Predictive Value of Delta-PNI on Major Pathological Response in Gastric Cancer Patients Treated With Neoadjuvant FLOT Regimen

Abstract

Objective: We aimed to investigate the predictive effect of prognostic nutritional index change (Delta-PNI) from initiation to completion of the neoadjuvant fluorouracil-oxaliplatin-docetaxel (FLOT) regimen on the major pathological response (mPR) in patients with non-metastatic gastric cancer. Material and Methods: A single-center, retrospective study was conducted, screening the patients treated at Antalya Training and Research Hospital between 2019 and 2024. The difference between the PNI values prior to the initiation of FLOT and after the completion of four cycles of FLOT was calculated as Delta-PNI. The patients were dichotomised by the median of Delta-PNI value 5.4 (15,55 - 19,70). Results: A total of 41 patients were included (n=41). The median age was 63 years (40-79) and nine patients (22%) were female. Thirteen patients (31.7%) had mPR, while five patients (12.1%) had tumor progression after neoadjuvant chemotherapy. In the univariate analysis, the high delta-PNI value (≥5.4) and low delta-PNI (<5.4) groups had similar rates of mPR [35.0% vs. 28.6%, respectively; p=0.744)]. In the multivariate analysis, the odds ratio for having mPR was 0.99, 95% CI (0.18-5.40) for patients with a higher delta-PNI value compared to those with a lower delta-PNI value (p=0.994). The other variables were also not significant: pretreatment PNI (p=0.412), sex (p=0.068), histological differentiation (p=0.248), clinical T stage (p=0.999), and N stage (p=0.256). Conclusion: The delta-PNI was not a significant predictor of mPR. This study is the first to evaluate dynamic changes in PNI values in the literature. Future studies with larger cohorts are needed to highlight this topic.

Keywords

• Gastric cancer
• Prognostic Nutritional Index
• Neoadjuvant treatment

Neoadjuvan FLOT Rejimi ile Tedavi Edilen Mide Kanseri Tanılı Hastalarda Delta-PNI Değerinin Majör Patolojik Yanıt Üzerine Prediktif Etkisi

Öz

ÖZ Amaç: Bu çalışmada, neoadjuvan florourasil-oksaliplatin-dosetaksel (FLOT) rejiminin başlanması ile tamamlanması arasındaki prognostik nutrisyon indeks farkının (Delta-PNI), metastatik olmayan mide kanseri hastalarında majör patolojik yanıt (mPR) üzerindeki öngörücü etkisini araştırmayı amaçladık. Gereç ve Yöntemler: Bu çalışma, 2019-2024 yılları arasında Antalya Eğitim ve Araştırma Hastanesi'nde tedavi edilen hastaların tarandığı, tek merkezli, retrospektif bir çalışma olarak gerçekleştirilmiştir. FLOT rejiminin başlangıcından önceki ve dört kürün tamamlanmasından sonraki PNI değerleri arasındaki fark Delta-PNI olarak hesaplanmıştır. Hastalar, Delta-PNI medyan değeri olan 5,4'e (15,55 - 19,70) göre iki gruba ayrılmıştır. Bulgular: Çalışmaya toplam 41 hasta (n=41) dahil edilmiştir. Medyan yaş 63 (40-79) olup, 9 hasta (%22) kadındır. On üç hasta (%31,7) mPR elde ederken, 5 hasta (%12,1) neoadjuvan kemoterapi sonrasında progresyon görülmüştür. Univariate analizlerde, yüksek Delta-PNI değeri (≥5,4) grubuyla düşük Delta-PNI (<5,4) grubunun mPR oranları benzer bulunmuştur [%35,0 vs. %28,6; p=0,744]. Multivariate analizlerde, yüksek Delta-PNI değeri olan hastaların mPR elde etme olasılığı, düşük Delta-PNI değerine sahip hastalara kıyasla 0,99 (%95 CI 0,18-5,40; p=0,994) olarak hesaplanmıştır. Diğer değişkenler de anlamlı bulunmamıştır; tedavi öncesi PNI (p=0,412), cinsiyet (p=0,068), histolojik farklılaşma (p=0,248), klinik T evresi (p=0,999) ve N evresi (p=0,256). Sonuç: Delta-PNI, mPR için anlamlı bir prediktif belirteç olarak bulunmamıştır. Bu çalışma, literatürde PNI dinamik değişimini değerlendiren ilk çalışmadır. Gelecekte daha fazla hasta sayısı ile yapılacak çalışmalar bu konuyu aydınlatabilir.

Anahtar Kelimeler

• Mide kanseri
• Prognostik beslenme indeksi
• Neoadjuvan tedavi

References

1. 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021; 71:209–49.
2. 2. Qiu H, Cao S, Xu R. Cancer incidence, mortality, and burden in China: a time-trend analysis and comparison with the United States and United Kingdom based on the global epidemiological data released in 2020. Cancer Commun (Lond) 2021; 41:1037–48.
3. 3. Wagner AD, Syn NLX, Moehler M, Grothe W, Yong WP, Tai BC, Ho J, Unverzagt S. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 2017; 8(8):CD004064.
4. 4. Guan WL, He Y, Xu RH. Gastric cancer treatment: recent progress and future perspectives. Journal of Hematology & Oncology 2023; 16:1–28.
5. 5. Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, von Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Weniger J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Jäger E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; 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.
6. 6. Kaltenmeier C, Althans A, Mascara M, Nassour I, Khan S, Hoehn R, Zureikat A, Tohme S. Pathologic Complete Response Following Neoadjuvant Therapy for Gastric Adenocarcinoma: A National Cancer Database Analysis on Incidence, Predictors, and Outcomes. Am Surg 2020; 87:1145.
7. 7. Wu CX, Zhu ZH. Diagnosis and evaluation of gastric cancer by positron emission tomography. World Journal of Gastroenterology : WJG 2014; 20:4574.
8. 8. Lai MY, Kang SY, Sun YT, Quan TT, Lu SX, He CY, Zhou ZW, Yang LQ, Luo HY, Wang FH, Li YH, Xu RH, Guan WL, Qiu MZ. Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systemic therapy of gastric cancer. BMC Cancer 2022; 22:1–10.

9. 9. Baker A, Wooten LA, Malloy M. Nutritional considerations after gastrectomy and esophagectomy for malignancy. Curr Treat Options Oncol 2011; 12:85–95.
10. 10. Topçu A, Yasin Aİ. Impact of Malnutrition on Prognosis in Patients with HER2-negative Metastatic Gastric Cancer. Medical Journal of Bakirkoy 2022; 18:258–65.
11. 11. Küçükarda A, Gökyer A, Gökmen İ, Özcan E, Hacıoğlu MB, Erdoğan B, Uzunoğlu S, Çiçin İ. Prognostic nutritional index is an independent prognostic factor for treatment response, survival and drug choice in metastatic castration-resistant prostate cancer treated with abiraterone acetate or enzalutamide. Actas Urológicas Españolas (English Edition) 2022; 46:301–9.
12. 12. Tsekrekos A, Detlefsen S, Riddell R, Conner J, Mastracci L, Sheahan K, Shetye J, Lundell L, Vieth M. Histopathologic tumor regression grading in patients with gastric carcinoma submitted to neoadjuvant treatment: results of a Delphi survey. Hum Pathol 2019; 84:26–34
13. 13. Shi C, Badgwell BD, Grabsch HI, Gibson MK, Hong SM, Kumarasinghe P, Lam AK, Lauwers G, O'Donovan M, van der Post RS, Tang L, Ushiku T, Vieth M, Selinger CI, Webster F, Nagtegaal ID. Data Set for Reporting Carcinoma of the Stomach in Gastrectomy. Arch Pathol Lab Med 2022; 146:1072–83.
14. 14. Mirza A, Naveed A, Hayes S, Formela L, Welch I, West CM, Pritchard S, Navarro A, Stringer A, Yazawa T. Assessment of histopathological response in gastric and gastro‐oesophageal junction adenocarcinoma following neoadjuvant chemotherapy: which scoring system to. Wiley Online LibraryA Mirza, A Naveed, S Hayes, L Formela, I Welch, CM West, S PritchardInternational Scholarly Research Notices, 2012•Wiley Online Library. 2012; 1–8.
15. 15. Onodera T GNKG. Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients. Nihon Geka Gakkai Zasshi 1984; 85(9):1001–5.
16. 16. Tohme S, Chidi AP, Sud V, Tsung A. Prognostic Nutritional Index Is Associated with Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Radioembolization. J Vasc Interv Radiol 2017; 28:470–72.
17. 17. Suárez-Llanos JP, Vera-García R, Contreras-Martinez J. The Determination of a Consensus Nutritional Approach for Cancer Patients in Spain Using the Delphi Methodology. Nutrients 2022; 14(7):1404.
18. 18. Fujitani K, Tsujinaka T, Fujita J, Miyashiro I, Imamura H, Kimura Y, Kobayashi K, Kurokawa Y, Shimokawa T, Furukawa H. Prospective randomized trial of preoperative enteral immunonutrition followed by elective total gastrectomy for gastric cancer. Br J Surg 2012; 99:621–9.
19. 19. Jiang N, Deng JY, Ding XW, Ke B, Liu N, Zhang RP, Liang H. Prognostic nutritional index predicts postoperative complications and long-term outcomes of gastric cancer. World Journal of Gastroenterology : WJG 2014; 20:10537.
20. 20. Mao C, Xu W, Ma W, Wang C, Guo Z, Yan J. Prognostic Value of Pretreatment Prognostic Nutritional Index in Patients With Renal Cell Carcinoma: A Meta-Analysis. Front Oncol 2021; 11:719941.
21. 21. Melekoglu E, Bayram E, Secmeler S, Mete B, Sahin B. Pretreatment Modified Glasgow Prognostic Score for Predicting Prognosis and Survival in Elderly Patients with Gastric Cancer Treated with Perioperative FLOT. Nutrients 2023; 15:4156.
22. 22. Wang P, Wang H, Qiu G, Liu J, Fan L, Liao X, Che X. A Nomogram Model Involving Preoperative Fibrinogen and Prognostic Nutritional Index Score for Predicting Postoperative Outcome in Patients with Gastric Cancer. Cancer Manag Res 2021; 13:4191–4201.
23. 23. Shen D, Zhou G, Zhao J, Wang G, Jiang Z, Liu J, Wang H, Deng Z, Ma C, Li J. A novel nomogram based on the prognostic nutritional index for predicting postoperative outcomes in patients with stage I–III gastric cancer undergoing robotic radical gastrectomy. Front Surg 2022; 9:928659.
24. 24. Du Z, Sun H, Zhao R, Deng G, Pan H, Zuo Y, Huang R, Xue Y, Song H. Combined with prognostic nutritional index and IgM for predicting the clinical outcomes of gastric cancer patients who received surgery. Front Oncol 2023; 13:1113428.
25. 25. Yun JH, Song GJ, Son MW, Lee MS. Global Leadership Initiative on Malnutrition Criteria and Immunonutritional Status Predict Chemoadherence and Survival in Stage II/III Gastric Cancer Treated with XELOX Chemotherapy. Nutrients 2024; 16:3468.
26. 26. Bossi P, De Luca R, Ciani O, D’Angelo E, Caccialanza R. Malnutrition management in oncology: An expert view on controversial issues and future perspectives. Front Oncol 2022; 12:910770.
27. 27. Choi WJ, Kim J. Nutritional Care of Gastric Cancer Patients with Clinical Outcomes and Complications: A Review. Clin Nutr Res 2016; 5:65.
28. 28. Ding D, Feng Y, Song B, Gao S, Zhao J. Effects of preoperative and postoperative enteral nutrition on postoperative nutritional status and immune function of gastric cancer patients. Turk J Gastroenterol 2015; 26:181–5.