Retrospective Study Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Jun 27, 2024; 16(6): 1618-1628
Published online Jun 27, 2024. doi: 10.4240/wjgs.v16.i6.1618
Correlation between postoperative chemotherapy regimen and survival in patients with resectable gastric adenocarcinoma accompanied with vascular cancer thrombus
Ze-Feng Yang, Chen-Jie Dai, Li-Zheng Fu, Hong-Mei Yu, Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Zhuan-Xia Dong, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Hong-Mei Yu, Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan 030001, Shanxi Province, China
Hong-Mei Yu, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Yu-Sheng Wang, Department of Oncology Digestive, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Yu-Sheng Wang, Department of Digestive Oncology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
ORCID number: Ze-Feng Yang (0009-0009-0330-8311); Zhuan-Xia Dong (0009-0005-9271-9606); Chen-Jie Dai (0009-0003-6212-050X); Li-Zheng Fu (0009-0000-3621-712X); Hong-Mei Yu (0000-0002-9852-2485); Yu-Sheng Wang (0000-0002-9681-2876).
Author contributions: Wang YS, Yu HM and Yang ZF designed the research study; Yang ZF prepared the materials; Yang ZF, Dong ZX, Dai CJ, Fu LZ collected the data; Wang YS, Yu HM and Yang ZF analyzed the data; Yang ZF wrote the manuscript and edited it; Wang YS contributed to the writing review; Wang YS and Yang ZF completed the writing–final draft; Wang YS contributed fund support.
Supported by Shanxi Provincial Health Commission, No. 20222025; and Four “Batches” Innovation Project of Invigorating Medical Cause through Science and Technology of Shanxi Province, No. 2023XM024.
Institutional review board statement: This study was approved by the Clinical Research Ethics Committee of Shanxi Cancer Hospital (Ethical number: KY2023010).
Informed consent statement: All patients provided written pan-informed consent for the collection and release of their medical information during their first visit to the hospital.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The data will be shared on reasonable request to the corresponding author.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yu-Sheng Wang, Doctor, MD, Chief Doctor, Deputy Director, Professor, Vice General Manager, Department of Oncology Digestive, The First Hospital of Shanxi Medical University, No. 85 South Jiefang Road, Taiyuan 030001, Shanxi Province, China. wangyusheng@sxmu.edu.cn
Received: January 18, 2024
Revised: April 11, 2024
Accepted: April 23, 2024
Published online: June 27, 2024
Processing time: 163 Days and 18.9 Hours

Abstract
BACKGROUND

Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus (RGAVCT) have a poor prognosis, with a 5-year survival rate ranging from 18.42%-53.57%. These patients need a reasonable postoperative treatment plan to improve their prognosis.

AIM

To determine the most effective postoperative chemotherapy regimen for patients with RGAVCT.

METHODS

We retrospectively collected the clinicopathological data of 530 patients who underwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer embolus. Furthermore, we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by assessing the clinical and pathological features of the patients who met the inclusion criteria. We also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate analyses. The subgroups of patients with stages I, II, and III disease who received single-, dual-, or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R 4.3.0.

RESULTS

In all, 530 eligible individuals with RGAVCT were enrolled in this study. The median overall survival (OS) of patients with RGAVCT was 24 months, and the survival rates were 80.2%, 62.5%, and 42.3% at 12, 24, and 59 months, respectively. Preoperative complications, tumor size, T stage, and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model. A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage I or II RGAVCT; however, chemotherapy did have an effect on OS of stage III patients. Stage III patients who were treated with chemotherapy consisting of dual- or triple-agent regimens had better survival than those treated with single-agent regimens, and no significant difference was observed in the survival of patients treated with chemotherapy consisting of dual- or triple-agent regimens.

CONCLUSION

For patients with stage III RGAVCT, a dual-agent regimen of postoperative chemotherapy should be recommended rather than a triple-agent treatment, as the latter is associated with increased frequency of adverse events.

Key Words: Vascular cancer embolism, Postoperative chemotherapy regimen, Gastric adenocarcinoma, Risk factors, Survival

Core Tip: In patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus (RGAVCT), postoperative chemotherapy has an independent effect on overall survival and may even improve survival. Patients with stage I and II RGAVCT should not receive postoperative chemotherapy, and low-toxicity single-agent therapy is advised even in the presence of high-risk variables. For patients with stage III RGAVCT, a dual-agent regimen of postoperative chemotherapy should be recommended rather than a triple-agent treatment, as the latter is associated with increased risks.



INTRODUCTION

According to the 2020 Tumor Report[1], gastric cancer (GC) ranked fourth among all cancers according to the number of new cases, with approximately 1.1 million cases per year. GC ranked third in terms of mortality rate, with approximately 760000 deaths per year. GC is an important life-threatening disease and one of the most common malignant tumors worldwide. China ranks second and third in terms of new cases and deaths related to GC, respectively[2]. Studies by Zhang[3] and the Asian Cancer Research Group[4] marked significant advancements in the molecular typing of GC, thereby leading to enhanced medical treatment strategies. For stage III GC, the 5-year survival rate following surgery is 34.8%-54.6%[5], and radical surgical resection remains the preferred course of treatment. When tumor cells infiltrate the interior of lymphatic or vascular vessels, which are composed of endothelial cells, the condition is referred to as lymphatic and blood vessel invasion (LBVI)[6]. The literature indicates a 5-year survival rate of 18.42%-53.57% for patients with postoperatively resectable stomach cancer and pathologically identified vascular thrombus, which indicates a poor prognosis[7]. Consequently, the presence of vascular thrombus plays a significant role in the poor prognosis of patients with stomach cancer. Currently, few exploratory investigations on vascular tumor thrombus in gastric adenocarcinoma have been published, and thus the clinicopathological characteristics of this condition remain unknown. To identify alternative therapies to increase the survival of patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus (RGAVCT), we retrospectively examined the clinical and pathological features of 530 patients with RGAVCT and conducted pertinent survival analyses. This manuscript was written according to the STROBE checklist.

MATERIALS AND METHODS
Clinical information

Clinicopathological data were retrospectively collected from 530 patients (107 women and 423 men) who underwent radical surgery for GC at Shanxi Cancer Hospital between January 2017 and January 2022 and who were pathologically diagnosed with stomach adenocarcinoma with a vascular cancer embolus. Patient ages ranged from 28-83 years (median, 63 years). This study was approved by the Clinical Research Ethics Committee of Shanxi Cancer Hospital (approval number: KY2023010). During their first visit to the hospital, all patients provided written informed consent for the collection and release of their medical information.

Inclusion and exclusion criteria: The inclusion criteria were as follows: (1) Radical resection of GC at Shanxi Cancer Hospital; (2) postoperative pathological confirmation of gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction; (3) postoperative pathological evidence of vascular cancer thrombus; (4) clinical stage I, II, or III disease; and (5) availability of complete clinicopathological data. The exclusion criteria were as follows: (1) Presence of other tumors; (2) nonradical resection, such as surgery with positive margins or palliative surgery; and (3) incomplete or unavailable pathological data.

Staging and Ki-67 positivity: Pathological and histological staging was performed according to the 2019 version of the World Health Organization Classification of Tumors of the Digestive System. Ki-67 positivity < 30% was considered low expression, while Ki-67 positivity ≥ 30% was considered high expression.

Follow-up: Regular gastroenterology outpatient reviews, hospitalization, and telephone interviews were used for patient survival follow-up. The deadline for follow-up was March 2023. Overall survival (OS) was defined as the time from the date of surgery to the date of death or the end of follow-up.

Information collection

Clinical information: Patient information, including sex, age at the time of surgery, medical history, family history, preoperative complications, surgical procedures, and postoperative chemotherapy, was collected.

Pathological information: The pathology report included information regarding the location and size of the tumor, the degree of tumor differentiation, the Lauren classification, LBVI, neural invasion, the depth of invasion, the total number of cleared lymph nodes, and immunohistochemistry findings.

Research participants and chemotherapy regimens: To ensure the authenticity and reliability of our results, we collected information on patients who received postoperative adjuvant chemotherapy at our hospital.

Statistical analysis

SPSS (version 25.0; IBM, Armonk, NY) and R 4.3.0 (R Foundation, Vienna, Austria) were used for the statistical analysis. The rank-sum test was used to evaluate the skewed distributions, which are expressed as the mean and standard deviation of the quantitative data. Mantel-Cox univariate regression analysis was used to identify possible prognostic factors. The clinicopathological variables that affected survival time were then analyzed using a multivariate Cox regression model to identify significant factors that might affect the prognosis of patients with RGAVCT. The Kaplan-Meier method was used to calculate the survival rates, and the log-rank test was used for intergroup comparisons of the survival curves. The survival curves were compared between groups using R 4.3.0. In R 4.3.0, the forest plot of the factors that influenced the survival of patients with RGAVCT was plotted using the “survival” and “forest plot” packages; the Kaplan-Meier survival curves for patients with RGAVCT were drawn using the “ggplot2” and “survminer” programs. Statistical significance was established at P < 0.05. The statistical methods used in this study were reviewed by Professor Yu HM from the Department of Health Statistics, Shanxi Medical University.

RESULTS
Clinicopathologic features of patients with RGAVCT

The 530 patients with RGAVCT who met the inclusion criteria ranged in age from 28–83 (median, 63) years (Table 1). A 4:1 male-to-female ratio was noted, with 423 men and 107 women. A total of 9.2% of patients had a family history of tumors, and 86.4% of patients had no preoperative complications. For those patients who did experience preoperative complications, 7.7%, 1.9%, 1.1%, and 2.8% experienced gastrointestinal obstruction, gastrointestinal hemorrhage, other complications (such as perforation, gastric retention, and anemia), and multiple complications, respectively. Open surgery was performed in 61.9% of patients, laparoscopic surgery in 33.8%, and combined thoracic and abdominal surgery in 4.3%. Postoperative chemotherapy was administered to approximately 74.3% of patients.

Table 1 Univariate analysis of the demographic, clinical, and pathological risk variables in 530 patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus.
Characteristic
n (%)
χ2
P value
Age, yr
    < 60211 (39.8)5.9430.015
    ≥ 60319 (60.2)
Sex
    Male423 (79.8)7.5330.006
    Female107 (20.2)
Past history
    No289 (54.5)3.760.052
    Yes241 (45.5)
Family history
    No479 (90.4)4.7110.030
    Yes51 (9.6)
Preoperative complications
    No458 (86.4)1.9820.037
Digestive tract obstruction41 (7.7)
Alimentary tract hemorrhage10 (1.9)
    Others16 (1.1)
    ≥ 2 complications15 (2.8)
Surgical method
    Open abdominal328 (61.9)1.8530.396
    Laparoscopy179 (33.8)
Joint thoracoabdominal 23 (4.3)
Chemotherapy
    No136 (25.7)63.834<0.001
    Yes394 (74.3)
Tumor site
    Proximal286 (54)2.2170.330
    Distal144 (27.2)
    Body100 (18.9)
Differentiation
    Moderate54 (10.2)5.7420.057
    Moderate-poor188 (35.5)
    Poor288 (54.3)
Lauren classification
    Diffused type182 (34.3)11.8590.008
    Intestinal type62 (11.7)
    Mixed type252 (47.5)
    NA34 (6.4)
Neural invasion
    Absence247 (46.6)5.8990.015
    Presence 283 (53.4)
Tumor size, cm
    < 5231 (43.6)8.9760.003
    ≥ 5299 (56.4)
HER2 expression
    Negative458 (86.4)0.4950.482
    Positive72 (13.6)
MMR status
    dMMR14 (2.6)0.2290.633
    pMMR516 (97.4)
Ki-67 expression
    Low8 (1.5)6.0190.014
    High522 (98.5)
T stage
    244 (8.5)25.459< 0.001
    3374 (70.6)
    4a93 (17.5)
    4b18 (3.4)
N stage
    037 (7)42.8< 0.001
    1104 (19.6)
    2137 (25.8)
    3a158 (29.8)
    3b94 (17.7)
Stage
    IB10 (1.9)62.765< 0.001
    IIA43 (8.1)
    IIB80 (15.1)
    IIIA132 (24.9)
    IIIB171 (32.3)
    ШC94 (17.7)

According to the Union for International Cancer Control TNM staging system (8th edition), 10 patients (1.9%) were categorized as stage IB, 43 (8.1%) as stage IIA, 80 (15.1%) as stage IIB, 132 (24.9%) as stage IIIA, 171 (32.3%) as stage IIIB, and 94 (17.7%) as stage IIIC. The RGAVCT tumor sites were mainly distributed in the proximal (54%), distal (27.2%), and gastric bodies (18.9%). Tumors were predominantly poorly differentiated (54.3%), intermediate-poorly differentiated (35.5%), and moderately differentiated (10.2%); none were well differentiated.

The Lauren classification was predominantly mixed (47.5%) or diffused (34.3%), while the intestinal type was less frequent (11.7%). Neural invasion was observed in 53.4% of the patients. Tumors > 5 cm were found in 56.4% of the patients. Immunohistochemistry indicated Her-2 positivity (3+ or 2+ fluorescent in situ hybridization positivity) in approximately 13.6% of the patients. Moreover, mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) were absent in 2.6% and were expressed in 97.4% of the patients. Ki-67 was highly expressed in 98.5% of the patients.

Survival analysis of patients with RGAVCT

The median OS (mOS) of patients with RGAVCT was 24 months, with survival rates of 80.2%, 62.5%, 54.8%, and 42.3% at 12, 24, 37, and 59 months, respectively. The postoperative chemotherapy group had an mOS of 25 months, and the survival rates were 86.8%, 71.3%, 64.2%, and 52.8% at 12, 24, 37, and 53 months, respectively. The mOS was 15 months in the group that did not receive chemotherapy, and the survival rates were 61%, 38.1%, 28.5%, and 19% at 12, 24, 34, and 59 months, respectively. Patients with stage I and II cancer had an mOS of 27 months, with survival rates of 89.5%, 80%, 74.6%, and 52.2% at 12, 24, 34, and 59 months, respectively (Figure 1A). The mOS of patients with stage III cancer was 23 months, with survival rates of 77.8%, 57.8%, 49.5%, and 40.1% at 12, 24, 37, and 53 months, respectively. The best survival rate was observed in patients with stage IIIA cancer, followed by those with stage IIIB cancer, while the worst survival rate was observed in patients with stage IIIC cancer (Figure 1B).

Figure 1
Figure 1 Survival curve of resectable gastric adenocarcinoma accompanied by vascular cancer thrombus patients. A: Stage I and II; B: Stage III. OS: Overall survival.
Analysis of the factors influencing survival of patients with RGAVCT

The univariate analysis by Mantel-Cox regression revealed significant differences (P < 0.05) in age, sex, family history, preoperative complications, postoperative chemotherapy, Lauren classification, neural invasion status, tumor size, Ki-67 expression, T and N stage, and clinical stage, and these factors were significantly correlated with the OS of patients with RGAVCT. A multivariate Cox analysis of the significant influencing factors revealed that preoperative complications (P = 0.035), postoperative chemotherapy [P < 0.001; hazard ratio (HR) = 0.35; 95% confidence interval (CI) = 0.26-0.46], tumor size (P = 0.035; HR = 1.36; 95%CI = 1.02-1.80), and T stage (P = 0.005) were independent factors that affected OS (Figure 2).

Figure 2
Figure 2 Multivariate analysis of risk factors in 530 patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus.
RGAVCT postoperative chemotherapy regimen and survival correlation analysis

Of the 394 patients with RGAVCT who were administered postoperative adjuvant chemotherapy, 323 received chemotherapy at our institution (23 received a single-agent regimen, 272 received a dual-agent regimen, and 28 received a triple-agent regimen), and 71 received chemotherapy outside our hospital.

The univariate analysis revealed no significant difference between postoperative chemotherapy and survival in patients with stage I and II RGAVCT (P = 0.527). Preoperative complications, postoperative pathological neural invasion, and Ki-67 expression were factors that were found to influence the survival of patients with stage I and II RGAVCT (P < 0.05).

The Cox multivariate analysis revealed that preoperative complications (P = 0.021), neural invasion (P = 0.02; HR = 2.47; 95%CI = 1.16-5.28), and Ki-67 expression (P = 0.007; HR = 0.05; 95%CI = 0.01-0.44) were independent factors found to influence the survival of patients with stage I and II RGAVCT (Table 2). However, postoperative chemotherapy did not affect the OS of high-risk patients with stage I and II RGAVCT (P = 0.653).

Table 2 Univariate and multivariate analyses of 133 patients with stage I and stage II resectable gastric adenocarcinoma accompanied by vascular cancer thrombus to determine which clinicopathological characteristics are risk factors.
Characteristic
N
Univariate analysis
Multivariate analysis
χ2
P value
HR (95%CI)
P value
Preoperative complications
    No11527.724< 0.00110.021
    Digestive tract obstruction42.15 (0.50-9.32)0.304
    Alimentary tract hemorrhage12.90 (0.38-22.41)0.307
    Others137.07 (1.91-26.15)0.003
Neural invasion
    Absence7310.0140.0021
    Presence502.47 (1.16-5.28)0.02
Ki-67 expression
    Low15.580.0181
    High1220.05 (0.01-0.44)0.007

The Kaplan-Meier analysis revealed that postoperative chemotherapy affected the OS of patients with stage III RGAVCT (P < 0.001) (Figure 3A). Furthermore, compared with patients treated with a single-agent regimen, individuals who were treated with chemotherapy consisting of dual- or triple-agent regimens had higher survival rates (P = 0.047 and P = 0.034) (Figure 3B and C), and no significant difference was observed between the survival of patients treated with dual-agent regimens and that of those treated with triple-agent regimens (P = 0.646) (Figure 3D).

Figure 3
Figure 3 Comparison of chemotherapy schemes in 323 patients with stage Ш resectable gastric adenocarcinoma accompanied by vascular cancer thrombus. A: Comparison of chemotherapy schemes for Stage Ш patients; B: Comparison of single drug and double drug resistances; C: Comparison of single drug and triple drug resistances; D: Comparison of double drug and triple drug resistances. OS: Overall survival.
DISCUSSION

The aim of this study was to determine the most effective postoperative chemotherapy regimen for patients with RGAVCT. According to the analysis, no significant survival difference was observed between patients with stage III RGAVCT treated with double-drug regimens and those treated with triple-drug regimens, but their survival rates were better than those who received single-drug regimens. For patients with stage III RGAVCT, a dual-agent regimen of postoperative chemotherapy should be recommended rather than a triple-agent treatment, as the latter is associated with increased adverse events.

GC is a life-threatening disease and is one of the primary causes of cancer-related death worldwide. The introduction of novel anticancer medications, neoadjuvant radiation, adjuvant chemotherapy, and late-stage palliative care are among the numerous advancements in the systemic treatment of GC. These measures have significantly increased the survival rates of patients with GC. However, high postoperative recurrence and metastasis rates adversely affect the survival of patients with GC. The postoperative clinicopathological features of GC are also the primary prognostic factors associated with this disease. In a study by Chen et al[8], the depth of tumor infiltration, extent of lymph node metastasis, extent of distant metastasis, and pathological score were used to predict the prognosis and OS of patients with GC. The impact of vascular cancer embolism on the prognosis of malignant tumors has received considerable attention because of detailed research on tumor prognostic variables and the concept of micrometastasis[9,10]. Vascular cancer emboli are tumor cells that form aggregates with fibrin clots, coexist with erythrocytes, infiltrate the endothelial cell space arrangement of the surrounding tissue in the absence of erythrocytes, or invade the smooth muscle cell space arrangement[11,12].

Torre et al[13] reported a 2:1 male-to-female ratio in the global incidence of GC in 2012, while Sung et al[1] reported that the global incidence of GC in 2020 was approximately 7.2% for men and 4.4% for women. These studies show that the number of men with GC is greater than that of women. The male-to-female ratio of patients with RGAVCT in this study was 4:1, which was much higher than the global male-to-female ratio of GC patients. Consequently, vascular cancer emboli are more likely to occur in males with GC.

Regarding the baseline characteristics of patients with RGAVCT, our study revealed that the type of surgery (open, laparoscopic, or combined thoracoabdominal) had no effect on OS. Moreover, we found that surgeons involved in clinical assessments selected the appropriate surgical approach based on the specific conditions of the patients. In more than half (53.4%) of the patients with RGAVCT and concomitant neural invasion, we found that vascular cancer embolus and neural invasion were likely to occur simultaneously. Among the patients with RGAVCT who were analyzed, 10 had stage IB RGAVCT, 123 had stage II RGAVCT, and 397 had stage III RGAVCT, which accounted for 74.9% of all patients. This indicates that vascular cancer embolisms occurred more often in patients with advanced GC. The median survival time (mOS = 23 months) and survival rates at 12 months (77.8%), 24 months (57.8%), 34 months (49.5%), and 53 months (40.1%) of patients with stage III RGAVCT were significantly lower than those of patients with stages I and II RGAVCT (mOS = 27 months; 12 months, 89.5%; 59 months, 52.2%).

The risk factors for GC include many immutable variables, such as age[14], sex, and race/ethnicity. Additionally, some modifiable risk factors, such as Helicobacter pylori infection[15], smoking[16], and high nitrate and nitrite diets, have also been identified. Several known hereditary cancer syndromes are associated with GC, including hereditary diffuse GC (CDH1) syndrome, the most strongly associated syndrome, which occurs in approximately 80% of patients[17]. The multivariate analysis identified preoperative complications, postoperative chemotherapy, tumor size, and T stage as independent factors that affect the OS of patients with RGAVCT, with postoperative chemotherapy as the intervening factor. In addition, a previous study[18] showed that lymph node metastasis in early GC can be predicted using nomograms, decision trees, and deep learning models. To better understand the prognostic factors of patients with RGAVCT, the derived prognostic elements can be utilized to construct a deep learning model. This model can then be applied to validate these factors using external databases.

In this study, the mOS was 25 months in the chemotherapy group, which was greater than that in the nonchemotherapy group (15 months), which indicates that chemotherapy could prolong the survival of patients with RGAVCT. Several studies[19-21] have suggested that postoperative chemotherapy can improve the prognosis of patients with GC. However, postoperative chemotherapy is the only intervening factor among the independent factors that affect the OS of patients with RGAVCT, and a rational postoperative chemotherapy regimen can further improve the prognosis of these patients. A clinical consensus[22] has been established that postoperative adjuvant therapy should be recommended for patients who undergo D2 radical surgery and who do not receive preoperative treatment for postoperative pathological stage II and III progressive GC. In this study, 530 patients were evaluated based on clinical stage, and we found that postoperative chemotherapy did not affect the OS of patients with stage I and II RGAVCT. We further investigated whether postoperative chemotherapy influenced the survival of high-risk patients with stage I and II RGAVCT. We found that preoperative complications, postoperative pathological neural invasion, and Ki-67 expression were independent factors that affected the survival of patients with stages I and II RGAVCT according to the univariate and multivariate analyses. However, the OS of patients with stage I and II RGAVCT who had a combination of high-risk factors was not affected by postoperative chemotherapy.

We explored the effect of postoperative chemotherapy on the OS of patients with stage III RGAVCT (P < 0.001) and discovered a substantial difference in survival between patients who received postoperative chemotherapy and those who did not. The recent JACCRO GC-07 study[23], which investigated chemotherapy regimens and clinical outcomes, showed that the continuation of an oral S-1 monotherapy regimen (DS sequential S-1) after six cycles of postoperative docetaxel combined with S-1 improved the survival of patients with stage III GC compared with S-1 alone (3-year recurrence-free survival: S-1/docetaxel group, 65.9% vs S-1 group, 49.6%; P = 0.0007). Moreover, combination therapy inhibited hematologic, lymphatic, and peritoneal recurrence. An analysis of the effects of dosing regimens on the survival of patients with stage III RGAVCT who received postoperative adjuvant chemotherapy at our institution showed that postoperative chemotherapy prolonged survival, that dual- and triple-agent regimens resulted in an equal survival benefit, and that both were better than a single-agent regimen. The CLASSIC study[24] used capecitabine combined with oxaliplatin in a dual-agent adjuvant chemotherapy regimen for advanced GC. The 5-year disease-free survival rate (68%) and 5-year OS rate (78%) with this regimen were better than those in the observation group (53% and 69%, for the 5-year disease-free survival and the 5-year OS, respectively). Therefore, postoperative chemotherapy for advanced GC should involve a dual-agent regimen of capecitabine and oxaliplatin. Another study[25] showed that the XELOX double-agent regimen was as effective as both regimens in the first-line treatment of advanced GC, unlike the EOX triple-agent regimen. This study, for the first time, established the optimal two-drug chemotherapy strategy for patients with stage III RGAVCT and identified the clinical features of patients with RGAVCT. However, our chemotherapeutic program design was not standardized, and the sample size was small, which limits the accuracy of the data in this study. A deep learning model using external databases for predicting variables will be created in the future to confirm the predictions for patients with RGAVCT. Long-term, randomized, controlled clinical research is also necessary to investigate the effect of chemotherapy regimens on the survival of patients with RGAVCT.

CONCLUSION

Postoperative chemotherapy has an independent effect on OS in patients with RGAVCT and can increase survival. However, chemotherapy administered after surgery had little effect on the OS of patients with stage I and II RGAVCT. Moreover, triple-agent treatment is associated with more adverse events than other forms of treatment. Therefore, we recommend that patients with stage II RGAVCT receive dual-agent chemotherapy. The clinical implications and future scope are clear.

Footnotes

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Gastroenterology and hepatology

Country of origin: China

Peer-review report’s classification

Scientific Quality: Grade A

Novelty: Grade B

Creativity or Innovation: Grade B

Scientific Significance: Grade A

P-Reviewer: Park J S-Editor: Qu XL L-Editor: A P-Editor: Xu ZH

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