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Page 2 of 10                            Harada et al. J Cancer Metastasis Treat 2018;4:18  I  http://dx.doi.org/10.20517/2394-4722.2017.74

               Table 1. Summary of NCCN guideline for resectable gastric adenocarcinoma
                Stage     Treatment (recommendation category or comments)          Preferred regimen (recommendation category)
                cT1a        Surgery
                            Endoscopic resection
                cT1b        Surgery
                cT2 higher  Perioperative chemotherapy (1)      Fluorouracil and cisplatin (1)
                            (3 cycle preoperative and 3 cycle postoperative)  Fluoropyrimidine and oxaliplatin (1A)
                                                                Epirubicin, cisplatin/oxaliplatin, and fluoropyrimidine (2B)
                            Preoperative chemoradiation (2B)    Paclitaxel and carboplatin(1)
                                                                Fluorouracil and cisplatin (1)
                                                                Fluoropyrimidine and oxaliplatin (1)
                            Postoperative chemoradiation (1)    Fluoropyrimidine (1A)
                            (for patients without preoperative treatment)  (before and after fluoropyrimidine-based chemoradiation)
                            Postoperative chemotherapy (2A)     Capecitabine and oxaliplatin (1)
                            (for patients after D2 lymph node dissection)

               Location of GAC had dramatically changed in the USA. Most of GAC originate from the proximal lesser
               curvature, cardia, and the gastroesophageal junction . This location trend is considered due to environmental
                                                           [2]
               risk factors, such as Helicobacter pylori infection, smoking, high salt intake, and obesity.



               STANDARD TREATMENT FOR RESECTABLE GAC IN THE USA
               Resectable GAC patients with ≥ cT1b can proceed to surgery (in the community setting) or receive preoperative
               therapy (in the university setting)  [Table 1]. If GAC patients directly undergo surgery, postoperative
               chemoradiation is recommended based on the pathological stage or quality of surgery. Endoscopic resection
               is performed according to Japanese guideline , but early stage (stage I) GAC is rare in the USA.
                                                     [3]
               At our institution, we prefer the strategy of induction chemotherapy followed by chemoradiation and
               surgery . This strategy originated at our institution (also, feasible in multi-institutional settings) and has
                      [4,5]
               been pursued based on excellent results recently reported . Induction chemotherapy consists of 4 doses
                                                                 [5]
               5-fluorouracil (5-FU) and oxaliplatin administered every 2 weeks, and chemoradiotherapy consists of 45 Gy in
               25 fractions with concurrent 5-FU/capecitabine with or without another cytotoxic like a platinum compound
               or taxane (when gastroesophageal junction is involved). After 6-8 weeks from the end of chemoradiation, a
               D2 dissection is attempted.


               Postoperative chemoradaiation
               SWOG 908/INT-0116, which started in 1991, is one of the most cited trials showing the survival benefit
               of postoperative chemoradiation for resected GAC in the USA . In this trial, a total of 556 patients
                                                                       [6,7]
               who  underwent  R0  resection  were  randomly  assigned  to  surgery  alone  or  surgery  plus  postoperative
               chemoradiotherapy (bolus 5-FU and leucovorin with 45 Gy radiotherapy). Compared with surgery alone
               group, postoperative chemoradiotherapy group showed better overall survival (OS) and relapse-free survival
               (RFS); the hazard ratio (HR) for OS is 1.32 [95% confidence interval (CI) 1.10-1.60; P = 0.0046], and the HR
               for RFS is 1.51 (95% CI 1.25-1.83; P < 0.001). Both overall relapse and locoregional relapse were decreased in
               postoperative chemoradiotherapy group . According to these results, postoperative chemoradition therapy
                                                 [6,7]
               became the standard treatment. It is appropriate only for those patients who undergo suboptimal surgery
               and do not received preoperative chemotherapy.

               INT 0116 had some inherent drawbacks since surgical method was not part of the protocol. Thus, in the INT-
               0116 trial, D0, D1, and D2 lymph node dissections underwent in 54%, 36%, and 10% patients, respectively.
               Therefore, the efficacy of postoperative chemoradiation after D2 resection remains unclear. The ARTIST
               (Adjuvant Chemoradiation Therapy in Stomach Cancer) trial in Korea compared postoperative treatment with
               capecitabine plus cisplatin (XP) and XP plus radiation after curative resection with D2 lymph node dissection .
                                                                                                        [8]
               This trial showed that the estimated 3-year disease free survival rates were 78.2% in the chemoradiation
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