Table Info

Table 1.

Patient characteristics

Characteristics		Number (%)
Age	< 65 ≥ 65	66 (54.1) 56 (45.9)
Gender	Male Female	75 (61.5) 47 (38.5)
ECOG	0–1 2–3	77 (63.1) 45 (36.9)
Lauren type	Colonic Diffuse Mixed Not known	29 (23.8) 53 (43.4) 15 (12.3) 25 (20.5)
MSI status	MSI-H MSS Not known	27 (22.1) 71 (58.1) 24 (19.8)
PD-L1 (CPS)	PD-L1 negative PD-L1 CPS 1–9 PD-L1 CPS ≥ 10 Not known	7 (5.7) 57 (46.7) 14 (11.5) 44 (36.1)
HER2	Positive Negative Not known	19 (15.7) 88 (72.7) 15 (11.6)
Primary tumor	Presence Surgically removed	70 (57.4) 52 (42.6)
Number of organs with metastases	1–2 ≥ 3	77 (63.1) 45 (36.9)
Metastatic sites	Liver Lungs Peritoneum Lymphatic nodes Bones Other	46 (38) 16 (12.4) 54 (44.6) 64 (52.1) 12 (9.9) 15 (12.4)
Line of immunotherapy	First-line Second-line Third-line Fourth-line and subsequent	6 (4.9) 58 (47.5) 40 (32.8) 18 (14.8)
Number of lines after immunotherapy	0 1 2 ≥ 3	78 (64.5) 22 (18.2) 17 (13.2) 5 (4.1)

ECOG: Eastern Cooperative Oncology Group; MSI: microsatellite instability; MSI-H: high microsatellite instability; MSS: microsatellite stable; PD-L1: programmed death-ligand 1; CPS: combined positive score; HER2: human epidermal growth factor receptor 2

Declarations

Acknowledgments

Authors express their appreciation to Evdokimov V. I., Fedorinov D. S., and Tsaryova A. S. for their help in collecting data. Participating centers: N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; Moscow Multidisciplinary Clinical Center “Kommunarka”, Moscow Healthcare Department; Branch “Oncology Center No. 1 of the City Clinical Hospital named after S. S. Yudin of the Moscow Department of Health”; A.S. Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department; Moscow City Oncology Hospital No. 62, Moscow Healthcare Department.

Author contributions

AR: Investigation, Methodology, Writing—original draft. MF: Investigation, Methodology, Writing—review & editing, Formal analysis. DP, ML, LZ, DS, MV, IP, and NB: Writing—review & editing. AT: Conceptualization, Supervision, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The research proposal was submitted at the academic meeting and approved by the local ethics committee on 23.01.2021. The Local Committee of Scientific Research Ethics at N.N. Blokhin National Medical Research Center of Oncology was registered with the Federal Service for Supervision of Health and Social Development on 10.02.2006 (license number 01-3775/06).

Consent to participate

The Local Committee of Scientific Research Ethics at N.N. Blokhin National Medical Research Center of Oncology exempted informed consent to participate in this manuscript.

Consent to publication

Not applicable.

Availability of data and materials

Requests for accessing the datasets should be directed to [Alexey Tryakin, atryakin@gmail.com].

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Shakhzadova AO, Starinsky VV, Lisichnikova IV. Cancer care to the population of Russia in 2022. Siberian journal of oncology. 2023;22:5–13. Russian. [DOI]

Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, et al.; Arbeitsgemeinschaft Internistische Onkologie. Phase III Trial in Metastatic Gastroesophageal Adenocarcinoma with Fluorouracil, Leucovorin Plus Either Oxaliplatin or Cisplatin: A Study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008;26:1435–42. [DOI] [PubMed]

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al.; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97. [DOI] [PubMed]

Shah MA, Shitara K, Ajani JA, Bang YJ, Enzinger P, Ilson D, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29:2133–41. [DOI] [PubMed] [PMC]

Shitara K, Janjigian YY, Moehler MH, Garrido M, Gallardo C, Shen L, et al. Nivolumab (NIVO) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): Expanded efficacy, safety, and subgroup analyses from CheckMate 649. J Clin Oncol. 2022;40:240. [DOI]

Rha SY, Oh DY, Yañez P, Bai Y, Ryu MH, Lee J, et al.; KEYNOTE-859 investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24:1181–95. [DOI] [PubMed]

Muro K, Oh SC, Shimada Y, Lee KW, Yen CJ, Chao Y, et al. Subgroup analysis of East Asians in RAINBOW: A phase 3 trial of ramucirumab plus paclitaxel for advanced gastric cancer. J Gastroenterol Hepatol. 2016;31:581–9. [DOI] [PubMed]

Lorenzen S, Thuss-Patience P, Pauligk C, Gökkurtet E, Ettrich T, Lordick F, et al. FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel – results from the phase II RAMIRIS Study of the German Gastric Cancer Study Group at AIO. Eur J Cancer. 2022;165:48–57. [DOI]

Besova NS, Titova TA, Tryakin AA, Artamonova EV, Okarevich ES, Stroyakovsky DL, et al. Ramucirumab in combination with Paclitaksel or Folfiri in the second line of treatment of patients with disseminated stomach cancer after Docatoxel in the first line in routine clinical practice. Medical Council. 2021;64–78. Russian. [DOI]

10.

Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, et al. Regorafenib for the Treatment of Advanced Gastric Cancer (INTEGRATE): A Multinational Placebo-Controlled Phase II Trial. J Clin Oncol. 2016;34:2728–35. [DOI] [PubMed] [PMC]

11.

Tabernero J, Shitara K, Zaanan A, Doi T, Lorenzen S, Van Cutsem E, et al. Trifluridine/tipiracil versus placebo for third or later lines of treatment in metastatic gastric cancer: an exploratory subgroup analysis from the TAGS study. ESMO Open. 2021;6:100200. [DOI] [PubMed] [PMC]

12.

Kanagavel D, Fedyanin M, Tryakin A, Tjulandin S. Second-line treatment of metastatic gastric cancer: Current options and future directions. World J Gastroenterol. 2015;21:11621–35. [DOI] [PubMed] [PMC]

13.

Wainberg ZA, Shitara K, Van Cutsem E, Wyrwicz L, Lee KW, Kudaba I, et al. Pembrolizumab with or without chemotherapy versus chemotherapy alone for patients with PD-L1–positive advanced gastric or gastroesophageal junction adenocarcinoma: Update from the phase 3 KEYNOTE-062 trial. J Clin Oncol. 2022;40:243. [DOI]

14.

Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, et al. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024;42:2012–20. [DOI] [PubMed] [PMC]

15.

Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology. 2022;23:234–47. [DOI]

16.

Chao J, Fuchs CS, Shitara K, Tabernero J, Muro K, Van Cutsem E, et al. Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability-High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Clinical Trials. JAMA Oncol. 2021;7:895–902. [DOI] [PubMed] [PMC]

17.

Schoemig-Markiefka B, Eschbach J, Scheel AH, Pamuk A, Rueschoff J, Zander T, et al. Optimized PD-L1 scoring of gastric cancer. Gastric Cancer. 2021;24:1115–22. [DOI] [PubMed] [PMC]

18.

Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–71. [DOI] [PubMed]

19.

Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, et al. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 2018;4:e180013. [DOI] [PubMed] [PMC]

20.

Ratti M, Lampis A, Hahne JC, Passalacqua R, Valeri N. Microsatellite instability in gastric cancer: molecular bases, clinical perspectives, and new treatment approaches. Cell Mol Life Sci. 2018;75:4151–62. [DOI] [PubMed] [PMC]

21.

Sun H, Often S, Blackin A, Bugaev V, Stroganova A, Kuznetsova O, et al. The prognostic significance of microsatellite instability in patients with gastric cancer receiving neoadjuvant therapy. Questions of oncology. 2023;69:275–84. [DOI]

22.

Ignatova EO, Seryak DA, Fedyanin MY, Tryakin AA, Pokataev IA, Menshikova SF, et al. Molecular portrait of stomach cancer associated with the Epstein–Barr virus. Uspehi Molekularnoj Onkologii. 2020;7:27–36. [DOI]

23.

Liu Y, Sethi NS, Hinoue T, Schneider BG, Cherniack AD, Sanchez-Vega F, et al. Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas. Cancer Cell. 2018;33:721–35.e8. [DOI] [PubMed] [PMC]

24.

Bai Y, Xie T, Wang Z, Tong S, Zhao X, Zhao F, et al. Efficacy and predictive biomarkers of immunotherapy in Epstein-Barr virus-associated gastric cancer. J Immunother Cancer. 2022;10:e004080. [DOI] [PubMed] [PMC]

25.

Strickler JH, Hanks BA, Khasraw M. Tumor Mutational Burden as a Predictor of Immunotherapy Response: Is More Always Better? Clin Cancer Res. 2021;27:1236–41. [DOI] [PubMed] [PMC]

26.

Jang JY, Jeong SY, Kim ST. Tumor mutational burden as a potential predictive marker for the efficacy of immunotherapy in advanced gastric cancer. J Clin Oncol. 2023;41:324. [DOI]

27.

Kim YY, Lee J, Jeong WK, Kim ST, Kim J, Hong JY, et al. Prognostic significance of sarcopenia in microsatellite-stable gastric cancer patients treated with programmed death-1 inhibitors. Gastric Cancer. 2021;24:457–66. [DOI] [PubMed]

28.

Sano A, Sohda M, Nakazawa N, Ubukata Y, Kuriyama K, Kimura A, et al. Clinical features as potential prognostic factors in patients treated with nivolumab for highly pretreated metastatic gastric cancer: a multicenter retrospective study. BMC Cancer. 2022;22:22. [DOI] [PubMed] [PMC]

29.

Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell. 2011;144:646–74. [DOI] [PubMed]

30.

Ozveren A, Erdogan AP, Ekinci F. The inflammatory prognostic index as a potential predictor of prognosis in metastatic gastric cancer. Sci Rep. 2023;13:7755. [DOI] [PubMed] [PMC]

31.

Zhan H, Ma JY, Jian QC. Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in melanoma patients: A meta-analysis. Clin Chim Acta. 2018;484:136–40. [DOI] [PubMed]

32.

Vitorino M, Tomas T, Almeida S, Silva M. 176P Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC). Journal of Thoracic Oncology. 2021;16:S793–4. [DOI]

33.

Bayraktaroglu M, Yildiz BP. Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in non-small cell lung cancer. Medicine (Baltimore). 2023;102:e34180. [DOI] [PubMed] [PMC]

34.

Diem S, Schmid S, Krapf M, Flatz L, Born D, Jochum W, et al. Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Lung Cancer. 2017;111:176–81. [DOI] [PubMed]

35.

Matsas S, Aguiar Junior PN, Del Giglio A. Prognostic role of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in advanced gastric cancer treated with immunotherapy: A systematic review and meta-analysis. J Clin Oncol. 2024;42:397. [DOI]

36.

Shimozaki K, Nakayama I, Takahari D, Kamiimabeppu D, Osumi H, Wakatsuki T, et al. A novel clinical prognostic index for patients with advanced gastric cancer: possible contribution to the continuum of care. ESMO Open. 2021;6:100234. [DOI] [PubMed] [PMC]

37.

Rugambwa TK, Abdihamid O, Zhang X, Peng Y, Cai C, Shen H, et al. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as potential predictive markers of treatment response in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Front Oncol. 2023;13:1181248. [DOI] [PubMed] [PMC]

38.

Schlintl V, Huemer F, Rinnerthaler G, Melchardt T, Winder T, Reimann P, et al. Checkpoint inhibitors in metastatic gastric and GEJ cancer: a multi-institutional retrospective analysis of real-world data in a Western cohort. BMC Cancer. 2022;22:51. [DOI] [PubMed] [PMC]

39.

Takahashi Y, Sunakawa Y, Inoue E, Kawabata R, Ishiguro A, Kito Y, et al. Real-world effectiveness of nivolumab in advanced gastric cancer: the DELIVER trial (JACCRO GC-08). Gastric Cancer. 2022;25:235–44. [DOI] [PubMed]

40.

Ma J, Li J, Qian M, Han W, Tian M, Li Z, et al. PD-L1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28-8 and E1L3N). Diagn Pathol. 2018;13:91. [DOI] [PubMed] [PMC]

41.

Karalis JD, Ju MR, Feig R, Estrella R, Pettigrew MF, Alterio RE, et al. Intensifying supportive care is associated with improved survival in gastric cancer patients with malignant ascites. J Surg Oncol. 2024;129:718–27. [DOI] [PubMed]

42.

Donnenberg AD, Luketich JD, Dhupar R, Donnenberg VS. Treatment of malignant pleural effusions: the case for localized immunotherapy. J Immunother Cancer. 2019;7:110. [DOI] [PubMed] [PMC]

43.

Fucà G, Cohen R, Lonardi S, Shitara K, Elez ME, Fakih M, et al. Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers. J Immunother Cancer. 2022;10:e004001. [DOI] [PubMed] [PMC]

44.

Murakami Y, Saito H, Shimizu S, Kono Y, Shishido Y, Miyatani K, et al. Neutrophil-to-Lymphocyte Ratio as a Prognostic Indicator in Patients With Unresectable Gastric Cancer. Anticancer Res. 2019;39:2583–9. [DOI] [PubMed]

45.

Miyamoto R, Inagawa S, Sano N, Tadano S, Adachi S, Yamamoto M. The neutrophil-to-lymphocyte ratio (NLR) predicts short-term and long-term outcomes in gastric cancer patients. Eur J Surg Oncol. 2018;44:607–12. [DOI] [PubMed]

46.

Magdy M, Hussein T, Ezzat A, Gaballah A. Pre-treatment Peripheral Neutrophil-Lymphocyte Ratio as a Prognostic Marker in Gastric Cancer. J Gastrointest Cancer. 2019;50:763–8. [DOI] [PubMed]

47.

Gou M, Qu T, Wang Z, Yan H, Si Y, Zhang Y, et al. Neutrophil-to-Lymphocyte Ratio (NLR) Predicts PD-1 Inhibitor Survival in Patients with Metastatic Gastric Cancer. J Immunol Res. 2021;2021:2549295. [DOI] [PubMed] [PMC]

48.

Cho IR, Park JC, Park CH, Jo JH, Lee HJ, Kim S, et al. Pre-treatment neutrophil to lymphocyte ratio as a prognostic marker to predict chemotherapeutic response and survival outcomes in metastatic advanced gastric cancer. Gastric Cancer. 2014;17:703–10. [DOI] [PubMed]