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Objective: To compare the short-term and long-term efficacy of FLOT and FOLFOX in the treatment of advanced gastric cancer (GC), as well as their effects on serum tumor markers and NRP-2. Methods: 82 patients with advanced gastric cancer admitted to our hospital from March 2020 to February 2022 were selected and divided into FLOT group and FOLFOX group based on different chemotherapy methods, with 41 cases in each group. Compare the short-term and long-term efficacy, serum tumor markers and NRP-2 levels between two groups. Follow up until November 2023, record the survival status of two groups of patients and draw Kaplan-Meier survival curves. Results: The objective effective rate of FLOT group was higher than FOLFOX group (85.37% vs. 65.85%, P＜0.05) . The levels of serum carcinoembryonic antigen [ (12.77±1.85) ng/mL vs. (20.69±2.58) ng/mL], carbohydrate antigen 19-9 [ (20.46±5.20) U/m L vs. (29.41±8.04) U/m L], carbohydrate antigen 125 [ (14.90±5.61) U/m L vs. (20.72±6.23) ng/mL], and NRP-2 [ (13.01±2.11) ng/mL vs. (15.23 ±2.25) ng/mL] in the FLOT group were lower than the FOLFOX group after treatment, PFS [12.900 (95% CI:12.183～13.617) months vs. 9.600 (95% CI: 8.471～10.729) months] and OS [28.103 (95% CI: 25.209～30.996) months vs. 20.799 (95%CI: 18.482～23.115) months] were longer than the FOLFOX group (P＜0.05) . There was no difference in disease control rate and incidence of toxic side effects between the two groups (P＞0.05) . Conclusion: FLOT and FOLFOX are both effective chemotherapy regimens for mid to late stage GC, with consistent safety. However, the former has advantages in improving objective efficacy, reducing serum tumor markers and NRP-2 levels, and prolonging survival. [ABSTRACT FROM AUTHOR]

Background: The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer. Methods: Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m² docetaxel, 80 mg/m2 oxaliplatin, 200 mg/m² calcium levofolinate, 2600 mg/m² 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate. Results: Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8-42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgerywith anR0 resection rateof93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8-35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2-89.2%), 78.8% (95% CI, 65.1-95.5%), and 70.9% (95% CI, 54.8-91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3-93.1%) and 96.9%(95% CI, 84.3-99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade =3 treatmentrelated adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status. Conclusions: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population. [ABSTRACT FROM AUTHOR]

Background: Although the common treatment strategy for localized gastric cancer in Japan is gastrectomy followed by adjuvant chemotherapy, several randomized studies in non-Japanese populations have established perioperative chemotherapy as the standard treatment of localized gastric or gastroesophageal junction adenocarcinoma. Therefore, we have implemented this strategy in our institution. Patients and methods: We retrospectively reviewed the medical records of patients with resectable gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma who had received perioperative FLOT (5-fluorouracil plus docetaxel plus oxaliplatin plus leucovorin) from February 2020 to February 2023. Results: In this study, a total of 91 patients were analyzed, with a median age of 70 years (range: 29-82). At the time of diagnosis, 83 patients (91.2%) had T3 or higher-grade primary lesions, and 85 (93.4%) had lymph node metastasis. A total of 10 patients had resection before completing four cycles of preoperative chemotherapy, and 77 of 91 (84.6%) completed four cycles with 74 of them receiving radical resection. Among the 84 patients who had radical resection after FLOT, 82 (97.6%) achieved R0 resection, including 8 (9.5%) with a pathological complete response. After resection, 60 patients (65.9%) received at least one cycle of post-operative FLOT, and 47 (51.6%) completed eight cycles of FLOT treatment. Chemotherapy-related adverse events of grade 3 or higher occurred during the pre- and post-operative FLOT in 60 patients (65.9%), including leukopenia (30.8%), neutropenia (50.5%), febrile neutropenia (5.5%), and anorexia (7.7%). No treatment-related deaths occurred. Conclusions: These findings were comparable to those in the pivotal FLOT 4 trial, suggesting acceptable feasibility of the FLOT regimen in Japanese clinical practice.

Background and purpose: Perioperative 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) is recommended in resectable esophagogastric adenocarcinoma based on randomised trials. However, the effectiveness of FLOT in routine clinical practice remains unknown as randomised trials are subject to selection bias limiting their generalisability. The aim of this study was to evaluate the implementation of FLOT in real-world patients. Methods: Retrospectively collected data were analysed in consecutive patients treated before or after the implementation of FLOT. The primary endpoint was complete pathological response (pCR) and secondary endpoints were margin-free resection (R0), overall survival (OS), relapse-free survival (RFS) tolerability of chemotherapy and surgical complications. Results: Mean follow-up time for patients treated with FLOT (n = 205) was 37.7 versus 47.0 months for epirubicin, cis- or oxaliplatin, and capecitabine (ECX/EOX, n = 186). Surgical resection was performed in 88.0% versus 92.0%; pCR were observed in 3.8% versus 2.4%; and R0 resections were achieved in 78.0% versus 86.0% (p = 0.03) in the ECX/EOX and FLOT cohorts, respectively. Survival analysis indicated no significant difference in RFS (p = 0.17) or OS (p = 0.37) between the cohorts with a trend towards increased OS in performance status 0 (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.50–1.04). More patients treated with ECX/EOX completed chemotherapy (39% vs. 28%, p = 0.02). Febrile neutropenia was more common in the FLOT cohort (3.8% vs. 11%, p = 0.0086). 90-days mortality (1.2% vs. 0%) and frequency of anastomotic leakage (8% vs. 6%) were equal and low. Interpretation: Patients receiving FLOT did not demonstrate improved pCR, RFS or OS. However, R0 rate was improved and patients in good PS trended towards improved OS.

Background: The question of the ideal neoadjuvant therapy for locally advanced esophagogastric adenocarcinoma has not been answered to date. Multimodal treatment has become a standard treatment for these adenocarcinomas. Currently, perioperative chemotherapy (FLOT) or neoadjuvant chemoradiation (CROSS) is recommended. Methods: A monocentric retrospective analysis compared long-term survival after CROSS versus FLOT. The study enrolled patients with adenocarcinoma of the esophagus (EAC) or the esophagogastric junction type I or II undergoing oncologic Ivor–Lewis esophagectomy between January 2012 and December 2019. The primary objective was to determine the long-term outcome in terms of overall survival. The secondary objectives were to determine differences regarding the histopathologic categories after neoadjuvant treatment and the histomorphologic regression. Results: The findings showed no survival advantage for one or the other treatment in this highly standardized cohort. All the patients underwent open (CROSS: 9.4% vs. FLOT: 22%), hybrid (CROSS: 82% vs. FLOT: 72%), or minimally invasive (CROSS: 8.9% vs. FLOT: 5.6%) thoracoabdominal esophagectomy. The median post-surgical follow-up period was 57.6 months (95% confidence interval [CI] 23.2–109.7 months), and the median survival was longer for the CROSS patients (54 months) than for the FLOT patients (37.2 months) (p = 0.053). The overall 5-years survival was 47% for the entire cohort (48% for the CROSS and 43% for the FLOT patients). The CROSS patients showed a better pathologic response and fewer advanced tumor stages. Conclusion: The improved pathologic response after CROSS cannot be translated into longer overall survival. To date, the choice of which neoadjuvant treatment to use can be made only on the basis of clinical parameters and the patient's performance status. [ABSTRACT FROM AUTHOR]

Macroscopic type 4 and large type 3 gastric cancer, mostly overlapping with scirrhous or linitis plastica type, exhibit a highly invasive nature and show unfavorable prognosis after curative surgery, even with adjuvant chemotherapy. A randomized phase III trial (JCOG0501) failed to demonstrate a survival advantage of neoadjuvant chemotherapy with S-1 plus cisplatin for this population. The current authors initiated a randomized phase II study comparing neoadjuvant chemotherapy with 5-fluorouracil/oxaliplatin/docetaxel versus docetaxel/oxaliplatin/S-1 for type 4 and large type 3 gastric cancer. 76 patients are planned to be enrolled over two years. The primary end point is the proportion of patients with a pathological response (grade 1b or higher) and secondary end points include overall survival and adverse events. Clinical Trial Registration: jRCTs031230231 (rctportal.niph.go.jp). [ABSTRACT FROM AUTHOR]

The adverse effects of chemotherapy are more apparent in elderly patients and lead to worse prognosis and mortality. Identifying immunonutritional risk factors is of great importance in terms of treatment effectiveness, prognosis, and mortality in geriatric oncology. The modified Glasgow prognostic score (mGPS) is an immunonutritional index based on serum CRP and albumin levels. In this study, we aimed to investigate the role of mGPS in predicting prognosis and survival in elderly patients with gastric cancer receiving perioperative FLOT treatment. We retrospectively enrolled 71 patients aged over 65 years and grouped them according to their pretreatment mGPS score. Kaplan-Meier and Cox regression analysis showed overall survival was significantly worse in the mGPS 1 and mGPS 2 groups than in the mGPS 0 group (p = 0.005 and p < 0.001, respectively). Compared to the mGPS 0 group, the mGPS 1 group had a 6.25 times greater risk of death (95% CI: 1.61–24.28, p = 0.008), and the mGPS 2 group had a 6.59 times greater risk of death (95% CI: 2.08–20.85, p = 0.001). High BMI was identified as a significant risk factor for being in the mGPS 2 group (OR: 1.20, 95% CI: 1.018–1.425, p = 0.030). In conclusion, elevated pretreatment mGPS was associated with poor overall survival in elderly patients with gastric cancer treated with perioperative FLOT therapy. As such, pretreatment mGPS can be a simple and useful tool to predict mortality in this specific patient group. [ABSTRACT FROM AUTHOR]

Background: FLOT regimen is the standard perioperative treatment in Western countries for patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC). High microsatellite instability (MSI-H) and Mismatch Repair deficient (dMMR) demonstrated a favorable prognostic role and a concomitant negative predictive impact on the benefit of perioperative 5-fluorouracil-based doublets; however, its role in pts receiving FLOT chemotherapy is still unclear. Methods: This is a retrospective, multicenter observational study of 265 pts with GC/GEJC treated with perioperative FLOT regimen in 11 Italian oncology centers between January 2017 to December 2021 and analyzed for microsatellite status. Results: The MSI-H phenotype was found in 27 (10.2%) of 265 analyzed tumors. Compared to microsatellite stable (MSS) and Mismatch Repair proficient (pMMR) cases, MSI-H/dMMR were more frequently female (48.1% vs. 27.3%, p = 0.0424), elderly pts (age > 70 years, 44.4% vs. 13.4%, p = 0.0003), Laurens's intestinal type (62.5% vs. 36.1%, p = 0.02) and pts with a primary location tumor in the antrum (37 vs. 14.3%, p = 0.0004). A statistically significant difference in the rate of pathologically negative lymph node emerged (63% vs 30.7%, p = 0.0018). Compared to the MSS/pMMR tumor population, the MSI-H/dMMR subgroup had a better DFS (median not reached [NR] vs. 19.5 [15.59–23.59] mos, p = 0.031) and OS (median NR vs. 34.84 [26.68–47.60] mos, p = 0.0316). Conclusions: These real-world data confirm that FLOT treatment is effective in daily clinical practice for locally advanced GC/GEJC, also in the MSI-H/dMMR subgroup. It also showed a higher rate of nodal status downstaging and a better outcome of MSI-H/dMMR pts in comparison to MSS/pMMR. [ABSTRACT FROM AUTHOR]

Simple Summary: FLOT-based perioperative chemotherapy is the mainstay of treatment for patients with non-metastatic gastric cancer in Western countries. Although signet-ring cell histology has been proven to be associated with a lack of response to chemotherapy, there is a lack of data concerning whether FLOT-based chemotherapy might be less effective in patients with signet-ring histology. The aim of this retrospective study is to assess whether patients whose gastric cancer is signet-ring cell positive might benefit less compared to others when treated with perioperative FLOT. Background: FLOT perioperative chemotherapy represents the standard of care in non-metastatic gastric cancer patients. Signet-ring cell positivity is associated with a worse prognosis in patients with gastric cancer treated with chemotherapy. Comparison between FLOT perioperative chemotherapy vs. surgery followed by adjuvant chemotherapy based on signet-ring cell positivity is lacking. The aim of the analysis was to compare perioperative FLOT with adjuvant chemotherapy in gastric cancer patients stratified by signet-ring cell positivity. Methods: We conducted a retrospective multicenter analysis based on disease-free survival (DFS) and overall survival (OS) in patients with gastric cancer who received perioperative chemotherapy with a FLOT regimen and compared their survival with a historical cohort of patients treated with adjuvant chemotherapy, matched by cT and cN stage and by tumor histological features. Results: Seventy-six patients were enrolled and 24 (32%) were signet-ring cell positive. At a median follow-up time of 39 months, the median DFS was 26.3 months and the median OS was 37.3 months. Signet-ring cell positivity was associated with a shorter OS (median OS: 20.4 vs. 46.9 months, HR: 3.30, 95%CI: 1.56–6.99, p = 0.0018) and DFS (mDFS: 15.2 vs. 38.6 months, HR: 3.18, 95%CI: 1.55–6.54, p = 0.0016). This was confirmed by multivariate analysis for DFS (Exp(B): 2.55) and OS (Exp(B): 2.68). After propensity score matching, statistically significant shorter DFS (HR: 3.30, 95%CI: 1.50–7.35, p = 0.003) and OS (HR: 5.25, 95%CI: 2.18–12–68, p = 0.0002) were observed for patients with signet-ring cell positivity who received perioperative treatment vs. those who received surgery followed by adjuvant chemotherapy. Conclusions: Signet-ring positivity was associated with shorter DFS and OS in patients who received perioperative treatment with FLOT compared with surgery followed by adjuvant therapy. These data suggest that for patients with signet-ring cell histology, FLOT perioperative treatment might not always be the best choice of treatment, and further research should be focused on this group of patients. [ABSTRACT FROM AUTHOR]

This multicenter, randomized phase II/III study evaluated the addition of the vascular endothelial growth factor receptor‐2 inhibitor ramucirumab to FLOT as perioperative treatment for resectable esophagogastric adenocarcinoma. Patients received either FLOT alone (Arm A) or combined with ramucirumab followed by ramucirumab monotherapy (Arm B). The primary endpoint for the phase II portion was the pathological complete or subtotal response (pCR/pSR) rate. Baseline characteristics were comparable between both arms with a high rate of tumors signet‐ring cell component (A:47% B:43%). No between‐arm difference in pCR/pSR rate was seen (A:29% B:26%), therefore the transition to phase III was not pursued. Nevertheless, the combination was associated with a significantly increased R0‐resection rate compared with FLOT alone (A:82% B:96%; P =.009). In addition, the median disease‐free survival was numerically improved in Arm B (A:21 months B:32 months, HR 0.75, P = 0.218), while the median overall survival was similar in both treatment arms (A:45 months B:46 months, HR 0.94, P = 0.803). Patients with Siewert type I tumors receiving transthoracic esophagectomy with intrathoracic anastomosis showed an increased risk of serious postoperative complications after ramucirumab treatment, therefore recruitment of those patients was stopped after the first‐third of the study. Overall, surgical morbidity and mortality was comparable, whereas more non‐surgical grade ≥ 3 adverse events were observed with the combination, especially anorexia (A:1% B:11%), hypertension (A:4% B:13%) and infections (A:19% B:33%). The combination of ramucirumab and FLOT as perioperative treatment shows efficacy signals, particularly in terms of R0 resection rates, for a study population with a high proportion of prognostically poor histological subtypes, and further evaluation in this subgroup seems warranted. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the postoperative and pathological outcomes between carboplatin, paclitaxel, radiotherapy (CROSS) and 5-FU, leucovorine, oxaliplatin and docetaxel (FLOT) in esophageal adenocarcinoma (EAC) patients from an international, multicenter cohort. Summary of Background Data: Ongoing debate exists around optimum approach to locally advanced EAC, with proponents for perioperative chemotherapy, such as FLOT, or multimodal therapy, in particular the CROSS regimen. Methods: Patients undergoing CROSS (n = 350) and FLOT (n = 368), followed by curative esophagectomy for EAC were identified from the Oesophagogastric Anastomosis Audit. Results: The 90-day mortality was higher after CROSS than FLOT (5% vs 1%, P = 0.005), even on adjusted analyses [odds ratio (OR): 3.97, confidence interval (CI)95%: 1.34–13.67]. Postoperative mortality in CROSS were related to higher pulmonary (74% vs 60%) and cardiac complications (42% vs 20%) compared to FLOT. CROSS was associated with higher pathologic complete response (pCR) rates (18% vs 10%, P = 0.004) and margin-negative resections (93% vs 76%, P < 0.001) compared with FLOT. On adjusted analyses, CROSS was associated with higher pCR rates (OR: 2.05, CI95%: 1.26-3.34) and margin-negative resections (OR: 4.55, CI95%: 2.70-7.69) compared to FLOT. Conclusions: This study provides real-world data CROSS was associated with higher 90-day mortality than FLOT, related to cardio-pulmonary complications with CROSS. These warrant a further review into causes and mechanisms in selected patients, and at minimum suggest the need for strict radiation therapy quality assurance. Research into impact of higher pCR rates and R0 resections with CROSS compared to FLOT on long-term survival is needed. [ABSTRACT FROM AUTHOR]

Objective: The median survival time for metastatic gastric cancer that has a poor prognosis is usually shorter than 1 year. The fluorouracil, oxaliplatin, and docetaxel (FLOT) regimen is observed to be effective in the neo‑adjuvant treatment of gastric cancer. However, data on the FLOT regimen in metastatic gastric cancer are limited. The current study aims to evaluate the safety and efficacy of the FLOT regimen in metastatic gastric cancer in real life. Study Design: Retrospective study. Place and Duration of Study: The study was performed in an Institute of Oncology of a university and included the patients diagnosed between January 2015 and December 2020. Methodology: In addition to the clinicopathological data of patients with human epidermal growth factor receptor 2 (HER‑2)‑negative metastatic gastric cancer, we retrospectively evaluated the survival and treatment‑related toxicities. The FLOT regimen (Fluorouracil 2600 mg/m2 24 hours continuous intravenous infusion, leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and docetaxel 50 mg/m2 on day 1) every 2 weeks was used in all patients. Results: The study included 94 patients who were followed up for a median of 11.1 (min–max: 1.5–65.8) months. The number of male patients was 60 (63.4%), and the median age was 58 (min–max: 27–78) years. The primary tumor was located in the stomach (72.3%) and gastroesophageal junction (27.7%). The objective response rate was observed in 64.8% of the patients. The median overall survival was 13.5 (95% CI: 9.2–17.8) months, whereas the progression‑free survival was 7 (95% CI: 5.7–8.3) months. The 1‑year survival rate was 53.6%. Complete response was detected in 7.4% of the patients. Among grade 3–4 toxicities, neutropenia (44.6%), leukopenia (27.6%), neuropathy (12.7%), and fatigue (9.5%) were the most common observed toxicities. Conclusion: FLOT is a highly active option in the first‑line treatment of metastatic gastric cancer, with a favorable safety profile. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of oesophageal (OC), gastro-oesophageal junction (GOJ), and gastric cancer (GC) includes either neoadjuvant Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) for OC or GOJ or perioperative 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for OC, GOJ, and GC adenocarcinomas. This study aims to describe the real-world outcomes of patients with GC, GOJ, and OC treated with FLOT or CROSS and identify variables associated with efficacy through exploratory analysis. We also aimed to evaluate the comparison of FLOT and CROSS for the treatment of OC and GOJ adenocarcinomas. Methods: This is a retrospective observational study of patients with locally advanced OC, GOJ, or GC treated with FLOT or CROSS between January 2015 and June 2021 in 5 cancer centres across Sydney, Australia. Long-rank test was used to compare survival estimated between subgroups. Hazard ratios for univariate and multivariate analyses were estimated with Cox proportional regression. Results: The study included 168 patients. The 24-month relapse-free survival (RFS) and overall survival (OS) for FLOT were 59% and 69%, respectively. The median RFS was 29.6 months and median OS was not reached. For CROSS, the 24-month RFS and OS were 55% and 63% with a median RFS and OS of 28.5 and 40.2 months, respectively. There was no difference in OS and RFS between the treatments. FLOT was less tolerable than CROSS with more dose reductions, treatment discontinuation, and clinically relevant grade 3 and 4 toxicity. Neutrophil lymphocyte ratio was associated with survival for both treatments. Conclusion: Similar efficacy outcomes were seen in this real-world population compared to the clinical trials for FLOT and CROSS. [ABSTRACT FROM AUTHOR]

Background: The FLOT protocol and the CROSS trimodality regimen represent current standards in the management of locally advanced esophageal adenocarcinoma. In the absence of published Randomised Controlled Trial data, this propensity-matched comparison evaluated tolerance, toxicity, impact on sarcopenia and pulmonary physiology, operative complications, and oncologic metrics. Methods: Two hundred and twenty-two patients, 111 in each arm, were included from 2 high-volume centers. Computed tomography-measured sarcopenia, and pulmonary function (forced expiratory volume in first second/forced vital capacity/diffusion capacity for carbon monoxide) were compared pretherapy and posttherapy. Operative complications were defined as per the Esophageal Complications Consensus Group (ECCG) criteria, and severity per Clavien-Dindo. Tumor regression grade and R status were measured, and survival estimated per Kaplan-Meier. Results: A total of 83% were male, cT3/cN+ was 92%/68% for FLOT, and 86%/60% for CROSS. The full prescribed regimen was tolerated in 40% of FLOT patients versus 92% for CROSS. Sarcopenia increased from 16% to 33% for FLOT, and 14% to 30% in CROSS (P <0.01 between arms). Median decrease in diffusion capacity for carbon monoxide was −8.25% (−34 to 25) for FLOT, compared with −13.8%(−38 to 29), for CROSS (P =0.01 between arms). Major pathologic response was 27% versus 44% for FLOT and CROSS, respectively (P =0.03). In-hospital mortality, respectively, was 1% versus 2% (P =0.9), and Clavien Dindo >III 22% versus 27% (P =0.59), however, respiratory failure was increased by CROSS, at 13% versus 3% (P <0.001). Three-year survival was similar at 63% (FLOT) and 60% (CROSS) (P =0.42). Conclusions: Both CROSS and FLOT resulted in equivalent survival. Operative outcomes were similar, however, the CROSS regimen increased postoperative respiratory failure and atrial fibrillation. Less than half of patients received the prescribed FLOT regimen, although toxicity rates were acceptable. These data support clinical equipoise, caution, however, may be advised with CROSS in patients with greatest respiratory risk. [ABSTRACT FROM AUTHOR]

As gastric cancer is associated with poor prognosis, the preferred management of locally advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer in European patients is perioperative chemotherapy using the FLOT regimen. Previously published data demonstrate that such treatment is associated with improved disease-free survival (DFS) as well as overall survival (OS) compared to ECF/ECX regimen. In order to collect biomaterial for the identification of serum biomarkers of an early response to neoadjuvant chemotherapy, we performed a prospective study and here, we report the safety and clinical efficacy of this prospective cohort. It was an academic, nonrandomized, prospective study, conducted at Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland. Between January 2018 and November 2019, we analyzed a total of 61 patients aged 30-77 (median 63 years, 52.5% males and 47.5% females) with histologically confirmed GC or GEJ cancer. The patients were qualified by a multidisciplinary team for perioperative treatment (FLOT regimen). All cases of reported adverse events were recorded and analyzed. All patients received G-CSF prophylactically. After gastrectomy, an assessment of pathological regression was performed according to the Becker classification. A total of 93.4% (57) patients completed four cycles of preoperative chemotherapy and 78.7% (48) received postoperative chemotherapy. All of them experienced grade 1/2 toxicities. The common AE G1/G2 in preoperative versus postoperative chemotherapy were: fatigue (75% vs. 60%), anemia (64% vs. 62%), nausea (60% vs. 60%), peripheral neuropathy (60% vs. 60%), and oral mucositis (59% vs. 50%), respectively. Only 24.6% (15) had G3/4 adverse events during preoperative chemotherapy and only 20.8% (10) during postoperative chemotherapy. The estimated DFS at 3 years was 53% (95% CI 40.5-66.1%) and the estimated OS at 3 years was 60.2% (95% CI 45.1-72.3%). FLOT regimen significantly improved GC and GEJ cancer patients' prognosis with acceptable side-effect profiles. [ABSTRACT FROM AUTHOR]

Abstract Anant Ramaswamy Purpose Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) is a current standard of care for locoregionally advanced gastric adenocarcinomas. There is limited real world data with regard to the tolerance and efficacy of this regimen. Materials and Methods This is a retrospective analysis of gastric cancer patients who were offered neoadjuvant perioperative modified FLOT regimen between December 2016 and October 2018, at the Tata Memorial Hospital, Mumbai. Chemotherapy-related side-effects are reported along with overall survival (OS), as calculated by Kaplan-Meier method. Results Three hundred and forty-three consecutive patients were started on neoadjuvant chemotherapy (NACT) with mFLOT of which 298 patients (87%) completed the planned treatment. A total of 294 patients (86%) underwent curative resection of gastric cancer. Common grade 3 and grade 4 toxicities during NACT were diarrhea in 42 patients (12%) and febrile neutropenia in 27 patients (8%). Toxic death was seen in nine (2.6%) patients. A total of 264 patients (77%) completed planned adjuvant chemotherapy. Common grade 3 and grade 4 toxicities during adjuvant therapy were diarrhea in 42 patients (12%) and febrile neutropenia in 16 patients (6%). With a median follow-up of 19 months, the estimated 2-year median OS was 69.4%. Conclusion Administration of modified FLOT regimen in locoregionally advanced gastric cancers is feasible in clinical practice with high completion rates, though requiring dose modifications due to the incidence of clinically relevant grade 3 to 5 toxicities. Early outcomes with the regimen are on par with survivals from the FLOT-AIO study.

The adverse effects of chemotherapy are more apparent in elderly patients and lead to worse prognosis and mortality. Identifying immunonutritional risk factors is of great importance in terms of treatment effectiveness, prognosis, and mortality in geriatric oncology. The modified Glasgow prognostic score (mGPS) is an immunonutritional index based on serum CRP and albumin levels. In this study, we aimed to investigate the role of mGPS in predicting prognosis and survival in elderly patients with gastric cancer receiving perioperative FLOT treatment. We retrospectively enrolled 71 patients aged over 65 years and grouped them according to their pretreatment mGPS score. Kaplan-Meier and Cox regression analysis showed overall survival was significantly worse in the mGPS 1 and mGPS 2 groups than in the mGPS 0 group (p = 0.005 and p < 0.001, respectively). Compared to the mGPS 0 group, the mGPS 1 group had a 6.25 times greater risk of death (95% CI: 1.61–24.28, p = 0.008), and the mGPS 2 group had a 6.59 times greater risk of death (95% CI: 2.08–20.85, p = 0.001). High BMI was identified as a significant risk factor for being in the mGPS 2 group (OR: 1.20, 95% CI: 1.018–1.425, p = 0.030). In conclusion, elevated pretreatment mGPS was associated with poor overall survival in elderly patients with gastric cancer treated with perioperative FLOT therapy. As such, pretreatment mGPS can be a simple and useful tool to predict mortality in this specific patient group.

Background/aim: The aim of our study was to compare the efficacy and the safety of the FLOT and the modified DCF (mDCF) regimens in patients with metastatic gastric (GC) and gastroesophageal junction (GEJ) adenocarcinoma as first-line treatment. Materials and methods: The medical records of 72 patients were retrospectively reviewed. Survivals and hematological adverse events of the patients were examined. Factors affecting survivals were analyzed in univariate analysis. A multivariate analysis was performed with the factors contributing to survivals in univariate analysis. Results: The median PFS (mPFS) was 10.1 months (95% CI, 6.8-13.4) in the FLOT arm (n = 33) and 7.4 months (95% CI, 9.1-21.6) in the mDCF arm (n = 39) (p = 0.041). The median OS (mOS) was 12.9 months (95% CI, 9.7-16.1) in the FLOT arm and 15.4 months (95% CI, 9.1-21.6) in the mDCF arm (p = 0.622). It was found that all grade neutropenia was 51.3% vs. 72.7% (p = 0.063), febrile neutropenia was 8.3% vs. 6.3% (p = 0.743), and thrombocytopenia was 48.7% vs. 51.5% (p = 0.813) in the FLOT and mDCF arms, respectively. Anemia was 59% in the FLOT arm and 100% in the mDCF arm (p < 0.001). Grade 3-4 anemia was 7.7% in the FLOT arm and 24.2% in the mDCF arm (p = 0.052). Conclusion: It was shown that the mPFS was significantly increased in the FLOT arm compared to the mDCF arm as the first-line treatment in patients with metastatic GC and GEJC. Hematological adverse events were more favorable in the FLOT arm than in the mDCF arm. [ABSTRACT FROM AUTHOR]

Background: Although survival of patients with oesophagogastric adenocarcinomas has improved over the years, rates of cancer recurrence remain high. There is limited research on predictors of early recurrence (ER), especially in patients receiving FLOT chemotherapy. The aim of this study was to investigate ER and survival rates and identify risk factors for ER., Methods: Patients receiving neoadjuvant chemotherapy with FLOT for oesophagogastric adenocarcinoma at single high-volume centre between August 2018 and January 2023 were evaluated for early recurrence defined as disease present within 1 year of surgery. Multivariable analysis was conducted to identify risk factors for ER. Patients who died in-hospital or within 90 days of surgery and those with positive longitudinal margin were excluded., Results: 196 patients were included. 93.3 % and 40.3 % of patients completed all four neoadjuvant and adjuvant cycles of FLOT respectively. 54 patients (27.6 %) developed recurrence in the follow up period with 27 patients (13.8 %) having ER. Recurrence free survival and overall survival at one year were 83.7 % and 90.8 % respectively. The estimated median survival after recurrence was 4.1 months. Extracapsular spread was found to be independent risk factor for ER (OR 4.565, 95 % CI 1.450-14.369, p = 0.009) in multivariable analyses together with ypN3 stage (OR 7.978, 95 % CI 1.339-47.534, p = 0.023)., Conclusions: The variables identified in this study may be helpful in determining patients at a higher risk of ER following curative surgery. Understanding these predictors may help tailor the follow up care of these patients, such as regular surveillance imaging, treatment, and frequency of reviews., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Abstract Background Perioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) has recently become the gold standard treatment for fit patients with operable gastric (GC) or gastroesophageal (GEJ) adenocarcinoma, getting a 5-year overall survival (OS) of 45%, over 23% with surgery alone. Methods RealFLOT is an Italian, multicentric, observational trial, collecting data from patients with resectable GC or GEJ adenocarcinoma treated with perioperative FLOT. Aim of the study was to describe feasibility and safety of FLOT, pathological complete response rate (pCR), surgical outcomes and overall response rate (ORR) in an unselected real-world population. Additional analyses evaluated the correlation between pCR and survival and the prognostic role of microsatellite instability (MSI) status. Results Of 206 patients enrolled that received perioperative FLOT at 15 Italian centers, 124 (60.2%) received at least 4 full-dose cycles, 190 (92.2%) underwent surgery, and 142 (68.9%) started the postoperative phase. Among patients who started the postoperative phase, 105 (51.0%) received FLOT, while 37 (18%) received de-intensified regimens, depending on clinical condition or previous toxicities. pCR was achieved in 7.3% of cases. Safety profile was consistent with literature. Neutropenia was the most common G 3–4 adverse event (AE): 19.9% in the preoperative phase and 16.9% in the postoperative phase. No toxic death was observed and 30-day postoperative mortality rate was 1.0%. ORR was 45.6% and disease control rate (DCR) was 94.2%. Disease-free survival (DFS) and OS were significantly longer in case of pCR (p = 0.009 and p = 0.023, respectively). A trend towards better DFS was observed among MSI-H patients. Conclusions These real-world data confirm the feasibility of FLOT in an unselected population, representative of the clinical practice. pCR rate was lower than expected, nevertheless we confirm pCR as a predictive parameter of survival. In addition, MSI-H status seems to be a positive prognostic marker also in patients treated with taxane-containing triplets.

AimThe aim of the current study is to investigate the impact of primary compared to secondary chemotherapy-induced nausea and vomiting (CINV) prophylaxis with NK1 receptor antagonists (NK1-RA) in patients affected by gastrointestinal malignancies and treated with oxaliplatin- and/or irinotecan-based doublet or triplet regimens.Study design and methodsClinical data of patients affected by gastrointestinal malignancies, treated with an oxaliplatin and/or irinotecan-based doublet or triplet regimen as neo/adjuvant or advanced-line treatment, and who received NK1-RA as primary (from the first cycle of treatment) or secondary (after the onset of CINV with a previous regimen with 5HT3-RA and dexamethasone) prophylaxis for CINV, were retrospectively collected in an observational study involving 16 Italian centers. A propensity score matching was performed by taking into account the following stratification factors: sex (male vs. female), age (< vs. ≥70 years old), overweight (body mass index, BMI < vs. ≥25), underweight (BMI < vs. ≥19), disease spread (early vs. advanced/metastatic), tumor type (esophagogastric cancer vs. the rest, hepatobiliary tumor vs. the rest, colorectal cancer vs. the rest), type of NK1-RA used as primary/secondary prophylaxis (netupitant-palonosetron vs. fosaprepitant/aprepitant), concomitant use of opioids (yes vs. no), concomitant use of antidepressant/antipsychotic drugs (yes vs. no), Eastern Cooperative Oncology Group (ECOG) performance status at the start of NK1-RA treatment (0 vs. 1–2), and intensity of chemotherapy regimen (doublet vs. triplet).ResultsAmong 409 patients included from January 2015 to January 2022 and eligible for analysis, 284 (69%) and 125 (31%) were treated with NK1-RA as primary and secondary antiemetic prophylaxis, respectively. After matching, primary NK1-RA use was not associated with higher rates of protection from emesis regardless the emesis phase (acute phase, p = 0.34; delayed phase, p = 0.14; overall phase, p = 0.80). On the other hand, a lower rate of relevant nausea (p = 0.02) and need for rescue antiemetic therapy (p = 0.000007) in the overall phase was found in primary NK1-RA users. Furthermore, a higher rate of both complete antiemetic response (p = 0.00001) and complete antiemetic protection (p = 0.00007) in the overall phase was more frequently observed in primary NK1-RA users. Finally, chemotherapy delays (p = 0.000009) and chemotherapy dose reductions (p = 0.0000006) were less frequently observed in primary NK1-RA users.ConclusionIn patients affected by gastrointestinal malignancies, a primary CINV prophylaxis with NK1-RA, 5HT3-RA, and dexamethasone might be appropriate, particularly in those situations at higher risk of emesis and in which it is important to avoid dose delays and/or dose reductions, keeping a proper dose intensity of chemotherapy drugs.

Introduction: Leukocytoclastic vasculitis is a histopathological term describing vasculitis in which the inflammatory infiltrate in small vessels consists of neutrophils. Although FLOT is given perioperatively in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma, it has recently become a popular treatment option for metastatic cancers. In this case report, we present a case of FLOT-induced LCV. Case Report: We present a 52-year-old patient with metastatic gastric adenocarcinoma treated with FLOT. The patient developed necrotizing vasculitis in the lower extremity after 5 cycles of FLOT. Management & Outcome: After discontinuation of the FLOT regimen, the necrotizing morbid LCV gradually regressed with steroid therapy. Discussion: To the best of our knowledge, our case is the first case of LCV that developed after FLOT chemotherapy. The clinical appearance of the patient, occurrence after chemotherapy, erythematous rash developing on bilateral lower extremities, and palpable purpuric vasculitis made us suspect. We found a potential relationship between FLOT and vasculitis according to the Naranjo scale (score 4 +). [ABSTRACT FROM AUTHOR]

Purpose: The current study aimed at investigating the efficacy of aprepitant-containing triple antiemetic regimen in FLOT (fluorouracil + leucovorin + oxaliplatin + docetaxel) recipients as well as the emetogenic potential of FLOT regimen, through comparison of nausea and vomiting rates in a moderately emetogenic chemotherapy, FLOT, and a highly emetogenic chemotherapy recipients.Study: Patients planned to receive one of FLOT, FOLFOX (fluorouracil + leucovorin + oxaliplatin/moderate-emetic risk), or TAC (docetaxel + doxorubicin + cyclophosphamide/high-emetic risk) regimens were recruited. All patients were treated with the same triple antiemetic regimen containing aprepitant.Results: A total of 165 chemotherapy-naïve patients (52 FLOT recipients) were eligible to enter the study. At the end of day 5, "complete response" (primary efficacy endpoint) was achieved by 84.6%, 63.5%, and 61.5% of the FLOT-receiving patients in acute, delayed, and overall phases, respectively. A significant difference was seen among the odds of FLOT recipients and FOLFOX recipients concerning "complete response" achievement in delayed (p = 0.014) and overall (p = 0.017) phases, "no emesis" in delayed (p = 0.018) and overall (p = 0.010) phases, and also "complete protection" in acute (p = 0.023), delayed (p = 0.009), and overall (p = 0.006) phases; however, the difference between the odds of FLOT recipients and TAC recipients, in relation to achieving these endpoints, was insignificant. FLOT group showed significantly faster time-to-antiemetic regimen failure and time-to-first emetic episode in comparison with the FOLFOX group, which was insignificant in comparison with the TAC group.Conclusion: According to the findings, FLOT has to be considered as a high-emetic-risk regimen; provided that, as recommended by the antiemetic guidelines towards better management of delayed nausea and vomiting induced by highly emetogenic regimens, executing clinical trials concerning the efficacy of continuing dexamethasone on days 2-4 in aprepitant-containing triple antiemetic regimen schedule is required. [ABSTRACT FROM AUTHOR]

Yonglei Zhang,1 Bin Zhang,1 Jinpo Yang,2 Jindai Zhang,1 Wei Zhang3 1Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan Province, People’s Republic of China; 2Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan Province, People’s Republic of China; 3Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, Zhengzhou, 450008, Henan Province, People’s Republic of ChinaCorrespondence: Bin Zhang Email zhangbin19782020@163.comPurpose: The trend in neoadjuvant therapy for locally advanced gastric cancer (LAGC) is to use more drugs or therapies in combination. This study aimed to assess the safety and effectiveness of neoadjuvant chemotherapy with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) plus apatinib in the treatment of LAGC.Patients and Methods: We collected clinical data from patients with LAGC who received neoadjuvant FLOT and apatinib therapy and underwent surgery from January 2017 to December 2020. Patients were divided into either the FLOT group (in which patients received FLOT neoadjuvant therapy and surgery) or the FLOTA group (in which patients received FLOT plus apatinib neoadjuvant therapy and surgery).Results: The FLOT and FLOTA groups contained 44 and 31 patients, respectively. There were significant differences between the FLOT and FLOTA groups in the objective response rate (50.00% vs. 80.65%, respectively, p = 0.008) and average change from baseline in the target lesion size (− 26.16 ± 34.61 vs. − 54.32 ± 36.11, respectively, p < 0.001). There were also significant differences in the pretreatment clinical tumor-node-metastasis (cTNM) and post treatment cTNM stages for the FLOT group (p = 0.001) and for the FLOTA group (p < 0.001). There were no significant differences between the FLOT and FLOTA groups in post neoadjuvant therapy cTNM stages (p = 0.525), R0 rate (p = 0.397), tumor regression grade (p = 0.397), or post treatment pathological TNM stage (p = 0.180). Some neoadjuvant therapy-related adverse events occurred significantly more frequently in the FLOTA group, including diarrhea (all grades), pain (all grades), oral mucositis (all grades), and hand-foot syndrome (all grades).Conclusion: The FLOTA regimen can achieve better perioperative efficacy and acceptable toxicity compared with that of the FLOT regimen in neoadjuvant treatment of LAGC. The FLOTA regimen for neoadjuvant therapy for LAGC merits further study.Keywords: chemotherapy, FLOT, FLOTA, LAGC, toxicity

Abstract Background Despite obvious advances over the last decades, locally advanced adenocarcinomas of the gastroesophageal junction (GEJ) still carry a dismal prognosis with overall 5-year survival rates of less than 50% even when using modern optimized treatment protocols such as perioperative chemotherapy based on the FLOT regimen or radiochemotherapy. Therefore the question remains whether neoadjuvant chemotherapy or neoadjuvant radiochemotherapy is eliciting the best results in patients with GEJ cancer. Hence, an adequately powered multicentre trial comparing both therapeutic strategies is clearly warranted. Methods The RACE trial is a an investigator initiated multicenter, prospective, randomized, stratified phase III clinical trial and seeks to investigate the role of preoperative induction chemotherapy (2 cycles of FLOT: 5-FU, leucovorin, oxaliplatin, docetaxel) with subsequent preoperative radiochemotherapy (oxaliplatin weekly, 5-FU plus concurrent fractioned radiotherapy to a dose of 45 Gy) compared to preoperative chemotherapy alone (4 cycles of FLOT), both followed by resection and postoperative completion of chemotherapy (4 cycles of FLOT), in the treatment of locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction. Patients with cT3–4, any N, M0 or cT2 N+, M0 adenocarcinoma of the GEJ are eligible for inclusion. The RACE trial aims to enrol 340 patients to be allocated to both treatment arms in a 1:1 ratio stratified by tumour site. The primary endpoint of the trial is progression-free survival assessed with follow-up of maximum 60 months. Secondary endpoints include overall survival, R0 resection rate, number of harvested lymph nodes, site of tumour relapse, perioperative morbidity and mortality, safety and toxicity and quality of life. Discussion The RACE trial compares induction chemotherapy with FLOT followed by preoperative oxaliplatin and 5-Fluorouracil-based chemoradiation versus preoperative chemotherapy with FLOT alone, both followed by surgery and postoperative completion of FLOT chemotherapy in the treatment of locally advanced, non-metastatic adenocarcinoma of the GEJ. The trial aims to show superiority of the combined chemotherapy/radiochemotherapy treatment, assessed by progression-free survival, over perioperative chemotherapy alone. Trial registration ClinicalTrials.gov ; NCT04375605 ; Registered 4th May 2020;

Introduction: Locoregional gastric cancer is a still serious problem and perioperative treatments may improve the success of management. Different regimens were examined. The present study purposed to compare the efficacy of fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) and docetaxel-cisplatin-fluorouracil (DCF) regimens., Methods: A retrospective multicenter study assessed the patients with locoregional gastric cancer. There are 240 patients (137 DCF, 103 FLOT). Survival rates were compared., Results: Demographic features were similar between the two groups, but the time period was different. The FLOT group had 7.8% pathological complete response, while the DCF group did not. Disease-free survival was longer in the FLOT than in the 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 the FLOT group and 40% for the DCF group (log-rank; p = 0.015)., Conclusion: FLOT regimen was superior to DCF regimen for response and survival rates. DCF is a historical approach. Long-term follow-up period is needed for FLOT treatment., (© 2024 S. Karger AG, Basel.)

Background: Perioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) has recently become the gold standard treatment for fit patients with operable gastric (GC) or gastroesophageal (GEJ) adenocarcinoma, getting a 5-year overall survival (OS) of 45%, over 23% with surgery alone.Methods: RealFLOT is an Italian, multicentric, observational trial, collecting data from patients with resectable GC or GEJ adenocarcinoma treated with perioperative FLOT. Aim of the study was to describe feasibility and safety of FLOT, pathological complete response rate (pCR), surgical outcomes and overall response rate (ORR) in an unselected real-world population. Additional analyses evaluated the correlation between pCR and survival and the prognostic role of microsatellite instability (MSI) status.Results: Of 206 patients enrolled that received perioperative FLOT at 15 Italian centers, 124 (60.2%) received at least 4 full-dose cycles, 190 (92.2%) underwent surgery, and 142 (68.9%) started the postoperative phase. Among patients who started the postoperative phase, 105 (51.0%) received FLOT, while 37 (18%) received de-intensified regimens, depending on clinical condition or previous toxicities. pCR was achieved in 7.3% of cases. Safety profile was consistent with literature. Neutropenia was the most common G 3-4 adverse event (AE): 19.9% in the preoperative phase and 16.9% in the postoperative phase. No toxic death was observed and 30-day postoperative mortality rate was 1.0%. ORR was 45.6% and disease control rate (DCR) was 94.2%. Disease-free survival (DFS) and OS were significantly longer in case of pCR (p = 0.009 and p = 0.023, respectively). A trend towards better DFS was observed among MSI-H patients.Conclusions: These real-world data confirm the feasibility of FLOT in an unselected population, representative of the clinical practice. pCR rate was lower than expected, nevertheless we confirm pCR as a predictive parameter of survival. In addition, MSI-H status seems to be a positive prognostic marker also in patients treated with taxane-containing triplets. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy after surgery for gastric cancer improves survival but is difficult to administer due to poor tolerance. Combination chemotherapy with Docetaxel (Taxotere), Oxaliplatin (Eloxatin) and Capecitabine (Xeloda) (TEX) is used in the treatment of advanced gastric cancer. The efficacy and tolerability of this regimen (TEX) post resection of gastric cancer have not been studied. Materials and methods: Patients diagnosed with gastric adenocarcinoma, post resection without any prior chemotherapy between July 2007 and May 2011 and treated with TEX regimen administered as T 35 mg/m2 and E 50 mg/m2 on days (d) 1, 8 and X 625 mg/m2 bid (twice daily) on d 1-14 every 21 days were included in this retrospective analysis. Patient's electronic medical records were studied and data on tolerance, progression-free survival (PFS) and overall survival (OS) was collected. Results: Fifty-eight patients were treated with adjuvant TEX chemotherapy, majority 40 (68%) had distal gastric cancer. All patients underwent a D1 gastrectomy, and resection was performed for 44 (75%). Only 14 (24%) patients had more than 15 nodes studied in the resected specimen. Distribution for stages I, II and III is 14 (24%), 30 (52%) and 14 (24%), respectively. After a median follow-up of 40 months, the 3-year relapse free survival was 58% (95% CI: 42-68), and estimated median OS was 71 months (95% CI: 19-123 months). Twenty-three (40%) required dose reduction due to toxicity. Grade 3 or 4 toxicity was recorded for 22 (37%). Half (52%) of patients completed all planned chemotherapy of six cycles. Conclusion: Post resection of gastric adenocarcinoma adjuvant triplet TEX chemotherapy is a feasible and effective outpatient regimen. Diarrhoea, neutropenia and neuropathy were the common dose limiting toxicity. Post-surgery only half the numbers of patients are able to complete all planned cycles. [ABSTRACT FROM AUTHOR]

The plasma membrane in eukaryotic cells contains microdomains that are enriched in certain glycosphingolipids, gangliosides, and sterols (such as cholesterol) to form membrane/lipid rafts (MLR). These regions exist as caveolae, morphologically observable flask-like invaginations, or as a less easily detectable planar form. MLR are scaffolds for many molecular entities, including signaling receptors and ion channels that communicate extracellular stimuli to the intracellular milieu. Much evidence indicates that this organization and/or the clustering of MLR into more active signaling platforms depends upon interactions with and dynamic rearrangement of the cytoskeleton. Several cytoskeletal components and binding partners, as well as enzymes that regulate the cytoskeleton, localize to MLR and help regulate lateral diffusion of membrane proteins and lipids in response to extracellular events (e.g., receptor activation, shear stress, electrical conductance, and nutrient demand). MLR regulate cellular polarity, adherence to the extracellular matrix, signaling events (including ones that affect growth and migration), and are sites of cellular entry of certain pathogens, toxins and nanoparticles. The dynamic interaction between MLR and the underlying cytoskeleton thus regulates many facets of the function of eukaryotic cells and their adaptation to changing environments. Here, we review general features of MLR and caveolae and their role in several aspects of cellular function, including polarity of endothelial and epithelial cells, cell migration, mechanotransduction, lymphocyte activation, neuronal growth and signaling, and a variety of disease settings. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé.

Keshen Wang,1 Yanxian Ren,1 Zhijian Ma,2 Fan Li,1 Xiaocheng Cheng,1 Jingying Xiao,1 Shuze Zhang,1 Zeyuan Yu,1 Hanteng Yang,1 Huinian Zhou,1,2 Yuming Li,1,2 Hongbin Liu,3 Zuo-Yi Jiao1,21Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730010, People’s Republic of China; 2Cui-ying Experimental Center, Lanzhou University Second Hospital, Lanzhou, Gansu 730010, People’s Republic of China; 3Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of People’s Liberation Army, Lanzhou 730050, People’s Republic of ChinaIntroduction: Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) may improve overall survival (OS) in patients with locally advanced gastric cancer (LAGC); however, evidence for its use as a standard treatment has not been established in China. The aim of this study was to investigate the effectiveness, safety, and feasibility of the FLOT regimen as neoadjuvant chemotherapy in Chinese patients with resectable LAGC.Methods: We conducted an observational study to compare the effectiveness of FLOT regimen consisting of docetaxel (60 mg/m2,), oxaliplatin (85 mg/m2,), leucovorin (200 mg/m2,), and 5-fluorouracil (2,600 mg/m2, as a 24 hr infusion), all given on day 1 and administered every 2 weeks versus initial surgery followed by chemotherapy in patients with clinical T3–4 LAGC. OS was compared by using the Cox proportional hazards regression model and the Kaplan–Meier curve adjusted by inverse probability of treatment weighting (IPTW) and propensity score-matched (PSM) analysis. In addition, we performed subgroup analyses to determine the effectiveness of the FLOT regimen in clinically relevant patient subsets.Results: Overall, 47 patients who received initial FLOT chemotherapy and 269 patients who received initial surgery were enrolled in this study. In the PSM analysis, the FLOT-first group showed favorable OS compared with the surgery-first group (41 vs 41 [HR, 0.416; 95% CI, 0.218–0.794; P=0.008]), and 3-year survival rates were 58.7% and 30.9% in the FLOT-first group and surgery-first group, respectively. IPTW analysis showed similar results. However, the effect of FLOT was low (HR, 0.868; 95 CI%, 0.215–3.504) in patients without lymph node metastasis.Conclusion: Our study suggests that preoperative FLOT chemotherapy is safe and feasible. In terms of OS, FLOT may be superior to initial surgery followed by chemotherapy in reducing morbidity with resectable LAGC.Keywords: gastric cancer, preoperative chemotherapy, propensity score, FLOT, prognosis

Background: Gastric cancer is the fifth cause of cancer incidence worldwide. Multidisciplinary approaches that improve the survival are needed. Perioperative chemotherapies show improvement in pathological complete remission (pCR) and overall survival (OS), but less than 50% of the patients completed the chemotherapeutic regimen. The recent 5-fluorouracil, leucovorin, oxaliplatin, docetaxel-4 (FLOT4) study shows OS 50 months and pCR 16.6%, but only 46% of the patients completed pre- and postoperative treatment. This case series report evaluated pCR and safety in patients that received complete preoperative chemotherapeutic with FLOT. Methods: Patients received eight cycles FLOT regimen before surgery. Each cycle comprised 50 mg/m² docetaxel intravenous (iv) on day 1, 85 mg/m² oxaliplatin iv on day 1, 200 mg/m² leucovorin iv on day 1 and 2,600 mg/m² 5-fluorouracil iv in a 24-hour infusion on day 1, every 2 weeks. Results: Fifty-nine patients were evaluated, 58 patients received preoperative cycles. Thirty-one patients received all eight cycles of preoperative therapy. 65.5% patients presented any major adverse event. Thirty-nine patients underwent surgery. Thirty-three biopsy reports were obtained. Six patients (18.2%) presented pCR, 13 patients (39.4%) had no lymph node involvement. OS was 21.32 months. Patients with histology of signet ring carcinoma cells had a shorter survival than other histologies. Conclusion: Total neoadjuvant with FLOT chemotherapy presents an adequate safety profile, a similar pathologic regression rate, and a slightly higher rate of completing treatment to report in perioperative FLOT regimen studies. A prospective clinical study with suitable diagnostic, staging tools and an adequate follow-up may prove total neoadjuvant chemotherapy's efficacy. [ABSTRACT FROM AUTHOR]

Treatment strategies for oesophagogastric junction adenocarcinoma have not been standardized despite its poor prognosis due to differences in the incidence rates between Western countries and Asia. This randomized Phase II/III trial was initiated in June 2023 to determine which neoadjuvant chemotherapy regimen, docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel, is a more promising treatment in Phase II and confirm the superiority of neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel followed by surgery and postoperative chemotherapy over upfront surgery and postoperative chemotherapy in terms of overall survival in patients with Clinical Stage III or IVA oesophagogastric junction adenocarcinoma in Phase III. A total of 460 patients, including 150 patients in Phase II and 310 patients in Phase III, are planned to be enrolled from 85 hospitals in Japan over 5 years. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031230182 (https://jrct.niph.go.jp/latest-detail/jRCTs031230182)., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite obvious advances over the last decades, locally advanced adenocarcinomas of the gastroesophageal junction (GEJ) still carry a dismal prognosis with overall 5-year survival rates of less than 50% even when using modern optimized treatment protocols such as perioperative chemotherapy based on the FLOT regimen or radiochemotherapy. Therefore the question remains whether neoadjuvant chemotherapy or neoadjuvant radiochemotherapy is eliciting the best results in patients with GEJ cancer. Hence, an adequately powered multicentre trial comparing both therapeutic strategies is clearly warranted.Methods: The RACE trial is a an investigator initiated multicenter, prospective, randomized, stratified phase III clinical trial and seeks to investigate the role of preoperative induction chemotherapy (2 cycles of FLOT: 5-FU, leucovorin, oxaliplatin, docetaxel) with subsequent preoperative radiochemotherapy (oxaliplatin weekly, 5-FU plus concurrent fractioned radiotherapy to a dose of 45 Gy) compared to preoperative chemotherapy alone (4 cycles of FLOT), both followed by resection and postoperative completion of chemotherapy (4 cycles of FLOT), in the treatment of locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction. Patients with cT3-4, any N, M0 or cT2 N+, M0 adenocarcinoma of the GEJ are eligible for inclusion. The RACE trial aims to enrol 340 patients to be allocated to both treatment arms in a 1:1 ratio stratified by tumour site. The primary endpoint of the trial is progression-free survival assessed with follow-up of maximum 60 months. Secondary endpoints include overall survival, R0 resection rate, number of harvested lymph nodes, site of tumour relapse, perioperative morbidity and mortality, safety and toxicity and quality of life.Discussion: The RACE trial compares induction chemotherapy with FLOT followed by preoperative oxaliplatin and 5-Fluorouracil-based chemoradiation versus preoperative chemotherapy with FLOT alone, both followed by surgery and postoperative completion of FLOT chemotherapy in the treatment of locally advanced, non-metastatic adenocarcinoma of the GEJ. The trial aims to show superiority of the combined chemotherapy/radiochemotherapy treatment, assessed by progression-free survival, over perioperative chemotherapy alone.Trial Registration: ClinicalTrials.gov ; NCT04375605 ; Registered 4th May 2020. [ABSTRACT FROM AUTHOR]

In patients with gastic cancer, five-year survival is poor in the locally advanced stage. Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) combination regimen has been shown to provide a survival advantage in the locally advanced stage. In this study, we aimed to evaluate the efficacy and tolerability of FLOT with real-life data in patients with locally advanced gastric/esophagogastric junction cancers. This retrospective study was conducted between June 2016 - March 2020 and included 106 patients' data from six centers in Turkey. Median age was 60 (33-82). Primary tumor localization was stomach in 76 (71.7%) patients. Seventy-six (71.7%) patients were operated after median 4 (1-8 cycles) cycles of preoperative FLOT. Pathological complete regression (pCR)was obtained in 10 (13.1%) of the operated patients. Median follow-up was 9.1 (1.4-45.7) months. One-year DFS was 63.2% and the two-year OS was 65.1%. Three (2.8%) patients had chemotherapy-related deaths. Due to chemotherapy-related toxicity and intoleration, 19 (17.9%) patients had dose reduction. The pCR obtained by FLOT appears higher than other regimens. This study is one of the rare multicentric real-life data showing the efficacy and tolerability of the FLOT regimen in the perioperative treatment in GC and EJC. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin (HB) and red cell distribution width (RDW) are known to be prognostic in many cancer types. The HB-RDW ratio (HRR) is a new biomarker that has been shown to be predictive in some cancer types. However, the prognostic significance of HRR in patients with gastric cancer (GC) is unknown. Aims: In this study, we aimed to demonstrate the prognostic importance of HRR in GC patients treated with neoadjuvant fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT). Methods: Eighty-five GC patients who were treated with neoadjuvant FLOT in our center were included in the study, retrospectively. Associations between clinical and histopathological parameters with disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan–Meier curves and compared by the log-rank test. The optimal cutoff values were determined by a receiver operating characteristic (ROC) curve analysis. Neutrophil–lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and HRR were grouped based on a cutoff points 3.05, 802, and 0.89, respectively. Univariate and multivariate analyses were used to assess their prognostic values for DFS and OS. Results: Low NLR, low SII, and high HRR were found to be associated with longer DFS/OS. In univariate analysis, Eastern Cooperative Oncology Group performance status, grade, stage, response to neoadjuvant treatment, NLR, SII, and HRR were found to be significantly associated with DFS and OS. But in multivariate analysis, only HRR was demonstrated as an independent prognostic factor for DFS/OS (p 0.001, p 0.037, respectively). Conclusions: HRR is a new biomarker that can predict DFS and OS in GC patients treated with neoadjuvant FLOT. [ABSTRACT FROM AUTHOR]

Healthy Lifestyles were described among a senior group in a first level hospital in Norte de Santander, Colombia. The purpose was identified between lifestyle and socioeconomic conditions, in a quantitative, descriptive character and cross section study. A factorial and confirmatory model for lifestyles was analyzed. The main result established that there is no control over the nutrition, health responsibility, interpersonal support and actualization. In general, the health style level was 32% very good, 26% good, 20% excellent and 1.3 % bad.

Management of gastroesophageal junction (GEJ) adenocarcinoma is a controversial topic. The rising incidence of this cancer requires a clear consensus to ensure proper management. Application of oncological principles for tumors of the esophagus or stomach is not possible because of comparative differences in the biology of GEJ adenocarcinoma, leading to different therapeutic options. Staging work‐up with endoscopy, endosonography, and PET is essential to inform the choice of neoadjuvant treatment and surgical approach to GEJ adenocarcinoma. Surgery remains the only curative treatment and should be undertaken in specialized centers. Application of the oncological principles for tumors of the esophagus or stomach is not possible because of the differences in biological behavior and hence selection of therapeutic options. Staging work‐up with endoscopy, endosonography, and PET is essential because it will inform the choice of neoadjuvant treatment and surgical approach. Surgery remains the only curative treatment and should be undertaken in specialized centers. [ABSTRACT FROM AUTHOR]

According to the data of the GLOBOCAN-network of the World Health Organization, there were 952,000 (6.8% of the total) new cases of gastric cancer in 2012, making it the fifth most common malignancy in the world. It represents a substantive change since the very first estimates in 1975 when stomach cancer was the most common neoplasm. More than 70% of cases (677,000 cases) occur in developing countries, and half the world total occurs in Eastern Asia, mainly in China. Gastric cancer is the third leading cause of cancer death in both sexes worldwide (Globocan, Estimated cancer incidence, mortality and prevalence worldwide in 2012, http://globocan.iarc.fr, 2012). Annually, worldwide 723,000 patients die of this tumor entity. Interestingly, a strong change in incidence rates in relation to the anatomical-topographic localization of the primary tumors in the stomach and esophagus has been experienced. While the frequency of proximal gastric carcinoma and adenocarcinoma of the cardiac and subcardiac region in Europe and North America has been constantly rising, distal gastric carcinomas have become less common (Torre et al. in JAMA 65:87-108, 2015). Furthermore, the relative incidence of esophageal adenocarcinoma (mostly localized in the distal esophagus) has strongly increased (Jemal et al. in JAMA 58:71-96, 2008; Crew and Neugut 31:450-464, 2004; Pohl and Welch 97:142-146, 2005). [ABSTRACT FROM AUTHOR]

• 18F-FDG PET/CT may help perioperative decision-making in gastroesophageal cancer. • 18F-FDG PET/CT SUL peak might be correlated with pathological response to treatment. • 18F-FDG PET/CT semi-quantitative parameters may predict progression-free survival. To evaluate the prognostic role of [18F]FDG PET/CT metabolic parameters in gastric cancer (GC) and gastroesophageal adenocarcinoma (GEJAC) patients receiving neoadjuvant chemotherapy. In this retrospective study, 31 patients with biopsy-proven GC or GEJAC were included between August 2016 and March 2020. [18F]FDG PET/CT was performed before the neoadjuvant chemotherapy. Primary tumours' semi-quantitative metabolic parameters were extracted. All patients received a perioperative FLOT regimen thereafter. Post-chemotherapy [18F]FDG PET/CT was performed in most patients (17/31). All patients underwent surgical resection. Histopathology response to treatment and progression-free survival (PFS) were evaluated. Two-sided p-values < 0.05 were considered statistically significant. Thirty-one patients (mean age = 62 ± 8), including 21 GC and 10 GEJAC patients, were evaluated. 20/31(65%) patients were histopathology responders to neoadjuvant chemotherapy, including twelve complete and eight partial responders. During the median follow-up of 42.0 months, nine patients experienced recurrence. The median PFS was 60(95% CI:32.9–87.1) months. Pre-neoadjuvant chemotherapy SULpeak was significantly correlated with pathological response to treatment (p-value = 0.03;odds ratio = 16.75). In survival analysis, SUVmax (p-value = 0.01;hazard ratio[HR] = 1.55), SUVmean (p-value = 0.04;HR = 2.73), SULpeak (p-value < 0.001;HR = 1.91) and SULmean (p-value = 0.04;HR = 4.22) in the post-neoadjuvant chemotherapy pre-operative [18F]FDG PET/CT showed significant correlation with PFS. Additionally, aspects of staging were significantly correlated with PFS (p-value = 0.01;HR = 2.21). Pre-neoadjuvant chemotherapy [18F]FDG PET/CT parameters, especially SULpeak, could predict the pathological response to treatment in GC and GEJAC patients. Additionally, in survival analysis, post-chemotherapy metabolic parameters significantly correlated with PFS. Thus, performing [18F]FDG PET/CT before chemotherapy may help to identify patients at risk for inadequate response to perioperative FLOT and, after chemotherapy, may predict clinical outcomes. [ABSTRACT FROM AUTHOR]