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Gastric cancer (GC) is the fourth most common cancer in men and the fifth most common cancer in women worldwide.
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Surgery is the key for curing patients with localized GC. However, surgery alone is insufficient to achieve the highest possible cure rate, which can be obtained by the addition of adjunctive therapies.
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Advanced GC is an incurable condition; however, it is now possible to prolong survival with oncologic therapies.
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Patients with advanced GC with Her2-neu protein overexpression can
Modern Oncological Approaches to Gastric Adenocarcinoma
Section snippets
Key points
Localized gastric cancer (LGC)
Baseline clinical stage should be established meticulously.3 Although baseline clinical stage is not as highly associated with long-term outcome as the surgical pathology stage,4 the baseline clinical stage does help to define the short-term therapeutic strategy. It is important to emphasize that physician(s) from one discipline (eg, a gastroenterologist or a surgeon) should not decide the initial therapeutic strategy of LGC but that a consensus decision, derived from a multidisciplinary
Postoperative Adjuvant Chemoradiation
The most important study that established this strategy firmly in the West is the Intergroup 0116 trial, headed by the Southwest Oncology Group.7 This trial was based on prior nonrandomized observations in patients with LGC who received chemoradiation therapy. This trial was a phase 3 study that compared observation after surgery (control) with chemoradiation adjuvant after following surgery (experimental arm).7 Key points about the INT0116 trial Recruitment duration: 1991–1998 Total number of
Advanced GC (AGC)
There are only a few agents that are associated with level 1 evidence for an overall survival advantage in AGC. These are docetaxel,20 cisplatin,21 and trastuzumab.22
It is also clear that giving 2 cytotoxic agents together is better than giving one alone.21 Whether there is an additional advantage from combining 3 cytotoxic agents is often debated, but it is likely minor. From a drug development perspective, most regulatory agencies currently accept a 2-cytotoxic-agent combination of a platinum
Important genes and pathways in GC
Alterations in the following pathways seem important in the pathobiology of GC: ERBB2 (Her-2), angiogenesis, phosphatidyl inositol-3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR), c-MET, and fibroblast growth factor receptor 2 (FGFR2). However, further research is expected to uncover more targets.
Summary
When evaluating newly diagnosed patients with GC, one must first establish whether a patient has AGC or LGC. Patients with LGC must undergo multidisciplinary evaluation and discussion before starting therapy. Surgery alone is inadequate in most patients with LGC, and adjunctive therapies should be considered. Surgery should be performed by an experienced high-volume surgeon, and at least 15 nodes must be evaluated.
For patients with AGC, much more research focusing on the molecular biology of GC
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This work was supported in part by The Park Family, Caporella Family, Bikoff Family, Cantu Family, Fairman Family, Dallas Family, Oaks Family, Sultan Family, Dio Family, Frazier Family, the Kevin Fund, the Schecter Private Foundation, and the Rivercreek Foundation.