Efficacy and safety of modified FLOT chemotherapy in gastric or gastroesophageal junction adenocarcinoma: a retrospective cohort study

Introduction

Gastric and gastroesophageal junction (GEJ) adenocarcinoma are aggressive malignancies with relatively poor long-term survival despite advances in multimodality therapy. The MAGIC trial established perioperative chemotherapy as a standard of care, demonstrating a survival benefit with ECF [epirubicin, cisplatin, and 5-fluorouracil (5-FU)] compared to surgery alone (1). Subsequently, the landmark FLOT-4 trial compared FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) to ECF/ECX (epirubicin, cisplatin, and capecitabine) regimens and demonstrated superior outcomes (2). Patients receiving FLOT had a median overall survival (OS) of 50 months compared to 35 months with ECF/ECX, with superior pathological complete response (pCR) rates and improved R0 resection rates. These findings established FLOT as the preferred perioperative chemotherapy regimen for resectable gastric and GEJ adenocarcinoma. However, in routine clinical practice, treatment delivery often requires pragmatic dose or schedule adjustments, and outcome data for commonly used modified FLOT approaches, particularly from U.S. centers, remain limited.

Given the clear survival benefit, FLOT became the new standard of care in gastric cancer. In contrast, GEJ adenocarcinomas were treated by one of two approaches, perioperative FLOT or neoadjuvant chemoradiation followed by surgery (CROSS) (3). Most recently, the ESOPEC study directly compared perioperative FLOT to trimodality therapy (CROSS) demonstrating improved OS with perioperative chemotherapy, which established FLOT as the standard treatment regimen (4). Beyond its established role as a standard of care, FLOT has also become the backbone for ongoing trials investigating the addition of immunotherapy in the perioperative setting, reinforcing the importance of optimizing FLOT tolerability to support completion of multimodality therapy. For example, the recently reported MATTERHORN trial demonstrated that adding perioperative FLOT plus durvalumab improved 2-year event-free survival and pCR (5). In the final analysis presented at ESMO 2025, FLOT plus durvalumab also showed a statistically significant OS benefit compared with FLOT plus placebo, with improvements observed irrespective of PD-L1 status (6). Additionally, patients receiving durvalumab had higher rates of nodal clearance (ypN-) and improved event-free survival across all degrees of pathological response. Despite these advances, the routine clinical application of FLOT is frequently limited by treatment-related toxicity, often necessitating dose modifications or delays (7-9).

In the FLOT-4 trial, the incidence of grade ≥3 adverse events was notably high, with more than 50% of patients experiencing grade 3 neutropenia which contributed to an 18% grade 3 infection rate (2). These toxicities have frequently led to deviations from the planned treatment course, underscoring the challenges of maintaining dose intensity in routine clinical practice. In real-world settings, this toxicity burden can limit treatment completion, particularly among older patients and those with comorbidities, highlighting the need to better characterize pragmatic approaches aimed at improving treatment deliverability.

Emerging data from the metastatic setting further support the feasibility and efficacy of modified FLOT-based regimens. The phase 3 GASTFOX (PRODIGE 51) trial compared TFOX, a modified FLOT regimen, with FOLFOX as first-line therapy in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric or GEJ adenocarcinoma (10). In this study of 507 patients, TFOX demonstrated superior progression-free survival (PFS), OS, and objective response rate (ORR) compared with FOLFOX, albeit with higher rates of grade 3 or 4 gastrointestinal, neurologic, and hematologic toxicities. These findings support the clinical activity of a dose- and schedule-modified triplet platform and underscore ongoing interest in optimizing tolerability and treatment delivery across disease settings.

To date, there are no large prospective trials evaluating modified or reduced-intensity FLOT regimens in the curative setting. Given the frequency of dose reductions and treatment delays observed in clinical practice, there is a need to evaluate predefined, upfront modifications to the FLOT regimen aimed at improving tolerability and treatment delivery. Strategies such as reducing docetaxel and/or 5-FU doses, prolonging infusion times, and omitting the bolus have been adopted in some centers, but their safety and efficacy remain inadequately characterized.

In this context, we report a multi-institutional retrospective cohort of patients treated with a modified perioperative FLOT regimen, focusing on treatment delivery, safety, and clinical outcomes. We present this article in accordance with the STROBE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0111/rc).

Methods

This retrospective cohort study assessed the safety, treatment delivery, and clinical outcomes of a modified FLOT chemotherapy regimen in patients with resectable GEJ and gastric adenocarcinoma. A chart review was conducted for patients 18 years and older treated at Mayo Clinic Arizona, Mayo Clinic Florida, and Hospital Israelita Albert Einstein in São Paulo, Brazil, between January 2019 and January 2025. Patient demographics and clinical outcomes, including survival and safety data, were extracted. Pathologic staging was determined based on the American Joint Committee on Cancer (AJCC) criteria (11). Data were de-identified and stored in an encrypted database. Pathological response, including pCR, was determined from routine institutional pathology reports following surgical resection.

The standard FLOT regimen consists of perioperative docetaxel (50 mg/m²), oxaliplatin (85 mg/m²), leucovorin (200 mg/m²), and 5-FU (2,600 mg/m²) administered as a 24-hour infusion on day 1. In this retrospective study, the predefined modified FLOT regimen consisted of 5-FU at 2,400 mg/m² over 46–48 hours, oxaliplatin at 85 mg/m², and docetaxel at 40–50 mg/m². Leucovorin (200 mg/m²) was administered at the investigator’s discretion. Treatment cycles were repeated every 2 weeks. Dose modifications and use of granulocyte colony-stimulating factor (G-CSF) were also left to the discretion of the treating physician.

Safety was assessed by recording the incidence and severity of treatment-related adverse events within the cohort, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Data were collected on hematologic toxicities, including anemia, thrombocytopenia, and neutropenia, as well as objective non-hematologic toxicities such as transaminitis. Infectious complications attributed to perioperative chemotherapy were also captured.

The study was approved by the ethics committees of Hospital Israelita Albert Einstein (CAAE: 81744017.6.0000.0071) and the Mayo Clinic Arizona (IRB No. 24-007794). The requirement for informed consent was waived given the retrospective design and minimal risk to participants. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Statistical analysis

Efficacy was evaluated using OS and recurrence-free survival (RFS), estimated by the Kaplan-Meier method. OS was defined as the time from treatment initiation of perioperative chemotherapy to death from any cause, while RFS was defined as the time from surgical resection to the first documented recurrence or death. All analyses were conducted using R version 4.4.1.

Results

Baseline characteristics

A total of 29 patients were included in the analysis (Table 1). The median age at diagnosis was 66 years, and 62% were male. The cohort was ethnically diverse, comprising 59% White, 24% Hispanic, 3% Asian, and 3% Black. Gastric adenocarcinoma was the predominant cancer type (59%), followed by GEJ adenocarcinoma (34%). Clinical staging data showed the majority of tumors were T3 (45%) or T2 (24%), with 41% of patients staged as node-negative and 34% as node-positive (24% N1, 10% N2). Mismatch repair (MMR) status was assessed in 25 of 29 patients, all of whom were MMR proficient. Most patients (n=24, 83%) had a diagnostic laparoscopy completed prior to surgical resection; of these, 83% were performed before the initiation of chemotherapy and the remaining 17% before surgery.

Treatment summary

All 29 patients in the cohort received modified FLOT with a 2,400 mg/m² infusion of 5-FU administered over 46–48 hours. Over half of the patients received docetaxel at 40 mg/m² on day 1 (n=16, 55%), while the remaining patients received the 50 mg/m² dose. All patients received oxaliplatin at 85 mg/m² on day 1. Two patients received trastuzumab at 6 mg/m² in addition to chemotherapy for HER2 overexpression identified on IHC. The average number of modified FLOT cycles administered was 6.6 per patient (range, 4–8). Most patients (n=19, 66%) received total neoadjuvant treatment. There were ten patients who received adjuvant chemotherapy, including two patients with total adjuvant therapy. Both patients who had total adjuvant chemotherapy received all eight cycles. One patient initially had pT1b disease with a positive deep margin identified on endoscopic submucosal dissection (ESD), followed by an Ivor Lewis esophagectomy that revealed N1 nodal involvement. The other patient was referred following a partial gastrectomy performed at an outside institution, which demonstrated pT2, pN2 disease, and had not received neoadjuvant therapy for reasons that were not documented. Two separate patients received neoadjuvant chemoradiation at 50 Gy over 25 fractions with concurrent carboplatin plus paclitaxel after completion of neoadjuvant FLOT. These treatment variations reflect individualized, real-world management decisions within the context of a predefined modified FLOT backbone.

Toxicity data

Toxicity data were collected for all 29 patients who received the modified perioperative FLOT and are summarized in Figure 1. Grade 1–2 anemia occurred in 79%, while grade ≥3 anemia was reported in 7%. Neuropathy was observed in 72% of patients with grade 1–2 symptoms, while none had grade ≥3 neuropathy. Neutropenia of grade 1–2 severity was observed in 17%, with 34% experiencing grade ≥3. This led to grade 1–2 infection rate of 17% and grade ≥3 infection rate of 10%. Granulocyte colony stimulating factor (G-CSF) prophylaxis was given to 79% of our cohort (59% primary prophylaxis, 21% secondary prophylaxis). Thrombocytopenia was observed in 55% of patients at grade 1–2 severity, with no grade ≥3 events. Transaminitis was observed in 41% of patients at grade 1–2 severity, and 3% experienced grade ≥3 events. No treatment-related deaths were reported. Treatment delays and dose reductions occurred in 45% and 48% of patients within our cohort, respectively, most often due to hematologic toxicity such as neutropenia.

Figure 1 Perioperative toxicity data.

Clinical and survival outcomes

At a median follow-up of 30.3 months, 25 of the 29 patients (86%) had undergone curative-intent surgical resection (Table 2). Out of the four patients who did not undergo resection, three had developed metastatic disease (initially staged as T3N0, T2N0, and TXNX, respectively). The fourth patient declined surgery after receiving both neoadjuvant chemotherapy and chemoradiation with carboplatin plus paclitaxel.

Among all resected patients (n=25), an R0 resection was achieved in 22 cases (88%). pCR was observed in 4 patients (16%). Recurrence occurred in 8 patients (32%). Most recurrences (n=6, 75%) were distant metastases (including peritoneum, lungs, and bone), followed by local recurrence and regional lymph nodes. In the recurrent population, five patients had received all eight doses of perioperative FLOT while the remaining three received less than cohort average. Pathological characteristics of the recurrent population included 75% pT3 tumors or larger, 75% poorly differentiated grade, 63% gastric cancer (all of which were diffuse subtype), 50% with signet ring cell features, 38% with lymphovascular or perineural invasion (LVI/PNI), and 25% who had R1 resection. Compared to the non-recurrent population, the recurrent cohort demonstrated a higher proportion of T3–T4 disease. In contrast, the non-recurrent cohort showed higher rates of T1–T2 disease, with overall similar rates of node-positive disease between groups. In the overall population, median OS was 53.6 months, with 3-year OS rate of 75.3% (Figure 2). In the resected patient population, median OS was 62.2 months, with 3-year OS rate of 81.7%. Median RFS was 46.1 months, with 3-year RFS rate of 52.4%.

Figure 2 Overall survival of the entire cohort (A) plus resected patients (B) and recurrence free survival of resected patients (C).

Discussion

This retrospective study evaluated a predefined, modified perioperative FLOT regimen in patients with resectable gastric and GEJ adenocarcinoma and demonstrated feasible treatment delivery with acceptable safety and clinical outcomes in routine practice. Our findings support the real-world feasibility of a dose-adjusted perioperative chemotherapy strategy, especially for patients who may not tolerate standard FLOT due to age, comorbidities, or prior toxicities. Notably, almost one-third of our patients were aged 70 years or older, compared with 24% in the FLOT-4 trial, underscoring the applicability of this approach in an older and potentially more vulnerable population. The median follow-up duration of 30.3 months is shorter than the estimated median OS and RFS, and a proportion of patients remain censored. Therefore, survival outcomes should be interpreted with caution and are best considered descriptive of observed outcomes within this cohort rather than definitive estimates of long-term survival.

Among resected patients, the R0 resection rate of 88% and pCR rate of 16% were observed, consistent with ranges reported in prior perioperative FLOT studies (2,12). Moreover, the majority of patients in our cohort received total neoadjuvant treatment, reflecting a broader shift in practice toward front-loaded systemic therapy to enhance downstaging and improve surgical margins (13,14). Recurrences were identified in 32% of patients, primarily at distant sites such as the peritoneum and lung, consistent with known patterns of relapse in gastric and GEJ cancer (15). A high proportion of patients who recurred exhibited adverse histopathologic features such as signet ring cells, diffuse histology, poor differentiation, and lymphovascular or perineural invasion, underscoring the challenge of achieving durable control in biologically aggressive tumors (16).

The modified FLOT regimen in our cohort demonstrated encouraging tolerability, with manageable rates of hematologic and non-hematologic toxicity. High-grade infections were limited to 10%, and most other toxicities including neuropathy and transaminitis were mild (grade 1–2). Importantly, interpretation of the observed toxicity profile should consider the interplay between predefined regimen modifications, supportive care strategies, and subsequent cycle level adjustments. In our cohort, treatment delays occurred in 45% of patients and dose reductions in 48%. Direct comparison with FLOT-4 is limited by differences in reporting methodology and supportive care practices. In FLOT-4, dose modifications were reported as any modification, including non-toxicity-related changes, with 19% of patients affected during the preoperative phase and 46% during the postoperative phase, and dose delays were reported at the cycle rather than patient level. In addition, G-CSF use was substantially lower in FLOT-4 compared with our cohort, where primary prophylaxis was routinely administered. Accordingly, the observed lower rate of severe neutropenia in our cohort is likely multifactorial, reflecting both upfront dose modification and intensive growth factor support rather than regimen modification alone.

Reported toxicity rates in other real-world studies are variable, particularly with respect to neutropenia. In FLOT-4, G-CSF was administered mainly as secondary prophylaxis, whereas some more recent studies have employed it upfront (2). For example, the multicenter prospective RealFLOT study, which used a 2,400 mg/m² dose of 5-FU over 24 hours, reported grade 3–4 neutropenia in approximately 20% of patients (7). Importantly, a high proportion of patients in that study received primary G-CSF prophylaxis, which may have contributed to the low rate (6%) of grade ≥3 infections. A separate single-center study from Asia using routine primary G-CSF prophylaxis showed favorable toxicity and efficacy outcomes to standard dose FLOT (17). Rates of grade ≥3 neutropenia were low (5%), with grade ≥3 infections occurring in only 2%.

Modified FLOT regimens have also demonstrated feasibility in separate large real-world cohorts. One study analyzed outcomes in 343 patients using a regimen that matched our retrospective cohort (5-FU 2,400 mg/m² infusion over 46 hours, leucovorin 200 mg/m², oxaliplatin 85 mg/m², docetaxel 50 mg/m²) (18). Rates of high grade toxicity were low, including grade 3–4 diarrhea in 12%, febrile neutropenia in 8%. The 2-year OS was 69.4%. In a separate matched-pair analysis, dose-adjusted FLOT compared with EOX (epirubicin, oxaliplatin, and capecitabine) showed no significant differences in survival or pathological response, suggesting comparable effectiveness in routine practice (19).

Our observed survival outcomes including OS and RFS align with previously reported data from both clinical trials and real-world studies. The FLOT-4 trial reported a median OS of 50 months and durable RFS among patients treated with perioperative FLOT (2). Similarly, large retrospective cohorts and registry studies have demonstrated long-term survival with FLOT in routine practice, with R0 resection and pCR rates comparable to the results observed in our study (7,17,20). For instance, a separate retrospective study of perioperative FLOT at a single Asian center showed similar 3-year DFS of 46.5% (compared to 52.4% in our cohort). These outcomes provide contextual reassurance that long-term survival observed with perioperative FLOT in clinical trials can also be achieved in routine practice. Notably, these outcomes were observed using a modified regimen with acceptable rates of high-grade toxicity.

Collectively, these findings demonstrate that modified FLOT regimen can be delivered safely while maintaining key clinical milestones such as completion of perioperative therapy and advancing to surgery. As perioperative FLOT continues to serve as the backbone for combination strategies, including chemo-immunotherapy approaches such as MATTERHORN, optimizing tolerability and treatment delivery will be increasingly important in real-world practice.

Further perspective can be drawn from the recently published phase III PRODIGE 51 (GASTFOX) trial, which evaluated a modified FLOT regimen, TFOX (docetaxel 50 mg/m², folinic acid 400 mg/m², and oxaliplatin 85 mg/m², and 5-FU 2,400 mg/m² as a continuous 46 h infusion every 2 weeks), in advanced gastric and GEJ adenocarcinoma (10). In this first line setting, TFOX demonstrated superior efficacy compared with FOLFOX across key clinical endpoints including PFS, OS, and ORR. Notably, hematologic toxicity appeared manageable despite the use of triplet chemotherapy.

Consistent with these findings, our perioperative cohort demonstrated acceptable hematologic toxicity in the curative-intent setting. Collectively, these data support the concept that rational modification of the FLOT regimen may preserve antitumor efficacy while meaningfully reducing hematologic toxicity, thereby improving treatment tolerability and feasibility in broader clinical practice. The modification of 5-FU from 2,600 mg/m² over 24 hours to 2,400 mg/m² over 46 hours represents a modest absolute dose reduction, although the longer infusion duration may alter pharmacokinetic exposure and toxicity profiles. Patients with high-risk features such as diffuse histology, signet ring cell features, and lymphovascular invasion should be considered for individualized treatment strategies. These findings support further prospective evaluation of optimized dosing approaches in clinically heterogeneous populations.

Limitations

This study has several limitations, including its retrospective design and small sample size, which introduce selection bias and limit generalizability. Pathological response assessment was based on routine institutional reporting without standardized tumor regression grading or centralized review, which may limit comparability with clinical trial data. Practice patterns varied across the three participating institutions, potentially affecting supportive care, chemotherapy dosing, toxicity reporting, and the use of primary or secondary G-CSF prophylaxis. Given this heterogeneity and the limited cohort size, a matched standard FLOT comparison group was not included, and outcomes were instead benchmarked against historical data.

Conclusions

Modified perioperative FLOT, incorporating reduced and prolonged infusion of 5-FU, was well-tolerated and feasible in this diverse cohort of patients with resectable gastric and GEJ adenocarcinoma. These findings support the real-world use of tailored chemotherapy regimens, particularly in patients at risk of treatment-related complications. Modifications implemented by other real-world studies which incorporate routine use of G-CSF prophylaxis have also shown promising results and improved tolerability. Prospective studies with longer follow-up data are warranted to validate these results and clarify the impact of treatment modifications on long-term survival outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0111/rc

Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0111/dss

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0111/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0111/coif). C.W. reports advisor board roles for: Seagen, Exelixis, Pfizer, Merck, Natera, DoMore Diagnostics, GlaxoSmithkline, and Exelixis. T.B.S. reports research funding (to institution): Agios, Arys, Arcus, Atreca, Boston Biomedical, Bayer, Eisai, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Genentech, Novartis, Mirati, Merus, Abgenomics, Incyte, Pfizer, BMS, and Revolution Medicine; consulting (to institution): Servier, Ipsen, Arcus, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, Eisai, Merus, Merck KGaA, Revolution Medicines and Merck; consulting (to self): Stemline, AbbVie, Blueprint Medicines, Boehringer Ingelheim, Janssen, Daiichi Sankyo, Natera, Takeda, TreosBio, Celularity, Caladrius Biosciences, Exact Science, Sobi, Beigene, Kanaph, Astra Zeneca, Deciphera, Zai Labs, Exelixis, MJH Life Sciences, Aptitude Health, Illumina, Foundation Medicine and Sanofi. Glaxo SmithKline, Arsenal Bio, Xilio and RYGHT AI; IDMC/DSMB: The Valley Hospital, Fibrogen, Suzhou Kintor, Astra Zeneca, Exelixis, Merck/Eisai, PanCan and 1Globe. Scientific Advisory Board: Imugene, Immuneering, Xilis, Replimune, Artiva and Sun Biopharma; royalties: Uptodate; Inventions/Patents: WO/2018/183488: HUMAN PD1 PEPTIDE VACCINES AND USES THEREOF – Licensed to Imugene WO/2019/055687: METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA – Licensed to Recursion. M.B.S. reports consulting (self): Novartis; consulting (institution): Boehringer Ingelheim; and research support (institution): Taiho, and Eli Lilly. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics committees of Hospital Israelita Albert Einstein (CAAE: 81744017.6.0000.0071) and the Mayo Clinic Arizona (IRB No. 24-007794). The requirement for informed consent was waived given the retrospective design and minimal risk to participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11-20. [Crossref] [PubMed]
2. Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 2019;393:1948-57. [Crossref] [PubMed]
3. van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012;366:2074-84. [Crossref] [PubMed]
4. Hoeppner J, Brunner T, Schmoor C, et al. Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer. N Engl J Med 2025;392:323-35. [Crossref] [PubMed]
5. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer. N Engl J Med 2025;393:217-30. [Crossref] [PubMed]
6. Tabernero J, Al-Batran SE, Wainberg ZAA, et al. LBA81 Final overall survival (OS) and the association of pathological outcomes with event-free survival (EFS) in MATTERHORN: A randomised, phase III study of durvalumab (D) plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ann Oncol 2025;36:S1623-S1624. [Crossref]
7. Giommoni E, Lavacchi D, Tirino G, et al. Results of the observational prospective RealFLOT study. BMC Cancer 2021;21:1086. [Crossref] [PubMed]
8. Egebjerg K, Andersen TS, Bæksgaard L, et al. Implementation of perioperative FLOT compared to ECX/EOX chemotherapy regimens in resectable esophagogastric adenocarcinomas: an analysis of real-world data. Acta Oncol 2024;63:322-9. [Crossref] [PubMed]
9. Möhring C, Mańczak A, Timotheou A, et al. Perioperative therapy with FLOT4 significantly increases survival in patients with gastroesophageal and gastric cancer in a large real-world cohort. Int J Cancer 2023;153:609-22. [Crossref] [PubMed]
10. Zaanan A, Bouché O, de la Fouchardière C, et al. TFOX versus FOLFOX in first-line treatment of patients with advanced HER2-negative gastric or gastro-oesophageal junction adenocarcinoma (PRODIGE 51- FFCD-GASTFOX): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol 2025;26:732-44. [Crossref] [PubMed]
11. Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin 2017;67:93-9.
12. Al-Batran SE, Hofheinz RD, Pauligk C, et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 2016;17:1697-708. [Crossref] [PubMed]
13. Yang J, Greally M, Strong VE, et al. Perioperative versus total neoadjuvant chemotherapy in gastric cancer. J Gastrointest Oncol 2023;14:1193-203. [Crossref] [PubMed]
14. Tokunaga M, Kurokawa Y, Fukagawa T, et al. Neoadjuvant chemotherapy for locally advanced gastric cancer in Japan: Consensus meeting at the 77th general meeting of the Japanese Society of Gastroenterological Surgery. Ann Gastroenterol Surg 2023;7:856-62. [Crossref] [PubMed]
15. Toriumi T, Terashima M, Mizusawa J, et al. Recurrence patterns after curative gastrectomy for pStage II/III gastric cancer: Exploratory analysis of the randomized controlled JCOG1001 trial. Eur J Surg Oncol 2023;49:838-44. [Crossref] [PubMed]
16. Dong X, Sun G, Qu H, et al. Prognostic Significance of Signet-Ring Cell Components in Patients With Gastric Carcinoma of Different Stages. Front Surg 2021;8:642468. [Crossref] [PubMed]
17. Kee W, Ng KYY, Liong SZ, et al. Real-World Outcomes for Localised Gastro-Oesophageal Adenocarcinoma Cancer Treated with Perioperative FLOT and Prophylactic GCSF Support in a Single Asian Centre. Cancers (Basel) 2024;16:3697. [Crossref] [PubMed]
18. Bhargava P, Das S, Ostwal V, et al. An Analysis of Tolerance and Early Survival Outcomes with Perioperative Modified FLOT in Gastric Cancers. South Asian J Cancer 2022;11:112-7. [Crossref] [PubMed]
19. Ramaswamy A, Bhargava P, Srinivas S, et al. Perioperative Modified FLOT Versus EOX in Locally Advanced Resectable Gastric and Gastro-Oesophageal Junction Adenocarcinoma: Results of a Matched-Pair Analysis. J Gastrointest Cancer 2023;54:820-8. [Crossref] [PubMed]
20. Sisic L, Crnovrsanin N, Nienhueser H, et al. Perioperative chemotherapy with 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) for esophagogastric adenocarcinoma: ten years real-life experience from a surgical perspective. Langenbecks Arch Surg 2023;408:81. [Crossref] [PubMed]