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      Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group)

      research-article
      1 , * , , 2 , 3 , 4 , 4 , 5 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 12 , 13 , 13 , 14 , 14 , 15 , 16 , 1 , 17 , 18 , 19 , 20 , 21 , 22 , 22 , 23 , 24 , 25 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 31 , 32 , 33 , 34 , 1 , 1 , 1 , 3 , 6 , 1
      Turkish Journal of Medical Sciences
      Scientific and Technological Research Council of Turkey (TUBITAK)
      FLOT chemotherapy, perioperative treatment, gastric cancer, GEJ tumor, prognostic factor

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          Abstract

          Background/aim

          Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors.

          Materials and methods

          The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded.

          Results

          A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5–20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3–4 toxicity was seen in 23.6% patients.

          Conclusion

          Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

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          Most cited references21

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          Macrophage diversity enhances tumor progression and metastasis.

          There is persuasive clinical and experimental evidence that macrophages promote cancer initiation and malignant progression. During tumor initiation, they create an inflammatory environment that is mutagenic and promotes growth. As tumors progress to malignancy, macrophages stimulate angiogenesis, enhance tumor cell migration and invasion, and suppress antitumor immunity. At metastatic sites, macrophages prepare the target tissue for arrival of tumor cells, and then a different subpopulation of macrophages promotes tumor cell extravasation, survival, and subsequent growth. Specialized subpopulations of macrophages may represent important new therapeutic targets. Copyright 2010 Elsevier Inc. All rights reserved.
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            Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.

            A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer. We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival. ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P=0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001). In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival. (Current Controlled Trials number, ISRCTN93793971 [controlled-trials.com].). Copyright 2006 Massachusetts Medical Society.
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              Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis.

              Inflammation may play an important role in cancer progression, and a high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a poor prognostic indicator in several malignancies. Here we quantify the prognostic impact of this biomarker and assess its consistency in solid tumors. A systematic review of electronic databases was conducted to identify publications exploring the association of blood NLR and clinical outcome in solid tumors. Overall survival (OS) was the primary outcome, and cancer-specific survival (CSS), progression-free survival (PFS), and disease-free survival (DFS) were secondary outcomes. Data from studies reporting a hazard ratio and 95% confidence interval (CI) or a P value were pooled in a meta-analysis. Pooled hazard ratios were computed and weighted using generic inverse-variance and random-effect modeling. All statistical tests were two-sided. One hundred studies comprising 40559 patients were included in the analysis, 57 of them published in 2012 or later. Median cutoff for NLR was 4. Overall, NLR greater than the cutoff was associated with a hazard ratio for OS of 1.81 (95% CI = 1.67 to 1.97; P < .001), an effect observed in all disease subgroups, sites, and stages. Hazard ratios for NLR greater than the cutoff for CSS, PFS, and DFS were 1.61, 1.63, and 2.27, respectively (all P < .001). A high NLR is associated with an adverse OS in many solid tumors. The NLR is a readily available and inexpensive biomarker, and its addition to established prognostic scores for clinical decision making warrants further investigation. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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                Author and article information

                Journal
                Turk J Med Sci
                Turk J Med Sci
                Turkish Journal of Medical Sciences
                Scientific and Technological Research Council of Turkey (TUBITAK)
                1300-0144
                1303-6165
                2022
                22 May 2022
                : 52
                : 4
                : 1022-1032
                Affiliations
                [1 ]Department of Medical Oncology, Faculty of Medicine, Ankara Yıldırım Beyazıt University, Ankara, Turkey
                [2 ]Department of Medical Oncology, Faculty of Medicine, Van Yüzüncü Yıl University, Van, Turkey
                [3 ]Department of Medical Oncology, School of Medicine, Marmara University, İstanbul, Turkey
                [4 ]Department of Medical Oncology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
                [5 ]Department of Medical Oncology, Ankara Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkey
                [6 ]Department of Medical Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
                [7 ]Department of Medical Oncology, Konya Meram State Hospital, Konya, Turkey
                [8 ]Department of Medical Oncology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
                [9 ]Department of Medical Oncology, Göztepe Training and Research Hospital, İstanbul Medeniyet University, İstanbul, Turkey
                [10 ]Department of Medical Oncology, Derince Training and Research Hospital, Kocaeli, Turkey
                [11 ]Department of Medical Oncology, Prof. Dr. A. İlhan Özdemir Education and Research Hospital, Giresun University, Giresun, Turkey
                [12 ]Department of Medical Oncology, Faculty of Medicine, Sakarya University, Sakarya, Turkey
                [13 ]Department of Medical Oncology, Faculty of Medicine, Gazi University, Ankara, Turkey
                [14 ]Department of Medical Oncology, Institute of Oncology, İstanbul University, İstanbul, Turkey
                [15 ]Department of Medical Oncology, Faculty of Medicine, Fırat University, Elazığ, Turkey
                [16 ]Department of Medical Oncology, Ankara City Hospital, Ankara, Turkey
                [17 ]Department of Medical Oncology, Çanakkale Mehmet Akif Ersoy State Hospital, Çanakkale, Turkey
                [18 ]Department of Medical Oncology, Faculty of Medicine, Çukurova University, Adana, Turkey
                [19 ]Department of Medical Oncology, Dışkapı Training and Research Hospital, Ankara, Turkey
                [20 ]Department of Medical Oncology, Faculty of Medicine, İnönü University, Malatya, Turkey
                [21 ]Department of Medical Oncology, Adıyaman Training and Research Hospital, Adıyaman, Turkey
                [22 ]Department of Medical Oncology, Ümraniye Education and Research Hospital, İstanbul, Turkey
                [23 ]Department of Medical Oncology, Memorial Ankara Hospital, Ankara, Turkey
                [24 ]Department of Medical Oncology, Gülhane Education and Research Hospital, Ankara, Turkey
                [25 ]Department of Medical Oncology, Faculty of Medicine, Ege University, İzmir, Turkey
                [26 ]Department of Medical Oncology, Kahramanmaraş Necip Fazıl City Hospital, Kahramanmaraş, Turkey
                [27 ]Department of Medical Oncology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
                [28 ]Department of Medical Oncology, Cerrahpaşa School of Medicine, İstanbul University, İstanbul, Turkey
                [29 ]Department of Medical Oncology, Zonguldak Atatürk State Hospital, Zonguldak, Turkey
                [30 ]Department of Medical Oncology, Tekirdağ State Hospital, Tekirdağ, Turkey
                [31 ]Department of Medical Oncology, Acıbadem Maslak Hospital, İstanbul, Turkey
                [32 ]Department of Medical Oncology, Faculty of Medicine, Osmangazi University, Eskişehir, Turkey
                [33 ]Department of Medical Oncology, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey
                [34 ]Department of Medical Oncology, Anadolu Medical Center, Kocaeli, Turkey
                Author notes
                [* ]Correspondence: chan_erol@ 123456hotmail.com
                Author information
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                Article
                turkjmedsci-52-4-1022
                10.55730/1300-0144.5404
                10387859
                36326360
                58c47eb7-99a4-469e-b50f-9c1744b41205
                © TÜBİTAK

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 07 February 2022
                : 10 August 2022
                : 22 May 2022
                Categories
                Research Article

                flot chemotherapy,perioperative treatment,gastric cancer,gej tumor,prognostic factor

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