Abstract
Objective: Perioperative 5-fluorouracil, oxaliplatin, and docetaxel (FLOT) chemotherapy is the gold standard treatment for locally
advanced gastric cancer (LAGC). The present study aimed to evaluate the efficacy and safety of perioperative FLOT and the prognostic role of
the associated clinicopathological factors. Material and Methods: A retrospective analysis was conducted with 48 patients having gastric adenocarcinoma
(stage cT2-4 and/or N+ M0) who received perioperative FLOT (four preoperative and four postoperative 2-week cycles) and underwent
surgery for LAGC. The clinical and demographic characteristics of the patients, pretreatment laboratory values, and histological features
were recorded. Univariate and multivariate Cox regression analyses were conducted. Results: The median age of the patients was 59.5 years (age
range, 28-73 years). R0 resection was possible in 86% of the patients who underwent surgery. The objective response rate was 58.3%, the median
disease-free survival was 25.4 months (95% CI, 13.2-37.6), and the median overall survival (OS) was 42.9 months (95% CI,-/-). The 2-year
OS was 69.1%. It was revealed that ≥ pN2 disease, a positive surgical margin (SM), the presence of perineural invasion (PNI), a poor pathological
response to neoadjuvant therapy, and the use of an adjuvant chemotherapy regimen other than FLOT exerted a negative effect on survival.
In the multivariate analysis, PNI and SM were revealed as independent factors. Conclusion: The study presents real-life data that demonstrate
the effectiveness and feasibility of perioperative FLOT. The presence of PNI and positive SM were revealed to be the negative prognostic parameters
for survival.
Keywords:
Chemotherapy, gastric cancer, perioperative treatment
References
1Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33.
2Guan WL, He Y, Xu RH. Gastric cancer treatment: recent progress and future perspectives. J Hematol Oncol. 2023;16(1):57.
3Stahl M, Mariette C, Haustermans K, Cervantes A, Arnold D; ESMO Guidelines Working Group. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24 Suppl 6:vi51-6.
4Al-Batran SE, Homann N, Pauligk C, et al; FLOT4-AIO Investigators. 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(10184):1948-1957.
5Zhu Z, Gong YB, Xu HM. Neoadjuvant therapy strategies for advanced gastric cancer: Current innovations and future challenges. Chronic Dis Transl Med. 2020;6(3):147-157.
6McMillan DC. Cancer and systemic inflammation: stage the tumour and stage the host. Br J Cancer. 2013 6;109(3):529.
7Wang K, Diao F, Ye Z, et al. Prognostic value of systemic immune-inflammation index in patients with gastric cancer. Chin J Cancer. 2017;36(1):75.
8Xu SS, Li S, Xu HX, et al. Haemoglobin, albumin, lymphocyte and platelet predicts postoperative survival in pancreatic cancer. World J Gastroenterol. 2020;26(8):828-838.
9Feng JF, Wang L, Yang X. The preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) score is a useful predictor in patients with resectable esophageal squamous cell carcinoma. Bosn J Basic Med Sci. 2021;21(6):773-781.
10Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11-20.
11Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29(13):1715-1721.
12Arefpour AM, Hosseini S, Basi A, Novin K, Foroughi A, Garousi M. Evaluation of pathological response rate and complications of FOLFOX versus FLOT regimen in perioperative chemotherapy for resectable gastric cancer: a prospective study. Asian Pac J Cancer Prev. 2023;24(8):2791-2797.
13Farrokhi P, Sadeghi A, Sharifi M, Riechelmann R, Moghaddas A. Efficacy and safety of FLOT regimen vs DCF, FOLFOX, and ECF regimens as perioperative chemotherapy treatments for resectable gastric cancer patients; a report from the middle east. Res Pharm Sci. 2022;17(6):621-634.
14Möhring 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(3):609-622.
15Giommoni E, Lavacchi D, Tirino G, et al. Results of the observational prospective RealFLOT study. BMC Cancer. 2021;21(1):1086.
16Tomás TC, Eiriz I, Vitorino M, et al. Neutrophile-to-lymphocyte, lymphocyte-to-monocyte, and platelet-to-lymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer. World J Gastrointest Oncol. 2022;14(7):1307-1323.
17Puhr HC, Weirauch CC, Selimi F, et al. Systemic inflammatory biomarkers as prognostic tools in patients with gastroesophageal adenocarcinoma. J Cancer Res Clin Oncol. 2023;149(19):17081-17091.
18Qiu Y, Zhang Z, Chen Y. Prognostic value of pretreatment systemic immune-inflammation index in gastric cancer: a meta-analysis. Front Oncol. 2021;11:537140.
19Erol C, Sakin A, Başoğlu T, et al. Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group). Turk J Med Sci. 2022;52(4):1022-1032.
20Duzkopru Y, Kocanoglu A, Dogan O, Sahinli H, Cilbir E, Altinbas M. Hemoglobin, albumin, lymphocyte, and platelet score as a predictor of prognosis in metastatic gastric cancer. World J Gastrointest Oncol. 2023;15(9):1626-1635.
