Gastric transcatheter chemoembolization combined with systemic chemotherapy vs. systemic chemotherapy alone for patients with advanced gastric cardiac cancer presenting with dysphagia: A case control study
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- Published online on: June 12, 2024 https://doi.org/10.3892/ol.2024.14500
- Article Number: 367
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Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Abstract
Introduction
Advanced gastric cardiac cancer (AGCC) is a challenging malignancy that typically presents with dysphagia and primarily affects the proximal stomach, often extending to the gastroesophageal junction. Previous studies showed that 23.3% of early gastric cancer was gastric cardiac carcinoma in China (1), which is a higher rate compared with the 7.0% recorded in Japan (2) and the 11.9% recorded in a Western cohort (3). Patients with AGCC face the risk of malnutrition and decreased quality of life (QoL) (4–8). In one study, the 5-year survival rate was <10% at the advanced stage (9). Dysphagia further complicates treatment, as it hampers the delivery of oral medications, reducing the effectiveness of systemic chemotherapy (SYS). As a result, malignant dysphagia is a common and difficult clinical manifestation in cases of AGCC, necessitating effective symptom management for enhanced patient comfort (4–6,10). According to literature reports, 60–90% of patients with cancer at the gastroesophageal junction experience significant swallowing difficulties (11–14). SYS is the mainstay treatment for AGCC, aiming to improve symptom remission rates and prolong patient survival; however, the efficacy of SYS alone is limited, highlighting the need for alternative approaches (15).
Endoscopic stent implantation is a conventional treatment option for alleviating dysphagia caused by AGCC; however, stent placement carries the risk of complications such as stent obstruction, migration and perforation (7,16–19). Other interventions, such as percutaneous gastrostomy and naso-jejunal feeding, have demonstrated a certain amount of symptomatic relief, but are associated with higher risks of complications, including infections, bleeding and dislodgement (20,21). Therefore, gastric transcatheter chemoembolization (GTC), a minimally invasive technique, has emerged as a promising therapeutic option for AGCC with dysphagia. This technique involves the intra-arterial infusion of chemotherapeutic drugs directly into the tumor-feeding artery, followed by the injection of embolic agents to induce ischemic necrosis of the tumor. GTC allows for high local drug concentrations, effectively reducing tumor vascularity and size, thereby improving dysphagia control in patients with AGCC (4–6,10,22–24).
Despite its potential benefits, the use of GTC in combination with SYS for AGCC with dysphagia remains controversial, and comparative studies with SYS alone are lacking. Therefore, the objective of the present retrospective study is to evaluate the efficacy of combining GTC with SYS compared with SYS alone in patients with AGCC and dysphagia.
Materials and methods
Study design and participants
A retrospective review was performed of consecutive patients with AGCC who presented with dysphagia and underwent either SYS alone or a combination of GTC and SYS between January 2018 and December 2022. The patients and their families made the decision to undergo GTC after consultation with the multidisciplinary team of experts from the gastric cancer group of the Affiliated Cancer Hospital of Shandong First Medical University of China (Jinan, China). This decision was influenced by the presence of dysphagia symptoms, irrespective of tumor size. AGCC diagnosis was confirmed through endoscopy and biopsy, and staging was performed using the 8th edition of the American Joint Committee on Cancer (AJCC) criteria (25). To be included in the present study, patients had to meet the following criteria: i) Histologically-confirmed AGCC; ii) advanced stage of the disease (AJCC stage III or IV); iii) dysphagia as a presenting symptom [at least Ogilvie Dysphagia Scale (26) grade 1]; iv) age ≥18 years; v) Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; vi) treatment with either GTC combined with SYS or SYS alone; and vii) sufficient medical records available for review. The exclusion criteria included the following: i) Previous treatment for AGCC; ii) co-existing malignancies; and iii) other significant comorbidities.
Procedures
Systemic chemotherapyThe SYS group received a combination of two first-line chemotherapy regimens: tegafur-gimeracil-oteracil (S-1) plus oxaliplatin (SOX) (27)r capecitabine and oxaliplatin (XELOX) (28). In the SOX regimen, patients took oral S-1 at a dosage of 40–60 mg twice a day on days 1–14, every 3 weeks, and received intravenous oxaliplatin at a dosage of 130 mg/m2 on day 1, every 3 weeks. For the XELOX regimen, patients took oral capecitabine at a dosage of 1,000 mg/m2 twice a day on days 1–14, every 3 weeks, and received intravenous oxaliplatin at a dosage of 130 mg/m2 over 2 h on day 1, every 3 weeks.
Second-line chemotherapy regimens included irinotecan (29) and paclitaxel monotherapy (30). In the irinotecan monotherapy regimen, patients received intravenous irinotecan at a dosage of 150 mg/m2 on days 1 and 15, every 4 weeks. For the paclitaxel monotherapy regimen, patients received intravenous paclitaxel at a dosage of 60 mg/m2 on days 1 and 8, every 3 weeks.
The decision to switch from first-line to second-line chemotherapy was based on several factors, including disease progression, treatment response and tolerance. The specific timing and criteria for switching were determined by the treating oncologist.
GTC
GTC was performed by an experienced interventional radiologist under local anesthesia and conscious sedation. The patient was positioned supine, and access to the right femoral artery was obtained using the Seldinger technique. A 5-French (5-F) sheath was inserted, and a 5-F diagnostic catheter was advanced into the abdominal aorta under fluoroscopic guidance. Arteriography of the abdominal trunk was then performed to identify the supply arteries of the tumor. If necessary, additional arterial angiography, including the right gastric artery, short gastric arteries, posterior gastric artery, gastro-epiploic artery and left inferior phrenic artery, was performed to gain a comprehensive understanding of the blood supply arteries of the tumor. If the tumor received blood supply from sources other than the left gastric artery, 300–500-µm Embosphere microspheres (Merit Medical Systems, Inc.) were used to embolize certain non-primary blood supply arteries. Subsequently, a 0.022-inch microcatheter (PROGREAT®; Terumo Medical Corporation) was inserted into the left gastric artery, and fluorouracil (5-FU) (at a dose of 1,000 mg/m2) was slowly injected via the microcatheter over a period of >10 min. Following the chemotherapy infusion, Embosphere microspheres (300–500 µm) were injected to embolize the left gastric artery. The procedure was determined to be successful when angiography demonstrated that there was no residual arterial flow to the tumor. The imaging data for a 55-year-old patient diagnosed with AGCC who underwent GTC are presented in Fig. S1A-M.
After the intervention, pressure was applied to the femoral artery for 15 min, and patients were closely monitored for 24 h post-procedure to detect any signs of abdominal pain, fever or other complications. Routine blood tests, including liver and kidney function tests, were performed before and after the procedure to identify any changes.
Each cycle was scheduled at intervals of 4 weeks, and patients received GTC treatment once within each cycle. The number of cycles administered to each patient varied based on their response to treatment and the discretion of the treating physician.
Assessment of dysphagia severity, nutritional status, QoL and adverse events (AEs)
The primary outcome measure of the present study was symptom remission, which included improvement in dysphagia severity, QoL and nutritional status. These measures were evaluated at baseline, 4 weeks, and 8 weeks after the first cycle of SYS, and were regularly assessed via telephone or at an outpatient clinic visit.
Dysphagia was evaluated using the Ogilvie Dysphagia Scale, which grades dysphagia into 5 levels: 0, no dysphagia; 1, normal diet with certain food restrictions (such as raw apple and steak); 2, semi-solid diet; 3, fluids only; and 4, complete dysphagia, even for liquids.
Nutritional status was assessed by experienced dietitians using the scored Patient-Generated-Subjective Global Assessment (PG-SGA) scale (31). The PG-SGA scale consists of two parts: Patient self-assessment and assessment by medical staff. It evaluates weight, intake, symptoms affecting intake, functional capacity, metabolic demands and physical assessment. Patients assessed the first four aspects themselves, whilst medical staff assessed the last two. Each item was given a score of 0–4 based on its impact on nutritional status, and the total scores were then summed. Nutritional status was categorized as well-nourished (0–1 points), suspected malnutrition (2–3 points), moderate malnutrition (4–8 points), or severe malnutrition (≥9 points) based on the total score.
QoL was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G)7 scale (32), which is a condensed version of the FACT-G scale (33). It includes three items from the physical wellbeing subscale (fatigue, pain and nausea), one item from the emotional wellbeing subscale (concern about the condition worsening), and three items from the functional wellbeing subscale (enjoyment of life, contentment with QoL and sleep). Each item is graded on a 5-point scale, ranging from ‘not at all’ (0) to ‘very much’ (4). The functional wellbeing subscale is directly scored from 0–4 points, whilst the physical wellbeing subscale and emotional wellbeing are scored in reverse. The scores from FACT-G7 are summed on a scale of 0–28, with higher scores indicating a better QoL.
AEs were recorded and graded according to the Common Terminology Criteria for Adverse Events version 5.0 (34). Specific AEs related to GTC such as fever, abdominal pain and gastrointestinal ulcers were also assessed.
Treatment response
All patients were regularly followed up after receiving treatment. The response to treatment was assessed using computed tomography (CT) or magnetic resonance imaging at 1, 2 and 6 months after the first cycle of GTC. Evaluation of treatment response was performed in accordance with the Response Evaluation Criteria in Solid Tumors version 1.1 (35). Overall survival (OS) was defined as the duration from the initiation of treatment to either death from any cause or the last follow-up. Progression-free survival (PFS) was defined as the period from the start of treatment to disease progression or death from any cause. Objective response rate (ORR) was defined as the % of patients who achieved either a complete response (CR) or partial response (PR) to the treatment. CR was defined as the disappearance of all target lesions, whilst PR was defined as a ≥30% decrease in the sum of the diameters of target lesions. Disease control rate (DCR) was defined as the % of patients who achieved CR, PR or stable disease (SD). SD was defined as neither PR nor PD.
Statistical analysis
All statistical analyses were performed using MatchIt package version 4.5.5 (36) and the R software version 4.2.2 (R Core Team; http://www.R-project.org/). Baseline characteristics are presented as the median (interquartile range) for continuous variables and the n (%) for categorical variables. The maximum diameter of the tumor at the cardia, Ogilvie score, PG-SGA score and FACT-G7 score were compared between the two groups at 4 and 8 weeks after the first cycle of SYS. For comparison between groups of categorical data, Fisher's exact test or the χ2 test was used. The Wilcoxon rank sum test was used for the analysis of continuous variables. Univariate and multivariate logistic regression analysis was performed to determine the independent factors associated with presence of dysphagia after 8 weeks of the first cycle of SYS. Kaplan-Meier curves and the log-rank test were used to compare the OS and PFS between the groups. Subgroup analyses were performed to evaluate the impact of baseline characteristics on OS, and the interaction between the treatment groups and subgroups was tested using Cox proportional hazards regression analysis. P<0.05 was considered to indicate a statistically significant difference.
Propensity score matching (PSM) was used to minimize the influence of confounding factors and improve the validity of the findings, making the results more applicable to real-world clinical practice. PSM were calculated using logistic regression, accounting for the aforementioned demographic and clinical characteristics. Furthermore, 1:1 greedy nearest neighbor matching was performed with a caliper of 0.3. The method functionally relied on the MatchIt R package. The distance between the unit of one group and another was calculated, and each unit was assigned a control unit as a match. The matching was ‘greedy’ as no action was taken to optimize an overall criterion; each match was selected without accounting for the other matches that may have subsequently occurred. Fig. S2 presents the balance of baseline covariates before and after PSM for both the GTC + SYS and SYS alone groups.
Results
Study population
Initially, 954 patients were screened, and a total of 295 patients with AGCC presenting with dysphagia, who matched the inclusion criteria, were included in the present retrospective study. Of these, 138 patients received GTC combined with SYS, whilst 157 patients received SYS alone. PSM yielded 114 well-balanced pairs in terms of baseline demographics and clinical characteristics. A notable reduction in SMDs after matching can be observed, indicating that the PSM effectively improved the balance of covariates between the two treatment groups. This improvement in balance allowed for a more reliable comparison of treatment effectiveness, as the potential influence of confounding factors was minimized. The screening process is presented in Fig. 1.
Table I presents the baseline characteristics of the study population before and after PSM. Prior to PSM, there were significant differences in ECOG, WBC, Ogilvie score, PG-SGA score, and the first-line chemotherapy regimen between the two groups. Following PSM, the baseline characteristics were well balanced between the two groups and there were no significant differences. The majority of participants were male, accounting for 73% in the GTC + SYS group and 70% in the SYS group. The age distribution showed a median of 62 years in both groups. Biomarker analysis revealed no significant differences between the two groups. The main tumor characteristics also did not significantly differ. The median follow-up time for the GTC + SYS group was 12 months (range, 6–24 months), whilst it was 10 months (range, 5–22 months) for the SYS alone group. There was no statistically significant difference in the follow-up time between the two groups (P=0.234). In the GTC + SYS group, the median number of GTC procedures performed was 2, with a range of 1–4 procedures.
Comparison of the clinical symptoms and clinical symptom relief between the two groups
Comparison of the severity of dysphagia between the groupsAt baseline, there were no significant differences in the severity of dysphagia between the two treatment groups (P>0.05). After 4 weeks of the initial cycle of SYS, the severity of dysphagia in the SYS group was significantly higher compared with the GTC + SYS group (P<0.001). Following the initial treatment period, it was observed that ~25% of patients in the GTC + SYS group no longer experienced symptoms of dysphagia, whilst all patients in the SYS group continued to report difficulties with swallowing. This trend persisted at 8 weeks after the first cycle of SYS, with the SYS group also experiencing significantly more severe dysphagia than the GTC + SYS group (P<0.001; Table SI). Specifically, at both 4 and 8 weeks, the GTC + SYS group demonstrated significantly lower median Ogilvie scores than the SYS only group (Table II). Additionally, at 8 weeks after the initial treatment, the percentage of patients with dysphagia in the SYS group was significantly higher compared with that in the GTC + SYS group (84 vs. 28%; P<0.001). Regarding clinical symptom relief, the GTC + SYS group had a significantly higher rate of improvement in dysphagia compared with the SYS group (P<0.05). Specifically, 110/114 patients in the GTC + SYS group reported improvement in dysphagia symptoms, whilst only 86/114 patients in the SYS group reported similar improvements at 8 weeks after the first cycle of SYS (96 vs. 75%; P<0.001) (data not shown).
 | Table II.Summary of symptom scores and maximum diameter of the tumor at the cardia of patients before and after treatment. |
Comparison of nutritional status and QoL between groups
There were significant differences for nutritional status and QoL between the groups at 4 and 8 weeks following the initial cycle of SYS. Specifically, both at 4 and 8 weeks post the first cycle of SYS, the GTC + SYS group demonstrated significantly lower median PG-SGA scores and significantly higher median FACT-G7 scores compared with the SYS group (P<0.001; Table II). At 4 weeks post the initial SYS cycle, there was a significantly higher proportion of well-nourished individuals in the GTC + SYS group than in the SYS group, whilst the SYS group had a significantly higher proportion of severe and moderate malnutrition cases than the GTC + SYS group (P<0.001; Table SI). By the end of 4 weeks of treatment, ~41% of patients in the GTC + SYS group no longer displayed signs of malnutrition, whereas all patients in the SYS group still exhibited varying degrees of malnutrition (Table SI). This pattern persisted at 8 weeks post the first SYS cycle, with a significantly higher proportion of well-nourished individuals in the GTC + SYS group than the SYS group, and the SYS group displaying significantly more cases of suspected, moderate and severe malnutrition than the GTC + SYS group (P<0.001). After 8 weeks following the initial SYS cycle, the improvement in malnutrition status was compared between the two groups. In the GTC + SYS group, 99 patients (87%) showed notable improvements in their malnutrition status, whilst in the SYS alone group, only 8 patients (7%) showed a marked improvement. The difference in improvement rates between the two groups was found to be statistically significant (P<0.001; Table SI).
Comparison of the maximum diameter of the tumor at the cardia between groups
A similar trend was observed for the maximum diameter of the tumor at the cardia. Significant reductions in tumor size were seen in the GTC + SYS group compared with the SYS group at 4 and 8 weeks after the first cycle of SYS. Specifically, after 4 weeks of the first cycle of SYS, the median reduction in the maximum tumor diameter in the GTC + SYS group was 1.7 cm, compared with 0.8 cm in the SYS alone group (P<0.001). Similarly, after 8 weeks of the first cycle of SYS, the median reduction in the maximum tumor diameter in the GTC + SYS group was 2.7 cm, compared with 1.3 cm in the SYS alone group (P<0.001). After 4 weeks of the first cycle of SYS, the median maximum tumor diameter at the gastric cardia in the GTC + SYS group was significantly smaller than in the SYS alone group (P<0.001). This difference was even more pronounced at 8 weeks after the first cycle of SYS, with the median maximum tumor diameter being significantly smaller in the GTC + SYS group compared with the SYS alone group (P<0.001; Table II).
Independent predictors of the presence of dysphagia at 8 weeks after the first cycle of SYS
Univariate logistic regression analysis of factors associated with presence of dysphagia at 8 weeks after the first cycle of SYS demonstrated that treatment with GTC + SYS was the only significant independent factor for reducing the occurrence of dysphagia [odds ratio (OR)=0.07; 95% CI, 0.04–0.14; P<0.001). Multivariable logistic regression then confirmed that treatment with GTC + SYS remained the only significant factor for reducing the occurrence of dysphagia at 8 weeks after the first cycle of SYS (OR=0.07; 95% CI, 0.03–0.13; P<0.001; Table III). The model coefficients for dysphagia and the model fit measures are shown in Tables SII and SIII, respectively, and the Omnibus likelihood ratio tests are shown in Table SIV.
| Table III.Univariate and multivariate analysis of predictive factors for presence of dysphagia symptoms after 8 weeks of the first cycle of SYS. |
Comparison of treatment prognosis between groups
Short-term treatment efficacyThere were no cases of complete remission in either treatment group. The rates of CR and PR, SD and PD were not significantly different between the two groups. Additionally, the ORR (45% vs. 45%) and DCR) (82% vs. 79%) showed no statistically significant difference between the two groups (P>0.05) (data not shown).
Long-term treatment efficacy
The Kaplan-Meier survival curves for OS and PFS before and after PSM are presented in Figs. 2 and 3, respectively. The median OS was significantly higher in the GTC + SYS group than in the SYS group before (Fig. 2A) and after (Fig. 2B) PSM. Before PSM, the median OS was 13.0 months (95% CI, 12.0–14.0) in patients who received GTC + SYS vs. 11.0 months (95% CI, 10.0–12.0) in patients who received SYS alone (log-rank P=0.001). After PSM, the median OS was 13.0 months (95% CI, 12.0–14.0) in patients who received GTC + SYS vs. 11.0 months (95% CI, 10.0–12.0) in patients who received SYS alone (log-rank P=0.002) (data not shown). However, there was no significant difference in PFS between the two groups before (Fig. 3A) and after (Fig. 3B) PSM (Table IV). Before PSM, the median PFS was 6.7 months (95% CI, 6.0–8.0) in patients who received GTC + SYS vs. 7.0 months (95% CI, 6.0–7.0) in patients who received SYS alone (log-rank P=0.330). After PSM, the median PFS was 6.7 months (95% CI, 6.0–8.5) in patients who received GTC + SYS vs. 7.0 months (95% CI, 6.0–7.0) in patients who received SYS alone (log-rank P=0.570). Furthermore, 12-month OS was 53.5% in the GTC + SYS group and 35.1% in the SYS alone group. 12-month OS results were generally consistent across patient subgroups and did not differ significantly (Fig. 4).
The logistic regression analysis revealed that the number of GTC treatment sessions was not significantly associated with the 12-month survival rate of patients (Table SV) or the presence of dysphagia at 8 weeks after initial treatment (Table SVI; P>0.05).
Comparison of AEs between groups
In the GTC + SYS group, the most common severe AEs (grades 3/4) were leukopenia (7.3%), neutropenia (7.3%), and nausea and vomiting (7.3%). In the SYS group, the most common severe AEs were neutropenia (9.8%) and thrombocytopenia (8.2%). No patients in either group discontinued treatment or died due to AEs. The incidence of AEs was similar between the two groups, with no significant difference in the incidence of grade 3/4 events (Table SVII). Out of the 114 patients in the GTC + SYS group, 14 patients experienced superficial mucosal ulceration in the gastric body along the lesser curvature proximate to the fundus. This was confirmed by upper abdominal pain and subsequent gastric endoscopy. These patients were managed with symptomatic supportive treatment and showed improvement without any serious complications such as perforation (data not shown).
Discussion
In the present retrospective study, the effectiveness of GTC combined with SYS compared with SYS alone in the treatment of AGCC presenting with dysphagia was assessed. The findings highlight that GTC may reduce the local tumor burden in the cardia more rapidly and efficiently than SYS alone, leading to improved dysphagia symptom remission, enhanced nutritional status, and an improved QoL for patients. Additionally, GTC + SYS was associated with a longer OS. Overall, the results of the present study suggest that GTC + SYS, as a therapeutic intervention, holds promise in effectively managing dysphagia symptoms and improving outcomes in patients with AGCC. However, it is important to note that data on endoscopic evaluation of esophageal-gastric stenosis and gastric cancer size were not included in the present study. The main reason for excluding endoscopic evaluation data was the retrospective nature of this study. The endoscopic report for patients in the present study described the size of the tumor along the lower end of the esophagus and the longitudinal axis of the cardia but did not specify the thickness of the tumor protruding into the lumen. The thickness of the tumor protruding into the gastric cavity directly influences the degree of stenosis. Therefore, the maximum diameter of the cardiac tumor on the CT image of the patient before initial treatment was considered as a quantitative and accurate index, without including the content of the endoscopic report as a matching factor. Additionally, in certain patients with severe stenosis, the endoscope could not pass through the stenosis segment, limiting the information available about the mass and the stenosis segment. This limitation is one reason why the content of the endoscopic report was not used as a matching factor.
Several studies have reported the use of GTC in the treatment of gastric cancer, highlighting its potential benefits in terms of symptom remission and survival outcomes (1,3,6,16). Peng et al (6) evaluated the safety and efficacy of GTC in 42 patients with advanced gastric cancer with obstruction and reported that GTC could be an alternative treatment for advanced gastric cancer with obstruction. Similarly, Li et al (10) reported that GTC could shrink tumors and improve QoL in elderly patients with advanced gastric cancer. Wang et al (5) performed a retrospective analysis of patients with advanced gastric cardiac cancer who underwent GTC and reported a marked improvement in dysphagia symptom remission rates, with 100% of patients experiencing complete or partial relief. However, the study design lacked a control group receiving only systematic chemotherapy, which is the unique advantage of the present study.
One of the crucial decisions in the present study was the selection of 5-FU as the primary treatment for GTC. This choice is supported by existing literature, which has demonstrated the effectiveness of 5-FU in treating advanced gastric cancer (27,28). These agents have shown efficacy in both first-line and adjuvant settings, and their use in GTC can complement SYS by directly targeting the tumor. Additionally, 5-FU has shown favorable tolerability and safety profiles, making it suitable for combination therapy regimens. Furthermore, the selection of 5-FU for GTC is supported by its ability to exert local cytotoxic effects on the tumor whilst minimizing systemic toxicity (37,38). By delivering the chemotherapy directly to the tumor via the gastric arteries, GTC allows for a higher concentration of the drug at the tumor site, potentially enhancing its antitumor effects. The present study demonstrated that patients in the GTC + SYS group experienced a more rapid and significant reduction in cardia tumor diameter at both the 4- and 8-week follow-up compared with those in the SYS alone group. This suggests that the addition of GTC to SYS resulted in a more effective shrinking of localized tumors in the cardia, leading to a more pronounced alleviation of dysphagia symptoms.
Embospheres are biocompatible and biodegradable, and they have been demonstrated to effectively occlude the blood vessels supplying the tumor without causing significant adverse events. Several studies have investigated the safety of using embospheres for embolization in GTC (39,40). An important factor that has been reported to influence the occurrence of postoperative complications in GTC is the size of the embospheres. Smaller diameter microspheres have been associated with a higher risk of complications such as ischemic necrosis, gastric ulcers and gastric perforation. Conversely, larger microspheres have been reported to have a higher embolization efficacy but may also increase the risk of non-target embolization (41). Consistent with these studies, embolization using 300–500 µm-sized embospheres was well tolerated in patients with AGCC in the present study, without any major complications such as gastric perforation, hepatic infarction or embolic events.
Limitations of the present study need to be acknowledged. Firstly, the study was retrospective and performed at a single center, which may limit the generalizability of the findings. To address this, future studies should consider employing a prospective design with randomization in multiple centers. Secondly, the study lacked long-term follow-up data on the dysphagia, nutritional status and QoL of the patients, which could provide more comprehensive insights into the efficacy and safety of GTC combined with SYS in the treatment of AGCC. Further research with longer-term follow-up is required to validate the efficacy of GTC in improving the nutritional status and QoL of patients. Another limitation of the present study is the lack of data on endoscopic evaluation of esophageal gastric stenosis and gastric cancer size. This information could have provided valuable insights into the severity of dysphagia and the extent of disease in patients. Future studies should consider incorporating these parameters to enhance the robustness of the findings.
In conclusion, the findings of the present study suggest that combining GTC with SYS may be a more effective treatment approach for AGCC presenting with dysphagia than SYS alone. The higher dysphagia symptom remission and improved nutritional status and QoL in the combined treatment group indicate that this approach may help improve OS for these patients. However, further studies are needed to confirm these findings and determine the optimal treatment approach for this challenging condition.
Supplementary Material
Supporting Data
Supporting Data
Acknowledgements
Not applicable.
Funding
The present study was funded by the Natural Science Foundation of Shandong Province (grant no. ZR2023QH127).
Availability of data and materials
The data generated in the present study may be requested from the corresponding author.
Authors' contributions
ZL, PS and RX contributed to the study conception and design, as well as material preparation, data collection and analysis. The first draft of the manuscript was written by ZL and all authors commented on previous versions of the manuscript. All authors have read and approved the final manuscript. ZL and PS confirm the authenticity of all the raw data.
Ethics approval and consent to participate
The present study was approved by the Ethics Committee of Shandong Cancer Hospital and Institute (Jinan, China; approval no. SDTHEC 2023004007; approved 4/14/2023). The need for informed consent was waived due to the retrospective nature of the study.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Authors' information
The ORCID of ZL is 0000-0002-8886-4764. The ORCID of PS is 0000-0001-5141-6039.
Glossary
Abbreviations
Abbreviations:
|
GTC |
gastric transcatheter chemoembolization |
|
SYS |
systemic chemotherapy |
|
AGCC |
advanced gastric cardiac cancer |
|
QoL |
quality of life |
|
PSM |
propensity score matching |
|
FACT-G7 |
Functional Assessment of Cancer Therapy-General 7 |
|
PG-SGA |
Patient-Generated Subjective Global Assessment |
|
OS |
overall survival |
|
PFS |
progression-free survival |
|
AE |
adverse effect |
References
|
Chen L, Wang YH, Cheng YQ, Du MZ, Shi J, Fan XS, Zhou XL, Zhang YF, Guo LC, Xu GF, et al: Risk factors of lymph node metastasis in 1620 early gastric carcinoma radical resections in Jiangsu Province in China: A multicenter clinicopathological study. J Dig Dis. 18:556–565. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Hoteya S, Matsui A, Iizuka T, Kikuchi D, Yamada A, Yamashita S, Furuhata T, Domon K, Nakamura M, Mitani T, et al: Comparison of the clinicopathological characteristics and results of endoscopic submucosal dissection for esophagogastric junction and non-junctional cancers. Digestion. 87:29–33. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Tate DJ, Klein A, Sidhu M, Desomer L, Awadie H, Lee EYT, Mahajan H, McLeod D and Bourke MJ: Endoscopic submucosal dissection for suspected early gastric cancer: Absolute versus expanded criteria in a large Western cohort (with video). Gastrointest Endosc. 90:467–479.e4. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Yang J, Li J, Deng Q, Chen Z, He K, Chen Y and Fu Z: Effect of neoadjuvant chemotherapy combined with arterial chemoembolization on short-term clinical outcome of locally advanced gastric cancer. BMC Cancer. 23:2462023. View Article : Google Scholar : PubMed/NCBI | |
|
Wang S, Yin M, Ma Y, Li X, Jin S, Liu T, Zhu M, Liu C and Wu G: Transcatheter arterial chemoembolization with lipiodol for advanced gastric fundus and cardia cancer. Eur J Cancer Prev. 32:305–306. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Peng D, Zhang B, Yuan C, Tong Y and Zhang W: Gastric transcatheter chemoembolization can resolve advanced gastric cancer presenting with obstruction. Front Surg. 9:10040642022. View Article : Google Scholar : PubMed/NCBI | |
|
Sunde B, Ericson J, Kumagai K, Lundell L, Tsai JA, Lindblad M, Rouvelas I, Friesland S, Wang N and Nilsson M: Relief of dysphagia during neoadjuvant treatment for cancer of the esophagus or gastroesophageal junction. Dis Esophagus. 29:442–447. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Cools-Lartigue J, Jones D, Spicer J, Zourikian T, Rousseau M, Eckert E, Alcindor T, Vanhuyse M, Asselah J and Ferri LE: Management of dysphagia in esophageal adenocarcinoma patients undergoing neoadjuvant chemotherapy: Can invasive tube feeding be avoided? Ann Surg Oncol. 22:1858–1865. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Arnold M, Moore SP, Hassler S, Ellison-Loschmann L, Forman D and Bray F: The burden of stomach cancer in indigenous populations: A systematic review and global assessment. Gut. 63:64–71. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Li N, Wang G, Duan G, Li Z, Zheng Y, Wang Z and Li G: Clinical observation of transcatheter arterial chemoembolization in super-aged patients with advanced gastric cancer. Support Care Cancer. 30:1441–1450. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Siddiqui AA, Sarkar A, Beltz S, Lewis J, Loren D, Kowalski T, Fang J, Hilden K and Adler DG: Placement of fully covered self-expandable metal stents in patients with locally advanced esophageal cancer before neoadjuvant therapy. Gastrointest Endosc. 76:44–51. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Di Fiore F, Lecleire S, Pop D, Rigal O, Hamidou H, Paillot B, Ducrotté P, Lerebours E and Michel P: Baseline nutritional status is predictive of response to treatment and survival in patients treated by definitive chemoradiotherapy for a locally advanced esophageal cancer. Am J Gastroenterol. 102:2557–2563. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Lagergren J and Lagergren P: Recent developments in esophageal adenocarcinoma. CA Cancer J Clin. 63:232–248. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Nagaraja V, Cox MR and Eslick GD: Safety and efficacy of esophageal stents preceding or during neoadjuvant chemotherapy for esophageal cancer: A systematic review and meta-analysis. J Gastrointest Oncol. 5:119–126. 2014.PubMed/NCBI | |
|
Tey J, Soon YY, Koh WY, Leong CN, Choo BA, Ho F, Vellayappan B, Lim K and Tham IW: Palliative radiotherapy for gastric cancer: A systematic review and meta-analysis. Oncotarget. 8:25797–25805. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Kato H, Tsutsumi K and Okada H: Recent advancements in stent therapy in patients with malignant gastroduodenal outlet obstruction. Ann Transl Med. 5:1862017. View Article : Google Scholar : PubMed/NCBI | |
|
Hori Y, Naitoh I, Hayashi K, Ban T, Natsume M, Okumura F, Nakazawa T, Takada H, Hirano A, Jinno N, et al: Predictors of stent dysfunction after self-expandable metal stent placement for malignant gastric outlet obstruction: tumor ingrowth in uncovered stents and migration of covered stents. Surg Endosc. 31:4165–4173. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Mariette C, Gronnier C, Duhamel A, Mabrut JY, Bail JP, Carrere N, Lefevre JH, Meunier B, Collet D, Piessen G, et al: Self-expanding covered metallic stent as a bridge to surgery in esophageal cancer: Impact on oncologic outcomes. J Am Coll Surg. 220:287–296. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Lee H, Min BH, Lee JH, Shin CM, Kim Y, Chung H and Lee SH: Covered metallic stents with an anti-migration design vs. uncovered stents for the palliation of malignant gastric outlet obstruction: A multicenter, randomized trial. Am J Gastroenterol. 110:1440–1449. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Sinapi I, Navez B, Hamoir M, Schmitz S, Machiels JP, Deprez PH and Van den Eynde M: Seeding of the percutaneous endoscopic gastrostomy site from head and neck carcinoma: Case report and review of the literature. Head Neck. 35:E209–E212. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Mariette C, De Botton ML and Piessen G: Surgery in esophageal and gastric cancer patients: What is the role for nutrition support in your daily practice? Ann Surg Oncol. 19:2128–2134. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Chen L, Shi H, Che Y, Sun W, Niu X and Lu W: Efficacy of endostatin combined with continuous transcatheter arterial infusion and chemoembolization on gastric cancer with liver metastasis and analysis of prognosis. J BUON. 25:1469–1475. 2020.PubMed/NCBI | |
|
Wu P and Wang J: Efficacy of interventional therapy and effect on inflammatory factors in patients with gastric cancer after chemotherapy. Oncol Lett. 18:1733–1744. 2019.PubMed/NCBI | |
|
Wang J, Shi H, Yang G, Han G, Zhao M, Duan X, Mi L, Han X, Li N, Shi J, 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. 15:5662–5670. 2018.PubMed/NCBI | |
|
Huang SF, Chien TH, Fang WL, Wang F, Tsai CY, Hsu JT, Yeh CN, Chen TC, Wu RC, Chiu CT and Yeh TS: The 8th edition American Joint Committee on gastric cancer pathological staging classification performs well in a population with high proportion of locally advanced disease. Eur J Surg Oncol. 44:1634–1639. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Ogilvie AL, Dronfield MW, Ferguson R and Atkinson M: Palliative intubation of oesophagogastric neoplasms at fibreoptic endoscopy. Gut. 23:1060–1067. 1982. View Article : Google Scholar : PubMed/NCBI | |
|
Xu RH, Wang ZQ, Shen L, Wang W, Lu JW, Dai G, Xu JM, Zhang YQ, Chen XB, Deng YH, et al: S-1 plus oxaliplatin versus S-1 plus cisplatin as first-line treatment for advanced diffuse-type or mixed-type gastric/gastroesophageal junction adenocarcinoma: A randomized, phase 3 trial. J Clinical Oncol. 37:40172019. View Article : Google Scholar | |
|
Luo HY, Xu RH, Wang F, Qiu MZ, Li YH, Li FH, Zhou ZW and Chen XQ: Phase II trial of XELOX as first-line treatment for patients with advanced gastric cancer. Chemotherapy. 56:94–100. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Hawkes E, Okines AF, Papamichael D, Rao S, Ashley S, Charalambous H, Koukouma A, Chau I and Cunningham D: Docetaxel and irinotecan as second-line therapy for advanced oesophagogastric cancer. Eur J Cancer. 47:1146–1151. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, et al: Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 31:4438–4444. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Gabrielson DK, Scaffidi D, Leung E, Stoyanoff L, Robinson J, Nisenbaum R, Brezden-Masley C and Darling PB: Use of an abridged scored Patient-Generated Subjective Global Assessment (abPG-SGA) as a nutritional screening tool for cancer patients in an outpatient setting. Nutr Cancer. 65:234–239. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Yanez B, Pearman T, Lis CG, Beaumont JL and Cella D: The FACT-G7: A rapid version of the functional assessment of cancer therapy-general (FACT-G) for monitoring symptoms and concerns in oncology practice and research. Ann Oncol. 24:1073–1078. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Chiu L, Chiu N, Chow E, Cella D, Beaumont JL, Lam H, Popovic M, Bedard G, Poon M, Wong E, et al: Comparison of three shortened questionnaires for assessment of quality of life in advanced cancer. J Palliat Med. 17:918–923. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Freites-Martinez A, Santana N, Arias-Santiago S and Viera A: Using the common terminology criteria for adverse events (CTCAE-Version 5.0) to evaluate the severity of adverse events of anticancer therapies. Actas Dermosifiliogr (Engl Ed). 112:90–92. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Nishino M, Jagannathan JP, Ramaiya NH and Van den Abbeele AD: Revised RECIST guideline version 1.1: What oncologists want to know and what radiologists need to know. AJR Am J Roentgenol. 195:281–289. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao QY, Luo JC, Su Y, Zhang YJ, Tu GW and Luo Z: Propensity score matching with R: conventional methods and new features. Ann Transl Med. 9:8122021. View Article : Google Scholar : PubMed/NCBI | |
|
Li M, Zhang J, Wang D, Zhong B, Tucker S, Lu C, Cheng J, Cao C, Xu J, Xu J and Pan H: A phase II study of intra-arterial chemotherapy of 5-fluorouracil, cisplatin, and mitomycin C for advanced nonresectable gastric cancer. Anticancer Drugs. 20:941–945. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang CW, Zou SC, Shi D and Zhao DJ: Clinical significance of preoperative regional intra-arterial infusion chemotherapy for advanced gastric cancer. World J Gastroenterol. 10:3070–3072. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Fu Y, Weiss CR, Paudel K, Shin EJ, Kedziorek D, Arepally A, Anders RA and Kraitchman DL: Bariatric arterial embolization: Effect of microsphere size on the suppression of fundal ghrelin expression and weight change in a swine model. Radiology. 289:83–89. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Bai ZB, Qin YL, Deng G, Zhao GF, Zhong BY and Teng GJ: Bariatric embolization of the left gastric arteries for the treatment of obesity: 9-Month data in 5 patients. Obes Surg. 28:907–915. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Weiss CR, Akinwande O, Paudel K, Cheskin LJ, Holly B, Hong K, Fischman AM, Patel RS, Shin EJ, Steele KE, et al: Clinical safety of bariatric arterial embolization: Preliminary results of the BEAT obesity trial. Radiology. 283:598–608. 2017. View Article : Google Scholar : PubMed/NCBI |
