Radiotherapy Improves the Prognosis in Signet Ring Cell Carcinoma and Non-Signet Ring Cell Gastric Adenocarcinoma Patients: A SEER Database Analysis

Research Article

Austin J Pulm Respir Med. 2021; 8(2): 1075.

Radiotherapy Improves the Prognosis in Signet Ring Cell Carcinoma and Non-Signet Ring Cell Gastric Adenocarcinoma Patients: A SEER Database Analysis

Wang C1#, Li H2#, Luo J3#, Liu R4, Ma T5 and Yu L1*

1Departments of Intervention, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China

2Center for Digestive Diseases, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China

3Guangxi Huiren Medical Technology Co., Ltd, Nanning, Guangxi, China

4Departments of Hepatobiliary and Endocrine Surgery, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China

5School of Pharmaceutical Sciences & Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education, Zhengzhou University, Zhengzhou, China

#Contributed equally to this Work

*Corresponding author: Lei Yu, Departments of Intervention, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, China

Received: June 17, 2021; Accepted: July 12, 2021; Published: July 19, 2021

Abstract

Objective: To investigate the effect of radiotherapy on prognosis in gastric signet ring cell carcinoma (SRCC) and gastric non-signet ring cell adenocarcinoma (NSRCC) patients.

Methods: A total of 23,971 patients diagnosed with gastric cancer were collected from 2004 to 2013 by SEER database, including 17,679 NSRCC patients and 6,292 SRCC patients. Patients were divided to two groups and compared according to whether radical gastrectomy was performed on them. After clinic pathological characteristics of the two groups were balanced by the propensity score matching (PSM) method, survival rates of the two groups were then compared.

Results: The Over Survival (OS) and Cancer-Specific Survival (CSS) time of SRCC and NSRCC patients in the radiotherapy groupwere significantly better than those in the non-radiotherapy group. But the clinical and pathological characteristics (gender, age, pathological differentiation degree, T stage, N stage, and metastasis) of the two groups were significantly unbalanced (p<0.001). After 1:1 PSM matching, it was found that radiotherapy had no significant effect on OS and CSS time of NSRCC patients, but radiotherapy could significantly improve OS and CSS time of SRCC patients.

Conclusion: SRCC patients are more sensitive to radiotherapy than NSRCC patients. Although the prognosis of SRCC is far less than that of NSRCC patients, the treatment strategy of surgical resection of primary lesions combined with radiotherapy should be recommend for SRCC patients, and whether radiotherapy benefits NSRCC patients still needs to be further studied.

Keywords: Over Survival; NSRCC; Cancer-Specific Survival; gastric cancer; SEER; Radiotherapy

Abbreviations

SRCC: Signet Ring Cell Carcinoma; NSRCC: Non-Signet Ring Cell Adenocarcinoma; PSM: Propensity Score Matching; OS: Over Survival; CSS: Cancer-Specific Survival Time

Introduction

Gastric Cancer (GC) is the fourth - common malignant tumor in the world and is the third leading cause of cancer-related death [1]. Gastric carcinoma has many histological types and classifications, such as Lauren [2], Japanese [3] and Ming classifications [4]. Among of all these classifications, each histological type has its own characteristics. Therefore, different histological types of gastric cancer might determine they have different treatment strategies. Adenocarcinoma is the most common pathological type of gastric cancer and it includes a special type named as Signet Ring Cell Carcinoma gastric carcinoma (SRCC), which accounts for 15.1-28.2 % of gastric cancer [5]. SRCC was once thought to be a histological type characterized with poor prognosis and high possibility of infiltrating the stomach [6]. Therefore, SRCC has been widely reported as an independent predictor of poor prognosis especially in Western countries. The majority of these tumors are diagnosed at an advanced stage, with higher lymph node metastasis rates, higher incidence of peritoneal cancer and lower chemotherapy sensitivity [7]. SRCC is considered a unique pathological entity in the pathological types of gastric cancer. Some studies have shown that SRCC is always associated with the rejuvenation, higher stage of differentiation and lower survival rate compared to gastric adenocarcinoma [8].

In recent years, treatment levels in gastric cancer patients have been rapidly improved especially for local advanced gastric cancers. The United States NCCN Guide or the European ESMO Guidelines recommended perioperative radiotherapy and chemotherapy treatment model, so the therapeutic effect of local advanced gastric cancer has been improved obviously. With the development and widespread popularization of D2 surgery, the indications of radiotherapy and the scope of radiotherapy have become the scholars’ focus [9]. Radiotherapy can be used for early shrinkage of tumors before surgery and can helpimprove the likelihood of therapeutic resection [10]. In gastric cancer patients with distant metastasis, it is recommended that some treatment methods such as irradiating the primary focus or metastatic cooker to reduce the obstruction, compression, bleeding or pain should be carried out in order to improve the life quality of patients. A large amount of samples data show that adjuvant radiotherapy can effectively improve the survival and prognosis of gastric adenocarcinoma patients [11]. In clinical practices, it could be found that the effects of radiotherapy in Non- Signet Rings Cell Gastric Adenocarcinoma (NSRCC) and SRCC patients are different. A retrospective study on two large samples found that in phase II and III, rectal ring cell carcinoma patients undergoing radiotherapy had a statistically worse CSS time than rectal non-ring cell carcinoma patients [12], indicating that in SRCC and NSRCC patients there might also be differences in the sensitivity to radiotherapy. In order to explore the effect of radiotherapy on gastric SRCC and NSRCC patients, we selected and studied the patients with gastric cancer through SEER database and divided them into SRCC and NSRCC patients according to the pathological types of gastric cancer. By comparing the effect of radiotherapy on the survival and prognosis of SRCC and NSRCC patients, we can provide a basis for clinical rational application of radiotherapy.

Materials and Methods

Patient samples collection

In this study, we investigated the clinical value of radiotherapy for SRCC and NSRCC patients using SEER database (http://seer. cancer.gov/about/overview.html), which is maintained by the National Cancer Institute and includes 18 population-based cancer registries with information of cancer morbidity and mortality in the United States [13]. This version of the SEER database we used was released in April 2014 (submitted in November 2013). All TNM classifications are defined according to the criteria described in the Cancer staging manual of the United States Joint Commission on Cancer (AJCC) (6th edition 2004, Paras. I, II, III and IV). Histological classifications were divided into well differentiation (G1), moderately differentiation (G2), poor differentiation (G3) and un-differentiation (G4) groups. CSS time was calculated from the diagnosis beginning date to the specific death date of tumor patients or the end date of follow-up. SEER database includes the diagnostic information such as age, sex, race, years of diagnosis, numbers of tumors, tumors size, TNM staging, histological type, histological classification, surgical and radiotherapy status for each patient. Tumors are classified according to the International Classification of Tumor Diseases (ICD-O). We obtained 150,265 patients who were encoded as the primary site of “stomach”, excluding patients without pathological diagnosis (n=7432), patients without pathological staging (n=40193), patients with pathology as simple parasites (n=167), patients with pathological diagnosis of cancer only (n=2656), patients with pathological diagnosis of neuroendocrine tumor (n=1604), patients lack of TMN staging (n=74242). Finally, 23,971 patients was included in our study. Of these, there are 17,679 NSRCC patients and 6,292 SRCC patients. The groupcomparison was carried out according to whether radical resection was performed on these patients.

Ethics Statement

This study is conducted based on data from the public SEER database, which does not contain any identifiers. Due to the retrospective nature of the study, the patient’s informed consent is not required. The analysis does not involve interactions with human subjects or use their personally identifiable information. Prior to the analysis, patient records/information are anonymous and deidentified, and these methods are in accordance with the guidelines of the Ethics Committee of the People’s Hospital of Guangxi Zhuang Autonomous Region. This study protocol was approved by the Ethics Committee of the People’s Hospital of Guangxi Zhuang Autonomous Region.

Statistical analysis

Compare classification variables between two treatment groups using Pearson’s Χ2 for statistical analysis, while discontinuous variables use ANOVA. The survival curve is calculated by Kaplan- Meier method and the Log-rank test is compared. When the survival curve is intersected and p<0.05, the intersection is obtained by landmark. Discovery and the segmented statistical analysis is carried out according to the pvalue of each segment [14]. Cox proportional risk regression model is used to identify the risk factors that affects CSS and OS time independently in gastric SRCC and NSRCC patients. The effect of radiotherapy on the survival prognosis of SRCC and NSRCC is compared by tendency score matching analysis (propensity score-matched analyses, PSM). The nearest neighbor matching method is used to complete the one-to-one match (age, sex, race, years of diagnosis, numbers of tumors, tumors size, TNM staging, histological type, histological classification and other variables) without replacement. Caliper width is 0.05 times the standard deviation of the tendentious score logit, and it is estimated that the co-construction variable deviation of >99% can be eliminated [15].

Results

Patient characteristics

A total of 23971 GC patients were included in this study, most of them were diagnosed with NSRCC (n=17679, 73.75%). There are more people diagnosed at age <65 years in the SRCC groupthan in the NSRCC group(54.52% vs. 37.89%, p< 0.001). The occurrence frequency of low differentiation tumors in SRCC patients was also higher than that in NSRCC patients (97.35% vs. 59.66%, p<0.001). And the frequency of lymph node metastasis in SRCC patients was higher than that in NSRCC patients (57.54% vs. 52.39%, p<0.001). Moreover, the frequency of distant metastasis in SRCC patients was higher than that in NSRCC patients (45.01% vs. 26.39%, p<0.001). In addition, the SRCC groupcontained more female patients (48.90% vs. 31.01%, p<0.001) (Table 1-4).