 17% (16/94), while in the perioperative group, it was 13,5% (12/89) (p=0,54). For Mandard grade 1-2 pathomorphologic responses, the neoadjuvant chemotherapy group exhibited a frequency of 40,4% (38/94), surpassing the perioperative chemotherapy group at 23,6% (21/89) (p=0,02). Additionally, the neoadjuvant chemotherapy group demonstrated a higher incidence of tumor stage reduction compared to the perioperative chemotherapy group, recording rates of 60,6% (57/94) and 46,1% (41/89), respectively (p=0,05). An independent favorable factor linked to a reduced risk of recurrence was a decrease in tumor stage (OR 0,4, 95% CI, 0,22-0,726, p=0,0001).

Conclusions. Among patients with locally advanced cancer and gastroesophageal junction cancer, the application of total neoadjuvant chemotherapy following the FLOT regimen over 8 courses resulted in a notable escalation in the frequency of pathomorphological responses, as observed in our study. The multivariate analysis highlighted that the reduction in the cancer stage serves as a favorable factor, significantly contributing to the mitigation of recurrence risk.

Key words: gastric cancer, gastroesophageal junction cancer, locally advanced gastric cancer, perioperative chemotherapy, total neoadjuvant chemotherapy, pathomorphological regression, gastrectomy, pathomorphosis, complete pathomorphological response.