2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

prematurely due to poor accrual. 18 In addition, Mariette and
colleagues demonstrated that for early-stage esophageal
adenocarcinoma, there appears to be no added benefit of
CRT to surgical resection. 19
Influence of Disease Heterogeneity on Treatment
Gastric cancer is a heterogeneous disease and subtypes
of gastric cancer exist. 20,21 More than 95% of all cancers of
the stomach are adenocarcinomas. A common distinguishing
feature is histopathology, such as the Lauren’s classification,
which distinguishes intestinal and diffuse gastric cancer
subtypes. The well-differentiated intestinal type tends
to expand through the stomach wall, whereas the Lauren’s
diffuse-type is more commonly poorly differentiated and
spreads as individual discohesive cells in an infiltrative
pattern. Diffuse gastric cancer is associated with loss of the
cell-surface protein E-cadherin and germ-line mutations in
CDH1 are associated with the familial form of diffuse gastric
cancer, hereditary diffuse gastric cancer. 22 Intestinal gastric
cancers predominate in high-incidence areas (e.g., China),
and this histology is responsible for much of the ethnic
variation across the globe.
Gastric cancers may have different outcomes depending
on disease subtype. More proximal GEJ and cardia tumors
tend to have a worse prognosis compared with distal pyloric,
antral, and curvature cancers. 23 Data are also just now
emerging on the potential influence of disease subtype on
treatment outcome. For example, HER2 amplification and
Author’s Disclosure of Potential Conflicts of Interest
Author
Manish A. Shah*
*No relevant relationships to disclose.
Employment or
Leadership
Positions
Consultant or
Advisory Role
1. Ajani JA, Barthel JS, Bentrem D, et al. Esophageal and esophagogastric
junction cancers. National Comp Canc Netw. 2011;2.2011:1-97.
2. Ajani JA, Barthel JS, Bentrem D, et al. Gastric cancer. National Comp
Canc Netw. 2011;2.2011:1-84.
3. Bang YJ, Kim YW, Yang HK, et al. Adjuvant capecitabine and oxaliplatin
for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label,
randomised controlled trial. Lancet. 2012;379:315-321.
4. Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy
for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. Nov 1
2007;357:1810-1820.
5. GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research International
Collaboration) Group, Paoletti X, Oba K, et al. Benefit of adjuvant
chemotherapy for resectable gastric cancer: a meta-analysis. JAMA. 2010;
303:1729-1737.
6. Strong VE, Song KY, Park CH, et al. Comparison of gastric cancer
survival following R0 resection in the United States and Korea using an
internationally validated nomogram. Ann Surg. 2010;251:640-646.
7. Di Costanzo F, Gasperoni S, Manzione L, et al. Adjuvant chemotherapy
in completely resected gastric cancer: a randomized phase III trial conducted
by GOIRC. J Natl Cancer Inst. 2008;100:388-398.
8. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy
versus surgery alone for resectable gastroesophageal cancer. N Engl
J Med. 2006;355:11-20.
9. Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared
with surgery alone for resectable gastroesophageal adenocarcinoma: an
FNCLCC and FFCD Multicenter phase III trial. J Clin Oncol. 2011;29:1715-
1721.
10. MacDonald JS, Smalley S, Benedetti J, et al. Chemoradiotherapy after
surgery compared with surgery alone for adenocarcinoma of the stomach or
gastroesophageal junction. N Engl J Med. 2001;345:725-730.
258
overexpression is far more prevalent in proximal/GEJ adenocarcinoma
than in diffuse gastric cancer. 24,25 In an exploratory
analysis, these proximal/GEJ tumors appeared to be
less sensitive to bevacizumab therapy than are diffuse and
distal nondiffuse gastric cancers. 26 Thus, disease biology
may indeed influence patient outcomes with specific treatments.
Implications for the Future
Where do we go from here? Because treatment paradigms
are defined on a global basis, it will be important to understand
the global heterogeneity of these diseases. The epidemiology,
risk factors, and patterns of care for cancers of the
upper GI tract are substantially different across the globe.
Disease biology in the various regions around the world may
also be different, although this needs to be more thoroughly
investigated. For example, proximal/GEJ adenocarcinomas
seem less frequent in the far East compared with Europe
and the Americas. However, it is not clear whether this
difference solely contributes to differences in patient outcome
between these two regions. Could it be practice patterns
(screening and early disease identification), use of
second-line therapy, 27 or disease biology 6 ? Our challenge is
to recognize the influence of disease biology and heterogeneity
on treatment paradigms in this disease. If we are able to
do so, we will be able to provide better treatment guidelines
for specific disease subtypes, and improve patient outcomes
in a more directed approach—a laudable goal, indeed!
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Ownership Honoraria
REFERENCES
Research
Funding
Expert
Testimony
MANISH A. SHAH
Other
Remuneration
11. Fuchs CS, Tepper JE, Niedzwiecki D, et al. Postoperative adjuvant
chemoradiation for gastric or gastroesophageal junction (GEJ) adenocarcinoma
using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and
after CI 5-FU and radiotherapy (CRT) compared with bolus 5-FV/LV before
and after CRT: Intergroup trial CALGB 80101. J Clin Oncol. 2011;29(suppl;
abstr 4003).
12. Lee J, Lim do H, Kim S, et al. Phase III trial comparing capecitabine
plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine
radiotherapy in completely resected gastric cancer with D2 lymph node
dissection: the ARTIST Trial. J Clin Oncol. 2012;30:268-273.
13. van der Gaast A, van Hagen P, Hulshof M, et al. Effect of preoperative
concurrent chemoradiotherapy on survival of patients with resectable esophageal
or esophagogastric junctino cancer: results from a multi-center randomized
phase III study. J Clin Oncol. 2010;28(suppl; abstr 4004).
14. Bedenne L, Michel P, Bouche O, et al. Chemoradiation followed by
surgery compared with chemoradiation alone in squamous cancer of the
esophagus: FFCD 9102. J Clin Oncol. 2007;25:1160-1168.
15. Stahl M, Stuschke M, Lehmann N, et al. Chemoradiation with and
without surgery in patients with locally advanced squamous cell carcinoma of
the esophagus. J Clin Oncol. 2005;23:2310-2317.
16. Tepper J, Krasna MJ, Niedzwiecki D, et al. Phase III trial of trimodality
therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared
with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol.
2008;26:1086-1092.
17. Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after
neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal
carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681-692.
18. Stahl M, Walz MK, Stuschke M, et al. Phase III comparison of
preoperative chemotherapy compared with chemoradiotherapy in patients