Perioperative chemotherapy and morphological response in the treatment of gastric cancer: A retrospective study

Aim. To analyze the treatment (8 cycle FLOT + surgery) to search for predictors of tumor pathomorphosis, assess the impact of chemotherapy on treatment results, and identify other factors that significantly influence treatment results.

Materials and methods. Included 119 patients who underwent perioperative chemotherapy (FLOT) in combination with surgery in 2023 on the basis of the Nizhny Novgorod Regional Clinical Oncological Dispensary. This study consisted of two blocks: Identification of relationships between the analyzed parameters and the pathomorphological response, the development of postoperative complications. Analysis of overall and disease-free survival (DFS). In the analysis of nominal indicators, the first step was to use χ2 Pearson and Fisher's exact test. At the second stage, when statistical significance was achieved, the strength of the relationship was calculated for variables with two levels of the factor – Cramer’s V on the Rea & Parker scale, odds ratio (OR) with a 95% confidence interval (CI), for variables with more than two factors, post-hoc analysis was performed with Benjamini–Hochberg correction for multiple comparisons. All quantitative indicators in the published sample have a distribution other than normal. The measure of central tendency is the median with 25th and 75th percentiles. When comparing two groups of quantitative indicators, the Mann–Whitney test was used; when comparing a larger number of groups, the Kruskal–Wallis test was used with post-hoc analysis using the Dunn test (if statistically significant differences were achieved at the first stage).

Results. Analyzing the relationship between neo-adjuvant chemotherapy according to the FLOT regimen and the presence of response (TRG I–II), there was a lack of respondents in the subgroup who received neo-adjuvant chemotherapy according to regimens other than FLOT (p=0.019). Patients with stage I disease have a comparatively higher response rate to treatment compared with patients with ≥ stage III disease (post-hoc p-value=0.006). In the group of respondents there are fewer patients with positive lymph nodes compared to the group that did not respond to treatment (8.7% and 91%), the result is statistically significant (p-value <0.001). The presence of a response (TRG I–II) statistically significantly reduces the chance of positive tests by 7.30 times – OR 0.137 (95% CI 0.044–0.421). When conducting a subgroup analysis, the median age of patients with complications of types I–IIIa by Clavien–Dindo is statistically significantly lower compared to complications of types IIIb–V. There was no statistically significant relationship between tumor differentiation and response to treatment (p=0.3). When analyzing overall survival, there was a statistically significant increase in the risk of death with an increase in the number of postoperative days by 1 by 1.134 times or 13.4% (p=0.004). An increase in the number of metastatic lymph nodes by 1 increased the risk of death by 1.091 times or 9.1% (p=0.017). When analyzing DFS, a statistically significant increase in the risk of progression was revealed with an increase in the degree of pathomorphosis according to Mandard by 1 degree (starting from I) by 1.423 times or by 42.3% (p=0.042), an increase in the degree of pN-status by 1 (starting from N1) by 1.290 times or by 29.0% (p=0.011), an increase in the number of postoperative days by 1 by 1.099 times or by 9.9% (p=0.025). When analyzing the overall survival of the subgroup who received adjuvant chemo, there was a statistically significant increase in the risk of death in the subgroup of patients with adjuvant cgemo with an increase in the number of metastatic nodes by 1 by 1.087 times or by 8.7% (95% CI 1.009–1.172; p=0.029). When analyzing DFS of the subgroup who received adjuvant chemo, there was a statistically significant increase in the risk of progression in the subgroup of patients who received adjuvant chemo with an increase in the degree of pN status by 1 (starting from N1) by 1.252 times or 25.2% (p=0.040). When determining the effect of adjuvant chemo on overall survival and DFS using the Cox regression method, no statistically significant results were obtained. However, taking into account the p-value close to 0.05, the regression coefficient and most of the 95% CI (less than 1), it can be assumed that conducting adjuvant chemo reduces the risks of death and disease progression, and to achieve statistically significant results, a larger number of and observation time, number of outcomes.

Conclusion. Neo-adjuvant FLOT is associated with a large number of TRG I–II in patients with an early stage of the disease in comparison with advanced forms of the disease. There was no effect of tumor differentiation or its histological subtype on the degree of TRG. Perioperative chemotherapy does not increase the incidence or severity of postoperative complications. Metastatic lesions of the lymph nodes significantly worsen overall survival and DFS; in the group of patients with TRG grade I–II, the frequency of metastatic lymph node lesions is lower compared to patients with TRG III–V. There is no significant data on the need for adjuvant chemo in the presence or absence of pathomorphosis, however, it can be assumed that performing adjuvant chemo reduces the risks of death and disease progression.