Stomach NeoplasmsNCT07899775
Lymph Node Metastasis Pattern After Neoadjuvant Chemoimmunotherapy in LAGC
An observational study of Stomach Neoplasms and Gastric Cancer (Diagnosis), run by Hainan General Hospital.
Trial summary
The purpose of this observational study is to learn how stomach cancer that has spread to nearby lymph nodes responds to standard chemotherapy combined with immunotherapy given before surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stomach Neoplasms, Gastric Cancer (Diagnosis), Gastric Adenocarcinoma
- What is being tested?
- Neoadjuvant SOX chemotherapy combined with PD-1 inhibitor
- How many people
- 103 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2027to 31 Dec 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population consists of adult patients (aged ≥ 18 years) with pathologically confirmed locally advanced gastric adenocarcinoma at clinical stage cT3-4aN+M0. These patients have successfully completed standardized clinical routine neoadjuvant therapy, specifically the SOX chemotherapy regimen combined with an anti-PD-1 immunotherapy, for at least two cycles. Following the completion of neoadjuvant treatment, they are scheduled to undergo, or have already undergone, a standard distal or total D2 radical gastrectomy at the participating medical centers.
Who may be able to join
- Age ≥ 18 years, regardless of gender
- Gastric adenocarcinoma pathologically confirmed by gastroscopic biopsy, with a clinical stage of cT3-4aN+M0
- Standardized completion of neoadjuvant chemotherapy combined with immunotherapy for the scheduled cycles (≥ 2 cycles)
- Planned for or have undergone standard D2 radical gastrectomy following the completion of neoadjuvant therapy
- The number of harvested lymph nodes in the postoperative specimen is ≥ 16, and the pathology report can clearly distinguish the metastasis status of lymph nodes in each anatomical station, providing complete station-specific pathological data
- Patients volunteer to participate in this study and have signed a written informed consent form
Who cannot join
- Pathologically confirmed non-gastric adenocarcinoma, such as gastric squamous cell carcinoma, neuroendocrine tumors, or metastatic gastric tumors
- Advanced patients with distant metastasis that precludes radical gastrectomy
- Patients who have received prior preoperative anti-tumor treatments other than the study protocol, such as radiotherapy, targeted therapy, chemotherapy alone, or monotherapy immunotherapy; or patients with a previous history of gastric surgery or other malignancies
- Patients who experience disease progression, severe immune-related adverse events, or chemotherapy intolerance leading to treatment termination during neoadjuvant therapy, or those complicated with severe organ failure (e.g., heart, liver, kidney, lung) rendering them unable to undergo radical surgery
- Cases where a standard D2 radical gastrectomy was not performed, the extent of lymph node dissection was insufficient, the number of dissected lymph nodes was < 16, or the pathology report lacks data on station-specific lymph node metastasis, precluding statistical analysis
- Missing clinical data or poor compliance with follow-up, posing a high risk of loss to follow-up
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Prospective Multicenter Study on the Patterns and Clinical Significance of Lymph Node Metastasis in Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy Combined With Immunotherapy
The purpose of this observational study is to learn how stomach cancer that has spread to nearby lymph nodes responds to standard chemotherapy combined with immunotherapy given before surgery. In people with locally advanced gastric cancer, this pre-surgery treatment can shrink the tumor and clear cancer cells from some lymph nodes. However, it is not clear which groups of lymph nodes around the stomach still contain cancer cells after treatment. The study will also examine whether dense scarring (fibrosis) around the tumor is linked to a lower chance of cancer remaining in the lymph nodes. This information may help doctors in the future decide whether some lymph node groups can be safely left in place during surgery for people with severe scarring.
Participants in this study will receive standard pre-surgery treatment with SOX chemotherapy (S-1 plus oxaliplatin) and a PD-1 inhibitor for at least 2 cycles. After treatment, they will undergo standard gastrectomy with D2 lymph node dissection, which is the routine surgical removal of the main lymph node groups around the stomach. During surgery, the surgeon will record the degree of scarring and difficulty in separating the tissues. Lymph nodes will be collected and labeled by station so that each group can be examined separately. The study will then describe how often cancer is found in each lymph node station after treatment and explore whether scarring is related to cancer remaining in the nodes. The study will also track surgical outcomes and follow participants for up to 3 years to assess cancer recurrence and survival.
Approximately 103 participants will be enrolled. The study is expected to run from January 2027 through December 2029. Each participant will be followed for about 3 years after surgery, with clinic visits every 3 months for the first 2 years and every 6 months in the third year. This study does not assign participants to different treatments; all participants receive standard care, and the study only observes and records the results.
Read the detailed description
Background and Rationale Currently, the treatment of locally advanced gastric cancer (LAGC) has evolved into a multidisciplinary comprehensive treatment model combining surgery and perioperative systemic therapy. Neoadjuvant chemotherapy combined with immunotherapy (such as PD-1 inhibitors) has been proven to further improve the pathological complete response (pCR) rate of LAGC. However, after treatment with this regimen, the distribution patterns of lymph node metastasis in various perigastric stations and the characteristics of residual lesions remain unclear. Current guidelines still recommend standard D2 lymphadenectomy for resectable gastric cancer patients receiving neoadjuvant therapy. In addition, it has been observed in clinical practice that neoadjuvant chemo-immunotherapy significantly increases edema and fibrosis in the peritumoral tissue. These changes in the local microenvironment cause the disappearance of anatomical planes and dense adhesions, which significantly increase surgical difficulty and risks. Currently, there is insufficient prospective evidence to answer whether the extent of lymphadenectomy can be safely reduced (omitting the dissection of specific stations) for patients with severe local tissue fibrosis after treatment.
Study Design and Interventions This is a prospective, multicenter, single-arm observational cohort study with a planned enrollment of 103 patients. The study will include patients with pathologically confirmed locally advanced gastric adenocarcinoma at clinical stage cT3-4aN+M0. All enrolled patients will receive standardized clinical routine neoadjuvant treatment, namely the SOX regimen (S-1 + oxaliplatin) combined with an anti-PD-1 inhibitor (including toripalimab, sintilimab, tislelizumab, or nivolumab), and complete at least 2 cycles of treatment. Following the completion of neoadjuvant therapy, patients will undergo standard distal or total D2 radical gastrectomy.
Imaging and Intraoperative Assessments Subjects will undergo standardized contrast-enhanced abdominal CT (or PET-CT as needed) assessments at baseline and at the end of neoadjuvant therapy (2-3 weeks pre-surgery). In addition to defining the treatment response of target lesions using the iRECIST criteria, the imaging evaluation will specifically record local microenvironment changes indicative of tissue edema and fibrosis, such as increased density, exudation, and stranding in the peritumoral space.
During the surgery, the primary surgeon will objectively assess the degree of edema, fibrosis, and dense adhesions in the peritumoral tissue, drainage areas, and roots of major blood vessels based on a semi-quantitative grading scale (grades 0 to 3). Researchers will quantitatively record the total operative time, dissection time, intraoperative blood loss, and whether any collateral damage occurs. After the specimen is extracted, the surgical team will immediately and strictly sort the perigastric lymph nodes (No. 1 to No. 16) station by station on the operating table. Each station will be independently marked, separately fixed, and sent for pathological examination. Mixed submission is strictly prohibited to ensure the accuracy of station-specific data.
Pathological Evaluation and Follow-up Pathologists, blinded to the patients' preoperative imaging results and clinical treatment information, will independently and accurately count and assess the residual metastasis status (ypN) of lymph nodes from stations No. 1 to No. 16. Furthermore, the study will record the incidence of complications within 30 and 90 days post-surgery and conduct a safety assessment using the Clavien-Dindo classification system. Long-term follow-up will be conducted within 1 to 3 years post-surgery to dynamically track the patients' disease-free survival (DFS) and overall survival (OS) through regular imaging and tumor marker reviews.
Interpretation and Limitations This study aims to answer questions that the overall ypN0 rate cannot address: the location of residual lesions after combined neoadjuvant chemo-immunotherapy, and whether the severity of peritumoral fibrosis carries information regarding this distribution. The study does not randomize participants to different extents of dissection, does not compare restricted dissection with standard D2 dissection, and does not provide a direct test of oncological non-inferiority for any restricted dissection strategy. Its value lies in generating prospective, station-resolved, and pathologically validated data that may indicate whether this strategy warrants formal evaluation, and in describing the relationship between treatment-induced fibrosis and surgical complexity. If the data show that residual lesions remain distributed across D1 and D2 stations regardless of the severity of fibrosis, the current standard of complete D2 dissection will be reinforced. If reproducible low-risk station profiles emerge in a definable subgroup, this finding will provide a rationale-but not evidence-for subsequent comparative studies.
- Being tested
- Neoadjuvant SOX chemotherapy combined with PD-1 inhibitor
- Medical subject headings
- Stomach Neoplasms, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant SOX chemotherapy combined with PD-1 inhibitorDrug
- Intervention Name: SOX regimen (S-1 and Oxaliplatin)
Intervention Description:
Patients will receive the standard SOX chemotherapy regimen, consisting of S-1 and oxaliplatin, as part of their neoadjuvant treatment. The treatment will be administered in clinical routine for a minimum of two cycles prior to surgery. 2. Intervention Name: Anti-PD-1 inhibitor
Intervention Description:
Patients will receive an anti-PD-1 inhibitor (which may include Toripalimab, Sintilimab, Tislelizumab, or Nivolumab) in combination with the SOX chemotherapy regimen as part of their neoadjuvant treatment. This immunotherapy will be administered for a minimum of two cycles prior to surgery. 3. Intervention Name: D2 radical gastrectomy
Intervention Description:
Following the completion of neoadjuvant therapy, patients will undergo a standard distal or total gastrectomy with D2 lymph node dissection. During the procedure, surgeons will objectively assess local tissue edema and fibrosis. Post-resection, t
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant Chemo-immunotherapy Cohort | All enrolled participants receive standard neoadjuvant SOX chemotherapy combined with a PD-1 inhibitor for at least 2 cycles, followed by gastrectomy with D2 lymphadenectomy. No control group is assigned. Participants are observed prospectively from baseline through surgery and up to 3 years postoperatively. Receives: Drug: Neoadjuvant SOX chemotherapy combined with PD-1 inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Station-specific lymph node metastasis positivity rate after neoadjuvant chemoimmunotherapy
The primary outcome is the station-specific lymph node metastasis positivity rate after neoadjuvant chemoimmunotherapy, assessed by station-by-station pathologic examination of gastrectomy specimens. Each dissected nodal station (No. 1-No. 16, as applicable) is evaluated separately. For each station, the positivity rate is defined as the number of evaluable participants with at least one pathologically confirmed positive lymph node at that station divided by the number of evaluable participants in whom that station was pathologically assessed. A positive node is defined as a lymph node containing viable tumor cells on hematoxylin and eosin staining. Pathologic assessment is performed blinded to preoperative imaging, iRECIST response, and clinical treatment information. The outcome is assessed at postoperative pathology after D2 gastrectomy.
Measured: Up to 2 weeks
Secondary outcomes (1)
Degree of Peritumoral Edema and Fibrosis
To evaluate the extent of peritumoral tissue edema, fibrosis, and dense adhesions during the surgical procedure. The primary surgeon will objectively assess these local microenvironment changes using a semi-quantitative grading scale ranging from Grade 0 (normal anatomical planes, no obvious adhesions) to Grade 3 ("frozen" extremely dense adhesions, anatomical planes completely disappeared). The study will also analyze the correlation between the degree of edema/fibrosis and surgical complexity metrics, such as total surgical time and intraoperative blood loss.
Measured: Perioperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2026
- Study start1 Jan 2027 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Stomach NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 103 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hainan General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Second Affiliated Hospital of Hainan Medical University, Sichuan Cancer Hospital and Research Institute
- Responsible party
- Principal investigator, Liang Xianwen, Hainan General Hospital
- Investigators
- Xianwen Liang, Study chair, Hainan General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07899775
- Sponsor's protocol ID
- HGH-GC-01
- Status last verified
- Oct 2026
- First submitted
- 18 Oct 2026
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) underlying the results reported in this study, along with the study protocol and statistical analysis plan (SAP), will be shared. Data will be available beginning 6 months and ending 36 months following the publication of the primary research article. Access will be granted to qualified researchers who provide a methodologically sound proposal for achieving aims specified in the approved proposal, such as individual patient data meta-analysis. Proposals should be directed to the Principal Investigator via email. Data requestors will be required to sign a data access agreement and obtain appropriate ethical approval before data transfer.
Publications
Janjigian YY, Al-Batran SE, Wainberg ZA, Muro K, Molena D, Van Cutsem E, Hyung WJ, Wyrwicz L, Oh DY, Omori T, Moehler M, Garrido M, Oliveira SCS, Liberman M, Oliden VC, Smyth EC, Stein A, Bilici M, Alvarenga ML, Kozlov V, Rivera F, Kawazoe A, Serrano O, Heilbron E, Negro A, Kurland JF, Tabernero J; MATTERHORN Investigators. Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer. N Engl J Med. 2025 Jul 17;393(3):217-230. doi: 10.1056/NEJMoa2503701. Epub 2025 Jun 1.
PubMed 40454643Shitara K, Rha SY, Wyrwicz LS, Oshima T, Karaseva N, Osipov M, Yasui H, Yabusaki H, Afanasyev S, Park YK, Al-Batran SE, Yoshikawa T, Yanez P, Dib Bartolomeo M, Lonardi S, Tabernero J, Van Cutsem E, Janjigian YY, Oh DY, Xu J, Fang X, Shih CS, Bhagia P, Bang YJ; KEYNOTE-585 investigators. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. 2024 Feb;25(2):212-224. doi: 10.1016/S1470-2045(23)00541-7. Epub 2023 Dec 19.
PubMed 38134948Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, Lee KW, Omori T, Shitara K, Sakuramoto S, Chung IJ, Yamaguchi K, Kato K, Sym SJ, Kadowaki S, Tsuji K, Chen JS, Bai LY, Oh SY, Choda Y, Yasui H, Takeuchi K, Hirashima Y, Hagihara S, Boku N. 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. Lancet Oncol. 2022 Feb;23(2):234-247. doi: 10.1016/S1470-2045(21)00692-6. Epub 2022 Jan 11.
PubMed 35030335Al-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, Lohr 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, Guntner M, Hozaeel W, Reichart A, Jager E, Kraus T, Monig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; 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 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11.
PubMed 30982686Ajani JA, D'Amico TA, Bentrem DJ, Corvera CU, Das P, Enzinger PC, Enzler T, Gerdes H, Gibson MK, Grierson P, Gupta G, Hofstetter WL, Ilson DH, Jalal S, Kim S, Kleinberg LR, Klempner S, Lacy J, Lee B, Licciardi F, Lloyd S, Ly QP, Matsukuma K, McNamara M, Merkow RP, Miller AM, Mukherjee S, Mulcahy MF, Perry KA, Pimiento JM, Reddi DM, Reznik S, Roses RE, Strong VE, Su S, Uboha N, Wainberg ZA, Willett CG, Woo Y, Yoon HH, McMillian NR, Stein M. Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology. J Natl Compr Canc Netw. 2025 May;23(5):169-191. doi: 10.6004/jnccn.2025.0022.
PubMed 40341199
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Multicenter Study on the Patterns and Clinical Significance of Lymph Node Metastasis in Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy Combined With Immunotherapy
- ClinicalTrials.gov ID
- NCT07899775
- Acronym / sponsor ID
- HGH-GC-01
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 103 participants (estimated)
- Lead sponsor
- Hainan General HospitalUniversity, hospital or other
- Collaborators
- The Second Affiliated Hospital of Hainan Medical University, Sichuan Cancer Hospital and Research Institute
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 28 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this observational study is to learn how stomach cancer that has spread to nearby lymph nodes responds to standard chemotherapy combined with immunotherapy given before surgery. In people with locally advanced gastric cancer, this pre-surgery treatment can shrink the tumor and clear cancer cells from some lymph nodes. However, it is not clear which groups of lymph nodes around the stomach still contain cancer cells after treatment. The study will also examine whether dense scarring (fibrosis) around the tumor is linked to a lower chance of cancer remaining in the lymph nodes. This information may help doctors in the future decide whether some lymph node groups can be safely left in place during surgery for people with severe scarring.
Participants in this study will receive standard pre-surgery treatment with SOX chemotherapy (S-1 plus oxaliplatin) and a PD-1 inhibitor for at least 2 cycles. After treatment, they will undergo standard gastrectomy with D2 lymph node dissection, which is the routine surgical removal of the main lymph node groups around the stomach. During surgery, the surgeon will record the degree of scarring and difficulty in separating the tissues. Lymph nodes will be collected and labeled by station so that each group can be examined separately. The study will then describe how often cancer is found in each lymph node station after treatment and explore whether scarring is related to cancer remaining in the nodes. The study will also track surgical outcomes and follow participants for up to 3 years to assess cancer recurrence and survival.
Approximately 103 participants will be enrolled. The study is expected to run from January 2027 through December 2029. Each participant will be followed for about 3 years after surgery, with clinic visits every 3 months for the first 2 years and every 6 months in the third year. This study does not assign participants to different treatments; all participants receive standard care, and the study only observes and records the results.
Detailed description
Background and Rationale Currently, the treatment of locally advanced gastric cancer (LAGC) has evolved into a multidisciplinary comprehensive treatment model combining surgery and perioperative systemic therapy. Neoadjuvant chemotherapy combined with immunotherapy (such as PD-1 inhibitors) has been proven to further improve the pathological complete response (pCR) rate of LAGC. However, after treatment with this regimen, the distribution patterns of lymph node metastasis in various perigastric stations and the characteristics of residual lesions remain unclear. Current guidelines still recommend standard D2 lymphadenectomy for resectable gastric cancer patients receiving neoadjuvant therapy. In addition, it has been observed in clinical practice that neoadjuvant chemo-immunotherapy significantly increases edema and fibrosis in the peritumoral tissue. These changes in the local microenvironment cause the disappearance of anatomical planes and dense adhesions, which significantly increase surgical difficulty and risks. Currently, there is insufficient prospective evidence to answer whether the extent of lymphadenectomy can be safely reduced (omitting the dissection of specific stations) for patients with severe local tissue fibrosis after treatment.
Study Design and Interventions This is a prospective, multicenter, single-arm observational cohort study with a planned enrollment of 103 patients. The study will include patients with pathologically confirmed locally advanced gastric adenocarcinoma at clinical stage cT3-4aN+M0. All enrolled patients will receive standardized clinical routine neoadjuvant treatment, namely the SOX regimen (S-1 + oxaliplatin) combined with an anti-PD-1 inhibitor (including toripalimab, sintilimab, tislelizumab, or nivolumab), and complete at least 2 cycles of treatment. Following the completion of neoadjuvant therapy, patients will undergo standard distal or total D2 radical gastrectomy.
Imaging and Intraoperative Assessments Subjects will undergo standardized contrast-enhanced abdominal CT (or PET-CT as needed) assessments at baseline and at the end of neoadjuvant therapy (2-3 weeks pre-surgery). In addition to defining the treatment response of target lesions using the iRECIST criteria, the imaging evaluation will specifically record local microenvironment changes indicative of tissue edema and fibrosis, such as increased density, exudation, and stranding in the peritumoral space.
During the surgery, the primary surgeon will objectively assess the degree of edema, fibrosis, and dense adhesions in the peritumoral tissue, drainage areas, and roots of major blood vessels based on a semi-quantitative grading scale (grades 0 to 3). Researchers will quantitatively record the total operative time, dissection time, intraoperative blood loss, and whether any collateral damage occurs. After the specimen is extracted, the surgical team will immediately and strictly sort the perigastric lymph nodes (No. 1 to No. 16) station by station on the operating table. Each station will be independently marked, separately fixed, and sent for pathological examination. Mixed submission is strictly prohibited to ensure the accuracy of station-specific data.
Pathological Evaluation and Follow-up Pathologists, blinded to the patients' preoperative imaging results and clinical treatment information, will independently and accurately count and assess the residual metastasis status (ypN) of lymph nodes from stations No. 1 to No. 16. Furthermore, the study will record the incidence of complications within 30 and 90 days post-surgery and conduct a safety assessment using the Clavien-Dindo classification system. Long-term follow-up will be conducted within 1 to 3 years post-surgery to dynamically track the patients' disease-free survival (DFS) and overall survival (OS) through regular imaging and tumor marker reviews.
Interpretation and Limitations This study aims to answer questions that the overall ypN0 rate cannot address: the location of residual lesions after combined neoadjuvant chemo-immunotherapy, and whether the severity of peritumoral fibrosis carries information regarding this distribution. The study does not randomize participants to different extents of dissection, does not compare restricted dissection with standard D2 dissection, and does not provide a direct test of oncological non-inferiority for any restricted dissection strategy. Its value lies in generating prospective, station-resolved, and pathologically validated data that may indicate whether this strategy warrants formal evaluation, and in describing the relationship between treatment-induced fibrosis and surgical complexity. If the data show that residual lesions remain distributed across D1 and D2 stations regardless of the severity of fibrosis, the current standard of complete D2 dissection will be reinforced. If reproducible low-risk station profiles emerge in a definable subgroup, this finding will provide a rationale-but not evidence-for subsequent comparative studies.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Chemo-immunotherapy Cohort | – | Drug: Neoadjuvant SOX chemotherapy combined with PD-1 inhibitorAll enrolled participants receive standard neoadjuvant SOX chemotherapy combined with a PD-1 inhibitor for at least 2 cycles, followed by gastrectomy with D2 lymphadenectomy. No control group is assigned. Participants are observed prospectively from baseline through surgery and up to 3 years postoperatively. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population consists of adult patients (aged ≥ 18 years) with pathologically confirmed locally advanced gastric adenocarcinoma at clinical stage cT3-4aN+M0. These patients have successfully completed standardized clinical routine neoadjuvant therapy, specifically the SOX chemotherapy regimen combined with an anti-PD-1 immunotherapy, for at least two cycles. Following the completion of neoadjuvant treatment, they are scheduled to undergo, or have already undergone, a standard distal or total D2 radical gastrectomy at the participating medical centers.
Key inclusion criteria (6 listed)
- Age ≥ 18 years, regardless of gender
- Gastric adenocarcinoma pathologically confirmed by gastroscopic biopsy, with a clinical stage of cT3-4aN+M0
- Standardized completion of neoadjuvant chemotherapy combined with immunotherapy for the scheduled cycles (≥ 2 cycles)
- Planned for or have undergone standard D2 radical gastrectomy following the completion of neoadjuvant therapy
- The number of harvested lymph nodes in the postoperative specimen is ≥ 16, and the pathology report can clearly distinguish the metastasis status of lymph nodes in each anatomical station, providing complete station-specific pathological data
Key exclusion criteria (6 listed)
- Pathologically confirmed non-gastric adenocarcinoma, such as gastric squamous cell carcinoma, neuroendocrine tumors, or metastatic gastric tumors
- Advanced patients with distant metastasis that precludes radical gastrectomy
- Patients who have received prior preoperative anti-tumor treatments other than the study protocol, such as radiotherapy, targeted therapy, chemotherapy alone, or monotherapy immunotherapy; or patients with a previous history of gastric surgery or other malignancies
- Patients who experience disease progression, severe immune-related adverse events, or chemotherapy intolerance leading to treatment termination during neoadjuvant therapy, or those complicated with severe organ failure (e.g., heart, liver, kidney, lung) rendering them unable to undergo radical surgery
- Cases where a standard D2 radical gastrectomy was not performed, the extent of lymph node dissection was insufficient, the number of dissected lymph nodes was < 16, or the pathology report lacks data on station-specific lymph node metastasis, precluding statistical analysis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neoadjuvant SOX chemotherapy combined with PD-1 inhibitor1. Intervention Name: SOX regimen (S-1 and Oxaliplatin) Intervention Description: Patients will receive the standard SOX chemotherapy regimen, consisting of S-1 and oxaliplatin, as part of their neoadjuvant treatment. The treatment will be administered in clinical routine for a minimum of two cycles prior to surgery. 2. Intervention Name: Anti-PD-1 inhibitor Intervention Description: Patients will receive an anti-PD-1 inhibitor (which may include Toripalimab, Sintilimab, Tislelizumab, or Nivolumab) in combination with the SOX chemotherapy regimen as part of their neoadjuvant treatment. This immunotherapy will be administered for a minimum of two cycles prior to surgery. 3. Intervention Name: D2 radical gastrectomy Intervention Description: Following the completion of neoadjuvant therapy, patients will undergo a standard distal or total gastrectomy with D2 lymph node dissection. During the procedure, surgeons will objectively assess local tissue edema and fibrosis. Post-resection, t | Drug | Neoadjuvant Chemo-immunotherapy Cohort |
Primary outcome
Station-specific lymph node metastasis positivity rate after neoadjuvant chemoimmunotherapy
Time frame: Up to 2 weeks
The primary outcome is the station-specific lymph node metastasis positivity rate after neoadjuvant chemoimmunotherapy, assessed by station-by-station pathologic examination of gastrectomy specimens. Each dissected nodal station (No. 1-No. 16, as applicable) is evaluated separately. For each station, the positivity rate is defined as the number of evaluable participants with at least one pathologically confirmed positive lymph node at that station divided by the number of evaluable participants in whom that station was pathologically assessed. A positive node is defined as a lymph node containing viable tumor cells on hematoxylin and eosin staining. Pathologic assessment is performed blinded to preoperative imaging, iRECIST response, and clinical treatment information. The outcome is assessed at postoperative pathology after D2 gastrectomy.
1 secondary outcome
Degree of Peritumoral Edema and Fibrosis
Time frame: Perioperative
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Results publication: PubMed 40454643Janjigian YY, Al-Batran SE, Wainberg ZA, Muro K, Molena D, Van Cutsem E, Hyung WJ, Wyrwicz L, Oh DY, Omori T, Moehler M, Garrido M, Oliveira SCS, Liberman M, Oliden VC, Smyth EC, Stein A, Bilici M, Alvarenga ML, Kozlov V, Rivera F, Kawazoe A, Serrano O, Heilbron E, Negro A, Kurland JF, Tabernero J; MATTERHORN Investigators. Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer. N Engl J Med. 2025 Jul 17;393(3):217-230. doi: 10.1056/NEJMoa2503701. Epub 2025 Jun 1.
- Results publication: PubMed 38134948Shitara K, Rha SY, Wyrwicz LS, Oshima T, Karaseva N, Osipov M, Yasui H, Yabusaki H, Afanasyev S, Park YK, Al-Batran SE, Yoshikawa T, Yanez P, Dib Bartolomeo M, Lonardi S, Tabernero J, Van Cutsem E, Janjigian YY, Oh DY, Xu J, Fang X, Shih CS, Bhagia P, Bang YJ; KEYNOTE-585 investigators. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. 2024 Feb;25(2):212-224. doi: 10.1016/S1470-2045(23)00541-7. Epub 2023 Dec 19.
- Results publication: PubMed 35030335Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, Lee KW, Omori T, Shitara K, Sakuramoto S, Chung IJ, Yamaguchi K, Kato K, Sym SJ, Kadowaki S, Tsuji K, Chen JS, Bai LY, Oh SY, Choda Y, Yasui H, Takeuchi K, Hirashima Y, Hagihara S, Boku N. 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. Lancet Oncol. 2022 Feb;23(2):234-247. doi: 10.1016/S1470-2045(21)00692-6. Epub 2022 Jan 11.
- Results publication: PubMed 30982686Al-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, Lohr 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, Guntner M, Hozaeel W, Reichart A, Jager E, Kraus T, Monig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; 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 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11.
- Results publication: PubMed 40341199Ajani JA, D'Amico TA, Bentrem DJ, Corvera CU, Das P, Enzinger PC, Enzler T, Gerdes H, Gibson MK, Grierson P, Gupta G, Hofstetter WL, Ilson DH, Jalal S, Kim S, Kleinberg LR, Klempner S, Lacy J, Lee B, Licciardi F, Lloyd S, Ly QP, Matsukuma K, McNamara M, Merkow RP, Miller AM, Mukherjee S, Mulcahy MF, Perry KA, Pimiento JM, Reddi DM, Reznik S, Roses RE, Strong VE, Su S, Uboha N, Wainberg ZA, Willett CG, Woo Y, Yoon HH, McMillian NR, Stein M. Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology. J Natl Compr Canc Netw. 2025 May;23(5):169-191. doi: 10.6004/jnccn.2025.0022.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) underlying the results reported in this study, along with the study protocol and statistical analysis plan (SAP), will be shared. Data will be available beginning 6 months and ending 36 months following the publication of the primary research article. Access will be granted to qualified researchers who provide a methodologically sound proposal for achieving aims specified in the approved proposal, such as individual patient data meta-analysis. Proposals should be directed to the Principal Investigator via email. Data requestors will be required to sign a data access agreement and obtain appropriate ethical approval before data transfer.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Xianwen Liang study chair
Hainan General Hospital
Questions about this trial
What is this clinical trial studying?
An observational study of Stomach Neoplasms and Gastric Cancer (Diagnosis), run by Hainan General Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xianwen Liang, Doctorate (+8613016221186, 184241@hainanu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Station-specific lymph node metastasis positivity rate after neoadjuvant chemoimmunotherapy (time frame: Up to 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07899775, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.