REVIEW ARTICLE
Oncology
doi: 10.25005/2074-0581-2026-28-3-771-781
COMPREHENSIVE TREATMENT OF LOCALLY ADVANCED AND METASTATIC GASTRIC CANCER: THE ROLE OF NEOADJUVANT INTRA-ARTERIAL CHEMOTHERAPY

A.R. SABUROV1, K.S. KEMELBEKOV1, Z.KH. KHUSEYNZODA2, D.T. ARYBZHANOV3, D.S. TURSUMETOV4, B.A. ABDURAKHMANOV1

1South Kazakhstan Medical Academy, Shymkent, Republic of Kazakhstan
2Avicenna Tajik State Medical University, Dushanbe, Republic of Tajikistan
3Regional Multidisciplinary Clinic, Taldykorgan, Republic of Kazakhstan
4Bashkir State Medical University, Ufa, Russian Federation

Objective: To evaluate contemporary therapeutic strategies for locally advanced and metastatic GC, with a specific focus on the clinical role of neoadjuvant intra-arterial chemotherapy (IACT) and its impact on achieving R0 resection margins and enhancing pathological response rates, including the pCR rate.

Methods: We conducted a comprehensive literature search in PubMed/MEDLINE, Scopus, Web of Science, and eLIBRARY.ru from 2014 to 2025. We used the following Medical Subject Headings (MeSH) keywords and their Russian-language equivalents: "gastric cancer", "neoadjuvant chemotherapy", "regional chemotherapy", "intra-arterial chemotherapy", "hyperthermic intraperitoneal chemotherapy", "conversion therapy", "perioperative treatment", and "hepatic metastasis". Of the 642 publications identified, we excluded duplicates and irrelevant works, leaving 48 articles for final analysis. We prioritized randomized controlled trials, prospective cohort studies, and meta-analyses.

Results: Neoadjuvant IACT showed higher rates of significant tumor regression and pCR than isolated systemic chemotherapy. Multiple series reported a higher proportion of R0 resections, including cases initially classified as unresectable disease. The systemic toxicity profile was generally no higher than that observed with intravenous cytostatics; however, rigorous monitoring for localized vascular complications remains necessary.

Conclusion: Neoadjuvant IACT is a promising component of multimodal treatment that can increase rates of radical surgery and improve locoregional disease control. Further validation of its long-term efficacy requires standardized, prospective studies with unified patient selection criteria.

Keywords: Gastric cancer, neoadjuvant therapy, intra-arterial chemotherapy, regional chemotherapy, conversion treatment, pathological response, resectability.

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References
  1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-63. https://doi.org/10.3322/caac.21834
  2. Japanese Gastric Cancer Association. Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition). Gastric Cancer. 2023;26(1):1-25. https://doi. org/10.1007/s10120-022-01331-8
  3. Smyth EC, Nilsson M, Grabsch HI, van Grieken NCT, Lordick F. Gastric cancer. Lancet. 2020;396(10251):635-48. https://doi.org/10.1016/S0140-6736(20)31288-5
  4. Lordick F, Carneiro F, Cascinu S, Fleitas T, Haustermans K, Piessen G, et al. ESMO Clinical Practice Guidelines for gastric cancer. Ann Oncol. 2022;33(10):1005-20. https://doi.org/10.1016/j.annonc.2022.07.004
  5. Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, 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):1948-57. https://doi.org/10.1016/S0140-6736(18)32557-1
  6. Kumar V, Soni P, Garg M, Kamholz S, Chandra AB. Emerging therapies in advanced gastric cancer. Front Pharmacol. 2018;9:404. https://doi.org/10.3389/ fphar.2018.00404
  7. Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19(11):1437-48. https://doi.org/10.1016/S1470- 2045(18)30739-3 Erratum in: Lancet Oncol. 201819(12):e668. https://doi. org/10.1016/S1470-2045(18)30843-X
  8. Ha GY, Yang SH, Kang HJ, Lee HL, Kim J, Kim YJ, et al. First-line trastuzumabcontaining chemotherapy in HER2+ gastric cancer. Korean J Clin Oncol. 2020;16(2):63-70. https://doi.org/10.14216/kjco.20011
  9. Zhang CW, Zou SC, Shi D, Zhao DJ. Clinical significance of preoperative regional intra-arterial infusion chemotherapy for advanced gastric cancer. World J Gastroenterol. 2004;10(20):3070-2. https://doi.org/10.3748/wjg.v10.i20.3070
  10. Kodera Y, Fujitani K, Fukushima N, Ito S, Muro K, Ohashi N, et al. Surgical resection of hepatic metastasis from gastric cancer: a review and new recommendation in the Japanese gastric cancer treatment guidelines. Gastric Cancer. 2014;17(2):206- 12. https://doi.org/10.1007/s10120-013-0299-x
  11. Coccolini F, Montori G, Ceresoli M, Cima S, Valli MC, Nita GE, et al. Advanced gastric cancer: What we know. World J Gastroenterol. 2016;22(3):1139-59. https://doi.org/10.3748/wjg.v22.i3.1139
  12. Degiuli M, De Manzoni G, Di Leo A, D'Ugo D, Galasso E, Marrelli D, et al. Lymph node dissection in gastric cancer. World J Gastroenterol. 2016;22(10):2875-93. https://doi.org/10.3748/wjg.v22.i10.2875
  13. Sato Y, Ohnuma H, Nobuoka T, Hirakawa M, Sagawa T, Fujikawa K, et al. Conversion therapy using DCS regimen. Gastric Cancer. 2017;20(3):517-26. https://doi.org/10.1007/s10120-016-0633-1
  14. Graversen M, Lundell L, Fristrup C, Pfeiffer P, Mortensen MB. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) as an outpatient procedure. Pleura Peritoneum. 2018;3(4):20180128. https://doi.org/10.1515/pp-2018-0128
  15. Gingrich AA, Flojo RB, Walsh A, Olson J, Hanson D, Bateni SB, et al. Are palliative interventions worth the risk in advanced gastric cancer? A systematic review. J Clin Med. 2024;13(19):5809. https://doi.org/10.3390/jcm13195809
  16. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11-20. https://doi.org/10.1056/NEJMoa055531
  17. Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27-40. https://doi.org/10.1016/S0140-6736(21)00797-2
  18. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. 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(9742):687-97. https://doi.org/10.1016/S0140-6736(10)61121-X
  19. Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, et al. Pembrolizumab in HER2-positive gastric cancer. N Engl J Med. 2024;391(14):1360-2. https://doi. org/10.1056/NEJMc2408121
  20. Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): A multicentre, randomised, doubleblind, phase 3 trial. Lancet. 2023;401(10389):1655-68. https://doi.org/10.1016/ S0140-6736(23)00620-7
  21. 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(8):2133-41. https://doi.org/10.1038/s41591-023-02465-7
  22. Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27-40. https://doi.org/10.1016/S0140-6736(21)00797-2
  23. Chung HC, Kang YK, Chen Z, Bai Y, Wan Ishak WZ, Shim BY, et al. Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients. Cancer. 2022;128(5):995-1003. https://doi.org/10.1002/cncr.34019
  24. Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224-35. https://doi.org/10.1016/S1470-2045(14)70420-6
  25. Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020;382(25):2419-30. https://doi.org/10.1056/NEJMoa2004413
  26. Yoshida K, Yamaguchi K, Okumura N, Tanahashi T, Kodera Y. Is conversion therapy possible in stage IV gastric cancer: The proposal of new biological categories of classification. Gastric Cancer. 2016;19(2):329-38. https://doi.org/10.1007/ s10120-015-0575-z
  27. Ohnuma H, Sato Y, Hirakawa M, Kikuchi S, Miyanishi K, Sagawa T, et al. Docetaxel, cisplatin and S-1 (DCS) combination chemotherapy for gastric cancer patients with peritoneal metastasis: A retrospective study. Cancer Chemother Pharmacol. 2018;81(3):539-48. https://doi.org/10.1007/s00280-018-3523-x
  28. Rihuete Caro C, Manzanedo I, Pereira F, Carrion-Alvarez L, Serrano Á, PérezViejo E. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with gastric cancer and peritoneal carcinomatosis. Eur J Surg Oncol. 2018;44(11):1805-10. https://doi. org/10.1016/j.ejso.2018.06.036
  29. Lei Z, Wang J, Li Z, Li B, Luo J, Wang X, et al. Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: A multicenter propensity score-matched cohort study. Chin J Cancer Res. 2020;32(6):794-803. https://doi.org/10.21147/j.issn.1000-9604.2020.06.12
  30. Quik JSE, Vollebergh MA, Retèl VP, van der Sluis K, Koemans WJ, van der Kaaij RT, et al. Systemic therapy, gastrectomy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy versus systemic therapy alone for gastric cancer with limited peritoneal metastases (PERISCOPE II): Final results of a multicentre, randomised, controlled, phase 3 trial after an unplanned commissioned interim analysis. Lancet Oncol. 2026;27(8):1031-42. https://doi.org/10.1016/S1470- 2045(26)00144-0
  31. Jain AJ, Badgwell BD. Current evidence for the use of HIPEC and cytoreductive surgery in gastric cancer metastatic to the peritoneum. J Clin Med. 2023;12(20):6527. https://doi.org/10.3390/jcm12206527
  32. Yonemura Y, Canbay E, Li Y, Coccolini F, Glehen O, Sugarbaker PH, et al. A comprehensive treatment for peritoneal metastases from gastric cancer with curative intent. Eur J Surg Oncol. 2016;42(8):1123-31. https://doi.org/10.1016/j. ejso.2016.03.016
  33. Lin W, Huang Z, Du Z, Wang Y, Zuo T. Case report: Clinical application of continuous arterial infusion chemotherapy in neoadjuvant therapy for locally advanced gastric cancer. Front Oncol. 2023;13:1214599. https://doi.org/10.3389/ fonc.2023.1214599
  34. Wang J, Shi H, Yang G, Han G, Zhao M, Duan X, et al. Combined intra-arterial and intravenous chemotherapy for unresectable, advanced gastric cancer has an improved curative effect compared with intravenous chemotherapy only. Oncol Lett. 2018;15(4):5662-70. https://doi.org/10.3892/ol.2018.8068
  35. Li B, Tang R, Zhang G, Cheng J, Chao M, Ding K. The efficacy and safety of continuous intra-arterial infusion neoadjuvant chemotherapy with surgery for locally advanced gastric cancer: A preliminary pilot study. J Gastrointest Oncol. 2022;13(3):968-76. https://doi.org/10.21037/jgo-22-304
  36. Wu ZF, Cao QH, Wu XY, Chen C, Xu Z, Li WS, et al. Regional arterial infusion chemotherapy improves the pathological response rate for advanced gastric cancer with short-term neoadjuvant chemotherapy. Sci Rep. 2015;5:17516. https://doi.org/10.1038/srep17516
  37. Yang Z, Lu S, Shi M, Yuan H, Wang Z, Ni Z, et al. Oncological outcomes of conversion therapy in gastric cancer patients with peritoneal metastasis: A largescale retrospective cohort study. Gastric Cancer. 2024;27(2):387-99. https://doi. org/10.1007/s10120-023-01452-8
  38. Han S, Han S, Qian J, Guo M, Fan J. Analysis of the therapeutic effect and influencing factors on unresectable gastric cancer treated with conversion therapy.
  39. Han S, Han S, Qian J, Guo M, Fan J. Analysis of the therapeutic effect and influencing factors on unresectable gastric cancer treated with conversion therapy. Front Oncol. 2024;14:1435398. https://doi.org/10.3389/fonc.2024.1435398
  40. Yang S, Feng R, Pan ZC, Jiang T, Xu Q, Chen Q. A comparison of intravenous plus intraperitoneal chemotherapy with intravenous chemotherapy alone for the treatment of gastric cancer: A meta-analysis. Sci Rep. 2015;5:12538. https://doi. org/10.1038/srep12538
  41. Xu W, Wang L, Yan C, He C, Lu S, Ni Z, et al. Neoadjuvant chemotherapy versus direct surgery for locally advanced gastric cancer with serosal invasion (cT4NxM0): A propensity score-matched analysis. Front Oncol. 2021;11:718556. https://doi.org/10.3389/fonc.2021.718556
  42. Tang R, Chen GF, Jin K, Zhang GQ, Wu JJ, Han SG, et al. Efficacy of continuous gastric artery infusion chemotherapy in relieving digestive obstruction in advanced gastric cancer. World J Gastrointest Oncol. 2023;15(7):1283-94. https://doi.org/10.4251/wjgo.v15.i7.1283
  43. Yang Q, Lv S, Li Q, Lan L, Liu N, Wang M, et al. Neoadjuvant arterial infusion chemotherapy combined with immunotherapy in treating locally advanced lower esophageal and esophagogastric junction cancer. J Thorac Dis. 2025;17(4):2273- 85. https://doi.org/10.21037/jtd-24-1908
  44. Chen S, Zhao N, Li X, Cao D. Analysis of complications of giant gastric ulcers induced by hepatic arterial infusion chemotherapy or combined immunotherapy: A report of three cases. Exp Ther Med. 2024;28(5):418. https://doi.org/10.3892/ etm.2024.12707
  45. Li Y, Zhong Y, Xu Q, Zhu Z, Tian Y. Prognostic significance of signet ring cells in gastric cancer: The higher proportion, the better survival. Front Oncol. 2021;11:713587. https://doi.org/10.3389/fonc.2021.713587
  46. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The eighth edition AJCC cancer staging manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-9. https://doi.org/10.3322/caac.21388
  47. Lee IS, Kang HJ, Park YS, Ryu MH, Yook JH, Kang YK, et al. Prognostic impact of extranodal extension in stage 1B gastric carcinomas. Surg Oncol. 2018;27(2):299- 305. https://doi.org/10.1016/j.suronc.2018.05.014
  48. Xu J, Shen L, Shui Y, Yu W, Guo Q, Yu R, et al. Patterns of recurrence after curative D2 resection for gastric cancer: implications for postoperative radiotherapy. Cancer Med. 2020;9(13):4724-35. https://doi.org/10.1002/cam4.3085
  49. Lee JH, Chang KK, Yoon C, Tang LH, Strong VE, Yoon SS. Lauren histologic type is the most important factor associated with pattern of recurrence following resection of gastric adenocarcinoma. Ann Surg. 2018;267(1):105-13. https://doi. org/10.1097/SLA.0000000000002040

Authors' information:

Saburov Alisher Radzhapbaevich,
Assistant Professor, Department of General Medical Practice-3, South Kazakhstan Medical Academy
Researcher ID: HCI-7367-2024
Scopus ID: 57194709214
ORCID ID: 0000-0002-6698-2831
SPIN: 2308-9483
Author ID: 916776
E-mail: alisher_saburov@internet.ru

Kemelbekov Kanatzhan Saukhanbekovich,
PhD, Head of the Department of Pediatrics-1, South Kazakhstan Medical Academy
Researcher ID: ILU-4137-2023
Scopus ID: 56050252100
ORCID ID: 0000-0003-4980-8987
SPIN: 2234-1379
Author ID: 700152
E-mail: kanat-270184@mail.ru

Khuseynzoda Zafar Khabibullo,
Doctor of Medical Sciences, Professor, Vice-Rector for Clinical Affairs, Avicenna Tajik State Medical University
Researcher ID: IVF-1790-2021
Scopus ID: 6506960235
ORCID ID: 0000-0002-4823-8531
SPIN: 9316-4084
Author ID: 1111789
E-mail: zafhab@mail.ru

Arybzhanov Dauranbek Tursunkulovich,
Candidate of Medical Sciences, Deputy Director for Clinical Affairs, Regional Multidisciplinary Clinic
Researcher ID: IJX-7095-2022
Scopus ID: 57273495200
ORCID ID: 0000-0002-0237-9064
SPIN: 1009-9780
Author ID: 720677
E-mail: davran_a@mail.ru

Tursumetov Davlat Saytmuratovich,
Candidate of Medical Sciences, Associate Professor, Department of Oncology and Clinical Morphology, Bashkir State Medical University
Researcher ID: KKR-6126-2024
Scopus ID: 57991242900
ORCID ID: 0000-0003-4069-6594
SPIN: 6094-8362
Author ID: 898784
E-mail: ufa.davlat@gmail.com

Abdurakhmanov Babur Anvarovich,
Doctor of Medical Sciences, Acting Professor, Head of the Department of Surgery and Oncology, South Kazakhstan Medical Academy
ORCID ID: 0009-0004-6967-385X
E-mail: babur_ad@mail.ru

Information about support in the form of grants, equipment, medications

The authors did not receive financial support from manufacturers of medicines and medical equipment

Conflicts of interest: No conflict

Address for correspondence:

Saburov Alisher Radzhapbaevich
Assistant Professor, Department of General Medical Practice-3, South Kazakhstan Medical Academy

160019, Republic of Kazakhstan, Shymkent, Al-Farabi Ave., 1

Tel.: +7 (775) 6345500

E-mail: alisher_saburov@internet.ru


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

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