Patients and study design
GC patients who received radical surgery after neoadjuvant chemotherapy from February 2016 to December 2019 at Peking Union Medical College Hospital were screened for inclusion. The inclusion criteria were as follows: (1) Patients were diagnosed as gastric adenocarcinoma by endoscopic biopsy; (2) Patients were evaluated as advanced GC by imaging examination, mainly by contrast-enhanced computed tomography (CT) and endoscopic ultrasonography (EUS). The clinical stages were identified as T2 or T2+ (any N) according to the 8th edition American Joint Committee on Cancer (AJCC) Staging Manual . (3) Patients received neoadjuvant chemotherapy first, and then received radical gastrectomy for cancer. (4) Postoperative pathological evaluation was complete including tumor regression grading. The exclusion criteria were as follows: (1) Patients were evaluated as early GC by imaging examination, mainly by contrast-enhanced CT and EUS. The clinical stages were identified as T1a or T1b (any N) according to the 8th edition AJCC Staging Manual. (2) Patients received radical gastrectomy for cancer directly without neoadjuvant chemotherapy. (3) Patients received chemotherapy or radiotherapy before the diagnosis of GC. (4) Patients were evaluated as late GC and lost the opportunity for radical surgery. Finally, 203 GC patients who received neoadjuvant chemotherapy followed by radical surgery were enrolled in the study. We further retrospectively collected the clinicopathological data of these patients to analyze the factors influencing the effect of neoadjuvant chemotherapy. This retrospective study was reviewed and approved by the Institutional Review Board of Peking Union Medical College Hospital. Each patient provided written informed consent.
Histological type of biopsy
The diagnosis of GC depends on the biopsy of gastroscope. According to the Department of Pathology in our hospital, biopsy pathologies of GC were classified into four types: well-differentiated adenocarcinoma, moderately-differentiated adenocarcinoma, poorly-differentiated adenocarcinoma and signet-ring cell carcinoma. Signet-ring cell carcinoma (SRCC) is a histological type based on more than 50% of the tumor containing abundant intracytoplasmic mucin pushing nucleus to the periphery, according to the WHO classiﬁcation . We regarded well-differentiated adenocarcinoma or moderately-differentiated adenocarcinoma as low grade group and poorly-differentiated adenocarcinoma or signet-ring cell carcinoma as high grade group in our study for comparison.
Neoadjuvant chemotherapy regimen
According to the National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) guidelines, GC patients with clinical T stages T2 or T2+ are supposed to receive neoadjuvant chemotherapy regardless of the N stages [13,14]. In the current study, our included patients’ clinical T stages were T2, T3, T4a or T4b. Oxaliplatin plus S-1 (SOX) regimen was applied as the neoadjuvant chemotherapy regimen: S-1 was administered orally 80 mg/m2/d on day1-14, while oxaliplatin was administered intravenously 130mg/m2 on day 1. The treatment was repeated every 3 weeks. Since there were no clear criteria about how many courses of neoadjuvant chemotherapy should be performed before surgery, we usually performed 2-4 cycles for patients mainly according to their clinical T stages. More courses should be performed when the tumor stage was later. The interval between the last neoadjuvant chemotherapy and surgery was generally one month.
In our study, the body weights of the patients were recorded at two individual time-points. We weighed the patients for the first time before starting neoadjuvant chemotherapy. Before the surgery but after the last neoadjuvant chemotherapy, we weighed the patients again. Patients with body weight declined during the neoadjuvant chemotherapy were classified as weight loss group. Patients with body weight maintained or increased during the neoadjuvant chemotherapy were classified as no weight loss group.
Tumor regression grading
In our study, the pathological response evaluation system of neoadjuvant chemotherapy referred to the College of American Pathologists (CAP) . There are four grades in this tumor regression grading system: CAP 0 represents complete response: no viable cancer cells can be found; CAP 1 represents near complete response: single cells or rare small groups of cancer cells can be found. CAP 2 represents partial response: there is residual tumor with evident tumor regression; CAP 3 represents poor or no response: there is extensive residual tumor with no evident tumor regression (Fig. 1). In our study, CAP 0, CAP 1 and CAP 2 were defined as pathological response, which indicated good effect of neoadjuvant chemotherapy; while CAP 3 was defined as no pathological response, which indicated poor effect of neoadjuvant chemotherapy. To gain the CAP value, the pathological report of each patient was preliminarily written by one junior pathologist and then reviewed by another senior pathologist. Both of them were specialized in gastrointestinal diseases.
Descriptive statistics of categorical variables focused on frequencies and proportions. Medians (ranges) were reported for continuous variables. The chi-square tests and multivariate logistic regression models tested the association between clinicopathological factors and pathological response to neoadjuvant chemotherapy. Receiver operating characteristic (ROC) curve analysis was used to figure out the cut-off value of variables which significantly influenced the effect of neoadjuvant chemotherapy. Statistical tests were performed using the Statistical Package for the Social Sciences (SPSS), version 23 (SPSS Inc., IBM Corp., Armonk, NY, USA). All tests were two sided, with a significance level set at 0.05.