Nie SF, Wang CY, Li L, Yang C, Zhu ZM, Fei JD. Tumor recurrence and survival prognosis in patients with advanced gastric cancer after radical resection with radiotherapy and chemotherapy. World J Gastrointest Surg 2024; 16(6): 1660-1669 [DOI: 10.4240/wjgs.v16.i6.1660]
Corresponding Author of This Article
Jian-Dong Fei, Doctor, Department of General Surgery, The First Affiliated Hospital of Hebei North University, No. 12 Changqing Road, Qiaoxi District, Zhangjiakou 75000, Hebei Province, China. 20669645@qq.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Shuang-Fa Nie, Chen-Yang Wang, Lei Li, Cheng Yang, Jian-Dong Fei, Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 75000, Hebei Province, China
Zi-Ming Zhu, Department of Gastrointestinal Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, China
Author contributions: Nie SF wrote the manuscript; Wang CY, Li L, Yang C and Zhu ZM collected the data; and Fei JD guided the study. All authors reviewed, edited, and approved the final manuscript and revised it critically for important intellectual content, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.
Supported bythe Hebei Provincial Department of Finance and the Hebei Provincial Health Commission, No. ZF2023242.
Institutional review board statement: This study has been approved by the Medical Research Ethics Committee of our hospital.
Informed consent statement: Informed consent of patients and their families has been obtained for this study, and informed consent has been signed.
Conflict-of-interest statement: All the authors declare no conflict of interest.
Data sharing statement: Statistical analysis plan, informed consent form, and clinical study report will also be shared if requested. Emails could be sent to the address below to obtain the shared data: 20669645@qq.com.
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: Jian-Dong Fei, Doctor, Department of General Surgery, The First Affiliated Hospital of Hebei North University, No. 12 Changqing Road, Qiaoxi District, Zhangjiakou 75000, Hebei Province, China. 20669645@qq.com
Received: February 7, 2024 Revised: April 24, 2024 Accepted: May 9, 2024 Published online: June 27, 2024 Processing time: 143 Days and 23.6 Hours
Abstract
BACKGROUND
Advanced gastric cancer is a common malignancy that is often diagnosed at an advanced stage and is still at risk of recurrence after radical surgical treatment. Chemoradiotherapy, as one of the important treatment methods for gastric cancer, is of great significance for improving the survival rate of patients. However, the tumor recurrence and survival prognosis of gastric cancer patients after radiotherapy and chemotherapy are still uncertain.
AIM
To analyze the tumor recurrence after radical radiotherapy and chemotherapy for advanced gastric cancer and provide more in-depth guidance for clinicians.
METHODS
A retrospective analysis was performed on 171 patients with gastric cancer who received postoperative adjuvant radiotherapy and chemotherapy in our hospital from 2021 to 2023. The Kaplan-Meier method was used to calculate the recurrence rate and survival rate; the log-rank method was used to analyze the single-factor prognosis; and the Cox model was used to analyze the prognosis associated with multiple factors.
RESULTS
The median follow-up time of the whole group was 63 months, and the follow-up rate was 93.6%. Stage II and III patients accounted for 31.0% and 66.7%, respectively. The incidences of Grade 3 and above acute gastrointestinal reactions and hematological adverse reactions were 8.8% and 9.9%, respectively. A total of 166 patients completed the entire chemoradiotherapy regimen, during which no adverse reaction-related deaths occurred. In terms of the recurrence pattern, 17 patients had local recurrence, 29 patients had distant metastasis, and 12 patients had peritoneal implantation metastasis. The 1-year, 3-year, and 5-year overall survival (OS) rates were 83.7%, 66.3%, and 60.0%, respectively. The 1-year, 3-year, and 5-year disease-free survival rates were 75.5%, 62.7%, and 56.5%, respectively. Multivariate analysis revealed that T stage, peripheral nerve invasion, and the lymph node metastasis rate (LNR) were independent prognostic factors for OS.
CONCLUSION
Postoperative intensity-modulated radiotherapy combined with chemotherapy for gastric cancer treatment is well tolerated and has acceptable adverse effects, which is beneficial for local tumor control and can improve the long-term survival of patients. The LNR was an independent prognostic factor for OS. For patients with a high risk of local recurrence, postoperative adjuvant chemoradiation should be considered.
Core Tip: This study analyzed the tumor recurrence and survival prognosis of patients with advanced gastric cancer after radical radiotherapy and chemotherapy, and explored the related influencing factors. By collecting clinical data of patients for analysis, we will reveal the actual situation of postoperative recurrence rate and survival rate, and further explore the possible influencing factors, so as to provide scientific basis for clinical practice. The innovation of this study lies in the in-depth analysis of the recurrence pattern and prognostic factors of gastric cancer patients after radical radiotherapy and chemotherapy, which provides a new idea for the formulation of individualized treatment plan, and is expected to provide an important reference for the management and prognosis assessment of patients with advanced gastric cancer.
Citation: Nie SF, Wang CY, Li L, Yang C, Zhu ZM, Fei JD. Tumor recurrence and survival prognosis in patients with advanced gastric cancer after radical resection with radiotherapy and chemotherapy. World J Gastrointest Surg 2024; 16(6): 1660-1669
Globally, the incidence and mortality of gastric cancer rank fifth and third, respectively, among all tumor diseases[1-3]. Between 2013 and 2023, the overall survival (OS) of gastric cancer patients in China significantly improved[4]. However, the prognosis of patients who have received radical gastrectomy and postoperative adjuvant chemotherapy is still not ideal, especially within 2 years after surgery, when more than 60% of patients relapse[5]. Although the clinical significance of adjuvant chemoradiation (CRT) after D0 or D1 Lymph node dissection has not been confirmed by large randomized clinical trials, with the release of the INT-0116 study results, postoperative adjuvant CRT is still the standard treatment for these gastric cancer patients[6]. At present, there is no global consensus on the optimal treatment for locally advanced gastric cancer[7-10].
Current guidelines in China recommend D2 radical surgery as the standard procedure for locally advanced gastric cancer. However, even in some of the best gastric cancer diagnosis and treatment centers in China, nearly half of the patients with advanced gastric cancer do not receive a standard D2 radical operation[11]. In other hospitals, especially primary hospitals, the proportion of patients receiving standard D2 radical surgery may be lower. Radiotherapy is an effective local treatment and can be used as a supplement to surgical treatment, so adjuvant chemoradiotherapy is crucial for the treatment of gastric cancer[12]. At present, the clinical evidence of adjuvant CRT after D2 radical surgery, especially for patients with different relapse patterns, is insufficient.
Therefore, this study reviewed and analyzed the recurrence pattern and related influencing factors of patients with locally advanced gastric cancer in our hospital, providing a new clinical basis for the choice of treatment for these patients.
MATERIALS AND METHODS
Entry criteria
(1) Gastric cancer patients who received postoperative CRT treatment in Zhongshan Hospital Affiliated to Fudan University from September 2021 to September 2023; (2) Receiving R0 resection of gastric cancer and > D 1 lymph node dissection (according to the definition of lymph node dissection in the 3rd edition of Japanese gastric cancer stage); (3) No distant metastasis or peritoneal implantation metastasis; (4) Regular follow-up after treatment; and (5) Complete clinical data.
Treatment plan
All patients underwent radical resection. A total of 44.4% (76 patients) underwent distal subtotal gastrectomy, 15.2% (26 patients) underwent proximal subtotal gastrectomy, 33.9% (58 patients) underwent total gastrectomy, and 6.5% (11 patients) underwent combined organ resection. Patients received intensity-modulated radiotherapy (IMRT) at a median dose of 45 Gy (41.1–50.4 Gy) or 1.8 Gy/time once a day. The range of irradiation included the tumor bed, anastomosis, duodenal stump, and a specific lymph node drainage area. Radiation was not considered in the tumor bed area of patients with PT-1 and PT-2M0 gastric cancer. The delineation range of the lymph node drainage area (including residual and perigastric lymph nodes, peritruncus lymph nodes, hilar splenic lymph nodes, hepatoduodenal lymph nodes or hilar hepatic lymph nodes, pancreaticoduodenal lymph nodes, and paraaortic lymph nodes) depends on the tumor site. The median duration of radiotherapy was 35 days (30–45 d).
All enrolled patients received adjuvant chemotherapy before and after radiotherapy. The chemotherapy regimens used were as follows: capecitabine + oxaliplatin (81 patients, 47.4%), Ticeo + oxaliplatin (29 patients, 17.0%), epirubicin + oxaliplatin + fluorouracil (14 patients, 8.2%), oxaliplatin + fluorouracil + calcium folinate (15 patients, 8.8%), and other regimens. Adjuvant chemotherapy was administered from 3 to 8 wk after surgery, and simultaneous chemoradiotherapy was administered from 8 to 18 wk after surgery.
Follow-up information
The median follow-up period was 63 months (3–144 months) as of September 30, 2023. The first patient underwent radical gastrectomy in July 2021, and the last patient was treated in April 2023. During follow-up, 11 of 171 patients (6.4%) were lost to follow-up. All patients who completed adjuvant CRT therapy were regularly followed up, including medical history, physical examination, routine blood, biochemical and electrolyte tests, tumor marker analysis, chest, abdominal, and pelvic computed tomography (positron emission tomography-computed tomography if necessary), and endoscopy. All patients were followed up every 3 months for the first 2 years after completion of treatment, every 6 months for patients 2 to 5 years old, and annually for patients over 5 years old.
Recurrence pattern definition
Local recurrence refers to the recurrence of anastomosis, duodenal stump, tumor bed, or stomach stump. Regional recurrence refers to recurrence in areas such as the perigastric, hilar, peripancreatic, and paraaortic lymph node drainages. Peritoneal metastasis refers to peritoneal, colorectal, and ovarian metastases. Distant metastasis refers to metastasis to distant organs such as the liver, bone, or lungs or to lymph nodes other than regional lymph nodes.
All patients' medical records were retrospectively analyzed, and all relapses or metastases were recorded. If two or more sites recurred or metastasized at the same time, they were counted separately. The OS period was defined as the time from surgery to death, including tumor-specific death or death from any other cause. Disease-free survival (DFS) was defined as the time from surgery to initial progression or death. Local relapse-free survival (LFFS), regional relapse-free survival (RFFS), peritoneal metastasis-free survival (PFFS), and distant metastasis-free survival (DFFS) refer to the time from surgery to local recurrence, regional recurrence, peritoneal metastasis, and distant metastasis, respectively.
Statistical analysis
The Kaplan-Meier method in SPSS 25.0 software was used to calculate the OS rate, DFS rate, LFFS rate, RFFS rate, PFFS rate, DFFS rate, and locoregional failure-free survival (LRFFS) rate curves. Factors including age, sex, hospital of surgery, mode of surgery, primary tumor location, pathological type, Lauren classification, number of lymph nodes dissected, lymph node metastasis rate (LNR), postoperative T stage, postoperative N stage, postoperative TNM stage, lymphatic vessel invasion (LVI), peripheral nerve invasion (PNI), and concurrent chemical and adjuvant chemotherapy were analyzed. The Kaplan-Meier method was used to analyze the relationships between the prognosis and survival curves of different LNR subgroups, and a log-rank test was performed to compare the differences between groups. Multivariate prognosis analysis was performed by the Cox regression model, and P < 0.05 was considered to indicate statistical significance.
RESULTS
General clinical data analysis
A total of 171 patients were enrolled, including 124 males and 47 females aged 27–76 years (median 60 years). The primary lesions were located in the upper 1/3 of the stomach, the middle 1/3 of the stomach, the lower 1/3 of the stomach, and the whole stomach in 43 patients (25.2%), 37 patients (21.6%), 76 patients (44.4%), and 15 patients (8.8%), respectively. Nearly half (42.7%) of the enrolled patients had N stage N3 disease, 5-56 lymph nodes (median 19), and 0-47 positive lymph nodes (median 5). Patients with stages IIA, IIB, IIIA, IIIB, and IIIc accounted for 17.5%, 13.5%, 24.6%, 26.3%, and 15.8%, respectively, of the patients, as shown in Table 1.
Table 1 Clinical data of 171 gastric cancer patients.
Project
n (%)
Project
n (%)
Age (yr)
T staging
≤ 40
6 (3.5)
T1
8 (4.7)
41-65
126 (73.7)
T2
21 (12.3)
≥ 66
39 (22.8)
T3
86 (50.3)
Gender
T4a
31 (18.1)
Male
124 (72.5)
T4b
25 (14.6)
Female
47 (27.5)
N stages
Surgical hospital
N0
24 (14.0)
Court
102 (59.6)
N1
33 (19.3)
Outer courtyard
69 (40.4)
N2
41 (24.0)
Operation
N3a
58 (33.9)
Subtotal proximal gastrectomy
26 (15.2)
N3b
15 (8.8)
Subtotal distal gastrectomy
76 (44.4)
Clinical stages
Total gastrectomy
58 (33.9)
IB
4 (2.3)
Gastrectomy and other organ
11 (6.5)
IIA
30 (17.5)
Primary lesion site
IIB
23 (13.5)
1/3 upper stomach
37 (21.6)
IIIA
42 (24.6)
1/3 stomach
76 (44.4)
IIIB
45 (26.3)
1/3 subgastric
15 (8.8)
IIIC
27 (15.8)
Whole stomach
15 (8.8)
Lymphatic invasion
Pathological type
Negative
82 (48.0)
Medium to high differentiation
58 (33.9)
Positive
89 (52.0)
Poorly differentiated
91 (53.2)
Peripheral nerve invasion
Mucinous adenocarcinoma
9 (5.3)
Negative
91 (53.2)
Signet-ring cell carcinoma
12 (7.0)
Positive
80 (46.8)
Neuroendocrine degeneration
1 (0.6)
Synchronous chemotherapy
Lauren typing
Capecitabine
95 (55.6)
Intestinal
69 (40.4)
Tegafur
25 (14.6)
Diffuse
95 (55.5)
Other
51 (29.8)
Mixed unclassified
7 (4.1)
Adjuvant chemotherapy regimen
Number of lymph nodes cleaned
XELOX
81 (47.4)
< 15
57 (33.3)
SOX
29 (17.0)
≥ 15
114 (66.7)
FOLFOX
15 (8.8)
Positive lymph nodes
EOF
14 (8.2)
LNR ≤ 0.3
89 (52.0)
FLOT
5 (2.9)
0.3 < LNR ≤ 0.7
58 (33.9)
other
27 (15.7)
LNR > 0.7
24 (14.1)
Age [yr, median (range)]
60 (27-76)
Number of lymph nodes cleaned [n, median (Range)]
19 (5-56)
Number of positive lymph nodes [n, median (Range)]
5 (0-47)
Survival and prognosis analysis
As of September 2020, 60 patients (35.1%) had died, and 47 patients (27.5%) experienced recurrence or metastasis. As shown in Figure 1A, the 1-year, 3-year, and 5-year OS rates and 1-year, 3-year, and 5-year DFS rates of the enrolled patients were 83.7%, 66.3%, 60.0%, 75.5%, 62.7%, and 56.5%, respectively. Single-factor analysis revealed that the Lauren classification, LNR, PNI, T stage, and N stage were factors affecting OS. The LNR, T stage, and N stage are factors affecting DFS. Multifactor analysis revealed that T stage, the LNR, and the PNI were independent prognostic factors affecting OS (Table 2). As shown in Figure 1B, the 5-year survival rates of the different LNR subgroups were 75.6%, 54.8%, and 26.2%, respectively. T stage was an independent prognostic factor for DFS (Table 3).
Figure 1 Kaplan-Meier curves in patients with gastric cancer.
A: Overall survival (OS) and disease-free survival; B: OS between different lymph node metastasis rate subgroups; C: Local relapse-free survival, regional relapse-free survival, locoregional failure-free survival, peritoneal metastasis-free survival and distant metastasis-free survival. OS: Overall survival; DFS: Disease-free survival; LNR: Lymph node metastasis rate; LFFS: Local relapse-free survival; RFFS: Regional relapse-free survival; LRFFS: Locoregional failure-free survival; PFFS: Peritoneal metastasis-free survival; DFFS: Distant metastasis-free survival.
Table 2 Multivariate analysis of prognostic factors related to overall survival rate.
Factors
Univariate analysis
Multivariate analysis
Hazard ratio
95%CI
P value
Age
0.092
1.659
0.977-2.815
0.061
Pathological type
0.063
0.826
0.263-2.593
0.743
Lauren typing
0.037
0.488
0.054-4.449
0.525
LNR
< 0.001
2.174
1.115-3.862
0.015
T stage
0.005
1.636
1.108-2.415
0.013
N stage
< 0.001
1.135
0.774-1.665
0.516
PNI
0.008
1.719
1.006-2.937
0.047
Table 3 Multivariate analysis of prognostic factors related to disease-free survival rate.
Factors
Univariate analysis
Multivariate analysis
Hazard ratio
95%CI
P value
Pathological type
0.096
0.850
0.276-2.618
0.778
Lauren typing
0.053
0.521
0.058-4.705
0.561
LNR
< 0.001
1.182
0.792-1.763
0.413
T stage
0.002
1.573
1.102-2.245
0.013
N stage
< 0.001
1.310
0.918-1.869
0.136
PNI
0.054
1.395
0.853-2.282
0.185
Analysis of recurrence
During follow-up, 47 patients (27.5%) had a total of 60 recurrences and metastases. Local recurrence, regional recurrence, abdominal metastasis, and distant metastasis accounted for 2.9%, 8.2%, 7.0%, and 17.0%, respectively. In terms of the recurrence mode (Table 4), 34 patients (72.3%) had a single recurrence mode, and 13 patients (27.7%) had a double recurrence mode. Distant metastases were the most common single-recurrence-mode metastases. In contrast, abdominal metastasis, regional recurrence, and local recurrence were less common. Four patients developed regional recurrence plus distant metastasis, a combination that was most common in the dual recurrence pattern group. As shown in Tables 5 and 6, in patients with recurrence and metastasis, the proportions of liver, bone, lung, brain, spleen, and adrenal gland metastases were 29.8%, 23.4%, 21.3%, 8.5%, 2.1%, and 2.1%, respectively.
Table 4 The proportion of different recurrence patterns in 47 recurrent gastric cancer patients out of 171 cases.
Recurrence pattern
Cases
Proportion (%)
Recurrence pattern
Cases
Proportion (%)
Single mode
34
72.3
Dual mode
13
27.7
Local recurrence
1
2.1
Local recurrence + abdominal metastasis
2
4.3
Regional recurrence
5
10.6
Local recurrence + regional recurrence
2
4.3
Abdominal metastasis
5
10.6
Regional recurrence + abdominal metastasis
3
6.4
Distant metastasis
23
48.9
Regional recurrence + distant metastasis
4
8.5
Multi mode
0
0
Abdominal metastasis + distant metastasis
2
4.3
Table 5 Recurrence patterns in 47 out of 171 gastric cancer patients with relapses of proportion a.
Recurrence pattern
Cases
Proportion a (%)
Recurrence pattern
Cases
Proportion a (%)
Local recurrence
5
10.6
Distant metastasis
29
61.7
Gastric stump
1
2.1
Liver
14
29.8
Anastomotic opening
4
8.5
Bone
11
23.4
Regional recurrence
14
29.8
Lungs
10
21.3
Abdominal metastasis
12
25.5
Brain
4
8.5
Peritoneum
9
19.1
Spleen
1
2.1
Ovary
2
4.3
Adrenal gland
1
2.1
Colorectal
1
2.1
Non regional Lymph nodes
1
2.1
Table 6 Recurrence patterns in 47 out of 171 gastric cancer patients with relapses of proportion b.
Recurrence pattern
Cases
Proportion b (%)
Recurrence pattern
Cases
Proportion b (%)
Local recurrence
5
2.9
Abdominal metastasis
12
7.0
Regional recurrence
14
8.2
Distant metastasis
29
17.0
Survival analysis of each recurrence mode
As shown in Figure 1C, the 3-year LFFS rate, PFFS rate, RFFS rate, LRFFS rate, and DFFS rate were 95.3%, 91.2%, 90.7%, 87.7%, and 82.0%, respectively. The 3-year survival of patients with each recurrence mode was as follows: 2 of 5 patients with local recurrence died; of the 14 patients with regional recurrence, 6 died. Of the 12 patients with abdominal metastasis, nine died. Of the 29 patients with distant metastasis, 23 died. Univariate analysis revealed that N stage was the most influential factor for all failure modes except abdominal metastasis, while T stage only affected LRFFS. LVI is the factor that affects PFFS, while the LNR is the factor that affects DFFS. Multifactor analysis revealed that T stage was an independent prognostic factor for LRFFS (P = 0.006) and PFFS (P = 0.003), as shown in Tables 7 and 8. No independent prognostic factors for DFFS were found in this study.
Table 7 Analysis of prognostic factors related to local recurrence.
Factors
Univariate analysis
Multivariate analysis
Hazard ratio
95%CI
P value
Gender
0.210
0.961
0.561-1.648
0.886
Pathological type
0.109
0.547
0.216-1.387
0.204
LNR
0.079
1.253
0.850-1.846
0.255
T stage
0.040
1.643
1.155-2.337
0.006
N stage
0.020
1.271
0.902-1.790
0.171
LVI
0.060
1.211
0.742-1.975
0.443
Table 8 Analysis of prognostic factors related to abdominal metastasis.
Factors
Univariate analysis
Multivariate analysis
Hazard ratio
95%CI
P value
Pathological type
0.149
0.462
0.189-1.132
0.091
Cleaning lymph nodes
0.161
0.923
0.550-1.551
0.763
T stage
0.195
1.700
1.199-2.410
0.003
LVI
0.012
1.221
0.745-2.002
0.428
Adverse reaction analysis
Of all the patients, only five did not complete radiotherapy. All patients received concurrent chemotherapy, and 26 of them experienced dose reduction or a longer interval between treatments. The incidences of Grade 3 and above acute gastrointestinal reactions and hematological adverse reactions were 8.8% and 9.9%, respectively.
DISCUSSION
Although the incidence and mortality of gastric cancer have decreased in recent decades, the number of new cases per year is still very high due to population aging[13]. There are few specific clinical manifestations in patients with early gastric cancer, and with the exception of South Korea and Japan, gastric cancer screening is not routinely performed in other countries worldwide, fewer than half of patients receive D2 radical surgery, even in several good gastric cancer diagnosis and treatment centers[14-16]. Multiple studies have shown that even if the standard R0/D2 radical surgery requirements are met, the local recurrence rate after surgery can still reach 20% to 40%[17]. Radiotherapy is an effective local treatment that can compensate for incomplete surgical lymph node dissection to a certain extent. Therefore, adjuvant radiotherapy for gastric cancer is highly important for improving the local control rate of tumors and the long-term survival rate of patients.
The American INT-0116 study used adjuvant CRT as the standard treatment for high-risk gastric cancer patients undergoing radical resection[6]. However, there are some difficulties and challenges in adopting this scheme in China. One of the greatest problems we had was incomplete lymph node dissection; only 10% of patients met the criteria for D2 dissection. Another factor was the high rate of adverse reactions; 17% of patients in the INT-0116 study stopped treatment because of adverse reactions to adjuvant therapy. Since 2010, the guidelines for the diagnosis and treatment of gastric cancer issued by the National Health Commission have been updated to the third edition, which emphasizes the need for adjuvant radiotherapy and chemotherapy for high-risk locally advanced gastric cancer patients with one of the following conditions: patients who underwent R1 or R2 resection; patients who underwent D0 or D1 resection with pathological stage T 3-4 and/or N+ without distant metastasis; and patients who underwent R0 or D2 resection with pathological stage T 3-4 or more regional lymph node metastases. Because standard D2 radical surgery is uncommon in Chinese patients with stomach cancer, the goal of this retrospective study was to determine how well and how badly adjuvant CRT works after surgery, how often treatment fails, and how often clinical data related to recurrence patterns are available for patients who underwent > D1 resection and adjuvant CRT. At the same time, patients enrolled in this study were treated from 2008 to 2020, with a span of 12 years. To avoid heterogeneity caused by improvements in the scope and number of lymph nodes removed by radical gastrectomy and advancements in radiotherapy technology, patients who underwent gastric cancer D1 resection, conventional radiotherapy, or 3D-CRT were excluded from this study. Patients with gastric cancer > D1 who underwent IMRT after resection were selected for analysis. First, the 3-year OS and DFS rates of this study were 66.3% and 62.7%, respectively, and the 5-year OS and DFS rates were 60.0% and 56.5%, respectively, which were more favorable than the results of the INT-0116 study. However, this approach is slightly inferior to that used by artists[6,9,18]. This may be due to the earlier stage of tumors in the Korean ARTIST study and more aggressive lymph node dissection. In the ARTIST study, only 40% of patients with stage III disease were enrolled, while in this study, the proportion of patients with stage III disease was as high as 66.7%, which may be related to the lack of large-scale gastric cancer screening programs in China. Second, the study revealed that both local (2.9%) and regional (8.1%) recurrence rates were low. These rates were much lower than those found in previous clinical studies from Western countries and were similar to those found in South Korea. This finding showed that chemoradiotherapy after surgery may help control tumors locally and regionally. In this study, distant metastasis was the most common failure mode. In addition, the local recurrence rate in China is 32.4%, and previous studies have shown that the incidence of local recurrence in patients after adjuvant chemotherapy is 7.8%-29.3%[5,18,19].
Traditional postoperative adjuvant chemotherapy and perioperative chemotherapy for gastric cancer have a high adverse reaction rate and a low completion rate. The previous Korean CLASSIC study, Japanese ACTS GC study, European FNCLCC/FFCD study, and MAGIC study had grade 3–4 adverse reaction rates as high as 56.0%, 20.7%, 40.0%, and 38.0%, respectively. However, the completion rates were only 67.0%, 65.8%, 49.5%, and 23.0%, respectively[20-23]. At present, a number of studies on adjuvant therapy for gastric cancer have shown that combining chemotherapy with radiotherapy can reduce the number of cycles of chemotherapy and the total dose of chemotherapy drugs to a certain extent and alleviate related adverse reactions, thus improving the completion rate of postoperative adjuvant therapy[24]. In the ARTIST study, patients with gastric cancer after radical surgery were randomly assigned to the chemotherapy alone group or the combined chemoradiotherapy group. The results showed that the completion rate of the combined chemoradiotherapy group reached 81.7%, which was greater than that of the chemotherapy alone group (75.4%). At the same time, the adverse reaction rate of the combined group was lower. Compared with the INT-0116 study and the ARTIST study, this study revealed a lower incidence of grade 3–4 gastrointestinal adverse reactions, which may be partly related to the application of IMRT[25]. Studies have confirmed that IMRT is superior to 2D or 3D radiotherapy because it provides a more accurate dose distribution for the planned target area and reduces the risk of radiation-related adverse reactions[26-28]. Using IMRT technology, under the premise of effectively controlling the tumor, the dose of exposure to the surrounding normal tissue can also be reduced.
CONCLUSION
Postoperative IMRT and chemotherapy given at the same time are well tolerated and have acceptable side effects in the Chinese population. This approach helps control local tumors and improves long-term survival for people with locally advanced gastric cancer > D1 after resection. The LNR can be used as an important prognostic indicator for patients with gastric cancer > D1 undergoing adjuvant chemoradiotherapy after resection.
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 A
Creativity or Innovation: Grade A
Scientific Significance: Grade A
P-Reviewer: Stan FG, Romania S-Editor: Lin C L-Editor: A P-Editor: Che XX
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