FLOT Regimen Research Articles

OGC SO42 - A comparison of body composition changes between neoadjuvant FLOT and MAGIC regimes in patients with locally advanced oesophageal cancer

Abstract Background Several studies have documented the changes in body composition that can occur between pre and post neoadjuvant chemotherapy for locally advanced OGA. However, none have compared the changes between different neoadjuvant regimes following the shift in practice from MAGIC to FLOT neoadjuvant chemotherapy. Specifically, given that the FLOT regimen has been thought to be more toxic than MAGIC regimen, it is unclear whether this toxicity is measurable and clinically significant with regards to body composition. This study aims to compare the changes in body composition between these two regimens in patients with locally advanced oesophageal cancer. Method We conducted a retrospective cohort study comparing changes in body composition between patients receiving either MAGIC or FLOT neoadjuvant chemotherapy. 115 patients treated with FLOT (n = 61) or MAGIC (n = 54) who underwent an oesophagectomy for OGA between 2008 and 2020 at Queen Elizabeth Hospital, Birmingham, UK were ultimately enrolled in the study. Changes in body composition between pre- and post-neo-adjuvant chemotherapy were determined by analysis of computed tomography (CT) imaging. Slice-O-Matic is a software tool allowing segmentation of body tissues into different classes Including skeletal muscle and fat based on the Hounsfield units. Results Our findings showed a statistically significant difference in the weight loss of participants enrolled the MAGIC group compared to FLOT (FLOT -0.6 ±6.9 vs MAGIC -3.4 ±1.2, p=0.034) which was therefore also reflected in BMI differential before and after neoadjuvant chemotherapy (FLOT -0.2 ± 2.2 vs MAGIC -1.2 ± 2.7, p=0.024). However, there was no statistically significant difference in the L3 skeletal muscle index in both regimes (FLOT -2.8 ± 4.1 vs MAGIC -2.9 ± 4.1; p=0.93). Finally, changes in L3 fat index between the two cohorts did not demonstrate statistically significant difference in our study (FLOT -0.9 ± 22.6 vs MAGIC -5.6 ± 24.8; p=0.29). Conclusion Our study suggests that a large proportion of patients with locally-advanced OGA were sarcopenic prior to starting chemotherapy and this proportion increased post treatment. There was no statistically significant loss of muscle mass or fat during treatment with either MAGIC or FLOT. Despite this, weight loss and decreases in BMI were greater in the MAGIC group compared to FLOT, suggesting FLOT may have a more favourable toxicity profile with regard to body composition. Overall, our findings support the safety profile of FLOT chemotherapy with regard to body composition changes and illustrates a superior pathological response to FLOT therapy for OGA.

OGC O05 - Utilising patient derived organoids to predict the response to treatment in gastric cancer

Abstract Background Gastric adenocarcinoma remains a significant global health burden. For advanced disease, treatment remains multi-modal with neoadjuvant chemotherapy followed by resectional surgery. Although the FLOT4-AIO trial has established the regimen of 5-fluorauracil, Leucovorin, Oxaliplatin and Docetaxel (FLOT) as the gold standard, some patients demonstrate a poor or no response to treatment, resulting in adverse oncological outcomes. Currently there are no accurate biomarkers to assess or predict the treatment response to neoadjuvant therapy. This study aims to explore the potential of patient-derived organoids as a predictive model to assess the treatment response to neoadjuvant chemotherapy in gastric adenocarcinoma. Method Patient derived organoids are a novel, 3 dimensional in-vitro model which recapitulates the different cells that constitute the tissue of origin. From June 2023 to June 2024, 25 patients with a confirmed diagnosis of gastric adenocarcinoma, were recruited for tissue acquisition for organoid generation. Endoscopic biopsies of cancer tissue taken during OGD and staging laparoscopy were used to generate organoids from each patient. Organoids were subsequently expanded to a sufficient volume to allow cytotoxicity assays in response to different doses of the FLOT regimen. The organoid cytotoxicity response was compared to the patients radiological and pathological response following treatment. Results Organoids were successfully generated from 76% of recruited patients (n=19). Of these, 4 patients and were excluded due to being unfit for neoadjuvant chemotherapy, whilst 2 were excluded due to the confirmation of metastatic disease, precluding neoadjuvant treatment. Finally a single patient was excluded due to mortality during neoadjuvant treatment. Of the remaining organoids, 5 were subjected to FLOT treatment within 2 weeks of tissue acquisition. Organoids demonstrated unique dose response profiles following with statistically significant differences in the IC50 values (p =0.048). The organoid responses corresponded to the clinical responses demonstrated by the patient they were derived from. Conclusion In conclusion, this study underscores the potential of patient-derived cancer organoids as a predictive model for assessing the response to neoadjuvant chemotherapy in gastric adenocarcinoma. The generation of organoids from a significant proportion of patients and the subsequent drug response testing within 2 weeks of tissue acquisition suggests this novel method has the potential to become a valuable tool for predicting patient-specific responses and guiding personalised treatment plans. As such, further research is warranted to further assess the validity of this model, refine the existing techniques and explore its potential integration into clinical practice.

Comparison of the efficacy of neoadjuvant chemotherapy with FLOT regimen and adjuvant chemotherapy with XELOX/FOLFOX regimen in patients with locally advanced gastric cancer: A retrospective study

Background. To date, there is no consensus on the preferred sequence of combined treatment in patients with locally advanced gastric cancer (perioperative chemotherapy – POCT or primary surgical treatment). No direct comparison of these approaches had been conducted before. Aim. To compare, in retrospective analysis, 3-year relapse-free (RFS) and overall survival (OS) in patients receiving POCT FLOT or adjuvant chemotherapy XELOX/FOLFOX for locally advanced gastric cancer. Materials and methods. The assessment included 153 patients who underwent POCT FLOT and 171 patients who underwent surgical treatment at the first stage. When evaluating the initial characteristics, it was shown that patients with ECOG (The Eastern Cooperative Oncology Group) stage 1-2, clinical stage cT4a-b, cN2-3 and Bormann type 4 to were significantly more common in the POCT group. Morphological characteristics: grade, presence of signet cell carcinoma, HER2/neu overexpression, microsatellite instability, sensitivity to immunotherapy (Combined Positive Score) didn't differ. Results. With a median follow-up of 40 months, it was shown that the long-term results assessed in all included patients were better in the group with primary surgical treatment: 3-year RFS was 55 and 40% (risk ratio – RR 1.33, 95% confidence interval – CI 1.08–1.64; р=0.007). 3-year OS was 68 and 56% (RR 1.36, 95% CI 1.02–1.8; р=0.04), respectively. However, when evaluating patients who received surgical treatment in the POCT group (n=121, 79%), the results did not differ: 3-year RFS 55 and 50% (RR 0.9, 95% CI 0.71–1.16; р=0.97), 3-year OS 68 and 63% (RR 1.1, 95% CI 0.84–1.59; р=0.97). Insufficient volume of adjuvant chemotherapy (75% of the dose) significantly worsened long-term results (3-year OS 43 and 71%; p=0.002). Conclusion. The obtained data of a retrospective analysis did not reveal the advantages of any of the approaches provided that the surgical stage was performed in patients receiving POCT. To obtain more objective results, it is necessary to conduct randomized multicenter studies in the high volume centers, providing the necessary sample capacity, quality of diagnosis and treatment. Thus, the design of future studies should be based on the hypothesis of non-inferiority, which inevitably entails a significant increase in the required number of observations to obtain reliable sampling power.

Tolerability of perioperative chemotherapy for gastric cancer in real clinical practice

Background. The choice of the optimal scheme of perioperative chemotherapy of locally advanced gastric cancer is an urgent problem in real clinical practice. Aim. To analyze therapy tolerability in this cohort of patients. Materials and methods. Perioperative chemotherapy of gastric cancer was performed in 90 patients in the Chemotherapy Department of the Oncology Center №1 of the Yudin City Clinical Hospital from January 2021 to February 2024. Results. The incidence of severe complications at the preoperative stage was 41.9% for the FOLFOX regimen and 40.7% for the FLOT regimen, at the adjuvant stage – 17.4 and 43.2%, respectively. Operative treatment was successfully performed in 79 (87.8%) patients, and the full scope of combined treatment of locally advanced gastric cancer was completed in 59 (65%) patients. 80.8% of pathomorphologic responses in the FOLFOX group and 67.9% in the FLOT group were TRG3-4, with complete response noted in only one patient. Conclusion. High toxicity rates in elderly and comorbid patients on the FOLFOX regimen require the development of an individualized approach to the treatment of this group of patients.

Tumor-Infiltrating Lymphocytes in Resected Esophageal and Gastric Adenocarcinomas Do Not Correlate with Tumor Regression Score After Neoadjuvant Chemotherapy: Results of a Case-Series Study.

Background/Objectives: Adenocarcinomas of the esophagogastric junction and stomach present clinical entities with significant cancer-related morbidity and mortality, often requiring multimodal treatments. Preoperative chemotherapy, mainly the FLOT regimen, is increasingly being utilized in the neoadjuvant setting for the treatment of these malignancies, with varying degrees of tumor response. Methods: We conducted a retrospective, single-institution review on 75 patients operated on for adenocarcinoma of the esophagogastric junction and stomach after neoadjuvant FLOT. We investigated whether tumor response correlates with disease response in lymph nodes examined on surgical specimens. We also investigated the role of tumor-infiltrating lymphocytes (TILs) in correlation with primary tumor response and disease response in lymph nodes on pathological specimens. Results: Our results suggest that TILs correlate in a differential manner with regards to primary tumors versus lymph nodes, thus suggesting that there are different biologic processes in place. Conclusions: Our results provide unique evidence on tumor-infiltrating lymphocytes in the adenocarcinoma histology of the esophagogastric junction and stomach and might be important for further studies.

Risk of cardiac arrhythmias and outcomes with perioperative FLOT vs CROSS regimens for esophageal adenocarcinoma

Risk of cardiac arrhythmias and outcomes with perioperative FLOT vs CROSS regimens for esophageal adenocarcinoma

Efficacy and Safety of First-Line Palliative Chemotherapy with Fluorouracil Plus Leucovorin, Oxaliplatin, and Docetaxel (FLOT) in HER2-Negative Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: A Single-Institutional Real-World Experience from Eastern India

Background Fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) is one of the preferred perioperative chemotherapy regimens in locally advanced resectable gastric cancer (GC). Till date, there are very few published data from India, regarding the outcomes of this relatively well-tolerated biweekly triplet regimen as first-line palliative chemotherapy in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Materials and Methods In the present retrospective study, we evaluated the efficacy and safety of first-line FLOT regimen in Indian patients with HER2-negative metastatic adenocarcinoma of stomach or GEJ. The primary endpoint was overall survival (OS). Progression-free survival (PFS), overall response rate (ORR), and toxicity profile were taken as secondary endpoints. Results Between January 2021 and June 2024, 88 patients were treated with FLOT. The median age was 52 years (range, 23–68); 69.3% were males and 37.5% of the patients had ≥ 3 metastatic disease sites involvement at baseline. Dose reductions due to toxicity were required in 25% of the patients. The ORR was 68.2%; median PFS and OS were 6.3 months (95% confidence interval [CI]: 5.3–7.4) and 12.5 months (95% CI: 11.3–14.2), respectively. The most frequent grade 3 to 4 adverse events were diarrhea (15.9%), fatigue (13.6%), and neutropenia (12.5%). Younger patients (aged < 55 years) had much less ≥ grade 3 diarrhea (7.5%, n = 4), compared with patients aged ≥ 55 years (28.6%, n = 10). There was one toxicity-related death. Conclusion In the present study, biweekly FLOT regimen with primary prophylactic granulocyte colony-stimulating factor demonstrated encouraging efficacy with a favorable nongastrointestinal toxicity profile in Indian patients with HER2-negative metastatic gastric or GEJ adenocarcinoma. Clearly, this well-tolerated triplet regimen should be explored further through large prospective randomized trials in Asian patients.

The Comparison of FLOT and DCF Regimens as Perioperative Treatment for Gastric Cancer.

Locoregional gastric cancer is a still serious problem and perioperative treatments may improve success of management. Different regimens were examined. The present study purposed to compare efficacy of FLOT and DCF regimens. Retrospective multicenter study assesed the patients with locoregional gastric cancer. There are 240 patients (137 DCF, 103 FLOT). Survival rates were compared. Demographic features were similar between two groups, but time period was different. FLOT group had 7.8% pathological complete response, while DCF group did not have. Disease-free survival was longer in FLOT than DCF group (median not reached-13.94 months respectively). Median overall survival was similar (30.9 vs 37.8 months) but median follow-up affected the analysis. Survival for 36 months was 63% for FLOT and 40% for DCF group (p=0.015). FLOT regimen was superior on DCF regimen for response and survival rates. DCF is historical approach. Long term follow up period needed for FLOT treatment.

Diagnostic Potential of miR-143-5p, miR-143-3p, miR-551b-5p, and miR-574-3p in Chemoresistance of Locally Advanced Gastric Cancer: A Preliminary Study.

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Although the incidence is decreasing in developed countries, the treatment results are still unsatisfactory. The standard treatment for locally advanced gastric cancer (LAGC) is gastrectomy with perioperative chemotherapy. The association of selected microRNAs (miRNAs) with chemoresistance was assessed using archival material of patients with LAGC. Histological material was obtained from each patient via a biopsy performed during gastroscopy and then after surgery, which was preceded by four cycles of neoadjuvant chemotherapy (NAC) according to the FLOT or FLO regimen. The expression of selected miRNAs in the tissue material was assessed, including miRNA-21-3p, miRNA-21-5p, miRNA-106a-5p, miRNA-122-3p, miRNA-122-5p, miRNA-143-3p, miRNA-143-5p, miRNA-203a-3p, miRNA-203-5p, miRNA-551b-3p, miRNA-551b-5p, and miRNA-574-3p. miRNA expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The response to NAC was assessed using computed tomography of the abdomen and chest and histopathology after gastrectomy. The statistical analyses were performed using GraphPad Prism 9. The significance limit was set at p < 0.05. We showed that the expression of miR-143-3p, miR-143-5p, and miR-574-3p before surgery, and miR-143-5p and miR-574-3p after surgery, decreased in patients with GC. The expression of miR-143-3p, miR-143-5p, miR-203a-3p, and miR-551b-5p decreased in several patients who responded to NAC. The miRNA most commonly expressed in these cases was miRNA-551b-5p. Moreover, it showed expression in a patient whose response to chemotherapy was inconsistent between the histopathological results and computed tomography. The expression of miR-143-3p, miR-143-5p, miR-203a-3p, and miR-551b-5p in formalin-fixed paraffin-embedded tissue (FFPET) samples can help differentiate between the responders and non-responders to NAC in LAGC. miR-143-3p, miR-143-5p, and miR-574-3p expression may be used as a potential diagnostic tool in GC patients. The presence of miR-551b-5p may support the correct assessment of a response to NAC in GC via CT.

Immunotherapy plus chemotherapy versus chemotherapy alone in perioperative treatment for locally advanced gastric cancer: A systematic review and meta-analysis.

e16083 Background: The standard care for locally advanced gastric (LAGC) or gastroesophageal junction (GEJ) cancer is perioperative chemotherapy (CTX) with surgery. The therapeutic landscape has evolved with PD-1 and PD-L1 inhibitors, showing promise in advanced or metastatic disease. Investigating their role in locally advanced disease is an active research area. In response, we conducted a meta-analysis to evaluate the effectiveness of perioperative immunotherapy with CTX in LAGC/GEJ patients. Methods: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) comparing perioperative PD-1 and PD-L1 inhibitors in combination with CTX versus CTX alone for LAGC/GEJ. Evaluated outcomes included pathological complete response (pCR), R0 resection rate, downstaging rate, and treatment-related adverse events (TRAE) with a grade ≥ 3. Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis. Statistical analyses were performed using R software version 4.3.2. Results: Among 2,452 patients from six RCTs, 1,228 (50.08%) received immunotherapy. Combining immunotherapy with CTX showed substantial improvements in pCR (RR 2.83; 95% CI 1.78-4.50; p &lt; 0.001). This effect persisted in the FLOT CTX subgroup (RR 2.15; 95% CI 1.37-3.38; p &lt; 0.001). Additionally, downstaging outcomes were superior in the immunotherapy group, with ypT0 (RR 1.96; 95% CI 1.50-2.55; p &lt; 0.001) and ypN0 (RR 1.36; 95% CI 1.19-1.54; p &lt; 0.001). However, no significant differences were observed in the R0 resection rate (RR 1.01; 95% CI 0.98-1.04; p = 0.603) and TRAE grade 3 or higher (RR 1.05; 95% CI 0.98-1.13; p = 0.177). Conclusions: These findings emphasize the effectiveness of combining PD-1 and PD-L1 inhibitors with CTX, indicating an improved pathological response compared to CTX alone. As expected, these positive outcomes persisted in the FLOT regimen. Our results provide evidence supporting the combination of immunotherapy and CTX as a perioperative treatment option for LAGC/GEJ patients.

Long-term survival comparison of adjuvant FLOT versus XELOX chemotherapy for locally advanced gastric cancer in a large real-world cohort.

4080 Background: Recent Attraction-5 study has shown that logically advanced gastric cancer (LAGC) patients can't benefit from postoperative immunochemotherapy. The preferred adjuvant regimen for LAGC remains two-drug based chemotherapy as XELOX protocol, though three-drug based adjuvant FLOT regimen has not been well studied yet. This studyaimsto explore 10-year survival advantages of adjuvant FLOT versus XELOX regimen for LAGC. Methods: We retrospectively collected and analyzed data from 248 LAGC patients mainly composed of pathological T (pT) 3-4 stage, who received at least 4 cycles of FLOT or XELOX adjuvant chemotherapy at Lanzhou University Second Hospital from 2013 to 2018. To eliminate interference of confounding factors, we conducted a propensity score matching (PSM). The median follow-up time for all patients was 90.90 months. Results: After PSM, the median overall survival (OS) was 44.80 months in FLOT group and 34.87 months in XELOX group, with 5-year OS rate of 41.4% versus 25.3% and 10-year OS rate of 31.9% versus 11.8%. Subgroup analysis showed that patients with ECOG performance status 0 or pT3-4 stage attained significant survival benefits from adjuvant FLOT regimen. Grade 3-4 treatment-related adverse events occurred in 57.9% patients of FLOT group and 33.6% patients of XELOX group, while most of them were manageable. Conclusions: This study demonstrates that adjuvant FLOT regimen exhibits significantly long-term survival advantages for LAGC patients with good performance status and late disease stage compared with XELOX regimen, facilitating adjuvant FLOT regimen as a prospectively alternative option for LAGC.

Neoadjuvant therapy using PD-1 inhibitor plus chemotherapy with different intervals between chemotherapy cycles for locally advanced gastric or gastroesophageal junction cancer: A randomized phase 2 study.

4064 Background: To explore the influence of reducing dose-intensity of chemotherapeutic agents by prolonging the interval of chemotherapeutic cycles on clinical efficacy, especially when combined with immune checkpoint inhibitors, we conducted a single-center, prospective, randomized, phase II exploratory study in patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer. Methods: Patients were randomly assigned to receive either toripalimab plus FLOT regimen for four biweekly cycles or three triweekly cycles before the operation. The primary endpoint was pathological complete response (pCR) rate, the secondary endpoints were major pathological response (MPR) rate, event-free survival (EFS), and safety. Results: 70 patients were enrolled; of these, 69 were eligible for inclusion. The overall pCR rate was 26.1% and the MPR rate was 55.1%. There were no statistical differences in pCR rates and MPR rates between the two groups. Although no statistical differences were found among the subgroups, the pCR rate for patients with PD-L1 CPS ≥1 was 42.1% (8/19) while 6.7% (1/15) for PD-L1 CPS&lt;1 in the triweekly group ( P=0.047). Analysis of lymphocyte subsets in peripheral blood showed that CD3+CD8+PD-1+Ki-67+ T lymphocyte absolute counts were elevated in triweekly group and reduced in biweekly group before the second and third cycle of therapy. The incidence rates of pyrexia and myelosuppression in the biweekly group were higher than those in the triweekly group. Conclusions: These data support the idea that the efficacy of toripalimab plus FLOT, given triweekly for three cycles, was not inferior to its administration biweekly for four cycles in locally advanced G/GEJ cancer. The finding is particularly significant for those with PD-L1 CPS ≥1 and warrants further validation. Clinical trial information: NCT04891016 .

Pathologic Response Rates in Patients with Gastric Cancer Following FLOT Neoadjuvant Chemotherapy

Background: Gastric adenocarcinoma is among the most prevalent cancers associated with a high mortality rate. The multidrug neoadjuvant chemotherapy administered before and after surgery has attracted attention as a beneficial standard of care for managing this malignancy. Objectives: This study assessed the pathologic response of patients with gastric cancer who were treated with fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). Methods: Patients with pathologically confirmed gastric adenocarcinoma without distant metastases were enrolled in this retrospective cohort study conducted at Imam Reza and Ghaem hospitals in Mashhad. Data regarding demographics, tumor status, treatment toxicity, and pathology results were collected using a predesigned questionnaire after four cycles of FLOT neoadjuvant chemotherapy. SPSS-26.0 was utilized to analyze the data, and a significance level of P &lt; 0.05 was applied. Results: We evaluated data from 53 cases with a mean age of 51.1 ± 9.7 years. Diffuse adenocarcinoma was the most common finding in histology (54.7%). Pathologic complete response was observed in 16 (30.2%) patients. Most (69.8%) patients received only 7 out of 8 planned cycles. Concerning surgical margin, 46 (86.8%) patients achieved R0 tumor resection. Pathologic complete response was not significantly linked with age (P = 0.91), sex (P = 0.65), performance status (P = 0.2), tumor histology (P = 0.14), tumor grading (P = 0.07), tumor location (P = 0.8), and the number of neoadjuvant chemotherapy cycles (P = 0.9). Conclusions: Our findings demonstrated the relative clinical efficacy of neoadjuvant chemotherapy with the FLOT regimen administered before and after surgery. However, due to chemotherapy-related side effects, patients may not adhere to all eight prescribed cycles of chemotherapy.

Efficacy of total neoadjuvant chemotherapy in the FLOT regimen in patients with locally advanced gastric and gastroesophageal junction: results of a phase II study

Background. The established approach notably improving the therapeutic outcomes for locally advanced gastric cancer and gastroesophageal junction cancer, presently entails the amalgamation of perioperative chemotherapy aligned with the FLOT protocol and surgical intervention. However, this approach harbors limitations, as only half of the patient cohort successfully completes the entire prescribed course of drug therapy. The potential solution to this problem lies in the complete transfer of the chemotherapy volume to the preoperative period and the execution of total neoadjuvant chemotherapy with FLOT regimen.Aim. Aim is to conduct a comparative assessment of the efficacy and safety between total neoadjuvant and perioperative chemotherapy with FLOT regimen for patients with locally advanced gastric cancer and gastroesophageal junction cancer.Materials and methods. In a retrospective study we enrolled patients with histologically confirmed locally advanced gastric cancer and gastroesophageal junction cancer meeting clinical stage criteria T2–4 and N0–3, without of distant metastases, treated between 2014 and 2020 at Federal State Budgetary Institution “N. N. Blokhin National Medical Research Center of Oncology” оf the Ministry of Health of the Russian Federation and Moscow City Oncologic Hospital No. 62 Department of Healthcare of Moscow. Participants in the control group underwent 8 courses of perioperative chemotherapy (4 preoperatively and 4 postoperatively), while those in the experimental group received 8 courses of total neoadjuvant chemotherapy. Both groups received drug therapy according to the FLOT protocol: 5-fluorouracil 2600 mg/m2 , intravenous drip, over 24 hours, leucovorin 200 mg/m2 , intravenous drip, oxaliplatin 85 mg/m2 , intravenous drip, docetaxel 50 mg/m2 , intravenous drip, on day 1, with a 14-day intercourse interval. The primary endpoint was one-year progression-free survival.Results. In the study included 187 patients. Participants were divided into two groups: 95 in the total neoadjuvant chemotherapy group and 92 in the perioperative chemotherapy group. The one-year progression-free survival was higher in the total neoadjuvant chemotherapy group at 79 %, compared to 68 % in the perioperative chemotherapy group (HR 0.54, 95 % confidence interval 0.32–0.9, p = 0.02). Median disease-free survival was 27.2 and 19.5 months in the neoadjuvant and perioperative chemotherapy groups, respectively. The tolerability of the entire planned drug treatment regimen was superior in the total neoadjuvant chemotherapy group, reaching 88.4 %, as opposed to 57.6 % in the perioperative chemotherapy group (p = 0.0001).Conclusion. Among patients with locally advanced gastric cancer and gastroesophageal junction cancer, the application of total neoadjuvant chemotherapy according to the FLOT protocol, administered over 8 courses, demonstrated enhanced one-year progression-free survival and improved tolerability of the entire planned treatment regimen.

Assessment of the safety and feasibility of neoadjuvant chemotherapy (2 cycles of FLOT chemotherapy + chemoradiotherapy) followed by surgery in the treatment of locally advanced gastric cancer

The aim of the study was to analyze of the safety and feasibility of neoadjuvant chemotherapy (2 cycles of FLOT chemotherapy + chemoradiotherapy) followed by surgery in the treatment of locally advanced gastric cancer. Material and Methods. The phase II clinical trial included 47 patients with histologically verified locally advanced gastric cancer (cT3/T4a-b: 26/21 and cN0/N1–3: 20/27) treated at the A.F. Tsyba MRRC from 2018 to 2021. Lesion location was: upper third in 19 patients (esophageal invasion in 9 patients), middle third in 13 patients, lower third in 14 patients, and entire stomach in 1 patient. The tumor grade was G3 in 23 patients, G2 in 13 patients and G1 in 7 patients. Signet ring cell carcinoma was revealed in 4 patients. The patients received 2 cycles of induction chemotherapy with FLOT regimen (85 mg/m2 oxaliplatin + 200 mg/m2 calcium folinate + 50 mg/m2 docetaxel on day 1 + 2600 mg/m2 fluorouracil as 24-hour infusion from day 1; every 2 weeks) followed by 3d-conformal external beam radiotherapy (46 Gy in daily fractions of 2 Gy) combined with chemotherapy with capecitabine and oxaliplatin). The patients then underwent follow-up examination to exclude disease progression and to plan surgery. Postoperative complications were analyzed using the Clavien-dindo classification. Results. Induction chemotherapy followed by concurrent chemoradiotherapy was well tolerated. Forty-five (95.7 %) patients underwent surgery, 97.7 % of them underwent radical surgery. Postoperative complications were observed in 11 (23.4 %) patients. Grade III and more severe complications were observed in 3 (6.4 %) patients. It should be noted that postoperative mortality rate was low, amounting to 2.2 % (1 patient). Conclusion. Induction FLOT polychemotherapy followed by concurrent chemoradiotherapy was shown to be safe, feasible, and tolerable. Moreover, this treatment regimen did not reduce the frequency of R0 surgeries and did not increase incidence and severity of postoperative complications.

Interleukin-6 as a Predictive Factor of Pathological Response to FLOT Regimen Systemic Treatment in Locally Advanced Gastroesophageal Junction or Gastric Cancer Patients.

Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in the Western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was the identification of serum biomarkers of early response to NAC. We conducted this prospective study in the MSCNRIO in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers gave informed consent. Complete blood count, carcinoembryonic antigen (CEA), carcinoma antigen 125 (CA125), carcinoma antigen 19.9 (CA19.9), and fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3). Of all the measured parameters, only the IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in the complete pathological response (pCR) vs. the non-pCR group (3.71 pg/mL vs. 7.63 pg/mL, p = 0.004). In all patients with an IL-6 level below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to the Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs. ypN0 (7.69 pg/mL vs. 2.89 pg/mL, p = 0.022). The trial showed that an elevated level of IL-6 prior to treatment and C2 might be a predictor of pathological response to NAC.

FLOT compared to FOLFOX/XELOX as a neoadjuvant chemotherapy in locally advanced gastric cancer: Experience of two clinics.

361 Background: The optimal regimen of neoadjuvant chemotherapy (NCT) in locally advanced gastric cancer (GC) remains controversial, especially whether triplet (FLOT) or duplet (FOLFOX/XELOX) regimen is superior since escalation does not always lead to significant clinical improvement. The aim of this study is to assess efficacy of triplet and duplet chemotherapy regimens as a neoadjuvant approach in locally advanced GC via retrospective data. Methods: We queried the data for 334 patients with locally advanced GC (cT2-4 or cN+) diagnosed in 2016–2023 yy administered with multi-agent NCT: FLOT or XELOX/FOLFOX. The primary endpoints were the ratio of patients with disease progression on NCT, rates of ypN0, and rates of pathological complete response (pCR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). Results: 156 patients (out of total 334 included in the study) received doublet NCT (FOLFOX/XELOX, 8/6 cycles respectively), 61.5% were males, median age was 67.4 (range 21.3-85.4) years, 88.2% had cT3-4. and 22.4% had locally advanced gastroesophageal junction (GEJ) adenocarcinoma. 177 patients were treated with triple NCT (FLOT, 8 cycles), 62.1% were males, median age was 59.9 years, 89.2% had cT3-4, and locally advanced GEJ adenocarcinoma was diagnosed in 21.0%. At a median follow up of 34.7 months (mth) using FLOT regimen as NCT was associated with better clinical outcomes. The ratio of patients who have progressed on NCT was 21.5% and 31% in triplet and doublet arms, respectively (p=0.098). Rates of ypN0 were 50.5% in FLOT arm and 43.7% in XELOX/FOLFOX arm (p=0.36). pCR was achieved in 8.2% and 6.3% in FLOT and XELOX/FOLFOX arms, respectively (p=0.59). Median PFS was 20.3 mth in FLOT arm in comparison to 15.7 mth in FOLFOX/XELOX arm (p=0.012). Median OS was not reached (NR) for triplet arm and was 25.1 mth for doublet arm (p= 0.003). Patients who conversed resectable disease had median PFS of 34.5 and 23.1 months for FLOT and FOLFOX/XELOX arms, respectively (p=0.024). Median OS in these subgroups was NR and 37.0 mth (p=0.003). Conclusions: We report that triplet regimen (FLOT) in comparison with doublet (FOLFOX/XELOX) regimen is the more favorable option as a neoadjuvant setting in locally advanced gastric cancer. FLOT NCT is associated with increased ypN0, pCR and shows statistically significant difference in PFS and OS.

Chemotherapy and chemoradiotherapy for adenocarcinoma of the esophagus and junction with oligometastases: Results of the TNT-OES-1 trial.

328 Background: Chemotherapy (FLOT) and chemoradiotherapy (CROSS) are effective as neoadjuvant regimens for esophageal and junction cancer. Total Neoadjuvant Therapy (TNT) aims to increase efficacy by combining chemotherapy with chemoradiotherapy. Although TNT is increasingly used in rectal cancer, there are no data on combining FLOT and CROSS in esophageal cancer. This study aimed to evaluate the feasibility and safety of the FLOT-CROSS combination in esophageal and junction adenocarcinoma patients with oligometastatic disease. Methods: This phase-II study included patients with oligometastatic (a maximum of four lesions in up to two organs, excluding lymph nodes) esophageal adenocarcinoma. Patients were treated with four biweekly cycles of FLOT. Response was evaluated by CT-scan 4-6 weeks after completion of FLOT. If patients showed regression or stable disease (SD) based on RECIST criteria (v1.1), they received CROSS. Four to six weeks after completion of CROSS, response was assessed by CT-scan, endoscopy with biopsies and endoscopic ultrasonography. The multidisciplinary tumor board discussed whether patients could proceed to four additional cycles of FLOT or local therapy of metastases and/or esophagectomy. Primary endpoint was tolerability of FLOT-CROSS, defined as the proportion completing the full regimens. Secondary endpoints included disease control rate (DCR), objective response rate, toxicity and the proportion proceeding to local therapy of metastases and/or esophagectomy. Results: Twenty patients were included, the majority was male (85%) with a median age of 62.5 years (interquartile range 58-66) Most patients (80%) had a single metastatic lesion. 14 of 20 patients (70%) successfully completed the FLOT regimen, four are still in therapy and two patients died. Eleven of 14 patients completed FLOT-CROSS and three patients showed disease progression following FLOT. Toxicity mainly consisted of grade 1-2 leukopenia/neutropenia during FLOT, leading to treatment delay in seven patients. One patient had malaise grade 2. No grade 3-4 toxicities or treatment delays/discontinuations occurred during CROSS. Following FLOT-CROSS, seven patients underwent four additional cycles of FLOT. Six patients underwent esophagectomy and two of those also underwent local treatment of metastases. A pathologically complete response was seen in two of these six patients (33%). Three of seven patients had a clinically complete response and opted for active surveillance after shared decision making. Three months after completion of FLOT-CROSS, the DCR was 82%. Conclusions: This study showed that sequencing FLOT-CROSS in patients with oligometastatic esophageal adenocarcinoma is feasible and comes with manageable toxicity. We saw promising efficacy, with 82% having disease control three months after FLOT-CROSS. Survival data are expected mid-2024. Clinical trial information: NL9269 .

Evaluating the effect and mechanism of Yiqi Huayu Jiedu decoction combined with FLOT regimen neoadjuvant chemotherapy for the patients with locally advanced gastric cancer: protocol for a prospective, double-arm, randomized controlled clinical trial

Evaluating the effect and mechanism of Yiqi Huayu Jiedu decoction combined with FLOT regimen neoadjuvant chemotherapy for the patients with locally advanced gastric cancer: protocol for a prospective, double-arm, randomized controlled clinical trial

CT sarcometry in the prediction of postoperative complications in patients with gastric cancer: Retrospective cohort study

Aim. Computed tomographic preoperative assessment of sarcopenia in patients with gastric cancer as a part of combined treatment and the study of the relationship between sarcopenia and postoperative complications.&#x0D; Materials and methods. We analyzed retrospectively the data of 65 patients with morphologically verified diagnosis of stage IIA–IIIC gastric cancer. All patients at stage I of the combined treatment received neoadjuvant chemotherapy (NCT) according to the FLOT regimen, and then a gastrectomy with D2 lymph node dissection was performed. Computed tomography (CT) scans were performed before NCT initiation and 3.5 to 5 weeks after NCT completion for preoperative staging and assessment of tumor response. Using the obtained CT data, CT sarcometry was performed by calculating the cross-sectional area of skeletal muscles at the LIII vertebra level and the “skeletal-muscular index”. Postoperative complications were assessed using the Clavien–Dindo classification. Non-parametric comparison methods were used to assess the significance of differences between groups and subgroups (Wilcoxon T-test, Pearson χ2 test). Differences were considered statistically significant at p0.05.&#x0D; Results. We analyzed the incidence of sarcopenia in the examined patients before the NCT and immediately before the surgery. Sarcopenia was noted in 41 (63.1%) of 65 patients before NCT and in 50 (76.9%) patients after NCT, which indicates its high prevalence in patients with stomach cancer and the adverse effect of NCT on the muscular status of patients (76.9% versus 63.1%). Postoperative complications were diagnosed in 12 of 65 patients (18.5%). The rate of postoperative complications in patients with and without sarcopenia was not statistically significantly different (p=0.392); however, complications of Clavien–Dindo grade ≥IIIb occurred only in patients with sarcopenia (p0.001).&#x0D; Conclusion. According to our data, NCT in gastric cancer aggravates preoperative nutritional disorders. CT, as a standard method of staging and assessing the tumor response to NCT for gastric cancer, provides a tool to assess the state of muscle mass in patients before and after NCT. Preoperative sarcopenia is a risk factor for severe postoperative complications in patients with gastric cancer after gastrectomy.