The 2014 American Society of Clinical Oncology (ASCO) Gastrointestinal Tract Oncology Symposium (2014 ASCO GI) was held on January 16 in San Francisco, CA, USA. The 3-day conference program featured presentations and discussions by experts and scholars from around the world on a variety of GI-related research. In this conference, more than 100 studies on gastric cancer were presented, covering prevention, screening, diagnosis, translational research and multidisciplinary collaborative treatment of gastric cancer. In this paper, we will summarize and interpret the gastric cancer-related studies in this conference and share the latest progress of international research on gastric cancer with our domestic colleagues. Eun Ran Kim reviewed the long-term follow-up results of patients after endoscopic resection for early gastric cancer and proposed a follow-up strategy for patients with early gastric cancer after endoscopic resection based on the incidence and pattern of local recurrence, heterochronic recurrence and extragastric recurrence. A total of 1,803 early gastric cancer patients with 1,855 lesions were reviewed in this study, of which 1,406 lesions met the absolute indication sign for endoscopic resection of early gastric cancer and 446 lesions met the extended indication sign. The incidence of local recurrence was 0.35% in the absolute indication group and 0.22% in the extended indication group, with a median recurrence time of 13.5 months. 3.1% of the patients had heterochronic recurrence of early gastric cancer at follow-up, with a median recurrence time of 27.3 months, and there were significant differences between patients with and without heterochronic recurrence in terms of gender and histological type of lesions, while other The differences in clinicopathological characteristics did not reach statistical differences. In addition, there was one extra-gastric recurrence in each of the absolute and expanded indications with an interval of 62 and 48 months, respectively, and no evidence of tumor recurrence was found at the endoscopic lesion excision scar in either of these patients. The long-term follow-up results of this study showed that expanded indications for endoscopic resection of early gastric cancer are feasible, and patients need to be followed up closely for 5 years after endoscopic resection. Patients with absolute and expanded indications should undergo CT and endoscopic examinations during the follow-up process to avoid local recurrence of tumor and missed diagnosis of extra-gastric recurrence. With the popularity of endoscopic screening for gastric cancer in Japan, Korea and other East Asian countries, related studies also took a place in this session. Hwoon-Yong Jung from Korea analyzed the clinicopathological characteristics of 327 gastric cancer patients identified in 109,530 endoscopic screenings and suggested that independent risk factors for gastric cancer development included H. pylori serologic positivity (odds ratio (OR) 2.933, p<0.001), elevated carcinoembryonic antigen (CEA) (OR 8.633, p=0.004 ), family history of gastric cancer (OR 2.254, p=0.007), and alcohol consumption (OR 3.312, p<0.001), while protective factors included aspirin application (OR 0.445, p=0.012). In addition, independent risk factors for death in patients with gastric cancer detected by screening included low-density lipoprotein (risk ratio (HR) 0.987, p=0.005), cancer antigen 19-9 (CA19-9) (HR 21.713, p<0.001), tumor resectability (HR 59.833, p<0.001), and family history (HR 0.308, p=0.009). Meanwhile, the 5-year survival rate of gastric cancer patients detected by screening was significantly better than that of gastric cancer patients seen in outpatient clinics (p<0.001). In addition to the patient-specific study, Yong Chan Lee of Korea shared the scoring system used to assess the ability of endoscopists to detect early gastric cancer during screening. In addition to endoscopic screening and surgery, studies related to anterior lymph nodes have also emerged in studies of early gastric cancer. Hiroya Takeuchi et al. from Japan used one-step nucleic acid amplification (OSNA) based on PCR to detect sentinel lymph nodes and demonstrated its feasibility for intraoperative detection of early gastric cancer sentinel lymph nodes. Hirohito Fujikawa from Japan reviewed the pattern of lymph node metastasis in 511 patients with stage T1 gastric cancer and suggested that the risk factors for lymph node metastasis in stage T1 include depth of infiltration, pathological type, and tumor size, and established a model for the assessment of lymph node metastasis based on this method, with the sensitivity and specificity of predicting pathological lymph node metastasis reaching 67.4% and 71.6%, respectively. . 2. Studies related to resectable progressive gastric cancer 2.1 Studies related to perioperative gastric cancer The most compelling study on gastric cancer surgery in this meeting came from Linda X. Jin from the U.S. This study analyzed 953 gastric cancer surgery patients from 7 centers in the U.S. By analyzing the relationship between surgical complications and patients' overall survival (OS) and disease-free survival (DFS), it was concluded that complications were associated with patients with decreased postoperative survival (Table 1). The median follow-up of patients in this study was 32 months, and the overall complication rate (complications within 90 days postoperatively and without death within 30 days postoperatively) was 40%, with the most common complications being infection (25%) and anastomotic leak (6%), and a secondary surgery rate of 7%. In survival analysis, 5-year OS was significantly lower in patients with postoperative complications than in patients without complications (39% vs. 54%, p=0.001), as was 5-year DFS (49% vs. 61%, p=0.002). In addition, a lower percentage of patients with postoperative complications received postoperative adjuvant therapy (42% vs. 55%, p<0.001). Based on this result, the investigators concluded that post-radical gastric cancer complications are one of the factors that reduce the survival of gastric cancer patients, and the reason for this may be related to the low percentage of patients with complications receiving postoperative adjuvant therapy. Therefore, the reduction of postoperative complications by delicate surgical manipulation is as important for short-term surgical outcomes as for long-term oncologic outcomes after surgery. Numerous other studies have made numerous important observations related to gastric cancer surgery and the perioperative period, including that decreased preoperative muscle strength is a risk factor for complications in gastric cancer surgery, that perioperative blood transfusions are associated with decreased overall and disease-free survival after radical gastric cancer surgery, that postoperative nutritional support with oral elements of diet can prevent postoperative weight loss after gastric cancer surgery, and that preoperative planned physical exercise for early gastric cancer patients with combined metabolic syndrome is safe. Physical exercise to reduce the risk of surgery is safe and feasible, etc. Norihiko Sugisawa from Japan confirmed the important role of diagnostic laparoscopic techniques in the staging of type 4 (diffusely invasive) gastric cancer. A retrospective study of 169 cases of type 4 gastric cancer excluding distant metastases showed that the proportion of abdominal implant metastases was around 40% and the proportion of positive abdominal free cytology was even higher at around 70%. This study further clarifies the importance of diagnostic laparoscopic techniques in the diagnosis of gastric cancer staging and provides evidence-based medical evidence for the development of indications for diagnostic laparoscopic techniques. 2.2 Studies related to adjuvant chemotherapy for gastric cancer In this meeting, there were fewer studies on the selection of adjuvant chemotherapy drug regimens for gastric cancer, and the main research hotspots were focused on the tolerance of adjuvant chemotherapy after gastric cancer surgery in different patients. Jae-Cheol Jo from Korea confirmed the potential survival benefit of adjuvant chemotherapy after D2 radical surgery for stage II/III gastric cancer patients older than 70 years old in a retrospective study, while Daisuke Kobayashi from Japan suggested that women, advanced age, low creatinine clearance and significant weight loss after surgery were relevant factors influencing the compliance of postoperative S-1 single-agent adjuvant chemotherapy in gastric cancer patients. factors. In addition, Kazumasa Fujitani suggested that the reduction of skeletal muscle volume after total gastrectomy would be further aggravated by postoperative adjuvant chemotherapy, so this group of patients should pay attention to enhancing postoperative nutrition to ensure the successful implementation of postoperative adjuvant chemotherapy. 2.3 Studies related to neoadjuvant chemotherapy for gastric cancer In terms of neoadjuvant chemotherapy for gastric cancer, the only phase III clinical study in this meeting is the RESONANCE study, a multicenter randomized controlled study led by the PLA General Hospital in China, which intends to evaluate the 3-year disease-free survival rate of S-1 + oxaliplatin regimen (SOX regimen) as a neoadjuvant chemotherapy regimen followed by radical surgery for gastric cancer D2, which is currently study is still in the patient enrollment phase. From February 2012 to August 2013, 231 patients were enrolled in the study, including 128 in the neoadjuvant chemotherapy group and 103 in the adjuvant chemotherapy group, and analysis of early results showed that the SOX regimen had a clinical remission rate of 70% and a pathological remission rate of 14% in patients treated with neoadjuvant chemotherapy. This head-to-head study is expected to confirm the superiority of neoadjuvant chemotherapy combined with D2 radical surgery over adjuvant chemotherapy for gastric cancer, but the final results need to be further confirmed. A phase II clinical study from Korea showed no significant difference in survival between neoadjuvant and adjuvant chemotherapy with docetaxel in combination with cisplatin in patients with locally progressive gastric cancer. Another hot topic in neoadjuvant chemotherapy studies for gastric cancer is the evaluation of patient outcomes. Jonathan M. Hernandez from the United States demonstrated in a retrospective study of 216 patients that the change in SUV values for evaluation of neoadjuvant chemotherapy with PET correlated significantly with histopathological remission, and with OS and DFS. Haruhiko Cho, Japan, assessed the prognosis of 22 patients who visited a medical center with a pathological evaluation of pCR after neoadjuvant chemotherapy for gastric cancer by administering a questionnaire to these patients. Of these patients, 95.4% had stage III/IV tumors, 61.9% had diffuse pathology, and 77.2% required combined organ resection during surgical treatment. During follow-up, 86.3% of the patients had no tumor recurrence, none of the 10 patients who received postoperative adjuvant chemotherapy had recurrence, and 3 of the 12 patients who did not receive postoperative adjuvant chemotherapy had recurrence, including 2 deaths due to gastric cancer (71 and 9 months postoperatively, respectively), and these patients had 5-year OS and DFS of 85.1% and 75.1%, respectively. Despite the small number of cases and the low level of methodological evidence, this study reflects to some extent the excellent prognosis of patients with gastric cancer in complete pathological remission, and further confirmation of this conclusion is needed in larger prospective studies. Regarding the safety of neoadjuvant chemotherapy, Takaki Yoshikawa from Japan concluded from data mining of previous phase II prospective randomized clinical trials of neoadjuvant chemotherapy for gastric cancer that low creatinine clearance after chemotherapy is one of the major risk factors for complications of radical surgery for gastric cancer after neoadjuvant chemotherapy, and therefore special attention should be paid to patients' renal function to ensure the safety of surgery. 2.4 Studies related to radiotherapy for gastric cancer Perioperative radiotherapy for gastric cancer was also one of the hot topics in this meeting. Asiam Ejaz from USA reviewed the prognosis of 294 patients who received perioperative radiotherapy and radical surgery for gastric cancer. Compared with perioperative chemotherapy, perioperative radiotherapy was an independent factor for improvement in DFS and OS, and both DFS (HR 0.43, p<0.001) and OS (HR 0.41, p<0.001) were improved in these patients. Mai Tsutsui from Japan also reviewed 109 patients with progressive gastric cancer (11 in stage IIIA, 10 in stage IIIB, 14 in stage IIIC, and 74 in stage IV) who received postoperative adjuvant concurrent radiotherapy. The adjuvant treatment used in this study was postoperative S-1/cisplatin regimen chemotherapy with a synchronous radiotherapy regimen of 2 Gy/day, 5 days/week, i.e., radiation therapy on treatment days 1-5,8-15,15-19,22-26. There was no complete tumor remission in patients who still had evaluable lesions after surgery, but the percentage of partial tumor remission was as high as 70% and the percentage of disease progression was 5%. The most common adverse events of adjuvant therapy in this study were hematologic toxicities, including leukopenia, neutropenia, and thrombocytopenia. The median survival time at patient follow-up was 537 days. Although there was no complete tumor remission in patients treated with concurrent radiotherapy in this study, we should note that patients enrolled in this study had predominantly stage IV gastric cancer and a high proportion of partial tumor remission with tolerable treatment toxicities and side effects, and patient survival still provides supporting evidence for radiation therapy for gastric cancer patients. Another study of radiation therapy for gastric cancer was conducted by Ferdinando De Vita, an Italian academic, which focused on postoperative adjuvant radiotherapy based on the FOLFOX4 regimen after R1 resection for gastric cancer. The study reviewed 43 patients after R1 resection for gastric cancer, and enrolled patients were treated with 8 cycles of FOLFOX4-based chemotherapy and 2 cycles of chemotherapy followed by concurrent radiotherapy (45 Gy over 25 days and 5 weeks). The study had a median follow-up of 36 months, a 3-year OS of 19%, a median disease-free survival of 14.5 months, and a median overall survival of 16 months. This retrospective study suggests a survival benefit after R1 resection in approximately 19% of gastric cancer patients, but the evidence-based medical evidence is not yet sufficient and further validation in larger clinical studies is still needed. Treatment of advanced gastric cancer The most notable treatment for advanced gastric cancer in this meeting is the global phase III randomized double-blind clinical study RAINBOW. Several studies have confirmed that second-line treatment of metastatic gastric cancer can prolong survival, and the single-week regimen of paclitaxel has similar efficacy and better tolerability than other regimens; angiogenesis-related growth factor VEGF-2 and its ligands play an important role in the development of gastric cancer, so it may become an important target for gastric cancer treatment. ramucirumab is a monoclonal humanized IgG1 targeting VEGFR-2 humanized IgG1 monoclonal antibody against VEGFR-2. The objective of this study was to observe the efficacy of Ramucirumab in combination with paclitaxel in the second-line treatment of metastatic gastric cancer. Patients with metastatic or inoperable advanced gastric cancer who failed first-line fluorouracil or platinum-based therapy were the primary study population and were randomized 1:1 to receive Ramucirumab or placebo in combination with paclitaxel (PTX) (Ramucirumab or placebo 8 mg/kg/d d1,15; PTX 80 mg/m2/d d1,8, 15 ;q28d) until disease progression or intolerable toxic effects. The primary study endpoint was OS, and secondary endpoints included progression-free survival (PFS), time to progression (TTP), objective response rate (ORR), safety, and quality of life evaluation (EORTC-QLQ-C). EORTC-QLQ-C30 and EQ-5D), efficacy, pharmacokinetics and immunogenicity. A total of 170 centers in 27 countries and regions worldwide participated in this study, including Korea, Japan, Hong Kong, Taiwan and Singapore in Asia. From December 2010 to September 2012, 665 patients were enrolled in the study, including 223 cases in Asia, 330 in the RAM+PTX group and 335 in the placebo+PTX group. As of July 12, 2013, there were 516 deaths in the enrolled patients, with median overall survival of 9.63 months and 7.36 months in the two groups (HR 0.807, 95% CI: 0.678- 0.962, p=0.0169), and 6- and 12-month survival rates of 72% vs. 57% and 40% vs. 30%, respectively. PFS was 4.4 and 2.86 months, respectively, p<0.0001, and ORR was 28% and 16%, respectively, p=0.0001. OS analysis of the main subgroups showed statistically significant differences between the two groups in the non-Asian population, time to first-line disease progression R6 months, age <65 years, intestinal type, and occurrence in the gastroesophageal junction; OS in the Asian population was 12.1 and 10.5 months in the two groups, respectively and 10.5 months (HR 0.99, 95% CI: 0.73-1.34), PFS 5.5 months and 2.8 months (HR 0.63, 95% CI: 0.47-0.83), ORR 33.9% and 20.2% (HR 2.24, 95% CI: 1.18-4.24), respectively, in the Asian population; OS 8.5 months and OS was 8.5 and 5.9 months (HR 0.73, 95% CI: 0.59-0.91), PFS was 4.2 and 2.9 months (HR 0.64, 95% CI: 0.52-0.79), and ORR was 24.9% and 14.0% (HR 2.09, 95% CI: 1.28-3.41) in the non-Asian population, respectively. Common adverse reactions There was a significant increase in hematologic toxicity in the test group, with 40.7% vs. 18.8% neutropenia above grade 3 and a slight increase in non-hematologic toxicity (above grade 3) mainly malaise (11.9% vs. 5.5%), abdominal pain (6.1% vs. 3.3%) and neurotoxicity (8.3% vs. 4.6%); for anti-angiogenesis-related adverse reactions. Gastrointestinal bleeding 10.1 vs 3.7%, epistaxis 30.6% vs 7.0%, hypertension 25.1% vs 5.8% (degree 3 or higher 14.7% vs 2.7%), proteinuria 16.8% vs 6.1%, and others including gastrointestinal perforation, arterial and venous thrombosis, and heart failure <5% incidence. The incidence of treatment-related death was similar in both groups (4% vs. 4.6%). The findings suggest that Ramucirumab in combination with PTX regimen in second-line treatment of advanced or metastatic gastric cancer may prolong OS and reduce the risk of death. Both this study and the recently published REGARD study confirm that Ramucirumab is a new and effective agent for advanced or metastatic gastric cancer that has failed first-line therapy, and also suggest that effective second-line therapy may improve survival in advanced or metastatic gastric cancer. The efficacy of chemotherapy for advanced gastric cancer has long been at a bottleneck stage, and targeted therapy has become the most important research direction to obtain breakthroughs. In recent years, drugs targeting EGFR, HER-2, VEGF, mTOR and other targets have been studied in gastric cancer, but except for trastuzumab, which significantly improved survival in combination with chemotherapy in first-line HER-2-positive gastric cancer, all other phase III studies obtained negative results. In this context, the positive results of the RAINBOW study are certainly encouraging, and Ramucirumab becomes the second targeted agent after trastuzumab that has been shown to be effective in the treatment of advanced gastric cancer, but a review of previous studies suggests that anti-angiogenic drugs are not the first attempt to be used in the treatment of advanced gastric cancer; bevacizumab, which is widely used in the treatment of metastatic colorectal cancer ( Bevacizumab), which is widely used in the treatment of metastatic colorectal cancer, was combined with capecitabine + cisplatin regimen in the AVAGAST study for the first-line treatment of inoperable resectable or metastatic gastric cancer, and got a negative conclusion, while clinical studies of the same anti-angiogenic drugs targeting VEGF had different results, the reasons of which are worthy of consideration. Although two studies on Ramucirumab have obtained positive results in the second-line treatment of advanced or metastatic gastric cancer, it should also be considered that the efficacy of the drug in the Asian population is still controversial, and as to whether the drug can be used for first-line treatment, corresponding clinical studies still need to be continued, which also deserve our attention. 4. HER2-related research in gastric cancer HER2-related research in gastric cancer is still one of the hot spots in this meeting. For the diagnosis of gastric cancer patients, the detection of HER2 status is still one of the difficult points. Dominique Werner from Germany proposed to combine HER2 gene amplification and protein overexpression in the same platform for the detection of HER2 status in gastric cancer, which is the first time to be used for gastric cancer detection. As for the HER2-targeted drug trastuzumab, this meeting mainly focused on phase II clinical studies, including the effectiveness and safety analysis of trastuzumab combined with paclitaxel regimen as second-line treatment for patients with progressive or recurrent HER2-positive gastric cancer, evaluation of trastuzumab combined with XELOX regimen for progressive gastric cancer and trastuzumab combined with S-1/cisplatin as first-line regimen. evaluation of trastuzumab in combination with XELOX and trastuzumab in combination with S-1/cisplatin as first-line regimen. In addition to clinical studies, HER2-related translational studies are also a hot topic of research. The role of HER3, Heregulin, H. pylori Cag A and other related molecules and proteins on the regulation of HER2 gene amplification, protein expression and activity in gastric cancer was proposed and evaluated in combination with trastuzumab efficacy. 5.Translational Research on Gastric Cancer The conference was full of exciting translational research on gastric cancer. Hark K. Kim from Korea demonstrated that E-cadherin and Smad4 deletion combined with p53 deletion promote the progression and metastasis of gastric cancer using a new genetically engineered mouse model, which reveals the important role of epithelial mesenchymal transition (EMT) in gastric cancer metastasis and provides an important model for drug testing for gastric cancer metastasis treatment. The significance The research on c-MET-related pathways is also a hot topic. Studies by scholars from various countries have suggested that increased MET protein expression in gastric cancer patients is associated with poor prognosis and may become a new target for gastric cancer treatment in the future. Other translational medicine research has also addressed topics such as the study of CDH1 mutations in China, the regulation of STAT3 activity by DARPP-32, the relationship between tumor-associated macrophages and tumor angiogenesis in gastric cancer, and the inhibition of gastric cancer cell migration and infiltration through JAK2 targeting by snail-regulated MiR-375. In addition to the above studies, there are still many research advances related to gastric cancer in this meeting, which cannot be listed due to the limitation of space. From these research hotspots, we can see that the overall pattern of gastric cancer treatment has been standardized, but there is still a long way to go. In the future, the research and treatment of gastric cancer will start to move toward individualization. For patients with different clinical characteristics, stages, types and molecular phenotypes of gastric cancer, based on standardized treatment and guided by multidisciplinary collaborative treatment, individualized treatment plans and follow-up strategies will be formulated to achieve the best survival benefit for patients.