Page 238 - Read Online

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