FLOT Regimen Research Articles

Body Composition Changes in Gastric Cancer Patients during Preoperative FLOT Therapy: Preliminary Results of an Italian Cohort Study.

Background: The impact of the new chemotherapy, fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) on body composition in gastric cancer (GC) patients remains unknown. We assessed body composition changes of GC patients receiving the FLOT regimen and their impact on treatment outcomes. Methods: Preoperative pre- and post-FLOT computed tomography (CT) scans of advanced GC patients were studied. Lumbar skeletal muscle index (SMI) and adipose indices were calculated before and after FLOT. Results: A total of 26 patients were identified between April 2019 and January 2020. Nineteen patients were sarcopenic at diagnosis. The mean BMI decreased (from 24.4 ± 3.7 to 22.6 ± 3.1; p < 0.0001) as well as the SMI (from 48.74 ± 9.76 to 46.52 ± 9.98; p = 0.009) and visceral adipose index (VAI) (from 49.04 ± 31.06 to 41.99 ± 23.91; p = 0.004) during preoperative FLOT therapy. BMI, SMI, and VAI variations were not associated with toxicity, Response Evaluation Criteria in Solid Tumors (RECIST), response, delay and completion of perioperative FLOT chemotherapy, and the execution of gastrectomy; a decrease of SMI ≥ 5% was associated with a higher Mandard tumor regression grade (p = 0.01). Conclusions: Almost three-quarters (73.1%) of GC patients were sarcopenic at diagnosis. Preoperative FLOT was associated with a further reduction in SMI, BMI, and VAI. These changes were not associated with short-term outcomes.

CROSS or FLOT in Distal Esophageal and Gastroesophageal Cancer.

To compare the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) and continuous infusion 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) protocols administered in distal esophageal and gastroesophageal junction (GEJ) tumors in terms of effectiveness and toxicity. Descriptive study. Ankara Oncology Training and Research Hospital, Turkey between 2015 and 2020. Patients diagnosed with distal esophageal and GEJ squamous cell carcinoma (SCC) or adenocarcinoma (ADC), older than 18 years of age, in localised or locally advanced stage were included. Metastatic stages were excluded. Kaplan-Meier was used for survival analysis, log-rank test was performed for comparisons between groups. A total of 25 patients (44.6%) were treated with CROSS protocol (15 distal esophageal and 10 GEJ tumor), 31 patients (55.4%) with GEJ tumors were treated with the FLOT regimen. Eight of the patients who were administered the CROSS protocol before the operation demonstrated complete pathologicial response, no patients in the FLOT group had complete response to the treatment. In patients with GEJ tumors and ADC histopathology, CROSS and FLOT group had similar second years survival (60% and 59.3%, respectively) (p = 0.803). The frequency of neutropenia was significantly higher in the CROSS group compared to the FLOT group (p = 0.004.) Conclusion: Postoperative pathological response rate in the CROSS group was significantly higher compared to the FLOT group. CROSS and FLOT protocols contributed to survival similarly in patients with GEJ ADC, hematological side effects were more pronounced in patients receiving CRT. Key Words: GEJ cancer, Esophageal cancer, Cross, Flot.

Perioperative Safety and Effectiveness of Neoadjuvant Therapy with Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel Plus Apatinib in Locally Advanced Gastric Cancer.

PurposeThe 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 MethodsWe 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).ResultsThe 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).ConclusionThe 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.

Neoadjuvant and perioperative treatment of gastric cancer, current studies and new biomarkers

According to current German and European clinical practice guidelines perioperative chemotherapy is the recommended standard of care for localized gastric cancer beyond early cancers, i.e. in stage IB (T2 N0 M0 and T1 N1 M0) or greater. For patients who are able to tolerate intensive chemotherapy, the FLOT regimen (5-fluorouracil, folinic acid, oxaliplatin, docetaxel) should be administered preoperatively and postoperatively for four cycles each. Locally advanced nonmetastatic adenocarcinoma of the esophagogastric junction (AEG) should be treated with perioperative chemotherapy as for gastric cancer or alternatively with neoadjuvant chemoradiotherapy. The best approach for AEG is currently being investigated in ongoing clinical trials. The recommendation of perioperative treatment applies to all histopathological subtypes of gastric cancer. The article summarizes the contemporary data and provides an outlook on current progress in the field of medicinal perioperative treatment.

Phase II study of systemic chemotherapy with S-1 plus oxaliplatin followed by surgery in patients with cT3-T4a and/or node-positive advanced adenocarcinoma of the esophagogastric junction: Primary endpoint results of the ESOX trial.

214 Background: Perioperative chemotherapy has been suggested to be beneficial in patients with advanced gastric cancer. Based on the German FLOT-4 study, the FLOT regimen is considered as the new standard perioperative chemotherapy regimen for resectable gastric cancer in Europe. However, most clinical trials have included few or no cases of esophagogastric junction (EGJ) cancer, because of the difference in surgical procedures. The benefit of neoadjuvant chemotherapy in patients with advanced adenocarcinoma of the EGJ thus remains controversial in Japan. Methods: We conducted a phase II study in 13 Japanese institutions. Eligible patients had histopathologically confirmed adenocarcinoma of the EGJ (Siewert type I or II with invasion of the esophagus ≥30 mm) with clinical T3/4a and/or node-positive on imaging findings, who required thoracic surgery to achieve R0 resection. Patients received three cycles of S-1 (80 mg/m2) twice a day on days 1–14 and oxaliplatin (130 mg/m2) (SOX) on day 1 of a 21-day cycle before surgery. The primary endpoint was R0 resection rate and the secondary endpoints were overall response rate, pathological complete response (pCR) rate, 2-year and 3-year disease-free survival, overall survival, and toxicity. The planned sample size was 50 patients based on an expected R0 resection rate of 85% and the threshold was 70%, with a one-sided alpha of 0.1 and power of 80%. Results: Fifty patients were enrolled in this study between June 2016 and April 2020. Totals of 21/29 and 7/4/22/8/8/1 had Siewert type I/II and clinical stage IIA/IIB/IIIA/IIIB/IIIC/IV disease, respectively. The completion rates for preoperative chemotherapy and surgery were 92% and 88%, respectively. Neoadjuvant therapy resulted in downstaging in 46% of patients (95% confidence interval (CI) 31.8%-60.7%). The pCR rate was 18% (95% CI 8.6%-31.4%) and the R0 resection rate was 82.0% (95% CI 68.6%-91.4%, 80% CI 73.1%-88.9%). Adverse events ≥ grade 3 during chemotherapy included thrombocytopenia (10%), neutropenia (8%), anemia (4%), anorexia (4%), nausea(2%), hypocalcemia(2%), hyponatremia(2%) and diarrhea (2%). Surgical morbidity was acceptable (Clavien-Dindo Grade IIIa surgical complications included anastomotic leakage (6.3%), pleural effusion (4.2%), thromboembolism (2.1%), and anastomotic infection (2.1%)). Conclusions: Neoadjuvant SOX met the primary endpoint of R0 resection rate 82% ( &gt; 70%), with acceptable adverse effects and no impression on surgeries, suggesting that neoadjuvant SOX might be a new treatment strategy for patients with EGJ adenocarcinoma in Japan. Clinical trial information: 000020815.

Phase II study of sintilimab combined with FLOT regimen for neoadjuvant treatment of gastric or gastroesophageal junction (GEJ) adenocarcinoma.

216 Background: Perioperative treatments have significantly improved survival in patients with resectable gastric cancer, increasing 5-year overall survival from 23% with surgery alone to 45% with FLOT, Although FLOT has been recognized as the first choice for neoadjuvant chemotherapy in gastric or GEJ adenocarcinoma, its efficacy needs to be improved. Sintilimab, a fully human IgG4 monoclonal antibody that binds to programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. We aimed to assess the activity and safety profile of the combination of FLOT and sintilimab for neoadjuvant treatment of gastric or GEJ adenocarcinoma. Methods: In this ongoing, single-arm, phase II study, we recruited patients from Henan Cancer Hospital in China with histopathologically diagnosed resectable gastric or GEJ adenocarcinoma who had clinical T3/N+ or higher stage. Patients were given 4 cycles of FLOT (docetaxel 50 mg/m2, oxaliplatin 80 mg/m2, leucovorin 200 mg/m2, fluorouracil 2600 mg/m2, 24-h infusion on day 1, q2w) in combination with 3 cycles of sintilimab (200mg, iv, d1, q3w), followed by D2 surgery and 4 postoperative cycles of FLOT. The primary endpoint was pathological complete response (pCR). The secondary endpoints included major pathological remission (MPR) and R0 resection rate and adverse events . Results: A total of 20 patients were enrolled in the study between Aug 10 2019 and Sep 15 2020. One patient refused surgery, one person's disease progressed. Two patients have not yet completed neoadjuvant treatment . 16 pts who experienced D2 resection, 10 (62.5%) achieved major pathologic response (MPR), including 3 (18.8%) with a pathologic complete response (pCR) in primary tumor. The R0 resection rate was up to 93.8%, The grade 3 or 4 treatment-related adverse events (TRAE) included lymphopenia(25%), anaemia (20%),fatigue (20%),leucopenia (15%), neutropenia (5%), diarrhea(5%), Alanine aminotransferase increased(5%),There was no surgical delays or unexpected surgical complications related to drug toxicity. Conclusions: Neoadjuvant combination of sintilimab and FOLT is a safe and efficacious treatment option for patients with gastric or GEJ adenocarcinoma, 18.8% pCR rate and 62.5%MPR rate is encouraging. Our clinical study is still enrolling, and the survival effects are under follow up. Clinical trial information: NCT04341857.

Feasibility and Safety of Perioperative Chemotherapy With Fluorouracil Plus Leucovorin, Oxaliplatin, and Docetaxel for Locally Advanced Gastric Cancer Patients in China.

BackgroundNeoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries. We conducted a prospective study on the safety and feasibility of the FLOT regimen in Chinese patients.MethodsPatients with adenocarcinoma of the stomach or esophagogastric junction received four cycles of neoadjuvant chemotherapy (NAC) and four cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities, and pathological tumor regression were analyzed. The 2-year overall survival (OS) and relapse-free survival are presented.ResultsAltogether, 10 patients were enrolled, and all patients completed four cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and three patients had complete or subtotal pathological tumor regression. Nine patients completed four cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, eight patients achieved the overall survival endpoint, and seven patients had relapse-free survival for this period. Two patients died of disease progression.ConclusionsOur study demonstrates that the neoadjuvant FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort. The trial is registered with ClinicalTrials.gov (number NCT03646591).

Neoadjuvant FLOT versus SOX phase II randomized clinical trial for patients with locally advanced gastric cancer

Neoadjuvant chemotherapy with docetaxel, oxaliplatin, fluorouracil, and leucovorin (FLOT regimen) has shown promising results in terms of pathological response and survival rate in patients with locally advanced resectable gastric cancer (LAGC). However, tegafur gimeracil oteracil potassium capsule (S-1) plus oxaliplatin (SOX regimen) is the preferred chemotherapy regimen in Eastern countries. Here, we conduct an open label, two-arm, phase II randomized interventional clinical trial (Dragon III; ClinicalTrials.gov: NCT03636893) to evaluate the safety and efficacy of both regimens. Patients with LAGC are randomly assigned to receive either 4 cycles of the neoadjuvant FLOT regimen (40 patients) or 3 cycles of the SOX regimen (34 patients) before gastrectomy. The primary endpoint is the comparison of complete (TRG1a) or subtotal (TRG1b) tumor regression grading in the primary tumor. There are no significant differences in adverse effects or postoperative morbidity and mortality between the two groups. No significant differences in the proportion of tumor regression grading between the FLOT group and the SOX group are found. Complete or subtotal TRG is 20.0% in the FLOT group versus 32.4% in the SOX group. Therefore, our study does not find statistically significant differences between neoadjuvant FLOT and SOX regimens for the primary outcomes reported here in locally advanced gastric cancer.

160P Phase II study of sintilimab combined with FLOT regimen for neoadjuvant treatment of gastric or gastroesophageal junction (GEJ) adenocarcinoma

Although FLOT has been recognized as the first choice for neoadjuvant chemotherapy in gastric or GEJ adenocarcinoma, its efficacy needs to be improved. Sintilimab, a fully human IgG4 monoclonal antibody that binds to programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. We aimed to assess the activity and safety profile of the combination of FLOT and sintilimab for neoadjuvant treatment of gastric or GEJ adenocarcinoma. In this ongoing, single-arm, phase II study, we recruited patients from Henan Cancer Hospital in China with histopathologically diagnosed resectable gastric or GEJ adenocarcinoma who had clinical T3/N+ or higher stage. Patients were given 4 cycles of FLOT (docetaxel 50 mg/m2, oxaliplatin 80 mg/m2, leucovorin 200 mg/m2, fluorouracil 2600 mg/m2, 24-h infusion on day 1, q2w) in combination with 3 cycles of sintilimab (200mg, iv, d1, q3w), followed by surgery and 4 postoperative cycles of FLOT. The primary endpoint was pathological complete response (pCR). The secondary endpoints included major pathological remission (MPR) and objective response rate (ORR). Between Aug 10, 2019, and Jul 15, 2020, 19 patients were enrolled and commenced treatment. The grade 3 or 4 treatment-related adverse events (TRAE) included diarrhea (10.5%), leukopenia (5.3%), neutropenia (5.3%), anaemia (10.5%). Most frequent grade 1 or 2 TRAE were leukopenia (42.1%), neutropenia (31.6%) and Glutamic-pyruvate transaminase increased (42.1%). A total of 17 patients (89.4%) were eligible for efficacy assessment, and among 9 patients who experienced D2 resection, 6 (66.7%) achieved MPR, including 2 (22.2%) with pCR. According to RECIST v1.1, 6 of 17 patients (35.3%) achieved partial response (PR), and 11 of 17 patients (64.7%) achieved stable disease (SD). The ORR and disease control rate (DCR) for 17 patients were 35.3% and 100%, respectively. Neoadjuvant combination of sintilimab and FOLT is a safe and efficacious treatment option for patients with gastric or GEJ adenocarcinoma, and 22.2% pCR rate is encouraging. Our clinical study (NCT04341857) is still enrolling, and the survival effects are under follow up.

RACE-trial: neoadjuvant radiochemotherapy versus chemotherapy for patients with locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction - a randomized phase III joint study of the AIO, ARO and DGAV

BackgroundDespite 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.MethodsThe 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.DiscussionThe 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 registrationClinicalTrials.gov; NCT04375605; Registered 4th May 2020;

1440P Safety and efficacy of FLOT regimen neoadjuvant treatment in Polish population: Interim analysis of prospective biomarker study

Gastric cancer is associated with poor prognosis. Currently in Europe the preferred management of locally advanced gastric cancer is perioperative chemotherapy using FLOT regimen. According to previously published data, such treatment is associated with improved relapse-free survival (RFS) as well as overall survival (OS) compared to ECF/ECX. We aimed at a prospective study in order to collect biomaterial for identification of serum biomarkers of early response to neoadjuvant chemotherapy. Here we report the safety and clinical efficacy of this prospective cohort.

P-334 Perioperative chemotherapy in the treatment of resectable and locally advanced gastric and junctional esophagogastric adenocarcinoma: Experience of a Portuguese central hospital

Gastric cancer is the 5th most prevalent cancer in Portugal and the 3rd most deadly worldwide. Currently, perioperative chemotherapy is the standard of care for resectable and locally advanced gastric and junctional esophagogastric (JEG) adenocarcinoma. During several years, the MAGIC study catapulted ECF/ECX/CF regimens into the spotlight. Since publishing the FLOT4-AIO trial results in 2017 - associated with higher R0 resection and pathological response ≤T1 rates, as well as extended overall survival in 15months - the FLOT regimen has become the preferred perioperative option in most national and international clinical centers. The aim of this study was to compare in the real-life setting the FLOT vs ECF/ECX/CF perioperative regimens used in the treatment of resectable and locally advance gastric adenocarcinoma, in terms of safety and efficacy. We conducted a retrospective and observational study, which included patients diagnosed with resectable and locally advanced gastric and JEG adenocarcinoma treated with perioperative chemotherapy regimens between 01/01/2016 and 31/06/2019, namely FLOT (Group A) and ECF/ECX/CF (Group B). Toxicity assessment was made according to CTCAE V.5.0. The study included 64 patients [A:58%(n=37); B:42%(n=27)]. Most patients were male [A:57%(n=21); B:82%(n=22)], median age was 64 years old [A:63 years[39-78]; B:70 years[53-79]] and had cT3/T4 [A:70%(n=26); B:85%(n=23);p=0,164] and cN+ [A:67%(n=25); B:93%(n=25);p=0,017] disease at diagnosis. The median follow-up time was 10 months [2-22] and 21 months [0-37] for groups A and B, respectively. The preoperative regimen was completed by 81% of patients in both groups. Most patients underwent curative surgery [A:84%(n=31); B:81%(n=22);p=0,533]. Most patients initiated postoperative cycles [A:54%(n=20); B:63%(n=17)] but only 43% (n=16) of the patients in group A and 63%(n=17) of group B completed the perioperative treatment. Treatment readjustments was performed in 70% of patients in the group A and 96% of the group B, including delays [A: 40%(n=15); B: 44%(n=12);p=0,755], suspension [A: 27%(n=10); B: 96%(n=26);p< 0,01] and dose reduction [A: 27%(n=10); B: 41%(n=11);p=0,249]. Except for one patient in group A who had R1, all the other patients in the two groups had R0 resection. Compete pathological response (ypT0N0) was reported in 13% of the patients in group A and 9% of group B (p=0,511). Overall survival (OS) was 19 (IC95% 17-21) and 26 months (IC95% 21-32) (p=0,368) and Disease-Free Survival (DFS) was 20 (IC95%:18-22) and 31 months (IC95%:27-36) (p=0,098) in groups A and B, respectively. During the perioperative treatment, the majority of patients experienced grade 3-4 toxicity at some point in treatment [A:57%(n=21); B:70%(n=19);p=0,267], most common being neutropenia [A:35%(n=13); B:63%(n=17);p=0,028]. Two patients died of infectious complications in group A. According to our study, there was no significant difference between the two groups regarding complete pathological response (ypT0N0). The higher incidence of grade 3-4 toxicity especially neutropenia and treatment suspension seemed to occur in the ECX/ECF/CF group. The short follow-up time and small sample size can justify the OS and DFS results.

P-75 Retrospective comparison between FLOT perioperative chemotherapy vs surgery followed by adjuvant chemotherapy: Results from a multicenter analysis

Most guidelines concerning patients with not-metastatic gastric cancer, particularly in western countries, suggest that perioperative chemotherapy with FLOT regimen should be considered the standard of care. Albeit FLOT proves to be more effective compared with ECX/ECF, there is a lack of data comparing patients treated with this strategy versus surgery followed by adjuvant chemotherapy. We conducted a retrospective analysis with the aim of identifying whether there are factors that might reduce perioperative FLOT effectiveness compared with surgery followed by adjuvant chemotherapy.

P-296 Chemosensitivity and outcome in advanced and metastatic gastric signet-ring cell carcinoma (GSRC)

GSRC accounts for 4-17% of all cases of gastric cancer (GC), is associated with a worse prognosis compared with non-SRC, and its chemosensitivity is uncertain. A retrospective analysis of all patients (pts) with locally advanced and metastatic GSRC treated in our oncology department from Jan 2012 to Dec 2017 was done to characterize clinical, demographic, and treatment data, and to evaluate the response to chemotherapy (CT) and overall survival (OS). From the 560 pts with GC treated in our Institution, a total of 71 with GSRC were included with a median age of 65 years (range, 21-83). Localized disease was present in 70% (50 pts) and metastatic in 30%. The anatomic site was esophagus/cardia in 15 pts and others in 56 pts. Total/subtotal gastrectomy was performed in 47pts. Perioperative CT was given to 31 pts, mostly with epirubicin (E), cisplatin (C), and capecitabine (X), with minimal histological tumor regression in 85% and moderate in 15%. N2/N3 was found in 16 operated pts. Twelve pts underwent primary surgery, followed by adjuvant CT with doublet or triplet oxaliplatin-X (in association with E). Twenty-four pts recurred (50%); 20 with metastasis. The median time to relapse was 11 months. A first-line palliative CT for metastatic or recurrent disease was administered in 33 pts. Response was complete in 1 pt, partial in 3, stable disease in 2; 28 progressed. The regimen most used in first-line CT was ECX. The 1-year OS for metastatic pts was 33%. The 5-year OS for localized GSRC was 34.4% and 25% for the global cohort. Neoadjuvant CT use did not result in tumor downstaging/downsizing. The observation of a group of CT responses in the neoadjuvant and metastatic settings presents the possibility of subtypes with better prognosis despite high lymph node involvement. Further studies are required to clarify the differences between subgroups and to explore the effectiveness of the new docetaxel-based triplet FLOT regimen.

Resectable locally advanced gastric adenocarcinoma: interim analysis

Background: The MAGIC and ACCORD 07 trials have established the role of perioperative chemotherapy in locally advanced gastric adenocarcinoma. A more recent study has demonstrated the superiority of the FLOT perioperative regimen. The best strategy to improve outcomes has yet to be determined. Aims of the study were to evaluate perioperative chemotherapy in terms of morbidity and tolerance of FLOT regimen with modification and histopathological responseMethods: This prospective study was started after ethical committee approval in February 2019 at a tertiary cancer center in South India for a period of 1 year up till February 2020. Patients fulfilling inclusion criteria were enrolled. Perioperative chemotherapy was given as scheduled regimen and adverse effects and response to preoperative chemotherapy were recorded. Radical D2 gastrectomy and histopathology assessed analysed by using IBM SPSS statistics ver. 21 and descriptive statistics used.Results: From February 2019 till February 2020, a total of 24 patients of newly diagnosed adenocarcinoma of the stomach of which 18 patients were nonmetastatic on workup. Moderately different (38.8%), well-differentiated in 11.2%, poorly differentiated in 50%. Total 66.7% were diagnosed as metastatic on staging laparoscopy, peritoneal wash cytology in 50% was negative. The cardiopulmonary resuscitation was seen in two patients.Conclusions: Even though it is an interim analysis with less number of patients enrolled, so far it can be concluded that all patients where surgery is planned should undergo peritoneal lavage cytology and FLOT regimen can be practised with acceptable morbidity. Long term results after completion of study will definitely throw more light.

Perioperative FLOT in elderly patients with resectable gastric cancer: Subgroup analysis from the observational RealFLOT study.

4548 Background: The treatment strategy for patients with resectable gastric cancer changed in the last few years with perioperative treatments. FLOT regimen (fluorouracil, oxaliplatin, docetaxel) turned out to be feasible and effective, offering significant improvement in survival outcomes. However, the safety profile of triplet therapies for elderly patients deserves a special attention and, consequently, the best treatment strategy for these patients is still debated. Methods: Focusing on the elderly patient population (age ≥65 years), real-world data from patients with resectable gastric or gastro-oesophageal junction (GEJ) adenocarcinoma (T≥2 and/or N+) enrolled in the observational RealFLOT study were collected. Results: A total of 206 patients with resectable gastric or GEJ adenocarcinoma received perioperative FLOT at 15 Italian centers in routine clinical practice, between September 2016 and September 2019. The median age was 63 years (range 36-77) and 43% of patients enrolled (n = 89) were ≥65 years. Among elderly patients, 46 (52%) received FLOT for at least 4 full-dose cycles in the preoperative phase, 82 (92%) underwent surgery, and 56 (62%) started the postoperative phase. The primary end point of the study, pathological complete response (pCR) rate, was similar among patients aged ≥65 and &lt; 65 (6.7% vs 7.7%, respectively). The distribution of pathological stages did not differ according to age (p = 0.473), and disease-free survival (DFS) is unrelated to the age of patients (log-rank 0.57; p = 0.89). The incidence of grade (G) 3-4 adverse events (AEs) was similar in the two age groups (Table) and the 30-day mortality rates after surgery did not differ according to age. Conclusions: FLOT regimen demonstrated to be feasible and safe in elderly patients since no differences were observed in terms of pCR, DFS and safety profile according to age. [Table: see text]

Tumor response score with neoadjuvant FLOT versus FOLFOX in gastric cancer patients: Results from a United States-based cohort.

e16573 Background: A recent RCT comparing FLOT and ECF regimens for locally advanced gastric cancer found FLOT to be superior in pathologic complete response (PCR) rates: 16% versus 6%. We evaluated patients who underwent resection after FLOT and FOLFOX in a diverse US population. Methods: Patients diagnosed with gastric adenocarcinoma at a single institution who underwent preoperative chemotherapy either with FLOT or FOLFOX between 2017 and 2019 were evaluated for pathologic response. Results: Fifty-nine patients underwent gastrectomy for adenocarcinoma. Of these, 59% underwent neoadjuvant chemotherapy: FLOT 20 patients, FOLFOX 12 patients, ECF 1 patient, other regimen 2 patients. Racial/ethnic background of patients were 20% non-Hispanic white, 23% Hispanic/Latino, 40% Asian, 6% black, and 6% other. Three patients (8.6%) had PCR, two received FLOT and one FOLFOX. Four patients had a near complete response (tumor regression score 1), all of whom received FLOT. In total, 16 of 20 patients who received FLOT had at least a partial response whereas only 5 of 12 patients who received FOLFOX had any tumor response (p = 0.027). Among all patients receiving neoadjuvant chemotherapy, 66% had poorly differentiated tumors. Only 1 of these patients experiencing a complete or near complete response compared to 50% of patients with non-poorly differentiated tumors (p = 0.001). Conclusions: In an ethnically diverse US population, tumor regression rates were improved with FLOT when compared to FOLFOX. For medically appropriate patients, strong consideration should be given for FLOT in the neoadjuvant setting.

Trastuzumab with FLOT Regimen for the Perioperative Treatment of Resectable HER2 + Advanced Gastric Cancer: A Retrospective Study.

BackgroundThe aim of this study was to evaluate the efficacy and safety of trastuzumab, combined with the FLOT regimen, in the perioperative treatment of resectable HER-2-positive advanced gastric cancer.MethodsOverall, 45 patients were divided into two groups; 29 patients in the experimental group were treated with trastuzumab combined with FLOT and 16 patients in the control group were treated with FLOT alone. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), tumor regression grade (TRG), surgical margin, side effects, and overall survival.ResultsIn the experimental and control groups, ORR was 72.4% and 43.8% (p=0.226), DCR was 89.7% and 87.5%, R0 resection rate was 96.5% and 93.7%, total/subtotal tumor regression grade was 17.2% and 6.3%, partial tumor regression grade was 27.6% and 18.7% (p=0.468), and 2-year survival rate was 78.1% and 73.9% (p=0.932), respectively. The common side effects were agranulocytosis and vomiting. There was no significant difference between the two groups.ConclusionTrastuzumab combined with FLOT has a good curative effect and safety profile in the perioperative treatment of patients with resectable HER-2-positive advanced gastric cancer. In addition, trastuzumab + FLOT had the same result as FLOT alone, as there was no significant benefit with the addition of T in the group studied.

The potential and challenges of patient-derived organoids in guiding the multimodality treatment of upper gastrointestinal malignancies.

The incidence of adenocarcinoma at the gastrooesophageal junction increased over the last years. Curative treatment for patients with upper gastrointestinal (UGI) malignancies, such as oesophageal and gastric tumours, is challenging and requires a multidisciplinary approach. Radical surgical resection with complete lymphadenectomy is the cornerstone of UGI cancer treatment. Combined with peri-operative treatment (i.e. by applying CROSS, EOX or FLOT regimen), the survival is even better than with surgery alone. However, peri-operative treatment is not effective in all patients, and the most effective strategy is a topic of active debate, as is reflected by varying treatment guidelines between countries. UGI cancers are (epi)genetically highly heterogeneous. It is thus not likely that a uniform treatment will benefit all patients equally well. Over recent years, patient-derived organoids (PDOs) gained more and more interest as an in vitro prediction model that may assist as a diagnostic tool in the future to select and eventually optimize the best peri-operative treatments for each patient. PDOs can be derived from endoscopic tumour biopsies, which maintain heterogeneity in culture. They can be rapidly established and expanded in a relatively short time for in vitro drug screening experiments. This review summarizes the clinical and molecular aspects of oesophageal and gastric tumours, as well as the current progress and remaining challenges in the use of PDOs for drug and radiation screens.

Neoadjuvant chemotherapy for gastric cancer. Frequent overtreatment or meaningful concept?

Neoadjuvant or perioperative therapy with radical surgery is ameaningful approach to improve the prognosis of gastric cancer. The FLOT regimen (5-fluorouracil, leucovorin, oxaliplatin, docetaxel) has been established as a perioperative concept in Germany and is also increasingly being used internationally. The prognostic significance of neoadjuvant chemoradiotherapy has to be awaited based on the results of currently active studies. The microsatellite instability (MSI) status has increasingly gained in importance with respect to decision-making processes in the interdisciplinary tumor board as patients with MSI tumors probably do not benefit from neoadjuvant therapy. Patients with only initial stages of locally advanced MSI tumors (cT2, N0) and those with comorbidities could be spared from neoadjuvant therapy. This article critically deals with the current state of the art concepts as well as with ongoing studies with respect to neoadjuvant and perioperative treatment of gastric cancer. For this purpose, the essential already published and the active studies are presented.