Does Dose Reduction Compromise Pathological Response in Perioperative Gastric Cancer Chemotherapy? A Real-World Observational Analysis of FLOT and EOX
- Authors
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Jithin T. Chand
Department of Surgical Oncology, Vydehi Cancer Centre, Bangalore, India and Department of GI Surgery & Liver Transplantation, Caritas Hospital, Kottayam, Kerala, India -
Abhinay Reddy
Department of Surgical Oncology, Vydehi Cancer Centre, Bangalore, India and Department of Surgical Oncology, Sparsh Hospital, Bangalore, India -
C.M. Giridhar
Department of Surgical Oncology, Vydehi Cancer Centre, Bangalore, India and Department of Surgical Oncology, Apollo Hospital, Bangalore, India -
M.S. Ganesh
Department of Surgical Oncology, Vydehi Cancer Centre, Bangalore, India
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- Keywords:
- Locally advanced gastric cancer, perioperative chemotherapy, tumor regression grade, FLOT, EOX, dose modification of FLOT, dose modification of EOX, relative dose intensity
- Abstract
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Introduction: Standard of care of locally advanced gastric and Type III GE junction tumors is perioperative chemotherapy followed by radical surgery. There is clear evidence of FLOT outperforming other regimens in current literature. However, there is scarce data on dose modifications of various regimens and its effect on pathological tumor regression grade.
Material and Methods: This is retrospective study from a single institution between 2022 and 2024. Patients diagnosed with locally advanced gastric and Type III GE junction tumors, who underwent perioperative chemotherapy followed by radical surgery were included. Data including histopathological report, tumor regression grade following perioperative chemotherapy, chemotherapy regimen, chemotherapy dose intensity, and completion of chemotherapy, were collected from the medical records.
Results: Forty-one patients diagnosed as locally advanced gastric or GE junction cancers. Twenty patients (61%) received 3 cycles of perioperative EOX and 16 patients (39%) received 4 cycles of FLOT. Pathological complete response was higher in the EOX group than FLOT (75% vs 25%). Among patients receiving <80% of planned chemotherapy dose, none of the FLOT patients achieved TRG 0, whereas 36.4% of EOX patients did. Among patients receiving ≥80% of planned dose, the rate of TRG 0 was similar between regimens: EOX: 35.7%, FLOT: 30%. On logistic regression analysis, dose intensity ≥80% demonstrated higher odds of achieving major tumor regression. Distal tumors and dose intensity >80% increased the odds of improved tumor regression.
Conclusion: EOX regimen numerically showed more pCR rates than FLOT regimen. Dose density of >80% and distal tumors were predictors of better TRG scores.
- References
-
[1] Morgan E, Arnold M, Camargo MC, Gini A, Kunzmann AT, Matsuda T, et al. The current and future incidence and mortality of gastric cancer in 185 countries, 2020-40: A population-based modelling study. eClinicalMedicine 2022; 47: 101404.
[2] Banik A, Biswas L, Saha A, Ojha D. Carcinoma stomach in Eastern India—An audit from a tertiary health care center. Journal of Cancer Research and Therapeutics 2024; 20(1): 39-45.
[3] Mousavi SE, Ilaghi M, Elahi Vahed I, Nejadghaderi SA. Epidemiology and socioeconomic correlates of gastric cancer in Asia: results from the GLOBOCAN 2020 data and projections from 2020 to 2040. Sci Rep 2025; 15(1): 6529.
[4] Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, et al. Perioperative Chemotherapy Compared With Surgery Alone for Resectable Gastroesophageal Adenocarcinoma: An FNCLCC and FFCD Multicenter Phase III Trial. JCO 2011; 29(13): 1715-21.
[5] Cunningham D, Allum WH, Stenning SP, Thompson JN, Van De Velde CJH, Nicolson M, et al. Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer. N Engl J Med 2006; 355(1): 11-20.
[6] Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, 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. The Lancet 2019; 393(10184): 1948-57.
[7] Chen Y, He J, Zheng J, Lin Y, Wang H, Lian L, et al. Impact of pathological complete response on survival in gastric cancer after neoadjuvant chemotherapy: a propensity score matching analysis. BMC Gastroenterol 2025; 25(1): 11.
[8] Li Z, Shan F, Wang Y, Zhang Y, Zhang L, Li S, et al. Correlation of pathological complete response with survival after neoadjuvant chemotherapy in gastric or gastroesophageal junction cancer treated with radical surgery: A meta-analysis. Chang YJ, editor. PLoS ONE 2018; 13(1): e0189294.
[9] Bacha D, Mallek I, Ben-Rejeb S, Attia M, Gharbi L, Lahmar A, et al. Histological response of gastric adenocarcinomas after chemotherapy in the Tunisian population. ABCD, Arq Bras Cir Dig 2025; 38: e1901.
[10] Fonseca T, Coimbra M, Barbosa E, Barbosa J. Gastric cancer: histological response of tumor and metastatic lymph nodes for perioperative chemotherapy. CIRU 2022; 90(92): 8179.
[11] Mousavi SE, Ilaghi M, Elahi Vahed I, Nejadghaderi SA. Epidemiology and socioeconomic correlates of gastric cancer in Asia: results from the GLOBOCAN 2020 data and projections from 2020 to 2040. Sci Rep 2025; 15(1): 6529.
[12] Sinnamon AJ, Savoldy M, Mehta R, Dineen SP, Peña LR, Lauwers GY, et al. Tumor Regression Grade and Overall Survival following Gastrectomy with Preoperative Therapy for Gastric Cancer. Ann Surg Oncol 2023; 30(6): 3580-9.
[13] Ramirez R, Rosales-Lopez DE, Dominguez J, Camey C, Ovalle J. Tumor regression grade after neoadjuvant chemotherapy in patients with locally advanced gastric cancer treated with modern chemotherapy (FLOT): Experience in patients in Guatemala. JCO 2024; 42(3_suppl): 287-287.
[14] Mirshahvalad SA, Seyedinia SS, Huemer F, Schweighofer-Zwink G, Koch O, Hitzl W, et al. Prognostic value of [18F]FDG PET/CT on treatment response and progression-free survival of gastroesophageal cancer patients undergoing perioperative FLOT chemotherapy. European Journal of Radiology 2023; 163: 110843.
[15] Bhargava P, Das S, Ostwal V, Srinivas S, Bhandare M, Chaudhari V, et al. An Analysis of Tolerance and Early Survival Outcomes with Perioperative Modified FLOT in Gastric Cancers. South Asian J Cancer 2022; 11(02): 112-7.
[16] Bhandare MS, Gundavda KK, Yelamanchi R, Chopde A, Batra S, Kolhe M, et al. Impact of pCR after neoadjuvant chemotherapy and radical D2 dissection in locally advanced gastric cancers: Analysis of 1001 cases. European Journal of Surgical Oncology 2024; 50(6): 108343.
[17] Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer. N Engl J Med 2008; 358(1): 36-46.
[18] Sirohi B, Barreto S, Singh A, Batra S, Mittra A, Rastogia S, et al. Epirubicin, oxaliplatin, and capectabine is just as “MAGIC”al as epirubicin, cisplatin, and fluorouracil perioperative chemotherapy for resectable locally advanced gastro-oesophageal cancer. J Can Res Ther 2014; 10(4): 866.
[19] Kalachand RD, Mongan AM, Doherty M, King S, O’Farrell N, Reynolds JV, et al. Perioperative epirubicin, oxaliplatin, and capectabine (EOX) in locally advanced resectable gastroesophageal junction and gastric adenocarcinoma. JCO 2013; 31(15_suppl): e15142-e15142.
[20] Chen W, Shen J, Pan T, Hu W, Jiang Z, Yuan X, et al. FOLFOX versus EOX as a neoadjuvant chemotherapy regimen for patients with advanced gastric cancer. Experimental and Therapeutic Medicine 2014; 7(2): 461-7.
[21] Ramaswamy A, Bhargava P, Srinivas S, Kannan S, Bhandare M, Chaudhari V, 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 Canc 2023; 54(3): 820-8.
[22] Massaro G, Lavacchi D, Conticello C, Giommoni E, Brugia M, Pratesi L, et al. Impact of relative dose intensity (RDI) of perioperative FLOT in resectable and locally advanced gastric and gastroesophageal junction adenocarcinoma. JCO 2025; 43(16_suppl).
[23] Singh N, Selvarajan G, Seshadri RA. Perioperative FLOT vs EOX regimen and non-metastatic gastric carcinoma survival outcomes: Real-world data from a tertiary cancer centre, India. JCO 2025; 43(16_suppl).
[24] Silva IMMD, Oliveira JP, Maia M, De Liz CD, Oliveira ACFD, Alves ACF. Immunotherapy plus chemotherapy versus chemotherapy alone in perioperative treatment for locally advanced gastric cancer: A systematic review and meta-analysis. JCO 2024; 42(16_suppl): e16083-e16083.
[25] Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, et al. Perioperative Chemotherapy Compared With Surgery Alone for Resectable Gastroesophageal Adenocarcinoma: An FNCLCC and FFCD Multicenter Phase III Trial. JCO 2011; 29(13): 1715-21.
[26] Nakagawa M, Nakajima M, Yoshimatsu M, Ueta Y, Inoue N, Ochiai T, et al. An Overview of the Treatment Strategy of Esophagogastric Junction Cancer. Cancers 2025; 17(12): 1961.
[27] Lordick F, Rha SY, Muro K, Yong WP, Lordick Obermannová R. Systemic Therapy of Gastric Cancer—State of the Art and Future Perspectives. Cancers 2024; 16(19): 3337.
[28] Gaber CE, Sarker J, Abdelaziz AI, Okpara E, Lee TA, Klempner SJ, et al. Pathologic complete response in patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: A systematic review and meta‐analysis. Cancer Medicine 2024; 13(4): e7076.
[29] Lin JX, Tang YH, Zheng HL, Ye K, Cai JC, Cai LS, et al. Neoadjuvant camrelizumab and apatinib combined with chemotherapy versus chemotherapy alone for locally advanced gastric cancer: a multicenter randomized phase 2 trial. Nat Commun 2024; 15(1): 41.
[30] Jiang Z, Xie Y, Zhang W, Du C, Zhong Y, Zhu Y, et al. Perioperative chemotherapy with docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) for the treatment of locally advanced gastric or gastro-esophageal junction adenocarcinoma (MATCH): an open-label, randomized, phase 2 clinical trial. Gastric Cancer 2024; 27(3): 571-9.
[31] Wang X, Lu C, Wei B, Li S, Li Z, Xue Y, et al. Perioperative versus adjuvant S-1 plus oxaliplatin chemotherapy for stage II/III resectable gastric cancer (RESONANCE): a randomized, open-label, phase 3 trial. J Hematol Oncol 2024; 17(1): 17.
[32] Cunningham D, Stenning SP, Smyth EC, Okines AF, Allum WH, Rowley S, et al. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. The Lancet Oncology 2017; 18(3): 357-70.
[33] Lorenzen S, Pauligk C, Homann N, Schmalenberg H, Jäger E, Al-Batran SE. Feasibility of perioperative chemotherapy with infusional 5-FU, leucovorin, and oxaliplatin with (FLOT) or without (FLO) docetaxel in elderly patients with locally advanced esophagogastric cancer. Br J Cancer 2013; 108(3): 519-26.
[34] Herng SC, Htet NH, Naing C. A comparison of neoadjuvant therapies for gastroesophageal and gastric cancer on tumour resection rate: A network meta-analysis. Pasquali S, editor. PLoS ONE 2022; 17(9): e0275186.
[35] Monti M, Morgagni P, Nanni O, Framarini M, Saragoni L, Marrelli D, et al. Preoperative or Perioperative Docetaxel, Oxaliplatin, Capecitabine Gastrodoc Regimen in Patients with Locally Advanced Resectable Gastric Cancer: A Randomized Phase II Trial. SSRN Journal 2018.
[36] Back J, Sallinen V, Bonsdorff A, Kokkola A, Puolakkainen P. Short- and long-term outcomes after perioperative EOX therapy versus upfront surgery for gastric cancer: a single-centre propensity score-matched cohort study. BMC Surg 2025; 25(1): 184.
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