23Mirroring the result of the Intergroup 0113 study, the com-
pleteness of resection was a major determining factor for clinical
outcomes. The 3-year survival for R0, R1, and R2 resection was
42.4%, 18.0%, and 8.6%, respectively. The Intergroup 0113 and
the MRC OE02 study reported different magnitude of benefit
with preoperative chemotherapy but the latter is more commonly
referred to in clinical practice due to its better statistical power and
more convenient chemotherapy regimen. Nevertheless, meta-
analyses have reported an overall survival benefit with neoadjuvant
chemoradiation for both esophageal adenocarcinoma and squa-
mous cell carcinoma [ 13 , 14 ]. Patients who underwent neoadju-
vant chemoradiotherapy were more likely to have R0 resection and
improved 3-year survival. The survival benefit was more pro-
nounced with concurrent chemoradiotherapy [ 13 ].
In a recent meta-analysis by the Australasian Gastro-Intestinal
Trials Group, 4188 patients with resectable esophageal carcinoma
from 24 trials were analyzed [ 15 ]. Compared to surgery alone,
neoadjuvant chemoradiotherapy led to a 22% reduction in the risk
of all-cause mortality while the reduction in risk was 13% for neo-
adjuvant chemotherapy alone. The survival advantage of neaoad-
juvant chemoradiotherapy was significant for both squamous cell
carcinoma and adenocarcinoma. On the other hand, statistically
significant survival benefit for neoadjuvant chemotherapy was
only demonstrated in adenocarcinoma but not for squamous cell
carcinoma. When neoadjuvant chemoradiotherapy and chemo-
therapy were directly compared, there was weak evidence in favor
of the former.Two studies in the European countries have established periopera-
tive chemotherapy as a standard treatment option for patients with
resectable adenocarcinoma of the lower esophagus and gastro-
esophageal junction. In the MRC MAGIC study, 503 patients with
resectable adenocarcinoma of the stomach, gastroesophageal junc-
tion or lower esophagus were randomized to surgery alone or peri-
operative chemotherapy with epirubicin, cisplatin, and 5FU [ 16 ].
The proportion of patients with adenocarcinoma of the lower
esophagus and the gastroesophageal junction were 14.5% and
11.5%, respectively. Chemotherapy had an obvious downstaging
effect since patients in the perioperative chemotherapy arm had
significantly more T1 and T2 tumor as well as N0 and N1
disease.
Perioperative chemotherapy appears to be safe and does not
increase the rate of morbidity and mortality of surgery. After a
median follow-up of 49 months, a significant reduction in the risk
of progression by 34% and the risk of death by 25% was demon-
strated with perioperative chemotherapy. The treatment effect was
regardless of the site of tumors at lower esophagus, gastroesopha-
geal junction, or stomach.1.1.2 Perioperative
Chemotherapy
Chemotherapy